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Biomedical subjects

L M Williamson

Publications and source records attributed to L M Williamson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Screening programmes for foetomaternal alloimmune thrombocytopenia.

Screening to detect pregnancies at risk of severe thrombocytopenia due to Foetomaternal alloimmunisation to Human Platelet Alloantigens (FAIT) is not yet a standard of care. Screening may be performed antenatally with the possibility of early intervention/therapy. Post natal measurement of cord platelet count may not always prevent fetal damage but may detect severe thrombocytopenia from other causes. Assessment of FAIT screening against World Health Organisation standards for screening programmes helps define areas where knowledge is still lacking and where research effort should be directed. Limitations to screening have been lack of reliable assays for typing and antibody detection, a limited understanding of the relationship between the presence of alloantibodies and clinical disease, inability to predict non-invasively which cases will have a severe outcome, and controversy as to which antenatal therapy is optimal for cases at high risk of a poor outcome.

Adult↗
PubMed1998

A randomized trial of solvent/detergent and standard fresh frozen plasma in the treatment of the coagulopathy seen during Orthotopic Liver Transplantation.

BACKGROUND: Viral transmission remains a residual risk in single unit blood component therapy. Virus inactivation of pooled fresh frozen plasma (FFP) by the solvent/detergent (SD) method can be used to reduce this risk but results in some loss of factor activity including factor VIII and (2-antiplasmin. This study was aimed at assessing the clinical effectiveness solvent/detergent treated pooled fresh frozen plasma (SDFFP) in the correction of the coagulopathy seen during Orthotopic Liver Transplantation (OLT) as compared with standard FFP. METHOD: Twenty eight patients with an underlying derangement of coagulation and who were due to undergo OLT were randomized to receive either FFP or SDFFP. They were assessed for side effects, correction of coagulopathy, and seroconversion for viral markers. RESULTS: Patients undergoing OLT showed equal correction of clotting factors and partial thromboplastin time (PTT) when treated with FFP or SDFFP. There was also a similar time course to return to baseline values in each group. There was no significant difference in correction of INR in either group. Usage of other blood components during the operation was identical in the two groups. No seroconversions were seen for HIV, HBC or HCV but only 12 patients were available for long term follow-up. CONCLUSION: SDFFP is an efficacious and safe source of coagulation factors for patients with liver disease undergoing Orthotopic Liver Transplantation. No adverse effects were seen during its administration. Further work is required to ascertain long term possibilities of seroconversion.

Adult↗
PubMed1997

Activation during preparation of therapeutic platelets affects deterioration during storage: a comparative flow cytometric study of different production methods.

Three different separation methods, all using centrifugation, are routinely used to prepare therapeutic platelet concentrates from human donor blood. Platelet concentrates derived from platelet-rich plasma (PRP-PC), buffy coat (BC-PC) and apheresis (AP-PC) were investigated at the end of production, and over an 8 d storage period. Change in platelet surface markers were measured by flow cytometry, using fluorescein-conjugated antibodies to fibrinogen, P-selectin (CD62P), GPIIb-IIIa (CD41), GPIb alpha (CD42b) and GPV (CD42d), and fluorescein-conjugated Annexin V was used to measure expression of anionic phospholipid. All concentrates showed some changes during preparation but PRP-PC underwent the greatest changes with significantly higher levels of P-selectin (P<0.001) and bound Annexin V (P=0.001) than AP-PC or BC-PC, and lower levels of GPIb alpha (P=0.002) and GPV (P<0.001). These changes were attributable to component separation rather than venesection. These markers all continued to change on storage with a strong positive correlation between the changes seen during production and those after 5 d storage. PRP-PC continued to show the greatest changes whereas BC-PC showed the least. Fibrinogen was bound to 40-50% of platelets in all preparations and this did not alter significantly on storage whereas total expression of GPIIb-IIIa remained unchanged throughout. There was no evidence that the platelet surface changes were thrombin-mediated and leucocyte depletion of BP-PC by filtration had no effect on the changes. It is proposed that the deterioration of platelet concentrates during storage may be related to activation occurring during preparation. 'Whole blood' flow cytometry using a panel of fluorescein-labelled reagents provides an informative method for evaluating platelet concentrates.

Annexin A5↗
PubMed1997

Cryoprecipitate prepared from plasma virally inactivated by the solvent detergent method.

There remains a small risk of viral transmission from single-donor blood components such as fresh frozen plasma (FFP) and cryoprecipitate which have not been subjected to a viral inactivation procedure. It is now possible to subject pooled FFP to viral inactivation by the solvent detergent (SD) treatment method, but with some loss of coagulation factors. To establish whether cryoprecipitate prepared from SD plasma would be suitable for the treatment of hypofibrinogenaemia and von Willebrand's disease (VWD), control and SD cryoprecipitate were assayed for factor VIII. von Willebrand factor (VWF) and fibrinogen content. In SD cryoprecipitate, levels of VWF activity and antigen were only 36% and 37% of control values respectively, whereas fibrinogen was 72%. The highest molecular weight multimer of VWF:Ag were absent from both SD plasma and SD cryoprecipitate. SD cryoprecipitate would thus be unsuitable for treating VWD, but would provide an alternative to untreated individual donor units of cryoprecipitate for the treatment of hypofibrinogenaemic states.

Blood Preservation↗
PubMed1997

Immunoglobulin G subclasses of anti-human platelet antigen 1a in maternal sera: relation to the severity of neonatal alloimmune thrombocytopenia.

The monoclonal antibody immobilization of platelet antigen (MAIPA) technique was employed to detect and semiquantitatively assess total IgG anti-HPA-1a and its subclasses in sera of mothers who gave birth to severely thrombocytopenic (< 50 x 10(9) platelets/L)(n = 14) or mildly thrombocytopenic/unaffected (> 50 x 10(9) platelets/L)(n = 13) neonates. There was no statistically significant difference between the IgG anti-HPA-1a subclass composition of the 2 groups of sera. The majority of sera (26/27, 96%) showed IgG1 + IgG3 while 17/27 (63%) had all 4 subclasses of the antibody. No significant differences between the severely thrombocytopenic and mildly thrombocytopenic/unaffected groups were detected in the levels of IgG, IgG1, IgG2 or IgG4 of the antibody. However, the values of IgG3 anti-HPA-1a were significantly higher in the severely thrombocytopenic than in the mildly thrombocytopenic/unaffected group of sera with only little overlap (median 2.94 vs. 1.68, range 1.36-9.71 vs. 1.50-2.84, respectively; p < 0.01). The results suggest that maternal IgG3 anti-HPA-1a has predictive value for severe thrombocytopenia of the neonate. However, a prospective study of IgG HPA-1a subclasses in a greater number of maternal sera at different times of pregnancy is needed to test if IgG3 anti-HPA-1a is predictive of the degree of fetal/neonatal thrombocytopenia.

Antigens, Human Platelet↗
PubMed1996

A whole blood assay for platelet HPA1 (PLA1) phenotyping applicable to large-scale screening.

Any future programme of antenatal screening of pregnancies for risk of neonatal alloimmune thrombocytopenia will have as a major requirement the availability of cost-effective assays which can be applied to large numbers of samples. To address this, we developed a competitive ELISA to type whole blood samples for the platelet alloantigen HPA1a, based on the use of purified glycoprotein (GP) IIb/IIIa from donors of known HPA1 genotype along with well characterized anti-HPA1a antiserum. Microtitre plates were coated with purified GPIIb/IIIa from donors of genotype HPA1a1a/3a3a. Anticoagulated whole blood of unknown HPA1 type was added to each well followed by anti-HPA1a. Residual antiHPA1a antibody not bound to the platelets in the test blood sample, bound to the immobilized HPA1a on the plate and was quantitated by standard ELISA. 475 blood donors were typed by the assay and the results compared in a blinded comparison with typing in the Capture-Ptm assay. Concordance was 100% (468 HPA1a positive and seven HPA1a negative). The HPA1 type of control samples stored as whole blood could be discriminated by this assay for up to 23 d of storage at 4 degrees C. This assay should be suitable for use in large-scale population screening programmes.

Antigens, Human Platelet↗
PubMed1996

Safety and efficacy of hepatitis C virus antibody screening of blood donors with two sequential screening assays.

BACKGROUND: Reactive samples in hepatitis C virus (HCV) antibody screening of blood donors are currently referred for a confirmatory assay. This scheme is not optimally efficient and is expensive because of the lack of specificity and cost of confirmatory tests, as well as the need to discard false-positive donations. As in some human immunodeficiency virus antibody-confirmatory schemes, the safety and efficacy of confirming anti-HCV with two sequential screening assays were evaluated. STUDY DESIGN AND METHODS: Three combinations of two anti-HCV screening assays were used to test 75,874 blood donors. Results were compared with the routine testing scheme and HCV RNA detection in any enzyme immunoassay-repeatably reactive samples. RESULTS: The use of an alternative screening assay for repeat testing decreased the proportion of enzyme immunoassay-positive donors from 0.28 to 0.05 percent. All samples that were "confirmed" as positive by the standard combination of immunoassays and all HCV RNA-positive samples were detected by the sequential screening assays. No samples that had discordant results on primary and secondary screening assays were confirmed by recombinant immunoblot assay or were found to contain detectable HCV RNA. CONCLUSION: The combination of screening assays for anti-HCV confirmation was as safe as, cheaper than, and nearly as efficient as the standard testing scheme.

Blood Donors↗