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Biomedical subjects

William G Murphy

Publications and source records attributed to William G Murphy.

5 recordsLinked to original sources
PubMed2006

Circulating microparticles: pathophysiology and clinical implications.

Microparticles (MP) derived from vascular endothelium or circulating blood cells circulate in the peripheral blood. They originate from blebbing and shedding from cell membrane surfaces in physiological and pathological conditions and are present in low concentrations in normal plasma. Increased levels are generated by a number of mechanisms including platelet activation, direct vascular endothelial damage, thrombin activity on the cell surface, C5b-9 activation, and PF4-heparin-antibody interaction. Several techniques are currently used to study the generation and nature of circulating microparticles. In particular, the genesis and role of microparticles, derived from platelets, endothelial cells and monocytes, in sepsis (especially meningococcal-induced), heparin-induced thrombocytopenia (HIT), thrombotic thrombocytopenic purpura (TTP), aplastic anaemia, paroxysmal nocturnal haemoglobinuria (PNH) and sickle cell disease (SCD) have been well studied, and provide important insights into the underlying diseases. A defect in the ability to form microparticles leads to the severe bleeding disorder of Scott syndrome, which in turn provides a revealing insight into the physiology of coagulation. In addition the complex role of microparticles in vascular and cardiovascular diseases is an area of immense interest, that promises to yield important advances into diagnosis and therapy.

Blood Cells↗
PubMed2003

Antenatal screening for human platelet antigen-1a: results of a prospective study at a large maternity hospital in Ireland.

OBJECTIVE: Fetomaternal mismatch for human platelet antigen (HPA)-1a accounts for approximately 85% of cases of neonatal alloimmune thrombocytopenia. The purpose of the study was to determine the prevalence of the HPA-1a negative platelet phenotype in a cohort of pregnant women in Ireland, the rate of alloimmunisation to HPA-1a in HPA-1 mismatched pregnancies and the associated incidence of neonatal alloimmune thrombocytopenia. DESIGN: A prospective case-control study. SETTING: The antenatal clinics of a large maternity teaching hospital. POPULATION OF SAMPLE: Pregnant women, regardless of parity, presenting at the antenatal clinics. METHODS: An enzyme-linked immunosorbent assay (ELISA) designed for simultaneous HPA-1a typing and antibody detection was used. Further analysis for HPA-1a alloantibodies was performed using commercial ELISA's (GTI PakPlus and Pak1) and the monoclonal antibody immobilisation of platelet antigens assay. Confirmation of serological typing was by the polymerase chain reaction technique using sequence-specific primers (PCR-SSP). MAIN OUTCOME MEASURES: The presence of the HPA-1a negative phenotype and its association with the development of maternal anti-HPA-1a and infant thrombocytopenia. RESULTS: Eighty-four of 4090 consecutive women enrolled in the study tested positive for HPA-1a in the screening ELISA. Confirmatory genotyping was performed on 67 women (representing 80% of the cohort), and 54 women (representing 3272 non-selected pregnancies), were homozygous for the HPA-1b allele (1.7%). Three of 34 (9%) women who delivered HPA-1a positive babies had detectable anti-HPA-1a and all three babies had neonatal alloimmune thrombocytopenia, for an overall incidence of 1:1100 non-selected pregnancies. CONCLUSIONS: The observed prevalence of 1.7% for the HPA-1a negative platelet phenotype is as expected from studies in other countries. While we have demonstrated the practicability of antenatal HPA-1a screening, further research is warranted to investigate maternal parameters predictive of severe fetal thrombocytopenia in HPA-1a alloimmunised pregnancies.

Antigens, Human Platelet↗
PubMed2002

QTc prolongation in apheresis platelet donors.

BACKGROUND: Citrate infusion during apheresis procedures can cause lowering of the plasma ionized calcium leading to prolongation of the QT interval and hypotension. At the myocardial level, QTc measurement is a sensitive marker of subphysiologic calcium values caused by citrate toxicity. STUDY DESIGN AND METHODS: Seventy-six regular platelet donors were recruited into this study. QTc intervals were measured continuously for 3 minutes at four different points during the apheresis procedures. The blood pressure was recorded every 5 minutes throughout the procedure. RESULTS: The baseline QTc value for men was 406.5 +/- 13.1 milliseconds(1/2) and for women was 417.6 +/- 13.3 milliseconds(1/2) (p = 0.0016). OTc prolongation occurred in all procedures in all donors. Maximum recorded values were significantly higher in women than in men (450.8 +/- 20.8 vs. 424.8 +/- 14.3 ms(1/2); p = 0.0025). All QTc values returned to baseline by 15 minutes after the procedure. Changes in blood pressure were minimal and no donor experienced severe symptoms. CONCLUSIONS: QTc prolongation always occurs during plateletpheresis. This prolongation is greater in women than in men. This study indicates that it may be advisable to assess donors for family or personal history of syncope and family history of sudden death to exclude those at increased risk of arrhythmias because of asymptomatic carriage of a long-QT gene. In addition baseline QTc measurement is a simple noninvasive procedure that could be applied to further studies with a view to enhancing donor safety in apheresis.

Adult↗
PubMed2002

Disease transmission by blood products: past, present and future.

Transfusion of blood and blood products has been associated with transmission of infectious agents. However, it is probable that blood products are currently very safe and that pooled virus-inactivated products from remunerated donors are now safer than untreated single voluntary donor components. Although the transmission events of the past and the present are reasonably well understood, reliance on a linear approach to predict safety in the future is open to criticism. Indeed, it was not possible to predict the extent or consequences of the AIDS epidemic or of hepatitis C transmission. Moreover, although variant Creutzfeldt-Jakob disease (vCJD) may not be transmitted to any large extent by transfusion of manufactured blood products, this will be due more to good fortune than good judgement - this agent could have escaped the screening, testing and eradication methods on which current confidence in blood product safety depends. Similarly, the emergence of a highly resistant non-enveloped virus, or even of another previously unrecognised disease-causing agent, could result in new threats from transfusion of blood components and products. The ecology of blood transfusion is exquisitely sensitive to variations in starting conditions, a situation typical of a chaotic rather than a linear system. Seemingly trivial events, often apparently unrelated to blood transfusion, have had enormous consequences in this field. Whatever the events that introduced simian immunodeficiency virus to humans or scrapie to cattle, they were a long way from those involved in the manufacture of blood products. In such a setting, reliance on methods that deal effectively with known threats (such as encapsulated viruses and bacteria) without adequate investigation and management of the intrinsic sensitivity to unpredictable events, leaves open the possibility of further infections emerging in the future. It is this reality that will ultimately result in the eradication of the transfusion of donor-derived blood and blood products in the developed world. In addition, all infections with a long disease-free incubation period in the host that can be transmitted in blood will eventually be over-expressed in groups that are exposed to blood either recreationally or professionally. As in the past, this could have occurred before testing or decontamination processes have been developed for emerging pathogens. Failure to be able to rely on completely risk-free donors, in both the voluntary and non-voluntary sides of the blood industry, continues to offer the potential for the transmission of infectious diseases in the future.

Blood Donors↗