Is Microangiopathic Hemolytic Anemia (MAHA) a form of hemolytic anemia?

Is Microangiopathic Hemolytic Anemia (MAHA) a Form of Hemolytic Anemia?

Yes, microangiopathic hemolytic anemia (MAHA) is definitively a specific type of hemolytic anemia characterized by intravascular red blood cell fragmentation due to mechanical destruction in abnormal small blood vessels. 1, 2

Definition and Core Characteristics

MAHA represents a distinct subtype of hemolytic anemia where red blood cells are mechanically fragmented as they pass through damaged small blood vessels containing platelet-rich thrombi and fibrin deposits. 1 This is fundamentally different from immune-mediated hemolytic anemias, as MAHA is a non-immune hemolytic process with a negative direct Coombs test. 1, 2

The mechanical destruction occurs when red blood cells become trapped and sheared within fibrin networks formed in the microvasculature, resulting in the characteristic fragmented cells (schistocytes, burr cells, helmet cells) visible on peripheral blood smear. 1, 2

Diagnostic Criteria

To diagnose MAHA, you must document both:

• Anemia with microangiopathic changes on peripheral blood smear showing schistocytes, burr cells, or helmet cells 2
• Laboratory evidence of hemolysis including:
  • Negative direct and indirect Coombs tests (confirming non-immune mechanism) 2
  • Elevated lactate dehydrogenase (LDH) 2
  • Reduced or absent haptoglobin 2
  • Elevated reticulocyte count 3

Relationship to Thrombotic Microangiopathy (TMA)

MAHA is the hematologic hallmark of thrombotic microangiopathy (TMA) syndromes. 4 When MAHA occurs with thrombocytopenia and organ dysfunction, it defines TMA, which encompasses conditions like thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). 3, 1

Critical clinical pitfall: Not all three features (anemia, thrombocytopenia, organ dysfunction) may be present initially—up to 50% of TMA cases at onset do not show all clinical signs clearly. 2 The presence of schistocytes on blood smear is critical for diagnosis and distinguishes MAHA from other causes of thrombocytopenia. 3

Major Etiologies

Primary causes:

• TTP (due to severe ADAMTS13 deficiency <10%) 1
• Typical HUS (following acute gastrointestinal illness) 1
• Atypical HUS (complement-mediated) 1, 5

Secondary causes:

• Disseminated intravascular coagulation (DIC) 4, 6
• Malignancy (widespread microvascular metastases or bone marrow involvement) 6
• Drug-induced (tacrolimus, cyclosporine, chemotherapy agents) 3, 6, 7
• Autoimmune diseases (SLE, antiphospholipid syndrome) 1
• Prosthetic heart valves or intravascular devices 8

Clinical Implications

The recognition that MAHA is a hemolytic anemia subtype is clinically vital because it triggers an urgent diagnostic algorithm to identify the underlying cause. 2 Once MAHA is confirmed on blood smear, you must immediately exclude DIC, assess for TTP with ADAMTS13 testing, evaluate for HUS, screen for malignancy, and review all medications. 2

The PLASMIC score can risk-stratify for TTP likelihood while awaiting ADAMTS13 results. 1, 2 Treatment must be directed at the specific underlying etiology—plasma exchange for TTP, eculizumab for complement-mediated TMA, or stopping offending drugs for drug-induced cases. 1