Management of thromboembolism in pregnancy

The incidence of venous thromboembolism is increased during pregnancy and the postpartum period. This risk is high for women with documented hereditary or acquired risk factors who have experienced a prior thrombotic event. These individuals require a minimum of prophylactic dose anticoagulation with unfractionated or low molecular weight heparin during pregnancy, with anticoagulation continuing for 4 to 6 weeks postpartum. Women receiving therapeutic dose anticoagulation with warfarin before pregnancy for a hereditary or acquired condition should be transitioned to therapeutic doses of unfractionated heparin or low molecular weight heparin before or within 6 weeks of becoming pregnant, and can then resume warfarin postpartum. Women experiencing a thromboembolic event during pregnancy should receive therapeutic treatment with unfractionated heparin or low molecular weight heparin during pregnancy, with anticoagulation continuing for 4 to 6 weeks postpartum, and for a total of at least 6 months.     

Thromboprophylaxis during pregnancy and the puerperium: highlights from current guidelines

Venous thromboembolism (VTE) is one of the leading causes of maternal deaths worldwide. Mortality and morbidity of VTE are potentially preventable, since two-thirds of these women have identifiable risk factors and may benefit from appropriate thromboprophylaxis. Individual and careful assessment of the personal and family history as well as the assessment of pre-existing and new-onset/transient risk factors during pregnancy and after delivery are mandatory for an effective prevention of VTE. Current guidelines (American College of Chest Physicians 2008, AWMF-Guideline 003/001 2009 and the Royal College Guideline No. 37 2009) provide practical recommendations for risk stratification regarding low, intermediate and high risk conditions. At high risk are women with previous VTE or thrombophilia. Corresponding to risk stratification grade C recommendations have been made for VTE prophylaxis during pregnancy and the puerperium. Prophylaxis with low molecular weight heparin (LMWH) should begin as early in pregnancy as practical. In women with lower risk mobilisation, avoidance of dehydration and mechanical methods (e. g., graduated compressive stockings) are sufficient. After delivery women with intermediate risk should be given LMWH for 7 days, women at high risk for 6 weeks or as long as additional risk factors are present. All women who have additional risk factors and who have had an elective Caesarean section should receive prophylactic LMWH for 7 days as should also all women who have had a Caesarean section in labour or an emergency Caesarean section. At the onset of labour, in case of any vaginal bleeding, prior to induction of labour or 12 h before an elective Caesarean section, antenatal LMWH prophylaxis should be discontinued, LMWH prophylaxis can be continued for 4-6 h after vaginal and for 6-12 h after Caesarean delivery when the women do not have an increased risk of haemorrhage. Current guidelines recommend than LMWH are the agents of choice for antenatal thromboprophylaxis; in comparison to unfractionated heparin, LMWH are associated with a substantially lower risk of heparin-induced thrombocytopenia and osteoporosis. Both oral anticoagulants and heparin are safe when breast-feeding.     

Use of Low Molecular Weight Heparin in Acute Venous Thromboembolic Events in Pregnancy

Objective: To compare the maternal and neonatal outcomes arising from the use of low molecular weight heparin (LMWH) or unfractioned heparin (UFH) in the treatment of acute venous thromboembolism (VTE) in pregnancy.Study Design: A retrospective review of the charts of all women treated for acute VTE in pregnancy at the Ottawa Hospital from January 1990 to December 1999.Results: Twenty-three cases were identified, of which 11 were treated with LMWH and 12 with UFH. Maternal and fetal outcomes were similar between the two groups. Hospital length of stay was shorter in the LMWH group. There was no difference in delivery management between the two groups. There was minor bleeding in 2 women in the UFH group and none in the LMWH group. There was one recurrent VTE during treatment in each of the groups.Conclusion: There is no difference in complication rate between LMWH and UFH in the treatment of acute VTE in pregnancy.     

PREVENTION AND TREATMENT OF VENOUS THROMBOEMBOLISM (VTE) IN OBSTETRICS

OBJECTIVE: to identify risk factors for venous thromboembolism (VTE) in the peripartum period and to provide guidelines for risk assessment and thromboprophylactic measures for VTE in pregnant women. Guidelines for diagnostic testing and for acute and long term treatment of VTE are also provided.OPTIONS: specific subgroups of pregnant women are defined and appropriate prophylactic measures are outlined. OUTCOMES: venous thromboembolism remains a major cause of morbidity and mortality in pregnancy and the postpartum period. Identification of risk and adequate prophylaxis can decrease the incidence of VTE.EVIDENCE: evidence was gathered using Medline (National Library of Medicine) to identify relevant studies and from bibliographies of articles thus identified.RECOMMENDATIONS: although evidence is lacking to date from Grade I studies (properly controlled randomized studies) in pregnant patients, there is good evidence to support the role of prophylaxis in reducing the incidence of VTE in patients identified to be at risk in the non-pregnant population (II B). Based on risk assessment more patients should be considered for thromboprophylaxis, including women with a past history of a VTE and a known thrombophilia on long-term anticoagulation, women with a past history of a VTE, women with a known thrombophilia who have never experienced a VTE and potentially considered in women at the time of Caesarean section (II B; III C). The occurrence of VTE is effectively reduced by the use of low dose unfractionated heparin. Experience with low molecular weight heparin and pregnancy is building, but is limited at present. Unfractionated heparin remains the standard for the treatment of VTE in pregnancy at the present time. Following initial heparinization for the treatment of VTE, patients should be continued on anticoagulation throughout pregnancy and for six to 12 weeks postpartum or a total of three months of anticoagulation (II A).     

Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period

Venous thromboembolism (VTE) in pregnancy and the postpartum is an important cause of maternal morbidity and mortality; yet, there are few robust data from clinical trials to inform an approach to diagnosis and management. Failure to investigate symptoms suggestive of pulmonary embolism (PE) is a consistent finding in maternal death enquiries, and clinical symptoms should not be relied on to exclude or diagnose VTE. In this consensus statement, we present our recommendations for the diagnosis and management of acute deep venous thrombosis (DVT) and PE. All women with suspected DVT in pregnancy should be investigated with whole leg compression ultrasonography. If the scan is negative and significant clinical suspicion remains, then further imaging for iliofemoral DVT maybe required. Imaging should be undertaken in all women with suspected PE, as the fetal radiation exposure with both ventilation/perfusion scans and CT pulmonary angiography is within safe limits. Low-molecular-weight heparin (LMWH) is the preferred therapy for acute VTE that occur during pregnancy. In observational cohort studies, using once-daily regimens appears adequate, in particular with the LMWH tinzaparin; however, pharmacokinetic data support twice-daily therapy with other LMWH and is recommended, at least initially, for PE or iliofemoral DVT in pregnancy. Treatment should continue for a minimum duration of six months, and until at least six weeks postpartum. Induction of labour or planned caesarean section maybe required to allow an appropriate transition to unfractionated heparin to avoid delivery in women in therapeutic doses of anticoagulation.     

A local risk score model for venous thromboembolism prophylaxis for caesarean section in Chinese women and comparison with international guidelines

ObjectiveRecommendations for venous thromboembolism (VTE) prophylaxis from authoritative guidelines for women undergoing caesarean delivery differed significantly and may not be applicable to Chinese populations. We aim to formulate a local risk model for VTE prophylaxis for caesarean section women.Material and methodsA local risk score model based on demographic, obstetric and medical parameters was used to assess the risk of VTE in women undergoing caesarean delivery from May 2017 to April 2018 in a regional obstetric unit. Women with increased risk (VTE Score ≥ 2) are given mechanical prophylaxis with pneumatic cuff and those with high risk (VTE Score ≥ 3) are additionally prescribed low molecular weight heparin (LMWH) as pharmacological prophylaxis in the early postpartum period. The risk scores obtained by applying other major guidelines were then compared.ResultsOf 859 patients were included for analysis, overweight (15.3%), advanced maternal age (9.7%), multiple pregnancy (5.1%), obesity (4.7%), and primary postpartum haemorrhage (4.1%) were the most common risk factors. Overall, 109 (12.7%) patients required mechanical prophylaxis and 28 (3.3%) patients required additional pharmacological prophylaxis. No patient had postpartum VTE events nor serious haemorrhage after receiving LMWH prophylaxis. In contrast, applying the Royal College of Obstetricians and Gynaecologists guidelines to our cohort, 649 (75.6%) patients would receive LMWH after caesarean section, compared with no patients under the American College of Obstetrics and Gynaecology guidelines.ConclusionsOur local risk score model avoided the need for large proportions of women to be subjected to pharmacological prophylaxis, and appeared safe and practical.     

Prevention and Treatment of Thrombo-embolic Disease in Gynaecological Surgery

Objective: to identify pre-operative risk factors for venous thrombo-embolism (VTE) and to provide guidelines for risk assessment and for thrombo-prophylactic measures for VTE in women undergoing gynaecological surgery. Guidelines for diagnostic testing and for acute and long-term treatment of VTE are also provided.Options: low, moderate and high-risk groups of patients are defined and appropriate prophylactic measures are outlined. Alternative measures to low-dose unfractionated heparin (LDUH), for example low molecular weight heparin (LMWH), leg stockings, dextran 70 and acetylsalicylic acid are discussed. Alternative methods for acute treatment of VTE are also provided.Outcomes: venous thrombo-embolism remains a major cause of morbidity and mortality following gynaecological surgery. Adequate prophylaxis can decrease the incidence of VTE.Evidence: evidence was gathered using MEDLINE (National Library of Medicine) to identify pertinent studies and from bibliographies of articles thus identified.Recommendations: prophylactic measures for VTE decrease its incidence (Level 1 evidence). Based on risk assessment, more patients should be considered for prophylaxis (Grade A recommendation). The occurrence of VTE is effectively reduced by the use of LDUH and maybe more soby the use of LMWH (Level 1 evidence). For treatment of VTE, unfractionated heparin (UH) has been standard, although LMWH has now been proven to be at least as effective and safe (Level 1 evidence). Based on this evidence, LDUH or LMWH should be used in prophylaxis when feasible and UH or LMWH in treatment of VTE (Grade A recommendation). Following initial heparinization for treatment of VTE, patients should receive oral anticoagulation for at least three months (Grade A recommendation). Consideration could be given to extending prophylaxis beyond hospital discharge in high-risk patients.     

Current management of thromboembolism in pregnancy and puerperium

Venous thromboembolism (VTE) remains the leading cause of maternal death. Today, various risk factors and conditions are known to increase the risk for VTE associated with pregnancy. Having identified the individual risk of a pregnant women, appropriate preventive measures can be taken. If VTE occurs during pregnancy, an appropriate immediate diagnostic work-up is essential in order to avoid further complications. For deep vein thrombosis (DVT) the diagnostic tool of choice is color-coded duplex-sonography, for pulmonary embolism (PE) perfusion/ventilation lung scan can be used. Integrating a detailed individual and family history, the presence of thrombophilia or other risk factors, a risk stratification can be undertaken. These risk categories are defined in the present paper and the appropriate treatment measures are described. As oral anticoagulants cross the placenta and may cause embryopathy in any trimester, oral anticoagulants should be avoided throughout pregnancy. Therefore, heparin is the anti-coagulant of choice for pregnant women, with low molecular weight heparins (LMWH) having distinctive pharmacological advantages over unfractionated heparins. Besides a potential for bleeding, the main side effects of heparin include heparin-induced thrombocytopenia which prompts for platelet monitoring, especially in the first weeks of heparin treatment, and, secondly, heparin-induced osteoporosis, which is a potential sequel of long-term heparin administration. Even though there are abundant reports in the literature on the use of LMWH in pregnant women, that show that they are safe and effective, LMWH are not specifically licensed for the use in pregnancy.     

Pharmacokinetics of low molecular weight heparin and unfractionated heparin in pregnancy

OBJECTIVE: Little pharmacokinetic data are available for either low molecular weight heparins (LMWHs) or unfractionated heparins (UFHs) in pregnancy. The objectives of this study were to determine whether differences exist in the pharmacokinetics of dalteparin and UFH before and during the first, second, and third trimesters of pregnancy in women with the antiphospholipid antibody syndrome (APS). Adjustments in our dosing protocol would be made if differences existed. METHODS: Women with APS who were contemplating pregnancy were randomized to dalteparin 2500 U, 2500 U, 5000 U, and 7500 U daily, or UFH 5000 U, 5000 U, 7500 U, and 10,000 U every 12 hours, prior to pregnancy and the first, second, and third trimesters, respectively. Serial plasma concentrations of heparin were measured during 4 blood sampling days by determining anti-factor Xa activity. RESULTS: Fifteen (n = 9 receiving dalteparin and n = 6 receiving UFH) completed all four sampling periods. For dalteparin, significant differences (P <.05) were detected, using area under the curve (AUC), between pre-pregnancy versus third trimester, first versus second trimester, first versus third trimester, and second versus third trimester. No significant differences were detected in the UFH group. CONCLUSION: In APS, our original dosing protocol of dalteparin yielded significant differences (P <.05) in drug exposure throughout pregnancy. Based on these results, we recommend a prophylactic dalteparin dosing regimen of 2500 U every 24 hours pre-pregnancy (and for 6 weeks postpartum), and 5000 U every 24 hours during the first, second, and third trimesters. Due to lack of significant differences in AUC throughout pregnancy for UFH, we recommend continuing with our original dosing protocol.     

Low-molecular-weight heparins for the prevention and treatment of venous thromboembolism in at-risk pregnant women: a review

Certain pregnant populations are at high risk of developing venous thromboembolism (VTE) during pregnancy. Patients at particularly high risk of VTE are those with a history of VTE, thrombophilia or adverse pregnancy outcomes or with mechanical heart valves. In these high-risk patients, evidence-based guidelines recommend the use of thromboprophylaxis. Low-molecular-weight heparin (LMWH) is a safe and effective thromboprophylaxis option in these patients and has a number of administrative and pharmacokinetic advantages over unfractionated heparin. Furthermore, LMWH has also been shown to be a safe and effective treatment for confirmed deep vein thrombosis in pregnant women.     

Use of low molecular weight heparin for prophylaxis and treatment of thromboembolism in pregnancy.

Low molecular weight heparin (LMWH) preserves the antithrombotic action but not the anticoagulant activity of heparin. LMWH is safe, does not cross the placenta and is administered as a single daily injection. We report our experience with 6 pregnant women given LMWH for treatment or prophylaxis of thromboembolism. The drug was successfully given to 5 women for periods of 6 weeks--6 months and no thromboembolic complications occurred during pregnancy or pueperium. There were no hemorrhagic complications and no excessive bleeding was observed during delivery. The sixth patient relapsed after 6 weeks of therapy. This patient also showed resistance to standard heparin administered intravenously at a very high dose. LMWH should be considered an alternative to standard heparin in pregnant women requiring antithrombotic prophylaxis and therapy.     

Evaluating patient values and preferences for thromboprophylaxis decision making during pregnancy: A study protocol

ABSTRACT: BACKGROUND: Pregnant women with prior venous thromboembolism (VTE) are at risk of recurrence. Low molecular weight heparin (LWMH) reduces the risk of pregnancy-related VTE. LMWH prophylaxis is, however, inconvenient, uncomfortable, costly, medicalizes pregnancy, and may be associated with increased risks of obstetrical bleeding. Further, there is uncertainty in the estimates of both the baseline risk of pregnancy-related recurrent VTE and the effects of antepartum LMWH prophylaxis. The values and treatment preferences of pregnant women, crucial when making recommendations for prophylaxis, are currently unknown. The objective of this study is to address this gap in knowledge. METHODS: We will perform a multi-center cross-sectional interview study in Canada (2 sites), USA, Norway and Finland. The study population will consist of 100 women with a history of lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE), and who are either pregnant, planning pregnancy, or may in the future consider pregnancy (women between 18 and 45 years). We will exclude individuals who are on full dose anticoagulation or thromboprophylaxis, who have undergone surgical sterilization, or whose partners have undergone vasectomy. We will determine each participant's willingness to receive LMWH prophylaxis during pregnancy through direct choice exercises based on real life and hypothetical scenarios, preference-elicitation using a visual analog scale ("feeling thermometer"), and a probability trade-off exercise. The primary outcome will be the minimum reduction (threshold) in VTE risk at which women change from declining to accepting LMWH prophylaxis. We will explore possible determinants of this choice, including educational attainment, the characteristics of the women's prior VTE, and prior experience with LMWH. We will determine the utilities that women place on the burden of LMWH prophylaxis, pregnancy-related DVT, pregnancy-related PE and pregnancy-related hemorrhage. We will generate a "personalized decision analysis" using participants' utilities and their personalized risk of recurrent VTE as inputs to a decision analytic model. We will compare the personalized decision analysis to the participant's stated choice. DISCUSSION: The preferences of pregnant women at risk of VTE with respect to the use of antithrombotic therapy remain unexplored. This research will provide explicit, quantitative expressions of women's valuations of health states related to recurrent VTE and its prevention with LMWH. This information will be crucial for both guideline developers and for clinicians.     

Enoxaparin versus unfractionated heparin in the management of recurrent abortion secondary to antiphospholipid syndrome

Objective

To determine whether low molecular weight heparin (LMWH) plus low-dose aspirin (LDA) is comparable in efficacy and safety to unfractionated heparin (UFH) plus LDA in the management of pregnant women with a history of recurrent spontaneous abortion secondary to antiphospholipid syndrome (APS).

Methods

In a randomized prospective study, 60 women with a history of 3 or more consecutive spontaneous abortions and positive antiphospholipid antibodies were assigned in equal numbers to receive either UFH (5000 units, twice daily) plus LDA, or LMWH (enoxaparin 40 mg, once daily) plus LDA as soon as pregnancy was diagnosed.

Results

Twenty-four women in the LMWH group (80%) and 20 women in the UFH group (66.67%) delivered a viable infant (P = 0.243). There were no significant differences in pregnancy complications or neonatal morbidity between the 2 groups. There were no incidences of excessive bleeding, thrombocytopenia, or osteoporotic fractures in either group.

Conclusion

LMWH plus LDA was successfully used as an alternative to UFH plus LDA in the management of recurrent abortion secondary to APS. The results highlight the need for a larger randomized controlled trial to determine whether LMWH plus LDA should be the treatment of choice for recurrent abortion secondary to APS.Clinicaltrials.govNCT01051778.     

Venous thromboembolism in pregnancy

Venous thromboembolism remains a common cause of direct maternal deaths in high-income settings such as the United Kingdom. Pregnancy alone increases the risk of deep vein thrombosis and pulmonary embolus at least five-fold, and many women develop or have additional risk factors for venous thrombosis during pregnancy and the puerperium, the latter representing the period of highest risk. Early and repeated risk stratification and adequate thromboprophylaxis, usually with low molecular weight heparin, is the key to preventing venous thromboembolism (VTE). Women with a past history of VTE, and those affected by thrombophilia, require multidisciplinary care involving an obstetric haematologist. Women suspected of having acute thromboembolism should be commenced on empirical treatment promptly prior to diagnostic confirmation. Pulmonary embolism should be considered as a differential diagnosis in maternal collapse.     

Low molecular weight heparin use during pregnancy and risk of postpartum hemorrhage: a systematic review and meta-analysis

Introduction: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide with a prevalence rate of approximately 6%. Although most cases of PPH have no identifiable risk factors, the incidence of PPH has been associated to the thromboprophylaxis in pregnancy with low molecular weight heparin (LMWH). Thus, the aim of the study is to evaluate the risk of PPH in cases of pregnant women exposed to LMWH.

Materials and methods: Electronic research was performed in OVID, Scopus, ClinicalTrials.gov, MEDLINE, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE, and the Cochrane Central Register of Controlled Trials through April 2016. We included randomized controlled trials, cohort and case-control studies of women who underwent thromboprophylaxis with LMWH during pregnancy compared to a control group (either placebo or no treatment). The primary outcome was the incidence of PPH. The summary measures were reported as relative risk (RR) or as mean differences (MD) with 95% confidence interval (CI).

Results: Eight studies including 22,162 women were analyzed. Of the 22,162 women, 1320 (6%) were administered LMWH, 20,842 (94%) women formed the nonexposed group (control group). Women treated with LMWH had a higher risk of PPH (RR 1.45, 95%CI 1.02–2.05) compared to controls; there was no difference in mean of blood loss at delivery (MD ?32.90, 95%CI 68.72–2.93) and in risk of blood transfusion at delivery (RR 1.24, 95%CI 0.62–2.51), respectively.

Conclusions: Women who receive LMWH during pregnancy have a significantly higher risk of developing PPH. Women who receive LMWH during pregnancy have neither significantly higher mean blood loss at delivery nor higher risk of blood transfusion.     

The use of unfractionated heparin and low molecular weight heparins in pregnancy

Currently unfractionated heparin (UH) and low molecular weight heparins (LMWH) are the agents of choice for anticoagulation in pregnancy. LMWH have been used safely without monitoring in nonpregnant patients; however, because of documented changes in the pharmacokinetics of these agents in pregnancy, monitoring with anti-Xa levels is necessary in pregnancy to maintain target therapeutic ranges. Patients requiring only prophylaxis during pregnancy with either UH or LMWH might benefit from occasional assessment of anti-Xa levels to confirm that target prophylactic ranges are being achieved. Although LMWH may cause less osteoporosis than UH at therapeutic doses, the incidence of heparin-induced osteoporosis seems to be low when only prophylactic dosing is used and therefore LMWH do not seem to offer this advantage at low doses. Experience with newer agents such as pentasaccharide inhibitors and direct thrombin inhibitors are limited in pregnancy and it remains to be seen what role these agents will play in women who require anticoagulation in pregnancy.     

The use of low-molecular-weight heparin for the management of venous thromboembolism in pregnancy

Thromboembolic disease is a rare, but important, complication of pregnancy that remains a leading non-obstetric cause of maternal death. The prevention and management of venous thromboembolism (VTE) in pregnant women is a complex area of medicine: a balance must be found between protecting the health of the mother and minimizing the risk to the unborn fetus. Until now, unfractionated heparin has been regarded as the drug of choice for the prevention and treatment of VTE during pregnancy. However, because of its significant side effects (osteoporosis and heparin-induced thrombocytopenia), the inconvenient mode of administration and need for monitoring, unfractionated heparin is now being replaced by low-molecular-weight heparin (LMWH). There is a convincing body of clinical evidence from well-designed studies and prospective case series that supports the efficacy and safety of LMWH in pregnant women. There are also encouraging observations on the efficacy of LMWH in the prevention of severe obstetric complications, which are frequently associated with inherited or acquired thrombophilias. The recently-published guidelines of The American College of Chest Physicians (ACCP), summarized in this review, allows the development of higher clinical standards. However, there is concern over the greater cost of LMWH compared with unfractionated heparin and oral anticoagulants, and cost-effectiveness studies are needed.     

Antiphospholipid antibodies associated with recurrent pregnancy loss: prospective, multicenter, controlled pilot study comparing treatment with low-molecular-weight heparin versus unfractionated heparin

OBJECTIVE: To evaluate the use of low-molecular-weight heparin (LMWH) in combination with low-dose aspirin (LDA) for the treatment of antiphospholipid antibody (APA)-associated recurrent pregnancy loss and to compare the results with the use of unfractionated heparin (UFH) plus LDA. DESIGN: Prospective, controlled, multicenter pilot study. SETTING: Two academically based reproductive health centers. PATIENT(S): Patients with three or more pregnancy losses and positive APA. INTERVENTION(S): Patients were treated with LMWH and LDA (n = 25) or UFH and LDA (n = 25). MAIN OUTCOME MEASURE(S): Fetal outcome and maternal complications from treatments were compared between the two treatment groups. RESULT(S): Of the 25 patients in the LMWH group, 21 (84%) delivered a viable infant and 4 (16%) miscarried. Of the 25 patients in the UFH group, 20 (80%) delivered a viable infant and 5 (20%) miscarried. These differences were not statistically significant. No major bleeding episodes occurred during pregnancy or at the time of delivery. No cases of deep venous thrombosis, thrombocytopenia, pre-eclampsia, gestational diabetes, or bone fractures were noted in either of the two groups. CONCLUSION(S): In this pilot study, the use of LDA in combination with LMWH during pregnancy for the prevention of recurrent pregnancy loss in women with antiphospholipid syndrome seems to be as safe as UFH plus LDA. Large, randomized trials will be required to determine differences in outcome with LMWH and LDA compared with treatment with UFH combined with LDA in this group of patients.     

Venous thromboembolism prevention in gynecologic cancer surgery: a systematic review

OBJECTIVES: Advanced age, pelvic surgery, and the presence of malignancy place gynecologic oncology patients at high risk for venous thromboembolism (VTE). This study was designed to systematically analyze the world's literature on VTE in these patients and determine the optimal prophylaxis regimen. METHODS: Computerized searches of Pubmed, Ovid, DARE, ACP Journal Club, Cochrane Database of Systematic Reviews, and Cochrane Controlled Trials Registry 1966-2005 were performed, as well as EMBASE 1980-2005. Major conferences and target references were hand-searched. Inclusion criteria were randomized controlled trials (RCTs) evaluating VTE prophylaxis with heparin, low-molecular-weight heparin (LMWH), and sequential compression devices (SCD). The search yielded 278 articles; 11 met inclusion criteria. Data were abstracted by one author and analyzed with the Mantel-Haenszel method. RESULTS: The analysis of heparin-versus-control revealed a significant decrease in DVT in patients receiving heparin (RR=0.58, 95% CI 0.35-0.95). There were no significant differences in EBL or transfusions between the two groups. In the 320 patients in the heparin vs. LMWH studies, there was no significant difference in DVT (RR 0.91, 95% CI 0.38-2.17), although power analysis demonstrated insufficient numbers to show a difference. No patient in either group required re-exploration for bleeding. CONCLUSIONS: All gynecologic cancer patients should receive VTE prophylaxis. Although heparin, LMWH, and SCD have been shown to be safe and effective, due to the paucity of data in the gynecologic oncology literature, no one prevention modality can be considered superior at this time. Adequately powered RCTs are urgently needed to determine the optimal regimen in these high-risk patients.