Microangiopathic Hemolytic Anemia (MAHA)

  • Microangiopathic Hemolytic Anemia (MAHA) refers to anemia caused by destruction of erythrocytes due to physical shearing as a result of passage through small vessels occluded by systemic microthrombi. MAHAs are characteristically accompanied by thrombocytopenia in the absence of defects in coagulation. Hemolytic Uremic Syndrome (HUS) and Thrombotic Thrombocytopenic Purpura (TTP) are the prototype MAHAs and likely represent a continuum of disease caused by a variety of etiological insults.
Etiology and Pathogenesis
  • MAHAs can be caused by a variety of inherited and acquired etiological insults; however, their final common pathway appears to be inappropriate systemic platelet plugging within small vessels, resulting in generation of microthrombi in the microcirculation of a number of organs. In the classic case of HUS caused by Shiga Toxin E. coli (STEC) strain 0157:H7, the shiga toxin damages endothelial cells, resulting in platelet aggregation and thus deposition of microthrombi. However, other causes for MAHAs have been recognized including other bacteria, inherited defects, drugs, malignancies, and in some cases idiopathic triggers.
  • The microthrombi generated in MAHAs are primarily composed of platelets and thus the classic laboratory feature of MAHAs is thrombocytopenia. Because the hemolytic anemia that develops is due to physical intravascular shearing of erythrocytes, the peripheral smear classically displays schistocytes. It is important to point out that unlike DIC, consumption of coagulation factors is not a prominent feature of HUS/TTP; consequently, coagulation studies such as PT/PTT are normal.
Clinical Consequences
  • Although originally described as distinct clinical entities, current thought is moving to a notion that TTP and HUS likely represent a clinical continuum. The final clinical consequences in any given patient is likely to represent the organ distribution of the microthrombi in that individual with the primary loci being that of glomerular capillaries and the CNS microcirculation. Consequently, the classic pentad of TTP was originally described as hemolytic anemia, thrombocytopenia, fever, acute renal failure, and fluctuating neurological impairments or AMS. Purpura is simply a consequence of the thrombocytopenia. In contrast, HUS was classically described as displaying the pentad of TTP findings without the neurological symptoms.
  • Traditionally, TTP was observed in middle-aged adults whereas HUS was typically thought to occur in children following a bout of bloody infectious diarrhea. While it is important to remember these classic presentations, it is also important to appreciate that significant overlap between these presentations may occur within these two demographic groups.