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The availability of factor VIII and factor IX concentrates has considerably improved substitution therapy in hemophilia A and B respectively. The desired activity levels and the corresponding factor VIII or factor IX dosage are indicated. Antifibrinolyics have a favorable action when given simultaneously, though hematuria is an absolute contraindication for antifibrinolytic treatment. The administration of factor IX concentrate in case of hemorrhage due to oral anticoagulation or to liver disease, or in newborns, should be used in emergency situations only, since this material may provoke either thrombosis or disseminated intravascular coagulation. Transmission of hepatitis is also possible.

Factor VIII procoagulant activity, antigen concentration and von Willebrand activity as ristocetin cofactor were determined several times in 10 patients with DIC. These is a significant negative correlation between the DIC-score and the VIII:C/von Willebrand activity ratio.

28 prospective, controlled, randomised studies on the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in surgical patients on dextran 70 prophylaxis are analysed. In all patients the diagnosis had been established by objective methods (fibrinogen test, phlebography, autopsy). In patients undergoing hip surgery (11 studies, mainly fractures of the upper end of the femur) the reduction in the number of DVT under dextran prophylaxis is the more evident the longer after operation phlebography is carried out. Coumarin and dextran prevention are equally effective. In 3 studies where diagnosis by the fibrinogen test was established during the first postoperative week only, no significant effect of dextran can be shown; there is no difference between the effect of dextran, coumarin or small doses of subcutaneous heparin. The effectiveness of dextran prophylaxis in reducing the DVT rate in general surgery (4 papers) is not clear, though 7 studies show that the number of fatal PE is reduced more than fivefold (p less than 0.0005). In patients on dextran prophylaxis, the incidence of DVT is equal to that in patients on coumarin prophylaxis before major gynecological surgery (4 papers). On postoperative initiation coumarin is significantly less effective than dextran. 2 further studies show that dextran is significantly effective as compared to controls and that there is no difference between dextran and heparin prophylaxis. Out of 1932 control patients 36 died of fatal PE verified at autopsy. Only 8 PE were seen in the group of 2011 patients receiving dextran prophylaxis (p less than 0.005). The effectiveness of dextran 70 corresponds to that of small doses of subcutaneous heparin. Dextran prevention is more effective in women than in men. Dextran prophylaxis is simple to carry out, has few contraindications, only rarely causes complications and is already effective during operation.

Between October 1982 and July 1984 systemic thrombolysis was carried out in 10 patients (5 males and 5 females aged 19 to 66 years) with massive pulmonary embolism (PE). Mean thrombolytic treatment duration was 77 hours. The main fibrinolytic agent used (9 cases) was streptokinase. Sequential treatment with streptokinase and urokinase was given to 2 patients and urokinase alone to one. 5 patients received porcine plasmin additionally, and one patient BRL 26921 (streptokinase-plasminogen complex) and human plasminogen. Pulmonary arterial pressures were recorded serially. Pulmonary angiograms were obtained before, occasionally during and after thrombolysis. Pulmonary arterial pressures (systolic: p less than 0.01, diastolic: p less than 0.05, mean: p less than 0.01, paired t-test, two tailed) and pulmonary angiograms (p less than 0.001, paired t-test, two tailed) all showed significant improvement. Thrombolytic treatment had to be discontinued in two patients due to side effects. Patients with the most recent PE showed the best response. Patients with recurrent PE and preexisting pulmonary hypertension showed no improvement. In PE without deep vein thrombosis (DVT), treatment duration of up to three days seems to be appropriate. In PE with concomitant DVT the treatment should be prolonged to achieve complete lysis of thrombi.

In 15 patients on long-term oral anticoagulation the new antirheumatic drug tolmetin (Tolectin) was administered over a period of 10 days. Based on 11 parameters of coagulation, no interaction between the drug and phenprocoumon was found. A significant though clinically irrelevant prolongation of bleeding time was observed.

The radio-fibrinogen test is a simple and sensitive method for diagnosing deep vein thrombosis. Intravenously administered radioactive labelled fibrinogen is incorporated as radioactive fibrin in freshly developing thrombi, and such labelled thrombi may be detected on the body surface with nuclear medical equipment. Homologous iodine 125 labelled fibrinogen is chiefly used since it is known not to transmit viral hepatitis. The weak gamma emittor 125-I allows the use of a portable scintillation detector rate meter with an easily moved measuring device. This bedside method does not involve discomfort for the patient. The correlation between ascending phlebography and the radioactive fibrinogen test is more than 90 percent. The radiofibrinogen test may be used to study thromboembolic diseases, to evaluate drugs for prevention of thromboembolic complications and to confirm clinically suspected fresh deep vein thrombi. Details of the method as used in several thousand measurements are given.

Use of the 125I-fibrinogen-uptake test for detection of freshly developing thrombi is well known. The administration of radiofibrinogen to detect preformed thrombus - the retrospective variant of the 125I-fibrinogen-uptake test - allows the diagnosis of established thrombosis. The correlation with ascending phlebography is 90%. 125I-Fibrinogen cannot be used for scanning, due to its low energy, while 131I-fibrinogen if used involves a high radiation dose to the patient. First experiments with new radiopharmaceuticals for detection of deep vein thrombosis are proposed. Indication lists for the retrospective variant of the 125I-fibrinogen-uptake test are given.

If blood for monitoring of heparin therapy is collected through indwelling catheters it may be contaminated by exogenous heparin. A prospective study comparing thrombin times in plasma obtained by venipuncture and by collection through heparin perfused catheters showed that 26 out of 77 catheter samples were contaminated. In 16 of these 26 cases, overestimation of the heparin effect would have led to incorrect dosage recommendations. It is concluded that blood for laboratory monitoring of heparin treatment should be collected by venipuncture.

Extensive haemostasis analysis in 373 patients with recurrent idiopathic venous thrombosis revealed insufficient fibrinolysis activation by the venous occlusion test in 48%. A case with antithrombin III dysfunction was the only inherited anomaly.

Using one-stage quantitative factor VIII assay and the quantitative immunoelectrophoretic method of LAURELL a good correlation has been found between factor VII activity and protein concentration. In 80% of the known hemophilia A carriers the protein concentration was about twice as high as in normals as compared to the factor VIII activity, whereas about 20% of the known carriers have the same ratio between factor VIII protein and factor VIII activity as normals. The reliability of the test and its usefulness for the detection of hemophilia A carriers are discussed.

Specific antibodies against human factor VIII have been prepared in rabbits and ducks. These antibodies differ from each other in that duck anti VIII antibody precipitates human and rabbit factor VIII, whereas rabbit antibody does not precipitate its own factor VIII. It is possible that the two antisera detect carriers differently.

Evaluation of the therapeutic range of oral anticoagulation for different commercial thromboplastins in comparison with Quick's human brain thromboplastin and Thrombotest is based on simultaneous performance of all methods for each blood sample, on strict adherence to the manufacturer's instructions and on adequate statistical analysis.

1. The effectiveness of 3 X 5000 IU s. c. heparin daily (starting preoperatively) for the prevention of postoperative deep vein thrombosis was evaluated in a prospective, controlled, randomized study including general surgical and urological patients. 125I-fibrinogen test was performed daily in all patients. 2. 178 patients fulfilled the conditions of the protocol. 35.8% of the 95 patients in the control group developed deep vein thrombosis, but only 13.3% of 83 subjects in the heparin group did so. The difference is statistically highly significant (p less than 0.001). 3. The vast majority of all thrombi in both groups appeared before the 3rd postoperative day. 4. With 1 exception, all deep vein thrombi in the heparin group started in the mid-calf region. In the control group 5 deep thrombi originated in the popliteal vein. 5. Heparin displays a better effect in males (n = 34; p less than 0.01) than in females (n = 49; p less than 0.025). 6. In patients undergoing surgery for malignant disease heparin does not reduce the incidence of deep vein thrombosis. 7. Heparin is far more effective in patients under 60 years of age than in those over 60 (p less than 0.005). 8. Heparin is more effective in obese patients than in those of normal body build. 9. Heparin prophylaxis also reduces the incidence of deep vein thrombosis in patients who exhibit predisposing factors. In patients of the control group with preexisting disease of the venous system, there were significantly more deep vein thrombi (p less than 0.01) than in those without predisposing factors. 10. In the heparin group 29% of all thrombin time determinations show a definite prolongation of more than 26 sec (normal value 15 sec). 11. In 14 patients (=16.9%) of the heparin group, 21 side effects or complications were seen. Bleeding complications were the main problem, comprising 5 wound hematomas and hematomas at the injection site, 4 postoperative bleeding episodes and 2 reoperations. There were no complications in the control group. 12. According to the results of 10 well controlled studies, there is no doubt that in general surgery small doses of subcutaneous heparin, commencing preoperatively, do reduce the incidence of postoperative deep vein thrombosis to a significant degree. However, whether this form of prophylaxis is also effective in patients with fractures of the hip and in elective hip surgery cannot, on the evidence available, be decided. In the fields of gynecological surgery and urology as well, more data are needed before this form of heparin prophylaxis can be recommended.

Experience with different peptide substrates for coagulation and fibrinolysis is reported. As the specifity of these substrates is relative, appropriate characterization of the proteolytic activity of defibrination syndromes is only achieved by simultaneous assays with various substrates. The influence of contact activation on blood sampling must be strictly defined.

Human factor VIII has been dissociated into fragment VIII-C and fragment VIII-AG in the presence of calcium chloride (0.25 M). After removing the calcium, recombination of the molecule is obtained. Fragment VIII-C can be activated by thrombin in a similar manner to the coagulant activity of whole factor VIII. This activation is calcium-dependent. In rabbits immunized against purified F VIII, VIII-C and VIII-AG specific antisera against these three entities were obtained.

Studies on one-year function conducted by the European Multicenter Trial showed that, after renal allograft transplantation, bleeding complications were only found in patients treated with cyclosporin as compared with those treated with azathioprin/steroids. To investigate a possible relationship between the bleeding tendency and the cyclosporin treatment, 18 parameters of hemostasis were studied in 11 patients, 6 of whom received cyclosporin A and the other 5 conventional treatment with azathioprin/steroids. Bleeding tendency could not be related to any specific coagulation parameter. Of interest is that clot retraction was significantly lower in the cyclosporin group (88 +/- 9% vs. 125 +/- 10%). Considering the fact that the skin bleeding time according to Ivy was normal in all patients, the clinical significance of the lower levels of the clot retraction appears to be minor. Discriminant analysis showed that these significantly lower clot retraction values could not be related to the lower platelet count levels in platelet rich plasma (205 000 +/- 85 000/mm3 vs. 280 000 +/- 67 000/mm3) but were associated with cyclosporin A treatment. All factor-VIII related activities were elevated in both groups. The main difference between the cyclosporin group and the conventionally treated group was significantly elevated levels of factor VIII procoagulant antigen (VIII: CAg) (cyclosporin A treated group: VIII: CAg 435 +/- 145%, conventionally treated group: VIII: CAg 215 +/- 99%). These results suggest hypercoagulability rather than bleeding tendency under cyclosporin treatment.

Simultaneous determination of heparin cofactor II (HC II) immunologically as antigen (HC II:Ag) and functionally as heparin cofactor (H-HC II) and as dermatan sulfate cofactor (DS-HC II) renders possible a distinction between quantitative and qualitative deficiencies. The usefulness of these methods is demonstrated in the light of a family with several heterozygotes of quantitative HC II deficiency and two unrelated heterozygote men with defective dermatan sulfate cofactor function (DS HC II) and normal HC II:Ag and H-HC II.

A family with combined quantitative and qualitative protein C deficiency is presented. The probably double heterozygote propositus with 7% residual amidolytic protein C activity had deep leg vein thrombosis at the age of seventeen. Other family members were asymptomatic.

Since monitoring of oral anticoagulation (OA) by prothrombin time (PT) is a source of standardization difficulties, the authors have tested another approach. 107 patients under long term OA were monitored by both PT and a colorimetric factor X assay (in vitro activation of factor X with RVV and assessment of amidolytic activity towards S-2222). The PT values were between 10 and 34% (therapeutic range 15--25%), and factor X levels were between 10 and 44% (therapeutic range 16--24%). The correlation between the two methods was highly significant (r = 0.65, p less than 0.001). In 68% of the patients the two tests gave the same information (55 subjects were adequately, 16 insufficiently and 2 over-anticoagulated). For a slightly broader therapeutic range (PT 15--30%, corresponding to 16--28% factor X) concordant information was obtained in 82% of the patients. During stable OA, PT and factor X assay gave very similar information. An advantage of the latter method is the possibility of automation, while a disadvantage is its insensitivity to factor VII.