Blood Banking

Blood sample collection

Credit: Jeremy L. Grisham

A diagnostic system can detect sepsis pathogens with high sensitivity and specificity in 3 to 5 hours, eliminating the need for blood culture, according to a study published in Clinical Infectious Diseases.

The system consists of the T2Candida Panel and the T2Dx Instrument, and it provides direct detection of 5 yeast pathogens—Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei—in whole blood samples.

T2Candida and T2Dx were cleared for use by the US Food and Drug Administration in September. They are the first diagnostic products powered by T2MR, a magnetic resonance-based diagnostic technology platform that does not require blood culture and sample purification or preparation.

“The ability to determine the presence or absence of Candida within hours—compared to days [with blood culture]—is paradigm-changing for patients at risk for these infections,” said study author Eleftherios Mylonakis, MD, PhD, of Rhode Island Hospital and The Miriam Hospital in Providence.

“It will allow us to move from a ‘best-guess’ approach in treating high-risk patients, such as cancer and transplant patients and patients in the intensive care unit, to a more informed approach where we can quickly direct the best course of therapy, potentially improving patient outcomes and saving lives.”

Study findings

For this multicenter study, Dr Mylonakis and his colleagues collected blood specimens from 1801 hospitalized patients between the ages of 18 and 95 who had a blood culture ordered as part of routine care.

T2Candida and T2Dx demonstrated an overall specificity of 99.4% per assay and 98.1% per patient. The system yielded a specificity of 98.9% for C albicans/C tropicalis, 99.3% for C parapsilosis, and 99.9% for C krusei/C glabrata.

The system had an overall sensitivity of 91.1% per assay and 91.0% per patient. It yielded a sensitivity of 92.3% for C albicans/C tropicalis, 94.2% for C parapsilosis, and 88.1% for C krusei/C glabrata.

The mean time to a positive result for T2Candida and T2Dx was 4.4 hours, compared to 129 hours for blood culture and species identification. The mean time to negative result for T2Candida and T2Dx was 4.2 hours, compared to at least 120 hours for blood culture.

In one case described in the paper, T2Candida and T2Dx detected a Candida infection that blood culture missed in 12 successive tests.

Seven days after the T2Candida result was obtained, physicians performed an invasive procedure to obtain a tissue culture, which proved that the T2Candida result accurately identified a case of intra-abdominal candidiasis.

“Blood culture, the current standard of care for the diagnosis of Candida infections, is known to have poor sensitivity overall and has 38% sensitivity in proven and probable cases of invasive candidiasis,” said study author Cornelius J. Clancy, MD, of the University of Pittsburgh in Pennsylvania.

“In our case, the T2Candida Panel has shown that it can rapidly identify intra-abdominal candidiasis where 12 serial blood culture results were negative. In many patients at risk for candidiasis, the collection of tissue samples for diagnosis is not possible due to their underlying medical conditions. Achieving the level of sensitivity demonstrated in this case, without requiring an intra-abdominal sample, has the potential to positively impact the practice of medicine for these patients.”

Blood sample collection

Credit: Jeremy L. Grisham

A diagnostic system can detect sepsis pathogens with high sensitivity and specificity in 3 to 5 hours, eliminating the need for blood culture, according to a study published in Clinical Infectious Diseases.

The system consists of the T2Candida Panel and the T2Dx Instrument, and it provides direct detection of 5 yeast pathogens—Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei—in whole blood samples.

T2Candida and T2Dx were cleared for use by the US Food and Drug Administration in September. They are the first diagnostic products powered by T2MR, a magnetic resonance-based diagnostic technology platform that does not require blood culture and sample purification or preparation.

“The ability to determine the presence or absence of Candida within hours—compared to days [with blood culture]—is paradigm-changing for patients at risk for these infections,” said study author Eleftherios Mylonakis, MD, PhD, of Rhode Island Hospital and The Miriam Hospital in Providence.

“It will allow us to move from a ‘best-guess’ approach in treating high-risk patients, such as cancer and transplant patients and patients in the intensive care unit, to a more informed approach where we can quickly direct the best course of therapy, potentially improving patient outcomes and saving lives.”

Study findings

For this multicenter study, Dr Mylonakis and his colleagues collected blood specimens from 1801 hospitalized patients between the ages of 18 and 95 who had a blood culture ordered as part of routine care.

T2Candida and T2Dx demonstrated an overall specificity of 99.4% per assay and 98.1% per patient. The system yielded a specificity of 98.9% for C albicans/C tropicalis, 99.3% for C parapsilosis, and 99.9% for C krusei/C glabrata.

The system had an overall sensitivity of 91.1% per assay and 91.0% per patient. It yielded a sensitivity of 92.3% for C albicans/C tropicalis, 94.2% for C parapsilosis, and 88.1% for C krusei/C glabrata.

The mean time to a positive result for T2Candida and T2Dx was 4.4 hours, compared to 129 hours for blood culture and species identification. The mean time to negative result for T2Candida and T2Dx was 4.2 hours, compared to at least 120 hours for blood culture.

In one case described in the paper, T2Candida and T2Dx detected a Candida infection that blood culture missed in 12 successive tests.

Seven days after the T2Candida result was obtained, physicians performed an invasive procedure to obtain a tissue culture, which proved that the T2Candida result accurately identified a case of intra-abdominal candidiasis.

“Blood culture, the current standard of care for the diagnosis of Candida infections, is known to have poor sensitivity overall and has 38% sensitivity in proven and probable cases of invasive candidiasis,” said study author Cornelius J. Clancy, MD, of the University of Pittsburgh in Pennsylvania.

“In our case, the T2Candida Panel has shown that it can rapidly identify intra-abdominal candidiasis where 12 serial blood culture results were negative. In many patients at risk for candidiasis, the collection of tissue samples for diagnosis is not possible due to their underlying medical conditions. Achieving the level of sensitivity demonstrated in this case, without requiring an intra-abdominal sample, has the potential to positively impact the practice of medicine for these patients.”

Blood sample collection

Credit: Jeremy L. Grisham

A diagnostic system can detect sepsis pathogens with high sensitivity and specificity in 3 to 5 hours, eliminating the need for blood culture, according to a study published in Clinical Infectious Diseases.

The system consists of the T2Candida Panel and the T2Dx Instrument, and it provides direct detection of 5 yeast pathogens—Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei—in whole blood samples.

T2Candida and T2Dx were cleared for use by the US Food and Drug Administration in September. They are the first diagnostic products powered by T2MR, a magnetic resonance-based diagnostic technology platform that does not require blood culture and sample purification or preparation.

“The ability to determine the presence or absence of Candida within hours—compared to days [with blood culture]—is paradigm-changing for patients at risk for these infections,” said study author Eleftherios Mylonakis, MD, PhD, of Rhode Island Hospital and The Miriam Hospital in Providence.

“It will allow us to move from a ‘best-guess’ approach in treating high-risk patients, such as cancer and transplant patients and patients in the intensive care unit, to a more informed approach where we can quickly direct the best course of therapy, potentially improving patient outcomes and saving lives.”

Study findings

For this multicenter study, Dr Mylonakis and his colleagues collected blood specimens from 1801 hospitalized patients between the ages of 18 and 95 who had a blood culture ordered as part of routine care.

T2Candida and T2Dx demonstrated an overall specificity of 99.4% per assay and 98.1% per patient. The system yielded a specificity of 98.9% for C albicans/C tropicalis, 99.3% for C parapsilosis, and 99.9% for C krusei/C glabrata.

The system had an overall sensitivity of 91.1% per assay and 91.0% per patient. It yielded a sensitivity of 92.3% for C albicans/C tropicalis, 94.2% for C parapsilosis, and 88.1% for C krusei/C glabrata.

The mean time to a positive result for T2Candida and T2Dx was 4.4 hours, compared to 129 hours for blood culture and species identification. The mean time to negative result for T2Candida and T2Dx was 4.2 hours, compared to at least 120 hours for blood culture.

In one case described in the paper, T2Candida and T2Dx detected a Candida infection that blood culture missed in 12 successive tests.

Seven days after the T2Candida result was obtained, physicians performed an invasive procedure to obtain a tissue culture, which proved that the T2Candida result accurately identified a case of intra-abdominal candidiasis.

“Blood culture, the current standard of care for the diagnosis of Candida infections, is known to have poor sensitivity overall and has 38% sensitivity in proven and probable cases of invasive candidiasis,” said study author Cornelius J. Clancy, MD, of the University of Pittsburgh in Pennsylvania.

“In our case, the T2Candida Panel has shown that it can rapidly identify intra-abdominal candidiasis where 12 serial blood culture results were negative. In many patients at risk for candidiasis, the collection of tissue samples for diagnosis is not possible due to their underlying medical conditions. Achieving the level of sensitivity demonstrated in this case, without requiring an intra-abdominal sample, has the potential to positively impact the practice of medicine for these patients.”

Platelets for transfusion

Platelet transfusions may increase the risk of death in patients with platelet consumptive disorders, results of a large study suggest.

Investigators observed a 2-fold increase in the risk of death among patients with thrombotic thrombocytopenic purpura (TTP) who received platelet transfusions and a 5-fold increase among transfused patients with heparin-induced thrombocytopenia (HIT).

There was no increased risk among patients with immune thrombocytopenia (ITP), however.

Aaron Tobian, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in Blood. They were previously presented at the 2014 AABB Annual Meeting.

“Because these conditions are so rare, they’re difficult to study,” Dr Tobian noted. “There was some suggestion that transfusion may be harmful in these conditions, but it really was not known until now.”

“Our study is the first one to show that platelet transfusions are frequently administered to patients with ITP, HIT, and TTP, and that they’re associated with higher odds of arterial blood clots and mortality in TTP and HIT.”

For this study, Dr Tobian and his colleagues analyzed data from the Nationwide Inpatient Sample, a federal database that contains billing records for about 20% of all patients treated and discharged at about 1000 US community hospitals in 47 states.

The database contains information on about 8 million inpatient hospitalizations per year nationwide. The study covered the years 2007 to 2011.

During that time, there were 79,980 hospital admissions for ITP, 10,624 for TTP, and 6332 for HIT. Platelet transfusions were reported in 10.1% of hospitalizations for TTP, 7.1% for HIT, and 25.8% for ITP.

“Our analysis found no significantly increased risks from platelet transfusions in ITP,” said study author Ruchika Goel, MD, also of Johns Hopkins.

“But in TTP, a platelet transfusion increased the odds of a potentially lethal arterial blood clot more than 5-fold and doubled the odds of a heart attack.”

Specifically, in an age- and gender-adjusted analysis, the odds ratio (OR) for arterial thrombosis was 5.8, and the OR for acute myocardial infarction (AMI) was 2.0 in TTP patients who received platelet transfusions. The OR for stroke was 1.6, and the OR for venous thrombosis was 1.1.

Similarly, HIT patients had an increased risk of arterial thrombosis (OR=3.4) and AMI (OR=1.9) if they received a platelet transfusion. But they did not have an increased risk of venous thrombosis (OR=0.8) or stroke (OR=0.5).

Platelet transfusions among ITP patients were not significantly associated with venous thrombosis (OR=1.3), arterial thrombosis (OR=0.3), AMI (OR=1.3), or stroke (OR=1.3) after adjustment for age and gender.

The all-cause, in-hospital mortality rates were 8.8% for TTP patients, 3.4% for HIT patients, and 1.4% for ITP patients.

Patients with TTP and HIT had a significantly increased risk of all-cause mortality if they received platelet transfusions, with age- and gender-adjusted ORs of 2.0 and 5.2, respectively. But platelet transfusions were not significantly associated with mortality in ITP patients, with an OR of 1.1.

The investigators said they were surprised at the prevalence of platelet transfusions in this patient population, in spite of some practitioners’ concerns about the risks.

But Dr Tobian noted that, in some cases, doctors may not know a patient has a platelet disorder until they see the potentially deadly reaction to the transfusion. And in other cases, the transfusion may be used as a last resort.

He and his colleagues believe that, for patients with HIT and TTP, platelet transfusions should be reserved “only for severe, life-threatening bleeding refractory to other therapies or major surgery.”

Platelets for transfusion

Platelet transfusions may increase the risk of death in patients with platelet consumptive disorders, results of a large study suggest.

Investigators observed a 2-fold increase in the risk of death among patients with thrombotic thrombocytopenic purpura (TTP) who received platelet transfusions and a 5-fold increase among transfused patients with heparin-induced thrombocytopenia (HIT).

There was no increased risk among patients with immune thrombocytopenia (ITP), however.

Aaron Tobian, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in Blood. They were previously presented at the 2014 AABB Annual Meeting.

“Because these conditions are so rare, they’re difficult to study,” Dr Tobian noted. “There was some suggestion that transfusion may be harmful in these conditions, but it really was not known until now.”

“Our study is the first one to show that platelet transfusions are frequently administered to patients with ITP, HIT, and TTP, and that they’re associated with higher odds of arterial blood clots and mortality in TTP and HIT.”

For this study, Dr Tobian and his colleagues analyzed data from the Nationwide Inpatient Sample, a federal database that contains billing records for about 20% of all patients treated and discharged at about 1000 US community hospitals in 47 states.

The database contains information on about 8 million inpatient hospitalizations per year nationwide. The study covered the years 2007 to 2011.

During that time, there were 79,980 hospital admissions for ITP, 10,624 for TTP, and 6332 for HIT. Platelet transfusions were reported in 10.1% of hospitalizations for TTP, 7.1% for HIT, and 25.8% for ITP.

“Our analysis found no significantly increased risks from platelet transfusions in ITP,” said study author Ruchika Goel, MD, also of Johns Hopkins.

“But in TTP, a platelet transfusion increased the odds of a potentially lethal arterial blood clot more than 5-fold and doubled the odds of a heart attack.”

Specifically, in an age- and gender-adjusted analysis, the odds ratio (OR) for arterial thrombosis was 5.8, and the OR for acute myocardial infarction (AMI) was 2.0 in TTP patients who received platelet transfusions. The OR for stroke was 1.6, and the OR for venous thrombosis was 1.1.

Similarly, HIT patients had an increased risk of arterial thrombosis (OR=3.4) and AMI (OR=1.9) if they received a platelet transfusion. But they did not have an increased risk of venous thrombosis (OR=0.8) or stroke (OR=0.5).

Platelet transfusions among ITP patients were not significantly associated with venous thrombosis (OR=1.3), arterial thrombosis (OR=0.3), AMI (OR=1.3), or stroke (OR=1.3) after adjustment for age and gender.

The all-cause, in-hospital mortality rates were 8.8% for TTP patients, 3.4% for HIT patients, and 1.4% for ITP patients.

Patients with TTP and HIT had a significantly increased risk of all-cause mortality if they received platelet transfusions, with age- and gender-adjusted ORs of 2.0 and 5.2, respectively. But platelet transfusions were not significantly associated with mortality in ITP patients, with an OR of 1.1.

The investigators said they were surprised at the prevalence of platelet transfusions in this patient population, in spite of some practitioners’ concerns about the risks.

But Dr Tobian noted that, in some cases, doctors may not know a patient has a platelet disorder until they see the potentially deadly reaction to the transfusion. And in other cases, the transfusion may be used as a last resort.

He and his colleagues believe that, for patients with HIT and TTP, platelet transfusions should be reserved “only for severe, life-threatening bleeding refractory to other therapies or major surgery.”

Platelets for transfusion

Platelet transfusions may increase the risk of death in patients with platelet consumptive disorders, results of a large study suggest.

Investigators observed a 2-fold increase in the risk of death among patients with thrombotic thrombocytopenic purpura (TTP) who received platelet transfusions and a 5-fold increase among transfused patients with heparin-induced thrombocytopenia (HIT).

There was no increased risk among patients with immune thrombocytopenia (ITP), however.

Aaron Tobian, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in Blood. They were previously presented at the 2014 AABB Annual Meeting.

“Because these conditions are so rare, they’re difficult to study,” Dr Tobian noted. “There was some suggestion that transfusion may be harmful in these conditions, but it really was not known until now.”

“Our study is the first one to show that platelet transfusions are frequently administered to patients with ITP, HIT, and TTP, and that they’re associated with higher odds of arterial blood clots and mortality in TTP and HIT.”

For this study, Dr Tobian and his colleagues analyzed data from the Nationwide Inpatient Sample, a federal database that contains billing records for about 20% of all patients treated and discharged at about 1000 US community hospitals in 47 states.

The database contains information on about 8 million inpatient hospitalizations per year nationwide. The study covered the years 2007 to 2011.

During that time, there were 79,980 hospital admissions for ITP, 10,624 for TTP, and 6332 for HIT. Platelet transfusions were reported in 10.1% of hospitalizations for TTP, 7.1% for HIT, and 25.8% for ITP.

“Our analysis found no significantly increased risks from platelet transfusions in ITP,” said study author Ruchika Goel, MD, also of Johns Hopkins.

“But in TTP, a platelet transfusion increased the odds of a potentially lethal arterial blood clot more than 5-fold and doubled the odds of a heart attack.”

Specifically, in an age- and gender-adjusted analysis, the odds ratio (OR) for arterial thrombosis was 5.8, and the OR for acute myocardial infarction (AMI) was 2.0 in TTP patients who received platelet transfusions. The OR for stroke was 1.6, and the OR for venous thrombosis was 1.1.

Similarly, HIT patients had an increased risk of arterial thrombosis (OR=3.4) and AMI (OR=1.9) if they received a platelet transfusion. But they did not have an increased risk of venous thrombosis (OR=0.8) or stroke (OR=0.5).

Platelet transfusions among ITP patients were not significantly associated with venous thrombosis (OR=1.3), arterial thrombosis (OR=0.3), AMI (OR=1.3), or stroke (OR=1.3) after adjustment for age and gender.

The all-cause, in-hospital mortality rates were 8.8% for TTP patients, 3.4% for HIT patients, and 1.4% for ITP patients.

Patients with TTP and HIT had a significantly increased risk of all-cause mortality if they received platelet transfusions, with age- and gender-adjusted ORs of 2.0 and 5.2, respectively. But platelet transfusions were not significantly associated with mortality in ITP patients, with an OR of 1.1.

The investigators said they were surprised at the prevalence of platelet transfusions in this patient population, in spite of some practitioners’ concerns about the risks.

But Dr Tobian noted that, in some cases, doctors may not know a patient has a platelet disorder until they see the potentially deadly reaction to the transfusion. And in other cases, the transfusion may be used as a last resort.

He and his colleagues believe that, for patients with HIT and TTP, platelet transfusions should be reserved “only for severe, life-threatening bleeding refractory to other therapies or major surgery.”

Sleeping newborn

Credit: Vera Kratochvil

Results of a new study indicate that current guidelines for exchange transfusions in infants can successfully prevent kernicterus, a rare and life-threatening type of cerebral palsy triggered by escalating bilirubin that injures the brain.

However, the research also showed that only infants whose levels of bilirubin were well above the level for exchange transfusion actually developed kernicterus. And those infants all had additional risk factors for brain damage.

This suggests perhaps the threshold for exchange transfusion could safely be raised for infants with high bilirubin levels who have no other risk factors for brain injury, according to Yvonne W. Wu, MD, of the University of California, San Francisco (UCSF).

Dr Wu and her colleagues evaluated the health records of two groups of infants selected from 525,409 births. The children had been born at 15 hospitals within the Kaiser Permanente Northern California region from 1995 through 2011.

One group comprised 1833 newborns with levels of bilirubin above the level at which the American Academy of Pediatrics (AAP) recommends exchange transfusions.

The second group was made up of 104,716 randomly sampled newborns, born at at least 35 weeks’ gestation with lower levels of bilirubin. The two groups were followed for an average of 7 and 6 years, respectively.

The researchers confirmed 3 cases of kernicterus based on the brain MRIs of children with cerebral palsy. All 3 cases had occurred in newborns with the highest levels of bilirubin. But further study revealed that each child had 2 or more risk factors for brain damage.

”We found that cerebral palsy consistent with kernicterus did not occur in a single infant with high bilirubin without the presence of additional risk factors for neurotoxicity, such as prematurity, sepsis, and the hereditary blood disorder G6PD deficiency,” said Michael W. Kuzniewicz, MD, of UCSF. “This was the case even in infants with very high bilirubin.”

In 2004, the AAP published a guideline for treating infants whose bilirubin remained high despite phototherapy. It recommended exchange transfusions based on the level of bilirubin, the age of the infant, and other risk factors for brain damage.

“Our study was the first to evaluate how well the exchange transfusion guidelines predicted risk of cerebral palsy and kernicterus in babies with jaundice,” said Thomas B. Newman, MD, of UCSF.

“It was reassuring that brain injury due to high bilirubin was rare and that only those infants whose levels were well above exchange transfusion guidelines developed kernicterus.”

“Based on our study, the current guidelines for when to perform exchange transfusions have been quite successful in preventing kernicterus,” Dr Wu added. “However, our study also raises the question whether the threshold for exchange transfusion could be higher for infants with high bilirubin levels who are otherwise healthy and who have no other risk factors for brain injury.”

This is especially important, she noted, because exchange transfusions pose risks such as blood clot formation, blood pressure instability, bleeding, and changes in blood chemistry.

Dr Wu and her colleagues described this research in JAMA Pediatrics.

Sleeping newborn

Credit: Vera Kratochvil

Results of a new study indicate that current guidelines for exchange transfusions in infants can successfully prevent kernicterus, a rare and life-threatening type of cerebral palsy triggered by escalating bilirubin that injures the brain.

However, the research also showed that only infants whose levels of bilirubin were well above the level for exchange transfusion actually developed kernicterus. And those infants all had additional risk factors for brain damage.

This suggests perhaps the threshold for exchange transfusion could safely be raised for infants with high bilirubin levels who have no other risk factors for brain injury, according to Yvonne W. Wu, MD, of the University of California, San Francisco (UCSF).

Dr Wu and her colleagues evaluated the health records of two groups of infants selected from 525,409 births. The children had been born at 15 hospitals within the Kaiser Permanente Northern California region from 1995 through 2011.

One group comprised 1833 newborns with levels of bilirubin above the level at which the American Academy of Pediatrics (AAP) recommends exchange transfusions.

The second group was made up of 104,716 randomly sampled newborns, born at at least 35 weeks’ gestation with lower levels of bilirubin. The two groups were followed for an average of 7 and 6 years, respectively.

The researchers confirmed 3 cases of kernicterus based on the brain MRIs of children with cerebral palsy. All 3 cases had occurred in newborns with the highest levels of bilirubin. But further study revealed that each child had 2 or more risk factors for brain damage.

”We found that cerebral palsy consistent with kernicterus did not occur in a single infant with high bilirubin without the presence of additional risk factors for neurotoxicity, such as prematurity, sepsis, and the hereditary blood disorder G6PD deficiency,” said Michael W. Kuzniewicz, MD, of UCSF. “This was the case even in infants with very high bilirubin.”

In 2004, the AAP published a guideline for treating infants whose bilirubin remained high despite phototherapy. It recommended exchange transfusions based on the level of bilirubin, the age of the infant, and other risk factors for brain damage.

“Our study was the first to evaluate how well the exchange transfusion guidelines predicted risk of cerebral palsy and kernicterus in babies with jaundice,” said Thomas B. Newman, MD, of UCSF.

“It was reassuring that brain injury due to high bilirubin was rare and that only those infants whose levels were well above exchange transfusion guidelines developed kernicterus.”

“Based on our study, the current guidelines for when to perform exchange transfusions have been quite successful in preventing kernicterus,” Dr Wu added. “However, our study also raises the question whether the threshold for exchange transfusion could be higher for infants with high bilirubin levels who are otherwise healthy and who have no other risk factors for brain injury.”

This is especially important, she noted, because exchange transfusions pose risks such as blood clot formation, blood pressure instability, bleeding, and changes in blood chemistry.

Dr Wu and her colleagues described this research in JAMA Pediatrics.

Sleeping newborn

Credit: Vera Kratochvil

Results of a new study indicate that current guidelines for exchange transfusions in infants can successfully prevent kernicterus, a rare and life-threatening type of cerebral palsy triggered by escalating bilirubin that injures the brain.

However, the research also showed that only infants whose levels of bilirubin were well above the level for exchange transfusion actually developed kernicterus. And those infants all had additional risk factors for brain damage.

This suggests perhaps the threshold for exchange transfusion could safely be raised for infants with high bilirubin levels who have no other risk factors for brain injury, according to Yvonne W. Wu, MD, of the University of California, San Francisco (UCSF).

Dr Wu and her colleagues evaluated the health records of two groups of infants selected from 525,409 births. The children had been born at 15 hospitals within the Kaiser Permanente Northern California region from 1995 through 2011.

One group comprised 1833 newborns with levels of bilirubin above the level at which the American Academy of Pediatrics (AAP) recommends exchange transfusions.

The second group was made up of 104,716 randomly sampled newborns, born at at least 35 weeks’ gestation with lower levels of bilirubin. The two groups were followed for an average of 7 and 6 years, respectively.

The researchers confirmed 3 cases of kernicterus based on the brain MRIs of children with cerebral palsy. All 3 cases had occurred in newborns with the highest levels of bilirubin. But further study revealed that each child had 2 or more risk factors for brain damage.

”We found that cerebral palsy consistent with kernicterus did not occur in a single infant with high bilirubin without the presence of additional risk factors for neurotoxicity, such as prematurity, sepsis, and the hereditary blood disorder G6PD deficiency,” said Michael W. Kuzniewicz, MD, of UCSF. “This was the case even in infants with very high bilirubin.”

In 2004, the AAP published a guideline for treating infants whose bilirubin remained high despite phototherapy. It recommended exchange transfusions based on the level of bilirubin, the age of the infant, and other risk factors for brain damage.

“Our study was the first to evaluate how well the exchange transfusion guidelines predicted risk of cerebral palsy and kernicterus in babies with jaundice,” said Thomas B. Newman, MD, of UCSF.

“It was reassuring that brain injury due to high bilirubin was rare and that only those infants whose levels were well above exchange transfusion guidelines developed kernicterus.”

“Based on our study, the current guidelines for when to perform exchange transfusions have been quite successful in preventing kernicterus,” Dr Wu added. “However, our study also raises the question whether the threshold for exchange transfusion could be higher for infants with high bilirubin levels who are otherwise healthy and who have no other risk factors for brain injury.”

This is especially important, she noted, because exchange transfusions pose risks such as blood clot formation, blood pressure instability, bleeding, and changes in blood chemistry.

Dr Wu and her colleagues described this research in JAMA Pediatrics.

Cord blood donation

Credit: NHS

The US Food and Drug Administration (FDA) has granted orphan designation to a cord blood product called NiCord for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and myelodysplastic syndromes (MDS).

NiCord consists of cells from a single cord blood unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.

The FDA’s orphan drug designation for NiCord coincides with the positive opinion of the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products regarding NiCord as a treatment for AML. Gamida Cell, the company developing NiCord, intends to file for orphan drug status with the EMA for other indications as well.

“Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell’s commercialization plans a major step further, as both afford significant advantages,” said Yael Margolin, President and CEO of Gamida Cell.

Orphan drug designation provides various regulatory and economic benefits, including 7 years of market exclusivity upon product approval in the US and 10 years in the European Union.

Trials of NiCord

NiCord is currently being tested in a phase 1/2 study as an investigational therapeutic treatment for hematologic malignancies. In this study, NiCord is being used as the sole stem cell source.

In a previous study, presented at the 11th Annual International Cord Blood Symposium, researchers transplanted a NiCord unit and an unmanipulated cord blood unit in patients with ALL, AML, MDS, HL, or non-Hodgkin lymphoma.

A majority of patients in this small, phase 1/2 study achieved early platelet and neutrophil engraftment. And, in some patients, that engraftment persisted for 2 years.

Eight of the 11 patients enrolled achieved engraftment with the NiCord unit, and 2 engrafted with the unmanipulated cord blood unit. One patient had primary graft failure.

There were no adverse events attributable to the NiCord unit, but 4 patients developed grade 1-2 acute GVHD, and 1 patient developed limited chronic GVHD.

For more information on NiCord, visit the Gamida Cell website.

Cord blood donation

Credit: NHS

The US Food and Drug Administration (FDA) has granted orphan designation to a cord blood product called NiCord for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and myelodysplastic syndromes (MDS).

NiCord consists of cells from a single cord blood unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.

The FDA’s orphan drug designation for NiCord coincides with the positive opinion of the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products regarding NiCord as a treatment for AML. Gamida Cell, the company developing NiCord, intends to file for orphan drug status with the EMA for other indications as well.

“Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell’s commercialization plans a major step further, as both afford significant advantages,” said Yael Margolin, President and CEO of Gamida Cell.

Orphan drug designation provides various regulatory and economic benefits, including 7 years of market exclusivity upon product approval in the US and 10 years in the European Union.

Trials of NiCord

NiCord is currently being tested in a phase 1/2 study as an investigational therapeutic treatment for hematologic malignancies. In this study, NiCord is being used as the sole stem cell source.

In a previous study, presented at the 11th Annual International Cord Blood Symposium, researchers transplanted a NiCord unit and an unmanipulated cord blood unit in patients with ALL, AML, MDS, HL, or non-Hodgkin lymphoma.

A majority of patients in this small, phase 1/2 study achieved early platelet and neutrophil engraftment. And, in some patients, that engraftment persisted for 2 years.

Eight of the 11 patients enrolled achieved engraftment with the NiCord unit, and 2 engrafted with the unmanipulated cord blood unit. One patient had primary graft failure.

There were no adverse events attributable to the NiCord unit, but 4 patients developed grade 1-2 acute GVHD, and 1 patient developed limited chronic GVHD.

For more information on NiCord, visit the Gamida Cell website.

Cord blood donation

Credit: NHS

The US Food and Drug Administration (FDA) has granted orphan designation to a cord blood product called NiCord for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and myelodysplastic syndromes (MDS).

NiCord consists of cells from a single cord blood unit cultured in nicotinamide—a vitamin B derivative—and cytokines that are typically used for expansion—thrombopoietin, interleukin 6, FLT3 ligand, and stem cell factor.

The FDA’s orphan drug designation for NiCord coincides with the positive opinion of the European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products regarding NiCord as a treatment for AML. Gamida Cell, the company developing NiCord, intends to file for orphan drug status with the EMA for other indications as well.

“Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell’s commercialization plans a major step further, as both afford significant advantages,” said Yael Margolin, President and CEO of Gamida Cell.

Orphan drug designation provides various regulatory and economic benefits, including 7 years of market exclusivity upon product approval in the US and 10 years in the European Union.

Trials of NiCord

NiCord is currently being tested in a phase 1/2 study as an investigational therapeutic treatment for hematologic malignancies. In this study, NiCord is being used as the sole stem cell source.

In a previous study, presented at the 11th Annual International Cord Blood Symposium, researchers transplanted a NiCord unit and an unmanipulated cord blood unit in patients with ALL, AML, MDS, HL, or non-Hodgkin lymphoma.

A majority of patients in this small, phase 1/2 study achieved early platelet and neutrophil engraftment. And, in some patients, that engraftment persisted for 2 years.

Eight of the 11 patients enrolled achieved engraftment with the NiCord unit, and 2 engrafted with the unmanipulated cord blood unit. One patient had primary graft failure.

There were no adverse events attributable to the NiCord unit, but 4 patients developed grade 1-2 acute GVHD, and 1 patient developed limited chronic GVHD.

For more information on NiCord, visit the Gamida Cell website.

Blood for transfusion

Credit: UAB Hospital

The process of pathogen inactivation does not compromise the quality of red blood cells (RBCs), results of a phase 3 study suggest.

Researchers compared untreated RBCs and RBCs treated with the INTERCEPT Blood System, a pathogen inactivation system.

The two sets of RBCs, which were given to cardiovascular surgery patients with acute anemia, had comparable hemoglobin content and in vitro quality, according to Cerus Corporation, makers of the INTERCEPT system.

Cerus recently announced these results, and the researchers plan to submit data from this study for presentation at upcoming scientific congresses.

“In our prior US phase 3 study in a similar patient population, INTERCEPT red cells were shown to be noninferior to control red cells in 148 patients based on a composite endpoint of myocardial infarction, renal failure, and death,” said Laurence Corash, MD, Cerus’s chief medical officer.

“The data from the recent phase 3 study met the European criteria for red blood cell components for transfusion and demonstrated sufficient hemoglobin content and in vitro quality compared to untreated red cells. We believe that the successful results from this study, combined with data from the prior phase 3 study, support the safety and efficacy of the INTERCEPT RBC system for CE Mark registration.”

In the current trial, researchers evaluated the efficacy of the INTERCEPT system to process RBCs with quality and mean hemoglobin content (> 40 g) suitable to support transfusion according to the European Directorate for the Quality of Medicines.

The blood components were transfused in 51 cardiovascular surgery patients at 2 German trial sites. Patients undergoing procedures for coronary artery bypass grafting, valve repair, or combined procedures received transfusions during a 7-day treatment period that included the day of surgery and 6 days post-operatively.

The patients received either INTERCEPT-treated RBCs or control RBCs not treated for pathogen inactivation. RBC components for both clinical sites were manufactured at the German Red Cross blood center in Frankfurt, and the RBCs were stored for up to 35 days prior to transfusion.

The primary endpoint was the equivalence of mean hemoglobin content between INTERCEPT-treated RBCs and conventional RBCs. The mean hemoglobin content of INTERCEPT-treated RBCs on day 35 of storage (53.1 g) fell within the protocol-specified 5g equivalence margin, when compared to control RBCs (55.8 g).

The secondary efficacy endpoints also suggested INTERCEPT-treated RBCs were suitable for transfusion based on mean hematocrit of 60.4% (acceptance range: 55%-70%) and mean end-of-storage hemolysis rate of 0.28% (acceptance range < 0.8%).

There were no statistical differences in the adverse event rates between recipients of INTERCEPT-treated RBCs and control RBCs. There were no clinically relevant trends in severe or serious treatment-related adverse events by system organ class.

The observed adverse events were within the expected spectrum of comorbidity and mortality for patients of similar age and with advanced cardiovascular diseases undergoing cardiovascular surgery requiring RBC transfusion. And none of the patients exhibited an immune response to INTERCEPT-treated RBCs.

Blood for transfusion

Credit: UAB Hospital

The process of pathogen inactivation does not compromise the quality of red blood cells (RBCs), results of a phase 3 study suggest.

Researchers compared untreated RBCs and RBCs treated with the INTERCEPT Blood System, a pathogen inactivation system.

The two sets of RBCs, which were given to cardiovascular surgery patients with acute anemia, had comparable hemoglobin content and in vitro quality, according to Cerus Corporation, makers of the INTERCEPT system.

Cerus recently announced these results, and the researchers plan to submit data from this study for presentation at upcoming scientific congresses.

“In our prior US phase 3 study in a similar patient population, INTERCEPT red cells were shown to be noninferior to control red cells in 148 patients based on a composite endpoint of myocardial infarction, renal failure, and death,” said Laurence Corash, MD, Cerus’s chief medical officer.

“The data from the recent phase 3 study met the European criteria for red blood cell components for transfusion and demonstrated sufficient hemoglobin content and in vitro quality compared to untreated red cells. We believe that the successful results from this study, combined with data from the prior phase 3 study, support the safety and efficacy of the INTERCEPT RBC system for CE Mark registration.”

In the current trial, researchers evaluated the efficacy of the INTERCEPT system to process RBCs with quality and mean hemoglobin content (> 40 g) suitable to support transfusion according to the European Directorate for the Quality of Medicines.

The blood components were transfused in 51 cardiovascular surgery patients at 2 German trial sites. Patients undergoing procedures for coronary artery bypass grafting, valve repair, or combined procedures received transfusions during a 7-day treatment period that included the day of surgery and 6 days post-operatively.

The patients received either INTERCEPT-treated RBCs or control RBCs not treated for pathogen inactivation. RBC components for both clinical sites were manufactured at the German Red Cross blood center in Frankfurt, and the RBCs were stored for up to 35 days prior to transfusion.

The primary endpoint was the equivalence of mean hemoglobin content between INTERCEPT-treated RBCs and conventional RBCs. The mean hemoglobin content of INTERCEPT-treated RBCs on day 35 of storage (53.1 g) fell within the protocol-specified 5g equivalence margin, when compared to control RBCs (55.8 g).

The secondary efficacy endpoints also suggested INTERCEPT-treated RBCs were suitable for transfusion based on mean hematocrit of 60.4% (acceptance range: 55%-70%) and mean end-of-storage hemolysis rate of 0.28% (acceptance range < 0.8%).

There were no statistical differences in the adverse event rates between recipients of INTERCEPT-treated RBCs and control RBCs. There were no clinically relevant trends in severe or serious treatment-related adverse events by system organ class.

The observed adverse events were within the expected spectrum of comorbidity and mortality for patients of similar age and with advanced cardiovascular diseases undergoing cardiovascular surgery requiring RBC transfusion. And none of the patients exhibited an immune response to INTERCEPT-treated RBCs.

Blood for transfusion

Credit: UAB Hospital

The process of pathogen inactivation does not compromise the quality of red blood cells (RBCs), results of a phase 3 study suggest.

Researchers compared untreated RBCs and RBCs treated with the INTERCEPT Blood System, a pathogen inactivation system.

The two sets of RBCs, which were given to cardiovascular surgery patients with acute anemia, had comparable hemoglobin content and in vitro quality, according to Cerus Corporation, makers of the INTERCEPT system.

Cerus recently announced these results, and the researchers plan to submit data from this study for presentation at upcoming scientific congresses.

“In our prior US phase 3 study in a similar patient population, INTERCEPT red cells were shown to be noninferior to control red cells in 148 patients based on a composite endpoint of myocardial infarction, renal failure, and death,” said Laurence Corash, MD, Cerus’s chief medical officer.

“The data from the recent phase 3 study met the European criteria for red blood cell components for transfusion and demonstrated sufficient hemoglobin content and in vitro quality compared to untreated red cells. We believe that the successful results from this study, combined with data from the prior phase 3 study, support the safety and efficacy of the INTERCEPT RBC system for CE Mark registration.”

In the current trial, researchers evaluated the efficacy of the INTERCEPT system to process RBCs with quality and mean hemoglobin content (> 40 g) suitable to support transfusion according to the European Directorate for the Quality of Medicines.

The blood components were transfused in 51 cardiovascular surgery patients at 2 German trial sites. Patients undergoing procedures for coronary artery bypass grafting, valve repair, or combined procedures received transfusions during a 7-day treatment period that included the day of surgery and 6 days post-operatively.

The patients received either INTERCEPT-treated RBCs or control RBCs not treated for pathogen inactivation. RBC components for both clinical sites were manufactured at the German Red Cross blood center in Frankfurt, and the RBCs were stored for up to 35 days prior to transfusion.

The primary endpoint was the equivalence of mean hemoglobin content between INTERCEPT-treated RBCs and conventional RBCs. The mean hemoglobin content of INTERCEPT-treated RBCs on day 35 of storage (53.1 g) fell within the protocol-specified 5g equivalence margin, when compared to control RBCs (55.8 g).

The secondary efficacy endpoints also suggested INTERCEPT-treated RBCs were suitable for transfusion based on mean hematocrit of 60.4% (acceptance range: 55%-70%) and mean end-of-storage hemolysis rate of 0.28% (acceptance range < 0.8%).

There were no statistical differences in the adverse event rates between recipients of INTERCEPT-treated RBCs and control RBCs. There were no clinically relevant trends in severe or serious treatment-related adverse events by system organ class.

The observed adverse events were within the expected spectrum of comorbidity and mortality for patients of similar age and with advanced cardiovascular diseases undergoing cardiovascular surgery requiring RBC transfusion. And none of the patients exhibited an immune response to INTERCEPT-treated RBCs.

Blood for transfusion

Photo by Elisa Amendola

The US Food and Drug Administration (FDA) is recommending a change to the policy that prevents men who have sex with men (MSM) from donating blood, according to FDA Commissioner Margaret A. Hamburg.

The FDA would like to allow MSM to donate blood if they have abstained from sexual contact for 1 year.

The agency intends to issue a draft guidance recommending this policy change in 2015. The guidance will be open for public comment.

In a prepared statement, Hamburg said that, over the past few years, the FDA and other government agencies have carefully considered the scientific evidence relevant to the blood donor deferral policy for MSM.

This review, as well as the recommendations of advisory committees to the US Department of Health and Human Services (HHS) and the FDA, has prompted the FDA to recommend the change.

“This recommended change is consistent with the recommendation of an independent expert advisory panel, the HHS Advisory Committee on Blood and Tissue Safety and Availability, and will better align the deferral period with that of other men and women at increased risk for HIV infection,” Hamburg said.

“Additionally, in collaboration with the NIH’s National Heart Lung and Blood Institute (NHLBI), the FDA has already taken steps to implement a national blood surveillance system that will help the agency monitor the effect of a policy change and further help to ensure the continued safety of the blood supply.”

Blood for transfusion

Photo by Elisa Amendola

The US Food and Drug Administration (FDA) is recommending a change to the policy that prevents men who have sex with men (MSM) from donating blood, according to FDA Commissioner Margaret A. Hamburg.

The FDA would like to allow MSM to donate blood if they have abstained from sexual contact for 1 year.

The agency intends to issue a draft guidance recommending this policy change in 2015. The guidance will be open for public comment.

In a prepared statement, Hamburg said that, over the past few years, the FDA and other government agencies have carefully considered the scientific evidence relevant to the blood donor deferral policy for MSM.

This review, as well as the recommendations of advisory committees to the US Department of Health and Human Services (HHS) and the FDA, has prompted the FDA to recommend the change.

“This recommended change is consistent with the recommendation of an independent expert advisory panel, the HHS Advisory Committee on Blood and Tissue Safety and Availability, and will better align the deferral period with that of other men and women at increased risk for HIV infection,” Hamburg said.

“Additionally, in collaboration with the NIH’s National Heart Lung and Blood Institute (NHLBI), the FDA has already taken steps to implement a national blood surveillance system that will help the agency monitor the effect of a policy change and further help to ensure the continued safety of the blood supply.”

Blood for transfusion

Photo by Elisa Amendola

The US Food and Drug Administration (FDA) is recommending a change to the policy that prevents men who have sex with men (MSM) from donating blood, according to FDA Commissioner Margaret A. Hamburg.

The FDA would like to allow MSM to donate blood if they have abstained from sexual contact for 1 year.

The agency intends to issue a draft guidance recommending this policy change in 2015. The guidance will be open for public comment.

In a prepared statement, Hamburg said that, over the past few years, the FDA and other government agencies have carefully considered the scientific evidence relevant to the blood donor deferral policy for MSM.

This review, as well as the recommendations of advisory committees to the US Department of Health and Human Services (HHS) and the FDA, has prompted the FDA to recommend the change.

“This recommended change is consistent with the recommendation of an independent expert advisory panel, the HHS Advisory Committee on Blood and Tissue Safety and Availability, and will better align the deferral period with that of other men and women at increased risk for HIV infection,” Hamburg said.

“Additionally, in collaboration with the NIH’s National Heart Lung and Blood Institute (NHLBI), the FDA has already taken steps to implement a national blood surveillance system that will help the agency monitor the effect of a policy change and further help to ensure the continued safety of the blood supply.”

The US Food and Drug Administration (FDA) has approved the INTERCEPT Blood System for platelets, the first system of its kind to be approved in the US.

It is used to inactivate viruses, bacteria, spirochetes, parasites, and leukocytes in apheresis platelet components.

This can reduce the risk of transfusion-transmitted infection and, potentially, transfusion-associated graft-vs-host disease, although the system cannot inactivate all pathogens.

Certain non-enveloped viruses (such as HAV, HEV, B19, and poliovirus) and Bacillus cereus spores have demonstrated resistance to the INTERCEPT process.

Earlier this week, the FDA approved the INTERCEPT Blood System for plasma (also the first system of its kind to gain FDA approval).

The platelet and plasma systems use the same illumination device, the same active compound (amotosalen), and very similar production steps.

The INTERCEPT systems target a basic biological difference between the therapeutic components of blood. Platelets, plasma, and red blood cells do not require functional DNA or RNA for therapeutic efficacy. But pathogens and white blood cells do, in order to transmit infection.

The INTERCEPT systems use a proprietary molecule that, when activated by UVA light, binds to and blocks the replication of DNA and RNA, preventing nucleic acid replication and rendering the pathogen inactive.

The INTERCEPT Blood System for platelets has been approved in Europe since 2002 and is currently used in 20 countries.

The system was recently made available in the US and its territories under an investigational device exemption study to reduce the risk of transfusion-transmitted dengue and Chikungunya viruses, both of which are epidemic in the Caribbean region, including Puerto Rico, as well as sporadically in the southern US. No approved blood bank screening tests are available for either virus.

Researchers have evaluated INTERCEPT-processed platelets in 10 controlled clinical trials. Details on these trials can be found in the package insert.

The US Food and Drug Administration (FDA) has approved the INTERCEPT Blood System for platelets, the first system of its kind to be approved in the US.

It is used to inactivate viruses, bacteria, spirochetes, parasites, and leukocytes in apheresis platelet components.

This can reduce the risk of transfusion-transmitted infection and, potentially, transfusion-associated graft-vs-host disease, although the system cannot inactivate all pathogens.

Certain non-enveloped viruses (such as HAV, HEV, B19, and poliovirus) and Bacillus cereus spores have demonstrated resistance to the INTERCEPT process.

Earlier this week, the FDA approved the INTERCEPT Blood System for plasma (also the first system of its kind to gain FDA approval).

The platelet and plasma systems use the same illumination device, the same active compound (amotosalen), and very similar production steps.

The INTERCEPT systems target a basic biological difference between the therapeutic components of blood. Platelets, plasma, and red blood cells do not require functional DNA or RNA for therapeutic efficacy. But pathogens and white blood cells do, in order to transmit infection.

The INTERCEPT systems use a proprietary molecule that, when activated by UVA light, binds to and blocks the replication of DNA and RNA, preventing nucleic acid replication and rendering the pathogen inactive.

The INTERCEPT Blood System for platelets has been approved in Europe since 2002 and is currently used in 20 countries.

The system was recently made available in the US and its territories under an investigational device exemption study to reduce the risk of transfusion-transmitted dengue and Chikungunya viruses, both of which are epidemic in the Caribbean region, including Puerto Rico, as well as sporadically in the southern US. No approved blood bank screening tests are available for either virus.

Researchers have evaluated INTERCEPT-processed platelets in 10 controlled clinical trials. Details on these trials can be found in the package insert.

The US Food and Drug Administration (FDA) has approved the INTERCEPT Blood System for platelets, the first system of its kind to be approved in the US.

It is used to inactivate viruses, bacteria, spirochetes, parasites, and leukocytes in apheresis platelet components.

This can reduce the risk of transfusion-transmitted infection and, potentially, transfusion-associated graft-vs-host disease, although the system cannot inactivate all pathogens.

Certain non-enveloped viruses (such as HAV, HEV, B19, and poliovirus) and Bacillus cereus spores have demonstrated resistance to the INTERCEPT process.

Earlier this week, the FDA approved the INTERCEPT Blood System for plasma (also the first system of its kind to gain FDA approval).

The platelet and plasma systems use the same illumination device, the same active compound (amotosalen), and very similar production steps.

The INTERCEPT systems target a basic biological difference between the therapeutic components of blood. Platelets, plasma, and red blood cells do not require functional DNA or RNA for therapeutic efficacy. But pathogens and white blood cells do, in order to transmit infection.

The INTERCEPT systems use a proprietary molecule that, when activated by UVA light, binds to and blocks the replication of DNA and RNA, preventing nucleic acid replication and rendering the pathogen inactive.

The INTERCEPT Blood System for platelets has been approved in Europe since 2002 and is currently used in 20 countries.

The system was recently made available in the US and its territories under an investigational device exemption study to reduce the risk of transfusion-transmitted dengue and Chikungunya viruses, both of which are epidemic in the Caribbean region, including Puerto Rico, as well as sporadically in the southern US. No approved blood bank screening tests are available for either virus.

Researchers have evaluated INTERCEPT-processed platelets in 10 controlled clinical trials. Details on these trials can be found in the package insert.

Blood for transfusion

Credit: Elise Amendola

Two studies shed new light on the prevalence of transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) in the US.

The research showed that postoperative TRALI is significantly underreported and more common than previously thought, with an overall rate of 1.4%.

And the rate of TACO is on the decline, but the risk to surgical patients remains high, at 4%, similar to previous TACO estimates in non-surgical patients.

“An accurate understanding of the risks associated with blood transfusions is essential when determining the safety and appropriateness of transfusion therapies for patients,” said Daryl Kor, MD, senior author of both studies and an associate professor at Mayo Clinic in Rochester, Minnesota.

“Our research provides a greater awareness of the incidence of TRALI and TACO in surgical patients, a population that has been perhaps underrepresented in studies in this area. We believe this to be an important first step in our efforts to prevent these life-threatening transfusion complications.”

Dr Kor and his colleagues described this research in Anesthesiology alongside a related editorial.

In the two retrospective studies, the researchers examined the incidence of TRALI in 3379 patients and TACO in 4070 patients who received blood transfusions during non-cardiac surgery under general anesthesia in 2004 and 2011.

Using a novel algorithm, followed by a rigorous manual review, the team performed a detailed epidemiologic analysis for both complications.

The first study showed that TRALI occurred in 1.4% of surgical patients, with higher rates in specific surgical populations such as those having surgery inside the chest cavity, on major blood vessels, or having an organ transplant. Patients who received larger volumes of blood were also at increased risk.

Previous studies investigating TRALI rates have primarily focused on the critically ill and reported variable incidence rates. Many studies have reported incidences between 0.02% and 0.05%.

The second study showed that TACO occurs in 4.3% of surgical patients, with higher rates associated with increased volume of blood transfused, advanced age, and total intraoperative fluid balance. Again, patients having surgery inside the chest cavity, on major blood vessels, or organ transplants were at the greatest risk.

The study also revealed that the rate of TACO decreased significantly from 2004 to 2011—from 5.5% to 3%. This decline was not fully explained by any of the patient or transfusion characteristics evaluated in the study.

The researchers said future studies are needed to further explore which mechanisms and risk factors are responsible for TACO and TRALI.

“With improved understanding of the mechanisms underlying TRALI and TACO, we may be able to refine the novel electronic algorithms used to screen patients in these studies,” Dr Kor said. “Ultimately, we hope to develop a real-time prediction model for these complications so that we can identify those at greatest risk and perhaps implement strategies to reduce this risk.”

Blood for transfusion

Credit: Elise Amendola

Two studies shed new light on the prevalence of transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) in the US.

The research showed that postoperative TRALI is significantly underreported and more common than previously thought, with an overall rate of 1.4%.

And the rate of TACO is on the decline, but the risk to surgical patients remains high, at 4%, similar to previous TACO estimates in non-surgical patients.

“An accurate understanding of the risks associated with blood transfusions is essential when determining the safety and appropriateness of transfusion therapies for patients,” said Daryl Kor, MD, senior author of both studies and an associate professor at Mayo Clinic in Rochester, Minnesota.

“Our research provides a greater awareness of the incidence of TRALI and TACO in surgical patients, a population that has been perhaps underrepresented in studies in this area. We believe this to be an important first step in our efforts to prevent these life-threatening transfusion complications.”

Dr Kor and his colleagues described this research in Anesthesiology alongside a related editorial.

In the two retrospective studies, the researchers examined the incidence of TRALI in 3379 patients and TACO in 4070 patients who received blood transfusions during non-cardiac surgery under general anesthesia in 2004 and 2011.

Using a novel algorithm, followed by a rigorous manual review, the team performed a detailed epidemiologic analysis for both complications.

The first study showed that TRALI occurred in 1.4% of surgical patients, with higher rates in specific surgical populations such as those having surgery inside the chest cavity, on major blood vessels, or having an organ transplant. Patients who received larger volumes of blood were also at increased risk.

Previous studies investigating TRALI rates have primarily focused on the critically ill and reported variable incidence rates. Many studies have reported incidences between 0.02% and 0.05%.

The second study showed that TACO occurs in 4.3% of surgical patients, with higher rates associated with increased volume of blood transfused, advanced age, and total intraoperative fluid balance. Again, patients having surgery inside the chest cavity, on major blood vessels, or organ transplants were at the greatest risk.

The study also revealed that the rate of TACO decreased significantly from 2004 to 2011—from 5.5% to 3%. This decline was not fully explained by any of the patient or transfusion characteristics evaluated in the study.

The researchers said future studies are needed to further explore which mechanisms and risk factors are responsible for TACO and TRALI.

“With improved understanding of the mechanisms underlying TRALI and TACO, we may be able to refine the novel electronic algorithms used to screen patients in these studies,” Dr Kor said. “Ultimately, we hope to develop a real-time prediction model for these complications so that we can identify those at greatest risk and perhaps implement strategies to reduce this risk.”

Blood for transfusion

Credit: Elise Amendola

Two studies shed new light on the prevalence of transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) in the US.

The research showed that postoperative TRALI is significantly underreported and more common than previously thought, with an overall rate of 1.4%.

And the rate of TACO is on the decline, but the risk to surgical patients remains high, at 4%, similar to previous TACO estimates in non-surgical patients.

“An accurate understanding of the risks associated with blood transfusions is essential when determining the safety and appropriateness of transfusion therapies for patients,” said Daryl Kor, MD, senior author of both studies and an associate professor at Mayo Clinic in Rochester, Minnesota.

“Our research provides a greater awareness of the incidence of TRALI and TACO in surgical patients, a population that has been perhaps underrepresented in studies in this area. We believe this to be an important first step in our efforts to prevent these life-threatening transfusion complications.”

Dr Kor and his colleagues described this research in Anesthesiology alongside a related editorial.

In the two retrospective studies, the researchers examined the incidence of TRALI in 3379 patients and TACO in 4070 patients who received blood transfusions during non-cardiac surgery under general anesthesia in 2004 and 2011.

Using a novel algorithm, followed by a rigorous manual review, the team performed a detailed epidemiologic analysis for both complications.

The first study showed that TRALI occurred in 1.4% of surgical patients, with higher rates in specific surgical populations such as those having surgery inside the chest cavity, on major blood vessels, or having an organ transplant. Patients who received larger volumes of blood were also at increased risk.

Previous studies investigating TRALI rates have primarily focused on the critically ill and reported variable incidence rates. Many studies have reported incidences between 0.02% and 0.05%.

The second study showed that TACO occurs in 4.3% of surgical patients, with higher rates associated with increased volume of blood transfused, advanced age, and total intraoperative fluid balance. Again, patients having surgery inside the chest cavity, on major blood vessels, or organ transplants were at the greatest risk.

The study also revealed that the rate of TACO decreased significantly from 2004 to 2011—from 5.5% to 3%. This decline was not fully explained by any of the patient or transfusion characteristics evaluated in the study.

The researchers said future studies are needed to further explore which mechanisms and risk factors are responsible for TACO and TRALI.

“With improved understanding of the mechanisms underlying TRALI and TACO, we may be able to refine the novel electronic algorithms used to screen patients in these studies,” Dr Kor said. “Ultimately, we hope to develop a real-time prediction model for these complications so that we can identify those at greatest risk and perhaps implement strategies to reduce this risk.”

Blood for transfusion

Credit: UAB Hospital

Long-term mortality is not affected by the amount of blood a patient receives following surgery, according to research published in The Lancet.

Investigators compared a liberal transfusion strategy, in which patients received blood to maintain a hemoglobin level at 100 g/L or higher, and a restrictive strategy, in which patients received blood when hemoglobin levels were lower than 80 g/L or if they had symptoms of anemia.

And, at about 3 years of follow-up, there was no difference in mortality between the two groups.

Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School in New Jersey, and his colleagues conducted this research, analyzing data from the FOCUS trial, which included patients from 47 hospitals in the US and Canada.

The trial enrolled 2016 adults age 50 and older, with a history of or risk factors for cardiovascular disease, who had postoperative hemoglobin concentrations lower than 100 g/L within 3 days of surgery to repair a hip fracture.

Patients were randomized by a central telephone system to the liberal (n=1007) or restrictive (n=1009) transfusion groups. The investigators analyzed the long-term mortality of these patients, which was established by linking participants to national death registries in the US and Canada.

The results revealed no difference in mortality from cardiovascular disease, cancer, or severe infection due to the amount of the blood given after surgery.

This supports the initial results of the FOCUS trial, which Dr Carson and his colleagues published in NEJM in 2011 and which demonstrated the safety of fewer transfusions in the short-term.

For the current analysis, the median duration of follow-up was 3.1 years. Eight hundred and forty-one patients (42%) died during that time—432 in the liberal transfusion group and 409 in the restrictive transfusion group. This difference was not statistically significant, with a hazard ratio of 1.09 and a P value of 0.21.

“There has been a steady decline in the amount of blood in transfusions given to patients in the past 3 to 5 years,” Dr Carson noted. “I think it is very reassuring that we have found that using less blood is okay, not just from a short-term perspective, but also a long-term perspective.”

Medical experts had worried that larger amounts of transfused blood might suppress immune function—which could lead to death from infection or cancer—or that smaller transfusions might worsen a patient’s chronic heart disease by depriving the heart of oxygen and other nutrients that it might have absorbed by pumping more blood.

But in both instances, Dr Carson and his colleagues found no difference in long-term death rates, regardless of the number of transfusions.

Dr Carson noted that there are health conditions, such as heart attacks, where the effects of the two transfusion strategies are less certain. Preliminary evidence suggests heart attack patients need more blood, not less. But additional studies are needed to confirm that.

Blood for transfusion

Credit: UAB Hospital

Long-term mortality is not affected by the amount of blood a patient receives following surgery, according to research published in The Lancet.

Investigators compared a liberal transfusion strategy, in which patients received blood to maintain a hemoglobin level at 100 g/L or higher, and a restrictive strategy, in which patients received blood when hemoglobin levels were lower than 80 g/L or if they had symptoms of anemia.

And, at about 3 years of follow-up, there was no difference in mortality between the two groups.

Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School in New Jersey, and his colleagues conducted this research, analyzing data from the FOCUS trial, which included patients from 47 hospitals in the US and Canada.

The trial enrolled 2016 adults age 50 and older, with a history of or risk factors for cardiovascular disease, who had postoperative hemoglobin concentrations lower than 100 g/L within 3 days of surgery to repair a hip fracture.

Patients were randomized by a central telephone system to the liberal (n=1007) or restrictive (n=1009) transfusion groups. The investigators analyzed the long-term mortality of these patients, which was established by linking participants to national death registries in the US and Canada.

The results revealed no difference in mortality from cardiovascular disease, cancer, or severe infection due to the amount of the blood given after surgery.

This supports the initial results of the FOCUS trial, which Dr Carson and his colleagues published in NEJM in 2011 and which demonstrated the safety of fewer transfusions in the short-term.

For the current analysis, the median duration of follow-up was 3.1 years. Eight hundred and forty-one patients (42%) died during that time—432 in the liberal transfusion group and 409 in the restrictive transfusion group. This difference was not statistically significant, with a hazard ratio of 1.09 and a P value of 0.21.

“There has been a steady decline in the amount of blood in transfusions given to patients in the past 3 to 5 years,” Dr Carson noted. “I think it is very reassuring that we have found that using less blood is okay, not just from a short-term perspective, but also a long-term perspective.”

Medical experts had worried that larger amounts of transfused blood might suppress immune function—which could lead to death from infection or cancer—or that smaller transfusions might worsen a patient’s chronic heart disease by depriving the heart of oxygen and other nutrients that it might have absorbed by pumping more blood.

But in both instances, Dr Carson and his colleagues found no difference in long-term death rates, regardless of the number of transfusions.

Dr Carson noted that there are health conditions, such as heart attacks, where the effects of the two transfusion strategies are less certain. Preliminary evidence suggests heart attack patients need more blood, not less. But additional studies are needed to confirm that.

Blood for transfusion

Credit: UAB Hospital

Long-term mortality is not affected by the amount of blood a patient receives following surgery, according to research published in The Lancet.

Investigators compared a liberal transfusion strategy, in which patients received blood to maintain a hemoglobin level at 100 g/L or higher, and a restrictive strategy, in which patients received blood when hemoglobin levels were lower than 80 g/L or if they had symptoms of anemia.

And, at about 3 years of follow-up, there was no difference in mortality between the two groups.

Jeffrey L. Carson, MD, of Robert Wood Johnson Medical School in New Jersey, and his colleagues conducted this research, analyzing data from the FOCUS trial, which included patients from 47 hospitals in the US and Canada.

The trial enrolled 2016 adults age 50 and older, with a history of or risk factors for cardiovascular disease, who had postoperative hemoglobin concentrations lower than 100 g/L within 3 days of surgery to repair a hip fracture.

Patients were randomized by a central telephone system to the liberal (n=1007) or restrictive (n=1009) transfusion groups. The investigators analyzed the long-term mortality of these patients, which was established by linking participants to national death registries in the US and Canada.

The results revealed no difference in mortality from cardiovascular disease, cancer, or severe infection due to the amount of the blood given after surgery.

This supports the initial results of the FOCUS trial, which Dr Carson and his colleagues published in NEJM in 2011 and which demonstrated the safety of fewer transfusions in the short-term.

For the current analysis, the median duration of follow-up was 3.1 years. Eight hundred and forty-one patients (42%) died during that time—432 in the liberal transfusion group and 409 in the restrictive transfusion group. This difference was not statistically significant, with a hazard ratio of 1.09 and a P value of 0.21.

“There has been a steady decline in the amount of blood in transfusions given to patients in the past 3 to 5 years,” Dr Carson noted. “I think it is very reassuring that we have found that using less blood is okay, not just from a short-term perspective, but also a long-term perspective.”

Medical experts had worried that larger amounts of transfused blood might suppress immune function—which could lead to death from infection or cancer—or that smaller transfusions might worsen a patient’s chronic heart disease by depriving the heart of oxygen and other nutrients that it might have absorbed by pumping more blood.

But in both instances, Dr Carson and his colleagues found no difference in long-term death rates, regardless of the number of transfusions.

Dr Carson noted that there are health conditions, such as heart attacks, where the effects of the two transfusion strategies are less certain. Preliminary evidence suggests heart attack patients need more blood, not less. But additional studies are needed to confirm that.

The US Food and Drug Administration (FDA) has approved the INTERCEPT Blood System for plasma, the first pathogen inactivation system for the preparation of plasma to reduce the risk of transfusion-transmitted infections.

The system inactivates pathogens through a photochemical process involving controlled exposure to ultraviolet light and the chemical amotosalen. The plasma is then purified to remove the chemical and its byproducts.

The INTERCEPT Blood System for plasma can be used to reduce pathogens in plasma derived from whole blood and plasma obtained by apheresis.

The system has proven effective in reducing a broad spectrum of viruses, bacteria, spirochetes, and parasites. However, there is no pathogen inactivation process that has been shown to eliminate all pathogens. Certain viruses (eg, human parvovirus B19) and spores formed by certain bacteria are known to be resistant to the INTERCEPT process.

“The approval of devices like the INTERCEPT Blood System allows blood establishments to prepare plasma that carries a lower risk of transmitting infectious pathogens through transfusion,” said Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research.

The INTERCEPT Blood System for plasma, which is marketed by Cerus Corporation, has been approved in Europe since 2006 and was recently made available in the US under an Investigational Device Exemption study. The system is being used to prepare Ebola convalescent plasma for transfusion into acutely infected patients.

Clinical studies

Researchers investigated the safety and effectiveness of plasma prepared with the INTERCEPT Blood System in 6 clinical studies and 2 post-marketing studies.

The research showed no significant difference in coagulation factor activity between INTERCEPT-processed plasma and unprocessed fresh-frozen plasma (FFP) in healthy subjects.

There was no significant difference in prothrombin time or activated partial thromboplastin time between INTERCEPT-processed plasma and FFP in patients with coagulation factor deficiencies or in patients with liver disease.

In patients who underwent liver transplant, there was no significant difference in plasma use, hepatic artery thrombosis, or mortality whether patients received INTERCEPT-process plasma or FFP.

In a prospective, phase 3 trial and a retrospective study of patients with thrombotic thrombocytopenic purpura (TTP), there was no significant difference in the percentage of patients who achieved remission with INTERCEPT-treated plasma or FFP.

Adverse events

In a post-marketing study*, researchers analyzed acute transfusion reactions (ATRs) after 57,171 INTERCEPT-processed plasma components were transfused to 9669 patients. Thirty-two subjects (0.3%) experienced an ATR after 41 transfusion episodes (0.2%), including 5 subjects (0.05%) who experienced an ATR after more than 1 transfusion.

Six ATRs were considered serious and possibly or probably related to transfusion. There were 3 instances of allergic reaction or symptoms of allergic reaction (eg, rash, tachycardia, hypotension, respiratory symptoms, and chills), 2 cases of fluid overload, and 1 report of respiratory distress.

In another hemovigilance study, researchers compared the frequency of adverse events due to any of the 4 types of FFP prepared and delivered by the French Blood Establishment over a 10-year period—methylene blue, amotosalen, quarantine, and solvent-detergent.

The study showed that all types of FFP were associated with a low rate of adverse events. Per 10,000 deliveries, there were 7.14 events in the quarantine group, 4.86 in the solvent-detergent group, 4.16 in the amotosalen group, and 1.05 in the methylene blue group.

The package insert of the INTERCEPT Blood System for plasma warns that amotosalen-treated plasma has been associated with cardiac events.

In the aforementioned prospective trial of the system in patients with TTP, 5 patients treated with INTERCEPT-processed plasma and none with conventional plasma had adverse events in the cardiac system organ class.

This included angina pectoris (n=3), cardiac arrest (n=1), bradycardia (n=1), tachycardia (n=1), and sinus arrhythmia (n=1). None of the events resulted in documented myocardial infarction or death.

*Results have been updated since publication.

The US Food and Drug Administration (FDA) has approved the INTERCEPT Blood System for plasma, the first pathogen inactivation system for the preparation of plasma to reduce the risk of transfusion-transmitted infections.

The system inactivates pathogens through a photochemical process involving controlled exposure to ultraviolet light and the chemical amotosalen. The plasma is then purified to remove the chemical and its byproducts.

The INTERCEPT Blood System for plasma can be used to reduce pathogens in plasma derived from whole blood and plasma obtained by apheresis.

The system has proven effective in reducing a broad spectrum of viruses, bacteria, spirochetes, and parasites. However, there is no pathogen inactivation process that has been shown to eliminate all pathogens. Certain viruses (eg, human parvovirus B19) and spores formed by certain bacteria are known to be resistant to the INTERCEPT process.

“The approval of devices like the INTERCEPT Blood System allows blood establishments to prepare plasma that carries a lower risk of transmitting infectious pathogens through transfusion,” said Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research.

The INTERCEPT Blood System for plasma, which is marketed by Cerus Corporation, has been approved in Europe since 2006 and was recently made available in the US under an Investigational Device Exemption study. The system is being used to prepare Ebola convalescent plasma for transfusion into acutely infected patients.

Clinical studies

Researchers investigated the safety and effectiveness of plasma prepared with the INTERCEPT Blood System in 6 clinical studies and 2 post-marketing studies.

The research showed no significant difference in coagulation factor activity between INTERCEPT-processed plasma and unprocessed fresh-frozen plasma (FFP) in healthy subjects.

There was no significant difference in prothrombin time or activated partial thromboplastin time between INTERCEPT-processed plasma and FFP in patients with coagulation factor deficiencies or in patients with liver disease.

In patients who underwent liver transplant, there was no significant difference in plasma use, hepatic artery thrombosis, or mortality whether patients received INTERCEPT-process plasma or FFP.

In a prospective, phase 3 trial and a retrospective study of patients with thrombotic thrombocytopenic purpura (TTP), there was no significant difference in the percentage of patients who achieved remission with INTERCEPT-treated plasma or FFP.

Adverse events

In a post-marketing study*, researchers analyzed acute transfusion reactions (ATRs) after 57,171 INTERCEPT-processed plasma components were transfused to 9669 patients. Thirty-two subjects (0.3%) experienced an ATR after 41 transfusion episodes (0.2%), including 5 subjects (0.05%) who experienced an ATR after more than 1 transfusion.

Six ATRs were considered serious and possibly or probably related to transfusion. There were 3 instances of allergic reaction or symptoms of allergic reaction (eg, rash, tachycardia, hypotension, respiratory symptoms, and chills), 2 cases of fluid overload, and 1 report of respiratory distress.

In another hemovigilance study, researchers compared the frequency of adverse events due to any of the 4 types of FFP prepared and delivered by the French Blood Establishment over a 10-year period—methylene blue, amotosalen, quarantine, and solvent-detergent.

The study showed that all types of FFP were associated with a low rate of adverse events. Per 10,000 deliveries, there were 7.14 events in the quarantine group, 4.86 in the solvent-detergent group, 4.16 in the amotosalen group, and 1.05 in the methylene blue group.

The package insert of the INTERCEPT Blood System for plasma warns that amotosalen-treated plasma has been associated with cardiac events.

In the aforementioned prospective trial of the system in patients with TTP, 5 patients treated with INTERCEPT-processed plasma and none with conventional plasma had adverse events in the cardiac system organ class.

This included angina pectoris (n=3), cardiac arrest (n=1), bradycardia (n=1), tachycardia (n=1), and sinus arrhythmia (n=1). None of the events resulted in documented myocardial infarction or death.

*Results have been updated since publication.

The US Food and Drug Administration (FDA) has approved the INTERCEPT Blood System for plasma, the first pathogen inactivation system for the preparation of plasma to reduce the risk of transfusion-transmitted infections.

The system inactivates pathogens through a photochemical process involving controlled exposure to ultraviolet light and the chemical amotosalen. The plasma is then purified to remove the chemical and its byproducts.

The INTERCEPT Blood System for plasma can be used to reduce pathogens in plasma derived from whole blood and plasma obtained by apheresis.

The system has proven effective in reducing a broad spectrum of viruses, bacteria, spirochetes, and parasites. However, there is no pathogen inactivation process that has been shown to eliminate all pathogens. Certain viruses (eg, human parvovirus B19) and spores formed by certain bacteria are known to be resistant to the INTERCEPT process.

“The approval of devices like the INTERCEPT Blood System allows blood establishments to prepare plasma that carries a lower risk of transmitting infectious pathogens through transfusion,” said Karen Midthun, MD, director of the FDA’s Center for Biologics Evaluation and Research.

The INTERCEPT Blood System for plasma, which is marketed by Cerus Corporation, has been approved in Europe since 2006 and was recently made available in the US under an Investigational Device Exemption study. The system is being used to prepare Ebola convalescent plasma for transfusion into acutely infected patients.

Clinical studies

Researchers investigated the safety and effectiveness of plasma prepared with the INTERCEPT Blood System in 6 clinical studies and 2 post-marketing studies.

The research showed no significant difference in coagulation factor activity between INTERCEPT-processed plasma and unprocessed fresh-frozen plasma (FFP) in healthy subjects.

There was no significant difference in prothrombin time or activated partial thromboplastin time between INTERCEPT-processed plasma and FFP in patients with coagulation factor deficiencies or in patients with liver disease.

In patients who underwent liver transplant, there was no significant difference in plasma use, hepatic artery thrombosis, or mortality whether patients received INTERCEPT-process plasma or FFP.

In a prospective, phase 3 trial and a retrospective study of patients with thrombotic thrombocytopenic purpura (TTP), there was no significant difference in the percentage of patients who achieved remission with INTERCEPT-treated plasma or FFP.

Adverse events

In a post-marketing study*, researchers analyzed acute transfusion reactions (ATRs) after 57,171 INTERCEPT-processed plasma components were transfused to 9669 patients. Thirty-two subjects (0.3%) experienced an ATR after 41 transfusion episodes (0.2%), including 5 subjects (0.05%) who experienced an ATR after more than 1 transfusion.

Six ATRs were considered serious and possibly or probably related to transfusion. There were 3 instances of allergic reaction or symptoms of allergic reaction (eg, rash, tachycardia, hypotension, respiratory symptoms, and chills), 2 cases of fluid overload, and 1 report of respiratory distress.

In another hemovigilance study, researchers compared the frequency of adverse events due to any of the 4 types of FFP prepared and delivered by the French Blood Establishment over a 10-year period—methylene blue, amotosalen, quarantine, and solvent-detergent.

The study showed that all types of FFP were associated with a low rate of adverse events. Per 10,000 deliveries, there were 7.14 events in the quarantine group, 4.86 in the solvent-detergent group, 4.16 in the amotosalen group, and 1.05 in the methylene blue group.

The package insert of the INTERCEPT Blood System for plasma warns that amotosalen-treated plasma has been associated with cardiac events.

In the aforementioned prospective trial of the system in patients with TTP, 5 patients treated with INTERCEPT-processed plasma and none with conventional plasma had adverse events in the cardiac system organ class.

This included angina pectoris (n=3), cardiac arrest (n=1), bradycardia (n=1), tachycardia (n=1), and sinus arrhythmia (n=1). None of the events resulted in documented myocardial infarction or death.

*Results have been updated since publication.