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Biomedical subjects

Beverley J Hunt

Publications and source records attributed to Beverley J Hunt.

At least 19 recordsLinked to original sources
PubMed2006

Key issues in advanced bleeding care in trauma.

The incidence of hemostatic abnormalities in the early hours after traumatic incident is high and represents an independent predictor of mortality. Key factors in the development of traumatic coagulopathy include the severity of injury, hypothermia, acidosis, hemorrhagic shock, hemodilution, clotting factor consumption, and fibrinolysis. Assessment of bleeding includes evaluation of the mechanism of injury, vital signs, biochemistry, detection of external and internal bleeding sources, injuries found upon secondary investigation, and response to treatment. Priority in treating the bleeding trauma patient should be given to prevention of further bleeding, hypothermia, acidosis, coagulopathy, and maintenance of tissue oxygenation, achieved by careful physical handling, damage control surgery, analgesia, maintenance of normothermia, correction of coagulopathy, control of blood pH, and serum calcium. Priority during initial treatment is to restore tissue perfusion and achieve hemostasis in vital functions; other nonvital procedures may generally be delayed. This state-of-the-art review aims to address key issues in acute control of bleeding in the trauma patient.

Hemorrhage↗
PubMed2006

Managing antiphospholipid antibodies and antiphospholipid syndrome in children.

Antiphospholipid antibodies (aPL) and antiphospholipid syndrome (APS) are increasingly being recognized in children. Transient non-pathogenic aPL are often seen after childhood infections, while thrombotic events seem rare in those with true aPL. We discuss the main scenarios faced when dealing with children with aPL--asymtomatic aPL, primary APS and secondary APS. Children with thrombotic events present difficult management problems, as there is little evidence-based medicine in this area. We discuss the manifestations and management of childhood aPL--asymptomatic aPL, primary and secondary APS elucidated with case histories. Insufficient safety data on anticoagulation and limited information on the effects of warfarin, use of aspirin, duration and intensity of anticoagulation are some of the unresolved issues in managing aPL and APS in children. Multicenter randomized controlled trials may provide answers to some of these issues.

Adolescent↗
PubMed2006

Sudden sensorineural hearing loss and antiphospholipid syndrome.

The antiphospholipid syndrome is the association between the presence of antiphospholipid antibodies, thrombosis and/or pregnancy morbidity and mortality. This report presents two cases of antiphospholipid antibodies and sensorineural hearing loss and discusses the probable causative link. We recommend that patients presenting with sudden sensorineural hearing loss are investigated for evidence of antiphospholipid antibodies. Life long anticoagulation is necessary to prevent life threatening thrombotic or thromboembolic events.

Anticoagulants↗
PubMed2005

Low molecular weight heparin in pregnancy: current issues.

Low molecular weight heparin (LMWH) is now the most commonly used anticoagulant for prophylaxis and treatment of venous thromboembolism in pregnancy and the puerperium in the UK. The reliable pharmacokinetics of LMWHs and their long half-life, resulting in the need for less frequent injections than unfractionated heparin (UFH), makes them attractive for practical use in the 9 months of pregnancy. Widespread use over the last 10 years has shown that LMWHs are safer than UFH in pregnancy. There is, however, poor consensus and wide disparity of views among experts with regard to the appropriate dose for the varying indications, the duration of treatment, and whether and how LMWH should be monitored because of the lack of an evidence base. These areas of uncertainty reflect the fact that clinical practice has grown largely through the publication of small trials, observational studies, personal experience and anecdote. Good clinical trials are urgently required.

Anticoagulants↗
PubMed2005

Rapid and specific detection of clinically significant haemoglobinopathies using electrospray mass spectrometry-mass spectrometry.

Increasing demand for population screening for the haemoglobinopathies gives rise to a requirement for high throughput systems, which allow for cost effective, rapid, sensitive and specific screening of clinically significant haemoglobins. We have developed a practical and efficient approach using tryptic digestion and electrospray triple quadrupole mass spectrometry-mass spectrometry (MSMS) in multiple reaction monitoring acquisition mode for the identification of the clinically important haemoglobin variants, S, C, DPunjab, OArab, and E. A total of 200 blood samples, comprising 52 haemoglobin AA, 57 AS (sickle cell trait), 44 AC (C trait), 16 SC (SC disease), 14 SS (sickle cell disease), 10 AE (E trait), 2 ADPunjab (DPunjab trait) and 1 each of AOArab (OArab trait), CC (C disease), DPunjabDPunjab (DPunjab disease), OArabOArab (OArab disease), and EE (E disease), have been analysed in parallel with existing phenotype and molecular methods. All haemoglobin variants were correctly identified by MSMS, with no false positives or false negatives. The system detects both heterozygotes and homozygotes and has potential applications in neonatal and antenatal screening.

Hemoglobin C↗
PubMed2005

Markers of endothelial and haemostatic function in the treatment of relapsed myeloma with the immunomodulatory agent Actimid (CC-4047) and their relationship with venous thrombosis.

We evaluated the serum/plasma levels of cytokines [interleukin (IL)-6, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta2] and markers of coagulation, fibrinolysis, endothelial and platelet activation during the first 4 wk of treatment with the thalidomide analogue Actimid (CC-4047) in 15 patients with relapsed/refractory myeloma. There was evidence of activation of endothelium (soluble vascular cell adhesion molecule, sVCAM), coagulation (prothrombin fragment 1 + 2, PF1 + 2) and fibrinolysis (D-dimers) but no evidence of platelet activation or endothelial cell damage in myeloma patients. These parameters were not affected by the use of CC-4047. Three of four patients with baseline D-dimers levels >500 microg/L subsequently developed deep vein thrombosis (DVT). The hypothesis that D-dimer level >500 microg/L may predict for those patients most at risk of thromboembolism with multiple myeloma undergoing treatment is worthy of further study.

Aged↗
PubMed2005

The management and outcome of 18 pregnancies in women with polycythemia vera.

BACKGROUND AND OBJECTIVES: Polycythemia vera (PV) is rare in women of childbearing age with only 20 previous pregnancies reported. DESIGN AND METHODS: We report a series of 18 pregnancies (19 fetuses) in eight women with PV managed prior to or following implementation of management guidelines tailored to PV in pregnancy, and review the literature. RESULTS: Seven of these pregnancies were managed by standard antenatal care (group A) without specific attention to the women's PV. All remaining 11 pregnancies (group B) were managed following a formal protocol and received tailored management principally comprising tight control of the hematocrit by venesection, and the use of interferon ? in three patients, in addition to aspirin 75 mg, and prophylactic low molecular weight heparin (LMWH). Each pregnancy was monitored with uterine artery Doppler examinations and regular fetal scanning. In group A (n=7) there was one live birth, which required delivery at 34 weeks due to placental insufficiency, three first trimester miscarriages, two stillbirths and one combined stillbirth and neonatal death (twins) associated with placental dysfunction. All 11 patients in group B received aspirin and post-partum LMWH; four also received venesection (during pregnancy), three interferon-a and three antenatal LMWH. There were ten live births, nine at term, one first trimester miscarriage and no intrauterine growth retardation. INTERPRETATION AND CONCLUSIONS: Pregnancy in PV without meticulous attention to hematocrit is associated with poor fetal outcome. Aggressive intervention with control of hematocrit, aspirin and some LMWH appears to be associated with significantly better outcome (p=0.0017).

Adolescent↗
PubMed2004

"Off-license" use of recombinant activated factor VII.

Recombinant factor VIIa (rFVIIa) has been widely used in the treatment of bleeding episodes in haemophiliac patients with inhibitors. In haemostatic circles it has also been assessed in reversing oral anticoagulant therapy. Over the last few years, it has been used "off-label" in patients with uncontrolled bleeding due to haemostatic abnormalities due to trauma and/or massive blood loss, thrombocytopenia, platelet dysfunction or liver dysfunction. This review examines the proposed mechanism of action of rFVIIa in the context of current concepts of haemostasis and its pharmacological properties. The "off-license" use of rFVIIa is reviewed. The latter are reported mainly as case reports, case series. There is an overwhelming need for randomized controlled trials to assess rFVIIa's efficacy, dosing and safety in current "off-license" use.

Blood Coagulation Disorders↗
PubMed2003

Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction.

Cerebral small vessel disease (SVD) causes focal lacunar infarction and more diffuse ischaemia, referred to as leukoaraiosis. Endothelial dysfunction has been proposed as a causal mechanism in the disease. Homocysteine is toxic to endothelium. We determined whether elevated homocysteine levels and the methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism are risk factors for SVD as a whole, and for two different SVD subtypes: isolated lacunar infarction and ischaemic leukoaraiosis. We also determined whether any association was mediated by endothelial dysfunction, as assessed by circulating endothelial markers. One hundred and seventy-two Caucasian patients with SVD and 172 community controls of similar age and sex were studied. Serum homocysteine measurement and MTHFR genotyping was performed. Levels of intercellular adhesion molecule 1 (ICAM1) and thrombomodulin were measured in a subgroup. Mean homocysteine levels were higher in SVD than controls [14.55 micromol/l [95% confidence interval (CI) 13.78-15.35] versus 12.01 micromol/l (95% CI 11.42-12.64), P < 0.0005]. Homocysteine was a stronger risk factor in those with ischaemic leukoaraiosis [12.92 (95% CI 4.40-37.98), P < 0.0005) per micromol increase in log homocysteine concentration (P < 0.0005)] in comparison with isolated lacunar infarction [4.22 (95% CI 1.29-13.73), P = 0.02] after controlling for both conventional risk factors and age. The MTHFR 677T allele was a risk factor only in the ischaemic leukoaraiosis group [odds ratio (OR) 2.02 (95% CI 1.31-3.1), P = 0.001]. Inclusion of the endothelial markers ICAM1 and thrombomodulin in a logistic regression model resulted in the association between homocysteine and SVD no longer being significant. In conclusion, hyperhomocysteinaemia is an independent risk factor for SVD, particularly ischaemic leukoaraiosis, and this effect may be mediated via endothelial dysfunction. Homocysteine-lowering therapy may be particularly effective in this subgroup.

Aged↗
PubMed2003

Prevalence of complicated carotid atheroma as detected by magnetic resonance direct thrombus imaging in patients with suspected carotid artery stenosis and previous acute cerebral ischemia.

BACKGROUND: It is recognized that complicated plaque largely accounts for the morbidity and mortality from atherosclerosis. Ideally, investigation of symptomatic and asymptomatic patients would identify atheromatous plaques independently of stenosis. We have previously shown that a magnetic resonance direct thrombus imaging (MRDTI) technique demonstrates complicated atheroma as high signal within the carotid arterial wall. We used this technique to examine the prevalence of complicated carotid plaque in vivo in the ipsilateral arteries of recently symptomatic patients with suspected carotid artery stenosis and to compare this with their contralateral arteries and with those of healthy age- and sex-matched controls. METHODS AND RESULTS: The carotid arteries of 120 patients with suspected severe carotid artery stenosis and previous acute cerebral ischemia were imaged using MRDTI, as were 28 control arteries. High signal was not seen in any control artery. However, there was a 60% prevalence of high signal, suggestive of complicated plaque in the patients' ipsilateral arteries. The prevalence of high signal was significantly greater in the patients' ipsilateral vessels compared with the contralateral, asymptomatic side (60% versus 36%, chi2 P<0.001), particularly for vessels of only moderate stenosis. CONCLUSIONS: MRDTI high signal suggestive of complicated plaque is prevalent in the ipsilateral carotid arteries of patients with carotid stenosis and recent cerebral ischemic events. MRDTI has a potential role in identifying "at risk" plaque, studying atherogenesis and the effects of plaque-modifying strategies.

Brain Ischemia↗
PubMed2003

Characterization of complicated carotid plaque with magnetic resonance direct thrombus imaging in patients with cerebral ischemia.

BACKGROUND: Thromboembolic disease secondary to complicated carotid atherosclerotic plaque is a major cause of cerebral ischemia. Clinical management relies on the detection of significant (>70%) carotid stenosis. A large proportion of patients suffer irreversible cerebral ischemia as a result of lesser degrees of stenosis. Diagnostic techniques that can identify nonstenotic high-risk plaque would therefore be beneficial. High-risk plaque is defined histologically if it contains hemorrhage/thrombus. Magnetic resonance direct thrombus imaging (MRDTI) is capable of detecting methemoglobin within intraplaque hemorrhage. We assessed this as a marker of complicated plaque and compared its accuracy with histological examination of surgical endarterectomy specimens. METHODS AND RESULTS: Sixty-three patients underwent successful MRDTI and endarterectomy with histological examination. Of these, 44 were histologically defined as complicated (type VI plaque). MRDTI demonstrated 3 false-positive and 7 false-negative results, giving a sensitivity and specificity of 84%, negative predictive value of 70%, and positive predictive value of 93%. The interobserver (kappa=0.75) and intraobserver (kappa=0.9) agreement for reading MRDTI scans was good. CONCLUSIONS: MRDTI of the carotid vessels in patients with cerebral ischemia is an accurate means of identifying histologically confirmed complicated plaque. The high contrast generated by short T1 species within the plaque allows for ease of interpretation, making this technique highly applicable in the research and clinical setting for the investigation of carotid atherosclerotic disease.

Aged↗
PubMed2003

Risk of lymphoid neoplasia after cardiothoracic transplantation: the influence of underlying disease and human leukocyte antigen type and matching.

BACKGROUND: It has been known for more than 20 years that there is an increased risk of lymphoid neoplasia after cardiothoracic transplantation. Recent studies have demonstrated the importance of primary Epstein-Barr virus (EBV) infection and type of immunosuppressive therapy to the cause of these neoplasms, but the contribution of other factors remains equivocal. METHODS: The authors followed 1,562 patients undergoing cardiothoracic transplantation at Harefield Hospital, United Kingdom, and used standard cohort methods of analysis to examine whether posttransplant lymphoma risk was related to the underlying disease requiring transplantation or the human leukocyte antigen (HLA) type and matching. Lymphomas were categorized into EBV-associated lymphoproliferative disease (LPD) and EBV-negative non-Hodgkin's lymphoma (NHL), and the authors carried out separate analyses of these. RESULTS: The authors found no significant association between the underlying disease necessitating transplantation and the risk of lymphoid neoplasia. There was also no evidence of a relation of lymphoma risk with the presence or absence of any particular HLA antigen, although significant protective effects of HLA-B14 and -B57 were found when analyses were conducted without adjustment for multiple testing. Risk of LPD was not associated with degree of HLA mismatching, but there was a significant effect of mismatching on risk of EBV-negative tumors. CONCLUSIONS: The differential effect of HLA mismatching on the risks of LPD and EBV-negative NHL provides further evidence that these two tumors are distinct etiologic entities. The authors' results suggest that the immunologic cause of EBV-negative NHL may be different from that of LPD. Investigation of the relation of risk of EBV-negative NHL to degree of immunosuppression is needed.

Blood Group Incompatibility↗
PubMed2003

The management of perioperative bleeding.

Excess perioperative bleeding remains a major complication following surgery, resulting in increased morbidity and mortality. The principal causes of non-surgical haemostatic perioperative bleeding are a pre-existing undetected bleeding disorder, related to the nature of the operation itself or from coagulation abnormalities arising from massive blood loss. Very often, it is a combination and coexistence of various pathologies. Identifying patients at risk remains a major component of preventing excessive blood loss. Understanding the haemostatic changes occurring in the perioperative period, especially in complex procedures like cardiopulmonary bypass and orthotopic liver transplantation is crucial in developing new strategies for the management of perioperative bleeding. Pharmacological interventions, especially aprotinin, tranexamic acid, desmopressin and increasingly, recombinant VIIa are being used both in prophylaxis and therapeutically to stop bleeding. The use of near patient testing like thromboelastography and platelet function analyser has allowed for more detailed assessment of the various steps of haemostasis. One of the main goals is to reduce the usage of allogeneic blood transfusion and its attendant risks.

Aprotinin↗
PubMed2003

Longitudinal evaluation of markers of endothelial cell dysfunction and hemostasis in treated antiphospholipid syndrome and in healthy pregnancy.

OBJECTIVE: The purpose of this study was to determine whether primary antiphospholipid syndrome pregnancies are associated with endothelial cell activation in the maternal circulation. STUDY DESIGN: Markers of endothelial cell activation were measured every 4 weeks during pregnancy in the blood of 23 women with primary antiphospholipid syndrome and 19 control subjects. All women with antiphospholipid syndrome received anticoagulant treatment. Plasma concentrations of plasminogen activator inhibitor type 1, tissue plasminogen activator, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and soluble thrombomodulin were determined by enzyme-linked immunoassay. Concentrations of prothrombin fragments 1+2 and D-dimers were also determined. RESULTS: Three antiphospholipid syndrome pregnancies (13%) were complicated by intrauterine growth restriction and preeclampsia; one antiphospholipid syndrome pregnancy (4%) was complicated by preterm rupture of membranes. Six women with antiphospholipid syndrome (26%) had thrombotic events. Differences in concentrations of endothelial cell activation markers between antiphospholipid syndrome and control pregnancies were not significant. CONCLUSION: Despite poorer pregnancy outcome, there was no evidence of greater endothelial cell activation in antiphospholipid syndrome pregnancies that were treated.

Anticoagulants↗
PubMed2003

Longitudinal analysis of serum insulin-like growth factor-I and insulin-like growth factor binding protein-1 in antiphospholipid syndrome and in healthy pregnancy.

OBJECTIVE: The purpose of this study was to determine the concentrations of serum insulin-like growth factor-I and insulin-like growth factor binding protein-1 in pregnancies that are complicated with primary antiphospholipid syndrome. STUDY DESIGN: Longitudinal blood samples were collected from 8 weeks of gestation in 28 women with treated primary antiphospholipid syndrome and 19 control women. Serum insulin-like growth factor-I and insulin-like growth factor binding protein-1 were measured by immunoradiometric assay. RESULTS: Three antiphospholipid syndrome pregnancies miscarried, four pregnancies had intrauterine growth restriction and preeclampsia, six pregnancies had a thrombotic event, and one pregnancy had abruptio placentae. Mean (+/-SD) birth weight in antiphospholipid syndrome group was 2867 +/- 914 g (control, 3492 +/- 527 g; P =.02), and the mean gestation at delivery was 36.5 +/- 5.2 weeks (control, 40.3 +/- 0.7 weeks; P =.002). Insulin-like growth factor binding protein-1 and insulin-like growth factor-I concentrations increased with gestational age in both groups (2.8% and 2.4% per week), but insulin-like growth factor binding protein-1 was 61% higher in the antiphospholipid syndrome group (95% CI, 16%-122%; P =.004). Insulin-like growth factor-I was not significantly different (8% higher in antiphospholipid syndrome; 95% CI, -10% to 30%; P =.41). CONCLUSION: Serum concentrations of insulin-like growth factor binding protein-1 are abnormal in the antiphospholipid syndrome group and may reflect abnormalities in trophoblast invasion.

Abortion, Spontaneous↗