New diagnostic tool identifies severe ADAMTS13 deficiency

Researchers have developed and validated a new diagnostic tool – the PLASMIC score – that rapidly predicts severe ADAMTS13 deficiency in patients who present with thrombotic microangiopathy, effectively distinguishing those who have thrombotic thrombocytopenic purpura (TTP) from those with other disorders, according to a report published in Lancet Haematology.

Many disorders or clinical events can present as a thrombotic microangiopathy, including hemolytic uremic syndrome, disseminated intravascular coagulation, and malignant hypertension; this abnormality can even be an adverse effect of hematopoietic stem cell transplantation or solid-organ transplantation. Rapidly differentiating TTP from such disorders facilitates urgent treatment with plasma exchange or plasma transfusion. But testing for elevated ADAMTS13 levels to make this distinction currently requires long turnaround times and is unavailable in some locations, said Pavan K. Bendapudi, MD, of the division of hematology, Massachusetts General Hospital, Boston, and his associates.

The PLASMIC score “is designed specifically to aid practitioners who might have little experience managing thrombotic microangiopathy, and it can distinguish TTP from a broad range of thrombotic microangiopathy subtypes, including those that seem most similar to TTP,” they wrote.

The researchers developed a 7-point scoring system to predict the likelihood of elevated ADAMTS13 levels by analyzing 29 clinical and laboratory variables that would aid in diagnosis, using a cohort of 214 consecutive patients enrolled in a multicenter research registry in 2004-2012. They narrowed their initial finding of 11 key variables down to 5 key variables that best predicted severe ADAMTSD13 deficiency: platelet count lower than 29x10⁹ per liter, creatinine less than 1.8 mg/dL, international normalized ratio (INR) less than 1.3, mean corpuscular volume (MCV) less than 86.5/L, and a combined hemolysis variable based on reticulocyte count, the presence of haptoglobin, and bilirubin level.

Two additional variables – cancer diagnosed during the preceding year and the absence of stem cell or organ transplantation – were absent in all patients who had severe ADAMTS13 deficiency in this derivation cohort and were included in the PLASMIC score because of their high negative predictive value. Thus, the diagnostic score was named for its seven components: platelet count, combined hemolysis variable, absence of active cancer; absence of stem cell or solid-organ transplant, MCV, INR, and creatinine. Each component was assigned 1 point on the 7-point scale.

None of the 84 patients in this derivation cohort with a PLASMIC score of 0-4 had severe ADAMTS13 deficiency, while 81% of those with a score of 6 or 7 did have a severe ADAMTS13 deficiency. Patients who were eventually diagnosed as having TTP had a median score of 7. In contrast, patients with thrombotic microangiopathy traced to rheumatologic disorders had a median score of 5, those with drug-associated thrombotic microangiopathy had a median score of 4, and those with disseminated intravascular coagulation had a median score of 4. The PLASMIC score also appeared to discriminate among TTP, typical hemolytic uremia syndrome, and atypical hemolytic uremia syndrome, which have “strikingly similar clinical presentations,” Dr. Bendapudi and his associates said.

Unlike TTP, the disorders with lower PLASMIC scores tended to carry a much poorer prognosis. In this cohort, patients with higher PLASMIC scores had significantly better survival time (median survival not yet reached), compared with those who had a score of 5 (median survival, 1,670 days) and those with a score of 1-4 (median survival, 287 days).

The investigators then validated their findings in two independent cohorts: 154 people with thrombotic microangiopathy from the same patient registry but from more recent years (2012-2015), and 152 patients from an Alabama registry. In the first validation cohort, none of the 89 patients assigned a score of 0-4 had severe ADAMTS13 deficiency, while 62% of those given a score of 6 or 7 had a severe deficiency. In the second validation cohort, only two patients (4%) with scores of 0-4 had a severe ADAMTS13 deficiency, while 82% of those with a score of 6 or 7 had a severe deficiency.

Based on these findings, a PLASMIC score of 0-4 denotes low risk for ADAMTS13 deficiency, a score of 5 denotes intermediate risk, and a score of 6 or 7 denotes high risk and thus probable TTP, Dr. Bendapudi and his associates said (Lancet Haematol. 2017;4:e157-64).

The PLASMIC score was superior to both a two-component prediction tool currently used in France and to a clinical consensus score, “further demonstrating the real-world utility of our prediction tool,” the researchers wrote.

Researchers have developed and validated a new diagnostic tool – the PLASMIC score – that rapidly predicts severe ADAMTS13 deficiency in patients who present with thrombotic microangiopathy, effectively distinguishing those who have thrombotic thrombocytopenic purpura (TTP) from those with other disorders, according to a report published in Lancet Haematology.

Many disorders or clinical events can present as a thrombotic microangiopathy, including hemolytic uremic syndrome, disseminated intravascular coagulation, and malignant hypertension; this abnormality can even be an adverse effect of hematopoietic stem cell transplantation or solid-organ transplantation. Rapidly differentiating TTP from such disorders facilitates urgent treatment with plasma exchange or plasma transfusion. But testing for elevated ADAMTS13 levels to make this distinction currently requires long turnaround times and is unavailable in some locations, said Pavan K. Bendapudi, MD, of the division of hematology, Massachusetts General Hospital, Boston, and his associates.

The PLASMIC score “is designed specifically to aid practitioners who might have little experience managing thrombotic microangiopathy, and it can distinguish TTP from a broad range of thrombotic microangiopathy subtypes, including those that seem most similar to TTP,” they wrote.

The researchers developed a 7-point scoring system to predict the likelihood of elevated ADAMTS13 levels by analyzing 29 clinical and laboratory variables that would aid in diagnosis, using a cohort of 214 consecutive patients enrolled in a multicenter research registry in 2004-2012. They narrowed their initial finding of 11 key variables down to 5 key variables that best predicted severe ADAMTSD13 deficiency: platelet count lower than 29x10⁹ per liter, creatinine less than 1.8 mg/dL, international normalized ratio (INR) less than 1.3, mean corpuscular volume (MCV) less than 86.5/L, and a combined hemolysis variable based on reticulocyte count, the presence of haptoglobin, and bilirubin level.

Two additional variables – cancer diagnosed during the preceding year and the absence of stem cell or organ transplantation – were absent in all patients who had severe ADAMTS13 deficiency in this derivation cohort and were included in the PLASMIC score because of their high negative predictive value. Thus, the diagnostic score was named for its seven components: platelet count, combined hemolysis variable, absence of active cancer; absence of stem cell or solid-organ transplant, MCV, INR, and creatinine. Each component was assigned 1 point on the 7-point scale.

None of the 84 patients in this derivation cohort with a PLASMIC score of 0-4 had severe ADAMTS13 deficiency, while 81% of those with a score of 6 or 7 did have a severe ADAMTS13 deficiency. Patients who were eventually diagnosed as having TTP had a median score of 7. In contrast, patients with thrombotic microangiopathy traced to rheumatologic disorders had a median score of 5, those with drug-associated thrombotic microangiopathy had a median score of 4, and those with disseminated intravascular coagulation had a median score of 4. The PLASMIC score also appeared to discriminate among TTP, typical hemolytic uremia syndrome, and atypical hemolytic uremia syndrome, which have “strikingly similar clinical presentations,” Dr. Bendapudi and his associates said.

Unlike TTP, the disorders with lower PLASMIC scores tended to carry a much poorer prognosis. In this cohort, patients with higher PLASMIC scores had significantly better survival time (median survival not yet reached), compared with those who had a score of 5 (median survival, 1,670 days) and those with a score of 1-4 (median survival, 287 days).

The investigators then validated their findings in two independent cohorts: 154 people with thrombotic microangiopathy from the same patient registry but from more recent years (2012-2015), and 152 patients from an Alabama registry. In the first validation cohort, none of the 89 patients assigned a score of 0-4 had severe ADAMTS13 deficiency, while 62% of those given a score of 6 or 7 had a severe deficiency. In the second validation cohort, only two patients (4%) with scores of 0-4 had a severe ADAMTS13 deficiency, while 82% of those with a score of 6 or 7 had a severe deficiency.

Based on these findings, a PLASMIC score of 0-4 denotes low risk for ADAMTS13 deficiency, a score of 5 denotes intermediate risk, and a score of 6 or 7 denotes high risk and thus probable TTP, Dr. Bendapudi and his associates said (Lancet Haematol. 2017;4:e157-64).

The PLASMIC score was superior to both a two-component prediction tool currently used in France and to a clinical consensus score, “further demonstrating the real-world utility of our prediction tool,” the researchers wrote.

Researchers have developed and validated a new diagnostic tool – the PLASMIC score – that rapidly predicts severe ADAMTS13 deficiency in patients who present with thrombotic microangiopathy, effectively distinguishing those who have thrombotic thrombocytopenic purpura (TTP) from those with other disorders, according to a report published in Lancet Haematology.

Many disorders or clinical events can present as a thrombotic microangiopathy, including hemolytic uremic syndrome, disseminated intravascular coagulation, and malignant hypertension; this abnormality can even be an adverse effect of hematopoietic stem cell transplantation or solid-organ transplantation. Rapidly differentiating TTP from such disorders facilitates urgent treatment with plasma exchange or plasma transfusion. But testing for elevated ADAMTS13 levels to make this distinction currently requires long turnaround times and is unavailable in some locations, said Pavan K. Bendapudi, MD, of the division of hematology, Massachusetts General Hospital, Boston, and his associates.

The PLASMIC score “is designed specifically to aid practitioners who might have little experience managing thrombotic microangiopathy, and it can distinguish TTP from a broad range of thrombotic microangiopathy subtypes, including those that seem most similar to TTP,” they wrote.

The researchers developed a 7-point scoring system to predict the likelihood of elevated ADAMTS13 levels by analyzing 29 clinical and laboratory variables that would aid in diagnosis, using a cohort of 214 consecutive patients enrolled in a multicenter research registry in 2004-2012. They narrowed their initial finding of 11 key variables down to 5 key variables that best predicted severe ADAMTSD13 deficiency: platelet count lower than 29x10⁹ per liter, creatinine less than 1.8 mg/dL, international normalized ratio (INR) less than 1.3, mean corpuscular volume (MCV) less than 86.5/L, and a combined hemolysis variable based on reticulocyte count, the presence of haptoglobin, and bilirubin level.

Two additional variables – cancer diagnosed during the preceding year and the absence of stem cell or organ transplantation – were absent in all patients who had severe ADAMTS13 deficiency in this derivation cohort and were included in the PLASMIC score because of their high negative predictive value. Thus, the diagnostic score was named for its seven components: platelet count, combined hemolysis variable, absence of active cancer; absence of stem cell or solid-organ transplant, MCV, INR, and creatinine. Each component was assigned 1 point on the 7-point scale.

None of the 84 patients in this derivation cohort with a PLASMIC score of 0-4 had severe ADAMTS13 deficiency, while 81% of those with a score of 6 or 7 did have a severe ADAMTS13 deficiency. Patients who were eventually diagnosed as having TTP had a median score of 7. In contrast, patients with thrombotic microangiopathy traced to rheumatologic disorders had a median score of 5, those with drug-associated thrombotic microangiopathy had a median score of 4, and those with disseminated intravascular coagulation had a median score of 4. The PLASMIC score also appeared to discriminate among TTP, typical hemolytic uremia syndrome, and atypical hemolytic uremia syndrome, which have “strikingly similar clinical presentations,” Dr. Bendapudi and his associates said.

Unlike TTP, the disorders with lower PLASMIC scores tended to carry a much poorer prognosis. In this cohort, patients with higher PLASMIC scores had significantly better survival time (median survival not yet reached), compared with those who had a score of 5 (median survival, 1,670 days) and those with a score of 1-4 (median survival, 287 days).

The investigators then validated their findings in two independent cohorts: 154 people with thrombotic microangiopathy from the same patient registry but from more recent years (2012-2015), and 152 patients from an Alabama registry. In the first validation cohort, none of the 89 patients assigned a score of 0-4 had severe ADAMTS13 deficiency, while 62% of those given a score of 6 or 7 had a severe deficiency. In the second validation cohort, only two patients (4%) with scores of 0-4 had a severe ADAMTS13 deficiency, while 82% of those with a score of 6 or 7 had a severe deficiency.

Based on these findings, a PLASMIC score of 0-4 denotes low risk for ADAMTS13 deficiency, a score of 5 denotes intermediate risk, and a score of 6 or 7 denotes high risk and thus probable TTP, Dr. Bendapudi and his associates said (Lancet Haematol. 2017;4:e157-64).

The PLASMIC score was superior to both a two-component prediction tool currently used in France and to a clinical consensus score, “further demonstrating the real-world utility of our prediction tool,” the researchers wrote.