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Biomedical subjects

I D Walker

Publications and source records attributed to I D Walker.

At least 19 recordsLinked to original sources
PubMed2006

Thrombophilia in pregnancy: a systematic review.

Growing evidence suggests that thrombophilia is associated with venous thromboembolism (VTE) and adverse pregnancy outcomes. However, methodological limitations have made it difficult to obtain a clear overview of the overall risks. We conducted a systematic review to determine the risk of VTE and adverse pregnancy outcomes associated with thrombophilia in pregnancy. The effectiveness of prophylactic interventions during pregnancy was also evaluated. Major electronic databases were searched, relevant data abstracted and study quality assessed by two independent reviewers. Odds ratios (ORs) stratified by thrombophilia type were calculated for each outcome. A total of 79 studies were included in our review. The risks for individual thrombophilic defects were determined for VTE (ORs, 0.74-34.40); early pregnancy loss (ORs, 1.40-6.25); late pregnancy loss (ORs, 1.31-20.09); pre-eclampsia (ORs, 1.37-3.49); placental abruption (ORs, 1.42-7.71) and intrauterine growth restriction (ORs, 1.24-2.92). Low-dose aspirin plus heparin was the most effective in preventing pregnancy loss in thrombophilic women (OR, 1.62). Our findings confirm that women with thrombophilia are at risk of developing VTE and complications in pregnancy. However, despite the increase in relative risk, the absolute risk of VTE and adverse outcomes remains low. There is also a lack of controlled trials of antithrombotic intervention to prevent pregnancy complications. Thus, at present, universal screening for thrombophilia in pregnancy cannot be justified clinically.

Female↗
PubMed2006

Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study.

OBJECTIVES: To assess the risk of clinical complications associated with thrombophilia in three high-risk patient groups: women using oral oestrogen preparations, women during pregnancy and patients undergoing major orthopaedic surgery. To assess the effectiveness of prophylactic treatments in preventing venous thromboembolism (VTE) and adverse pregnancy outcomes in women with thrombophilia during pregnancy and VTE in patients with thrombophilia, undergoing major orthopaedic surgery. To evaluate the relative cost-effectiveness of universal and selective VTE history-based screening for thrombophilia compared with no screening in the three high-risk patient groups. DATA SOURCES: Electronic databases including MEDLINE, EMBASE, and four other major databases were searched up to June 2003. REVIEW METHODS: In order to assess the risk of clinical complications associated with thrombophilia, a systematic review of the literature on VTE and thrombophilia in women using oral oestrogen preparations and patients undergoing major orthopaedic surgery; and studies of VTE and adverse obstetric complications in women with thrombophilia during pregnancy was carried out. Meta-analysis was used to calculate pooled odds ratios (ORs) associated with individual clinical outcomes, stratified by thrombophilia type and were calculated for each patient group. To assess the effectiveness of prophylaxis, a systematic review was carried out on the use of prophylaxis in the prevention of VTE and pregnancy loss in pregnant women with thrombophilic defects and the use of thromboprophylaxis in the prevention of VTE in patients with thrombophilia undergoing major elective orthopaedic surgery. Relevant data were summarised according to the patient groups and stratified according to the types of prophylaxis. A narrative summary was provided; where appropriate, meta-analysis was conducted. An incremental cost-effectiveness analysis was then carried out, from the perspective of the NHS in the UK. A decision analytical model was developed to simulate the clinical consequences of four thrombophilia screening scenarios. Results from the meta-analyses, information from the literature and results of two Delphi studies of clinical management of VTE and adverse pregnancy complications were incorporated into the model. Only direct health service costs were measured and unit costs for all healthcare resources used were obtained from routinely collected data and the literature. Cost-effectiveness was expressed as incremental cost-effectiveness ratios (ICERs); an estimate of the cost per adverse clinical complication prevented, comparing screening with no screening, were calculated for each patient group. RESULTS: In the review of risk of clinical complications, 81 studies were included, nine for oral oestrogen preparations, 72 for pregnancy and eight for orthopaedic surgery. For oral contraceptive use, significant associations of the risk of VTE were found in women with factor V Leiden (FVL); deficiencies of antithrombin, protein C, or protein S, elevated levels of factor VIIIc; and FVL and prothrombin G20210A. For hormone replacement therapy (HRT), a significant association was found in women with FVL. The highest risk in pregnancy was found for FVL and VTE, in particular, homozygous carriers of this mutation are 34 times more likely to develop VTE in pregnancy than non-carriers. Significant risks for individual thrombophilic defects were also established for early, recurrent and late pregnancy loss; preeclampsia; placental abruption; and intrauterine growth restriction. Significant associations were found between FVL and high factor VIIIc and postoperative VTE following elective hip or knee replacement surgery. Prothrombin G20210A was significantly associated with postoperative pulmonary embolism. However, antithrombin deficiency, MTHFR and hyperhomocysteinaemia were not associated with increased risk of postoperative VTE. In the review of the effectiveness of prophylaxis, based on available data from eight studies, low-dose aspirin and heparin was found to be the most effective in preventing pregnancy loss in thrombophilic women during pregnancy, while aspirin alone was the most effective in preventing minor bleeding. All the studies on thrombophilia and major elective orthopaedic surgery included in the review of risk complications were also used in the review of the effectiveness of thromboprophylaxis. However, there were insufficient data to determine the relative effectiveness of different thromboprophylaxis in preventing VTE in this patient group. For the cost-effectiveness analysis, of all the patient groups evaluated, universal screening of women prior to prescribing HRT was the most cost-effective (ICER pound6824). In contrast, universal screening of women prior to prescribing combined oral contraceptives was the least cost-effective strategy (ICER pound202,402). Selective thrombophilia screening based on previous personal and/or family history of VTE was more cost-effective than universal screening in all the patient groups evaluated. CONCLUSIONS: Thrombophilia is associated with increased risks of VTE in women taking oral oestrogen preparations and patients undergoing major elective orthopaedic surgery, and of VTE and adverse pregnancy outcomes in women with thrombophilia during pregnancy. There is considerable difference in the magnitude of the risks among different patient groups with different thrombophilic defects. In women who are on combined oral contraceptives, the OR of VTE among those who are carriers of the FVL mutation was 15.62 (95% confidence interval 8.66 to 28.15). However, in view of the prevalence of thrombophilia and the low prevalence of VTE in non-users of combined oral contraceptives, the absolute risk remains low. Significant risks for VTE and adverse pregnancy outcomes have been established with individual thrombophilic defects. Thrombophilic defects including FVL, high plasma factor VIIIc levels and prothrombin G20210A are associated with the occurrence of postoperative VTE in elective hip or knee replacement therapy. These associations are observed in patients who were given preoperative thromboprophylaxis and are, therefore, of clinical significance. Universal thrombophilia screening in women prior to prescribing oral oestrogen preparations, in women during pregnancy and in patients undergoing major orthopaedic surgery is not supported by current evidence. The findings from this study show that selective screening based on prior VTE history is more cost-effective than universal screening. Large prospective studies should be undertaken to refine the risks and establish the associations of thrombophilias with VTE among hormone users and in patients undergoing orthopaedic surgery. The relative value of a thrombophilia screening programme to other healthcare programmes needs to be established.

Cost-Benefit Analysis↗
PubMed2005

Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT).

BACKGROUND: Reliable risk estimates for venous thrombosis in families with inherited thrombophilia are scarce but necessary for determining optimal screening and treatment policies. OBJECTIVES: In the present analysis, we determined the risk of a first venous thrombotic event in carriers of a thrombophilic defect (i.e. antithrombin-, protein C- or protein S deficiency, or factor V Leiden). PATIENTS AND METHODS: The asymptomatic carriers had been tested prior to this study in nine European thrombosis centers because of a symptomatic carrier in the family, and were followed prospectively for 5.7 years on average between March 1994 and January 2001. Annually, data were recorded on the occurrence of risk situations for venous thrombosis and events (e.g. venous thrombosis, death). RESULTS: Twenty-six of the 575 asymptomatic carriers (4.5%) and seven of the 1118 controls (0.6%) experienced a first deep venous thrombosis or pulmonary embolism during follow-up. Of these events, 58% occurred spontaneously in the carriers compared with 43% in the controls. The incidence of first events was 0.8% per year (95% CI 0.5-1.2) in the carriers compared with 0.1% per year (95% CI 0.0-0.2) in the controls. The highest incidence was associated with antithrombin deficiency or combined defects, and the lowest incidence with factor V Leiden. CONCLUSIONS: The incidence of venous events in asymptomatic individuals from thrombophilic families does not exceed the risk of bleeding associated with long-term anticoagulant treatment in the literature (1-3%).

Adolescent↗
PubMed2004

'Last-ditch' use of recombinant factor VIIa in patients with massive haemorrhage is ineffective.

BACKGROUND AND OBJECTIVES: The aim of this retrospective study was to assess the effect of activated recombinant factor VII (rFVIIa) on the natural history of massive transfusion episodes. MATERIALS AND METHODS: During 2002, outcome parameters were assessed in 50 patients transfused with more than 10 units of packed red cells. The effect of the addition of rFVIIa in 10 patients, with intractable bleeding, was then observed. RESULTS: Overall mortality was 20% at 24 h and 34% at 7 days. Severe coagulopathy was confirmed as a serious negative prognostic factor and occurred in 42% of patients overall, but in 70% of rFVIIa-treated patients. Transient cessation or reduction of bleeding was noted in 60% of patients following rFVIIa infusion. However, 24-h and 7-day mortality rates were 40% and 70%, respectively, in this group. CONCLUSIONS: Last-ditch rFVIIa therapy in patients resistant to conventional treatment did not rescue these patients or significantly alter outcomes.

Adolescent↗
PubMed2004

Hereditary thrombophilia and fetal loss: a prospective follow-up study.

BACKGROUND: As the placental vessels are dependent on the normal balance of procoagulant and anticoagulant mechanisms, inherited thrombophilia may be associated with fetal loss. OBJECTIVES: We performed a prospective study to investigate the relation between inherited thrombophilia and fetal loss, and the influence of thromboprophylaxis on pregnancy outcome. PATIENTS AND METHODS: Women were enrolled in the European Prospective Cohort on Thrombophilia (EPCOT). These included women with factor (F)V Leiden or a deficiency of antithrombin, protein C or protein S. Controls were partners or acquaintances of thrombophilic individuals. A total of 191 women (131 with thrombophilia, 60 controls) had a pregnancy outcome during prospective follow-up. Risk of fetal loss and effect of thromboprophylaxis were estimated by frequency calculation and Cox regression modelling. RESULTS: The risk of fetal loss appeared slightly increased in women with thrombophilia without a previous history of fetal loss who did not use any anticoagulants during pregnancy (7/39 vs. 7/51; relative risk 1.4; 95% confidence interval 0.4, 4.7). Per type of defect the relative risk varied only minimally from 1.4 for FV Leiden to 1.6 for antithrombin deficiency compared with control women. Prophylactic anticoagulant treatment during pregnancy in 83 women with thrombophilia differed greatly in type, dose and duration, precluding solid conclusions on the effect of thromboprophylaxis on fetal loss. No clear benefit of anticoagulant prophylaxis was apparent. CONCLUSIONS: Women with thrombophilia appear to have an increased risk of fetal loss, although the likelihood of a positive outcome is high in both women with thrombophilia and in controls.

Adolescent↗
PubMed2004

Familial thrombophilia and lifetime risk of venous thrombosis.

BACKGROUND: We started a large multicenter prospective follow-up study to provide reliable risk estimates of venous thrombosis in families with various thrombophilic defects. OBJECTIVES: This paper describes data collected at study entry on venous events experienced before study inclusion, i.e. the baseline data. PATIENTS/METHODS: All individuals (probands, relatives) registered in nine European thrombosis centers with the factor (F)V Leiden mutation, a deficiency of antithrombin, protein C or protein S, or a combination of these defects, were enrolled between March 1994 and September 1997. As control individuals, partners, friends or acquaintances of the thrombophilic participants were included. Incidence and relative risk of objectively confirmed venous thrombotic events (VTEs) prior to entry were calculated for the relatives with thrombophilia and the controls. RESULTS: Of the 846 relatives with thrombophilia (excluding probands), 139 (16%) had experienced a VTE with an incidence of 4.4 per 1000 person years. Of the controls, 15 of the 1212 (1%) controls had experienced a VTE with an incidence of 0.3 per 1000 person years. The risk of venous thrombosis associated with familial thrombophilia was 15.7 (95% CI 9.2-26.8) and remained similar after adjustment for regional and sex-effects (16.4; 95% CI 9.6-28.0). The highest incidence per 1000 person years was found in relatives with combined defects (8.4; 95% CI 5.6-12.2), and the lowest incidence was found in those with the FV Leiden mutation (1.5; 95% CI 0.8-2.6). CONCLUSIONS: Considerable differences in the lifetime risk of VTE were observed among individuals with different thrombophilia defects.

Adolescent↗
PubMed2003

Interaction between hormone replacement therapy preparations and oral anticoagulant therapy.

There is limited information regarding the interaction of hormone replacement therapy (HRT) and oral anticoagulants. Following the acute over-anticoagulation of two women shortly after the initiation of tibolone, we have undertaken a retrospective review of anticoagulated women to determine if the dose of oral anticoagulants and quality of anticoagulant control are affected by the introduction of HRT. We demonstrate that acute over-anticoagulation consistently occurs following the commencement of tibolone and requires anticoagulant dose modification to re-establish target international normalised ratio (INR). In contrast, non-tibolone HRT preparations do not consistently alter anticoagulant control or dose requirements.

Administration, Oral↗
PubMed2002

Low molecular weight heparin for the treatment of venous thromboembolism in pregnancy: a case series.

OBJECTIVES: To assess the use of low molecular weight heparin for the treatment of venous thromboembolism in pregnancy. DESIGN: A prospective observational study. SETTING: The maternity units in two university teaching hospitals and one district general teaching hospital. POPULATION: Thirty-six consecutive women presenting with objectively diagnosed venous thromboembolism during pregnancy and the immediate puerperium. METHODS: Treatment with the low molecular weight heparin enoxaparin, approximately 1 mg/kg s.c., twice daily, based on early pregnancy weight. MAIN OUTCOME MEASURES: Peak anti-Xa activity (three hours post-injection), alterations in treatment, side effects and the use of regional anaesthesia. RESULTS: In 33 women, the initial dose of enoxaparin provided satisfactory peak anti-Xa activity (median 0.8 u/mL, range 0.44-1.0 u/mL) and was continued. Three women required dose reduction since peak anti-Xa activities were above the therapeutic range (1.2, 1.2 and 1.1 u/mL). No woman developed thrombocytopaenia, haemorrhagic complication or further thromboembolic episode. Two women developed allergic skin reactions on enoxaparin and were changed to tinzaparin. Fifteen women had regional anaesthesia for delivery, with a reduced dose of enoxaparin (40 mg once daily), all without complication. CONCLUSIONS: Enoxaparin is a safe and effective treatment for venous thromboembolism during pregnancy and confers a major advantage over unfractionated heparin through its simplified regimen of administration.

Adult↗
PubMed2001

Oral anticoagulation and hemorrhagic complications in an elderly population with atrial fibrillation.

BACKGROUND: Warfarin sodium therapy in patients with atrial fibrillation markedly reduces the incidence of embolic stroke. However, in elderly patients warfarin therapy is often underused owing to the perceived higher risk of hemorrhagic complications. OBJECTIVES: To assess the quality of anticoagulant control and the incidence of hemorrhagic complications and stroke in an elderly population (>75 years old) compared with a younger control group (between 60 and 69 years) and to assess the quality of anticoagulant control and incidence of hemorrhagic complications in those patients who recently commenced receiving warfarin therapy (first year of therapy). PATIENTS AND METHODS: In this retrospective follow-up study, anticoagulant control and the incidence of hemorrhagic complications and stroke were assessed in an elderly population (>75 years old) compared with a younger control group (between 60 and 69 years), all with atrial fibrillation(target international normalized ratio [INR] 2.5) and attending a hospital outpatient anticoagulant clinic. RESULTS: A total of 328 patients were studied over a 21-month period. There were 204 patients in the control group providing 288 patient-years of follow-up and 124 patients in the elderly group providing 170 patient-years of follow-up. The percentage of INR results in the target range was not statistically significantly different between the elderly and control groups (71.5% vs 66.1%) and the occurrences of incidences of INR greater than 7 were 4.2% in the control group and 4.7% in the elderly group (P =.96). The incidences of major hemorrhage were 2.8% per year in the elderly group and 2.9% per year in the control group (P =.96); overall incidence was 2.8% (95% confidence interval, 1.3%-4.4%). One hundred one of the 328 patients studied commenced warfarin therapy during or within 3 months of the start of the study. In this induction group, 62.1% of INRs were within the target range compared with 70.9% of INRs in patients who had been receiving warfarin therapy for more than 3 months at the start of the study (P =.002). The incidences of INR greater than 7 and major hemorrhage were 7.9% per year and 6.9% per year, respectively, in the cohort who recently began warfarin therapy compared with 3.4% per year and 1.7% per year in the group who were receiving warfarin therapy for more than 3 months. CONCLUSION: While it was impossible to consider any selection bias at the level of referral to the clinic, these findings suggest that the elderly population attending our anticoagulant clinic did not have poorer anticoagulant control or an increased incidence of hemorrhage while receiving warfarin therapy.

Aged↗
PubMed2001

Injecting drug use is a risk factor for deep vein thrombosis in women in Glasgow.

Three hundred and twenty-two consecutive women aged 16-70 years who presented with objectively confirmed symptomatic venous thromboembolism (VTE) were studied to determine precipitating factors for thrombosis. One hundred and eighty-seven presented with deep vein thrombosis (DVT), 116 with either definite or possible pulmonary embolism (PE) and 19 with both DVT and PE. Injecting drug use (IDU) via femoral vein puncture was a common risk factor for DVT, associated with 21.4% of all cases of DVT and 52.4% of cases of DVT in women under 40 years. All women with drug-related thrombosis presented with DVT. None presented with symptomatic PE. A number of clinically diagnosed DVT associated with IDU were also documented, suggesting that IDU may be the most common risk factor for DVT in our region. DVT associated with IDU presents significant management challenges.

Adolescent↗