The predictive value of vascular risk factors and gender for the development of thrombotic complications in essential thrombocythemia.

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.

Thromboprophylaxis with low molecular weight heparin (dalteparin) in pregnancy.

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.

Development of erythrocytosis in the course of essential thrombocythemia.

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.

Von Willebrand disease in Finland.

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.

Essential thrombocythemia at diagnosis: causes of diagnostic evaluation and presence of positive diagnostic findings.

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.

Clinical significance of hepatitis C antibodies in blood donors.

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)

Megakaryocyte and erythroid colony formation in essential thrombocythaemia and reactive thrombocytosis: diagnostic value and correlation to complications.

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.

Familial erythrocytosis genetically linked to erythropoietin receptor gene.

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.

Autosomal dominant erythrocytosis caused by increased sensitivity to erythropoietin.

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.

Low prevalence of antibodies against human immunodeficiency virus in Finnish haemophiliacs.

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.

Transmission of hepatitis C virus to sexual partners of seropositive patients with bleeding disorders: a rare event.

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.

Haemophiliacs with factor VIII inhibitors in Finland: prevalence, incidence and outcome.

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.

Dietary intervention in breast cancer patients: effects on dietary habits and nutrient intake.

Effects of dietary intervention on dietary habits and nutrient levels were studied in 240 women aged 50-65 years who had been operated for a stage I-II breast cancer. Following surgery the women who had participated in a dietary history interview were randomly assigned to one of two groups. The intervention group (n = 121) received individual dietary counselling aimed at reducing dietary fat intake to 20-25 per cent of energy (E per cent) while increasing intake of carbohydrates. No dietary advice was given to women assigned to the control group (n = 119). There was no significant difference between the groups in terms of base-line nutrient intake except for a higher energy intake in the control group (P less than 0.05). Sixty-three (52 per cent) of the women in the intervention group and 106 (89 per cent) of the women in the control group completed the 2-year follow-up. Energy intake decreased after 2 years in both groups and the difference between the groups remained (P less than 0.01). Total fat intake decreased in the intervention group by 12.9-23.3 E per cent after 2 years and by 3.1 E per cent in the control group. The intake of carbohydrates increased from 46.2 to 57.2 E per cent in the intervention group and from 46.2 to 48.9 E per cent in the control group. The study shows that dietary habits and intake of nutrients can be altered through dietary counselling to breast cancer patients, and that such changes are long lasting.

Dietary intervention as adjuvant therapy in breast cancer patients--a feasibility study.

To evaluate the feasibility of using a low-fat diet (i.e. 20-25% of energy (E%) as fat) as a component of adjuvant therapy for breast cancer patients, 240 females aged 50-65 years and operated for a stage I-II breast cancer were entered into a randomized study. The intervention group (n = 121) was to reduce dietary fat intake to 20-25 E% and to increase the intake of carbohydrates. Dietary counselling complemented other adjuvant treatments and the patients were followed for two years. No dietary advice was given to patients in the control group (n = 119). There was no significant difference between the groups in terms of base-line nutrient intake except for higher energy intake in the control group (p less than 0.05). Only 52% of the patients in the intervention group followed through with the dietary regimen for two years, and 89% of the patients in the control group had a two-year follow-up. Energy intake decreased in both groups after two years, and the difference between the two groups remained (p less than 0.01). Total fat intake decreased from 36.2 E% to 22.2 E% after one year in the intervention group and remained at that level after two years. Total fat intake in the control group decreased by 3.6 E% after two years. The low compliance raises concern about the protocol design. The study nevertheless indicates that a long-term reduction of dietary fat intake can be implemented in breast cancer patients.

Splenic dynamics of indium-111 labeled platelets in idiopathic thrombocytopenic purpura.

Splenic dynamics of 111In-labeled platelets and platelet-associated IgG in 33 patients with idiopathic thrombocytopenic purpura (ITP) were studied. Two half-lives were calculated for the biexponential splenic time-activity curve after i.v. injection of 111In-labeled platelets. There was no difference in the mean half-life of the rapid component of the splenic curve (ST1) when patients with negative or slightly positive platelet suspension immunofluorescence test (PSIFT) were compared to those with strongly positive PSIFT (3.0 +/- 0.7 min vs. 3.6 +/- 0.4, p greater than 0.05). Mean half-life of the slow component of the splenic curve (ST2) was found to be longer in patients with a strongly positive than a negative or weakly positive PSIFT (26 +/- 5 min vs. 13.2 +/- 1.0 min, p less than 0.01). It seems that determination of the two components of the splenic time-activity curve provides a useful method for studying platelet kinetics in ITP.