Congenital thrombotic thrombocytopenic purpura in adults: Manifestations and treatment

Introduction. Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare thrombotic microangiopathy that occurs due to a congenital deficiency of the ADAMTS13 enzyme. It can manifest both in childhood and in adulthood.

Aim: to analyze the manifestations and course of cTTP in adult patients. Materials and methods. Hemoglobin and platelet concentrations, a direct Coombs test, lactate dehydrogenase (LDH), ADAMTS13 activity, and ADAMTS13 inhibitor were studied in patients with suspected thrombotic thrombocytopenic purpura (TTP). In patients with ADAMTS13 activity< 10% and the absence of an ADAMTS13 inhibitor, the concentration of the ADAMTS13 antigen and mutations of the ADAMTS13 gene were studied. cTTP was diagnosed in the absence of ADAMTS13 inhibitor and the detection of mutations in ADAMTS13 gene.

Results. cTTP was diagnosed in 11 (9.5 %) patients (10 women, 1 man) among 115 adult patients with TTP. Mutations of ADAMTS13 gene were detected in all patients. Disease onset occurred between the ages of 20 and 33 years 33 (median 22 years). In 9 out of 10 women, the onset of the disease was associated with pregnancy. During TTP manifestation all patients had thrombocytopenia ((4–31)×109 /L, median 14×109 /L), anemia (hemoglobin 67 g/L), increased LDH activity (median 1300 U/L), low ADAMTS13 activity (median 2 %), and low ADAMTS13 antigen concentration (median 0.008 IU/ml). Neurological symptoms were present in 5 (45 %) of the 11 patients, and 2 of the 11 patients developed chronic renal failure. In clinical remission, all patients had normal ranges of hemoglobin, platelets and LDH activity, however ADAMTS13 activity remained low (0–18 %, median 7.5 %). Treatment during exacerbation included plasma transfusions; 8 patients underwent plasma exchange. Prophylactically, most patients received plasma at a dose of 15 mL/kg every 3–4 weeks. Three patients were treated with recombinant ADAMTS13 at a dose of 40 IU/kg intravenously once every 2 weeks. The therapy was well tolerated, and there was an increase of platelet level after drug administration.

Conclusion. cTTP can manifest in adulthood. In remission, cTTP patients need laboratory monitoring and preventive treatment.

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