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Biomedical subjects

H A Doughty

Publications and source records attributed to H A Doughty.

10 recordsLinked to original sources
PubMed1997

Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk pregnancies.

Venous thromboembolic disease remains the commonest cause of maternal death. The management of thromboprophylaxis in high risk women during pregnancy is contentious. Low molecular weight heparins (LMW) have theoretical advantages compared with unfractionated heparin and warfarin but have been poorly studied in pregnancy. We report on the use of LMW heparin (Fragmin) as thromboprophylaxis in thirty four high risk pregnancies. All the women had a previous thrombosis or a thrombosis in their current pregnancy +/- a recognised thrombophilic state (eleven had the antiphospholipid syndrome). Fragmin was given subcutaneously to maintain trough anti-Xa activity of 0.15-0.2 U/ml and 2 h post injection levels of 0.4-0.6 U/ml. The levels were checked monthly during pregnancy. Most women required 5,000U Fragmin once daily during the first trimester unless they were greater than 100 kg at the start of pregnancy. The mean time for dosage increase was 20.5 week (S.D. 8.2). 26/34 pregnancies (76%) required 5,000 twice daily at the end of pregnancy. Epidural anaesthesia was managed by omitting Fragmin dose or inserting the needle 6 hours after the previous Fragmin injection. There were no thromboembolic events thrombocytopenias or excessive haemorrhage. One woman had osteoporotic vertebral collapse post partum, she had no other risk factors for osteoporosis. LWM heparin (Fragmin) appears to be efficacious in preventing recurrent thromboembolic disease in pregnant women at high risk, but it is notable that osteoporotic fractures occurred post partum in one woman. Further trials are required to determine optimal dosage and safety.

Adult↗
PubMed1996

Experience with the Port-A-Cath in sickle cell disease.

Peripheral vein access is often a problem in patients with sickle cell disease (SCD). Totally implantable venous access devices (TIVAD) have offered other groups of patients safe long-term venous access. We reviewed our own experience with the use of a Port-A-Cath device in five patients with SCD undergoing exchange transfusion programmes. All five lines required removal due to infection associated with SBE, septic arthritis, pulmonary embolus and axillary vein thrombosis. The organisms involved were Staphylococcus aureus (3), Staphylococcus epidermidis (1) and Streptococcus sp. (1). The median working life of the catheters was 240 days (range 61-428). The median length of time from presentation to the diagnosis of a line-associated infection was 29 days (range 1-58). The rate of complications (0.4 per 100 patient days) in this small group of patients contrasts with the lower rates in patients with HIV and malignancy (0-0.1 per 100 patient days). Our results suggest that patients with SCD suffer an unacceptable incidence of infective complications associated with the Port-A-Cath. Bone infection is more common where there is pre-existing infarcted tissue. While these systems provide a valuable tool, our experience has led us to discontinue the use of TIVADs in SCD.

Adult↗
PubMed1995

The successful removal of a bleeding intracranial tumour in a severe haemophiliac using an adjusted dose continuous infusion of monoclonal factor VIII.

Ten per cent of patients with haemophilia A develop intracranial haemorrhage (ICH) with a mortality rate of 30% and an incidence of psycho-neurological sequelae in 50% of survivors. ICH may be spontaneous or in association with trauma and other pathology. The generally recommended management is conservative replacement therapy using bolus injections of factor VIII and no neurosurgical intervention. Adjusted dose continuous infusion therapy provides an alternative method of factor VIII administration that is simple, more cost effective and safer through the maintenance of stable plasma VIII:C levels. This method has been successfully used to cover general surgery and the conservative treatment of subarachnoid haemorrhage but is not widely used due to unfamiliarity with the technique. This paper describes the use of continuous infusion of factor VIII concentrates to cover the successful neurosurgical management of a young man with severe haemophilia A who presented with an ICH associated with a bleeding choroid plexus tumour. Surgery was complicated by the development of a factor VIII inhibitor which disappeared following treatment with an immune-tolerance induction programme.

Adolescent↗
PubMed1995

The use of recombinant factor VIIa in a patient with acquired haemophilia A undergoing surgery.

An elderly woman with acquired haemophilia A secondary to a monoclonal gammopathy, required elective surgery for a parotid tumour but was unable to tolerate conventional treatment. Recombinant activated factor VII (rVIIa) was used successfully to cover a biopsy and then subsequent resection of the tumour. The use of rVIIa in the management of acquired inhibitors is discussed.

Aged↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Bleeding time at altitude.

Disorders of coagulation during ascent to high altitude in the unacclimatized are well recognized. In order to document the sequence of haematological changes, the bleeding time was estimated weekly in six climbers during a six week climb. The median bleeding time was shown to increase by 50% between the first and fourth week, it then plateaued during continued ascent to 5700 m. During the sixth week the bleeding time rapidly reverted to baseline levels whilst still at altitude. The observations might be explained by the compensatory changes in coagulation factors following the initial prothrombotic phase, compounded by increased capillary fragility. Acclimatization to altitude is accompanied by a series of complex haematological changes. The temporal sequence should be considered when devising a strategy to reduce the risk of thrombosis.

Altitude↗