Significant Risk Of Venous Thromboembolism Research Articles

Standard or extended-duration prophylaxis in medical patients? A review of the evidence

Acutely ill medical patients are at significant risk of venous thromboembolism (VTE). Thromboprophylaxis can substantially reduce the incidence of VTE, but to be optimally effective must consist of the correct choice of agent, at an appropriate dose, and for sufficient duration. Increasing evidence suggests that VTE risk persists beyond the standard period of prophylaxis. Although there is evidence that extended-duration prophylaxis is beneficial in preventing late VTE complications in high-risk surgical patients, few data exist in medical patients. The recent EXCLAIM study demonstrated that, subsequent to a standard prophylaxis regimen of 10±4days with enoxaparin 40mg once daily, extended-duration prophylaxis (28±4days) with enoxaparin reduced total VTE events compared with placebo: 2.5% versus 4.0%; (absolute risk difference -1.53%; 95.8% confidence interval [CI] -2.54 to -0.52), with parallel increases in major bleeding rates (0.8% vs. 0.3%; absolute risk difference 0.51%; 95% CI 0.12-0.89%). The reduction in total VTE was principally driven by a decrease in symptomatic deep-vein thrombosis (absolute risk difference -0.60%; 95.8% CI -1.00 to -0.19%). Favorable benefit-to-risk ratios were observed in certain high-risk patient groups: level 1 immobility, women, and age>75years. In addition to their underlying medical condition, medical patients often have multiple risk factors, placing them at sustained risk of VTE. Extended-duration prophylaxis might be most relevant in such patients. The development of appropriate risk assessment tools could help identify medical patients at greatest risk of late VTE events who might benefit most from extended-duration prophylaxis.

Prophylactic Inferior Vena Cava Filters in High-Risk Bariatric Surgery

Bariatric patients are at significant risk for venous thromboembolism (VTE) and a subset may benefit from retrievable inferior vena cava filters (rIVCFs). Optimal VTE prophylaxis and a consensus on factors which make bariatric patients high risk have not been established. This study describes our experience with the use of rIVCFs in combination with chemoprophylaxis for high-risk bariatric surgery patients. A retrospective review was performed of high-risk patients bariatric surgery patients. Patients with a hypercoaguable condition, prior history of VTE, body mass index (BMI) > 55kg/m(2), and severe immobility were considered high risk. Patients underwent rIVCF placement and standard chemoprophylaxis. A venogram was performed at retrieval. Forty-four patients, age of 48 ± 12years and BMI of 58.4 ± 9.4kg/m(2) underwent gastric bypass with rIVCF placement. Follow-up was 204days. One patient had a preoperative deep venous thrombosis (DVT). All patients received chemoprophylaxis and rIVCF placement. Indications for rIVCF were BMI (68%), prior VTE (30%), and immobility (2%). The operation was performed laparoscopically in all patients, and the mean operative time was 106.1 ± 21.6min and length of stay was 3.1 ± 1.2days. Postoperative venous duplex revealed two DVTs (5%). Retrieval was successful in 28 patients. No significant thrombus was found on venogram. Two minor complications of filter placement occurred. One mortality occurred due to MI, and no pulmonary emboli were clinically evident. rIVCFs in our cohort of high-risk bariatric surgery patients was associated with an acceptably low incidence of DVT (5%) and no clinically evident PE. Despite safe removal after long dwell times, previous data suggest that rIVCFs are associated with a higher incidence of VTE. Thus, filters, if placed, should be removed once the risk of VTE has passed. Larger multicenter studies are needed to truly identify long-term safety and efficacy of rIVCFs.

Venous thromboembolism risk assessment and thromboprophylaxis among hospitalized acute medical patients in China – the RAMP study

Background In developed countries, hospitalized patients with acute medical conditions are at significant risk for venous thromboembolism (VTE). Little is known about VTE risk and prophylaxis practices in China. Objective To determine the VTE risk and the frequency of recommended VTE prophylaxis in hospitalized Chinese patients with acute medical conditions. Methods Multi-center, cross-sectional, observational study. Eligibility criteria: ≥ 30 years, admitted to an intensive care unit (ICU)/coronary care unit (CCU) for acute medical illness, had ≥ 1 VTE risk factor/1 disease that predisposes to VTE, and provided informed consent. We used 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines to assess VTE risk and the frequency of recommended VTE prophylaxis. Results 1247 patients from 19 hospitals in 11 cities across 11 provinces of China were enrolled from July 2007 to June 2008. 57.3% patients had > 2 VTE risk factors. Only 20.2% received ACCP-recommended VTE prophylaxis (CCU patients: 22.7%, ICU patients: 16.9%, p = 0.0117). Limitations Excluding some patients with VTE risk factors did not allow assessment of the prevalence of VTE risk in the acute hospital-care setting. We could not determine whether the duration of prophylaxis complied with the ACCP recommendations. Our results may not be representative of hospitals in small cities/rural areas in China. Conclusions The prevalence of VTE risk factors in Chinese patients was similar to that in developed countries; however, only a small proportion of eligible patients received the recommended VTE prophylaxis. Our findings highlight the need for dissemination and implementation of appropriate VTE prophylaxis guidelines in China.

Comparison of the 2-Year Clinical Outcomes of VTE Prophylaxis Options in Medical Patients at Risk of VTE.

Background: Hospitalized medical patients are at significant risk of venous thromboembolism (VTE). Although evidence-based guidelines exist which provide recommendations for thromboprophylaxis in hospitalized medical patients, the optimum regimen for prophylaxis is not clear. We have therefore created a model, based on established literature, which examines the 2-year clinical outcomes following no prophylaxis, thromboprophylaxis with unfractionated heparin (UFH), or thromboprophylaxis with low-molecular-weight heparin (LMWH) in medical patients at risk of VTE.Methods: A decision-analytic model was developed that replicates and extends an existing, published VTE model (McGarry et al. Am J Manag Care. 2004; 10:632–42) from 30 days to 2 years. Hypothetical cohorts of 10,000 medically ill patients at risk of VTE (according to MEDENOX criteria) were assembled, using a Markov chain model with resampling, to compare the rates of primary VTE events and related outcomes at 90 days and VTE complications and recurrent events at 2 years. Clinical outcomes were estimated from published clinical trial and observational data, and compared between three interventions, namely no prophylaxis, UFH, and the LMWH enoxaparin. Outcomes included in the analysis were clinical or venographically detected primary VTE, major and minor bleeds, asymptomatic or symptomatic heparin-induced thrombocytopenia, and death within the first 90 days, as well as VTE recurrence, post-thrombotic syndrome, pulmonary hypertension, and death within 2 years. Sensitivity and threshold analyses were performed to test the general applicability of the model. The simulation model was run using TreeAge software (Williamstown, USA).Results: VTE rates and death were the lowest in the enoxaparin prophylaxis cohort, followed by the UFH and no prophylaxis cohorts respectively (Table 1). Adverse events were lowest in the no prophylaxis group, followed by the enoxaparin group and the UFH group (Table 1).Conclusion: In this Markov model, based on robust data from clinical trials and observational studies, prophylaxis with enoxaparin reduced VTE occurrence and mortality over two years when compared with no prophylaxis or UFH prophylaxis in hospitalized medical patients at risk of VTE. Enoxaparin was also associated with a reduced incidence of adverse events when compared with UFH.Table 1Two-year outcomes in simulated cohorts of hospitalized medical patients at risk of VTEOutcome (n)Enoxaparin (n=10,000)Unfractionated heparin (n=10,000)No prophylaxis (n=10,000)VTE at 2 years6837911787DVT5456331426PE138158361Death157316001745Adverse events at 90 days364725314Minor bleed285510244Major bleed6511655Asymptomatic HIT6457Symptomatic HIT8548

Operationalizing the Concept of “Immobility” for Better Targeting of Thromboprophylaxis in Medical Patients: How the Literature Falls Short.

Background: Venous thromboembolism (VTE) is one of the most common, serious and preventable complications in hospitalized medical patients. Based on data from randomized trials, current guidelines recommend that pharmacologic thromboprophylaxis be administered to such patients until they are ambulatory, as immobility is a significant VTE risk factor. Hence, assessment of the ambulatory status of hospitalized patients is a key element in (1) identifying risk of VTE; and (2) decision-making regarding when to initiate and when to discontinue VTE prophylaxis. Audits continue to show low rates of thromboprophylaxis in medical patients, which could be due in part to difficulties operationalizing the terms “ambulatory” and “immobile” in the clinical setting. Clearer definitions of these terms could improve practitioners' adherence to thromboprophylaxis guidelines.Objectives: We conducted a systematic review of trials of thromboprophylaxis in hospitalized medical patients to characterize how ambulation and immobility were defined and operationalized, and for what purpose.Methods: Pubmed and CINHAL electronic databases were searched up to August 2007 for randomized controlled trials of VTE prophylaxis in medical patients, including patients with stroke. Articles retrieved were hand-searched to identify additional trials. Definitions of “immobility”, “mobility”, “bedridden”, “bedrest”, and “confined to bed/chair” were extracted, and how the concept of mobility/immobility was used was documented.Results: Seventeen randomized controlled trials were retrieved. All studies provided definitions of the concept of “ambulation”, “mobility” or “immobility”, however definitions varied widely across studies. Twelve studies defined the concept in terms of time (definition of “ambulatory” ranged widely from <20 hours/day spent in bed, to >28 days of full “mobilizing”), 2 studies defined the concept in terms of distance (e.g. ambulatory if able to walk 10 meters), 14 studies defined the concept in terms of degree of activity (e.g. “ambulatory” if not confined to bed/chair; or if able to walk autonomously) and 11 studies used definitions that combined time or distance with degree of activity. Overall, only 11/17 studies used definitions that were clearly operationalized and could be objectively replicated. In terms of how the concept of mobility was utilized, 16 studies used the concept in inclusion or exclusion criteria, of which 11 studies provided clearly operationalized definitions; 5 studies used the concept to guide treatment (e.g. “continue treatment until patient is ambulatory”), of which 4 provided clearly operationalized definitions; and 7 studies discussed mobility in the study's results or conclusions (e.g. “prophylaxis is appropriate in all immobilized patients”), of which 5 provided clear and operationalized definitions.Conclusions: Although all trials of VTE prophylaxis in medical patients provided definitions of the concept of mobility/immobility, there was a marked lack of consistency of such definitions across trials, many definitions could not be readily operationalized by a practitioner in clinical practice and the purpose for using mobility as a concept differed greatly among trials. In order to help clinicians better assess thrombosis risk and thereby use thromboprophylaxis more consistently in hospitalized medical patients, further research is needed to define, standardize and operationalize the concept of mobility/immobility in such patients.

Predictors of thrombotic events during pregnancy

Predictors of thrombotic events during pregnancy

Are temporary inferior vena cava filters really temporary?

Background Despite significant risk for venous thromboembolism, severely injured trauma patients often are not candidates for prophylaxis or treatment with anticoagulation. Long-term inferior vena cava (IVC) filters are associated with increased risk of postphlebitic syndrome. Retrievable IVC filters potentially offer a better solution, but only if the filter is removed; our hypothesis is that the most of them are not. Methods This retrospective study queried a level I trauma registry for IVC filter insertion from September 1997 through June 2004. Results One IVC filter was placed before the availability of retrievable filters in 2001. Since 2001, 27 filters have been placed, indicating a change in practice patterns. Filters were placed for prophylaxis (n = 11) or for therapy in patients with pulmonary embolism or deep vein thrombosis (n = 17). Of 23 temporary filters, only 8 (35%) were removed. Conclusions Surgeons must critically evaluate indications for IVC filter insertion, develop standard criteria for placement, and implement protocols to ensure timely removal of temporary IVC filters.

Enoxaparin for Thromboprophylaxis in Morbidly Obese Patients Undergoing Bariatric Surgery: Findings of the Prophylaxis Against VTE Outcomes in Bariatric Surgery Patients Receiving Enoxaparin (PROBE) Study

Obese patients undergoing bariatric surgery are at significant risk for venous thromboembolism (VTE). We performed a multicenter, retrospective survey to evaluate the safety and efficacy of enoxaparin for thromboprophylaxis in patients with morbid obesity undergoing primary bariatric surgery. From January to December 2002, 668 patients who underwent primary bariatric surgery at 5 centers were analyzed retrospectively. Baseline patient demographics, objectively diagnosed cases of VTE, and bleeding events were recorded. Patients received enoxaparin preoperatively (30 mg) or postoperatively (40 mg) every 12 or 24 hours or upon discharge (30 mg every 24 hours for 10 days). Overall, there were 6 (0.9%) pulmonary embolisms (PE) and 1 (0.1%) occurrence of deep vein thrombosis (DVT); all but 1 occurred after the cessation of thromboprophylaxis. The highest incidence of VTE was at Center B, which did not administer perioperative thromboprophylaxis (1 DVT and 2 PEs). There were 6 (0.9%) severe bleeding complications: 3 at center D and 3 at center E. In Center B, 2 deaths were recorded (0.3%): 1 due to sepsis and 1 due to bleeding, with both occurring after thromboprophylaxis was discontinued. The administration of enoxaparin, in various dosing regimens, is safe for thromboprophylaxis in morbidly obese patients undergoing bariatric surgery. Fewer events occurred with perioperative prophylaxis initiated in the hospital. Because all thromboembolic events occurred after the cessation of thromboprophylaxis, extended thromboprophylaxis may be of value.

Comparison of incidence/risk of venous thromboembolism (VTE) among selected clinical and hereditary risk markers: A community-based cohort study

BackgroundLittle information is available from community-based long-term VTE cohort studies to compare the absolute thrombosis risk of established clinical and genetic risk factors.Materials and methodsThe occurrence of venous thromboembolism (VTE) was observed during a 10-year observation period in the BAvarian ThromboEmbolic Risk (BATER) study, a cohort study of 4337 women (age 18–55 years). We collected data on demographics, reproductive life, lifestyle, conditions/diseases, and particularly potential risk factors for VTE with a self-administered questionnaire. The objective was to present incidence rates of VTE and to show relative risk estimated associated with different clinical and genetic risk factors.Results34 new, by diagnostic means confirmed VTE events occurred during the observation time of 32,656 women-years (WY). The overall incidence of VTE was 10.4 per 104 WY. The incidence rates varied markedly among different risk cohorts. The highest incidence was observed in women with previous history of VTE, followed by family history of VTE. None of the measured "genetically-related risk markers" (antithrombin, protein C, FVL, prothrombin mutation, or MTHFR) showed a significant VTE risk.ConclusionMost of the discussed VTE risk factors showed no significant association with the occurrence of new VTEs due to smallness of numbers. Only first-degree family history of VTE and own history of a previous VTE event depicted a significant association with future VTE. Clinical information seems to be more important to determine future VTE risk than genetically related laboratory tests.

Prolonged placement of the new temporary Montanari's vena cava filter

Trauma patients are often at significant risk for venous thromboembolism, a multifactorial disease often manifesting clinically with pulmonary embolism, resulting in high morbidity and mortality rates. Multiple studies have reported the benefit of prophylactic positioning of inferior vena cava temporary filters, but these devices may only be placed for a relatively short time. In a 41-year-old man, admitted to the intensive care unit for multiple trauma, and at high risk for pulmonary embolism, the new definitive/temporary Montanari's vena cava filter (ALN) was positioned at the lower level of the renal veins, and maintained for ten months, much longer than is usual at the present time. The ALN filter was removed through the right jugular vein and no signs of alterations were noted in the removed device. At 1-year follow-up after the device removal, no related adverse events were seen. Since ALN filter does not require anticoagulant treatment, it was also possible to avoid administration of heparin, a high-risk treatment considering the patient's condition and the surgical treatment required.

Prolonged placement of the new temporary Montanari's vena cava filter

Trauma patients are often at significant risk for venous thromboembolism, a multifactorial disease often manifesting clinically with pulmonary embolism, resulting in high morbidity and mortality rates. Multiple studies have reported the benefit of prophylactic positioning of inferior vena cava temporary filters, but these devices may only be placed for a relatively short time. In a 41-year-old man, admitted to the intensive care unit for multiple trauma, and at high risk for pulmonary embolism, the new definitive/temporary Montanari’s vena cava filter (ALN) was positioned at the lower level of the renal veins, and maintained for ten months, much longer than is usual at the present time. The ALN filter was removed through the right jugular vein and no signs of alterations were noted in the removed device. At 1-year follow-up after the device removal, no related adverse events were seen. Since ALN filter does not require anticoagulant treatment, it was also possible to avoid administration of heparin, a high-risk treatment considering the patient’s condition and the surgical treatment required.

Venous thromboembolism in medically ill patients: Identifying risk and strategies for prevention

Venous thromboembolism (VTE) is a condition that has multiple causes but few warning signs. Consequently, the 2 manifestations of VTE-pulmonary embolism and deep vein thrombosis-often go unpredicted. This is especially true for medical patients. Treatment guidelines indicate that most hospitalized patients should receive prophylaxis for VTE. This report discusses these guidelines, the high prevalence of VTE among medical patients, and clinical studies of thromboprophylaxis in medically ill patients. VTE prophylaxis continues to be underutilized in medically ill patients. These patients are at significant risk of VTE and require prophylaxis, an objective that is supported by the recent guidelines of the American College of Chest Physicians. In addition, several lines of clinical evidence support the use of prophylaxis in this subgroup of patients. Improved systems are needed in medically ill patients to help improve outcomes and compliance for the use of VTE prophylaxis.

Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients

Hospitalized patients with acute medical conditions are at significant risk of venous thromboembolism (VTE): approximately 10-30% of general medical patients may develop deep-vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Despite consensus-group recommendations that at-risk medical patients should receive thromboprophylaxis, there is currently no consensus as to which patients are at risk, and many patients may not receive appropriate thromboprophylaxis. This paper reviews evidence for the risk of VTE associated with different medical conditions and risk factors, and presents a risk-assessment model for risk stratification in medical patients. Medical conditions associated with a moderate to high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious diseases. Importantly, analyses of data from the MEDENOX study show that thromboprophylaxis significantly reduces the risk of VTE in these patient subgroups. Risk factors in medical patients include a history of VTE, history of malignancy, increasing age, thrombophilia, prolonged immobility, and obesity. These medical conditions and risk factors are included in a risk-assessment model which is hoped will provide a simple means of assisting clinicians in deciding whether thromboprophylaxis should be used in an individual patient.

Identification of Medical Patients Who Should Receive Venous Thromboembolism Prophylaxis.

Introduction Despite various medical illnesses/conditions and patient-related factors known to increase venous thromboembolism (VTE) risk in medical patients, there is no worldwide consensus regarding which of these patients should receive VTE prophylaxis. As a result, many medical patients remain at risk from this potentially fatal disease. Our objective was to develop a simple risk assessment model (RAM) that could be used at the bedside to identify medical patients who should receive prophylaxis.Methods Acute medical illnesses/conditions and risk factors were included in the RAM if there was strong evidence from prospective clinical studies to show that they significantly increase VTE risk in medical patients, or VTE prophylaxis was beneficial in these cases. If strong evidence was not available, the illness/condition or factor was only included if there was consensus from the authors that VTE prophylaxis is beneficial for these patients.Results Table 1 shows acute medical illnesses/conditions and factors associated with significant VTE risk that are included in the RAM. If a medical patient is >40 years old with an acute medical illness and reduced mobility and has one of the illnesses/conditions or factors shown in Table 1, the RAM recommends prophylaxis with low-molecular-weight heparin (LMWH: enoxaparin 40 mg o.d. or dalteparin 5000 IU o.d.) or unfractionated heparin (5000 IU q8h). LMWH is preferred due to a better safety profile. If pharmacologic prophylaxis is contraindicated, mechanical prophylaxis is recommended.Conclusion Acute medical illnesses/conditions and patient-related factors that increase the risk for VTE in medical patients have been identified and used to develop a novel RAM. The RAM is evidence-based wherever possible, and can be easily revised as new evidence becomes available. The RAM is simple in design, and can assist physicians to assess whether VTE prophylaxis is warranted in an individual medical patient.Table 1. Factors that increase the risk of VTE in medical patientsAcute medical illnesses/conditions RiskfactorsEvidence-based: Acute MI, acute heart failure (NYHA III/IV), active cancer requiring therapy, severe infection/sepsis, respiratory disease (respiratory failure with/without mechanical ventilation, exacerbation of chronic respiratory disease), rheumatic disease (including acute arthritis of lower extremities, and vertebral compression), ischemic stroke*, paraplegia Consensus view only: Inflammatory disorder with immobility, inflammatory bowel diseaseEvidence-based: History of VTE, history of malignancy, concurrent acute infectious disease, age >75 years Consensus-based from strong evidence in other settings: Prolonged immobility, age >60 years, varicose veins, obesity, hormone therapy, pregnancy/postpartum, nephrotic syndrome, dehydration, thrombophilia, thrombocytosis*Note: The risk of hemorrhagic transformation should be assessed before giving VTE prophylaxis.

Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial

Elective hip-replacement surgery carries significant risk of venous thromboembolism, despite use of thromboprophylaxis. We aimed to see whether the pentasaccharide fondaparinux, the first drug of a new class of synthetic antithrombotic agents, could reduce this risk to a greater extent than other available treatments. In a double-blind study, we randomly assigned 2275 consecutive patients aged 18 years or older who were undergoing elective hip-replacement surgery to receive postoperative subcutaneous injections of either 2.5 mg fondaparinux once daily or 30 mg enoxaparin twice daily. The primary efficacy outcome was venous thromboembolism to day 11. The main safety outcomes were bleeding and death. Patients were followed up for 6 weeks. We assessed venous thromboembolism to day 11 in 1584 (70%) of 2275 patients. By day 11, venous thromboembolisms were recorded in 48 (6%) of 787 patients on fondaparinux and in 66 (8%) of 797 patients on enoxaparin. The relative reduction in risk was 26.3% (95% CI -10.8 to 52.8, p=0.099). The two groups did not differ in the number of patients who died or in the number who had clinically relevant bleeding. In patients undergoing elective hip-replacement surgery, 2.5 mg fondaparinux once daily was not significantly more effective than 30 mg enoxaparin twice daily in reducing risk of venous thromboembolism. However, the lower risk recorded with fondaparinux than enoxaparin was clinically important, with no increase in clinically relevant bleeding.

Benefits of deep-vein thrombosis prophylaxis in the nonsurgical patient: The MEDENOX trial

Venous thromboembolism (VTE) is a common complication of hospitalized patients, imposing a major clinical and economic burden. Three of four cases of fatal pulmonary embolism occur in nonsurgical settings, but thromboprophylaxis is far less common in medical than in surgical patients. This is mainly attributable to the heterogeneity of nonsurgical populations and lack of high-quality evidence to support specific thromboprophylactic measures. The recent Prophylaxis of Venous Thromboembolism in MEDical Patients With ENOXaparin (MEDENOX) trial addressed this deficiency by assessing the need for and the benefit:risk ratio of thromboprophylaxis in a well-defined group of medical patients immobilized with severe illness. The MEDENOX study showed that these patients are at significant risk of VTE. Enoxaparin, 40 mg once daily for 6 to 14 days, reduced the risk of VTE by 63% without increasing adverse events. It is anticipated that data from the MEDENOX study will be incorporated into future consensus guidelines on the prevention of VTE. Further studies are required to assess the benefit:risk ratio of therapy in other clearly-defined medical groups.

Prothrombin and Factor V Mutations in Women With a History of Thrombosis During Pregnancy and the Puerperium

Although venous thromboembolism remains a prominent cause of illness and death during and after pregnancy, the role of genetic abnormalities remains incompletely understood. This study measured antithrombin, protein C, protein S, and lupus anticoagulant in 119 women with a history of thromboembolism during pregnancy or the puerperium and in 233 age-matched women without a history of thromboembolism (control subjects). In addition, genetic analyses were performed detect the factor V Leiden mutation (G1691A mutation in the factor V gene), the G20210A mutation in the prothrombin gene, and the C677T mutation in the gene for methylenetetrahydrofolate reductase. The factor V Leiden mutation is found in 20 percent of patients with initial venous thrombosis and in as many as half of those with recurrences. The other mutations are both associated with an increased risk of venous thrombosis. About half of the study group had deep venous thromboembolism during pregnancy, most often during the third trimester, and the rest were affected during the postpartum period. The factor V Leiden mutation was identified significantly more often in women with a history of thromboembolism than in the control group. The same was true for the prothrombin gene mutation, and both mutations were found in 9.3 percent of the study group. None of the control women had this combination of mutations. The prevalence of deficient antithrombin, protein C, or protein S was 25 percent in the study group and 11 percent in the control group. Antithrombin deficiency was documented in nearly one in five women with a history of thromboembolism. On logistic regression analysis, the only independent risk factors predicting thrombosis in women with a history of thromboembolism were antithrombin deficiency and the factor V Leiden and G20210A mutations. Women with recurrent thromboembolism were significantly more likely to have combined genetic effects than those having a first episode. Assuming an overall risk of 1 in 1500 pregnancies, the estimated risk of thrombosis was 0.2 percent for carriers of the factor V Leiden mutation, 0.5 percent for carriers of the prothrombin gene mutation, and 4.6 percent for those carrying both defects. The factor V Leiden mutation and other inherited markers of thrombotic risk have low predictive value in pregnant women. Only women with both the factor V Leiden and prothrombin gene mutations have a significant risk of venous thromboembolism. N Engl J Med 2000;342:374–380

Meta-analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease.

Elevated plasma homocysteine (Hcy) levels are implicated in the development of atherosclerotic and venous thromboembolic disease. A meta-analysis of the risk for venous thromboembolism (VTE) in the presence of hyperhomocysteinemia (hyper-Hcy) was performed. Studies were identified through MEDLINE (January 1980 to August 1997) using search terms related to both Hcy and VTE. The bibliographies of all review articles and letters were searched for additional relevant articles. English-language studies were selected if they included 10 or more human subjects; a measurement of the plasma, serum, or whole-blood Hcy level; the presence of VTE; and primary data that were not published elsewhere. Seventy-two articles were retrieved, of which 9 met all inclusion criteria. Data were extracted on the study type, subject demographics, methods for matching control subjects with case patients, whether an objective method was used to diagnose VTE, and whether other causes of thrombophilia and elevated Hcy levels were considered. The mean Hcy levels, both in the fasting state and following methionine loading, if done, were recorded, as were the number of patients and control subjects with Hcy levels greater than 2 SDs or greater than the 95th percentile above the mean value of the control group. Nine case-control studies measured fasting plasma Hcy levels, and 5 also measured Hcy values after methionine loading. All 9 studies showed a similar qualitative trend in fasting levels in the associated risk for hyper-Hcy and VTE. The corresponding pooled odds ratio was 2.95 (95% confidence interval, 2.08-4.17; 2-sided P<.001), with no evidence for heterogeneity across the studies (P = .50). Following methionine loading, the trend was also toward increasing the risk of VTE with hyper-Hcy (odds ratio, 2.15; 95% confidence interval, 1.20-3.85; 2-sided P = .01). Again, no evidence of heterogeneity was found (P = .65). The pooled odds ratio for VTE in the presence of hyper-Hcy rose to 4.37 (95% confidence interval, 1.94-9.84) when studies with patients older than 60 years were excluded. Limitations of the individual studies included a lack of proper matching of patients with control subjects, a limited description of subject recruitment, and a failure to test for other hypercoagulable mechanisms and other causes of elevated Hcy levels, such as renal insufficiency or folate deficiency. A significant risk for VTE in the presence of hyper-Hcy apparently exists among a spectrum of patients with first or recurrent venous thromboembolic events. This risk appears to be most significant for patients with VTE disease before age 60 years. A well-designed prospective study is needed to confirm these findings.

Perioperative asymptomatic venous thrombosis: Role of duplex scanning versus venography

We compared combined B-mode/Doppler (duplex) ultrasonic scanning and venography in routine preoperative and postoperative screening for major proximal deep vein thrombosis in 78 patients undergoing total hip or knee arthroplasty. Of 309 extremity examinations, duplex scanning had an overall sensitivity of 85.7% (12/14) and a specificity of 97.3% (287/295). The preoperative prevalence and postoperative incidence of major deep vein thrombosis were 2.5% and 14.1% of patients, respectively, despite intensive mechanical and pharmacologic prophylaxis. In addition, venography documented a preoperative prevalence and postoperative incidence of isolated calf deep vein thrombosis in 2.5% and 16.7% of patients, respectively. Whereas such disease extended proximally even in the absence of anticoagulation in only 18% of patients studied by serial duplex scans, calf deep vein thrombosis accounted for the only two instances of pulmonary embolism in this study. There were no deaths related to pulmonary embolism. This study suggests that duplex scanning is useful in screening for perioperative deep vein thrombosis in patients undergoing total hip or knee arthroplasty, which carries a significant risk of venous thromboembolism despite routine prophylaxis.