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Biomedical subjects

M F Murphy

Publications and source records attributed to M F Murphy.

At least 127 records · Page 7Linked to original sources

Platelet transfusions: the problem of refractoriness.

Refractoriness is a complication of multiple platelet transfusions in 30-70% of patients with bone marrow failure. The major causes are HLA alloimmunisation and non-immune platelet consumption; the latter is usually found in patients with DIC, septicaemia or splenomegaly. Initial management of alloimmunised patients who are refractory to platelet transfusions from random donors is the use of HLA-matched platelet donors; this results in improved responses to platelet transfusions in about 65% of these patients. Platelet crossmatching may reveal the presence of platelet-specific antibodies in some patients who are refractory to platelet transfusions from HLA-matched donors and may assist in the selection of compatible platelet donors. The identification of compatible donors is not possible in all refractory patients; alternative approaches such as plasma exchange and high dose intravenous gammaglobulin have been used in such patients with variable results. Insights into the mechanism of HLA alloimmunisation have suggested methods for its prevention. Primary HLA alloimmunisation is dependent on the presence in transfusions of contaminating cells bearing HLA class II antigens; pure platelet concentrates are non-immunogenic as platelets only express HLA class I antigens. Studies using leucocyte-poor blood components for multitransfused patients have demonstrated a reduction in HLA alloimmunisation from about 50-20% and a decrease in the incidence of refractoriness. Improvements in the techniques for leucocyte depletion of red cell and platelet concentrates and the possibility of inactivation of the HLA class II antigen-bearing cells by UV irradiation might make prevention of alloimmunisation an attainable goal in the near future.

Blood Platelets↗

Management of fetal alloimmune thrombocytopenia by weekly in utero platelet transfusions.

Alloimmune neonatal thrombocytopenia (ANT) may cause intracranial haemorrhage in utero as well as at delivery. Recent management has concentrated on attempts to minimise fetal thrombocytopenia and prevent its complications. This report describes further experience with the use of repeated intravascular transfusions of compatible platelets in utero. The patient studied had already had one infant with intracranial haemorrhage due to ANT. In her next pregnancy, weekly intra-uterine platelet transfusions were given from 26 weeks, but intra-uterine death occurred at 30 weeks after the mother had a heavy fall. In her most recent pregnancy, weekly intravascular transfusions of platelets were given by cordocentesis from 29 to 34 weeks. The fetal platelet count was maintained above 30 X 10(9)/l for almost all of the last 6 weeks of pregnancy before delivery of a normal infant by Caesarean section at 35 weeks' gestation. This approach is effective in preventing severe fetal thrombocytopenia in the last trimester of pregnancy and is contrasted with alternative treatments of ANT. Further data are required to determine the efficacy and risks of these treatments.

Blood Transfusion, Intrauterine↗

Is there an increased risk of twinning after discontinuation of the oral contraceptive pill?

We investigated whether conception soon after cessation of use of oral contraceptives affects the chance of bearing twins. Unpublished data from a large sample survey of contraceptive practice in Scotland were used to derive oral contraceptive discontinuation rates by month over the decade 1972-82 and these were related to estimated monozygotic and dizygotic twin birth rates and proportions by month in Scotland from 1974-82, using regression techniques. The results provide some support for the hypothesis that there is an increased risk of conceiving monozygotic twins within a year of ceasing to use oral contraceptives.

Adolescent↗

Twenty years' screening for cancer of the uterine cervix in Great Britain, 1964-84: further evidence for its ineffectiveness.

The effects of the screening programme for cancer of the uterine cervix in Great Britain are disputed, and the subject has been underexplored. Accordingly, we have related routinely available data on screening effort in Scotland, Wales, and the 14 English Health Regions to various incidence and mortality outcome measures, from 1967 to the present day. Although such an approach is imperfect, the results support the belief that the screening programme has been largely unsuccessful.

Adolescent↗

Local anesthetic agents.

The rational selection and safe use of local anesthetic solutions is of paramount importance to the practice of emergency medicine. Such decisions are based on a sound knowledge of the pharmacology and toxicity of those agents one uses clinically in day to day practice. In addition, such information explains what one actually sees clinically following the injection of a local anesthetic solution, and, more importantly, what one ought to expect.

Anesthetics, Local↗

Regional anesthesia in the emergency department.

Relatively few emergency physicians are aware of the spectrum of regional anesthesia and the advantages it has to offer in the day-to-day practice of the specialty. Understanding the types of block and the principles that apply to neural blockade are only a beginning in the appropriate use of blockade techniques. A detailed knowledge of anatomy is essential to successful and safe practice; however, only repeated performance of the blocks will lead to predictable success!

Emergencies↗

Disappearance of HLA and platelet-specific antibodies in acute leukaemia patients alloimmunized by multiple transfusions.

Alloimmunization by platelet transfusions was studied in 154 patients with acute leukaemia. 17 patients had HLA antibodies at initial presentation induced by previous transfusions or pregnancies; one of these also had platelet-specific antibodies and one other patient had platelet-specific antibodies alone. A further 38 patients developed HLA antibodies during therapy; three also had platelet-specific antibodies and two patients developed platelet-specific antibodies alone. Of these, 37 patients with HLA antibodies including three with platelet-specific antibodies and one patient with platelet-specific antibodies alone survived their initial therapy and formed the basis of this study. Antibodies once detected persisted throughout the study in seven of the 37 patients with HLA antibodies including one patient with platelet-specific antibodies and in the patient with platelet-specific antibodies alone. HLA antibodies disappeared after discontinuation of transfusions in six patients, and after switching to HLA matched platelet transfusions and leucocyte-poor blood in eight patients; two of the latter patients also had platelet-specific antibodies which disappeared. The other 16 patients with HLA antibodies lost their antibodies despite continued transfusions.

Acute Disease↗

Incidence and mechanism of neutropenia and thrombocytopenia in patients with human immunodeficiency virus infection.

The incidence of lymphopenia, thrombocytopenia and neutropenia was studied in 105 homosexual men with HIV infection. Lymphopenia was common in patients with AIDS (75%), but its incidence in PGL (24%) was not significantly different from that in asymptomatic anti-HIV positive (15%) homosexual men. Neutropenia and thrombocytopenia were found in patients with AIDS or PGL, but not in asymptomatic anti-HIV positive homosexuals. The study suggests that the neutropenia and thrombocytopenia in these patients were due to autoimmune destruction of neutrophils and platelets.

Acquired Immunodeficiency Syndrome↗

Post-transfusion purpura associated with anti-Baka and anti-PIA2 platelet antibodies and delayed haemolytic transfusion reaction.

The occurrence of post-transfusion purpura (PTP) in a 16-year-old girl with sickle/beta-thalassaemia is described. Clinically this was a typical case of PTP, but it was unusual serologically. Anti-Baka and anti-PIA2 platelet-specific antibodies were identified and the patient's platelets were typed as homozygous PIA1-positive and Baka-negative. The patient also developed red-cell, granulocyte and lymphocytotoxic antibodies in response to the blood transfusion and had a delayed haemolytic transfusion reaction.

Adolescent↗

Sudden infant death syndrome and environmental temperature: an analysis using vital statistics.

We examined the relation between the daily numbers of deaths ascribed to sudden infant death syndrome (SIDS) (n = 6226) and daily temperature in England and Wales over the five year period 1979-83. When the data were filtered to remove the dominant seasonal trend, and residual autocorrelation, we found a significant negative correlation of deaths with both the level and rate of change of temperature four to six days earlier, irrespective of age at death. Place of usual residence was obtained for 909 SIDS cases occurring during the unusually severe winter of 1981-82, and, using space-time clustering techniques, we confirmed previous findings of the lack of 'epidemicity' for this condition. These results are compatible with several previous hypotheses of the relation between the weather and SIDS and directly incriminate drops in temperature in the occurrence of the condition.

Cold Temperature↗

Megaloblastic anaemia due to vitamin B12 deficiency caused by small intestinal bacterial overgrowth: possible role of vitamin B12 analogues.

Megaloblastic anaemia due to bacterial overgrowth of the small intestine is due to vitamin B12 malabsorption. This report describes a patient with bacterial overgrowth of the small intestine who had megaloblastic anaemia and malabsorption of vitamin B12, but persistently normal levels of serum vitamin B12 and normal serum and red cell folate levels. However, there was evidence of vitamin B12 deficiency as shown by an abnormal deoxyuridine suppression test and by the response to treatment with physiological doses of vitamin B12. A relative increase in biologically inactive vitamin B12 analogues may be the explanation for the normal vitamin B12 level in this patient.

Aged↗

Use of leucocyte-poor blood components and HLA-matched-platelet donors to prevent HLA alloimmunization.

Recent studies have shown that the incidence of alloimmunization due to repeated platelet transfusions from random donors may be reduced by the use of leucocyte-poor blood components. These results were confirmed by this study, where 16% of patients with acute leukaemia undergoing initial chemotherapy and receiving leucocyte-poor blood components developed lymphocytotoxic antibodies, compared with 48% of patients in a control group receiving standard (non-leucocyte-depleted) blood components. In a third group, who received leucocyte-poor blood components and HLA-matched platelets, none of the patients developed lymphocytotoxic antibodies. There was a low incidence of platelet-specific antibodies (8%) but no difference between the three groups. Improved methods of removing leucocytes from blood components appear to offer the best approach for minimizing HLA alloimmunization, as the provision of HLA-matched platelet donors for prophylactic platelet support of all patients is not feasible.

Adolescent↗

Autoimmune thrombocytopenia and neutropenia after remission induction therapy for acute leukaemia.

Patients with acute leukaemia who are exposed to intensive chemotherapy, with or without radiotherapy, may remain thrombocytopenic or neutropenic in remission. The incidence of these prolonged cytopenias was examined retrospectively in 46 patients in remission and prospectively in 14 patients. The patients were tested for the presence of autoantibodies to platelets and neutrophils using a fluorescent antihuman globulin technique with paraformaldehyde-fixed cells. In the retrospective study nine patients (20%) had neutrophil autoantibodies and seven (15%) had platelet autoantibodies; only one of the former had neutropenia and one of the latter thrombocytopenia. In the prospective study three (21%) had neutrophil autoantibodies and seven (50%) had platelet autoantibodies. One of the patients with platelet autoantibodies had transient thrombocytopenia, and shortened platelet survival was demonstrated. None of the patients with neutrophil autoantibodies had neutropenia. The rare occurrence of cytopenias in association with these autoantibodies was possibly due to bone marrow compensation for antibody-mediated cell destruction, although other possible mechanisms are discussed.

Acute Disease↗