The incidence and risk factors of recurrent venous thromboembolism during pregnancy

Introduction

Recurrent venous thromboembolism (VTE) during pregnancy is a challenging topic with relatively few publications. The aim of this study was to identify the incidence and the risk factors of recurrent antepartum VTE in women with a history of at least one previous VTE episode.

Materials and Methods

This observational cohort study involved 270 pregnant women (369 pregnancies) with at least one previous episode of VTE. The risk factors of recurrent antepartum VTE were identified by using group A (women without recurrent venous thromboembolism VTE) as a control group for group B (women with recurrent VTE despite LMWH (low molecular weight heparin) prophylaxis) and C (women with VTE recurrence in early pregnancy before the planned initiation of LMWH prophylaxis).

Results and Conclusions

The incidence of recurrent VTE was 7.6% (n = 28).Twelve recurrent VTEs in ten women (3.3%) developed during early pregnancy before initiation of LMWH and sixteen recurrent VTEs (4.3%) developed in 15 women despite LMWH prophylaxis.In women with recurrent antepartum VTE, the incidence of a history of two or more previous VTEs (group A vs. B: 5.7% vs. 40.0%, p < 0.001; group A vs. C: 5.7% vs. 30.0%, p = 0.022), previous VTE in connection with antiphospholipid antibody syndrome (group A vs. B: 2.6% vs. 20.0%, p = 0.012) and a history of VTE related to hormonal risk factors (group A vs. B: 60.4% vs. 93.3%, p = 0.011) was significantly higher compared to those with successful LMWH-prophylaxis. The percentage of the women with long-term anticoagulation was also significantly higher among the women with recurrent antepartum VTE (group A vs. B: 7.6% vs. 46.7%, p < 0.001) compared to those with successful LMWH-prophylaxis. The risk of antepartum recurrent VTE is considerable in women with a history of two or more previous VTEs, antiphospholipid antibody syndrome or long-term anticoagulation. The antepartum prophylaxis with prophylactic dose of LMWH or even with intermediate dose of LMWH might not be sufficient in this high-risk population.     

Thromboprophylaxis patterns,risk factors,and outcomes of care in the medically ill patient population

Introduction

Medically ill, hospitalized patients are at increased risk for venous thromboembolism (VTE) after discharge. This study aimed to examine thromboprophylaxis patterns, risk factors, and post-discharge outcomes.

Methods

This was a retrospective claims analysis involving administrative claims data and in-patient data abstracted from a sample of hospital charts. Patients aged ≥ 40 years hospitalized for ≥ 2 days for nonsurgical reasons between 2005 and 2009 were included. Hospital chart data were abstracted for a random sample of patients without evidence of anticoagulant use at 30 days post-discharge. The combined data determined whether in-patient thromboprophylaxis (anticoagulant or mechanical prophylaxis) reduces risk of VTE at 90 days post-discharge. Hazard ratios (HR) and odds ratios (OR) were calculated using Cox proportional hazard models and logistic regression.

Results

Of 141,628 patients in the claims analysis, 3.9% received anticoagulants (3.6% warfarin). VTE, rehospitalization, and mortality rates were 1.9%, 17.2%, and 6.2%, respectively. The strongest predictors of post-discharge VTE were history of VTE (HR = 4.0, 95% confidence interval [CI]: 3.3-4.8), and rehospitalization (HR = 3.9, 95% CI: 3.6-4.3). Of 504 medical charts, 209 (41.5%) reported in-patient thromboprophylaxis. There was no statistically significant difference in post-discharge VTE rates between patients who did and did not receive in-patient thromboprophylaxis. All-cause mortality was greater among patients without use of VTE prophylaxis.

Conclusion

Utilization rates of in-hospital and post-discharge VTE prophylaxis were low. In-hospital VTE prophylaxis did not reduce the risk of post-discharge VTE in the absence of post-discharge anticoagulation. Combined in-patient and post-discharge thromboprophylaxis lowered the odds of short-term, all-cause post-discharge mortality.     

High prevalence of recurrent thrombosis in subsets of cancer patients with isolated gonadal vein thrombosis: A single center retrospective study

Purpose

Cancer patients are a high-risk population for venous thromboembolism (VTE); the natural history of gonadal vein thrombosis (GVT) occurring in cancer patients is not well described in the medical literature.

Methods

Utilizing a software program the computerized tomographic scan reports of patients at a single cancer center from January 1, 2004 to June 30, 2011 were searched for the term GVT. Patients included in this analysis had a diagnosis of cancer, an isolated GVT (i.e. no evidence of thrombosis at another site), no symptoms referable to the GVT, and at least six months of follow-up information. All subsequent recurrent VTE events were confirmed by imaging studies.

Results

196 cancer patients with GVT were identified. The majority of patients in this analysis had metastatic disease (118, 61.2%) as well as active cancer (167, 85.2%). Twenty patients (10.8%) developed recurrent VTE (median follow-up 14.5 months); median time to recurrent VTEs was 5.5 months (range 0–19 months). When considering only patients with without a recent history of gynecologic surgery, VTE recurrence rates were 14.3%. Active cancer was the only risk factor significantly associated with recurrent VTE (P = 0.047).

Conclusions

Based upon the patient’s risk factors for VTE, treatment of an incidentally detected GVT in cancer patients with anticoagulation, as per guidelines for other VTE sites, may be indicated in certain high risk subgroups, especially those patients with active cancer who have not had prior pelvic surgery.     

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.     

Risk factors for recurrent venous thromboembolism in young and middle-aged women

Background

It is a matter of debate whether women with an episode of VTE associated with estrogen have a lower risk of recurrence than women with an unprovoked VTE.

Objectives

To identify risk factors for recurrent VTE in women and to assess the risk of recurrent VTE associated with combined oral contraceptives (CHC) or menopausal hormone treatment (HT), compared to surgery-related and unprovoked VTE.

Patients/Methods

A cohort of 974 women aged 18–64 years with a first episode of VTE were followed-up for a median time of 5.2 years. All women were previously included as cases in the Swedish nation-wide case–control study “Thrombo Embolism Hormone Study” (TEHS). Hazard ratios for recurrence were calculated using univariable and multivariable Cox proportional hazards model.

Results

A total of 102 patients (10%) suffered from recurrent VTE. The annual rate of recurrence was 1.0% in patients with surgery/cast, 2.0% in patients with CHC/HT and 3.2% in patients with unprovoked first VTE. Adjusted hazards ratio (HR_a) for recurrence was 0.35 (95% CI 0.20-0.61) in women with VT provoked by surgery/cast while women with estrogen-associated VTE had a HR_a of 0.70 (95% CI 0.43-1.20) compared to women with unprovoked VTE.

Conclusion

Women 18–64 years are at low risk of recurrent VTE. Women with hormone associated VTE had a lower risk of recurrence than women with unprovoked VTE, but not as low as surgery/cast provoked VTE.     

Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and risk of venous thromboembolism: A meta-analysis

Introduction

The plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism was considered to be associated with risk of venous thromboembolism (VTE), while evidence remains inadequate. To provide a more accurate estimation of this relationship, we performed an updated meta-analysis of all eligible studies.

Materials and Methods

A systematical search was performed in PubMed, EMBASE, Wanfang, China National Knowledge Infrastructure (CNKI) and Cqvip databases to identify relevant studies published before March 6^th 2014. The odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using the fixed/random-effects model using Review Manager 5.1 and STATA 12.0.

Results

A total of 34 studies with 3561 cases and 5693 controls were analyzed. Overall, significant association between the PAI-1 4G/5G variant and VTE risk in total population (dominant model: OR = 1.32, 95%CI: 1.13-1.54) was observed. And this variant was also related to the deep vein thrombosis risk (dominant model: OR = 1.60, 95%CI: 1.24-2.06, P = 0.0003). In the subgroup analyses on ethnicity, significant results were obtained in both Asians (dominant model: OR = 2.08, 95%CI: 1.29-3.35, P = 0.003) and Caucasians (dominant model: OR = 1.31, 95%CI: 1.10-1.56, P = 0.003). However, no significant association was found in patients with provoked VTE. In terms of subgroup analyses on co-existence of other thrombotic risk factors, the PAI-1 4G/5G polymorphism was significantly associated with VTE risk in patients with factor V Leiden mutation (dominant model: OR = 1.72, 95%CI: 1.17-2.53), but not in patients with cancer or surgery.

Conclusion

Our findings demonstrate the role of PAI-1 4G/5G polymorphism being a risk candidate locus for VTE susceptibility, especially in patients with other genetic thrombophilic disorders.     

The role of soluble P selectin in the diagnosis of venous thromboembolism

Introduction

Soluble P selectin (sPsel), a member of the selectin family of cell adhesion receptors, has been proposed as a key molecule in hemostasis and thrombosis mediating platelet rolling, generating procoagulant microparticles and enhancing fibrin deposition. The aim of this study was to examine the role of sPsel in the diagnosis of venous thromboembolism (VTE).

Materials and Methods

We performed a systematic review and we used meta-analysis to synthesize data from published studies reporting sPsel levels in patients with i) VTE (deep venous thrombosis; DVT or DVT and pulmonary embolism; PE) and ii) DVT only. Pooled Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were appropriately calculated among patients and controls. Diagnostic performance of sPsel was tested with pooled sensitivity, specificity, Diagnostic Odds Ratio (DOR) and summary receiver operator characteristic (SROC) curve.

Results

Eleven studies, comprising of 586 VTE patients and 1,843 controls were deemed eligible. The sPsel was significantly increased after VTE (OR = 2.89, 95%CI = 2.31-3.61, p < 0.001), or DVT only (OR = 2.64, 95%CI = 1.95-3.56, p < 0.001). Subgroup analysis evidenced that sPsel was also increased after VTE when evaluating only studies with patients that had no prior medical history (OR = 2.88, 95%CI = 1.98-4.19, p < 0.001). Exclusion of studies including patients with solid organ tumor, HIV or lupus anticoagulants positive patients did not alter findings. Pooled sensitivity and specificity of sPsel was 0.57 (95%CI = 0.30-082, p < 0.001) and 0.73 (95%CI = 0.51-0.90, p < 0.001), respectively and DOR was 4.31 (95%CI = 2.22-8.37, p < 0.01). SROC curve yielded in significant accuracy of sPsel performance (AUC = 0.74, p = 0.05).

Conclusions

The sPsel was significantly elevated in patients with DVT, both uncomplicated and complicated with PE and presented with high levels of diagnostic performance. sPsel is a plasma biomarker that may help in the diagnosis of VTE.     

Renal failure as a risk factor for venous thromboembolism in critically Ill patients: A cohort study

Rationale

The relationship between kidney function and venous thromboembolism (VTE) in critically ill patients is not well studied. The main objective of this study was to evaluate this relationship in patients admitted to a medical-surgical intensive care unit (ICU).

Methods

This was a retrospective study of 798 patients admitted to a tertiary-care ICU and prospectively followed for the development of clinically suspected and radiologically diagnosed deep venous thrombosis or pulmonary embolism. Patients were divided based on admission creatinine and dialysis history into five groups: normal kidney function, RIFLE classes R, I and F (combined = acute kidney injury [AKI]) and endstage renal disease (ESRD). We compared VTE prophylaxis practices and VTE incidence in these groups and evaluated renal failure as a VTE risk factor using multivariate Cox regression analysis.

Results

Of the 798 patients, 27.2% had AKI and 10.1% had ESRD. Unfractionated heparin use was similar in the five groups but enoxaparin use was less frequent in AKI (13.4%) and ESRD (3.8%) patients compared with patients with normal kidney function (39.0%). VTE occurred in 7.6% of patients with normal renal function, 7.8% AKI patients and 2.5% ESRD patients (p = 0.22). The adjusted hazard ratios for VTE compared to patients with normal kidney function were 0.35 (95% confidence interval [CI], 0.08-1.47) for RIFLE class R, 1.19 (95% CI, 0.83-1.70) for RIFLE class I, 0.82 (95% CI, 0.59-1.14) for RIFLE class F and 0.71 (95% CI, 0.49-1.02, p = 0.06) for ESRD.

Conclusions

Neither AKI nor ESRD was an independent risk factors for critically ill patients.     

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.     

Statins are Associated with Low Risk of Venous Thromboembolism in Patients with Cancer: A Prospective and Observational Cohort Study

Introduction

Patients with cancer are at risk of venous thromboembolism (VTE). Statin-use has been shown to be associated with low risk of VTE in patients without cancer, but data in cancer patients is scarce. The objective of this study was to evaluate the association of statins with risk of VTE in cancer patients in a prospective observational cohort study.

Materials and Methods

Patients with newly diagnosed cancer or progression of disease after remission were included and prospectively followed for a maximum of 2 years. Study endpoint was occurrence of symptomatic VTE.

Results

Patients (n = 1434) were followed over a median observation period of 729 days. VTE occurred in 107 (7.5%) patients. At study inclusion, 170 (11.9%) patients took statins. Simvastatin (n = 96) and atorvastatin (n = 48) were the most frequently prescribed statins. VTE occurred in 6 (3.5%) patients with statins. Patients with statins had a lower risk of VTE than patients without (subhazard ratio 0.43, 95% confidence interval 0.19 to 0.98; p = 0.04). In competing risk analysis, the cumulative probability of VTE in patients with statins was 2.94% after 12 months and 3.54% after 24 months, compared to 7.13% and 8.13% in the group without statins (Gray’s test: p = 0.04).

Conclusion

This study provides observational evidence for an association between statin use and low risk of VTE in patients with cancer. The role of statins for prevention of cancer-associated VTE needs to be confirmed in randomized, controlled trials.     

Meta-Analysis to Assess the Quality of International Normalized Ratio Control and Associated Outcomes in Venous Thromboembolism Patients

Introduction

Patients with venous thromboembolism (VTE) frequently require vitamin K antagonists (VKAs) to prevent recurrent events, but their use increases hemorrhage risk. We performed a meta-analysis to assess the quality of international normalized ratio (INR) control, identify study-level predictors of poor control and to examine the relationship between INR control and adverse outcomes in VTE patients.

Materials and Methods

We searched bibliographic databases (1990-June 2013) for studies of VTE patients receiving adjusted-dose VKAs that reported time in range (2.0-3.0) or proportion of INRs in range and/or reported INR measurements coinciding with thromboembolic or hemorrhagic events. Meta-analysis and meta-regression analysis was performed.

Results

Upon meta-analysis, studies found 59% (95%CI: 54-64%) of INRs measured and 61% (95%CI: 59-63%) of the time patients were treated were spent outside the target range of 2.0-3.0; with a tendency for under- versus over-anticoagulation. Moreover, this poor INR control resulted in a greater chance of recurrent VTE (beta-coefficient = -0.46, p = 0.01) and major bleeding (beta-coefficient = -0.30, p = 0.02). Patients with an INR < 2.0 made up 58% (95%CI: 39-77%) of VTE cases, while those with an INR > 3.0 made up 48% (95%CI: 34-61%) of major hemorrhage cases. Upon meta-regression, being VKA-naïve (-14%, p = 0.04) and treated in the community (-7%, p < 0.001) were associated with less time in range, while being treated in Europe/United Kingdom (compared to North America) was associated with (11%, p = 0.003) greater time.

Conclusions

Strategies to improve INR control or alternative anticoagulants, including the newer oral agents, should be widely implemented in VTE patients to reduce the rate of recurrent events and bleeding.     

Treatment patterns of venous thromboembolism in a real-world population: The Q-VTE study cohort

Background

Few studies have assessed treatment patterns of acute venous thromboembolism (VTE) in a real-world population. We aimed to describe anticoagulant treatment patterns for acute VTE using healthcare databases of Québec, Canada.

Methods

We used linked healthcare databases of the province of Québec, Canada to identify all incident cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) between 2000 and 2009. We formed two patient cohorts, one with definite cases (definite VTE cohort, N = 40,776) and the other including cases with definite or probable VTE (any VTE cohort, N = 54,803) that were followed until death, end of health coverage, or end of study (December 31, 2009).

Results

In the definite cohort, 73.6% of subjects were dispensed an anticoagulant following the diagnosis of VTE. Of those who were dispensed a vitamin K antagonist (VKA), median duration of use was 61 days (interquartile range 89). VKA initiation was more likely in patients with pulmonary embolism than deep vein thrombosis alone (HR 1.62, 95% CI (1.58-1.66)). Among outpatients, those managed initially in the outpatient setting were less likely to initiate VKA therapy (HR 0.75, 95% CI (0.68-0.77)), while those requiring admission to hospital for VTE management were more likely to initiate (HR 1.81, 95% CI (1.76-1.87)). Findings were similar in the any VTE cohort.

Conclusion

Our study describes VTE treatment patterns in a real-world setting and suggests that there may be important gaps. These may include significant numbers of patients who did not initiate oral anticoagulant therapy, particularly in the outpatient setting, and shorter duration of oral anticoagulant use than recommended.     

Incidence and risk factors of symptomatic venous thromboembolism related to implanted ports in cancer patients

Introduction

The true incidence of symptomatic implanted port related venous thromboembolism (VTE) in cancer patients is unclear and there is very limited data on its associated risk factors.

Materials and methods

We performed a retrospective cohort study of consecutive cancer outpatients who received an ultrasound guided implanted port insertion for the administration of chemotherapy. The primary outcome measure was symptomatic VTE. Univariable and multivariable logistic regression analyses were used to identify risk factors for symptomatic VTE.

Results

A total of 400 cancer patients with a newly inserted implanted port for deliverance of chemotherapy were included in the study. Median age was 58 years (range of 21 to 85 years) and 120 (30%) were males. Patients were followed for a median of 12 months and none received thrombophrophylaxis. Of the 400 patients included in the analysis, 34 patients (8.5%; 95% CI: 6.0 to 11.7%) had symptomatic VTE (16 DVTs, 16 PEs, and 2 with both). In the univariate analyses, metastatic disease, male gender and right sided implanted port insertion were significantly associated with the risk of VTE. In the multiple-variable analysis, male gender (OR 2.17, p = 0.04) and presence of metastases (OR 8.22, p < 0.01) were the two significant independent predictors of implanted port related VTE.

Conclusion

Symptomatic VTE is a frequent complication in cancer patients with implanted port receiving chemotherapy. Gender and presence of metastatic disease are independent risk factors for symptomatic VTE. Future trials assessing the role of thromboprophylaxis among these higher risk patients are needed.     

Risk-assessment and pharmacological prophylaxis of venous thromboembolism in hospitalized patients with chronic liver disease

Introduction

There is a lack of evidence regarding the need for thromboprophylaxis in hospitalized patients with liver disease. The purpose of this study was to evaluate the Padua Predictor Score (PPS) as a risk-stratification tool for the development of venous thromboembolism (VTE) in patients with chronic liver disease.

Methods

This was a retrospective cohort study conducted in an academic medical center in the United States. Consecutive adult patients admitted with chronic liver disease were included. Patients were categorized into two groups based on whether they developed a VTE or not. The risk for VTE in each patient was evaluated using the Padua Predictor Score (PPS). Patients were risk stratified using the PPS score as high-risk (score ≥ 4) and low-risk (score < 4). The risk of VTE based on PPS categorization was evaluated using logistic regression.

Results

A total of 163 patients with liver disease were included in the study cohort. Of these, 18 (11%) developed VTE. Mean PPS was significantly greater in the VTE group than the non-VTE group (5.8 ± 2.0 versus 3.0 ± 2.1, respectively; p < 0.001). In high-risk patients 22% (n = 16/72) developed VTE and in low-risk patients 2% (2/91) developed VTE (p < 0.001). High-risk patients were more likely to have VTE (OR 12.7, 95% CI 2.8 to 57.4, p = 0.001).

Conclusion

The PPS is an effective risk assessment tool for VTE in patients hospitalized with chronic liver disease.     

Cost-Effectiveness Analysis of Extended Duration Anticoagulation with Rivaroxaban to Prevent Recurrent Venous Thromboembolism

Introduction

Extended duration anticoagulation with rivaroxaban for an additional 6–12 months can reduce recurrent venous thromboembolic events (VTE) compared to placebo by ~ 82%, but at the detriment of increased bleeding. We sought to estimate the cost-effectiveness of extended duration prophylaxis of recurrent VTE with rivaroxaban.

Material and Methods

A Markov model was developed to estimate the cost-effectiveness of extended duration rivaroxaban, 20 mg daily, compared to placebo using a Medicare perspective, a one-month cycle length and a 40-year time horizon. The model assumed a cohort of 58-year-old patients who had already completed an initial 6–12 months of anticoagulation with rivaroxaban or a vitamin K antagonist; and whom prescribers had clinical equipoise with respect to the need for continued anticoagulation. Data sources included EINSTEIN-Extension and other published studies of VTE. Outcomes included direct treatment costs (in 2013US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).

Results

Extended duration rivaroxaban resulted in higher treatment costs ($22,645 vs. $22,083) but yielded greater QALYs (16.167 vs. 16.134) as compared to placebo; corresponding to an ICER of $17,030/QALY gained. Our model was most sensitive to the baseline risk of bleeding and recurrent VTE, the hazard ratio of developing a recurrent event while on rivaroxaban and time horizon. Monte Carlo Simulation suggested rivaroxaban would be cost-effective in 66% of 10,000 iterations, assuming a willingness-to-pay threshold of $50,000/QALY.

Conclusion

Despite the cost of rivaroxaban and an increased risk of bleeding, extending VTE treatment for an additional 6–12 months with rivaroxaban was found cost-effective compared to the placebo over a 40-year time horizon.     

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.     

A pilot study of eptifibatide for treatment of acute pain episodes in sickle cell disease

Introduction

The contribution of platelet activation to the pathogenesis of sickle cell disease (SCD) remains uncertain. We evaluated the safety and efficacy of eptifibatide, a synthetic peptide inhibitor of the αIIbβ3 receptor, in SCD patients during acute painful episodes.

Materials and Methods

In this single site, double-blind, placebo-controlled trial, eligible patients with SCD admitted for acute painful episodes were randomized to receive eptifibatide or placebo at a ratio of 2:1.

Results

Thirteen patients (SS - 10, Sβ⁰ - 2, SC - 1) were randomized to receive either eptifibatide (N = 9; 6 females; median age - 25 years) or placebo (N = 4; 3 females; median age - 31 years). In the intent-to-treat analysis, there were no major bleeding episodes in either the eptifibatide or placebo arms (point estimate of difference: 0.00, 95% CI; -0.604, 0.372). There was one minor bleeding episode in the eptifibatide arm (point estimate of difference for any bleeding: 0.11, 95% CI: -0.502, 0.494). There was no significant difference in the proportion of patients with thrombocytopenia between the treatment groups (point estimate of difference: 0.11, 95% CI: -0.587, 0.495). There were no differences in the median times to discharge, median times to crisis resolution or the median total opioid use.

Conclusions

In this small study, eptifibatide appeared to be safe, but did not improve the times to crisis resolution or hospital discharge. Adequately powered studies are required to evaluate the safety and efficacy of eptifibatide in SCD. Clinicaltrials.gov Identifier: NCT00834899.     

Apolipoprotein M and the risk of unprovoked recurrent venous thromboembolism

Introduction

Apolipoprotein M (ApoM) protects against atherosclerosis; however, it is unknown whether it also protects against recurrent venous thromboembolism (VTE).

Material and Methods

Patients in the Malmö Thrombophilia Study (MATS) were followed post-anticoagulant treatment until the diagnosis of recurrent VTE or the end of the study (mean follow-up 36 months). Among patients with a first episode of unprovoked VTE, we identified 43 patients (9.7%) with recurrent VTE during the follow-up period. Three age- and sex-matched control subjects without recurrent VTE were selected for each case (n = 129). Plasma levels of ApoM were quantified by a sandwich ELISA method.

Results

Among all patients, the plasma levels (mean ± SD) of ApoM were not significantly different between patients with recurrent (0.70 ± 0.2) and non-recurrent VTE (0.74 ± 0.2), p = 0.2. However, after stratification of data according to gender, male patients with recurrent VTE showed significantly (p = 0.02) lower ApoM levels (0.63 ± 0.2) as compared to those with non-recurrent VTE (0.74 ± 0.2). No significant differences in ApoM levels were found between recurrent (0.8 ± 0.2) and non-recurrent VTE (0.75 ± 0.2) in female patients, p = 0.3. Cox-regression analysis showed that the risk of recurrent VTE was 0.98 (95% CI, 0.96-0.99) for each 0.01 μM increase in ApoM level in male patients (p = 0.042), and this risk remained unchanged after adjusting for inherited thrombophilia and body mass index (p = 0.027). ApoM levels were not associated with the risk of recurrent VTE in female patients.

Conclusion

Our results show that levels of ApoM in recurrent VTE may differ according to gender and lower levels of ApoM may predict VTE recurrence in male patients.     

Effect of 200 μG/day of vitamin k1 on the variability of anticoagulation control in patients on warfarin: A randomized controlled trial

Background

Controversy exists whether low-dose vitamin K supplementation can improve anticoagulation control in patients with unstable anticoagulation under warfarin. In a single- centre randomized, double-blind, placebo-controlled study, we evaluated the effectiveness of 200 μg/day of vitamin K1 in patients with unstable control under warfarin.

Methods

Effectiveness of Vitamin K1 supplementation was primarily assessed by the percentage (%) of Time-in-Therapeutic-Range (TTR) and secondarily by the standard deviation (SD) of the patient’s INR values; the proportion of out-of-range INRs; and the number of dose changes on warfarin. Their change scores were obtained by subtracting the mean value in the 6 months pre-randomization from the mean value in the 6 months post-randomization. Multivariable linear-regressions identified factors associated with anticoagulation instability.

Results

Fifty out of 54 patients were analyzed (intervention: n = 26; placebo: n = 24). Most indications (87%) for anticoagulation were venous thromboembolism (VTE). The intervention was associated with a greater reduction in the change scores for the SD of INRs between the pre and post-randomization periods compared with placebo. The mean change score was -0.259 ± 0.307 with the intervention and -0.046 ± 0.345 with placebo (p = 0.026). There was no effect on the change scores of the (%) TTR (p = 0.98), the number of INRs out-of-range (p = 0.58) and the number of dose changes (p = 0.604). Factors independently associated with increased variability in the SD of INRs were increased alcoholic drinks/week (p = 0.017), dosing errors (p = 0.0009) and missed INR appointments (p = 0.035).

Conclusion

Vitamin K1 supplementation reduces the SD of INRs as an indicator of the variability in anticoagulation control in patients treated with warfarin for VTE.