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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.

The later history is described of four of 10 patients who were reported in 1969 as suffering from non-tropical 'idiopathic splenomegaly'. Two of the four patients developed malignant lymphomas 6 years and 2 years, respectively, after splenectomy but the two other patients have lived for 17 and 15 years, respectively, without developing any signs of a malignant tumour. Thus, four of the original 10 patients have developed malignant's lymphomas. The histology of the patients' spleens has been reviewed in the light of their clinical history, but no criteria have been found which are of clear prognostic value. However, with hindsight it was possible to recognize some cytological abnormality in the spleens in three out of the four patients who developed malignant lymphomas, and it appears that unless the cell population in both the red and white pulp is strictly normal, the patient is likely to develop a malignant lymphoma. The tumours which subsequently developed showed no special or characteristic features. The title 'idiopathic splenomegaly' is clearly unsatisfactory but the alternative 'chronic lymphocytic lymphoma with hypersplenism', although appropriate for the illness of the patients who developed malignant lymphomas, is inappropriate for those in which the pathological process seems not to be neoplastic.

Warm-type autoantibodies of autoimmune hemolytic anemia (AIHA) are usually IgG but may be IgM or IgA. They are usual Rh specific. Cold-type antibodies are IgM or IgG (Donath-Landsteiner [DL] antibody). IgM antibodies are usually anit-l (occasionally anti-i) and DL antibodies anti-P. The warm IgG antibodies do not fix complement (C); they cause red blood cell (RBC) destruction predominantly in the spleen as the result of interaction between fixing; they cause RBC destruction either by intravascular lysis (complement sequence completed) or by interaction between C3-coated RBCs and phagocytes in liver and spleen. Gentic factors, immunoglobulin deficiency, somatic mutation, viral infections and drugs, and failure of T-lymphocyte function, all probably play a part in breaking immunological tolerance and the development of AIHA.