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Biomedical subjects

A H Waters

Publications and source records attributed to A H Waters.

At least 19 recordsLinked to original sources

Personality characteristics of South African Navy submarine personnel.

This study aimed to determine the extent to which the Institute of Personality and Ability Testing Anxiety Scale and the 16 Personality Factor Questionnaire can be used to describe successful submariners in the South African Navy. The Anxiety Scale scores were within normal limits when the profiles of 85 submariners were analyzed to describe the personality characteristics of submarine personnel. Although no significant factors were found, the results indicate that four personality factors appeared to be most descriptive of the sample. They were adventurousness, confidence, group orientation, and self-sentiment. These factors appeared appropriate when discussed from an environmental demand perspective.

Adaptation, Psychological↗

Feto-maternal alloimmune thrombocytopenia: antenatal therapy with IvIgG and steroids--more questions than answers. European Working Group on FMAIT.

The optimal antenatal therapy for fetal thrombocytopenia has not been determined. We analysed 37 cases managed by maternal therapy and observed a successful outcome of maternal treatment in 26% of IvIgG cases and in 10% of steroid-treated cases. The significance of a plateau of the fetal platelet counts during pregnancy, 41% of IvIgG cases and 20%, of cases treated with steroids, is uncertain. It may indicate a stabilization of thrombocytopenia, hence a beneficial effect of therapy, or the natural course of the platelet count in a low-risk pregnancy. Overall outcome was unpredictable, but amongst the therapy failures there were proportionally more severely affected siblings. Further multicentre studies are necessary to establish the optimal antenatal management of high-risk pregnancies.

Adrenal Cortex Hormones↗

Severe fetomaternal alloimmune thrombocytopenia presenting with fetal hydrocephalus.

We report two patients where the finding of isolated fetal hydrocephalus led to the detection of severe fetal thrombocytopenia, using fetal blood sampling. Serological investigation led to the diagnosis of fetomaternal alloimmune thrombocytopenia (FMAIT) due to anti-HPA-1a. Both women had had previous unsuccessful pregnancies probably due to FMAIT; one had had four miscarriages at 17-18 weeks' gestation. The other had had one previous pregnancy complicated by severe fetal anaemia, and eventually hydrocephalus developed and the fetus died without the diagnosis of FMAIT being considered. Subsequent pregnancies in the two women were also affected by FMAIT, but prenatal treatment, predominantly with serial fetal platelet transfusions, resulted in a successful outcome in both cases. These observations suggest that FMAIT should be suspected if there is isolated fetal hydrocephalus, unexplained fetal anaemia, or recurrent miscarriages. The accurate diagnosis of FMAIT is important because recent advances in prenatal management can improve the outcome of subsequently affected pregnancies.

Abortion, Habitual↗

Antenatal screening for fetal alloimmune thrombocytopenia: the results of a pilot study.

Feto-maternal incompatibility for the human platelet antigen HPA-1a is an important cause of severe fetal thrombocytopenia. The incidence is 1 in 1000-2000 pregnancies, which is more common than other conditions for which screening is presently carried out. Antenatal diagnosis and management are now available, but only for subsequent siblings following diagnosis of a previously affected infant. This study describes a pilot prospective screening programme for the antenatal detection of fetomaternal alloimmune thrombocytopenia (FMAIT) due to HPA-1a incompatibility. 3473 women were typed for HPA-1a using a method designed for large-scale typing. 71 women found to be HPA-1a negative were further tested for HLA-DR52a as a risk factor for alloimmunization. All women were monitored for the development of anti-HPA-1a throughout pregnancy and a cord full blood count was taken at delivery. Two affected pregnancies were found and treated: a singleton pregnancy was treated antenatally and a twin pregnancy after delivery. The study showed that screening for FMAIT could be established within the pre-existing antenatal red cell serology programme. It was concluded that screening should be based on platelet typing and offered regardless of parity. Further stratification, combining DR52a typing and HPA-1a antibody screening, although focusing on the group of women at greater risk, may not identify all affected pregnancies. Confirmation of the diagnosis and severity of FMAIT continues to depend on fetal blood sampling during pregnancy or cord blood samples after birth.

Adult↗

A simplified method for large-scale HPA-1a phenotyping for antenatal screening.

A simplified method for large-scale HPA-1a phenotyping of platelets was developed for use in an antenatal screening programme for fetomaternal alloimmune thrombocytopenia (FMAIT). The test was based on the MAIPA assay, which was modified for antigen-typing with a well-characterized anti-HPA-1a reagent. The resulting assay gave reliable results, was inexpensive and allowed testing of large batches using semiautomated equipment.

Antibodies, Monoclonal↗

Antenatal management of fetomaternal alloimmune thrombocytopenia--report of 15 affected pregnancies.

The recognition that spontaneous intracranial haemorrhage (ICH) may occur in utero in fetomaternal alloimmune thrombocytopenia (FMAIT) led us to attempt to prevent this in 15 pregnancies of 11 women who had previously affected infants with FMAIT due to anti-HPA-1a. The antenatal management included fetal platelet transfusions and maternal steroids and/or high-dose intravenous immunoglobulin (IVIgG). In the first pregnancy, ICH occurred between 32 and 35 weeks' gestation before any treatment had been given, emphasizing the need for earlier intervention. Five of the 14 subsequent pregnancies in this study were considered to be severely affected (severe haemorrhagic complications in a previous infant and initial fetal platelet count < 20 x 10(9)/L in this study); four were managed successfully with weekly fetal platelet transfusions started between 18 and 29 weeks and continued until delivery at 33-35 weeks, and one severely affected case who was referred at 36 weeks was managed successfully with a single platelet transfusion prior to delivery. Five pregnancies were considered to be mildly affected (previous infants were unaffected by severe bleeding and initial fetal platelet count > 50 x 10(9)/L in this study). The platelet counts were maintained in one case with steroids and in three with IVIgG without the need for repeated platelet transfusions, but in the fifth the fetal platelet count fell despite steroids and IVIgG and serial platelet transfusions were required. Four pregnancies were unsuccessful; two pregnancies were terminated after severe ICH occurred at an early stage before fetal blood sampling had been carried out, one fetus died after the mother had a severe fall despite the successful initiation of fetal platelet transfusions and one died due to a cord haematoma which occurred at the time of the initial fetal blood sampling. The optimal management of FMAIT to reduce the risk of antenatal ICH remains uncertain. Steroids and IVIgG may be effective in some mildly affected cases but serial fetal platelet transfusions are the preferred therapy for those who are severely affected.

Antigens, Human Platelet↗

Relative importance of immune and non-immune causes of platelet refractoriness.

In this prospective study, 26 consecutive patients being treated for haematological malignancies receiving standard (i.e. non-leucocyte-depleted) blood components were observed for the development of refractoriness to platelet transfusions. One hundred and sixteen of the 266 (44%) platelet transfusions failed to produce a satisfactory response. In 102/116 (88%), the poor response was in the presence of non-immune factors known to be associated with platelet refractoriness. Non-immune factors were present alone in 78/116 (67%), and in combination with immune factors in a further 24/116 (21%). Immune factors (HLA and platelet-specific antibodies) were present during 29/116 (25%) of unsuccessful platelet transfusions. Statistical analysis confirmed that platelet refractoriness was significantly associated with the presence of non-immune factors. The non-immune factors associated with refractoriness were often multiple, most frequently a combination of fever, infection and antibiotic therapy. This study provides evidence that immune mechanisms were not the predominant cause of platelet refractoriness in the patient population studied. It also suggests that measures for the prevention of HLA alloimmunisation, such as leucocyte depletion, may have a limited impact in reducing the incidence of refractoriness to platelet transfusions.

Acute Disease↗

Antenatal management of severe feto-maternal alloimmune thrombocytopenia: HLA incompatibility may affect responses to fetal platelet transfusions.

In feto-maternal alloimmune thrombocytopenia (FMAIT), severe hemorrhage, particularly intracranial haemorrhage (ICH), may occur before delivery. Management strategies to prevent ICH in high-risk pregnancies include maternal administration of intravenous Ig with or without steroids and fetal platelet transfusions. This report describes a patient who lost three fetuses with ICH because of FMAIT due to anti-HPA-1a. ICH occurred earlier in successive pregnancies (at 28, 19, and 16 weeks of gestation) despite maternal treatment with intravenous Ig and steroids from 14 weeks of gestation in the third pregnancy. The fourth pregnancy was managed by administering weekly intraperitoneal injections of Ig to the fetus from 12 to 18 weeks of gestation. At 18 weeks, there was no evidence of ICH, but the fetal platelet count was only 12 x 10(9)/L. Serial fetal platelet transfusions were started, but there were poor responses because of immune destruction of the transfused platelets by maternal HLA antibodies. There were improved responses to transfusions prepared from the mother and from HLA-compatible HPA-1a-negative donors. At 35 weeks of gestation, a normal infant was delivered by Caesarean section after 20 platelet transfusions. There was prolonged thrombocytopenia in the baby for 15 weeks after birth, probably due to transfer of HPA-1a antibodies in the transfusions of unwashed maternal platelets. The optimal management of pregnancies likely to be severely affected by FMAIT is still evolving. Intensive management was successful in this case, but a successful outcome cannot be guaranteed in severely affected cases. This is the first time that HLA incompatibility has been found to complicate fetal transfusion therapy.

Adult↗

HPA-1 typing by PCR amplification with sequence-specific primers (PCR-SSP): a rapid and simple technique.

A DNA-based method was developed to genotype donors for the human platelet antigens HPA-1a and -1b. Sequence-specific primers (SSP) were used in the polymerase chain reaction (PCR) which allowed the HPA-1a/1a, -1b/1b and -1a/1b genotypes to be determined by PCR alone, no second analytical stage was required. 10 donors were tested by PCR-SSP and the results were concordant with serological phenotyping and independent DNA analysis.

Antigens, Human Platelet↗

Leucine33-proline33 substitution in human platelet glycoprotein IIIa determines HLA-DRw52a (Dw24) association of the immune response against HPA-1a (Zwa/PIA1) and HPA-1b (Zwb/PIA2).

Alloantibody formation against HPA-1a (Zwa/PIA1) has, to date, only been found in HLA-DRw52(a+) (Dw24) individuals. Alloimmunization against the product of the other HPA-1 allele, HPA-1b, is rare. We have been able to evaluate ten cases of HPA-1b alloimmunization in Europe in order to study whether there is an association between HLA phenotype and anti-HPA-1b antibody formation. HLA typing of these patients was performed with particular attention to the DRw52a specificity using specific T-cell clones. No association with DRw52a or any other known HLA phenotype was found. This finding implies that the amino acid substitution leucine33-proline33 in GPIIIa, responsible for HPA-1a/b, is of primary importance for the association of anti-HPA-1a antibody formation with DRw52a. These data show that the amino acid polymorphism affects the presentation of the immunogenic oligopeptides of HPA-1a and -1b in the HLA class-II groove.

Antigens, Human Platelet↗

Platelets as immunogens.

An immune response to human platelet antigens (HPA), as in neonatal alloimmune thrombocytopenia (NAIT) and post-transfusion purpura (PTP), is the exception rather than the rule and evidence is accumulating for the importance of human leucocyte antigen (HLA) class II restriction in this situation. Platelets have only HLA class I antigens and do not cause primary HLA alloimmunization; in platelet transfusions this is due to the contaminating leucocytes. Autoimmune thrombocytopenia is more common than the alloimmune conditions. The main target antigens for platelet autoantibodies are glycoproteins (Gp) IIb/IIIa and Ib/IX. The mechanism of drug-induced immune thrombocytopenia has been re-examined in relation to the target cell orientation of the antibody and of the drug.

Autoantibodies↗