Thrombotic microangiopathies: differential diagnostics and choice of treatment strategy

Thrombotic microangiopathies (TMAs) are a heterogeneous group of diseases with similar clinical and morphological picture, but different pathogenetic mechanisms of development and targeted approaches to treatment. TMA syndrome is characterized by a special type of vascular damage of the microcirculatory bed, which is based on endothelial damage with subsequent thrombus formation, and is manifested by the so-called thrombotic microangiopathic triad, which includes thrombocytopenia, microangiopathic hemolytic anemia and ischemic organ damage. Primary and secondary forms of TMA are distinguished. Primary TMAs include: thrombotic thrombocytopenic purpura (TTP), infection-induced TMA (STEC-HUS, SPA-HUS, virus-associated HUS), atypical hemolytic uremic syndrome (aHUS). Secondary TMAs can be associated with pregnancy, transplantation, medication, malignant arterial hypertension, oncopathology, autoimmune diseases, infections, cobalamin deficiency and account for 80-90% of all TMAs. Primary forms of TMAs are orphan diseases with a prevalence of up to 10 people per 1 million population, are characterized by a severe course and have features of pathogenetic therapy.

Verification of TMA syndrome based on the detection of thrombotic microangiopathic triad is the first stage of diagnosis of diseases of this group, and its confirmation serves as the basis for the initiation of therapy in the form of high-volume plasma exchanges (PE). The second stage of diagnostics involves verification of the etiologic diagnosis and transition to the final treatment protocol. The central place in the differential diagnostics of TMAs is the determination of the activity of metalloproteinase ADAMTS-13 in the blood plasma to exclude TTP, an urgent condition requiring the appointment of a specific treatment protocol, including PT, recombinant ADAMTS-13, immunosuppression, inhibitors of the interaction of von Willebrand factor with platelets. When TTP is excluded, further diagnostic search is based on clinical suspicion with subsequent performance of appropriate laboratory tests to verify STEC-HUS, secondary TMAs.

Atypical HUS, as a diagnosis of exclusion, refers to a severe form of TMA, which also requires a special therapeutic approach in the form of complement blocking therapy, which significantly improves survival and renal outcomes. In this case, atypical HUS should be suspected in all patients with TMA syndrome in the absence of an effect on the etiotropic, symptomatic treatment of any TMA-associated conditions.