Thrombotic microangiopathies are clinical syndromes in which blood clots occur in the smallest blood vessels in the body, and in multiple organ systems.
TMA is histopathologic with abnormalities in the arteriolar and capillary walls resulting in micro thrombi.
They are typically associated with a low platelet count and fragmented red blood cells.
Microangiopathichemolytic anemia is a subtype of intravascular hemolysis, characterized by red cell fragmentation due to direct trauma.
Thrombotic microangiopathy (TMA) may be associated with certain drugs and with stem cell transplantation.
numerous conditions can give rise to TMA, through one of three principle mechanisms: primary or secondary hemostatic derangements or endothelial injury.
TMA is associated with immune mediated thrombocytopenic purpura and atypical hemolytic uremic syndrome.
Syndromes of thrombotic microangiopathy are diverse and may be due to hereditary or acquired features.
Drug induced thrombotic microangiopathy can be classified into immune-mediated or non-immune mediated cytotoxicity, and is commonly seen with antibiotics, chemotherapy, immunosuppressants cardiac and narcotic medications.
Syndromes typically present with microangiopathic hemolytic anemia and thrombocytopenia due to microvascular thrombosis or occlusion, which reads to mechanical shearing of erythrocytes and the consumption of platelets.
ADAMTS13 tests and molecular of complement tests have increasingly recognized that thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome, Shiga toxin associated hemolytic syndrome may present without microangiopathic hemolytic anemia or thrombocytopenia.
It is believed that atypical hemolytic uremic syndrome is a disorder of complement dysregulation, in which the complement system is turned on and cannot be shut down, and is usually caused by defects in the genes that code for complement control proteins.
Microangiopathic hemolytic anemia confirmed by evidence of intravascular hemolysis and schistocytes.
Endothelial, activation, and thrombosis lead to microvascular occlusion, shearing of red cells, and platelet consumption.
It is spurred by mechanical destruction of erythrocytes as they negotiate blood vessels narrowed by damaged endothelium.
Can cause acute kidney injury via tubular renal damage by free hemoglobin.
TM maybe may occur in children and adults.
Pregnancy, drugs, infections, hypertension, and other illnesses are associated with thrombotic microangiopathies.
Onset may be sudden or gradual.
Clinical features include: microangiopathic hemolytic anemia, thrombocytopenia, and organ injury.
Pathologic manifests as vascular damage with arteriolar and capillary thrombosis.
Associated with endothelial and vessel wall abnormalities.
Associated with 5 mechanisms of vascular stenosis.
Thrombotic thrombocytopenia purpura Is the classic disorder of microangiopathic hemolytic anemia.
Thrombotic thrombocytopenia purpura usually associated with a severe deficiency of ADAMS13 leading to excessive accumulation of unfolded vWF in the microcirculation causing intravascular vWF-platelet and platelet-platelet aggregation with organ failure.
Patients with HUS or other thrombotic microangiopathic syndromes usually have a normal or at least detectable ADAMS13 activity.
A second type of vascular stenosis is related to a hypercoaguable state with systemic micro vascular thrombosis, as is seen with DIC, antiphospholipd syndrome, HELLP syndrome and HIT.
In the above mechanism low fibrinogen and prolonged coagulation times occur.
The third mechanism relates to micro vascular obstruction due to disseminated malignancy.
The fourth type of microangiopathic hemolytic anemia is associated with small blood vessel vasculitides.
The fifth mechanism is associated with vascular damage from platelet aggregation and vascular microcirculation dysfunction due to endothelial injury by complement activation.
Microvascular occlusive disorders with intra renal and systemic fibrinoid necrosis with accumulation of fibrin and platelet clots in the arteriolar lumen with eventual platelet consumption and RBC fragmentation.
Vascular devices such as prosthetic heart valves, ventricular assist devices, and extracorporeal membrane oxygenators are the most common causes of microangiopathic hemolytic anemia.
Excluding vascular devices and outbreaks of food poisoning due to Shiga toxin producing E. coli, thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome account for the majority of the cases presenting with microangiopathic hemolytic anemia and thrombocytopenia.
Can be triggered by toxin mediated endothelial damage from Shiga toxin-producing E.coli in hemolytic uremic syndrome.
Can be caused by injury due to congenital or acquired disorders in complement activation such as atypical hemolytic uremic syndrome.
Can be associated with hematopoietic stem cell transplantation.
May be associated with chemotherapy agents such as gemcitabine or mitomycin C.
May be associated with calcineurin inhibitors cyclosporine or tacrolimus.
Malignant hypertension and scleroderma can cause vascular hyperactivity and Endothelin-1 dysregulation that can cause thrombotic microangiopathy.
Complement activation is part of the pathogenesis of thrombotic microangiopathy with atypical hemolytic uremic syndrome and hematopoietic stem cell transplantation.
Eculizumab, a terminal complement inhibitor may be used to manage complement related microangiopathy.
Caplacizumab approved for acquired TTP in adults in combination with plasma exchange in immunosuppression is a nanobody that binds to a A1 domain of vonWillebrand’s factor and prevents it from binding platelets.