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Biomedical subjects

C A Ludlam

Publications and source records attributed to C A Ludlam.

At least 163 records · Page 9Linked to original sources

Platelet and coagulation function in patients with abnormal cardiac valves treated with sulphinpyrazone.

Eight patients on warfarin with rheumatic heart disease and prosthetic cardiac valves were selected for study on the basis of persistently elevated plasma beta-thromboglobulin (beta-tg) and platelet factor 4 (PF4) concentrations. Platelet mean lifespan and fibrinogen half life were short, and positively correlated, and both were inversely related to the plasma concentration of the platelet specific proteins. Antithrombin III (ATIII) levels were also reduced. Treatment with sulphinpyrazone resulted in lengthening of both platelet and fibrinogen survival, a rise in ATIII but no change in the beta tg or PF4 concentrations. It is concluded that patients with abnormal cardiac valves and raised plasma levels of beta tg or PF4 have, despite warfarin, a consumption coagulopathy that can be inhibited by sulphinpyrazone.

Adult↗

Carrier detection in haemophilia a by immunological measurement of factor VIII related antigen (VIIIRAg) and factor VIII clotting antigen (VIIICAg).

23 obligate carriers of mild and severe haemophilia A and 26 normal females were bled on three occasions, and their plasmas assayed for procoagulant factor VIII (VIIIC), factor VIII related antigen (VIIIRAg) and factor VIII clotting antigen (VIIICAg). A comparison of the ratios VIIIC/VIIIRAg and VIIICAg/VIIIRAg indicated that, although the two ratios gave the same proportional misclassification of carriers as normals (four of 23), the latter ratio showed greater discriminatory power when an unequal variances predictive method was used to calculate likelihood ratios (for carrier status). This greater power was shown to be due to a greater reproducibility between visits for the VIIICAg/VIIIRAg ratio. Discrimination was considerably better when the median of the three median values for each variable was analysed, compared to the median value obtained at the first visit. There was also no statistical difference between VIIICAg/VIIIRAg (or VIIIC/VIIIRAg) ratios obtained from carriers of severe compared to mild haemophilia.

Antigens↗

Factor VII and fibrinolytic response to deamino-8-D-argenine vasopressin in normal subjects and dissociate response in some patients with haemophilia and von Willebrand's disease.

Deamino-8-D-argenine vasopressin (DDAVP) was given by intravenous infusion to normal subjects, haemophiliacs and patients with von Willebrand's disease (vWd) and the factor VIII and plasminogen activator response was studied. In normal subjects and most patients with mild haemophilia and mild (intermediate) von Willebrand's disease there was an increase in plasminogen activator and all factor VIII related activities. In patients with mild vWd the prolonged bleeding time was shortened by DDAVP despite only a modest rise in factor VIII related Ristocetin cofactor activity (VIIIR:RiCoF). Sub-groups of patients have been characterized in whom atypical responses was observed. In two brothers with clinically severe haemophilia, but with 5--6 u/dl procoagulant factor VIII (VIIIC), there was an increase in VIIIC but no rise of the corresponding antigen, suggesting increased release of an antigenically abnormal poorly functioning molecule. A patient with intermediate vWd was studied in whom neither DDAVP, adrenaline infusion, nor venous occlusion resulted in an increase in either plasminogen activator or factor VIII related antigen (VIIRAg), although there was a significant increase in VIIIC. In a further patient with severe vWd, DDAVP failed to elicit any plasminogen activator or VIII response. The results obtained from these two patients suggested that in some individuals the presumed endothelial cell abnormality in vWd may be more extensive than a defect in VIIIRAg synthesis. Sub-groups of patients have been identified for whom treatment with factor VIII concentrates would be more appropriate than DDAVP prior to minor surgery.

Adolescent↗

An immunoradiometric assay for procoagulant factor VIII antigen: results in haemophilia, von Willebrand's disease and fetal plasma and serum.

An immunoradiometric assay (IRMA) has been developed based on the inhibitor which arose in a polytransfused severe haemophiliac. The two-site IRMA measures antigens closely associated with the procoagulant parts of the factor VIII complex, which are termed FVIIC antigens or FVIIICAG. FVIIICAG was present in normal plasma and also, at a slightly lower concentration, in normal serum. In 37 patients with haemophilia A, 36 had FVIIICAG levels of less than 10% of the normal plasma pool. In patients with von Willebrand's disease the levels of FVIIIC and FVIIICAG were in good agreement, both before and after treatment with cryoprecipitate or DDAVP. FVIIICAG was relatively stable in plasma at 37 degrees C and could also be detected in cord and fetal serum. The assay is of potential value for detecting reduced levels of factor VIII, for carrier detection and for the prenatal diagnosis of haemophilia.

Antigens↗

Evidence for the platelet specificity of beta-thromboglobulin and studies on its plasma concentration in healthy individuals.

The concentration of normal human platelet beta-thromboglobulin (beta-TG) was measured in various washed organ samples by a radioimmunoassay. As only trace amounts were detected, beta-TG appears to be a platelet specific protein. Assay of beta-thromboglobulin in plasma samples from 180 normal individuals gave a range of 10--65 mg/ml. In the 10 subjects studied, plasma beta-TG concentration was related to platelet lifespan but not to turnover. The plasma beta-TG concentration rose with increasing age but did not correlate with the whole blood platelet count or the percentage of megathrombocytes. These results provide further substantial evidence that measurement of plasma beta-TG concentration is useful for assessing the participation of platelets in various disease processes.

Adult↗

Three approaches to the radioimmunoassay of human beta-thromboglobulin.

Three radioimmunoassays for the measurement of beta-thromboglobulin are described. The standard method, using antiserum in solution, could be used to measure plasma concentrations of beta-thromboglobulin with the results available after 2-3 d. The use of a greater dilution of antiserum and tracer, with delayed addition of tracer, resulted in a more sensitive assay suitable for measuring b-thromboglobulin in urine. The use of a solid-couples antiserum under non-equilibrium conditions allowed the measurement of plasma levels of beta-thromboglobulin after an assay incubation time of 1 h. These three radioimmunoassay systems for beta-thromboglobulin cover the likely clinical requirements for the measurement of this platelet specific protein.

Beta-Globulins↗

Studies on liberation of beta-thromboglobulin from human platelets in vitro.

A platelet specific protein, beta-thromboglobulin, is liberated during the preparation of platelet poor plasma. Using combinations of different anticoagulant and anti-platelet compounds, this release can be significantly reduced. The best results were obtained when native blood was collected as soon as possible into a mixture of EDTA, prostaglandin E1 and theophylline and maintained and processed at a temperature between 0 and 4 degrees C. These technical innovations have permitted the use of a radioimmunoassay for beta-thromboglobulin on plasma samples in clinical practice.

Anticoagulants↗

New rapid method for diagnosis of deep venous thrombosis.

The plasma concentration of the platelet-specific protein beta-thromboglobulin was measured in fourteen patients who had been investigated for deep venous thrombosis by venography or 125I-fibrinogen scanning. All six patients with a proven thrombus had a raised plasma concentration of beta-thromboglobulin. Eight patients in whom no thrombus could be demonstrated had plasma concentrations of beta-thromboglobulin similar to a control group of thirty-five normal individuals. These results indicate that the measurement of plasma beta-thromboglobulin concentrations may be of use in the diagnosis of deep venous thrombosis.

Adult↗

Plasminogen assay by a haemagglutination inhibition technique.

Formaldehyde or gluteraldehyde cells treated with tannic acid were coated with plasminogen. These cells are agglutinated by plasminogen antiserum and this reaction can be quantitatively inhibited by purified plasminogen, plasma, and euglobulin. Correlation between this haemagglutination assay and a caseinolytic method is good. The sensitivity of the technique is high and compares favourably with other immunological methods and is approximately 10 times more sensitive than caseinolytic assays. The merits of this type of assay are discussed.

Aldehydes↗