Blood Banking

Blood for transfusion

Photo by Elise Amendola

Certain methods of manufacturing red cell concentrates (RCCs) may be less damaging than others, according to research published in Vox Sanguinis.

The study showed that damage-associated molecular patterns (DAMPs) in stored blood differ according to the process and materials used to collect or prepare RCCs for transfusion.

Researchers believe this discovery could help reduce adverse reactions in transfusion recipients and potentially impact how blood is collected around the world.

To conduct this study, the researchers compared RCCs collected at blood donation centers in the US and Canada. The team examined the influence of manufacturing methods on the levels of mitochondrial (mt) DNA and extracellular vesicle (EV) DAMPs in RCCs.

“Working with the American team at Blood Systems Research Institute was key to this research because of the wide variations in blood manufacturing processes present in the US,” said Jason Acker, PhD, of Canadian Blood Services’ Centre for Innovation in Edmonton, Alberta.

“In countries like Canada, where there is a national blood service, manufacturing methods are largely standardized, so it is difficult to compare various methods. But blood collection in the US is characterized by dozens of independent blood centers that use a variety of available manufacturing processes. The Americans provided the variations we needed to measure red cell damage and to ascertain whether it can be attributed to different manufacturing methods.”

Manufacturing methods

The researchers evaluated 87 RCCs prepared using 9 different methods, outlined in the following table.

Results

For all RCCs, the researchers assessed the levels of mtDNA and the number and cell of origin of EVs on storage days 5 and 42.

They observed a 100-fold difference in mtDNA levels between the different methods.

The highest mtDNA levels were in the non-leukoreduced RCCs, followed by the MCS+ and Trima apheresis RCCs. The mean levels were 5.3 x 10⁵ copies/µL, 1.3 x 10⁵ copies/µL, and 1.2 x 10⁵ copies/µL, respectively.

The lowest mtDNA levels were seen with the semi-automated methods. The mean levels ranged from 3.8 x 10³ copies/µL to 5.9 x 10³ copies/µL.

The researchers also saw a 10-fold difference in EV levels between the different methods.

The team detected red blood cell-derived CD235a+ EVs in fresh RCCs, which increased in most RCCs over the storage period (but not for FenBC and MCS+).

Platelet-derived CD41a+ EVs were highest in non-leukoreduced and Trima RCCs and did not change significantly during storage.

White blood cell-derived CD11b+ and CD66b+ EVs were low in most RCCs (though not in Trima and FenMAN-non-LR RCCs), and their levels did not significantly change during storage.

White blood cell-derived CD14+ EVs were negligible in fresh RCCs but increased in several RCCs during storage (FenMAN, Alyx, MCS+, and Trima).

Next steps

“There must be more testing of the apheresis collections equipment, blood bags, leukoreduction filters, and other variations in manufacturing methods to determine what single element or combination of elements in the various red blood cell manufacturing processes result in high levels of DAMPs and why,” said Michael Busch, MD, PhD, of Blood Systems Research Institute in San Francisco, California.

“We also need to understand how mitochondrial DAMPs are involved in adverse reactions to red blood cell transfusions,” added Sonia Bakkour, PhD, also from Blood Systems Research Institute.

“Some recently published studies on platelet components link high levels of mitochondrial DAMPs to adverse transfusion reactions. We need to see if DAMPs have similar adverse effects on recipients of red blood cell transfusions.”

“We think that our research could lead to finding the best way to manufacture red blood cells,” Dr Acker noted.

“It’s clear now that manufacturing methods matter. We . . . are keen to explore what’s in the blood bag or in the filters or in the tubing, for example, that can be minimized or eliminated, improving the outcome in patients who receive blood transfusions.”

Blood for transfusion

Photo by Elise Amendola

Certain methods of manufacturing red cell concentrates (RCCs) may be less damaging than others, according to research published in Vox Sanguinis.

The study showed that damage-associated molecular patterns (DAMPs) in stored blood differ according to the process and materials used to collect or prepare RCCs for transfusion.

Researchers believe this discovery could help reduce adverse reactions in transfusion recipients and potentially impact how blood is collected around the world.

To conduct this study, the researchers compared RCCs collected at blood donation centers in the US and Canada. The team examined the influence of manufacturing methods on the levels of mitochondrial (mt) DNA and extracellular vesicle (EV) DAMPs in RCCs.

“Working with the American team at Blood Systems Research Institute was key to this research because of the wide variations in blood manufacturing processes present in the US,” said Jason Acker, PhD, of Canadian Blood Services’ Centre for Innovation in Edmonton, Alberta.

“In countries like Canada, where there is a national blood service, manufacturing methods are largely standardized, so it is difficult to compare various methods. But blood collection in the US is characterized by dozens of independent blood centers that use a variety of available manufacturing processes. The Americans provided the variations we needed to measure red cell damage and to ascertain whether it can be attributed to different manufacturing methods.”

Manufacturing methods

The researchers evaluated 87 RCCs prepared using 9 different methods, outlined in the following table.

Results

For all RCCs, the researchers assessed the levels of mtDNA and the number and cell of origin of EVs on storage days 5 and 42.

They observed a 100-fold difference in mtDNA levels between the different methods.

The highest mtDNA levels were in the non-leukoreduced RCCs, followed by the MCS+ and Trima apheresis RCCs. The mean levels were 5.3 x 10⁵ copies/µL, 1.3 x 10⁵ copies/µL, and 1.2 x 10⁵ copies/µL, respectively.

The lowest mtDNA levels were seen with the semi-automated methods. The mean levels ranged from 3.8 x 10³ copies/µL to 5.9 x 10³ copies/µL.

The researchers also saw a 10-fold difference in EV levels between the different methods.

The team detected red blood cell-derived CD235a+ EVs in fresh RCCs, which increased in most RCCs over the storage period (but not for FenBC and MCS+).

Platelet-derived CD41a+ EVs were highest in non-leukoreduced and Trima RCCs and did not change significantly during storage.

White blood cell-derived CD11b+ and CD66b+ EVs were low in most RCCs (though not in Trima and FenMAN-non-LR RCCs), and their levels did not significantly change during storage.

White blood cell-derived CD14+ EVs were negligible in fresh RCCs but increased in several RCCs during storage (FenMAN, Alyx, MCS+, and Trima).

Next steps

“There must be more testing of the apheresis collections equipment, blood bags, leukoreduction filters, and other variations in manufacturing methods to determine what single element or combination of elements in the various red blood cell manufacturing processes result in high levels of DAMPs and why,” said Michael Busch, MD, PhD, of Blood Systems Research Institute in San Francisco, California.

“We also need to understand how mitochondrial DAMPs are involved in adverse reactions to red blood cell transfusions,” added Sonia Bakkour, PhD, also from Blood Systems Research Institute.

“Some recently published studies on platelet components link high levels of mitochondrial DAMPs to adverse transfusion reactions. We need to see if DAMPs have similar adverse effects on recipients of red blood cell transfusions.”

“We think that our research could lead to finding the best way to manufacture red blood cells,” Dr Acker noted.

“It’s clear now that manufacturing methods matter. We . . . are keen to explore what’s in the blood bag or in the filters or in the tubing, for example, that can be minimized or eliminated, improving the outcome in patients who receive blood transfusions.”

Blood for transfusion

Photo by Elise Amendola

Certain methods of manufacturing red cell concentrates (RCCs) may be less damaging than others, according to research published in Vox Sanguinis.

The study showed that damage-associated molecular patterns (DAMPs) in stored blood differ according to the process and materials used to collect or prepare RCCs for transfusion.

Researchers believe this discovery could help reduce adverse reactions in transfusion recipients and potentially impact how blood is collected around the world.

To conduct this study, the researchers compared RCCs collected at blood donation centers in the US and Canada. The team examined the influence of manufacturing methods on the levels of mitochondrial (mt) DNA and extracellular vesicle (EV) DAMPs in RCCs.

“Working with the American team at Blood Systems Research Institute was key to this research because of the wide variations in blood manufacturing processes present in the US,” said Jason Acker, PhD, of Canadian Blood Services’ Centre for Innovation in Edmonton, Alberta.

“In countries like Canada, where there is a national blood service, manufacturing methods are largely standardized, so it is difficult to compare various methods. But blood collection in the US is characterized by dozens of independent blood centers that use a variety of available manufacturing processes. The Americans provided the variations we needed to measure red cell damage and to ascertain whether it can be attributed to different manufacturing methods.”

Manufacturing methods

The researchers evaluated 87 RCCs prepared using 9 different methods, outlined in the following table.

Results

For all RCCs, the researchers assessed the levels of mtDNA and the number and cell of origin of EVs on storage days 5 and 42.

They observed a 100-fold difference in mtDNA levels between the different methods.

The highest mtDNA levels were in the non-leukoreduced RCCs, followed by the MCS+ and Trima apheresis RCCs. The mean levels were 5.3 x 10⁵ copies/µL, 1.3 x 10⁵ copies/µL, and 1.2 x 10⁵ copies/µL, respectively.

The lowest mtDNA levels were seen with the semi-automated methods. The mean levels ranged from 3.8 x 10³ copies/µL to 5.9 x 10³ copies/µL.

The researchers also saw a 10-fold difference in EV levels between the different methods.

The team detected red blood cell-derived CD235a+ EVs in fresh RCCs, which increased in most RCCs over the storage period (but not for FenBC and MCS+).

Platelet-derived CD41a+ EVs were highest in non-leukoreduced and Trima RCCs and did not change significantly during storage.

White blood cell-derived CD11b+ and CD66b+ EVs were low in most RCCs (though not in Trima and FenMAN-non-LR RCCs), and their levels did not significantly change during storage.

White blood cell-derived CD14+ EVs were negligible in fresh RCCs but increased in several RCCs during storage (FenMAN, Alyx, MCS+, and Trima).

Next steps

“There must be more testing of the apheresis collections equipment, blood bags, leukoreduction filters, and other variations in manufacturing methods to determine what single element or combination of elements in the various red blood cell manufacturing processes result in high levels of DAMPs and why,” said Michael Busch, MD, PhD, of Blood Systems Research Institute in San Francisco, California.

“We also need to understand how mitochondrial DAMPs are involved in adverse reactions to red blood cell transfusions,” added Sonia Bakkour, PhD, also from Blood Systems Research Institute.

“Some recently published studies on platelet components link high levels of mitochondrial DAMPs to adverse transfusion reactions. We need to see if DAMPs have similar adverse effects on recipients of red blood cell transfusions.”

“We think that our research could lead to finding the best way to manufacture red blood cells,” Dr Acker noted.

“It’s clear now that manufacturing methods matter. We . . . are keen to explore what’s in the blood bag or in the filters or in the tubing, for example, that can be minimized or eliminated, improving the outcome in patients who receive blood transfusions.”

Megakaryocytes

in the bone marrow

Researchers in the UK have developed a new method of producing megakaryocytes from human pluripotent stem cells (hPSCs).

The team said their method generated large quantities of functional megakaryocytes that produced functional platelets.

They believe this work brings us one step closer to manufacturing platelets for transfusion.

The research was published in Nature Communications.

“Making megakaryocytes and platelets from stem cells for transfusion has been a long-standing challenge because of the sheer numbers we need to produce to make a single unit for transfusion,” said study author Cedric Ghevaert, MD, PhD, of the University of Cambridge and NHS Blood and Transplant in Cambridge, UK.

“We have found a way to ‘rewire’ the stem cells to make them become megakaryocytes a lot faster and more efficiently. It is a major step forward towards our goal to one day make blood cells in the laboratory to transfuse to patients.”

Dr Ghevaert and his colleagues employed a “forward programming” strategy in which 3 transcription factors—GATA1, FLI1, and TAL1—were used drive the differentiation of hPSCs into megakaryocytes.

The team said the forward-programmed megakaryocytes matured into platelet-producing cells that could be cryopreserved, maintained, and amplified in vitro for more than 90 days. The average yield was 200,000 megakaryocytes per hPSC.

The researchers generated platelets from the forward-programmed megakaryocytes via culture. And tests suggested these platelets were functionally similar to donor-derived platelets.

“The success of this research team in producing megakaryocytes in the laboratory has paved the way for the ultimate goal—manufacturing platelets for transfusion,” said Edwin Massey, MBChB, associate medical director for diagnostic and therapeutic services at NHS Blood and Transplant, who was not involved in this research.

“It will, however, be many years before a process for the large-scale production of platelets is developed. Donated platelets will still be needed by patients for the foreseeable future, either as part of a blood donation or by dedicated platelet donation using a machine collection process.”

Megakaryocytes

in the bone marrow

Researchers in the UK have developed a new method of producing megakaryocytes from human pluripotent stem cells (hPSCs).

The team said their method generated large quantities of functional megakaryocytes that produced functional platelets.

They believe this work brings us one step closer to manufacturing platelets for transfusion.

The research was published in Nature Communications.

“Making megakaryocytes and platelets from stem cells for transfusion has been a long-standing challenge because of the sheer numbers we need to produce to make a single unit for transfusion,” said study author Cedric Ghevaert, MD, PhD, of the University of Cambridge and NHS Blood and Transplant in Cambridge, UK.

“We have found a way to ‘rewire’ the stem cells to make them become megakaryocytes a lot faster and more efficiently. It is a major step forward towards our goal to one day make blood cells in the laboratory to transfuse to patients.”

Dr Ghevaert and his colleagues employed a “forward programming” strategy in which 3 transcription factors—GATA1, FLI1, and TAL1—were used drive the differentiation of hPSCs into megakaryocytes.

The team said the forward-programmed megakaryocytes matured into platelet-producing cells that could be cryopreserved, maintained, and amplified in vitro for more than 90 days. The average yield was 200,000 megakaryocytes per hPSC.

The researchers generated platelets from the forward-programmed megakaryocytes via culture. And tests suggested these platelets were functionally similar to donor-derived platelets.

“The success of this research team in producing megakaryocytes in the laboratory has paved the way for the ultimate goal—manufacturing platelets for transfusion,” said Edwin Massey, MBChB, associate medical director for diagnostic and therapeutic services at NHS Blood and Transplant, who was not involved in this research.

“It will, however, be many years before a process for the large-scale production of platelets is developed. Donated platelets will still be needed by patients for the foreseeable future, either as part of a blood donation or by dedicated platelet donation using a machine collection process.”

Megakaryocytes

in the bone marrow

Researchers in the UK have developed a new method of producing megakaryocytes from human pluripotent stem cells (hPSCs).

The team said their method generated large quantities of functional megakaryocytes that produced functional platelets.

They believe this work brings us one step closer to manufacturing platelets for transfusion.

The research was published in Nature Communications.

“Making megakaryocytes and platelets from stem cells for transfusion has been a long-standing challenge because of the sheer numbers we need to produce to make a single unit for transfusion,” said study author Cedric Ghevaert, MD, PhD, of the University of Cambridge and NHS Blood and Transplant in Cambridge, UK.

“We have found a way to ‘rewire’ the stem cells to make them become megakaryocytes a lot faster and more efficiently. It is a major step forward towards our goal to one day make blood cells in the laboratory to transfuse to patients.”

Dr Ghevaert and his colleagues employed a “forward programming” strategy in which 3 transcription factors—GATA1, FLI1, and TAL1—were used drive the differentiation of hPSCs into megakaryocytes.

The team said the forward-programmed megakaryocytes matured into platelet-producing cells that could be cryopreserved, maintained, and amplified in vitro for more than 90 days. The average yield was 200,000 megakaryocytes per hPSC.

The researchers generated platelets from the forward-programmed megakaryocytes via culture. And tests suggested these platelets were functionally similar to donor-derived platelets.

“The success of this research team in producing megakaryocytes in the laboratory has paved the way for the ultimate goal—manufacturing platelets for transfusion,” said Edwin Massey, MBChB, associate medical director for diagnostic and therapeutic services at NHS Blood and Transplant, who was not involved in this research.

“It will, however, be many years before a process for the large-scale production of platelets is developed. Donated platelets will still be needed by patients for the foreseeable future, either as part of a blood donation or by dedicated platelet donation using a machine collection process.”

The US Food and Drug Administration (FDA) is allowing the use of an investigational test to screen blood donations for Zika virus.

The test, known as the cobas® Zika test, has not been granted FDA clearance or approval, but it may be used under an investigational new drug application protocol for screening donated blood in areas with active, mosquito-borne transmission of Zika virus.

This means the test can be used by US blood screening laboratories, but the laboratories will need to be enrolled in and contracted into a clinical trial for the test, as specified and agreed with the FDA’s Center for Biologics Evaluation and Research.

By authorizing use of the cobas® Zika test, the FDA is allowing blood establishments in Puerto Rico—a US territory with local, mosquito-borne transmission of the Zika virus—to resume collecting donations of whole blood and blood components.

“The availability of an investigational test to screen donated blood for Zika virus is an important step forward in maintaining the safety of the nation’s blood supply, especially for those US territories already experiencing active transmission,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

“In the future, should Zika virus transmission occur in other areas, blood collection establishments will be able to continue to collect blood and use the investigational screening test, minimizing disruption to the blood supply.”

About the test

The cobas® Zika test is a qualitative in vitro nucleic acid screening test for the direct detection of Zika virus RNA in plasma specimens from individual human

blood donors.

The test is based on fully automated sample preparation (nucleic acid extraction and purification), followed by PCR amplification and detection.

The cobas® Zika test is manufactured by Roche and is intended for use with Roche’s cobas® 6800/8800 Systems.

The cobas® 6800/8800 Systems consist of the sample supply module, the transfer module, the processing module, and the analytic module. Automated data management is performed by the cobas® 6800/8800 software, which assigns test results for all tests as non-reactive, reactive, or invalid.

“The cobas® Zika test has been specifically designed utilizing the generic cobas® omni Utility Channel on the cobas® 6800/8800 Systems,” said Roland Diggelmann, chief operating officer of Roche Diagnostics.

“These fully automated, high-volume systems provide solutions for blood services to detect the virus and ensure that potentially infected blood units are not made available for transfusion.”

Test availability

Initially, the cobas® Zika test will be deployed to screen blood donations collected locally in Puerto Rico. It is expected that this testing will enable the

reinstatement of the blood services in Puerto Rico and reduce the reliance of blood importation from other areas in the US.

The second stage of deployment for the cobas® Zika test will be to prepare for screening of blood donations collected by blood services in the southern US.

In addition, Roche said it is working with regulators around the world to determine the path forward to implement the cobas® Zika test for blood screening.

Implications for Puerto Rico

On February 16, the FDA issued a guidance for US blood establishments to reduce the risk of transfusion-transmitted Zika virus. In the guidance, the FDA recommended that areas with active transmission of Zika virus obtain whole blood and blood components from areas without active transmission of the virus.

As a result, local blood collection in Puerto Rico was suspended. On March 7, the Department of Health and Human Services announced that it arranged for shipments of blood products from the continental US to Puerto Rico.

The FDA guidance also states that establishments in areas with active Zika transmission may collect locally if a licensed or investigational test for screening donated blood is available.

Once screening of blood donations for Zika virus using the cobas® Zika test begins, blood establishments in Puerto Rico may resume collecting donations of whole blood and blood components. However, the FDA’s recommendations for Zika blood donor deferrals remain in place.

The US Food and Drug Administration (FDA) is allowing the use of an investigational test to screen blood donations for Zika virus.

The test, known as the cobas® Zika test, has not been granted FDA clearance or approval, but it may be used under an investigational new drug application protocol for screening donated blood in areas with active, mosquito-borne transmission of Zika virus.

This means the test can be used by US blood screening laboratories, but the laboratories will need to be enrolled in and contracted into a clinical trial for the test, as specified and agreed with the FDA’s Center for Biologics Evaluation and Research.

By authorizing use of the cobas® Zika test, the FDA is allowing blood establishments in Puerto Rico—a US territory with local, mosquito-borne transmission of the Zika virus—to resume collecting donations of whole blood and blood components.

“The availability of an investigational test to screen donated blood for Zika virus is an important step forward in maintaining the safety of the nation’s blood supply, especially for those US territories already experiencing active transmission,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

“In the future, should Zika virus transmission occur in other areas, blood collection establishments will be able to continue to collect blood and use the investigational screening test, minimizing disruption to the blood supply.”

About the test

The cobas® Zika test is a qualitative in vitro nucleic acid screening test for the direct detection of Zika virus RNA in plasma specimens from individual human

blood donors.

The test is based on fully automated sample preparation (nucleic acid extraction and purification), followed by PCR amplification and detection.

The cobas® Zika test is manufactured by Roche and is intended for use with Roche’s cobas® 6800/8800 Systems.

The cobas® 6800/8800 Systems consist of the sample supply module, the transfer module, the processing module, and the analytic module. Automated data management is performed by the cobas® 6800/8800 software, which assigns test results for all tests as non-reactive, reactive, or invalid.

“The cobas® Zika test has been specifically designed utilizing the generic cobas® omni Utility Channel on the cobas® 6800/8800 Systems,” said Roland Diggelmann, chief operating officer of Roche Diagnostics.

“These fully automated, high-volume systems provide solutions for blood services to detect the virus and ensure that potentially infected blood units are not made available for transfusion.”

Test availability

Initially, the cobas® Zika test will be deployed to screen blood donations collected locally in Puerto Rico. It is expected that this testing will enable the

reinstatement of the blood services in Puerto Rico and reduce the reliance of blood importation from other areas in the US.

The second stage of deployment for the cobas® Zika test will be to prepare for screening of blood donations collected by blood services in the southern US.

In addition, Roche said it is working with regulators around the world to determine the path forward to implement the cobas® Zika test for blood screening.

Implications for Puerto Rico

On February 16, the FDA issued a guidance for US blood establishments to reduce the risk of transfusion-transmitted Zika virus. In the guidance, the FDA recommended that areas with active transmission of Zika virus obtain whole blood and blood components from areas without active transmission of the virus.

As a result, local blood collection in Puerto Rico was suspended. On March 7, the Department of Health and Human Services announced that it arranged for shipments of blood products from the continental US to Puerto Rico.

The FDA guidance also states that establishments in areas with active Zika transmission may collect locally if a licensed or investigational test for screening donated blood is available.

Once screening of blood donations for Zika virus using the cobas® Zika test begins, blood establishments in Puerto Rico may resume collecting donations of whole blood and blood components. However, the FDA’s recommendations for Zika blood donor deferrals remain in place.

The US Food and Drug Administration (FDA) is allowing the use of an investigational test to screen blood donations for Zika virus.

The test, known as the cobas® Zika test, has not been granted FDA clearance or approval, but it may be used under an investigational new drug application protocol for screening donated blood in areas with active, mosquito-borne transmission of Zika virus.

This means the test can be used by US blood screening laboratories, but the laboratories will need to be enrolled in and contracted into a clinical trial for the test, as specified and agreed with the FDA’s Center for Biologics Evaluation and Research.

By authorizing use of the cobas® Zika test, the FDA is allowing blood establishments in Puerto Rico—a US territory with local, mosquito-borne transmission of the Zika virus—to resume collecting donations of whole blood and blood components.

“The availability of an investigational test to screen donated blood for Zika virus is an important step forward in maintaining the safety of the nation’s blood supply, especially for those US territories already experiencing active transmission,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

“In the future, should Zika virus transmission occur in other areas, blood collection establishments will be able to continue to collect blood and use the investigational screening test, minimizing disruption to the blood supply.”

About the test

The cobas® Zika test is a qualitative in vitro nucleic acid screening test for the direct detection of Zika virus RNA in plasma specimens from individual human

blood donors.

The test is based on fully automated sample preparation (nucleic acid extraction and purification), followed by PCR amplification and detection.

The cobas® Zika test is manufactured by Roche and is intended for use with Roche’s cobas® 6800/8800 Systems.

The cobas® 6800/8800 Systems consist of the sample supply module, the transfer module, the processing module, and the analytic module. Automated data management is performed by the cobas® 6800/8800 software, which assigns test results for all tests as non-reactive, reactive, or invalid.

“The cobas® Zika test has been specifically designed utilizing the generic cobas® omni Utility Channel on the cobas® 6800/8800 Systems,” said Roland Diggelmann, chief operating officer of Roche Diagnostics.

“These fully automated, high-volume systems provide solutions for blood services to detect the virus and ensure that potentially infected blood units are not made available for transfusion.”

Test availability

Initially, the cobas® Zika test will be deployed to screen blood donations collected locally in Puerto Rico. It is expected that this testing will enable the

reinstatement of the blood services in Puerto Rico and reduce the reliance of blood importation from other areas in the US.

The second stage of deployment for the cobas® Zika test will be to prepare for screening of blood donations collected by blood services in the southern US.

In addition, Roche said it is working with regulators around the world to determine the path forward to implement the cobas® Zika test for blood screening.

Implications for Puerto Rico

On February 16, the FDA issued a guidance for US blood establishments to reduce the risk of transfusion-transmitted Zika virus. In the guidance, the FDA recommended that areas with active transmission of Zika virus obtain whole blood and blood components from areas without active transmission of the virus.

As a result, local blood collection in Puerto Rico was suspended. On March 7, the Department of Health and Human Services announced that it arranged for shipments of blood products from the continental US to Puerto Rico.

The FDA guidance also states that establishments in areas with active Zika transmission may collect locally if a licensed or investigational test for screening donated blood is available.

Once screening of blood donations for Zika virus using the cobas® Zika test begins, blood establishments in Puerto Rico may resume collecting donations of whole blood and blood components. However, the FDA’s recommendations for Zika blood donor deferrals remain in place.

Blood samples

Photo by Graham Colm

In response to a request from the US Centers for Disease Control and Prevention (CDC), the US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the Trioplex Real-time RT-PCR Assay, a tool that can be used to detect Zika virus.

The assay allows doctors to tell if an individual is infected with chikungunya, dengue, or Zika virus using a single test, instead of having to perform 3 separate tests to identify the infection.

The Trioplex Real-time RT-PCR Assay can be used to detect virus RNA in serum, cerebrospinal fluid, urine, and amniotic fluid specimens.

The CDC hopes this EUA will allow the agency to more rapidly perform testing to detect acute Zika virus infection.

An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency. The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

The CDC said it will begin distributing the Trioplex Real-time RT-PCR Assay during the next 2 weeks to qualified laboratories in the Laboratory Response Network, an integrated network of domestic and international laboratories that respond to public health emergencies.

The test will not be available in US hospitals or other primary care settings.

Last month, the FDA issued an EUA for a different test used to detect the Zika virus, the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

This test was distributed to qualified laboratories in the Laboratory Response Network but was not made available in US hospitals or other primary care settings.

Blood samples

Photo by Graham Colm

In response to a request from the US Centers for Disease Control and Prevention (CDC), the US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the Trioplex Real-time RT-PCR Assay, a tool that can be used to detect Zika virus.

The assay allows doctors to tell if an individual is infected with chikungunya, dengue, or Zika virus using a single test, instead of having to perform 3 separate tests to identify the infection.

The Trioplex Real-time RT-PCR Assay can be used to detect virus RNA in serum, cerebrospinal fluid, urine, and amniotic fluid specimens.

The CDC hopes this EUA will allow the agency to more rapidly perform testing to detect acute Zika virus infection.

An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency. The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

The CDC said it will begin distributing the Trioplex Real-time RT-PCR Assay during the next 2 weeks to qualified laboratories in the Laboratory Response Network, an integrated network of domestic and international laboratories that respond to public health emergencies.

The test will not be available in US hospitals or other primary care settings.

Last month, the FDA issued an EUA for a different test used to detect the Zika virus, the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

This test was distributed to qualified laboratories in the Laboratory Response Network but was not made available in US hospitals or other primary care settings.

Blood samples

Photo by Graham Colm

In response to a request from the US Centers for Disease Control and Prevention (CDC), the US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the Trioplex Real-time RT-PCR Assay, a tool that can be used to detect Zika virus.

The assay allows doctors to tell if an individual is infected with chikungunya, dengue, or Zika virus using a single test, instead of having to perform 3 separate tests to identify the infection.

The Trioplex Real-time RT-PCR Assay can be used to detect virus RNA in serum, cerebrospinal fluid, urine, and amniotic fluid specimens.

The CDC hopes this EUA will allow the agency to more rapidly perform testing to detect acute Zika virus infection.

An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency. The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

The CDC said it will begin distributing the Trioplex Real-time RT-PCR Assay during the next 2 weeks to qualified laboratories in the Laboratory Response Network, an integrated network of domestic and international laboratories that respond to public health emergencies.

The test will not be available in US hospitals or other primary care settings.

Last month, the FDA issued an EUA for a different test used to detect the Zika virus, the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

This test was distributed to qualified laboratories in the Laboratory Response Network but was not made available in US hospitals or other primary care settings.

Blood sample

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has deemed a hospital-based test for the Zika virus “high risk,” as the test has not been cleared by the FDA.

The test was developed by scientists at Texas Children’s Hospital and Houston Methodist Hospital. It has been available at both hospitals since last month.

The FDA has requested more information on the test but has not asked the hospitals to stop using it.

According to the hospitals, the test identifies virus-specific RNA sequences to detect the Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections. And it can be performed on blood, amniotic fluid, urine, or spinal fluid.

In a letter to the hospitals, the FDA said this test appears to meet the definition of a device, as defined in section 201(h) of the Federal Food Drug and Cosmetic Act. Yet the test has not been granted premarket clearance, approval, or Emergency Use Authorization review by the FDA.

Therefore, the FDA has asked for information on the test’s design, validation, and performance characteristics. The agency said the Centers for Disease Control and Prevention (CDC) and the Centers for Medicare & Medicaid Services asked the FDA to review the science behind the test.

The FDA has not asked the hospitals to stop using the test while the review is underway, according to a statement from Texas Children’s Hospital.

Nevertheless, the Association for Molecular Pathology (AMP) said it is “concerned and disappointed” to see the FDA taking enforcement action regarding this test. The AMP said these types of tests are critical for patient care and should be made available to patients in need.

In fact, the AMP said this is an example of how FDA regulation of laboratory developed procedures would hinder patient access to vital medical services. That’s because the FDA’s Emergency Use Authorization for antibody testing at the CDC or state public health labs does not provide results in the timely fashion needed for immediate patient care.

The FDA recently issued Emergency Use Authorization for the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA), which was developed by the CDC.

The test was distributed to labs in the US and abroad, but it was not made available in US hospitals or other primary care settings.

Blood sample

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has deemed a hospital-based test for the Zika virus “high risk,” as the test has not been cleared by the FDA.

The test was developed by scientists at Texas Children’s Hospital and Houston Methodist Hospital. It has been available at both hospitals since last month.

The FDA has requested more information on the test but has not asked the hospitals to stop using it.

According to the hospitals, the test identifies virus-specific RNA sequences to detect the Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections. And it can be performed on blood, amniotic fluid, urine, or spinal fluid.

In a letter to the hospitals, the FDA said this test appears to meet the definition of a device, as defined in section 201(h) of the Federal Food Drug and Cosmetic Act. Yet the test has not been granted premarket clearance, approval, or Emergency Use Authorization review by the FDA.

Therefore, the FDA has asked for information on the test’s design, validation, and performance characteristics. The agency said the Centers for Disease Control and Prevention (CDC) and the Centers for Medicare & Medicaid Services asked the FDA to review the science behind the test.

The FDA has not asked the hospitals to stop using the test while the review is underway, according to a statement from Texas Children’s Hospital.

Nevertheless, the Association for Molecular Pathology (AMP) said it is “concerned and disappointed” to see the FDA taking enforcement action regarding this test. The AMP said these types of tests are critical for patient care and should be made available to patients in need.

In fact, the AMP said this is an example of how FDA regulation of laboratory developed procedures would hinder patient access to vital medical services. That’s because the FDA’s Emergency Use Authorization for antibody testing at the CDC or state public health labs does not provide results in the timely fashion needed for immediate patient care.

The FDA recently issued Emergency Use Authorization for the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA), which was developed by the CDC.

The test was distributed to labs in the US and abroad, but it was not made available in US hospitals or other primary care settings.

Blood sample

Photo by Juan D. Alfonso

The US Food and Drug Administration (FDA) has deemed a hospital-based test for the Zika virus “high risk,” as the test has not been cleared by the FDA.

The test was developed by scientists at Texas Children’s Hospital and Houston Methodist Hospital. It has been available at both hospitals since last month.

The FDA has requested more information on the test but has not asked the hospitals to stop using it.

According to the hospitals, the test identifies virus-specific RNA sequences to detect the Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections. And it can be performed on blood, amniotic fluid, urine, or spinal fluid.

In a letter to the hospitals, the FDA said this test appears to meet the definition of a device, as defined in section 201(h) of the Federal Food Drug and Cosmetic Act. Yet the test has not been granted premarket clearance, approval, or Emergency Use Authorization review by the FDA.

Therefore, the FDA has asked for information on the test’s design, validation, and performance characteristics. The agency said the Centers for Disease Control and Prevention (CDC) and the Centers for Medicare & Medicaid Services asked the FDA to review the science behind the test.

The FDA has not asked the hospitals to stop using the test while the review is underway, according to a statement from Texas Children’s Hospital.

Nevertheless, the Association for Molecular Pathology (AMP) said it is “concerned and disappointed” to see the FDA taking enforcement action regarding this test. The AMP said these types of tests are critical for patient care and should be made available to patients in need.

In fact, the AMP said this is an example of how FDA regulation of laboratory developed procedures would hinder patient access to vital medical services. That’s because the FDA’s Emergency Use Authorization for antibody testing at the CDC or state public health labs does not provide results in the timely fashion needed for immediate patient care.

The FDA recently issued Emergency Use Authorization for the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA), which was developed by the CDC.

The test was distributed to labs in the US and abroad, but it was not made available in US hospitals or other primary care settings.

Tranexamic acid

Photo courtesy of NIH

ORLANDO, FL—Results of a large, retrospective study suggest tranexamic acid (TXA) can reduce the need for transfusion in patients undergoing hip and knee replacement surgery without increasing the overall risk of venous thromboembolism (VTE).

However, patients treated with TXA were significantly more likely to develop deep vein thrombosis (DVT) than patients who did not receive the drug.

There was no significant difference between the treatment groups with regard to pulmonary embolism (PE).

These results were presented at the American Academy of Orthopaedic Surgeons (AAOS) 2016 Annual Meeting (abstract P101).

“[C]onflicting results have been published regarding the use of TXA in patients undergoing hip and knee replacement,” said study investigator Geoffrey Westrich, MD, of the Hospital for Special Surgery in New York, New York.

To assess the safety and efficacy of TXA in this patient population, Dr Westrich and his colleagues retrospectively reviewed the records of 4449 patients who had hip or knee replacement over a 6-month period.

There were 720 patients who received TXA topically, 636 who received TXA intravenously, and 3093 patients who did not receive the drug.

The investigators found that 9.7% of patients treated with either type of TXA received a blood transfusion, as did 22.1% of patients who were not treated with TXA.

TXA-treated patients received an average of 0.13 units of blood, compared to 0.37 units for patients in the non-TXA group.

The investigators said there was no significant difference in efficacy between topical and intravenous TXA.

“At our institution, TXA in either intravenous or topical form was effective in decreasing the amount of blood transfusions, as well as the number of units of blood transfused in primary and revision hip and knee replacement,” Dr Westrich said.

“Furthermore, when safety was evaluated, there was no statistically significant difference in blood clots in patients who received IV or topical TXA, reconfirming its safety.”

The odds of developing a hospital-acquired VTE was 1.63 among patients treated with TXA, which was not significantly higher than the odds for patients who did not receive the drug (P=0.24).

When the investigators evaluated DVT and PE separately, they found the TXA group had a significant increase in DVT (P=0.03) but not PE (P=0.94).

Tranexamic acid

Photo courtesy of NIH

ORLANDO, FL—Results of a large, retrospective study suggest tranexamic acid (TXA) can reduce the need for transfusion in patients undergoing hip and knee replacement surgery without increasing the overall risk of venous thromboembolism (VTE).

However, patients treated with TXA were significantly more likely to develop deep vein thrombosis (DVT) than patients who did not receive the drug.

There was no significant difference between the treatment groups with regard to pulmonary embolism (PE).

These results were presented at the American Academy of Orthopaedic Surgeons (AAOS) 2016 Annual Meeting (abstract P101).

“[C]onflicting results have been published regarding the use of TXA in patients undergoing hip and knee replacement,” said study investigator Geoffrey Westrich, MD, of the Hospital for Special Surgery in New York, New York.

To assess the safety and efficacy of TXA in this patient population, Dr Westrich and his colleagues retrospectively reviewed the records of 4449 patients who had hip or knee replacement over a 6-month period.

There were 720 patients who received TXA topically, 636 who received TXA intravenously, and 3093 patients who did not receive the drug.

The investigators found that 9.7% of patients treated with either type of TXA received a blood transfusion, as did 22.1% of patients who were not treated with TXA.

TXA-treated patients received an average of 0.13 units of blood, compared to 0.37 units for patients in the non-TXA group.

The investigators said there was no significant difference in efficacy between topical and intravenous TXA.

“At our institution, TXA in either intravenous or topical form was effective in decreasing the amount of blood transfusions, as well as the number of units of blood transfused in primary and revision hip and knee replacement,” Dr Westrich said.

“Furthermore, when safety was evaluated, there was no statistically significant difference in blood clots in patients who received IV or topical TXA, reconfirming its safety.”

The odds of developing a hospital-acquired VTE was 1.63 among patients treated with TXA, which was not significantly higher than the odds for patients who did not receive the drug (P=0.24).

When the investigators evaluated DVT and PE separately, they found the TXA group had a significant increase in DVT (P=0.03) but not PE (P=0.94).

Tranexamic acid

Photo courtesy of NIH

ORLANDO, FL—Results of a large, retrospective study suggest tranexamic acid (TXA) can reduce the need for transfusion in patients undergoing hip and knee replacement surgery without increasing the overall risk of venous thromboembolism (VTE).

However, patients treated with TXA were significantly more likely to develop deep vein thrombosis (DVT) than patients who did not receive the drug.

There was no significant difference between the treatment groups with regard to pulmonary embolism (PE).

These results were presented at the American Academy of Orthopaedic Surgeons (AAOS) 2016 Annual Meeting (abstract P101).

“[C]onflicting results have been published regarding the use of TXA in patients undergoing hip and knee replacement,” said study investigator Geoffrey Westrich, MD, of the Hospital for Special Surgery in New York, New York.

To assess the safety and efficacy of TXA in this patient population, Dr Westrich and his colleagues retrospectively reviewed the records of 4449 patients who had hip or knee replacement over a 6-month period.

There were 720 patients who received TXA topically, 636 who received TXA intravenously, and 3093 patients who did not receive the drug.

The investigators found that 9.7% of patients treated with either type of TXA received a blood transfusion, as did 22.1% of patients who were not treated with TXA.

TXA-treated patients received an average of 0.13 units of blood, compared to 0.37 units for patients in the non-TXA group.

The investigators said there was no significant difference in efficacy between topical and intravenous TXA.

“At our institution, TXA in either intravenous or topical form was effective in decreasing the amount of blood transfusions, as well as the number of units of blood transfused in primary and revision hip and knee replacement,” Dr Westrich said.

“Furthermore, when safety was evaluated, there was no statistically significant difference in blood clots in patients who received IV or topical TXA, reconfirming its safety.”

The odds of developing a hospital-acquired VTE was 1.63 among patients treated with TXA, which was not significantly higher than the odds for patients who did not receive the drug (P=0.24).

When the investigators evaluated DVT and PE separately, they found the TXA group had a significant increase in DVT (P=0.03) but not PE (P=0.94).

Cord blood donation

Photo courtesy of NHS

The US Food and Drug Administration (FDA) has issued a guidance document intended to help reduce the risk of Zika virus transmission via human cells, tissues, and cellular and tissue-based products (HCT/Ps).

The guidance addresses donation of HCT/Ps from both living and deceased donors, including donors of umbilical cord blood and hematopoietic stem/progenitor cells.

In this document, the FDA recommends a 6-month deferral period for most HCT/P donors who may have been exposed to the Zika virus.

The exception is donors of gestational tissues, who should be considered ineligible if they were at risk of contracting the virus at any time during their pregnancy.

The new guidance is a part of the FDA’s ongoing efforts to protect HCT/Ps and blood products from Zika virus transmission. Last month, the agency issued recommendations for reducing the risk of Zika virus transmission via blood transfusion.

There is a potential risk that Zika virus can be transmitted by HCT/Ps used as part of a medical, surgical, or reproductive procedure. HCT/Ps include products such as corneas, bone, skin, heart valves, hematopoietic stem/progenitor cells, gestational tissues such as amniotic membrane, and reproductive tissues such as semen and oocytes.

According to the Centers for Disease Control and Prevention, Zika virus can be spread by a man to his sexual partners. To date, there have been several cases of sexual transmission in the US.

Current information about Zika virus detection in semen suggests the period of deferral for HCT/P donors should be longer than the period recommended for donors of whole blood and blood components.

Therefore, the FDA has recommended that living donors of HCT/Ps be considered ineligible if they were diagnosed with Zika virus infection, were in an area with active Zika virus transmission, or had sex with a male with either of those risk factors within the past 6 months.

Donors of umbilical cord blood, placenta, or other gestational tissues should be considered ineligible if they have had any of the above risk factors at any point during their pregnancy.

Deceased donors should be considered ineligible if they were diagnosed with Zika virus infection in the past 6 months.

A deferral period of 6 months was chosen because of the limited data available on the length of time the virus can persist in all tissues. Zika virus has been detected in tissues and body fluids after the virus is no longer detectable in the blood stream and has been detected in semen possibly up to 10 weeks after the onset of symptoms.

Less evidence exists regarding the potential for transmission of Zika virus by HCT/Ps typically recovered from deceased donors. As more information becomes available, the understanding of the risks to recipients of HCT/Ps, including HCT/Ps recovered from deceased donors, may evolve.

The FDA said it will continue to monitor the situation and evaluate new information regarding the associated risks as it becomes available.

In addition, the FDA said it is prioritizing the development of blood donor screening and diagnostic tests that may be useful for identifying the presence of or recent infection with the Zika virus. The agency is prepared to evaluate investigational vaccines and therapeutics that might be developed and review technology that may help suppress populations of the mosquitoes that can spread the virus.

Cord blood donation

Photo courtesy of NHS

The US Food and Drug Administration (FDA) has issued a guidance document intended to help reduce the risk of Zika virus transmission via human cells, tissues, and cellular and tissue-based products (HCT/Ps).

The guidance addresses donation of HCT/Ps from both living and deceased donors, including donors of umbilical cord blood and hematopoietic stem/progenitor cells.

In this document, the FDA recommends a 6-month deferral period for most HCT/P donors who may have been exposed to the Zika virus.

The exception is donors of gestational tissues, who should be considered ineligible if they were at risk of contracting the virus at any time during their pregnancy.

The new guidance is a part of the FDA’s ongoing efforts to protect HCT/Ps and blood products from Zika virus transmission. Last month, the agency issued recommendations for reducing the risk of Zika virus transmission via blood transfusion.

There is a potential risk that Zika virus can be transmitted by HCT/Ps used as part of a medical, surgical, or reproductive procedure. HCT/Ps include products such as corneas, bone, skin, heart valves, hematopoietic stem/progenitor cells, gestational tissues such as amniotic membrane, and reproductive tissues such as semen and oocytes.

According to the Centers for Disease Control and Prevention, Zika virus can be spread by a man to his sexual partners. To date, there have been several cases of sexual transmission in the US.

Current information about Zika virus detection in semen suggests the period of deferral for HCT/P donors should be longer than the period recommended for donors of whole blood and blood components.

Therefore, the FDA has recommended that living donors of HCT/Ps be considered ineligible if they were diagnosed with Zika virus infection, were in an area with active Zika virus transmission, or had sex with a male with either of those risk factors within the past 6 months.

Donors of umbilical cord blood, placenta, or other gestational tissues should be considered ineligible if they have had any of the above risk factors at any point during their pregnancy.

Deceased donors should be considered ineligible if they were diagnosed with Zika virus infection in the past 6 months.

A deferral period of 6 months was chosen because of the limited data available on the length of time the virus can persist in all tissues. Zika virus has been detected in tissues and body fluids after the virus is no longer detectable in the blood stream and has been detected in semen possibly up to 10 weeks after the onset of symptoms.

Less evidence exists regarding the potential for transmission of Zika virus by HCT/Ps typically recovered from deceased donors. As more information becomes available, the understanding of the risks to recipients of HCT/Ps, including HCT/Ps recovered from deceased donors, may evolve.

The FDA said it will continue to monitor the situation and evaluate new information regarding the associated risks as it becomes available.

In addition, the FDA said it is prioritizing the development of blood donor screening and diagnostic tests that may be useful for identifying the presence of or recent infection with the Zika virus. The agency is prepared to evaluate investigational vaccines and therapeutics that might be developed and review technology that may help suppress populations of the mosquitoes that can spread the virus.

Cord blood donation

Photo courtesy of NHS

The US Food and Drug Administration (FDA) has issued a guidance document intended to help reduce the risk of Zika virus transmission via human cells, tissues, and cellular and tissue-based products (HCT/Ps).

The guidance addresses donation of HCT/Ps from both living and deceased donors, including donors of umbilical cord blood and hematopoietic stem/progenitor cells.

In this document, the FDA recommends a 6-month deferral period for most HCT/P donors who may have been exposed to the Zika virus.

The exception is donors of gestational tissues, who should be considered ineligible if they were at risk of contracting the virus at any time during their pregnancy.

The new guidance is a part of the FDA’s ongoing efforts to protect HCT/Ps and blood products from Zika virus transmission. Last month, the agency issued recommendations for reducing the risk of Zika virus transmission via blood transfusion.

There is a potential risk that Zika virus can be transmitted by HCT/Ps used as part of a medical, surgical, or reproductive procedure. HCT/Ps include products such as corneas, bone, skin, heart valves, hematopoietic stem/progenitor cells, gestational tissues such as amniotic membrane, and reproductive tissues such as semen and oocytes.

According to the Centers for Disease Control and Prevention, Zika virus can be spread by a man to his sexual partners. To date, there have been several cases of sexual transmission in the US.

Current information about Zika virus detection in semen suggests the period of deferral for HCT/P donors should be longer than the period recommended for donors of whole blood and blood components.

Therefore, the FDA has recommended that living donors of HCT/Ps be considered ineligible if they were diagnosed with Zika virus infection, were in an area with active Zika virus transmission, or had sex with a male with either of those risk factors within the past 6 months.

Donors of umbilical cord blood, placenta, or other gestational tissues should be considered ineligible if they have had any of the above risk factors at any point during their pregnancy.

Deceased donors should be considered ineligible if they were diagnosed with Zika virus infection in the past 6 months.

A deferral period of 6 months was chosen because of the limited data available on the length of time the virus can persist in all tissues. Zika virus has been detected in tissues and body fluids after the virus is no longer detectable in the blood stream and has been detected in semen possibly up to 10 weeks after the onset of symptoms.

Less evidence exists regarding the potential for transmission of Zika virus by HCT/Ps typically recovered from deceased donors. As more information becomes available, the understanding of the risks to recipients of HCT/Ps, including HCT/Ps recovered from deceased donors, may evolve.

The FDA said it will continue to monitor the situation and evaluate new information regarding the associated risks as it becomes available.

In addition, the FDA said it is prioritizing the development of blood donor screening and diagnostic tests that may be useful for identifying the presence of or recent infection with the Zika virus. The agency is prepared to evaluate investigational vaccines and therapeutics that might be developed and review technology that may help suppress populations of the mosquitoes that can spread the virus.

Blood in bags and vials

Photo by Daniel Gay

Red blood cell (RBC) transfusions do not increase the risk of a serious intestinal disorder in very low-birth-weight (VLBW) infants, according to a study published in JAMA.

Past research has suggested RBC transfusions increase the risk of necrotizing enterocolitis (NEC) among VLBW infants.

But other studies have shown no association between transfusions and NEC or suggested transfusions actually have a protective effect.

So researchers set out to determine whether RBC transfusions or severe anemia were associated with the rate of NEC among VLBW infants. The results suggested a significant association for severe anemia but not RBC transfusion.

To conduct this study, Ravi M. Patel, MD, of the Emory University School of Medicine in Atlanta, Georgia, and his colleagues assessed 598 VLBW infants from 3 neonatal intensive care units in Atlanta.

The team followed the infants for 90 days or until they were discharged from the hospital, transferred to a non-study-affiliated hospital, or died (whichever came first).

Forty-four (7.4%) infants developed NEC, and 32 (5.4%) died (of any cause). Roughly half of the infants (n=319, 53%) received RBC transfusions (n=1430).

The unadjusted cumulative incidence of NEC at week 8 was 9.9% in infants who received transfusions and 4.6% in those who did not.

However, in multivariable analysis, exposure to RBC transfusion in a given week was not significantly related to the rate of NEC. The hazard ratio was 0.44 (P=0.09).

On the other hand, the rate of NEC was significantly higher among infants with severe anemia in a given week than in those without severe anemia. The hazard ratio was 5.99 (P=0.001).

The researchers said these results suggest preventing severe anemia may be more clinically important than minimizing the use of RBC transfusion as a strategy to decrease the risk of NEC in VLBW infants.

However, such a strategy might impact other important neonatal outcomes, so further study is needed.

Blood in bags and vials

Photo by Daniel Gay

Red blood cell (RBC) transfusions do not increase the risk of a serious intestinal disorder in very low-birth-weight (VLBW) infants, according to a study published in JAMA.

Past research has suggested RBC transfusions increase the risk of necrotizing enterocolitis (NEC) among VLBW infants.

But other studies have shown no association between transfusions and NEC or suggested transfusions actually have a protective effect.

So researchers set out to determine whether RBC transfusions or severe anemia were associated with the rate of NEC among VLBW infants. The results suggested a significant association for severe anemia but not RBC transfusion.

To conduct this study, Ravi M. Patel, MD, of the Emory University School of Medicine in Atlanta, Georgia, and his colleagues assessed 598 VLBW infants from 3 neonatal intensive care units in Atlanta.

The team followed the infants for 90 days or until they were discharged from the hospital, transferred to a non-study-affiliated hospital, or died (whichever came first).

Forty-four (7.4%) infants developed NEC, and 32 (5.4%) died (of any cause). Roughly half of the infants (n=319, 53%) received RBC transfusions (n=1430).

The unadjusted cumulative incidence of NEC at week 8 was 9.9% in infants who received transfusions and 4.6% in those who did not.

However, in multivariable analysis, exposure to RBC transfusion in a given week was not significantly related to the rate of NEC. The hazard ratio was 0.44 (P=0.09).

On the other hand, the rate of NEC was significantly higher among infants with severe anemia in a given week than in those without severe anemia. The hazard ratio was 5.99 (P=0.001).

The researchers said these results suggest preventing severe anemia may be more clinically important than minimizing the use of RBC transfusion as a strategy to decrease the risk of NEC in VLBW infants.

However, such a strategy might impact other important neonatal outcomes, so further study is needed.

Blood in bags and vials

Photo by Daniel Gay

Red blood cell (RBC) transfusions do not increase the risk of a serious intestinal disorder in very low-birth-weight (VLBW) infants, according to a study published in JAMA.

Past research has suggested RBC transfusions increase the risk of necrotizing enterocolitis (NEC) among VLBW infants.

But other studies have shown no association between transfusions and NEC or suggested transfusions actually have a protective effect.

So researchers set out to determine whether RBC transfusions or severe anemia were associated with the rate of NEC among VLBW infants. The results suggested a significant association for severe anemia but not RBC transfusion.

To conduct this study, Ravi M. Patel, MD, of the Emory University School of Medicine in Atlanta, Georgia, and his colleagues assessed 598 VLBW infants from 3 neonatal intensive care units in Atlanta.

The team followed the infants for 90 days or until they were discharged from the hospital, transferred to a non-study-affiliated hospital, or died (whichever came first).

Forty-four (7.4%) infants developed NEC, and 32 (5.4%) died (of any cause). Roughly half of the infants (n=319, 53%) received RBC transfusions (n=1430).

The unadjusted cumulative incidence of NEC at week 8 was 9.9% in infants who received transfusions and 4.6% in those who did not.

However, in multivariable analysis, exposure to RBC transfusion in a given week was not significantly related to the rate of NEC. The hazard ratio was 0.44 (P=0.09).

On the other hand, the rate of NEC was significantly higher among infants with severe anemia in a given week than in those without severe anemia. The hazard ratio was 5.99 (P=0.001).

The researchers said these results suggest preventing severe anemia may be more clinically important than minimizing the use of RBC transfusion as a strategy to decrease the risk of NEC in VLBW infants.

However, such a strategy might impact other important neonatal outcomes, so further study is needed.

Blood samples

Photo by Jeremy L. Grisham

The US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for a laboratory test used to detect the Zika virus.

The test, which was developed by the Centers for Disease Control and Prevention (CDC), is called the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

It will be distributed to certain laboratories in the US and abroad over the next 2 weeks.

The test will not be available in US hospitals or other primary care settings.

The Zika MAC-ELISA test can detect human immunoglobulin M (IgM) antibodies to the Zika virus. These antibodies appear in the blood of an infected person 4 to 5 days after the start of the illness, and they remain in the blood for about 12 weeks.

The Zika MAC-ELISA test is intended for use in sera or cerebrospinal fluid when submitted with a patient-matched serum sample from individuals meeting CDC Zika clinical and epidemiological criteria for testing. This includes people with a history of symptoms associated with Zika and/or people who have recently traveled to an area that has active Zika transmission.

Results of Zika MAC-ELISA tests require careful interpretation. The test can give false-positive results when someone has been infected with a virus closely related to Zika (such as dengue virus).

When positive or inconclusive results occur, additional testing (plaque reduction neutralization test) to confirm the presence of antibodies to Zika virus will be performed by the CDC or a CDC-authorized laboratory.

Moreover, a negative test result does not necessarily mean a person has not been infected with Zika virus. If a sample is collected just after a person becomes ill, there may not be enough IgM antibodies for the test to measure, resulting in a false-negative.

Similarly, if the sample was collected more than 12 weeks after illness, it is possible that the body has successfully fought the virus and IgM antibody levels have dropped below the detectable limit.

The CDC will begin distributing the Zika MAC-ELISA test over the next 2 weeks to qualified laboratories in the Laboratory Response Network, an integrated network of domestic and international laboratories that can respond to public health emergencies.

About the EUA

An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency. The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

As there are no commercially available diagnostic tests approved by the FDA for the detection of Zika virus infection, the agency decided an EUA was crucial to ensure timely access to a diagnostic tool.

The FDA issued the EUA for the Zika MAC-ELISA test based on data submitted by the CDC and on the US Secretary of Health and Human Services’ declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and Zika virus infection. This EUA will end when the Secretary’s declaration ends, unless the FDA revokes it sooner.

Blood samples

Photo by Jeremy L. Grisham

The US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for a laboratory test used to detect the Zika virus.

The test, which was developed by the Centers for Disease Control and Prevention (CDC), is called the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

It will be distributed to certain laboratories in the US and abroad over the next 2 weeks.

The test will not be available in US hospitals or other primary care settings.

The Zika MAC-ELISA test can detect human immunoglobulin M (IgM) antibodies to the Zika virus. These antibodies appear in the blood of an infected person 4 to 5 days after the start of the illness, and they remain in the blood for about 12 weeks.

The Zika MAC-ELISA test is intended for use in sera or cerebrospinal fluid when submitted with a patient-matched serum sample from individuals meeting CDC Zika clinical and epidemiological criteria for testing. This includes people with a history of symptoms associated with Zika and/or people who have recently traveled to an area that has active Zika transmission.

Results of Zika MAC-ELISA tests require careful interpretation. The test can give false-positive results when someone has been infected with a virus closely related to Zika (such as dengue virus).

When positive or inconclusive results occur, additional testing (plaque reduction neutralization test) to confirm the presence of antibodies to Zika virus will be performed by the CDC or a CDC-authorized laboratory.

Moreover, a negative test result does not necessarily mean a person has not been infected with Zika virus. If a sample is collected just after a person becomes ill, there may not be enough IgM antibodies for the test to measure, resulting in a false-negative.

Similarly, if the sample was collected more than 12 weeks after illness, it is possible that the body has successfully fought the virus and IgM antibody levels have dropped below the detectable limit.

The CDC will begin distributing the Zika MAC-ELISA test over the next 2 weeks to qualified laboratories in the Laboratory Response Network, an integrated network of domestic and international laboratories that can respond to public health emergencies.

About the EUA

An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency. The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

As there are no commercially available diagnostic tests approved by the FDA for the detection of Zika virus infection, the agency decided an EUA was crucial to ensure timely access to a diagnostic tool.

The FDA issued the EUA for the Zika MAC-ELISA test based on data submitted by the CDC and on the US Secretary of Health and Human Services’ declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and Zika virus infection. This EUA will end when the Secretary’s declaration ends, unless the FDA revokes it sooner.

Blood samples

Photo by Jeremy L. Grisham

The US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for a laboratory test used to detect the Zika virus.

The test, which was developed by the Centers for Disease Control and Prevention (CDC), is called the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

It will be distributed to certain laboratories in the US and abroad over the next 2 weeks.

The test will not be available in US hospitals or other primary care settings.

The Zika MAC-ELISA test can detect human immunoglobulin M (IgM) antibodies to the Zika virus. These antibodies appear in the blood of an infected person 4 to 5 days after the start of the illness, and they remain in the blood for about 12 weeks.

The Zika MAC-ELISA test is intended for use in sera or cerebrospinal fluid when submitted with a patient-matched serum sample from individuals meeting CDC Zika clinical and epidemiological criteria for testing. This includes people with a history of symptoms associated with Zika and/or people who have recently traveled to an area that has active Zika transmission.

Results of Zika MAC-ELISA tests require careful interpretation. The test can give false-positive results when someone has been infected with a virus closely related to Zika (such as dengue virus).

When positive or inconclusive results occur, additional testing (plaque reduction neutralization test) to confirm the presence of antibodies to Zika virus will be performed by the CDC or a CDC-authorized laboratory.

Moreover, a negative test result does not necessarily mean a person has not been infected with Zika virus. If a sample is collected just after a person becomes ill, there may not be enough IgM antibodies for the test to measure, resulting in a false-negative.

Similarly, if the sample was collected more than 12 weeks after illness, it is possible that the body has successfully fought the virus and IgM antibody levels have dropped below the detectable limit.

The CDC will begin distributing the Zika MAC-ELISA test over the next 2 weeks to qualified laboratories in the Laboratory Response Network, an integrated network of domestic and international laboratories that can respond to public health emergencies.

About the EUA

An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency. The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

As there are no commercially available diagnostic tests approved by the FDA for the detection of Zika virus infection, the agency decided an EUA was crucial to ensure timely access to a diagnostic tool.

The FDA issued the EUA for the Zika MAC-ELISA test based on data submitted by the CDC and on the US Secretary of Health and Human Services’ declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and Zika virus infection. This EUA will end when the Secretary’s declaration ends, unless the FDA revokes it sooner.

Blood sample collection

Photo by Juan D. Alfonso

Two institutions in Houston, Texas, have developed the US’s first hospital-based, rapid diagnostic test for the Zika virus.

Pathologists and clinical laboratory scientists at Texas Children’s Hospital and Houston Methodist Hospital developed the test, which is customized to each hospital’s diagnostic laboratory and can provide results within several hours.

The test can be performed on blood, amniotic fluid, urine, or spinal fluid.

The test identifies virus-specific RNA sequences to detect Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections.

Right now, only registered patients at Texas Children’s or Houston Methodist Hospital can receive the test, but the labs will consider referral testing from other hospitals and clinics in the future.

Initially, the test will be offered to patients with a positive travel history and symptoms consistent with acute Zika virus infection (eg, rash, arthralgia, or fever) or asymptomatic pregnant women with a positive travel history to any of the Zika-affected countries.

The goal of hospital-based testing for Zika virus is to prevent the delays that may occur with testing conducted in local and state public health laboratories and the Centers for Disease Control and Prevention.

“Hospital-based testing that is state-of-the-art enables our physicians and patients to get very rapid diagnostic answers,” said James M. Musser, MD, PhD, of Houston Methodist Hospital.

“If tests need to be repeated or if our treating doctors need to talk with our pathologists, we have the resources near patient care settings.”

The collaboration between Texas Children’s and Houston Methodist Hospital was sponsored by the L.E. and Virginia Simmons Collaborative in Virus Detection and Surveillance. This program was designed to facilitate rapid development of tests for virus detection in a large metropolitan area.

Blood sample collection

Photo by Juan D. Alfonso

Two institutions in Houston, Texas, have developed the US’s first hospital-based, rapid diagnostic test for the Zika virus.

Pathologists and clinical laboratory scientists at Texas Children’s Hospital and Houston Methodist Hospital developed the test, which is customized to each hospital’s diagnostic laboratory and can provide results within several hours.

The test can be performed on blood, amniotic fluid, urine, or spinal fluid.

The test identifies virus-specific RNA sequences to detect Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections.

Right now, only registered patients at Texas Children’s or Houston Methodist Hospital can receive the test, but the labs will consider referral testing from other hospitals and clinics in the future.

Initially, the test will be offered to patients with a positive travel history and symptoms consistent with acute Zika virus infection (eg, rash, arthralgia, or fever) or asymptomatic pregnant women with a positive travel history to any of the Zika-affected countries.

The goal of hospital-based testing for Zika virus is to prevent the delays that may occur with testing conducted in local and state public health laboratories and the Centers for Disease Control and Prevention.

“Hospital-based testing that is state-of-the-art enables our physicians and patients to get very rapid diagnostic answers,” said James M. Musser, MD, PhD, of Houston Methodist Hospital.

“If tests need to be repeated or if our treating doctors need to talk with our pathologists, we have the resources near patient care settings.”

The collaboration between Texas Children’s and Houston Methodist Hospital was sponsored by the L.E. and Virginia Simmons Collaborative in Virus Detection and Surveillance. This program was designed to facilitate rapid development of tests for virus detection in a large metropolitan area.

Blood sample collection

Photo by Juan D. Alfonso

Two institutions in Houston, Texas, have developed the US’s first hospital-based, rapid diagnostic test for the Zika virus.

Pathologists and clinical laboratory scientists at Texas Children’s Hospital and Houston Methodist Hospital developed the test, which is customized to each hospital’s diagnostic laboratory and can provide results within several hours.

The test can be performed on blood, amniotic fluid, urine, or spinal fluid.

The test identifies virus-specific RNA sequences to detect Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections.

Right now, only registered patients at Texas Children’s or Houston Methodist Hospital can receive the test, but the labs will consider referral testing from other hospitals and clinics in the future.

Initially, the test will be offered to patients with a positive travel history and symptoms consistent with acute Zika virus infection (eg, rash, arthralgia, or fever) or asymptomatic pregnant women with a positive travel history to any of the Zika-affected countries.

The goal of hospital-based testing for Zika virus is to prevent the delays that may occur with testing conducted in local and state public health laboratories and the Centers for Disease Control and Prevention.

“Hospital-based testing that is state-of-the-art enables our physicians and patients to get very rapid diagnostic answers,” said James M. Musser, MD, PhD, of Houston Methodist Hospital.

“If tests need to be repeated or if our treating doctors need to talk with our pathologists, we have the resources near patient care settings.”

The collaboration between Texas Children’s and Houston Methodist Hospital was sponsored by the L.E. and Virginia Simmons Collaborative in Virus Detection and Surveillance. This program was designed to facilitate rapid development of tests for virus detection in a large metropolitan area.