Statins in the prevention of venous thromboembolism: a meta-analysis of observational studies

Introduction

Studies have established a relationship between inflammation and venous thromboembolism (VTE). Though statins modulate inflammation, it is uncertain if they prevent VTE in heterogeneous populations. A recent randomized trial demonstrated that statins prevent VTE in healthy older adults, yet this has not been well established in other groups, including younger individuals and individuals with comorbidities. The objective of this meta-analysis was to estimate the effect of statins on VTE in a heterogeneous group of adults.

Methods

We systematically reviewed the effect of statins in preventing VTE in adult inpatients and outpatients. We systematically searched MEDLINE (1966-Jan 2010), EMBASE (1980-Jan 2010), Google Scholar, Cochrane Library, PapersFirst, ProceedingsFirst, and ISI Web of Science, manually reviewed references, and contacted experts. Observational studies that compared any dose of statin to no statin or placebo, examined inpatients or outpatients, and assessed VTE, pulmonary embolism, and/or deep vein thrombosis were included. Study selection, data abstraction and study quality evaluation (using the Newcastle-Ottawa Scale) were independently conducted in duplicate.

Results

Four cohort studies and four case-control studies met criteria. Comparing statins to control, the odds ratio for VTE was 0.67 (95% confidence interval 0.53, 0.84), and for deep vein thrombosis was 0.53 (95% confidence interval 0.22, 1.29). The association was attenuated in lower-quality studies and studies enrolling older individuals.

Conclusions

Further well-designed trials are needed to evaluate the risks and benefits of statins in preventing VTE in heterogenous populations of adults, identify high-risk subgroups, and analyze cost-effectiveness of statin use for this indication.     

Circulating microparticles and risk of venous thromboembolism

Introduction

Circulating microparticles (MPs) may trigger a hypercoagulable state, leading to thrombotic complications. Data on their association with venous thromboembolism (VTE) are few and inconsistent.

Materials and methods

To investigate whether or not high levels of MPs are associated with an increased risk of VTE, we carried out a case-control study on 186 patients with a first, objectively diagnosed, episode of VTE and 418 healthy controls. Plasma levels of circulating MPs were measured by flow cytometry.

Results

Patients had higher median plasma levels of total MPs than controls (2184 per μL vs 1769 per μL, p < 0.0001). The risk of VTE increased progressively with increasing MPs, with a linear dose-response effect in the log odds. Individuals with MPs above the 90th percentile of the controls’ distribution (P₉₀ = 3263 per μL) had a 5-fold increased risk of VTE than those with MPs below the 10th percentile of controls (P₁₀ = 913 per μL), independently of sex, age, body mass index, thrombophilia, and plasma factor VIII levels [adjusted odds ratio: 5.30 (95%CI: 2.05-13.7)]. Using the 95th percentile of controls as cut-off (P₉₅ = 4120 per μL), the adjusted odds ratio was 2.20 (1.01-4.79) for individuals with MPs > P₉₅ compared with those having MPs ≤ P₉₅. After exclusion of individuals with antiphospholipid antibodies and hyperhomocysteinemia, the interaction between MPs > P₉₅ and thrombophilia increased the VTE risk from 1.63 (0.60-4.50) to 6.09 (1.03-36.1).

Conclusions

High levels of circulating MPs are a possible independent risk factor for VTE.     

Risk factors for venous thromboembolism in pre-and postmenopausal women

Introduction

Hemostasis in women is affected by changes of estrogen levels. The role of endogenous estrogens on risk of venous thromboembolism (VTE) remains unclear. The aim of this study was to investigate the importance of acquired and genetic risk factors for VTE in pre-and postmenopausal women.

Method

In a nationwide case-control study we included as cases 1470 women, 18 to 64 years of age with a first time VTE. The 1590 controls were randomly selected and matched by age to the cases. Information on risk factors was obtained by interviews and DNA-analyses. We used unconditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs).

Results

The ORs were generally of similar magnitude in pre- and postmenopausal women. The highest risk was for the combination of surgery and cast (adjusted OR 54.12, 95% CI 16.62-176.19) in postmenopausal women. The adjusted OR for use of menopausal hormone therapy was 3.73 (95% CI 1.86-7.50) in premenopausal and 2.22 (95% CI 1.54-3.19) in postmenopausal women. Overweight was linked to an increased risk and exercise to a decreased risk, regardless of menopausal status.

Conclusion

Menopausal status had only minor influence on the risk levels. Acquired transient risk factors conveyed the highest risks for VTE.     

Feasibility of an easy-to-use risk score in the prevention of venous thromboembolism and placental vascular complications in pregnant women: a prospective cohort of 2736 women

INTRODUCTION: Management of pregnant women at increased risk of venous thromboembolism (VTE) remains complex in the absence of an easy-to-use tool allowing individualised, risk-adapted prophylaxis. Our objective was to assess whether treatment based on risk score is feasible in these women. MATERIALS AND METHODS: A scoring system for VTE risk in pregnant women was developed, each score being associated with a specific treatment. This system was implemented in a prospective cohort of 2736 consecutive women delivered in our teaching hospital from July 2002 to June 2003. Thromboembolic and obstetrical outcomes during pregnancy and the early post-partum period were recorded. RESULTS: Treatment based on risk score was implemented in 2685 of the 2736 women included (98.1%). The scoring system identified 2431 women with no risk factor and 305 women (11%) with at least one risk factor. Eight women not at risk (0.3%, [95% CI: 0.1-0.5]) and one at risk (0.4%, [95% CI: 0-1.1]) experienced a VTE. This low event rate precluded estimation of the discriminatory power of the score. However, the benefit of the scoring system was evaluated indirectly by assessing VTE incidence in the 46 women at risk in whom it was not used (15.2%, [95% CI: 4.8-25.6]). CONCLUSIONS: Our simple scoring system offers an easily implemented procedure for risk-based VTE prophylaxis of pregnant women and the proposed therapeutic strategy appears to be effective and safe in reducing VTE. The discriminatory power of the score is currently being evaluated in a randomized, controlled trial.     

Pregnancy-related venous thromboembolism: risk and the effect of thromboprophylaxis

Venous thromboembolism (VTE) is a leading cause of maternal mortality and morbidity during pregnancy in developed countries. The incidence of VTE per pregnancy-year increases about 4-fold during pregnancy and at least 14-fold during the puerperium. Risk factors include a personal history of VTE, presence of inherited or acquired thrombophilia, a family history of VTE and general medical conditions, such as immobilisation, overweight, varicose veins, some haematological diseases and inflammatory disorders. VTE is considered potentially preventable with the prophylactic administration of anticoagulants, but there are no high quality randomized clinical trials that compared different strategies of thromboprophylaxis in pregnant women. Balancing the absolute risk of VTE against the risks of exposure to anticoagulants, this review provides advice regarding which women may benefit from thromboprophylaxis during and after pregnancy.     

Red cell distribution width and risk for venous thromboembolism: A population-based cohort study

Introduction

Red cell distribution width (RDW) has been associated with venous thromboembolism (VTE), but whether RDW is a predictor of first event of VTE is unknown. We investigated the association between RDW and incidence of first event of VTE in a population-based cohort.

Materials and Methods

RDW was measured in 27 042 subjects (aged 45–73 years, 60.6% women), without previous history of VTE or cancer within 5 years before follow-up, who participated in the Malmö Diet and Cancer study during 1991–1996. Incidence of VTE was identified from the patient register and the cause of death register during a mean follow-up of 13.8 years and studied in relation to RDW.

Results

During follow-up, 991 subjects (57.5% women) were affected by VTE (pulmonary embolism or deep venous thrombosis of the lower limbs). After adjustment for potential confounding factors the hazard ratios (HR) for VTE for the second, third and fourth RDW quartiles 1.15 (95% confidence interval 0.94–1.41), 1.41 (1.14–1.73), 1.74 (1.38–2.21), respectively, were compared with the bottom quartile of RDW. In the multivariate model subjects with the top 5% of RDW values compared with the bottom quartile had an even higher risk (HR = 2.51, 1.78–2.54). In receiver operating characteristic (ROC) analysis, the male specific area under the ROC curve (AUC) for RDW was 0.57 (95% CI 0.54–0.59). The female specific AUC was 0.56 (95% CI 0.53–0.58).

Conclusions

RDW was found to be associated with long-term incidence of first event of VTE among middle-aged subjects.     

Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and venous thrombosis. A meta-analysis

The effect of the 675 insertion/deletion (4G/5G) polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene on the risk of venous thromboembolism (VTE) remains controversial. In this study, we performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out up until September 2006. A total of 22 articles were included in the analysis that was performed using random effects models. Eighteen papers, concerning patients without another known risk factor, comprised 2,644 cases and 3,739 controls. The alleles contrast (4G vs. 5G allele) yielded a statistically significant odds ratio (OR) of 1.153 (95% confidence interval [CI]: 1.068-1.246). In a sub-analysis of five studies that included 256 cases with another genetic risk factor and 147 controls, the combined per-allele OR was still significant (OR: 1.833,95% CI: 1.325-2.536). On the contrary, the analysis of five studies regarding cases with a non-genetic risk factor for VTE (antiphospholipid antibody syndrome, Behcet disease) provided insignificant results in all aspects. There was no evidence for heterogeneity and publication bias in all analyses. Based on our findings, the 4G allele appears to increase the risk of venous thrombosis, particularly in subjects with other genetic thrombophilic defects. Recommendation for detection of this polymorphism in evaluating thrombophilia in such patients might be considered.     

The role of inherited thrombophilia in patients with isolated pulmonary embolism: A systematic review and a meta-analysis of the literature

Introduction

Venous thromboembolism (VTE) is a common vascular disease that results in deep venous thrombosis (DVT) and pulmonary embolism (PE). Factor V Leiden mutation (FVL) and G20210A prothrombin mutation (PTM) are associated with an increased risk of VTE. Recent studies have reported a lower prevalence of FVL in patients with isolated PE than in patients with DVT with or without PE, suggesting the possibility that the prevalence of FVL in patients with isolated PE may be not significantly different from that of the general population. To address this issue, we performed a systematic review and a meta-analysis of published studies that assessed the prevalence of FVL and/or PTM in patients with isolated PE and in controls without VTE.

Methods

MEDLINE and EMBASE databases were searched up to October 2013. Pooled odds Ratios (OR) and 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical heterogeneity was evaluated using the Cochran Q and I² statistics.

Results

Eighteen studies totalling more than 11,000 patients were included. FVL was found significantly more often in patients presenting isolated PE than in controls (OR 2.06; 95% CI 1.66, 2.56; p < 0.0001). The prevalence of PTM was also significantly different in patients presenting with isolated PE than in controls (OR 2.64, 95% CI 1.92, 3.63; p < 0.0001). Heterogeneity among studies was low.

Conclusion

FVL and PTM are both associated with isolated PE. However, the association magnitude between PE and FVL mutation appeared to be lower compared to that observed in the general population of VTE patients.     

Incidental venous thromboembolism in cancer patients: prevalence and consequence

Introduction

Careful re-evaluation of CT-scans for cancer staging frequently reveals unsuspected venous thromboembolism (VTE) on CT-scans. However, it is unknown how often these findings lead to anticoagulant treatment in daily clinical practice.

Methods

Reports from thoracic and/or abdominal CT-scans performed in a consecutive series of patients to stage cancer were retrospectively evaluated to determine the prevalence of incidental venous thromboembolism (iVTE). Presence of pre-existing signs of VTE, anticoagulant treatment and 3-month follow-up were analysed in patients with iVTE.

Results

A total of 1466 staging scans (838 patients) from the year 2006 were included in the analysis. The prevalence of VTE in patients was 2.5% (21/838 patients, 95% confidence interval 1.6-3.8%); the prevalence of VTE on scans was 1.4% (21/1466 scans, 95% CI 0.9-2.2%). Incidental PE or deep vein thrombosis (DVT) was observed in 11 (1.3%, 0.7-2.3%) and abdominal vein thrombosis in 9 patients (1.1%, 0.6-2.0%; in the portal (5), mesenteric (3) and renal vein (1), respectively). Nine out of eleven patients with PE/DVT were treated with anticoagulants, while none of the patients with thrombosis in other locations received anticoagulants. One of these patients developed symptomatic PE one month later; otherwise, follow up was uneventful in the untreated patients.

Conclusion

The prevalence of iVTE in patients with cancer in clinical practice is relatively low and most patients with PE or DVT are treated with anticoagulants. For patients with thrombi in other locations, further research is necessary to understand the natural history of these thrombi in order to develop adequate guidelines.     

Incidental venous thromboembolism detected by PET-CT in patients with cancer: Prevalence and impact on survival rate

Introduction

People with cancer are at increased risk of incidental venous thromboembolism (VTE) and PET-CT imaging is commonly used in this population. However, the prevalence of incidental VTE detected by PET-CT in patients with cancer and its impact on survival are unknown.

Materials and Methods

This retrospective study was approved by the local Institutional Review Board. 1331 consecutive adult patients with cancer who underwent PET-CT examination between 2009 and 2012 were included in the study (mean age: 57 ± 15 years). PET-CT reports were reviewed to identify patients with incidental VTE at the time of examination. Survival rates were assessed with Kaplan-Meier curves. The Cox proportional hazards model was used to determine the association between incidental VTE and overall survival, after controlling for clinical variables.

Results

Incidental VTE was detected in 19 patients (1.4%). Patients with genitourinary malignancies, colorectal cancer and lung cancer had the highest rates of incidental VTE at PET-CT. At multivariate analysis, incidental VTE detected by PET-CT was associated with worse overall survival independently of patient age, hospitalization status at time of PET-CT examination, and the presence of metastatic disease (Hazard ratio = 2.03; 95% confidence interval = 1.08-3.81, p = 0.028).

Conclusion

Incidental VTE was detected in 1.4% of adult patients with cancer undergoing PET-CT imaging. Diagnosis of incidental VTE at PET-CT imaging was associated with worse overall survival in this population.     

The impact of co-morbid conditions on family history of venous thromboembolism in Whites and Blacks

Introduction

Our objectives were to compare the magnitude of family history as a risk factor for venous thromboembolism (VTE) risk between Blacks and Whites, and to assess the impact of co-morbid conditions on familial risk for VTE.

Materials and methods

We used data from the Genetic Attributes Thrombosis Epidemiology (GATE) study, a matched case-control study which enrolled Blacks and Whites aged 18-70 years in Atlanta, Georgia. A total of 1,094 case patients with a deep vein thrombosis (DVT) or pulmonary embolism (PE) and 1,264 control patients were interviewed about their family history.

Results

Family history of VTE was a statistically significant risk factor for VTE among Blacks (odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.0-4.1; P value < 0.0001) and among Whites (OR = 2.7, 95% CI 1.9-3.7; P value < 0.0001); among Blacks and Whites who were obese or had hypertension; among Blacks who had diabetes mellitus or cancer; as well as among males and females, and across all age categories. Family history of VTE increased the risk of VTE among Blacks with cancer by about 6-fold, whereas among Blacks without cancer the increased risk due to a positive family history was about 3-fold; a 2-fold relative difference. In addition, family history was a risk factor for VTE among case patients with DVT only or with PE only. The effect of family history generally was stronger among those with recurrent episodes of VTE compared with a first episode of VTE. For example, family history of any VTE was a strong risk factor among Black females with recurrent VTE compared with Black females with first VTE (OR = 3.9, 95% CI 2.0-7.5; P value < 0.0001).

Conclusion

Our study indicated that the adjusted attributable fraction for VTE was 16.9% among Blacks vs. 18.3% among Whites, and certain co-morbid conditions could further increase the risk of VTE associated with a positive family history of VTE.     

The association of alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism in the LITE study

INTRODUCTION: The alpha-fibrinogen Thr312Ala variant has been shown to influence clot structure through increased factor XIII cross-linking and formation of thicker fibrin fibers. However, the effect of this common variant on risk of venous thromboembolism (VTE) is unclear. This paper reports the association between the Thr312Ala variant and VTE in the LITE study. MATERIALS AND METHODS: 506 cases and 1014 controls frequency matched on age, sex, race, and study were drawn from two prospective studies and included in the analysis. Logistic regression was used to examine the association between Thr312Ala and VTE. RESULTS: In a logistic regression model minimally adjusted for the matching variables, the Thr312Ala TA and AA genotypes were associated with a significantly higher risk of VTE than the TT genotype (TA OR and 95% confidence interval 1.27 [1.01-1.60], AA OR 1.49 [1.00-2.22]). Associations were similar in analyses of PE and DVT considered separately and across racial and study subgroups. The association between alpha-fibrinogen Thr312Ala and VTE was modified by both BMI and the FXIII Val34Leu variant; the combination of elevated BMI or FXIII Val34Leu with alpha-fibrinogen Thr312Ala conveyed lower odds of VTE than would be expected by an additive or multiplicative model of individual risk factors. CONCLUSIONS: These results suggest that alpha-fibrinogen Thr312Ala is involved in the pathogenesis of VTE and that its action may be modified by other VTE risk factors.     

Residual vein thrombosis and onset of post-thrombotic syndrome: Influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene

Background

Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades.In this prospective cohort analytic study, we investigated the role of this single nucleotide polymorphism in the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome.

Patients/Methods

In a group of 168 patients with post-surgical deep vein thrombosis of the legs, we analyzed the 4G/5G polymorphism in the promoter of PAI-1 gene and plasmatic PAI-1 activity.Enrolled patients were divided in two groups: patients with 4G/5G polymorphism and increased PAI-1 activity (n = 85) and patients without 4G/5G polymorphism and normal PAI-1 activity (n = 83). All patients were treated according to current protocols and re-examined after 3, 12 and 36 months in order to evaluate the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome.

Results

We found a significantly increased PAI activity in carrier of the 4G allele, who experienced much more frequently a persistence of thrombosis after 3, 12 and 36 months and/or the development of post-thrombosis syndrome, in spite of the anticoagulant treatment.

Conclusions

These data not only confirm the role played by PAI-1 activity and by the 4G/5G SNP of the PAI-1 gene, but also suggest that current therapeutic protocols, recommending the administration of low weight molecular heparin and oral anticoagulant for the treatment of deep vein thrombosis, could be non sufficient for patients genetically predisposed to a less efficient clot lysis.     

Old and new oral anticoagulants for venous thromboembolism and atrial fibrillation: a review of the literature

Heparin, fondaparinux and vitamin K antagonists (VKAs) are effective for the prevention and treatment of venous thromboembolism. VKAs reduce by almost 60% the rate of cardioembolic complications in patients with atrial fibrillation. The risk for bleeding and the inconvenience for laboratory monitoring, dose adjustment and drug or food interactions are the main limits for VKAs while parenteral administration is the main limit for heparin and fondaparinux. New oral anticoagulants with more predictable anticoagulant response and no need for laboratory monitoring have been shown to be effective for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with atrial fibrillation. The pharmacokinetic and pharmacodynamic profile of the new agents differ for mechanisms of action - mainly anti Xa and one antithrombin agent- bioavailability, half life, renal or live clearance. Drug interactions have been described with the new agents and inhibitors or inducers of P-gp or CYP3A4. Overall, in the prevention of venous thromboembolism after major elective orthopaedic surgery dabigatran was shown to be non-inferior, rivaroxaban and apixaban to be superior to enoxaparin. Both, rivaroxaban and dabigatran were shown to be non-inferior to low-molecular weight heparin and VKAs for the treatment of venous thromboembolism. Dabigatran 150 mg twice daily reduced the incidence of both ischemic and hemorrhagic stroke in patients with atrial fibrillation respect to warfarin. In these patients rivaroxaban and apixaban reduced the incidence of hemorrhagic stroke with a similar incidence of ischemic stroke. No bleeding concern emerged with the new anticoagulant agents in this indication.     

Lipoprotein (a) in patients with spontaneous venous thromboembolism

INTRODUCTION: Elevated lipoprotein (a) (Lp (a)) has been established as a risk factor of coronary heart disease and stroke. Findings concerning the risk of venous thromboembolism (VTE) in adults are contradictory. The aim of our study was to investigate, whether elevated Lp (a) levels are an independent risk factor of spontaneous symptomatic venous thromboembolism (VTE). Our study was further designed to detect differences in risk profiles between thrombosis patients with and without symptomatic PE. MATERIALS AND METHODS: We investigated Lp (a) in 128 patients with spontaneous symptomatic deep vein thrombosis (DVT, group 1), 105 with spontaneous symptomatic pulmonary embolism with or without DVT (PE, group 2) and 122 healthy controls. Lp (a) was measured with an immunoturbidimetric assay (Tina-quant(R), Roche, Grenzach-Wyhlen, Germany) on a Hitachi-Modular system. RESULTS: Lp (a) levels (mg/L) were not significantly different among groups, median levels (25th-75th percentiles) were 170 (51-386) in group 1, 140 (<20-427) in group 2 and 126 (54-331) in controls, respectively. As continuous variable, odds ratios for VTE for a 100 mg/L increase of Lp (a) were 1.1 [95% confidence interval 0.98-1.2] for group 1 versus controls and 1.1 [0.95-1.2] for group 2 versus controls. The prevalence of Lp (a) above 300 mg/L was not significantly different among patients and controls (group 1: 30%, group 2: 32% and controls: 25%, p=0.4, p=0.2, respectively). CONCLUSIONS: In conclusion we found no association between Lp (a) and VTE regardless whether DVT occurred together with PE or not.     

Lack of evidence for association between factor XIII-A Val34Leu polymorphism and ischemic stroke: A meta-analysis of 8,800 subjects

Introduction

Epidemiological studies have evaluated the association between factor XIII-A (FXIII-A) Val34Leu polymorphism and risk of ischemic stroke, but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies.

Methods

Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation (using the Newcastle-Ottawa Scale, NOS) were independently conducted in duplicate. Statistical analyses were performed using software Review Manager (Version 5.1.2) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by funnel plot, Egger's regression test and Begg's test. Sensitivity analysis was conducted by limiting the meta-analysis to the high quality studies (NOS score≥8).

Results

A total of 16 studies including 3,807 cases and 4,993 controls were combined showing no evidence of association between FXIII-A Val34Leu polymorphism and ischemic stroke (for Val/Leu vs. Val/Val : OR = 0.95, 95%CI = 0.77-1.16; for Leu/Leu vs. Val/Val: OR = 0.90, 95%CI = 0.73-1.11; for dominant model: OR = 0.97, 95%CI = 0.81-1.17; for recessive model: OR = 0.95, 95%CI = 0.77-1.17). In the subgroup analyses by study design, ethnicity and specific subtypes (small-vessel occlusive ischemic stroke and large-artery atherosclerotic ischemic stroke ), there was lack of evidence for the association.

Conclusions

This meta-analysis indicates that there is no evidence for association between factor XIII-A Val34Leu polymorphism and ischemic stroke.     

Fish intake and venous thromboembolism: A Danish follow-up study

Introduction

Data on the association between fish intake and venous thromboembolism (VTE) is sparse and inconsistent.

Objective

To investigate whether intake of total, lean or fatty fish is associated with development of incident VTE.

Material and methods

This study is based on the Danish follow-up study Diet, Cancer and Health including 27,178 men and 29,876 women aged 50–64 with no history of cancer. Participants were included between 1993 and 1997 and followed through 2006. Information on fish intake and potential confounders was obtained from baseline questionnaires. The outcome was incident VTE (all) and idiopathic VTE. We used Cox proportional hazard models with age as time axis. Separate analyses were performed for men and women. Adjustment was made for BMI, smoking, physical activity, energy intake and women’s use of hormone replacement therapy.

Results

During follow-up, 641 incident VTE events were verified. We found no association between total fish intake and VTE, but moderate intake of fatty fish was associated with a statistically non-significant 20-40% lower risk of idiopathic VTE compared with consumption of a low intake (less than 8 g) of fatty fish per day.

Conclusions

Intake of neither total nor fatty fish was statistically significantly associated with the incidence rate of VTE. However, intake of fatty fish may be associated with a reduction of the risk of idiopathic VTE.     

Association of blood transfusion and venous thromboembolism after colorectal cancer resection

Introduction

Red blood cell (RBC) transfusion is a common event in the perioperative course of patients undergoing surgery. Transfused blood can disrupt the balance of coagulation factors and modulates the inflammatory cascade. Since inflammation and coagulation are tightly coupled, we postulated that RBC transfusion may be associated with the development of venous thromboembolic phenomena. We queried the American College of Surgeons’ National Surgical Quality Improvement Program (ACS NSQIP) database to examine the relationship between intraoperative blood transfusion and development of venous thromboembolism (VTE) in patients undergoing colorectal resection for cancer.

Materials and Methods

We analyzed the data from 2005 to 2009 for patients undergoing colorectal resections for cancer based on the primary procedure CPT-4 code and operative ICD-9 diagnosis code. The primary outcome was 30-day deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Intraoperative transfusion of RBC's was categorized as: none, 1-2 units, 3-5 units and 6 units or more. DVT/PE occurrences were analyzed by multivariable forward stepwise regression (p for entry < .05, for exit > .10) to identify independent predictors of DVT.

Results

The database contained 21943 colorectal cancer resections. The DVT rate was 1.4% (306/21943) and the PE rate was 0.8% (180/21943). Patients were diagnosed with both only 40 times and the combined DVT or PE rate (VTE) was 2.0% (446/21943). After adjusting for age, gender, race, ASA (American Society of Anesthesiologists) class, emergency procedure, operative duration and complexity of the procedure (based on Relative Value Units, RVU's), along with six clinical risk factors, intraoperative blood transfusion was a significant risk factor for the development of VTE and the risk increased with increasing number of units transfused. Preoperative hematocrit did not enter the multivariable model as an independent predictor of VTE, nor did open versus laparoscopic resection or wound class.

Conclusion

In this study of 21943 patients undergoing colorectal resection for cancer, blood transfusion is associated with increased risk of VTE. Malignancy and surgery are known prothrombotic stimuli, the subset of patients receiving intraoperative RBC transfusion are even more at risk for VTE, emphasizing the need for sensible use of transfusions and rigorous thromboprophylaxis regimens.