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The increasing use of biomaterials in blood-contacting applications underlines the importance of an enhanced understanding of the interactions of blood with foreign surfaces. These interactions constitute a complex response involving the possible participation of proteins, platelets, the intrinsic coagulation, the fibrinolytic system, erythrocytes, leucocytes and the complement system. Interpretation of blood-biomaterial interactions and the development of improved biomaterials require the utilisation of in vitro, ex vivo or in vivo blood compatibility assessment procedures, although there is no ideal procedure for linking assessment to the potential clinical performance of a material. In clinical application, foreign surfaces represent only one of the factors influencing the blood response, with the response also influenced by the presence of antithrombotic agents, the blood condition and the nature of the application.

Fibrin deposition in rheumatoid arthritis may be responsible for some of the clinical manifestations of the disease. It has been shown that in severe rheumatoid arthritis fibrinolysis is decreased but can be stimulated using the fibrinolytic enhancing agent stanozolol. A prolonged increase in fibrinolysis may decrease joint fibrin deposition and lead to clinical improvement and we have therefore investigated stanozolol as a therapeutic agent. Forty patients were enrolled. Twenty patients received stanozolol 5 mg twice daily for six months and 20 received a matching placebo. Assessment of disease activity was made in the conventional way. Results show that the two groups were comparable. After six months nine of the control patients had withdrawn because of drug ineffectiveness compared with two stanozolol patients, and five control patients felt they had improved compared with 15 stanozolol patients. Disease activity had significantly decreased by the end of the study in the treated group, and detailed analysis showed improvement in ESR, articular index, duration of morning stiffness and visual analogue pain scale. We suggest that stanozolol may be of value in rheumatoid arthritis although this pilot study has looked at only small numbers of patients over a short period.

Elevated oestradiol (E2) levels may be a risk factor for ischaemic heart disease in men, although the mechanisms for the elevation of oestrogen and for its adverse effects remain unclear. We have studied 100 Caucasian males undergoing elective coronary angiography for ischaemic chest pain and measured serum oestradiol, a profile of haemostatic tests, extent of coronary artery disease and evidence of previous myocardial infarction in order to assess any relationships which could explain the effect of elevated serum oestradiol levels. Levels were significantly higher in men with a history of myocardial infarction compared to those without (p less than 0.01), but were unrelated to the extent of coronary disease or to the haemostatic tests. These results suggest that the association of oestradiol with coronary events relates to myocardial infarction, not to atherogenesis, and is not due to any currently measurable alterations of haemostasis. Current beta-adrenoceptor blocker treatment was associated with lower oestradiol and thromboxane B2 concentrations (both, p = 0.06). These incidental findings suggest that further studies of the effects of beta-blockade on oestradiol and thromboxane metabolism are indicated.

In systemic lupus erythematosus (SLE) the lupus anticoagulant is known to be associated with thrombosis. However, this anticoagulant only occurs in a small percentage of patients. Histopathological studies suggest a more generalized thrombotic tendency with platelets and fibrin within the microvasculature. Fibrinogen is elevated in SLE and this may lead to the fibrin deposition described. We wondered if decreased fibrinolysis contributed to this and we infused desamino D-arginine vasopressin (DDAVP) into ten patients with SLE and eight controls. DDAVP stimulates endothelial production of plasminogen activator (PA) and factor VIII. Baseline results showed a significant decrease in PA activity with a concomitant increase in fibrinogen in SLE. The t-PA and inhibitor levels were normal but factor VIII was increased. After infusion of DDAVP, results indicated that, despite baseline results, SLE patients were able to respond to stimulation and the increase in PA activity produced a decrease in plasma fibrinogen levels. These findings may have therapeutic implications.

The majority of severe haemophiliacs will develop a crippling arthritis consequent upon recurrent haemarthroses although the pathogenic mechanism remains unclear. We have carried out technetium-99 pertechnetate joint scans in the elbows, knees and ankles of 23 haemophilic patients and compared the isotope uptake of the 15 patients with clinical and radiological evidence of arthritis to that of eight patients without arthritis, to 13 age-matched healthy male controls, and to 10 age-matched males with active rheumatoid arthritis. Isotope uptake into the knee joints was significantly higher in haemophilic arthritis than in controls, haemophiliacs without arthritis, and patients with rheumatoid arthritis [median percentage uptake of administered technetium (Tc) dose X 10(3) in right knee = 9.4, 6.2, 6.4 and 6.6, respectively]: and the differences from haemophilic arthritis were all significant (p less than 0.01, Mann-Whitney U test). Similar differences were seen in the elbows and ankles. Increased Tc uptake correlated strongly with frequency of haemarthrosis, pain, synovitis, range of movement and radiological changes in knees and elbows, but poorly with the lesser changes seen in the ankles. These results would support the theory that haemophilic arthritis amongst the inflammatory arthropathies and that scanning is an appropriate technique for following progression of joint disease.

A detailed clinical and radiological examination of the joints and laboratory studies were carried out on 139 haemophiliacs attending a single centre. The group included more patients with mild and moderate haemophilia (factor levels 6 to 60 per cent) than in previous studies. Haemarthrosis, the most common bleeding manifestation, had affected more than two-thirds of patients including many with mild or moderate disease. Restriction and contracture of the knees and elbows were the most common clinical features and, with the ankles, these joints were most frequently affected both clinically and radiologically. Using a combination of clinical and radiological features, 42 per cent of the patients could be classed as having 'definite' and a further 14 per cent 'possible' haemophilic arthritis. Although haemarthroses were equally prevalent in patients with classical haemophilia and Christmas disease, arthritis was more frequently present in the former. Haemarthrosis and joint disease were exceptional in von Willebrand's disease. The prevalence of arthritis generally related to disease severity as measured by factor level but, in contrast to earlier studies, definite arthritis was seen in some patients with factor levels up to 20 per cent of normal although the number of affected joints was less in these patients with milder disease. Laboratory test abnormalities including circulating immune complexes and hypocomplementaemia were noted in some patients but the abnormalities correlated poorly with clinical features. The present results suggest a recent slight reduction in the prevalence or severity of haemophilic arthritis, possibly attributable to recent improvements in factor replacement treatment. Longer-term studies are required to show whether arthritis is indeed lessening or whether the onset is merely being delayed.

The viscosity of 10 specimens of rheumatoid synovial fluid was assessed using side-room tests as well as being measured in a viscometer. All of the tests, and particularly the 'mucin clot', correlated well with measured viscosity. We conclude that the mucin clot test does indeed reflect viscosity and can demonstrate the presence of inflammatory joint disease.

Vascular prostacyclin (PGI2) regulates platelet function and blood flow. In systemic sclerosis (SS) there is increased platelet aggregation (PA) but no information is available on the platelet/PGI2 relationship. We evaluated platelet sensitivity to a PGI2 analogue ZK36374 in 17 SS patients and 18 controls. The percentage (%) inhibition of PA was measured at two doses of ZK36374 with saline giving the 100% baseline. In the SS group 2 ng ZK36374 produced a percentage inhibition of 19 + 14 compared to a control value of 60 + 21, and 3 ng a percentage inhibition of 47 + 21 in the SS group and 82 + 20 in the controls. In 11 SS patients treated with either prostaglandin E or nifedipine the sensitivity approached normal. These data suggest that SS platelets are less sensitive to the inhibitory effect of PGI2 on PA. This may contribute to the vascular lesions of SS. Other cells are resistant to the effects of PGI2 and our findings support this picture of cellular resistance.

Abnormalities of haemostasis are common in diabetes mellitus. As indicators of fibrinolysis and coagulation, plasmin and thrombin activity were assessed by assay of the fibrinogen peptide derivatives B beta 15-42 and fibrinopeptide A respectively in 60 diabetic patients and 50 control subjects in a cross-sectional study. Glycosylated haemoglobin (HbA1) correlated with B beta 15-42 (r = -0.26, p less than 0.05) and fibrinopeptide A (r = 0.30, p less than 0.05) in the diabetic patients suggesting that poor glycaemic control (i.e. high HbA1 levels) was associated with depressed plasmin and enhanced thrombin activity. Compared to controls, fibrinopeptide A levels were increased in diabetics (p less than 0.001) irrespective of sex or type of diabetes. B beta 15-42 levels were normal in diabetic females but increased in diabetic men (p less than 0.001) possibly secondary to the activation of coagulation. These results suggest that in diabetes mellitus activation of coagulation is the dominant haemostatic abnormality and that better glycaemic control could influence in-vivo plasmin and thrombin activity favourably.

Viscosity measurements of serum and plasma have been suggested as improvements on other indicators of activity in the rheumatic diseases. We compared the clinical assessment of disease activity in 71 patients with rheumatoid arthritis against various laboratory tests including viscosity measurements. The effects of smoking were also studied. While many of the tests showed correlations with each other, none was found to correlate with any of the clinical parameters. Smoking lowered the ESR, but did not affect the plasma viscosity in these patients. Thus viscosity measurements were no improvement in assessing activity in a cross section of patients, though its lack of dependence on smoking habit may be an advantage in sequential studies.