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Previous Volume 333:1253-1259 November 9, 1995 Number 19 Next

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ABSTRACT

Background Paroxysmal nocturnal hemoglobinuria (PNH), which is characterized by intravascular hemolysis and venous thrombosis, is an acquired clonal disorder associated with a somatic mutation in a totipotent hematopoietic stem cell. An understanding of the natural history of PNH is essential to improve therapy.

Methods We have followed a group of 80 consecutive patients with PNH who were referred to Hammersmith Hospital, London, between 1940 and 1970. They were treated with supportive measures, such as oral anticoagulant therapy after established thromboses, and transfusions.

Results The median age of the patients at the time of diagnosis was 42 years (range, 16 to 75), and the median survival after diagnosis was 10 years, with 22 patients (28 percent) surviving for 25 years. Sixty patients have died; 28 of the 48 patients for whom the cause of death is known died from either venous thrombosis or hemorrhage. Thirty-one patients (39 percent) had one or more episodes of venous thrombosis during their illness. Of the 35 patients who survived for 10 years or more, 12 had a spontaneous clinical recovery. No PNH-affected cells were found among the erythrocytes or neutrophils of the patients in prolonged remission, but a few PNH-affected lymphocytes were detectable in three of the four patients tested. Leukemia did not develop in any of the patients.

Conclusions PNH is a chronic disorder that curtails life. A spontaneous long-term remission can occur, which must be taken into account when considering potentially dangerous treatments, such as bone marrow transplantation. Platelet transfusions should be given, as appropriate, and long-term anticoagulation therapy should be considered for all patients.

Source Information

From the Department of Haematology, Royal Postgraduate Medical School and Hammersmith Hospital, London (P.H., S.M.L., M.B., L.L., J.V.D.); the Haematological Malignancy Diagnostic Service, Institute of Pathology, General Infirmary at Leeds, Leeds, United Kingdom (P.H.); and the Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York (M.B., L.L.).

Address reprint requests to Dr. Hillmen at the Haematological Malignancy Diagnostic Service, Institute of Pathology, General Infirmary at Leeds, Great George St., Leeds LS1 3EX, United Kingdom.

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