Abstract
Background:
Thrombotic microangiopathy (TMA) is a hematologic emergency classically associated with thrombotic thrombocytopenic purpura (TTP). TMA can also be associated with other disorders such as disseminated intravascular coagulation, scleroderma, renal crisis, malignant hypertension and antiphospholipid syndrome. Here, we report how severe vitamin B12 deficiency can mimic TTP, presenting with microangiopathic hemolytic anemia, thrombocytopenia, and the presence of schistocytes on peripheral smear, potentially leading to misdiagnosis and unnecessary therapeutic intervention of plasmapheresis.
Methods:
We describe three patients (ages 47 - 73) who presented with fatigue, dyspnea, and pallor. Notably, physical exam findings of easy bruising, bleeding, and neurological symptoms were absent. Laboratory parameters revealed profound macrocytic anemia (Hgb 3.8-6.2, MCV 100.8 - 120.7), thrombocytopenia (PLT 53 - 121), reticulocyte production index (0.1-0.79), markedly elevated LDH (>1950), undetectable haptoglobin, schistocytes in peripheral smear, Vitamin B12 level < 160, a PLASMIC score of 5, and positive intrinsic factor antibodies. A detailed anemia work-up was initiated which included ADAMTS 13 activity (70 - 99%). Initial clinical diagnosis of TTP was made for two of three patients, who subsequently were treated with plasmapheresis.
Results:
In all patients, ADAMTS13 activity levels were preserved ruling out TTP; however, all had undetectable serum B12 levels, elevated methylmalonic acid and homocysteine, and positive intrinsic factor antibodies consistent with pernicious anemia. All three patients were initiated on intramuscular cyanocobalamin therapy with marked hematologic recovery, resolution of hemolysis, and recovery of platelet count. None required ongoing TMA-directed therapy after B12 repletion.
Conclusion:
Severe B12 deficiency is a critical TTP mimicker that can present with pseudo-thrombotic microangiopathy with hemolytic anemia. In any patient presenting with a differential diagnosis of microangiopathic hemolytic anemia, severe Vitamin B12 deficiency should be considered. Early identification is essential to avoid unnecessary plasmapheresis and expedite appropriate treatment. Vitamin B12 levels should be promptly checked in all patients presenting with features of TMA and macrocytosis.
