C.D. Forbes

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.

Contribution of the Haematocrit to the Bleeding Time

Bleeding time, platelet count and haematocrit were performed in 64 normal, anaemic and polycythaemic subjects with normal renal function and platelet counts over 100 X 10(9)/1. There was a significant inverse correlation between the bleeding time and haematocrit (r = -0.47) and an inverse correlation of the haematocrit and platelet count (r = -0.46). We suggest that the effect of the haematocrit on the bleeding time could explain the shorter bleeding time in men compared to women, and the shorter bleeding time in subjects with arterial disease, in whom an increased haematocrit is commonly found.

Immunological abnormalities in haemophilia: are they caused by American factor VIII concentrate?

Scottish patients with haemophilia, most of whom had received no American factor VIII concentrate for over two years, were found to have immunological abnormalities similar to those in their American counterparts--that is, a reduced proportion of T helper cells, an increased proportion of T suppressor cells, and a reduced response to concanavilin A. Factor VIII from both the United States and Scotland severely inhibited the in vitro lymphocyte response to mitogens in patients and controls. The American and Scottish concentrates could not be distinguished in terms of either patient usage or their effect in vitro. These results argue against a disease vector specific to American blood products.

SUBCUTANEOUS ANCROD IN PREVENTION OF DEEP-VEIN THROMBOSIS AFTER OPERATION FOR FRACTURED NECK OF FEMUR

In a randomised double-blind controlled trial 53 patients received 5 daily subcutaneous injections of ancrod (Arvin) after operation for fractured neck of femur, and 52 patients received saline fractured neck of femur, and 52 patients received saline injections. Deep-vein thrombosis (D.V.T.) was detected by bilateral ascending venography or necropsy 6--16 days after surgery. The frequency of D.V.T. and bilateral D.V.T. was significantly lower in the ancrod group (P less than 0.01). The frequency of major D.V.T. (thrombi in veins proximal to the calf, or calf-vein thrombi more than 3 cm long) was also significantly lower in the ancrod group (P less than 0.001). No complications of ancrod prophylaxis occurred. Ancrod reduced plasma-fibrinogen, and hence plasma and blood viscosity, during the first week after surgery; preoperative levels of fibrinogen and viscosity were not associated with post-operative D.V.T. Subcutaneous ancrod is a simple and effective alternative to oral anticoagulants for the reduction of the frequency of D.V.T. after operation for hip fracture, and merits assessment in other high-risk groups of patients.

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.

Inhibition of whole blood platelet aggregation by nicardipine, and synergism with prostacyclin in-vitro

Platelets are involved in the pathogenesis of vascular disease, and calcium channel blocking agents (CCB) such as nicardipine, are being used in the treatment of such disorders. CCBs are known to have minor anti-platelet actions from studies performed in platelet rich plasma (PRP). Recently it has become possible to study platelet aggregation in whole blood. The effects of nicardipine on whole blood platelet aggregation were studied in-vitro using the Clay-Adams Ultra Flo 100 whole blood platelet counter. Nicardipine inhibited aggregation to 0.5 micrograms/ml collagen, and 0.5 mM arachidonic acid in a dose dependent manner, but had minimal effects on aggregation to 10 microM ADP. Nicardipine also acted synergistically with prostacyclin to inhibit aggregation. The effect of nicardipine on generation of PGI2 and TxA2 from whole blood was studied. Nicardipine did not affect TxA2 production, but significantly increased PGI2 production at high concentration. The effect of nicardipine on vascular PGI2 production was also assessed using umbilical artery rings, but nicardipine had no effect on PGI2 production. This study confirms that CCBs have inhibitory actions on platelet aggregation, and this may be of value in the treatment of vascular disease.

Modification of induced ischaemic pain by transcutaneous electrical nerve stimulation

&NA; Endurance to ischaemic pain was assessed in healthy subjects receiving either continuous or trains of transcutaneous electrical nerve stimulation (TENS) at different intensity levels. Control subjects received no stimulation. Self‐reports of pain thresholds and pain tolerance levels were obtained and on‐going pain was assessed by means of two linear pain scales. At the end of each trial, descriptions of intolerable pain were obtained using the McGill Pain Questionnaire. High intensity continuous stimulation raised pain tolerances and endurance of pain, but was associated with higher levels of reported pain when tolerance was reached. Low intensity trains of stimulation raised pain thresholds and tolerance levels but did not increase endurance to induced ischaemic pain. Our results suggest that the response to induced ischaemic pain can be selectively modified by peripheral electrical stimulation depending on its temporal and intensity characteristics.