Pulmonary embolism and deep venous thrombosis (PE/DVT) are well-known lethal complications in autoimmune hemolytic anemia (AIHA). However, the impact of their treatment is unclear. Here, we describe three elderly Japanese patients with AIHA who developed PE/DVT early after glucocorticoid administration. All patients presented with active hemolysis and high D-dimer levels upon admission. Thromboembolism was confirmed within 2 weeks after starting glucocorticoid, suggesting that both active hemolysis and glucocorticoid administration synergistically contributed to the development of PE/DVT. Clinicians should consider that such synergism may increase the risk of thromboembolism in patients with AIHA, and prophylactic anticoagulation is worth considering in patients after starting glucocorticoid.
Mbtd1 (mbt domain containing 1 ) encodes a nuclear protein containing a zinc finger domain and four malignant brain tumor (MBT) repeats. We previously generated Mbtd1 -deficient mice and found that MBTD1 is highly expressed in fetal hematopoietic stem cells (HSCs) and sustains the number and function of fetal HSCs. However, since Mbtd1 -deficient mice die soon after birth possibly due to skeletal abnormalities, its role in adult hematopoiesis remains unclear. To address this issue, we generated Mbtd1 conditional knockout mice and analyzed adult hematopoietic tissues deficient in Mbtd1 . We observed that the numbers of HSCs and progenitors increased and Mbtd1 -deficient HSCs exhibited hyperactive cell cycle, resulting in a defective response to exogenous stresses. Mechanistically, we found that MBTD1 directly binds to the promoter region of FoxO3a , encoding a forkhead protein essential for HSC quiescence, and interacts with components of TIP60 chromatin remodeling complex and other proteins involved in HSC and other stem cell functions. Restoration of FOXO3a activity in Mbtd1- deficient HSCs in vivo rescued cell cycle and pool size abnormalities. These findings indicate that MBTD1 is a critical regulator for HSC pool size and function, mainly through the maintenance of cell cycle quiescence by FOXO3a.
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