Evaluation of recurrent venous thromboembolism in patients with Factor V Leiden mutation in heterozygous form

Introduction

To evaluate the risk for recurrence after first venous thromboembolism (VTE) among patients with or without Factor V Leiden (FVL) mutation.

Materials and Methods

A prospective population based study of 1465 consecutive unselected VTE patients was performed at Skåne University Hospital 1998-2008. The VTE was objectively verified and the patients answered questionnaire and left blood samples for evaluation.

Results

Out of 1465 patients (721[49%] men and 744[51%] women) thrombophilia data were available for 1267, and FVL mutation was found in heterozygous form in 339 (27). The homozygous form and prothrombin mutation (PTM) were much less common. Patients were followed during 4.8 ± 2.3 years (total 6133 patient years) and recurrence after first VTE (evaluated in 1108 patients) occurred in 131 (12%, 95%CI 10-14%), where of 49(37%) had heterozygous FVL mutation and 57(44%) were without thrombophilia. The remaining 25(19%) patients had either PTM, FVL in homozygous form, compound PTM/FVL or unknown thrombophilia status. Having FVL mutation in heterozygous form significantly increased the risk for VTE recurrence (odds ratio 2.4 (95 %CI 1.6-3.6; p < 0.01). In a Kaplan-Meier analysis the FVL group also differed significantly (p < 0.01) from the other patients concerning time to recurrence (almost 25% vs. 10% after 8 years).

Conclusions

FVL mutation in heterozygous form is common among VTE patients and significantly increases the risk for VTE recurrence.     

Clinical characteristics of patients with factor V Leiden or prothrombin G20210A and a first episode of venous thromboembolism. Findings from the RIETE Registry

Background

The clinical characteristics of patients with factor V Leiden or prothrombin G20210A presenting with a first episode of venous thromboembolism (VTE) have not been thoroughly studied.

Methods

RIETE is an ongoing registry of consecutive patients with acute VTE. We compared the clinical characteristics of patients with factor V Leiden, prothrombin G20210A, or no thrombophilia, at presentation with a first episode of VTE.

Results

As of May 2009, 22428 patients had been enrolled with a first episode of VTE. Of these, 345 had factor V Leiden, 261 had prothrombin G20210A, and 2399 tested negative. Sixty-two percent of the VTE episodes in women with factor V Leiden or prothrombin G20210A (40% in men) were associated with an acquired risk factor. Among women, pregnancy or contraceptive use accounted for 63% and 67% of such risk factors. Patients with factor V Leiden presented with pulmonary embolism (PE) less likely than those with prothrombin G20210A (31% vs. 51%; p < 0.001) or with negative testing (31% vs. 45%, p < 0.001). In addition, PE patients with Factor V Leiden presented with hypoxaemia (Sat O₂ levels < 90%) less likely than those with prothrombin G20210A (4.5% vs. 17%; p < 0.001) or with no thrombophilia (4.5% vs. 20%; p < 0.001).

Conclusions

Most VTE episodes in women (not men) with factor V Leiden or prothrombin G20210A were associated with an acquired risk factor (mostly pregnancy or contraceptive use). Only 4.5% of patients with factor V Leiden presenting with acute PE had hypoxaemia.     

Predicting recurrences or major bleeding in cancer patients with venous thromboembolism. Findings from the RIETE Registry

Cancer patients with acute venous thromboembolism (VTE) have an increased incidence of recurrences and bleeding complications while on anticoagulant therapy. Methods RIETE is an ongoing registry of consecutive patients with acute VTE. We tried to identify which cancer patients are at a higher risk for recurrent pulmonary embolism (PE), deep vein thrombosis (DVT) or major bleeding. Up to May 2007, 3,805 cancer patients had been enrolled in RIETE. During the first three months of follow-up after the acute, index VTE event, 90 (2.4%) patients developed recurrent PE, 100 (2.6%) recurrent DVT, 156 (4.1%) had major bleeding. Forty patients (44%) died of the recurrent PE,46 (29%) of bleeding. On multivariate analysis, patients aged <65 years (odds ratio [OR]: 3.0; 95% confidence interval [CI]: 1.9-4.9), with PE at entry (OR: 1.9; 95% CI: 1.2-3.1), or with <3 months from cancer diagnosis to VTE (OR: 2.0; 95% CI: 1.2-3.2) had an increased incidence of recurrent PE. Those aged <65 years (OR: 1.6; 95% CI: 1.0-2.4) or with <3 months from cancer diagnosis (OR: 2.4; 95% CI: 1.5-3.6) had an increased incidence of recurrent DVT. Finally, patients with immobility (OR: 1.8; 95% CI: 1.2-2.7), metastases (OR: 1.6; 95% CI: 1.1-2.3), recent bleeding (OR: 2.4; 95% CI: 1.1-5.1), or with creatinine clearance <30 ml/min (OR: 2.2; 95% CI: 1.5-3.4), had an increased incidence of major bleeding. With some variables available at entry we may identify those cancer patients withVTE at a higher risk for recurrences or major bleeding.     

Elevated white blood cell count and outcome in cancer patients with venous thromboembolism. Findings from the RIETE Registry

A significant association between elevated white blood cell (WBC) count and mortality in patients with cancer has been reported, but the predictive value of elevated WBC on mortality in cancer patients with acute venous thromboembolism (VTE) has not been explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We compared the three-month outcome of cancer patients with acute VTE according to their WBC count at baseline. As of May 2007, 3805 patients with active cancer and acute VTE had been enrolled in RIETE. Of them, 215 (5.7%) had low- (<4,000 cells/microl), 2,403 (63%) normal- (4,000-11,000 cells/microl), 1,187 (31%) elevated (>11,000 cells/microl) WBC count. During the study period 190 patients (5.0%) had recurrent VTE, 156 (4.1%) major bleeding, 889 (23%) died (399 of disseminated cancer, 113 of PE, 46 of bleeding. Patients with elevated WBC count at baseline had an increased incidence of recurrent VTE (odds ratio [OR]: 1.6; 95% confidence interval [CI]: 1.2-2.2), major bleeding (OR: 1.5; 95% CI: 1.1-2.1) or death (OR: 2.7; 95% CI: 2.3-3.2). Most of the reported causes of death were significantly more frequent in patients with elevated WBC count. Multivariate analysis confirmed that elevated WBC count was independently associated with an increased incidence of all three complications. In conclusion, cancer patients with acute VTE and elevated WBC count had an increased incidence of VTE recurrences, major bleeding or death. This worse outcome was consistent among all subgroups and persisted after multivariate adjustment.     

Certoparin versus UFH to prevent venous thromboembolic events in the very elderly patient: an analysis of the CERTIFY study

Introduction

There is an exponential rise of thromboembolic risk with age because of co-morbidities, immobility and pharmacotherapy. We aimed to investigate the benefits and risks of heparin prophylaxis in very elderly patients ≥ 80 years and the type of heparin used in a subgroup analysis of the CERTIFY trial.

Patients/methods

3,239 patients were randomized to 3,000 U aXa o.d. certoparin or 5,000 IU t.i.d. unfractionated heparin (UFH) for 8-20 days.

Results

Patients ≥ 80 years (n = 1,365) were more likely to be female, had a lower mean bodyweight, were more frequently using antiplatelets and had a GFR below 30 ml/min/1.73 m² more often than patients < 80 years (n = 1,875). The combined endpoint of proximal DVT, symptomatic non-fatal PE and VTE related death was experience by 5.26% of patients ≥ 80 years versus 3.51% in younger patients (OR 1.53; 95%CI 1.05-2.21; p = 0.03). There were no significant differences in both minor (OR 1.11; 95%CI 0.75-1.62) and major (OR 2.53; 95%CI 0.93-6.86) bleeding risks. Certoparin and UFH were equally effective in reducing thromboembolic risk in either age group. The risk of any (OR 0.45; 95%CI 0.26-0.79) and minor bleeding (OR 0.42; 95%CI 0.23-0.78) was reduced with certoparin in the very elderly only. There were more adverse events in elderly patients (OR 1.26; 95%CI 1.1-1.46), but rates were otherwise comparable.

Conclusions

The analysis confirmed the increased thromboembolic risk in very elderly patients, but demonstrated no increased bleeding risk. Certoparin and UFH were equally effective and safe with a reduced risk of minor bleeding complications with certoparin in the very elderly.     

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.     

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.     

Long-term death and recurrence in patients with acute venous thromboembolism: The MASTER registry

BACKGROUND: The long-term clinical outcome of VTE has been essentially assessed in cohorts of selected patients. The aim of this multicenter registry was to prospectively assess the long-term clinical outcome in a cohort of unselected patients with objectively confirmed acute VTE. MATERIALS AND METHODS: Death and VTE recurrence at 24months were the main study outcomes. Univariate and multivariate survival analyses were performed according to the Kaplan-Meyer and Cox proportional hazard model, respectively. RESULTS: 2119 patients with acute VTE were included in the registry: 1541 (72.7%) with deep vein thrombosis, 206 (9.7%) with pulmonary embolism and 372 (17.6%) with both. Information about death was available in 2021 patients (95.4%) and about recurrence in 1988 patients (93.8%). 167 patients (4.55% patient-year) died during follow-up. After adjusting for age, cancer (Hazard ratio [HR]: 7.2; 95%CI 4.8-10.8), long-term heparin treatment (HR: 2.5; 95%CI 1.8-3.5), in-hospital management of VTE (HR: 2.0; 95%CI 1.3-3.0), and ileo-caval thrombosis (HR: 1.7; 95%CI 1.2-2.4) were found to be independent predictors of death. 124 (3.63% patient-year) patients had a VTE recurrence during follow-up. In-hospital management of VTE (HR: 1.8; 95%CI 1.2-2.9), male gender (HR: 1.7; 95%CI 1.2-2.4) were independent risk factors for recurrent VTE. Cancer (HR: 1.6; 95%CI 1.0-2.8) showed a trend for increased risk of VTE recurrence (p=0.056). The reported rate of major bleeding was 2.5%. CONCLUSIONS: In a large cohort of unselected VTE patients, cancer, ileo-caval thrombosis, long-term heparin treatment and in-hospital management were associated with increased mortality during long-term follow-up. In-hospital management, male gender were associated with an increased risk of VTE recurrence.     

Haplotypes of TAFI gene and the risk of cerebral venous thrombosis - a case-control study

Introduction

Cerebral venous thrombosis (CVT) is an uncommon disease with some differences compared to other-site thrombosis, including a higher frequency in young people, female sex and oral contraceptive users. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a regulator of fibrinolysis, whose levels are genetically controlled and its increase is associated to thrombosis. Our objective was to investigate in a case-control study the association between CVT and TAFI single nucleotide polymorphisms (SNPs) and its haplotypes in comparison to other-site venous thrombosis and controls.

Materials and Methods

Seventy two patients with CVT were compared to 143 individuals with no history of thromboembolic events (control group) and to 128 patients with deep vein thrombosis in the limbs and/or pulmonary embolism (venous thromboembolism-VTE group). SNPs were genotyped by restriction fragment length polymorphism or allele-specific PCR for F2 20210G > A, F5 1691G > A, TAFI (-1053C > T, -438G > A, 505G > A, 1040C > T and + 1542C > G).

Results

The GTC haplotype for TAFI 505G > A/1040C > T/+ 1542C > G SNPs was associated with an increased risk of CVT compared to controls [odds ratio (OR) 2.67, 95% confidence interval (CI): 1.13 - 6.34) and VTE group (OR 2.51, 95%CI: 1.07 - 8.06). The CVT risk became even more pronounced when evaluating unprovoked or hormone-related thrombosis cases: CVT compared to controls (OR 3.24, 95%CI: 1.19 - 8.82) and VTE group (OR 4.32, 95%CI: 1.27 - 14.63).

Conclusions

Our data indicate that the GTC haplotype for TAFI 505G > A/1040C > T/+ 1542C > G SNPs increased the risk of CVT in comparison to controls and VTE cases. Further studies are required to confirm our findings.     

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.     

Maternal thrombophilias are not associated with early pregnancy loss

We investigated the association between inherited and acquired maternal thrombophilias and adverse pregnancy events. A cohort of 491 patients with a history of adverse pregnancy outcomes was evaluated for activated protein C resistance, factor V Leiden and prothrombin G20210A mutations, hyperhomocysteinemia, deficiencies of antithrombin, protein C and S and both anticardiolipin antibodies and lupus anticoagulants. The study had an 80% power to detect a 15% difference in the prevalence of thrombophilia for 1(st) trimester loss. In our high-risk cohort the presence of 1 maternal thrombophilia or more than one thrombophilia were found to be protective of recurrent losses at < 10 weeks (1 thrombophilia: OR: 0.55, 95% CI: 0.33-0.92; > 1 thrombophilia: OR: 0.48, 95%CI:0.29-0.78). In contrast, the presence of maternal thrombophilia(s) was modestly associated with an increased risk of losses > 10 weeks (1 thrombophilia: OR:1.76, 95%CI: 1.05-2.94, >1 thrombophilia: OR:1.66, 95%CI:1.03-2.68). Women who experienced only euploid losses were not more likely to have an identified thrombophilia than women who experienced only aneuploid losses (OR 1.03; 0.38-2.75). The presence of maternal thrombophilia was associated with an increased risk of fetal loss after 14 weeks, fetal growth restriction, abruption and preeclampsia. There was a significant "dose-dependent" increase in the risk of abruption (OR:3.60, 95%CI: 1.43-9.09) and preeclampsia (OR:3.21, 95%CI:1.20-8.58). In conclusion, these data indicate maternal thrombophilias are not associated with pregnancy wastage prior to 10 weeks of gestation.     

Statin use in patients with nephrotic syndrome is associated with a lower risk of venous thromboembolism

Background

Nephrotic syndrome (NS) is a well-known risk factor for venous thromboembolism (VTE), however preventive measures are not routinely taken. In non-renal populations, statins are associated with lower risk of VTE. Hence, we set up this single-center retrospective cohort study to assess whether statin use influenced VTE risk in NS subjects.

Methods

We analyzed 289 consecutive patients with NS (defined by proteinuria ≥ 3.5 g/day) who were aged > 18 years at the study entry and followed for at least 6 months. Use of statins and concomitant medication were determined.

Results

Of patients with NS (59% men; mean age, 42 years), 48% used statins for at least 1 month during NS. Using univariate and time-dependent Cox regression analyses, hazard ratio for VTE in statin users versus non-users was 0.2 (95%CI, 0.1-0.7) and 0.6 (95% CI, 0.2 -2.0), respectively. Adjustments for potential confounders did not change outcomes. Three VTE events occurred in a total of 812 statin-years, corresponding to an annual incidence of 0.37% (95%CI, 0.12-1.15). In contrast, 17 VTE occurred in a total of 2106 patient-years without statin exposure, annual incidence 0.81% (95%CI, 0.50-1.30).

Conclusions

Although statistically significant, the hazard ratio of 0.2 for VTE risk in statin users versus non-users could have been biased, but the time-dependent hazard ratio of 0.6 was probably not. As the association was in the same direction for both analyses, we conclude that statin use is associated with a lower risk of VTE in patients with NS.     

神经重症患者静脉血栓栓塞的发生率、危险因素及住院结局分析

目的 探讨神经重症患者静脉血栓栓塞（venous thromboembolism,VTE）的发生率,并分析VTE相关 的危险因素及其对住院结局的影响。 方法 基于电子病历系统数据回顾性分析2019年10月-2020年9月首都医科大学附属北京天坛医院 的神经重症患者,根据患者住ICU期间是否发生VTE分为VTE组和无VTE组,计算VTE的发生率,通过多 因素logistic回归分析神经重症患者VTE的危险因素,并比较两组间死亡率、住ICU时间、住院时间及住 院费用的差异。 结果 共纳入神经重症患者723例,年龄中位数52岁,男性383例（53.0%）,其中330例（45.6%）患 者发生VTE。多因素logistic回归分析结果显示,年龄（OR 1.078,95%CI 1.053～1.104）、BM（I OR 1.082, 95%CI 1.013～1.156）和D-二聚体水平（OR 1.042,95%CI 1.006～1.079）升高是发生VTE的独立危险 因素。两组死亡率无统计学差异（4.8% vs 3.6%,P =0.388）,VTE组住院天数（21 d vs 18 d）、住I CU天数 （8 d vs 5 d）及住院费用（121 358元 vs 93 717元）较无VTE组增加（均P＜0.001）。 结论 神经重症患者VTE的发生率为45.6%,年龄、BMI和D-二聚体水平升高是其独立危险因素。发 生VTE可延长患者住院时间、住ICU时间,增加患者住院费用。     

Thromboprophylaxis following cesarean delivery: one site prospective pilot study to evaluate the application of a risk score model

Background

Venous thromboembolism (VTE) remains an important cause of maternal mortality and morbidity. Cesarean delivery (CD) is a known risk factor for VTE. Data from clinical trials of thomboprophylaxis following CD are lacking and current guidelines are based on experts opinion. Our aim was to assess the efficacy of a risk score model, established at our institution, in preventing CD-related VTE.

Methods

Before undergoing CD women received a risk score assessment based on age, weight, history of thrombosis, thrombophilia, immobility, parity and varicose vein. Women at moderate-high risk received pharmacological prophylaxis; all patients wore antithrombotic stockings. They had a visit before discharge and were advised to come back for visit and ultrasound if required. All received a follow-up phone call after three months.

Results

501 consecutive women were included in the study; 233 (46.5%), at low risk, had no pharmacological prophylaxis; one of them developed a symptomatic leg deep vein thrombosis (DVT); 268 (53.5%), at moderate-high risk, received enoxaparin and none of them developed VTE. Two were lost at follow up. The incidence of DVT was 1/499 (0.2%; 95%CI 0-1.1%). The differences in major and minor bleeding were not significant between women who received or not prophylaxis respectively (1/267 vs 1/232, p = 1 and 3/267 vs 1/232, p = 0.62).

Conclusions

The risk score model applied proved effective in avoiding pharmacological prophylaxis in almost half of women and safe, since the rate of failure resulted very low (0.2%, C.I.95 0-1.1%) and there were not significant differences in bleeding in the two groups.     

Mutations in NSCLC and their link with lung cancer-associated thrombosis: A case-control study

Introduction

The association of venous thromboembolic events (VTE) and lung cancer is highly prevalent. Additionally, the occurrence of a VTE with cancer has been associated with a worse prognosis and a poor quality of life. Underlying cancer biological features such as tumour mutations may contribute to VTE risk and cancer prognosis. Since preclinical data suggest a link between thrombosis and KRAS mutations in tumours, we aimed to validate this association in a patient registry cohort. Methods: A retrospective case control study was performed using the CHUM NSCLC registry. Cases had VTE occurring 6 months previous to or after a diagnosis of NSCLC. Diagnosis of VTE (venous thrombosis, pulmonary embolism, and migratory superficial thrombophlebitis) was confirmed by a review of the imaging reports. Controls were patients with NSCLC without thrombosis matched for age and stage (I-IIIA/IIIB-IV). Exclusion criteria included insufficient tissue for KRAS/EGFR mutation analysis or insufficient clinical information.

Results

Between Jan 2000 and Dec 2009 a total of 57 cases with VTE and 102 controls without VTE were included. The OR for thrombosis in KRAS and EGFR mutated NSCLC patients are respectively 2.67 (1.12-6.42; p = 0.014) and 0.99 (0.27-3.48; p = 0.99).

Conclusions

KRAS mutation is associated with an increased risk of VTE in this NSCLC cohort. These findings are consistent with preclinical studies. Prospective data on VTE rates from clinical trials with molecularly defined NSCLC are needed to confirm these findings.     

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.     

Venous thromboembolism during pregnancy or postpartum: findings from the RIETE Registry

Venous thromboembolism (VTE) occurs infrequently during pregnancy, and issues concerning its natural history, prevention and therapy remain unresolved. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic acute VTE. In this analysis, we compared the clinical characteristics and outcome for all enrolled pregnant and postpartum women with acute VTE, and all non-pregnant women in the same age range. Up to May 2005, 11,630 patients were enrolled in RIETE, of whom 848 (7.3%) were women aged <47 years. Of them, 72 (8.5%) were pregnant, 64 (7.5%) postpartum. Pregnant women presented less often with symptomatic pulmonary embolism (11%) than non-pregnant women (39%). VTE developed during the first trimester in 29 (40%) pregnant patients; in the second in 13; in the third in 30. Thrombophilia tests were more often positive in women who had VTE during the first trimester (odds ratio [OR]: 4.4; 95% CI: 0.9-2.4; p=0.037). Most patients in all three groups were initially treated with low-molecular-weight heparin (LMWH). As for long-term therapy, 75% of pregnant women received LMWH until delivery. There were no maternal deaths, and no pregnant patient had recurrence or bled before delivery. However, after delivery one patient (1.4%) developed recurrent thrombosis, four (5.6%) had major bleeding. In conclusion, VTE developed during the first trimester in 40% of the pregnant women, thus suggesting that thromboprophylaxis, when indicated during pregnancy, should start in the first trimester. No patient showed recurrence or bled before delivery, but after delivery the risk of bleeding exceeded the risk of recurrences.     

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.     

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.