Therapeutic plasma exchange for thrombotic thrombocytopenic purpura with refractory thrombocytopenia

Thrombotic thrombocytopenic purpura (TTP) is an acute, life‐threatening illness with disseminated platelet‐rich thromboses of small vessels that variably presents with the classic clinical “pentad” of microangiopathic hemolytic anemia, thrombocytopenia, fever, altered mental status, and acute kidney injury. Most cases are caused by an acquired autoantibody to ADAMTS13, a metalloproteinase that cleaves large von Willebrand Factor (vWF) multimers. The mainstay of treatment is daily therapeutic plasma exchange (TPE), sometimes with adjunctive pharmacologic immunosuppression. TPE is generally continued until the platelet count is greater than 150 × 10³/µL and the lactate dehydrogenase is near normal for 2‐3 consecutive days. Unfortunately, there is no clear guidance for when thrombocytopenia is refractory for a prolonged period of time. The following case describes such a scenario in which consecutive ADAMTS13 activity and inhibitor levels were used to guide the decision to stop treatment with TPE in a patient who failed to recover their platelet count.     

A new variant of type II von Willebrand disease with aberrant multimeric structure of plasma but not platelet von Willebrand factor (type IIF)

A patient with a lifelong bleeding disorder was diagnosed as having Type II von Willebrand disease. The larger multimers of von Willebrand factor were absent from her plasma but present in platelets. A high- resolution electrophoretic technique was used to study the complex structure of individual von Willebrand factor multimers. In normal plasma, each multimer could be resolved into five bands: a more intense central one and four less intense, two moving faster and two slower than the central band. In normal platelets, each multimer could also be resolved into five bands. The central one had a mobility similar to that in plasma, whereas the four satellite bands had a mobility that differed from that of the corresponding plasma bands. In the patient, platelet von Willebrand factor antigen content and ristocetin cofactor activity were normal, and von Willebrand factor showed the same structure of individual multimers as seen in normal platelets. On the other hand, plasma von Willebrand factor antigen and ristocetin cofactor activity were decreased, and the structure of individual von Willebrand factor multimers was different from that of normal plasma and similar to that seen in normal and patient's platelets. After infusion of 1-deamino-8-D-arginine vasopressin, the largest von Willebrand factor multimers, as well as new satellite bands with a mobility similar to those in normal plasma, appeared in the patient plasma, and the levels of von Willebrand factor antigen and ristocetin cofactor activity became normal. Yet no relevant change in the prolonged bleeding time was observed. This new variant of von Willebrand disease, therefore, is characterized by the presence of a dysfunctional von Willebrand factor molecule that exhibits unique structural abnormalities in plasma but appears to be normal in platelets. The designation of Type IIF is proposed for this type of von Willebrand disease in accordance with the terminology that has been previously used.