microangiopathic hemolytic anemia

Pathophysiology: MAHA occurs when RBCs are physically sheared as they traverse partially occluded microvasculature, typically due to fibrin deposition (as in DIC), platelet-rich thrombi (as in TTP/HUS), or vessel wall abnormalities (as in malignant hypertension or vasculitis). This mechanical trauma produces fragmented erythrocytes called schistocytes, which appear as helmet cells, triangle cells, or other irregular shapes on peripheral smear.

Laboratory findings: Because hemolysis is intravascular, patients show elevated LDH, decreased haptoglobin, elevated indirect (unconjugated) bilirubin, hemoglobinemia, and hemoglobinuria. Reticulocytosis reflects bone marrow compensation. The direct Coombs test (DAT) is negative, distinguishing MAHA from autoimmune hemolytic anemia.

Key causes to know for boards: - TTP (Thrombotic Thrombocytopenic Purpura): ADAMTS13 deficiency leading to large vWF multimers causing platelet microthrombi; pentad includes fever, neuro symptoms, renal failure, thrombocytopenia, and MAHA. - HUS (Hemolytic Uremic Syndrome): Often triggered by Shiga toxin (E. coli O157:H7); triad of MAHA, thrombocytopenia, and acute renal failure, especially in children. - DIC: Widespread activation of coagulation cascade with fibrin deposition, consuming platelets and clotting factors; associated with sepsis, malignancy, obstetric complications. - HELLP syndrome: Hemolysis, Elevated Liver enzymes, Low Platelets—a severe variant of preeclampsia. - Malignant hypertension, disseminated malignancy, mechanical heart valves, and vasculitis can also cause MAHA.

Clinical significance: Recognizing MAHA is crucial because the underlying cause often requires urgent intervention (e.g., plasma exchange for TTP, treatment of underlying infection/malignancy for DIC). Differentiating between these causes relies on additional clinical features and lab findings (e.g., ADAMTS13 activity for TTP, coagulation studies for DIC, renal function and stool cultures for HUS).