阵发性睡眠性血红蛋白尿症患者血栓易发因素的初步研究

OBJECTIVE: To explore the high risk factors of thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). It has been reported that in Chinese patients with venous thrombosis, the mutation frequency in PROC c.574_576 del (rs199469469), PROC c.565C>T (rs146922325) and THBD c.-151G>T (rs1698852) was higher than that of normal controls, indicating its importance in thrombophilia pathogenesis. METHODS: 142 patients with PNH diagnosed between 2009 and 2015 were enrolled in the study. Clinical data were analyzed and thrombophilia risk factors, such as the level of protein C, protein S, antithrombin III, APC resistance, blood fat, phospholipid antibody, were evaluated. Samples from patients and 100 normal controls were detected for the mutations of PROC c.574_576 del (rs199469469), PROC c.565C>T (rs146922325) and THBD c.-151G>T (rs1698852) by Sanger sequence. RESULTS: Of the 142 PNH patients, 21 (14.8%) patients had at least 1 episode of thrombotic event. Only 2 patients had arterial thrombosis and 19 patients had venous thrombosis. The median age of patients with thrombosis was 35 years old, similar to those without episode (40 years old, P=0.687). The ratios of males and females were 1.33 in thrombosis group and 1.57 in non-thrombosis group (P=0.728), respectively. Patients with thrombosis had the same disease pattern compared with those without episode. Although there was no difference in the level of hemoglobin, WBC and PLT count, and LDH level between patients with thrombosis and those without episode, patients with thrombosis showed higher RBC, higher percentage of CD59(−) granulocytes and RBC, and Flaer(−) granulocytes compared with those without episode. The routine thrombophilia screening tests did not show any difference either between PNH patients and normal controls, or between patients with or without thrombosis. There were two mutations in rs199469469 and rs16984852 sites in patients with PNH, but the mutated patients did not have any thrombosis. Mutation rs146922325 was found in PNH patients. The mutation rate was similar between PNH patients and normal controls, thrombotic PNH and non-thrombotic PNH (P>0.05). CONCLUSION: Compared with non-thrombotic patients, PNH thrombotic patients have bigger PNH clone and higher RBC count. There are no differences among the routine thrombophilia factors and the three known venous eligible genes either between PNH patients and normal controls or between thrombotic and non-thrombotic PNH patients.