Haemophilia B Leyden in Greece.

In this paper, a five generation Greek family is described with haemophilia B. The disease is characterized by a normal ox-brain prothrombin time, normal levels of the vitamin-K dependent clotting factors VII and X and a proportional reduction of factor IX activity and antigen levels all of which is consistent with the cross-reacting material negative form of haemophilia B. However, in this family the factor IX levels in the three patients of generation V are around 1 U/dl while the three older patients in generation III have factor IX levels ranging from 28 to 44 U/dl. In the oldest patient of generation V we observed a rise of the factor IX level from 1 U/dl up to the age of 13 to 10 U/dl at age 14. In addition, the older patients have very mild bleeding symptoms or none at all, while the young ones have occasional spontaneous haemorrhages in muscles and joints, compatible with severe or moderately severe haemophilia. The disease appears to be similar to haemophilia B Leyden which has been described in a Dutch family.

Long lasting sitting position and haemostasis.

Blood coagulation, fibrinolysis and platelet aggregability were assessed in 8 physicians aged 30-40 years, who had travelled non-stop by car from Salonica to Athens (510 km) and returned to Salonica after 48 h of rest and after administration of 1 g of aspirin. At the end of journey A, platelet aggregability was found to be increased (6 out of 8 persons), AT III was decreased by 30% (p less than 0.001), the F VIII:C / F VIIIR: Ag ratio was decreased (p less than 0.02) and ELT was prolonged. At the end of journey B the findings were the following: platelet aggregation was not affected, the decrease of AT III was not statistically significant and ELT was significantly shortened (p less than 0.005). A common finding of both journeys was the increase of platelet counts at the end (p less than 0.005). The correlation between long lasting sitting and the response of the haemostatic balance is suggested. The influence of aspirin is discussed.

Abnormalities of lymphocyte subsets and anti-LAV/HTLV-III status in Greek hemophiliacs.

Peripheral blood lymphocyte subsets and the incidence of LAV/HTLV-III antibodies were studied in 63 patients with hemophilia A who had been transfused with a low dose regimen of commercial (U.S.A.) factor VIII concentrates. Five patients with hemophilia B were also included in this study. In hemophilia A patients a significant reduction in the percentage and absolute numbers of T4+ cells and of the T4/T8 ratio and a significant increase in the percentage of T8+ and Leu-7+ cells were observed. These abnormalities were independent of the presence of anti-LAV/HTLV-III. In hemophilia B patients a significant increase of T8+ cells and a decrease of T4/T8 ratio was noted while the percentage of Leu-7+ cells was normal. A significant negative correlation of F VIII units transfused and T4/T8 ratio was seen only in LAV/HTLV (-) patients, suggesting that F VIII per se could cause immunodysregulation. Seropositive patients were found to have consumed a larger amount of F VIII units than seronegative patients during the period 1980-1984 (p less than 0.005).

Marathon Run III: effects on coagulation, fibrinolysis, platelet aggregation and serum cortisol levels. A 3-year study.

Blood coagulation, fibrinolysis, platelet count-aggregation and cortisol were assessed in 35 Finnish amateur runners aged 27 to 56 years (mean 40) and three aged 65, 67, and 82 who had run a non-competitive Marathon in 1975, 1976 and 1977 over the classical itinerary. After the run, in all 3 years, APTT showed shortening (p < 0.001); prothrombin time and plasma fibrinogen were not significantly altered; euglobulin lysis time was shorter (p < 0.001) and FDP increased (p < 0.001); PSPT became positive in all subjects, whereas the ehtanol gelation test remained negative; no cryofibrinogen was detected. Platelet count and aggregation showed increase (p < 0.001) in 1975 (extreme heat, 25 degrees C) but remained unaltered in 1976, 1977 (15-18 degrees C). Cortisol levels were always significantly increased -- more markedly in 1975. Women's responses were similar to those of men. A possible correlation between physical fitness and the responses of haemostatic balance is suggested and the influence of weather is discussed.

Marathon run I: effects on blood coagulation and fibrinolysis.

Blood coagulation and fibrinolysis were assessed in 13 Finnish amateur runners aged 31 to 48, and one 65-year old taking part in a non-competitive marathon (42.2 km). After the run the mean values of partial thromboplastin time showed a very significant shortening, whereas the mean values of the prothrombin time and of plasma fibrinogen were not significantly altered. The mean values of euglobulin lysis time were significantly shorter and the mean values of fibrin degradation products increased highly significantly. After the run, protamine sulphate was positive or strongly positive in all subjects, whereas the ethanol gelation test was negative in all runners; no cryofibrinogen was detected in any participant. Thus, running a marathon race affects the haemostatic balance and activates the fibrinolytic mechanism. The effects of training and physical fitness on the above parameters are discussed.

Marathon run II: Effects on platelet aggregation.

Platelet count and aggregation were assessed in 9 Finnish amateur runners aged 34 to 48, and one 65-year old taking part in a non-competitive marathon race (42.2 km). After the run the mean value of platelet count showed a very significant rise (p less than 0.001). The platelets were markedly more sensitive to both ADP and collagen-induced aggregation. A highly significant increase (p less than 0.001) was noted for both the intensity and velocity of platelet aggregation. The finding of platelet by hyperaggregability after prolonged strenous exercise even in trained subjects is discussed. It is concluded that a through medical examination of the haemostatic balance is recommended before a marathon race.

Jaundice and hepatitis B surface antigen and antibody in Greek haemophiliacs.

The incidence of hepatitis B surface antigen (HBsAg) and antibody (HBsAb) in 101 Greek multitransfused haemophiliacs with or without a previous history of jaundice was studied. Using the haemagglutination inhibition assay, HbsAg was detected in 9.9%, HBsAb in 61.3% and HBsAg plus Ab in 11.8% of the cases. The incidence of jaundice was 14.8%. Liver function was tested by means of Normotest, SGOT, SGPT and serum protein electrophoresis. Abnormal values of liver function tests were found in 47% of the patients. The abnormal findings were related to the presence of HBsAg or Ab and to the history of jaundice. There was no significant difference between the various groups of patients.

Isoimmunization in haemophiliacs.

Serum samples from 134 Greek haemophiliacs multitransfused with fresh frozen plasma and factor--VIII or factor--IX concentrates were investigated for the presence of blood group antibodies. All samples were tested against a panel of selected cells of known but differing genotype. The incidence of blood group antibodies was 12.7%. Anti-D was found in 6 out of the 17 immunized patients, i.e., 35.3% of D-negative haemophiliacs were sensitized. It is concluded that the high incidence of immunization is a serious complication of repeated plasma transfusions.