Laboratory abnormalities in thrombotic thrombocytopenic purpura

Rock, Kristin; Kelton, John G.; Shumak, Kenneth H.; Buskard, Noel A.; Sutton, David; Benny, Barrett

doi:10.1046/j.1365-2141.1998.01080.x

Cited by 90 publications

(94 citation statements)

References 26 publications

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“…Treatment with PEX and corticosteroids significantly reduces the mortality to ;10% to 15%. 1,2 Acquired TTP is due to a deficiency of the von Willebrand factor (VWF) cleaving serine metalloprotease, called ADAMTS13. 3,4 Anti-ADAMTS13 autoantibodies contribute to the pathogenesis of acquired TTP.…”

Section: Introductionmentioning

confidence: 99%

How I treat refractory thrombotic thrombocytopenic purpura

Sayani¹,

Abrams

2015

Blood

143

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Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA) without an obvious cause, and may include fever, mild renal failure, and neurologic deficits. It is characterized by a deficiency of the von Willebrand factor (VWF) cleaving enzyme, ADAMTS13 (a disintegrin and metalloproteinase, with a thrombospondin type 1 motif, member 13), resulting in formation of microthrombi in the high sheer environment of the microvasculature. This causes microvascular occlusion, MAHA, and organ ischemia. Diagnosis is based on the presence of clinical symptoms, laboratory aberrations consistent with MAHA, decreased ADAMTS13 activity, and possibly presence of anti-ADAMTS13 autoantibodies. Upfront treatment of acute TTP includes plasma exchange and corticosteroids. A significant number of patients are refractory to this treatment and will require further interventions. There are limited data and consensus on the management of the refractory TTP patient. Management involves simultaneously ruling out other causes of thrombocytopenia and MAHA, while also considering other treatments. In this article, we describe our management of the patient with refractory TTP, and discuss use of rituximab, increased plasma exchange, splenectomy, and immunosuppressive options, including cyclophosphamide, vincristine, and cyclosporine. We also review recent evidence for the potential roles of bortezomib and N-acetylcysteine, and explore new therapeutic approaches, including recombinant ADAMTS13 and anti-VWF therapy. (Blood. 2015;125(25):3860-3867) Case A 25-year-old previously healthy woman presented with a 3-day history of fatigue, nausea, abdominal pain, and easy bruising. She was alert, oriented, afebrile, had mild abdominal tenderness, and purpura on her extremities. Her hemoglobin was 8.4 g/dL; platelets, 15 3 10 9 /L; creatinine, 1.1 mg/dL; and her lactate dehydrogenase and reticulocytes were increased. Schistocytes and nucleated red blood cells were easily seen on her peripheral blood smear. In the absence of other obvious precipitators of thrombocytopenia and microangiopathic hemolytic anemia (MAHA), she was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP). Blood samples were sent for ADAMTS13 (a disintegrin and metalloproteinase, with a thrombospondin type 1 motif, member 13) activity and inhibitor levels, and the patient was immediately started on plasma exchange (PEX) and prednisone 1 mg/kg per day. She responded well initially, and her platelets rose to 105 000/mL on day 4. However, on day 5, she was febrile and her platelets dropped to 40 000/mL. BackgroundAcquired TTP was initially characterized by thrombocytopenia, MAHA, renal failure, neurologic deficits, and fever. However, it is now well accepted that neither renal failure nor high fevers are key diagnostic features. Thrombocytopenia and MAHA are required for diagnosis when TTP is suspected. TTP is a hematologic emergency, with a mortality of 90% if untreated. Treatment with PEX and cortico...

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Section: Introductionmentioning

confidence: 99%

How I treat refractory thrombotic thrombocytopenic purpura

Sayani¹,

Abrams

2015

Blood

143

View full text Add to dashboard Cite

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“…7,8 A clinical picture of fever, neurological deficit and renal impairment is associated with thrombocytopenia and microangiopathic haemolysis. 9,10 Schistocyte detection is mandatory to confirm the TMA. 11 Thus, a schistocyte count is desirable for follow-up of TTP, particularly after BMT, and the identification and counting of schistocytes should be on-demand for emergency request as well as for permanent use in the laboratory.…”

Section: Discussionmentioning

confidence: 99%

Automated measurement of schistocytes after bone marrow transplantation

Salignac

Lecompte

et al. 2004

Bone Marrow Transplant

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Summary:Bone marrow transplantation-related thrombotic microangiopathy (BMT-TMA) is a severe complication partly suspected on the evidence of a microangiopathic haemolysis. Microscopic schistocyte observation confirms the mechanical origin of the haemolysis, but remains a tedious procedure that lacks standardization. Direct measurement of abnormal red blood cell (RBC) fragments is now available on some automated haematology systems. We compared in 131 patients (69 BMT with five BMT-TMA, 38 thrombotic thrombocytopenic syndromes, 11 macroangiopathies, 13 dyserythropoiesis) percentages of microscopic schistocytes and automated RBC fragments (Bayer ADVIA 120) to evaluate the clinical relevance of the automated measurements for BMT-TMA detection. The analyser correlated well with the microscope (intraclass correlation coefficient: 0.82) and quantified RBC fragments with a moderate overestimation ( þ 0.4%) as compared to microscopic counts. BMT patients had higher RBC fragments when they had TMA (1.1 vs 0.4% without TMA). Automated counting was useful to flag BMT-related TMA, particularly when RBC fragments were above 1%. As RBC fragments were frequently detected in BMT patients even without TMA, a threshold of less 1% that ruled out TMA was determined with a 98% negative predictive value. The new RBC fragment automated parameter proved its clinical value to assess BMT-TMA, which might be useful for day-to-day monitoring of the post BMT period.

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“…1 The requirement for PEX creates a crisis when a Jehovah's Witness patient presents with TTP because Jehovah's Witness doctrine is that refusal of transfusions of whole blood or any of its 4 primary components (red cells, white cells, platelets, and plasma) is mandatory. 2 Therefore, PEX cannot be performed.…”

Section: Introductionmentioning

confidence: 99%