The impact of the cardiovascular risk factors smoking, hypertension, hypercholesterolemia, and diabetes mellitus on the risk of thrombotic complications was evaluated retrospectively in 132 patients with essential thrombocythemia (ET). The median age at diagnosis was 51 years, and the median follow-up time was 65 months. Sixty-three out of 132 patients (48%) had one or more vascular risk factors, whereas 69 patients (52%) had no risk factors. Thirty-two patients were smokers, 27 had hypertension, 21 hypercholesterolemia, and four diabetes mellitus. During the follow-up, 53 patients (40%) had 98 arterial thrombotic events, half of which were disturbances of cerebral circulation. Fifteen patients (11%) experienced 27 venous thrombotic events. The presence of one or more vascular risk factors increased the risk of arterial thrombotic complications. Of the patients, 52% with one or more vascular risk factors and 29% of those without any risk factors had arterial thrombosis (P = 0.01). In multivariate analysis the only independent risk factor was smoking (P = 0.01). Male gender increased the risk of arterial thrombosis significantly. Thirty-six out of 62 men (58%) but only 17 out of 70 women (24%) had an arterial complication (P < 0.001). Smoking had a strong predictive value for the development of arterial complications in women but not in men. Among women 9/15 (60%) of the smokers and 12/82 (15%) of the non-smokers experienced arterial thrombosis (P = 0.002), whereas among men no difference between smokers and non-smokers could be found. According to the present findings, the male gender should be regarded as a risk factor when deciding about the indication for treatment. Smoking should be discouraged especially among women with ET.

Venous thromboembolism remains an important cause of maternal mortality. For women at risk during pregnancy, the recommended venous thromboembolismprophylaxis is unfractionated heparin. Low molecular weight heparins, such as dalteparin, also may be suitable, but randomised trials have not been performed. Pregnant women (105) with confirmed previous or current thromboembolism were randomised to receive either unfractionated heparin twice daily (mean 20569 IU/day) or dalteparin once daily (mean 4631 IU anti-factor Xa units/day) subcutaneously for thromboprophylaxis during pregnancy and postpartum period. Recurrence of venous thromboembolism and safety of treatments were assessed. Dalteparin administered once daily was safe and effective in thromboprophylaxis during pregnancy and postpartum.

The Finnish Red Cross Blood Transfusion Service has served as the national reference laboratory for haemostasis for more than 40 years and remains still the only one in the country to diagnose inherited coagulation factor deficiencies. By September 1997, 1076 patients with von Willebrand disease (vWD) were registered. The severity of bleeding symptoms leading to diagnosis varied according to the type of vWD. After prepubertal phase distinctly more female than male patients were diagnosed. The prevalence of severe type 3 vWD is 4:1 000 000.

Erythrocytosis is not a feature of essential thrombocythemia (ET); this is the most important difference between ET and polycythemia vera (PV). Transformation of ET to PV has only rarely been described. We have reviewed the blood cell counts of 170 ET patients with a median follow-up of 63 months (range 11-313). Eleven of 170 patients (6.5%) developed erythrocytosis at a median of 29 months (range 12-138) after the diagnosis of ET. According to the present results, the development of erythrocytosis in patients with ET is not a rare phenomenon.

The reasons for diagnostic evaluation and the clinical and laboratory data at diagnosis of 170 patients with essential thrombocythemia (ET) were studied retrospectively. The age distribution was 19-88 years (median 52 years), and 52 patients were under the age of 45 years. In 111 patients (65%) thrombocytosis was a chance finding, but the past history of 37 of these patients revealed symptoms known to be related to ET. The diagnosis was based on a chance finding in a significantly higher proportion of female (74%) than male (53%) patients. The diagnosis of ET is based mostly on negative findings, i.e., on the exclusion of other causes of thrombocytosis, and positive diagnostic tests would be useful. We evaluated the presence of positive diagnostic findings of myeloproliferative disorders in ET. Splenomegaly was seen in 26% and an abnormal karyotype in 5% of the patients. Abnormal megakaryocyte morphology was seen in 80%, abnormal in vitro growth of hematopoietic progenitors in 74%, and abnormal platelet function in 83% of the patients. Both in vitro cultures of hematopoietic progenitors and platelet functions were studied in 36 patients, and in only two of these were both tests normal. We conclude that in most patients with ET the diagnosis can be strongly supported by positive findings, especially by in vitro cultures of hematopoietic progenitors and studies of platelet function.

Department of Medicine, Helsinki University Central Hospital, Helsinki and Finnish Red Cross Blood Transfusion Service, FIN-00310 Helsinki, Finland

The clinical significance of hepatitis C antibodies (anti-HCV) in a healthy population was studied by liver function tests and liver biopsies. The patient population consisted of 195 (96.1%) of the 203 blood donors found to be either anti-HCV positive or indeterminate by a recombinant immunoblot assay (RIBA) during the first year of anti-HCV screening of 307,606 donors in Finland using a first generation enzyme-linked immunosorbent assay. Alanine aminotransferase (ALT) levels in 67 donors reacting positively and in 128 reacting indeterminately by a second generation RIBA (RIBA-4) were monitored to evaluate the prevalence of liver damage. Serum N-terminal type III procollagen (PIIINP) concentrations were measured in all donors who fulfilled our criterion for possible hepatitis C (ALT values over two times the normal upper limit on two occasions or over five times the normal upper limit on one occasion) and in 23 randomly selected RIBA-4 positive donors without ALT abnormalities (control group). Two (1.6%) of the RIBA-4 indeterminate donors had ALT values compatible with possible hepatitis C (negative by polymerase chain reaction) whereas there were 25 (37.3%) such individuals among the RIBA-4 positive donors (P < 0.0005). Twenty (80%) of the latter 25 RIBA-4 positive donors with possible hepatitis C consented to liver biopsy. Of these 20 donors, 11 (55.0%) were found to have chronic persistent hepatitis, four (20.0%) mild, three (15.0%) moderate, and two (10.0%) severe chronic active hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Familial erythrocytosis is heterogeneous with diverse causes. Using a highly informative, simple sequence repeat polymorphism in the 5' region of the erythropoietin receptor gene (EPOR), we did linkage analysis in a large family whose clinical and genealogical features were known. There were no recombinations between the disease phenotype and the polymorphism, the logarithm of odds score for linkage at zero recombination being 6.37. This highly significant linkage indicates that a mutation in EPOR is most probably responsible for the disease phenotype in this family.

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.

Sexual transmission of hepatitis C virus (HCV) was studied in 30 partners to anti-HCV positive multitransfused patients with a bleeding disorder. Anti-HCV ELISA C-100 was used as a screening test. Positive results were confirmed with the first generation RIBA test. Indeterminate samples were tested also with the second generation RIBA to verify the positivity. The time of sexual exposure added up was at least 95 years. 29 partners were anti-HCV seronegative. Only 1 partner was anti-HCV indeterminate. Thus sexual transmission of HCV was a rare event.

National yearly surveys were carried out between 1985 and 1989 to determine the prevalence of antibodies for human immunodeficiency virus (HIV) in Finnish patients with bleeding disorders. From 192 out of the 214 haemophiliacs (90%) tested, 2 patients were positive for anti-HIV. No seropositivities were found after 1985. Fourteen out of 21 patients (67%) with type III von Willebrand's disease, and 7 out of 8 patients (88%) with factor XIII deficiency were tested with negative results. The low prevalence of anti-HIV (0.94%; 2/213 tested), is mainly due to the self-sufficiency for clotting factors, the low prevalence of HIV in the population, and the use of cryoprecipitate during the critical period.

We describe here a family with autosomal dominant erythrocytosis. In in vitro cultures, performed using the methyl cellulose assay, the number of erythroid colonies was normal or marginally increased when a standard concentration of erythropoietin (Epo) was used, but at lower Epo concentrations, the investigated persons formed more colonies than the controls. The difference was generally greater the lower the Epo concentration became. Some erythroid colony growth was seen even in the absence of any added Epo (apart from the minute concentration found in fetal calf serum), a phenomenon not seen in the controls. This finding indicates that the erythrocytosis in this family is caused by hypersensitivity of erythroid progenitors to Epo. The serum Epo concentration was low or low normal in all of the investigated family members, which is in good accordance with hypersensitivity to Epo. The erythrocytosis has not had any obvious effect on the health or life- span of the affected individuals. Many of them have reached an advanced age, and one of the affected family members has won several Olympic gold medals and world championships in endurance sports.

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.

Erythroid colony formation in vitro was studied in 80 patients with erythrocytosis. 43 of the patients had polycythaemia vera (PV), 18 patients had secondary erythrocytosis, 6 had normal red cell mass, and 13 patients were regarded as unclassified. Spontaneous erythroid colony formation, in the absence of exogenous erythropoietin in the cultures, was discovered in all patients with PV, whereas no patient with secondary erythrocytosis or with normal red cell mass showed this phenomenon. 8 of the 13 patients with unclassified erythrocytosis spontaneously formed erythroid colonies. 7 patient with unclassified erythrocytosis have been followed for 5 yr. 3 of the 4 patients with spontaneous colony growth but none of the 3 without it can now be classified as PV. Thus, spontaneous erythroid colony formation indicates PV even in early and atypical cases. Therefore, the culture of erythroid progenitors is very useful in the differential diagnosis of problematic cases with erythrocytosis.

Megakaryocytic colony formation by progenitor cells of 18 patients with polycythaemia vera, seven with secondary erythrocytosis and four with erythrocytosis of unexplained origin was studied in vitro by the methyl cellulose culture assay. Fourteen of the 18 patients with polycythaemia vera showed spontaneous megakaryocytic colony formation, i.e. colony growth with normal human plasma as the only source of colony stimulation. None of the patients with secondary erythrocytosis or erythrocytosis of unknown origin or of the normal controls grew colonies in the presence of normal human plasma only. When the plasma of a patient with aplastic anaemia was used instead of normal human plasma and phytohaemagglutinin stimulated leucocyte conditioned medium (PHA‐LCM) was added to the culture medium, two of the patients with polycythaemia vera and one with secondary erythrocytosis formed slightly increased numbers of megakaryocytic colonies, while the rest of the patients showed normal colony formation. All of the patients with polycythaemia vera but none of those with secondary erythrocytosis or erythrocytosis of unknown origin showed spontaneous erythroid colony growth. The present study shows that most patients with polycythaemia vera form spontaneous megakaryocytic colonies in vitro. This phenomenon has recently also been demonstrated in essential thrombocythaemia and it is apparently analogous to spontaneous erythroid colony growth seen in all myeloproliferative disorders.

The clinical significance of platelet associated IgG in ITP detected by direct platelet suspension immunofluorescence test (PSIFT) was studied. The platelet mean life span (MLS) was measured with 111In-labelled platelets in 17 adult patients. All the patients had shortened platelet MLS. The direct PSIFT was positive in 14 patients. Patients were initially treated with prednisone; 12 patients with poor response to the drug were splenectomised. 8 of these 12 patients were treated with intravenous immunoglobulin (IvIg) before splenectomy. The response to IvIg was as good or better in the 3 patients with negative PSIFT, than in the 5 patients with positive PSIFT.