Thrombotic microangiopathies
Authors:
J. Novotný; M. Penka
Authors‘ workplace:
Oddělení klinické hematologie FN Brno, Jihlavská 20, 625 00 Brno
Published in:
Transfuze Hematol. dnes,1, 2019, No. Online only 1, p. 1-19.
Category:
Overview
Thrombotic microangiopathies are a group of heterogeneous disorders characterized by disseminated microthrombosis in arterioles and capillaries resulting in consumption of platelets and microangiopathic haemolytic anaemia with potential end organ injury. The diagnosis may be complicated because of overlapping presentations of these disorders. Thrombotic thrombocytopenic purpura (TTP) may be diagnosed on the basis of severely decreased ADAMTS 13 activity (a disintegrin and metalloprotease with thrombospondin motif 13), which is reduced below 10% with possible detection of an IgG inhibitor. The inherited form of TTP (Upshaw- Schulman syndrome) involves mutations of the ADAMTS 13 gene with no inhibitor. Severe reduction of ADAMTS 13 is activity leads to an increased concentration of ultra-large von Willebrand factor multimers with potent affinity to platelet glycoprotein Ib (GPIb) resulting in platelet aggregation. Treatment of choice of acquired TTP includes therapeutic plasma exchange with immunomodulation using corticoids and/or rituximab. The inherited form may be treated by plasma infusion only. Haemolytic-uremic syndrome is induced by shiga toxin producing Escherichia Coli mainly in young children (typical haemolytic uremic syndrome). Shiga toxins are toxic to the endothelium and activate platelets. In such cases, there is serious impairment of renal functions often necessitating haemodialysis and even renal transplantation in some cases. The manifestation of typical haemolytic uremic syndrome is preceded by haemorrhagic diarrhoea. Therapy is mainly supportive. Atypical haemolytic uremic syndromes are induced by inherited disorders of the alternative pathway of complement activation due to mutations in genes of regulatory complement proteins. Some patients have factor H inhibitors. The main therapeutic approach in these forms is the administration of the complement factor C5 inhibitor eculizumab. Secondary forms of thrombotic microangiopathies are mainly seen in association with disseminated malignancies, pregnancy, auto-aggressive disorders, cobalamin C defect (cblC), infections, following solid organ or haematopoietic stem cells transplantation of or solid organs, malignant hypertension and may also be drug induced. The main differential diagnosis involves exclusion of disseminated intravascular coagulation associated with prolongation of global coagulation tests- aPTT and PT.
Keywords:
HELLP syndrome – thrombotic microangiopathies – thrombotic thrombocytopenic purpura – haemolytic uremic syndrome – therapeutic plasma exchange – eculizumab
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Haematology Internal medicine Clinical oncologyArticle was published in
Transfusion and Haematology Today
2019 Issue Online only 1
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