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 reviewed 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 patients who develop thrombotic disease.

Methods: We searched Medline for papers published between January 1966 and April 1999. We also requested relevant unpublished data from speakers who attended a recent international workshop of paroxysmal nocturnal hemoglobinuria. References from all primary data and review publications were also examined. Only English language publications were included. Event rates for venous thromboembolism and death were pooled using a random effect technique. Reports of paroxysmal nocturnal hemoglobinuria during pregnancy were summarized using descriptive statistics only.

Results: Thirteen retrospective studies of paroxysmal nocturnal hemoglobinuria in nonpregnant individuals were found. The rates of venous thrombosis varied considerably, but were reported to affect 14.4% of all individuals [95% confidence interval (CI) 7.6-25.5]. Among patients from western nations, venous thromboembolism seemed to develop at a higher rate (30.3%, 95% CI 26. 1-34.9). The majority of venous thromboembolic events were intra-abdominal, principally within the hepatic and mesenteric veins. The likely cause of death among patients with paroxysmal nocturnal hemoglobinuria was described 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 pregnant women with paroxysmal nocturnal hemoglobinuria. Two women developed venous 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 (event rate 27.3%, 95% CI 13.7-43.5) were common, often necessitating red cell 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. Three 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 of venous thrombosis among pregnant and nonpregnant individuals with paroxysmal nocturnal hemoglobinuria, especially for fatal thrombosis, we developed practical recommendations for the prevention and treatment of venous thromboembolic disease in these groups.