Thrombotic Microangiopathy Mechanism and Management

Pathophysiological Process

Endothelial injury leads to platelet activation, coagulation cascade activation, and formation of platelet-rich thrombi that obstruct the microcirculation, resulting in organ damage, as noted by the European Heart Journal 1, 2
Endothelial detachment is a pathological hallmark of TMA, often resulting from high-shear forces, particularly in malignant hypertension, according to the European Heart Journal 1, 2
Subendothelial exposure triggers coagulation and platelet activation, as reported by the European Heart Journal 1
Thrombus formation leads to formation of a fibrin network and platelet-rich thrombi, as described by the European Heart Journal 2, 3
Microcirculation obstruction causes obliteration of the microcirculation, leading to organ damage, as stated by the European Heart Journal 1, 4
Hemolysis and thrombocytopenia occur due to erythrocytes being trapped and destroyed within the fibrin network and platelets being consumed in thrombi formation, as explained by the European Heart Journal 2, 3

Severe uncontrolled hypertension triggers a vicious cycle involving pressure-induced renal natriuresis, autoregulation failure, increased vascular resistance, and renin-angiotensin system activation, leading to microcirculatory damage, as noted by the European Heart Journal 1, 3
ADAMTS13 deficiency is characterized by severely reduced ADAMTS13 activity (<10%), leading to ultra-large vWF multimers that promote platelet adhesion and aggregation, as reported by Kidney International 5, 6
Complement dysregulation damages endothelial cells, as stated by Kidney International 5
Antiphospholipid antibodies promote thrombosis in the microvasculature and complement activation is involved in tissue injury, as described by Kidney International 5, 6

Laboratory findings include schistocytes on peripheral blood smear, elevated LDH, decreased haptoglobin, and thrombocytopenia, as reported by Kidney International 5, 6
Differential diagnosis is necessary to distinguish between TTP, complement-mediated TMA, and secondary forms, as stated by Kidney International 5, 6
The PLASMIC score can help identify patients at risk for TTP while awaiting ADAMTS13 results, as described by Kidney International 6, 8

Treatment for TTP includes plasma exchange, glucocorticoids, rituximab, and/or caplacizumab, as recommended by Kidney International 5, 6
Malignant hypertension-associated TMA requires aggressive blood pressure control, as noted by the European Heart Journal 1, 2
Complement-mediated TMA may be treated with eculizumab, as stated by Kidney International 5
Antiphospholipid syndrome treatment involves anticoagulation, sometimes with plasma exchange, as described by Kidney International 5