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.

Emerging Role of Direct Oral Anticoagulants in the Management of Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT) are rare but potentially limb- and life-threatening complications of heparin therapy. Continuation of heparin or low-molecular-weight heparin is contraindicated due to platelet activation in the presence of (heparin-dependent) HIT antibodies. Primary treatment options currently include argatroban, fondaparinux, or bivalirudin. However, the parenteral administration routes and interference of argatroban with traditional coagulation markers complicate management. The goal of this review is to assess the viability of direct oral anticoagulants as an alternative treatment option in patients with HIT/HITT. Their use in HIT/HITT is reasonable, given absent cross-reactivity preformed with HIT antibodies. Furthermore, their rapid onset of action and induction of effective anticoagulation provide a favorable basis for their use in this condition. Herein, we summarize 3 studies and 8 case reports comprising 56 patients in whom direct oral anticoagulants were used in the treatment of HIT/HITT.

Cytarabine Induced Acute Cerebellar Syndrome during Hyper-CVAD Treatment for B-Cell Acute Lymphoblastic Leukemia.

Acute cerebellar syndrome can be caused by high doses of cytarabine, but it has not been described in patients with acute lymphoblastic leukemia (ALL) who received hyper-CVAD chemotherapy. Herein, we report two cases with histories of positive Philadelphia chromosome B-cell ALL who developed acute cerebellar syndrome after the exposure to relatively low doses of cytarabine in the second cycle of hyper-CVAD regimen. The cerebellar symptoms were attenuated by cytarabine discontinuation and administration of steroids. This case report provides detailed discussions on the treatments, the potential role of methotrexate in cytarabine-induced cerebellar syndrome, and the importance of carefully monitoring renal function during hyper-CVAD treatment.