Microangiopathic hemolytic anemia is a direct antibody test-negative intravascular hemolysis caused by excessive shear or turbulence in the circulation.
(See also Overview of Hemolytic Anemia.)
Excessive shear or turbulence in the circulation causes trauma to red blood cells (RBCs) in the peripheral blood, leading to fragmented RBCs (eg, triangles, helmet shapes) called schistocytes (see photo Schistocytes). Schistocytes are characteristic, but not specific for microangiopathic hemolytic anemia (1). Schistocytes cause a high RBC distribution width, reflecting the anisocytosis.
Microangiopathic hemolytic anemia encompasses RBC fragmentation caused by microvascular injury as well as by mechanical devices. Causes of fragmentation hemolysis include
Disseminated intravascular coagulation, a consumptive process secondary to other disorders such as sepsis, cancer, pregnancy complications, trauma, or surgery. Coagulation studies are abnormal with very elevated D-dimer, distinguishing disseminated intravascular coagulation from thrombotic microangiopathies
Stenotic or mechanical heart valves, or prosthetic valve dysfunction (ie, perivalvular leak)
Hemolytic uremic syndrome (HUS—Shiga toxin or atypical/complement-mediated) or related disorders such as the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), and systemic sclerosis renal crisis
Rare cases of significant repetitive impact, such as foot strike hemolysis (march hemoglobinuria), karate strikes, swimming, or hand drumming
Symptoms are those of anemia and the underlying cause of the hemolytic anemia.
Treatment addresses the underlying process. Iron deficiency anemia occasionally is superimposed on the hemolysis as a result of chronic hemosiderinuria and, when present, responds to iron-replacement therapy. Keeping the hematocrit > 30 % can reduce hemolysis caused by turbulent flow in valvular hemolysis.
General reference
1. Schapkaitz E, Mezgebe MH. The Clinical Significance of Schistocytes: A Prospective Evaluation of the International Council for Standardization in Hematology Schistocyte Guidelines. Şistositlerin Klinik Önemi: Hematoloji Standardizasyon Uluslararası Komitesi Şistosit Kılavuzlarının Prospektif Bir Değerlendirmesi. Turk J Haematol 2017;34(1):59-63. doi:10.4274/tjh.2016.0359
Thrombotic Microangiopathy
Thrombotic microangiopathy (TMA) is one cause of microangiopathic hemolytic anemia. Thrombotic microangiopathies result from microvascular thrombus formation, which consume platelets and damage red blood cells, leading to ischemic organ damage. Primary thrombotic microangiopathies include the following:
Thrombotic thrombocytopenic purpura (both immune-mediated and congenital ADAMTS-13 deficiencies)
Hemolytic uremic syndrome (Shiga toxin-associated hemolytic uremic syndrome or complement-mediated hemolytic uremic syndrome also called atypical hemolytic uremic syndrome [AHUS])
TMA can also be secondary to the following:
Medications
Illicit drugs
Systemic rheumatic diseases (eg, systemic lupus erythematosus, scleroderma renal crisis, catastrophic antiphospholipid syndrome)
Hematopoietic or solid organ transplant
Pregnancy (eg, HELLP syndrome[Hemolysis, Elevated Liver Enzymes, and Low Platelets syndrome])
Evidence suggests that some secondary forms of TMA may be complement-mediated (1)
TMA may also be localized to specific organs (eg, the kidney).
TMA can be confirmed by biopsy, but is usually recognized by the following:
Microangiopathic hemolytic anemia
Thrombocytopenia
Compatible clinical findings
When TMA is suspected, the priority is to exclude TTP, which can be rapidly fatal. If patients have diarrhea or other suggestive findings, testing for HUS is indicated. Usually the platelet count is lower in TTP and renal impairment is less profound than in AHUS; however, particularly older patients may have less classical presentations (2).
Treatment is directed at the cause. In AHUS, use of complement inhibitors can be diagnostic as well as therapeutic.
Thrombotic microangiopathy references
1. Palma LMP, Sridharan M, Sethi S. Complement in Secondary Thrombotic Microangiopathy. Kidney Int Rep 2021;6(1):11-23. doi:10.1016/j.ekir.2020.10.009
2. Liu A, Dhaliwal N, Upreti H, et al. Reduced sensitivity of PLASMIC and French scores for the diagnosis of thrombotic thrombocytopenic purpura in older individuals. Transfusion 2021;61(1):266-273. doi:10.1111/trf.16188
