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Biomedical subjects

W G Murphy

Publications and source records attributed to W G Murphy.

At least 19 recordsLinked to original sources

Solvent-detergent plasma: use in neonatal patients, in adult and paediatric patients with liver disease and in obstetric and gynaecological emergencies.

The study was conducted to assess the efficacy and tolerance of solvent-detergent (SD) plasma in neonates, in obstetric and gynaecological patients and in patients with liver disease in three large hospitals in Dublin during the period 1 April 2002 (when SD plasma was introduced) through 31 October 2003. Forty-one neonates received 67 transfusions of SD plasma at a mean dose +/- standard deviation of 18.4 +/- 13.2 mL kg(-1). Thirty-one (75.6%) patients had coagulopathy without haemorrhage (either disseminated intravascular coagulopathy or other coagulopathy); a further eight (19.5%) had clinical haemorrhage (excluding intraventricular haemorrhage), which complicated a coagulopathy. Thirty-eight obstetric and gynaecological patients received 57 SD plasma transfusions at a mean dose of 15.3 +/- 7.7 mL kg(-1). Thirty-six women (94.7%) had haemorrhage with mean blood loss per patient of 3345.8 +/- 2738.1 mL. Fifteen children with liver disease received 33 SD plasma transfusions at a mean volume of 38.0 +/- 41.5 mL kg(-1) body weight. Seventeen adult patients with severe end-stage liver disease were transfused with SD plasma either following liver transplantation or prior to other invasive procedures, at a mean dose of 10.2 +/- 3.4 mL kg(-1). There were statistically significant decreases in mean activated partial thromboplastin time and prothrombin time in neonates, in obstetric and gynaecological patients and in patients with liver disease. Complete correction of coagulation parameters was not achieved in any case in the liver transplant group. No adverse reactions were observed for SD plasma infusion. Use of SD plasma in critically ill neonates, in women with obstetric and gynaecological emergencies and in patients with liver disease appears safe, and improves laboratory indices of coagulopathy.

Adolescent↗

Neonatal alloimmune thrombocytopenia in the Irish population: a discrepancy between observed and expected cases.

AIMS: To estimate the rate of detection of neonatal alloimmune thrombocytopenia (NAITP) in the Irish population, to investigate clinical presentation and outcome in affected infants, and to determine the extent, if any, to which this condition is underdiagnosed at present. METHODS: Cases were collected in a retrospective fashion from a review of platelet serology laboratory records from January 1992 to December 2000. Clinical data were obtained from hospital records. Testing for maternal antiplatelet antibody was by one or more of the following: the platelet suspension immunofluorescence test, a commercial antigen capture enzyme linked immunosorbent assay (GTI-PakPlus), and the monoclonal antibody immobilisation of platelet antigens assay. Platelet antigen typing was by the polymerase chain reaction technique with sequence specific primers. RESULTS: Twenty seven serologically verified cases of NAITP were identified in 18 families. Maternal antibody to human platelet antigen 1a accounted for 25 of the 27 confirmed cases. Twenty one of 26 infants were born with severe thrombocytopenia. Nineteen of 27 infants had bleeding manifestations at birth. Petechiae and bruising were most commonly observed (n = 17). There were no documented cases of intracranial haemorrhage in this group but systematic cranial ultrasound was not performed. CONCLUSIONS: Screening studies in predominantly white populations have estimated the incidence of NAITP to be between 1 in 1000 and 1 in 2000 live births. With 50 000 births each year in Ireland, these results give a clinical detection rate for NAITP of just 1 case in 16 500 live births, strongly suggesting that NAITP is currently underdiagnosed. Antenatal screening to detect women at risk of having babies with NAITP is now scientifically feasible and should be considered.

Antigens, Human Platelet↗

Haemolytic uraemic syndrome: prognostic factors.

Haemolytic uraemic syndrome (HUS) associated with Escherichia coli O157:H7 is the commonest cause of acute renal failure (ARF) in childhood. Production of verotoxin by the organism is pivotal in the pathogenesis of the disease. Verotoxin binds to a receptor on blood and endothelial cells, expressed as the P1 blood group antigen on red blood cells. A protective effect of the P1 phenotype has been proposed in this disease. This study investigates prognostic factors and the relationship between outcome and P1 phenotype in 27 cases of diarrhoea-associated HUS. A poor outcome as defined by the presence of chronic renal failure (CRF), hypertension or proteinuria on 6 month follow-up was associated with the age of the patient at presentation and with the following clinical markers: maximum WBC and duration of raised WBC, duration of anuria and duration of need for dialysis. None of these outcome measures or prognostic factors, and no extra-renal manifestations of the disease were associated with P1 phenotype.

Acute Kidney Injury↗

Coagulase-negative staphylococcal contamination of whole blood and its components: the effects of WBC reduction.

BACKGROUND: Most bacteria present in blood components are normal skin flora, particularly Staphylococcus epidermidis and other coagulase-negative staphylococci. Growth patterns of these bacteria and the effects of different methods of component preparation may depend on variations in behavior between different isolates of the same species. STUDY DESIGN AND METHODS: Whole-blood units were inoculated with 19 different coagulase-negative staphylococcus (CNS) isolates at 1 to 10 and 10 to 100 CFUs per mL. After overnight holding at 22 degrees C, the units were processed into components. The components were cultured before inoculation and during processing, including before and after WBC reduction. RESULTS: At low inoculum levels, CNS was detected in 15 (79%) of 19 whole-blood units and in 12 (63%) of 19 RBCs after separation; after filtration, bacteria were detected in 3 (16%) of 19 (p = 0.0069). For platelet concentrates, 6 (32%) of 19 grew bacteria before filtration and 1 of 18 after filtration (difference not statistically significant). Three (16%) of 19 plasmas were positive before and after freezing. At high inoculum levels, 16 (89%) of 18 whole-blood samples and RBCs were positive before filtration; 6 (33%) of 18 RBCs were positive after filtration (p = 0.0002); 8 (44%) of 18 platelets were positive before filtration; 3 (17%) of 18 were positive after filtration (difference not statistically significant), and 7 (37%) of 18 plasma samples were positive before and after freezing. CONCLUSION: The growth characteristics of CNS in blood components vary with differences either in the subtype of bacteria or in the donor blood. Filtration reduces but does not eradicate contamination of RBCs and platelets by CNS. Plasma may act as a reservoir for CNS infection.

Blood Component Removal↗

Effects of asymptomatic abdominal aortic aneurysm on the soluble coagulation system, platelet count and platelet activation.

OBJECTIVES: the aim of the study was to determine the effects of infrarenal asymptomatic abdominal aortic aneurysm (AAA) on platelet count and activation. DESIGN: prospective clinical study in a University Department of Vascular Surgery. PATIENTS: one hundred and five patients with AAA. Thirty-two control patients with symptomatic carotid artery stenoses. METHODS: platelet count (PC), plasma glycocalicin levels, prothrombin ratio (PTR), activated partial thromboplastin time (APPT), fibrinogen and D-dimer were measured in 23 patients with AAA and 16 control patients with symptomatic carotid artery stenoses. PC alone was measured in a further 84 patients with AAA and 16 with carotid artery stenoses. RESULTS: PC was below the normal range in 8/105 patients and mean PC (215x10(9)/l, S.D. 47.5) was significantly lower than that of a control population (242x10(9)/l, S.D. 16.8) and patients with carotid disease (269x10(9)/l, S.D. 57). Glycocalicin level was above the normal range in 7/23 patients and the median level (28 fg/plt) was significantly higher than that of a normal population (21.6 fg/plt) and patients with carotid disease (12.3 fg/plt). Fibrinogen levels, PTR and APPT were all within the normal range. One patient had a minimally elevated level of D-dimer. CONCLUSIONS: the combination of low PC and high glycocalicin levels suggests that there is increased platelet destruction, most likely due to activation within the aneurysm sac.

Aged↗

Developmental variation in stem-cell markers from human fetal liver and umbilical cord blood leukocytes.

Fetal tissues containing haematopoietic stem cells (HSC) are of potential value for allogeneic transplantation and gene therapy. Flow cytometry was used to investigate CD34+ cells from human fetal livers and umbilical cord (placental) blood (UCB). CD34+ cells, expressed as a proportion of CD45-positive leukocytes, were much more abundant in fetal livers (mean 38%) than in UCB (mean 0.3%), but fetal liver cells had lower proportions of CD34+HLA-DR+ and CD34+ CD38+ subsets. In fetal liver, there was a strong and highly significant inverse correlation between CD34+ cells (as a proportion of total leukocytes) and gestational age; no such relationship was found for subsets of CD34+ cells coexpressing CD38 or CDw90 (Thy-1), but CD34+HLA-DR+ cells were less abundant in first-compared to second-trimester livers. In UCB, a trend towards decreasing CD34+ cells (as a proportion of total leukocytes) with increasing gestational age in late pregnancy was also observed. The composition of fetal leukocytes changes during development, and therefore the timing of fetal HSC harvesting could be of relevance to transplantation outcome.

Antigens, CD↗

Plasma glycocalicin levels are not elevated in patients with a history of transient ischaemic event and are normal in aspirinated normal volunteers.

Glycocalicin (GC) is the soluble portion of platelet membrane protein GP1b, and may be cleaved from the platelet surface during platelet activation. Previous study has indicated that plasma glycocalicin/platelet (GC/plt) levels are elevated in patients presenting with acute stroke. The present study was undertaken to determine the GC/plt levels in patients being treated for transient ischaemic episodes, to assess whether the elevated GC/plt level in acute stroke is due to a detectable, constitutive premorbid state of platelet activation. In sixteen consecutive patients attending a vascular surgery clinic, GC levels were measured on a citrated plasma sample, and corrected for circulating platelet count. Since 15 of 16 patients were taking aspirin when seen at clinic, a control study was undertaken to assess the effect of aspirin on sequential plasma GC/plt levels measured over 10 days--5 pre and post daily aspirin for 5 days, 4 acting as non-aspirinated controls. Plasma GC/plt levels in normal plasma were 21.6 +/- 8.0 fg; mean +/- SD. In the 16 patients the GC/plt levels were 13.1 fg/plt; SD 5.4, range 2.9-24.3. All platelet counts were in the normal range in all patients involved. While a masking effect due to aspirin cannot be completely ruled out, these studies indicate that plasma GC/plt level is not useful as a predictor of acute stroke in the premorbid population.

Aspirin↗

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↗

Passive immunisation with IgG endotoxin core antibody hyperimmune fresh frozen plasma.

Postoperative complications have been associated with low pre-operative endotoxin core antibody (EndoCAb) status. Seventy-three patients scheduled to undergo elective cardiac surgery were screened for IgG EndoCAb levels 1 week prior to admission. Of these 73 patients, 39 had levels below the median of a healthy population (100 MU = median units/ml). Only 6 received an infusion of IgG EndoCAb hyperimmune fresh frozen plasma (FFP) due to surgical rescheduling or unavailability of compatible hyperimmune FFP. The 6 patients demonstrated significant elevation (p < 0.0001) of their IgG EndoCAb levels from a mean level of 43 MU/ml (range: 26-75) to a posttransfusion mean of 267 MU/ml (range: 227-300), which persisted until at least immediately prior to the operative period. We conclude that passive immunisation with EndoCAb hyperimmune FFP is possible prior to elective surgery and that the kinetic profile of such an administration will allow the FFP to be given the night prior to surgery and still maintain significantly elevated levels for surgery planned the following morning.

Adult↗

A randomised trial of fibrin sealant in peripheral vascular surgery.

In a prospective randomised trial 39 patients undergoing either arterial bypass surgery with a polytetrafluoroethylene (PTFE) bypass graft (n = 18) or aortic aneurysm repair with a woven Dacron graft (n = 21) were randomised either to receive fibrin sealant as a topical haemostatic agent at the arterial anastomosis or to act as control. The main outcome measure was the time taken to achieve haemostasis at the suture line. The median time to achieve haemostasis was 0.5 min (range 0-11 min) in the treatment group and 4 min (range 0-21 min) in the control group. This difference was statistically significant p < 0.014 by the Mann-Whitney test. Immediate haemostasis on release of the clamps was achieved in 13/21 patients in the treatment group and in 4/18 patients in the control group (p = 0.023 by Fisher's exact test). There was no difference in total operative time or operative blood loss. No patients in the treatment group suffered any perioperative thromboembolic event and 1 patient in the control group suffered an early graft occlusion. There was no evidence of transmission of hepatitis B or C, or parvovirus B19. In conclusion, fibrin sealant is an effective topical haemostatic agent for arterial suture lines involving PTFE or woven Dacron.

Aged↗

Failure to kill Yersinia enterocolitica by plasma diluted to the concentration found in red cell units.

The possibility that the use of additive solutions for red cell storage might impair the ability of plasma to kill Yersinia enterocolitica was investigated by studying killing of Y enterocolitica by neat and diluted plasma. The ability of neat citrated plasma to kill complement sensitive organisms was lost at around 26%, the dilution typically found in red cell units. These results should be considered in the light of evidence that killing in plasma is important in the protection of donated blood against growth of Y enterocolitica, and the observation that the increase in frequency of transfusion reactions caused by Y enterocolitica coincided with the widespread introduction of additive solutions. Taken together, these points support the suggestion that the introduction of additive solutions may have precipitated the problem of growth of Y enterocolitica in stored blood.

Blood Bactericidal Activity↗