ADAMTS13 peptide

Von Willebrand factor has a pivotal role in primary hemostasis. Its role in thrombotic microangiopathies (TMA), as well as cardiovascular disease, has been demonstrated. Thrombotic thrombocytopenic purpura (TTP), a thrombotic microangiopathy, is a life-threatening condition with a high mortality rate if untreated. Current management strategies comprise plasma exchange to remove autoantibodies and replenish ADAMTS13, along with immunosuppressive agents in immune TTP. This review focuses on novel antiplatelet strategies that target VWF and GPIb. The benefits of the nanobody caplacizumab in achieving faster normalization of platelet count, as well as reduced thromboembolic events were shown through TITAN and HERCULES trials, and these findings have been practice changing. The use of caplacizumab in patients with immune TTP (iTTP) has now become well established. Potential benefits of ARC1779 and N-acetylcysteine have also been shown on a small scale in iTTP, however these lack evidence through larger randomized controlled trials. Further therapies, some in early phase, others in clinical practice, target platelet aggregation within arteries and their utility is presented with cerebrovascular disorders.

BackgroundThe thrombotic microangiopathies (TMAs) is a heterogeneous group of relatively uncommon but serious disorders presenting with thrombocytopenia and microangiopathic haemolysis. Thrombotic thrombocytopenic purpura (TTP) is one of these microangiopathic processes. HIV infection is an acquired cause of TTP but the pathogenesis is poorly understood. HIV-associated TTP was previously described to be associated with advanced immunosuppression. The incidence of HIV-related TTP was expected to decline with access to anti-retroviral therapy (ART).MethodsWe undertook an observational study of patients with a diagnosis of TTP admitted to our hospital (CMJAH). The patient demographics, laboratory test results and treatment outcomes were recorded.ResultsTwenty-one patients were admitted with a diagnosis of TTP during the study period. All patients had schistocytes and severe thrombocytopaenia. The presenting symptoms were non-specific and renal dysfunction and neurological compromise were uncommon. 77% of the patients were HIV-infected and, in 7 patients, TTP was the index presentation. The remainder of the HIV infected patients were on ART and the majority were virologically suppressed. A significant female preponderance was present. Only 4 of the 21 patients tested HIV negative with a positive Coombs test in 2. All patients in this cohort received treatment with plasma exchange therapy for a median period of 12days with a 96.5% survival rate. Neither the baseline laboratory features nor the degree of immunosuppression was predictive of the duration of therapy needed for remission.ConclusionHIV-related TTP is still a cause of morbidity and the clinical presentation is heterogeneous which may present a diagnostic challenge in the absence of sensitive biomarkers. Early treatment with plasma exchange is effective but expensive and invasive.