<unk> , as with other microangiopathic hemolytic anemias (MAHAs), is caused by spontaneous aggregation of platelets and activation of coagulation in the small blood vessels. Platelets are consumed in the aggregation process and bind vWF. These platelet-vWF complexes form small blood clots which circulate in the blood vessels and cause shearing of red blood cells, resulting in their rupture and formation of schistocytes. The two best understood causes of<unk>  are due to autoimmunity and an inherited deficiency of ADAMTS13 (known as the Upshaw-Schülman syndrome). The majority of the remaining cases are secondary to some other factor. Autoimmune<unk>  of unknown cause was long known as idiopathic<unk>  but in 1998 the majority of cases were shown to be caused by the inhibition of the enzyme ADAMTS13 by antibodies. The relationship of reduced ADAMTS13 to the pathogenesis of<unk>  is known as the Furlan-Tsai hypothesis, after the two independent groups of researchers who published their research in the same issue of the New England Journal of Medicine. These cases are now classed as an autoimmune disease and are known as autoimmune<unk>  (not to be confused with immune/idiopathic<unk>  purpura). ADAMTS13 is a metalloproteinase responsible for the breakdown of von Willebrand factor (vWF), a protein that links platelets, blood clots, and the blood vessel wall in the process of blood coagulation. Very large vWF multimers are more prone to lead to coagulation. Hence, without proper cleavage of vWF by ADAMTS13, coagulation occurs at a higher rate, especially in the microvasculature, part of the blood vessel system where vWF is most active due to high shear stress. In idiopathic<unk> , severely decreased (<5% of normal) ADAMTS13 activity can be detected in most (80%) people, and inhibitors are often found in this subgroup (44–56%). Genetic<unk>  is inherited in an autosomal recessive manner. This condition may also be congenital. Such cases may be caused by mutations in the ADAMTS13 gene. This hereditary form of<unk>  is called the Upshaw–Schulman syndrome. People with this inherited ADAMTS13 deficiency have a surprisingly mild phenotype, but develop<unk>  in clinical situations with increased von Willebrand factor levels, e.g. infection. Reportedly, less than 1% of all<unk>  cases are due to Upshaw–Schulman syndrome. People with this syndrome generally have 5–10% of normal ADAMTS-13 activity. Secondary Secondary<unk>  is diagnosed when the person's history mentions one of the known features associated with<unk> . It comprises about 40% of all cases of<unk> . Predisposing factors are: * Cancer * Bone marrow transplantation * Pregnancy * Medication use: * Antiviral drugs (acyclovir) * Certain chemotherapy medications such as gemcitabine and mitomycin C * Quinine * Oxymorphone * Quetiapine * Bevacizumab * Sunitinib * Platelet aggregation inhibitors (ticlopidine, clopidogrel, and prasugrel) * Immunosuppressants (ciclosporin, mitomycin, tacrolimus/FK506, interferon-α) * Hormone altering drugs (estrogens, contraceptives, hormone replacement therapy) * HIV-1 infection The mechanism of secondary<unk>  is poorly understood, as ADAMTS13 activity is generally not as depressed as in idiopathic<unk> , and inhibitors cannot be detected. Probable etiology may involve, at least in some cases, endothelial damage, although the formation of thrombi resulting in vessel occlusion may not be essential in the pathogenesis of secondary<unk> . These factors may also be considered a form of secondary aHUS; people presenting with these features are, therefore, potential candidates for anticomplement therapy.
Thrombotic thrombocytopenic purpura
Atypical hemolytic uremic syndrome
Drug-induced thrombocytopenic purpura
Hemolytic–uremic syndrome
Immune thrombocytopenic purpura
Disseminated intravascular coagulation
Heparin-induced thrombocytopenia
Gray platelet syndrome