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Important advances have been made in the treatment of haemophilia during the past 30 years. We have analysed the data of all the known 163 patients with severe haemophilia A living in Finland in 1930-79 in order to study changes in the prognosis of severe haemophilia A. During the period of 50 years the mean age at death of the patients has increased from 7.8 years in 1930-39 to 25.5 years in 1970-79 and the annual death rate has markedly decreased in all age groups. The decline has been greatest in patients under 10 years of age. In this age group the annual death rate decreased from over 50 per thousand in 1930-39 and 1940-49 to 4.8 per thousand in 1970-79. The prognosis of patients with inhibitors has remained poor, however. Five of the six deaths during the last decade occurred in patients with inhibitors. The overall annual death rate of patients without inhibitors was only 1.2 per thousand in 1970-79, suggesting that at the present time the life expectancy of patients who do not develop inhibitors does not markedly differ from that of the general male population.

Megakaryocyte and erythroid colony formation in vitro by progenitors from the bone marrow and/or blood was studied in 61 patients with essential thrombocythaemia (ET) and 22 patients with reactive thrombocytosis (RT) using the methyl cellulose assay. 47 (77%) of the patients with ET showed megakaryocyte and/or erythroid spontaneous colony formation while 14 (23%) patients did not have any kind of spontaneous colonies. Spontaneous megakaryocyte colony formation was seen in 42 (69%) of the patients and 36 (59%) ET patients showed spontaneous erythroid growth. 31 patients had both types of spontaneous colonies. 11 patients showed only spontaneous megakaryocyte colony formation, and five patients only spontaneous erythroid growth. None of the patients with RT or of the normal controls showed either type of spontaneous growth. Neither the presence of spontaneous megakaryocyte colony formation nor the number of spontaneous colonies correlated with the platelet count. Patients with spontaneous megakaryocyte growth had significantly more often thromboembolic or haemorrhagic problems than those without spontaneous colony formation. In conclusion, it was found that a great majority of patients with ET but none of those with RT grow spontaneous megakaryocyte and/or erythroid colonies. Spontaneous colony formation is strong evidence for a myeloproliferative disorder. The presence of spontaneous colony growth is associated with an increased risk of thromboembolic or haemorrhagic complications regardless of the platelet count, particularly among young patients.

Twenty-five of the 139 Finnish patients (18.0%) with severe haemophilia A alive in 1960 or born later have or have had an inhibitor against factor VIII. 19 of the 110 patients alive have an inhibitor and the current prevalence is 17.3%. The incidence of new inhibitors was 10.3 per thousand patient years for the observation period starting from 1960, median 16 years. The age dependent cumulative risk of developing an inhibitor was 22% at the age of 10. There have been no deaths from bleeding since 1976, which has resulted in a marked decrease in mortality. The annual death rate of patients with inhibitors was 5.8 per thousand years of life in 1980-89 compared to 41.7 in the previous decade. The recent progress in the modalities for treatment of bleedings has markedly improved the outcome of patients with factor VIII inhibitors.

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