Cobalamin deficiency presenting with thrombotic microangiopathy (TMA) features: A systematic review.

INTRODUCTION: Cobalamin deficiency may result in hematologic characteristics similar to thrombotic microangiopathy (TMA). To facilitate diagnosis, we reviewed reported cases of acquired cobalamin deficiency presenting with TMA features (c.def-TMA).

METHODS: A literature search identified reports of c.def-TMA. Deficiency was defined as B12 levels of <118 pmol/L. Corrected reticulocyte counts and reticulocyte production indexes were calculated. Clinical features were presented as proportion abnormal and results summarized as medians and interquartile ranges (IQR).

RESULTS: Patient level data was extracted from 41 identified cases. Median age (years) was 43 (30-55) with 21/41 (51%) being female. Cobalamin deficiency was noted in 35/40 (87.5%) but fold increases in MMA and HC were 30 and 6, respectively. The etiology was pernicious anemia in 28/41 (68%) cases. Anemia was both universal and severe, with hemoglobin levels of 55 g/L (4.7-6.6). Hypersegmented neutrophils were noted in 23/37 (62%), schistocytes in 29/38 (76%) and median LDH levels 3981 U/L (2004-5467). The RPI was <3.0% in all patients. Thrombocytopenia occurred in 33/41 (80.5%) with a median platelet count of 91 × 109 /L (42-112). Plasma infusion or exchange was initiated in 14/41 (34%) with associated complications in 2 cases.

CONCLUSION: Reticulocytopenia (RPI of <3.0%) was a universal finding that aids in differentiating c.def-TMA from other causes of hemolysis. C.def-TMA was associated with severe anemia, generally mild-moderate thrombocytopenia, and significant elevations in LDH.