Paroxysmal nocturnal hemoglobinuria and the risk of venous thrombosis: Review and recommendations for management of the pregnant and nonpregnant patient

Background Paroxysmal nocturnal hemoglobinuria is a rare, clonal primitive hematopoietic cell disorder, often affecting middle-aged adults, including women of reproductive age. Major morbidity and mortality with this disease are often ascribed to the development of venous thromboembolism. We reviewe d the current literature on the risk of venous thrombosis among nonpregnant and pregnant patients, and generated recommendations for the prevention of venous thromboembolism, as well as duration of treatment for affected pati ents who develop thrombotic disease. Methods: We searched Medline for paper s published between January 1966 and April 1999. We also requested relevant unpublished data from speakers who attended a recent international worksho p of paroxysmal nocturnal hemoglobinuria. References from all primary data and review publications were also examined. Only English language publicati ons were included. Event rates for venous thromboembolism and death were po oled using a random effect technique. Reports of paroxysmal nocturnal hemog lobinuria during pregnancy were summarized using descriptive statistics onl y. Results: Thirteen retrospective studies of paroxysmal nocturnal hemoglob inuria in nonpregnant individuals were found. The rates of venous thrombosi s varied considerably, but were reported to affect 14.4% of all individuals [95% confidence interval (CI) 7.6-25.5]. Among patients from western natio ns, venous thromboembolism seemed to develop at a higher rate (30.3%, 95% C I 26.1-34.9). The majority of venous thromboembolic events were intra-abdom inal, principally within the hepatic and mesenteric veins. The likely cause of death among patients with paroxysmal nocturnal hemoglobinuria was descr ibed in nine studies: 22.2% of fatalities were due to venous thrombosis (95 % CI 11.8-38.0), more commonly in western countries (event rate 37.2%, 95% CI 21.6-56.0). Another 20 published reports described the outcome of 33 pre gnant women with paroxysmal nocturnal hemoglobinuria. Two women developed v enous thromboembolism during pregnancy and another 2 during the postpartum state for a combined event rate of 12.1% (95% CI 3.4-25.2), three of which resulted in death. The all-cause mortality rate was 20.8% (95% CI 7.3-39.0) . Both anemia (event rate 72.7%, 95% CI 56.5-86.3), and thrombocytopenia (e vent rate 27.3%, 95% CI 13.7-43.5) were common, often necessitating red cel l or platelet transfusions. Almost half of all infants (54.8%, 95% CI 36.1- 72.7) were delivered preterm, and had a mean live birth weight of 2,800 g. Th ree of 34 reported births ended in death (perinatal mortality rate 8.8%, 95% C 1.9-23.7). Conclusion: In accordance with the apparently high rate o f venous thrombosis among pregnant and nonpregnant individuals with paroxys mal nocturnal hemoglobinuria, especially for fatal thrombosis, we developed practical recommendations for the prevention and treatment of venous throm boembolic disease in these groups. Copyright (C) 2000 S. Karger AG, Basel.