C.R.M. Prentice

INCREASED BLOOD VISCOSITY AND FIBRINOLYTIC INHIBITOR IN TYPE II HYPERLIPOPROTEINAEMIA

Blood rheology and several haemostatic factors were studied in patients with type II hyperlipoproteinaemia (HLP) and matched controls. HLP patients had increased blood viscosity (p less than 0.01), the mean level being 18% higher at a low shear-rate (0.94 s-1) and 13% higher at a high shear-rate (94 s-1). The increased viscosity was due partly to a raised haematocrit (p less than 0.05), and partly to increased plasma viscosity (p less than 0.01) associated with increased plasma fibrinogen (p less than 0.02). Red cell deformability was normal, and viscosity was unrelated to either lipid or lipoprotein concentrations. Levels of the major fibrinolytic inhibitor. alpha 2-antiplasmin, measured by both functional and immunological techniques were higher in HLP patients (mean increase 30-32%). Plasminogen activator levels were normal in HLP patients and the ratio of fibrinolytic inhibitor to activator was therefore increased. Plasminogen concentrations were also increased. Levels of factor VIII activity and antigen, antithrombin III and anti-factor Xa activity, alpha 2-macroglobulin, platelet count, and platelet aggregation by adenosine diphosphate and adrenaline did not differ significantly in HLP patients and controls. These results suggest that the premature arterial disease associated with HLP may be related to increased blood viscosity, which reduces arterial blood flow, and increased alpha 2-antiplasmin, the major inhibitor of fibrinolysis.

EFFECT OF COMBINED ŒSTROGEN-PROGESTOGEN ORAL CONTRACEPTIVES, ŒSTROGEN, AND PROGESTOGEN ON ANTIPLASMIN AND ANTITHROMBIN ACTIVITY

Abstract Plasma antiplasmin and serum antithrombin activity together with other tests of coagulation and fibrinolysis were estimated in female volunteers during the normal menstrual cycle and during treatment with oestrogen, progestogen, and œstrogen-progestogen oral contraceptives. Œstrogen and combined œstrogen-progestogen therapy increased plasma antiplasmin and decreased serum antithrombin activity. These changes were accompanied by a rise in plasminogen and a small rise in fibrinogen. The combined preparations also shortened the kaolin partial thromboplastin-time and increased sensitivity to urokinase-induced fibrinolysis. In contrast, no significant changes were seen in coagulation or fibrinolysis during the normal menstrual cycle or progestogen therapy.

REDUCTION OF THROMBUS FORMATION ON DIALYSER MEMBRANES BY ASPIRIN AND RA 233

Abstract Thrombus formation, despite efficient heparin anticoagulation, takes place on the dialysis membranes of the Gambro-Alwall dialyser, causing a high blood-loss to the patient. This thrombus formation is associated with a fall in the patients platelet-count over the course of dialysis. To test the hypothesis that platelet retention on these membranes is an early step in the reaction leading to thrombus formation, a double-blind trial of anti-platelet agents (aspirin and a pyrimido-pyrimidine compound [RA 233]) was carried out. These agents significantly lowered platelet-adhesiveness, reduced the fall in platelet-count over the duration of dialysis, abolished the significant fall in plasminogen level seen during placebo therapy, and reduced the dialyser blood-loss. The results of the trial support the initial hypothesis and also suggest that these anti-platelet agents may be valuable in preventing thrombotic disease.

PREDICTION AND SELECTIVE PROPHYLAXIS OF VENOUS THROMBOSIS IN ELECTIVE GASTROINTESTINAL SURGERY

Clinical features were noted and routine and non-routine laboratory variables were measured before elective major gastrointestinal surgery in 63 patients aged 40 years or more. Deep-vein thrombosis (DVT), detected by routine 125I-fibrinogen leg scanning, developed in 21 patients. Five clinical variables but no laboratory variables were significantly associated with DVT: age; percent mean weight for age, sex, and height (%MW); presence of varicose veins; cigarette-smoking; and sex. The most useful discriminant index of these variables was age in years plus 1.3 x %MW. The index was validated prospectively in a further 41 patients, in 18 of whom DVT developed. The value of the index in selective prophylaxis was then assessed in a further 40 patients, of whom 24 (60%) with high-risk index received low-dose heparin (5000 units twice daily). DVT developed in 4 of the 40 patients, an incidence of 10% compared with the incidence of 37.5% (39 of 104) in the earlier studies with no prophylaxis.

Increased platelet aggregates in vascular and non-vascular illness: Correlation with plasma fibrinogen and effect of ancrod

Abstract Platelet aggregates were measured by the method of Wu and Hoak in patients with acute myocardial infarction, thrombotic stroke, chest infection, chronic peripheral arterial disease and bronchial carcinoma. All five groups had significantly higher levels of platelet aggregates and plasma fibrinogen than control patients and healthy volunteers. Platelet aggregate level was correlated with plasma fibrinogen (p

A Method of Antithrombin Estimation using Plasma Defibrinated with Ancrod

Summary. A method for the measurement of progressive antithrombin activity is described. Higher levels of antithrombin activity are found in plasma defibrinated with ancrod than in plasma defibrinated by heating to 56°C or by thrombin. As ancrod itself has no antithrombin activity, it is recommended as the best agent for defibrinating plasma prior to antithrombin estimation.

Soluble fibrinogen/fibrin complexes in pre-eclampsia.

Significantly increased concentrations of soluble fibrinogen/fibrin complexes were found in plasma samples from ten normal pregnant women when compared with ten non-pregnant age-matched controls. In ten women with pre-eclampsia mean soluble complex concentration was more than three times that in the age, parity, and gestation matched pregnant controls. Soluble fibrinogen/fibrin complexes are also found in the plasma of patients in various hypercoagulable and thrombotic states, including disseminated intravascular coagulation. These findings provide additional evidence that pre-eclampsia is associated with disseminated intravascular coagulation.

Blood Coagulation and Platelet Function following Maximal Exercise: Effects of Beta-Adrenoceptor Blockade

Alterations of platelet function and blood coagulation may occur with exercise or beta-adrenoceptor blockade. To determine if beta-blockade could modify exercise-induced changes in haemostatic factors we performed a double-blind study of acute strenuous exercise in normal males with and without beta-blockade. Exercise increased prostacyclin and plasminogen activator levels but there was no evidence of thrombin generation as indicated by unchanged platelet aggregation responses, beta-thromboglobulin and fibrinopeptide A levels. The only alteration in coagulation by beta-blockade was a reduction in the factor VIII:C and VIII:RAg rise after exercise and this modification may be relevant to the protective effect of these drugs in patients with coronary artery disease.

Total knee arthroplasty in haemophilic arthritis

The results of total knee replacement in five patients aged between 22 and 37 with severe haemophilia A or B are described. All patients had been managed conservatively without success. Frequent bleeds, severe pain and limitation of movement were the indications for operation. Despite close haematological surveillance, bleeding problems occurred in three of the patients and large quantities of plasma concentrates were required. Review of the patients over a period of 25 to 48 months after operation showed dramatic lessening of pain and maintenance of a satisfactory range of movement. The frequency of haemarthrosis diminished markedly and the requirements for factor concentrate in the years after operation fell substantially. Two patients returned to employment. Total knee replacement led to marked clinical improvement in all the patients, but the long-term results are not yet known.

EVIDENCE FOR A QUALITATIVE DEFECT IN FACTOR-VIII-RELATED ANTIGEN IN VON WILLEBRAND'S DISEASE

Abstract von Willebrands disease is an autosomal dominant bleeding disorder, characterised in most patients by an extended bleeding-time, low factor-VIII activity, and defective platelet adhesion to glass beads. Patients with von Willebrands disease have low levels of factor-VIII-related antigen and defective platelet aggregation in response to the antibiotic ristocetin. Factor-VIII activity, factor-VIII-related antigen, and ristocetin-induced platelet aggregation were studied in 12 patients with von Willebrands disease. Ristocetin-induced platelet aggregation was absent or grossly impaired in all patients. 6 of the 12 patients had detectable levels of factor-VIII-related antigen, ranging from 15 to 80% of normal. However, the presence of this antigenic material did not produce ristocetin-induced platelet aggregation, indicating that the antigen was qualitatively abnormal. The findings suggest that in von Willebrands disease impairment of ristocetin aggregation may be due to either a low concentration of or a qualitative defect in factor-VIII-related antigen.