From the Research
Vitamin B12 deficiency can indirectly cause schistocytes in the blood, but this is a rare presentation known as pseudo-thrombotic microangiopathy (pseudo-TMA), which mimics thrombotic microangiopathies but is actually due to severe B12 deficiency. Schistocytes are fragmented red blood cells typically associated with conditions involving mechanical damage to red blood cells, such as thrombotic microangiopathies (like thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), disseminated intravascular coagulation, or mechanical heart valves. Vitamin B12 deficiency instead causes megaloblastic anemia characterized by large, immature red blood cells (macrocytes) and hypersegmented neutrophils. The pathophysiology involves impaired DNA synthesis due to B12's role as a cofactor in converting homocysteine to methionine and methylmalonyl-CoA to succinyl-CoA.
Key Points to Consider
- Pseudo-TMA due to vitamin B12 deficiency presents with microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and schistocytes, but is distinct from primary thrombotic microangiopathies in its pathophysiology and treatment 1, 2, 3.
- The presence of schistocytes in vitamin B12 deficiency is not due to direct mechanical damage but rather a manifestation of the body's attempt to compensate for the deficiency, leading to intramedullary hemolysis and the appearance of fragmented red blood cells in the peripheral blood 1.
- Treatment for pseudo-TMA involves vitamin B12 supplementation, which can resolve the hemolysis and improve blood cell counts, unlike primary thrombotic microangiopathies which may require plasma exchange or other specific treatments 2, 3.
- It's crucial to differentiate pseudo-TMA from primary thrombotic microangiopathies to avoid unnecessary and potentially harmful treatments, emphasizing the importance of early and accurate diagnosis 1, 2, 3.
Clinical Implications
- Clinicians should be aware of the rare presentation of vitamin B12 deficiency as pseudo-TMA and consider this diagnosis in patients with unexplained hemolytic anemia, thrombocytopenia, and schistocytes, especially if there are signs of megaloblastic anemia or neurological symptoms suggestive of B12 deficiency 4, 1, 2, 3.
- A low reticulocyte count in the context of hemolysis should prompt an investigation for vitamin B12 deficiency, as this is a key distinguishing feature between pseudo-TMA and primary thrombotic microangiopathies 1, 3.
- Vitamin B12 supplementation is the mainstay of treatment for pseudo-TMA, and its initiation can lead to rapid improvement in hematological parameters and resolution of symptoms 2, 3.