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Biomedical subjects

D Leeming

Publications and source records attributed to D Leeming.

3 recordsLinked to original sources
PubMed2003

Role of plasminogen activator inhibitor-1 (PAI-1) levels in the diagnosis of BMT-associated hepatic veno-occlusive disease and monitoring of subsequent therapy with defibrotide (DF).

UNLABELLED: Hepatic veno-occlusive disease (VOD) is a common and potentially fatal complication of high dose chemotherapy with allogeneic/autologous stem cell transplant (SCT). The diagnosis and treatment of hepatic VOD is controversial. Clinical features are non-specific and may be mimicked by a number of other conditions causing hyperbilirubinaemia post-transplantation. Plasminogen activator inhibitor-1 (PAI-1) has been proposed as a specific marker of VOD [1]. Defibrotide (DF) is a polydeoxyribonucleotide, which has been found to have anti-thrombotic, anti-ischaemic and thrombolytic properties without causing significant anti-coagulation. Recent evidence [2,3] suggests that use of DF in patients with severe VOD results in a promising response rate without attributable significant toxicity. Between January 1998 and July 1999, PAI-1 levels were measured serially in 16 patients undergoing SCT who had subsequently developed hyperbilirubinaemia. Diagnosis of VOD was made by established clinical criteria [4,5]. At the time of diagnosis, PAI-1 levels (mean+/-SD) were significantly elevated in patients with VOD (90.7+/-47 ng/ml, n=7) when compared with patients with jaundice from other causes post transplantation (12.1+/-6.4 ng/ml, n=9). Five of the patients with VOD received treatment with DF. Four out of five patients showed an initial response to DF (significant fall in bilirubin and improvement in other signs/symptoms) with one of these patients having a complete response (bilirubin < 2.0 mg/dl and full resolution of signs/symptoms and end-organ toxicity). Following treatment with DF, a corresponding fall in PAI-1 levels was noted in those responding, with non-responders maintaining raised levels. CONCLUSION: Raised PAI-1 levels post stem cell transplant are specific for VOD and a subsequent decrease in levels following treatment with DF may be associated with response to treatment.

Adolescent↗
PubMed2000

The importance of locally derived reference ranges and standardized calculation of dilute Russell's viper venom time results in screening for lupus anticoagulant.

Three commercial dilute Russell's viper venom time (DRVVT) kits were evaluated at four UK centres experienced at performing lupus anticoagulant (LA) tests. Each centre established a normal reference range for the DRVVT ratio calculated against local pooled normal plasma from 20 healthy normal subjects. Plasma from LA-positive patients and LA-negative thrombophilia patients was also tested. DRVVT ratios and the degree of correction were assessed in a variety of ways to reflect not only the UK national Guidelines, but also the manufacturers' recommendations. The reference range data showed a normal distribution in each case, but considerable variation in the mean and SD between the centres and reagents, with the mean +2SD value ranging from 1.06 to 1.19. The use of an arbitrary DRVVT ratio of < 1.1 as the cut-off value for normality, which is applied in many laboratories, is therefore inappropriate. Although no single kit had a clear overall advantage in terms of sensitivity and specificity, the way in which the screen and confirmation data were analysed had a major impact on the interpretation of the results. A data analysis method employing a mean plus two standard deviations (SDs) cut-off for normality, and judgement regarding confirmation of LA based on a percentage correction of DRVVT ratio, was the simplest and most consistent, with overall sensitivity and specificity values of 81% and 94%, respectively, for uncomplicated LA-positive and LA-negative thrombophilia samples. We conclude that the 1991 BSCH Guidelines are in need of revision, each laboratory should establish its own normal reference range for the DRVVT ratio and a common method should be used for calculating the degree of correction with confirmation reagents, so that LA results can be correctly interpreted between laboratories. Standardizing DRVVT interpretation in this way should improve the consistency of LA detection.

Humans↗