Individual Venous Thromboembolism Risk Research Articles

Serum albumin, genetic susceptibility, and risk of venous thromboembolism

BackgroundPrevious research on the association between serum albumin (ALB) and venous thromboembolism (VTE) has produced inconclusive results. The polygenic risk score is constructed from a set of independent risk variants associated with a disorder, enabling the identification of a larger fraction of the population at comparable or greater disease risk. It is still unknown whether ALB and genetic factors jointly contribute to the incidence of VTE. ObjectivesThe present study aimed to explore ALB, genetic susceptibility, and the risk of VTE. MethodsThe present investigation was an analysis of prospectively collected data from UK Biobank, a population-based, longitudinal cohort. Cox proportional models were used to calculate hazard ratios and 95% CIs for VTE. The Kaplan–Meier curve was utilized to visualize the cumulative risk of VTE according to different serum ALB levels, and the restricted cubic spline model was leveraged to explore the exposure–response relationship among ALB levels and VTE risk. ResultsDuring median follow-up of 13.5 years, 11,502 cases with VTE were diagnosed among 417,113 participants in the UK Biobank. The lower ALB levels were associated with a higher risk for VTE. Individuals with both a high genetic risk and lowest ALB level had the highest risk of VTE (hazard ratio, 3.89; 95% CI, 3.41-4.43), compared with those with low genetic risk and highest ALB level. The positive joint effects of low ALB and polygenic risk score increased the risk of VTE in individuals with high genetic risk. This study excluded non-European patients and primarily focused on the European population, which may limit the generalizability of the findings. ConclusionLow serum ALB levels were linked to an increased risk of VTE, which was in accordance with a linear dose–response relationship. There was a positive additive effect of ALB and genetic susceptibility on the risk of VTE. ALB could serve as a biomarker for predicting the risk of VTE.

Establishing Expectancy Values for Fibrin Monomer in Uncomplicated Pregnancy.

Background During pregnancy, a physiological increase of molecular activation markers (MAM) of hemostasis such as prothrombin fragments 1 + 2, thrombin-antithrombin complex, and D-dimers (DD) occurs. Therefore, monitoring MAM levels during pregnancy to evaluate the risk of venous thromboembolism (VTE) may be unreliable; nevertheless, DD analysis in pregnancy is widely performed. In contrast to DD, fibrin monomer (FM) levels have been reported to remain stable during pregnancy. Objectives The main aim of this study was to define the expected range for FM levels in pregnant outpatients. In addition, we examined the impact of the individual VTE risk, as calculated by the pregnancy risk score of the Royal College of Obstetricians and Gynaecologists (RCOG), as well as that of antithrombotic treatment on FM levels. Methods A total of 342 pregnant women seen at our hemostasis unit were included throughout 350 pregnancies in 899 samples. Results Low-risk thrombophilia, but not the RCOG score itself, was found to influence all MAM levels, whereas antithrombotic treatment had only an impact on DD. For FM, a reference range could be calculated irrespective of the pregnancy term, in contrast to other MAMs, which fluctuated throughout pregnancy. Conclusions Our findings suggest a stronger impact of inherited thrombophilia on hemostasis activity during pregnancy as compared with acquired or other predisposing thrombophilic risk factors. FM levels showed a marginal increase during pregnancy in contrast to other MAM and remain a potential candidate to improve the laboratory assessment of VTE risk during pregnancy. Further prospective studies in pregnant patients with suspicion of VTE are needed.

Use of hormones and risk of venous thromboembolism.

•The risk of venous thromboembolism (VTE) is not increased in women using long-acting reversible contraceptive methods (LARCs) with progestogens. •Oral contraceptives with levonorgestrel or norgestimate confer half the risk of VTE compared to oral contraceptives containing desogestrel, gestodene or drospirenone. •Progestogen-only pills do not confer an increased risk of VTE. •Women using transdermal contraceptive patches and combined oral contraceptives (COCs) are at an approximately eight times greater risk of VTE than non-users of hormonal contraceptives (HCs), corresponding to 9.7 events per 10,000 women/years. •Vaginal rings increase the risk of VTE by 6.5 times compared to not using HC, corresponding to 7.8 events per 10,000 women/years. •Several studies have demonstrated an increased risk of VTE in transgender individuals receiving hormone therapy (HT). •Hormone therapy during menopause increases the risk of VTE by approximately two times, and this risk is increased by obesity, thrombophilia, age over 60 years, surgery and immobilization. •The route of estrogen administration, the dosage and type of progestogen associated with estrogen may affect the risk of VTE in the climacteric. •Combined estrogen-progesterone therapy increases the risk of VTE compared to estrogen monotherapy. •Postmenopausal HT increases the risk of thrombosis at atypical sites.

PB1052 Evaluating the Individual Risk of Venous Thrombo-Embolism in Patients with Liver Cirrhosis: Usefulness of in vivo and ex vivo Thrombin Generation Parameters

PB1052 Evaluating the Individual Risk of Venous Thrombo-Embolism in Patients with Liver Cirrhosis: Usefulness of in vivo and ex vivo Thrombin Generation Parameters

Complement factors B, D, C3bBbP and risk of future venous thromboembolism.

The complement system appears to be involved in the pathogenesis of venous thromboembolism (VTE). We investigated the association of complement factors (CF) B, D, and the alternative pathway convertase, C3bBbP, measured at inclusion, with the risk of future VTE in a nested case-control study; 380 VTE patients and 804 age- and sex-matched controls derived from the Tromsø study. Odds ratios (ORs) with 95% confidence intervals (95% CI) for VTE across tertiles of CF concentrations were estimated using logistic regression. There was no association between CFB or CFD and risk of future VTE. Higher levels of C3bBbP gave an increased risk of provoked VTE; subjects in Q4 had a 1.68-fold higher OR compared with Q1 in the age-, sex- and BMI-adjusted model (OR 1.68; 95% CI 1.08-2.64). There was no increased risk of future VTE in individuals with higher levels of complement factors B or D of the alternative pathway. Increased levels of the alternative pathway activation product, C3bBbP, showed an association with future risk of provoked VTE.

Biomarkers in pediatric venous thromboembolism: a systematic review of the literature

BackgroundAccurate prediction of the individual risk of venous thromboembolism (VTE) remains suboptimal in children, and biomarkers are currently not used to stratify the risk of VTE in children. ObjectivesThis study aimed to assess which biological or radiological biomarkers may predict VTE or VTE complications in children. Patients/MethodsA literature search was performed for peer-reviewed publications (1990-2022). We included studies addressing the use of biomarkers for patients aged 29 days to 18 years to predict VTE or its complications, including but not limited to TE-related death, VTE recurrence, or postthrombotic syndrome. Given the heterogeneity of the study designs, populations, and outcomes, no quantitative data synthesis was performed. ResultsForty studies were included, totaling 10,987 participants (median age: 4.7 years). Reports were often lacking critical methodological data, including blood collection method (68% of studies) and timepoints, laboratory testing technique (41%), or primary outcome definition (20%). Forty-six individual biomarkers were assessed for VTE prediction (32 studies, 9525 participants), including d-dimers, fibrinogen, platelet count, white blood cell count, and factor VIII. Albumin, C-reactive protein, d-dimers, factor VIII, and thrombin-antithrombin levels showed promising results for VTE prediction. In 9 studies (1606 participants), no biomarker was consistently predictive of postthrombotic syndrome, VTE persistence, or VTE recurrence in children. ConclusionsSeveral candidate biomarkers were promising in the prediction of VTE in children. Still, discrepancies between different studies and the high risk of bias from the current literature prevent their widespread use in the clinical setting. Further prospective research in various pediatric subpopulations is required.

Achieving Therapeutic Anti-Xa Levels Using Rivaroxaban for Venous Thromboembolism in a Morbidly Obese Patient with a BMI >70

Background: Anticoagulation (AC) is the cornerstone of treatment for venous thromboembolism (VTE). Direct oral anticoagulants (DOACs) have become the standard of care during the acute and extended phases of therapy for VTE, mostly due to their ease of use, efficacy, and safety profiles. There is a 9.2% prevalence of severe obesity (BMI>40) in Americans as of 2017-2020 with a 6.2-fold increased risk of VTE in obese individuals. The 2021 International Society on Thrombosis and Haemostasis (ISTH) guidelines recommend using standard dosages of DOACs in patients with a BMI >40 kg/m2 or weight >120 kg. Despite these recommendations, their use in severely obese individuals at extremes of weight like our patient with a BMI > 70 kg/m2 remains uncertain. Case Presentation Herein, we present a 38-year-old morbidly obese female with no significant past medical history who presented with an acute worsening of dyspnea on exertion saturating 60% on room air. The diagnosis of intermediate-high risk pulmonary embolism (PE) was made based on computed tomographic angiography (CTA) with right ventricular strain and elevated cardiac biomarkers. A concomitant proximal DVT from the left common femoral to the distal peroneal vein was also noted. The patient's weight was 243kg with a calculated BMI of 72.3 kg/m2. After the patient had received parenteral anticoagulation with heparin for 4 days, it was decided to switch to Rivaroxaban 15mg BID for 21 days followed by 20 mg daily. With a history of irregular menses, the patient developed heavy menstrual bleeding (HMB) following the initiation of rivaroxaban. Her hemoglobin remained stable with no blood transfusion requirements. However, this led to the decision to switch to rivaroxaban 20 mg PO daily earlier than planned due to a lack of improvement in menstrual bleeding which was considered to be clinically relevant non-major bleeding (CRNMB). Despite this switch, there was no effect on efficacy and the patient did not develop any signs or symptoms of VTE recurrence during her prolonged hospital stay with a significant improvement in her oxygenation levels and VTE symptomatology. In our patient, we demonstrated the use of rivaroxaban in a morbidly obese individual with a BMI>70 by achieving therapeutic anti-Xa levels. Figure 1 shows the therapeutic peak and trough anti-Xa levels throughout the patient's hospitalization. The highest Anti Xa level of 314 mcg/mL was reported on day 19 correlating with the patient's menorrhagia, which self-limited with the transition from rivaroxaban 15 mg twice daily to 20 mg daily. Discussion: Two pivotal clinical trials, the EINSTEIN-DVT/PE trials, where 14% of patients in both arms weighed >100 kg, showed that patients on rivaroxaban (15 mg BID for 3 weeks, followed by 20 mg once daily) vs those on enoxaparin followed by a vitamin K antagonist, had no significant difference in recurrence rates of VTE and bleeding rates [Moore KT, et Al. Influences of Obesity, Am J Med 2017]. A recent post-hoc analysis of the EINSTEIN DVT/PE trials also portrayed no correlation between weight/BMI and risk of recurrent VTE or bleeding in those who received rivaroxaban. Our case illustrates the attainment of therapeutic anti-Xa levels with no recurrent VTE in our morbidly obese patient. Despite her heavy menstrual bleeding, the bleeding was controlled once the switch to rivaroxaban 20mg daily was completed. Another study in which its heaviest participant at 172 kg, showed compelling evidence that morbid obesity has minimal influence on the safety and efficacy of rivaroxaban [Speed V, et al. Fixed dose rivaroxaban. JTH 2020]. This remains true for our patient at 243 kg. Conclusion: Our case demonstrates that standard doses of rivaroxaban for the treatment of DVT/PE in individuals with morbid obesity with BMI>70 kg/m2 can be effective, and safer for the initial phase of treatment for VTE and in prevention of VTE recurrence. It also portrays that increased dosages attempting to account for high bodyweight/fat can potentially result in major bleeding events. Despite the 2021 ISTH guidelines, further prospective studies and randomized controlled trials are warranted, to assess the safety and efficacy of DOACs in VTE, particularly in such challenging clinical scenarios like morbid obesity. Alongside clinical assessment, additional studies will be essential to evaluate the need for universal and external validation of anti-Xa levels in patients taking DOACs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Biomarkers to predict risk of venous thromboembolism in patients with rheumatoid arthritis receiving tofacitinib or tumour necrosis factor inhibitors

ObjectiveIn the ORAL (Oral Rheumatoid Arthritis triaL) Surveillance study of patients with rheumatoid arthritis aged ≥50 years with ≥1 additional cardiovascular risk factor, incidence of pulmonary embolism was higher with...

Anterior cruciate ligament tear increases the risk of venous thromboembolism: a population-based cohort study.

Previous studies highlighted an increased risk of venous thromboembolism (VTE) among patients with anterior cruciate ligament reconstruction (ACLR); however, the risk for those with ACL tear but without undergoing ACLR has not been reported yet. The aim of this study was to evaluate the risk of VTE among ACL tear individuals with or without ACLR derived from the general population. A cohort study was conducted using data from the IQVIA Medical Research Database of the United Kingdom. Up to five non-ACL tear individuals (n = 22,235) were matched to each case of ACL tear (n = 4474) by age, sex, body mass index and entry-time. The relation of ACL tear to VTE [pulmonary embolism (PE) and deep vein thrombosis (DVT)] was examined using a multivariable Cox proportional hazard model. A sub-cohort analysis, in which the ACL tear individuals were stratified into those with ACLR and those without ACLR, was also conducted. VTE developed in 13 individuals with ACL tear and nine individuals without ACL tear (incidence rates: 3.1 vs. 0.4/1000 person-years), with multivariable-adjusted hazard ratio (HR) being 6.59 (95% CI 2.28-19.08) in 1-year follow-up. For ACL tear individuals with ACLR, the HR was 11.44 (95% CI 2.71-48.28), and for those without ACLR, the HR was 6.02 (95% CI 1.44-24.25), compared with individuals without ACL tear. This large-sample population-based cohort study provides the first evidence on an increased risk of VTE in ACL tear individuals regardless of subsequent ACLR, which supports the necessity for monitoring venous-thromboembolic complications in the target population, including those without ACLR. III.

OP0269 BIOMARKERS TO PREDICT RISK OF VENOUS THROMBOEMBOLISM IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING TOFACITINIB OR TUMOUR NECROSIS FACTOR INHIBITORS

BackgroundIn the ORAL Surveillance study of patients (pts) aged ≥50 yrs with moderate to severe rheumatoid arthritis (RA) and ≥1 additional cardiovascular risk factor (NCT02092467), the incidence of pulmonary embolism was higher with tofacitinib than with tumour necrosis factor inhibitors (TNFi).1ObjectivesTo explore whether biomarkers explained the associations of tofacitinib vs TNFi with venous thromboembolism (VTE) in ORAL Surveillance.MethodsORAL Surveillance was a prospective, open-label, event-driven, noninferiority, post-authorisation safety study. Pts were randomised 1:1:1 to receive tofacitinib 5 or 10 mg twice daily or a TNFi (adalimumab 40 mg every 2 weeks or etanercept 50 mg once weekly). For this exploratory post hoc analysis, 294 soluble, proteomic, genetic and antibody biomarkers were assessed (of which 79 have a known role in inflammation, coagulation, vascular biology and/or Janus kinase signalling). Biomarkers were quantified in serum collected at baseline (BL) and Month (M)12 in VTE cases and 4:1 matched controls. D-dimer was analysed with a larger control group (all eligible pts without VTE) and final adjudicated data from BL, M12 and study end.ResultsOf the 4362 randomised and treated pts, D-dimer was quantified in 3732 pts (54 with VTE; 3678 without) and the remaining biomarkers were analysed in 285 pts (57 VTE cases; 228 matched controls). BL characteristics were generally similar in those with or without VTE and between treatment groups. At BL, D-dimer levels were ≥2×upper limit of normal for ~50% of controls and 67% of VTE cases. Mean D-dimer levels decreased from BL to M12 in controls across treatment groups (Figure 1). Key findings from the biomarker analyses are shown in the Table 1. No biomarker showed a clear mechanistic association with the increased risk of VTE for tofacitinib vs TNFi, or demonstrated adequate performance for prognostic use in pts with RA.Table 1.Summary of results from biomarker analysesBiomarkerKey resultsTier 1C-reactive protein•No association with VTE in any treatment arm at BL or M12D-dimer Thrombopoietin•Higher M12 levels were prospectively associated with greater risk of subsequent VTE with tofacitinib 10 mg BID ◦ For D-dimer, the same effect was observed with tofacitinib 5 mg BID •Treatment specificity of effects could not be establishedTier 2Factor VIII Thrombin–antithrombin complex Tissue factor pathway inhibitor Plasminogen activator inhibitor-1 Protein C Antithrombin Apolipoprotein C-III Leptin•No clinically meaningful differences across treatment armsTiers 3 & 4Exploratory proteomic assays (276 markers from multiplex panels)•Two biomarkers with no known relationship to VTE (angiogenin and TNFSF13B) showed significant associations with pulmonary embolism in the tofacitinib 10 mg BID arm ◦ Treatment specificity of effects could not be established for either analyteGenetic biomarkersFactor V Leiden R506Q, prothrombin G20210A and JAK2 V617F mutations•Factor V Leiden and prothrombin risk alleles, individually or combined, were associated with increased incidence of VTE but did not explain excess events with tofacitinib •No VTE cases or matched controls had the JAK2 mutationAntibody biomarkersACA IgG and IgM, anti-β2GP1 IgG and IgM•No statistical differences were observed between treatment arms or between VTE cases and matched controlsACA, anticardiolipin antibody; β2GP1, beta-2-glycoprotein 1; IgG, immunoglobulin G; IgM, immunoglobulin M; JAK2, Janus kinase 2; TNFSF13B, tumour necrosis factor ligand superfamily member 13BConclusionThis post hoc exploratory analysis did not identify biomarkers at BL or M12 that explain the increased VTE risk for tofacitinib vs TNFi. Notably, ORAL Surveillance was neither designed nor powered to compare the risk of VTE across treatments or to identify biomarkers with a mechanistic relationship to VTE. Individual VTE risk should be considered when making decisions about initiation or maintenance of tofacitinib treatment.

Elevated plasma D-dimer levels are associated with risk of future incident venous thromboembolism

BackgroundD-dimer, a global biomarker for activation of the coagulation and fibrinolysis systems, is useful in assessing individual risk of venous thromboembolism (VTE) recurrence. However, there is limited information on the association between D-dimer and risk of a first lifetime VTE event. ObjectivesTo investigate the association between plasma D-dimer levels and risk of future incident VTE. MethodsA population-based nested case-control study, comprising 414 VTE patients and 843 randomly selected age- and sex-matched controls, was derived from the Tromsø Study (1994–2007). D-dimer was measured in plasma samples collected at cohort baseline (1994–95). Odds ratios (ORs) for VTE with 95% confidence intervals (CIs) were estimated according to quartile cut-offs of D-dimer levels determined in controls. ResultsThe risk of VTE increased across quartiles of D-dimer levels (Ptrend = 0.014) in the age- and sex-adjusted model. Participants with plasma D-dimer levels in the highest quartile (≥152 ng/mL) had an OR for VTE of 1.65 (95% CI 1.14–2.40) compared with those in the lowest quartile (<94 ng/mL). The ORs were marginally attenuated after additional adjustment for body mass index (BMI) (OR 1.51, 95% CI 1.04–2.20) and C-reactive protein (CRP) (OR 1.34, 95% CI 0.90–1.98). Similar results were obtained for VTE subgroups, i.e. deep vein thrombosis, pulmonary embolism, and provoked/unprovoked events. ConclusionOur results indicate that elevated plasma D-dimer levels are associated with increased risk of incident VTE. However, the attenuation of risk estimates upon additional adjustment for BMI and CRP suggests that D-dimer partly reflects underlying conditions associated with obesity and an inflammatory state.

Severe alpha‐1‐antitrypsin deficiency increases the risk of venous thromboembolism

BackgroundSevere alpha‐1‐antitrypsin deficiency (AATD), phenotype PiZZ, is associated with increased risk of liver disease and chronic obstructive pulmonary disease (COPD), but the risk of venous thromboembolism (VTE) is unknown. Our aim was to evaluate the risk of VTE in individuals with severe AATD compared with control subjects from the general population. MethodsIndividuals with severe AATD (n = 1577) were recruited from the Swedish national AATD register. Control subjects (n = 5969) were selected from the OLIN (Obstructive Lung Disease in Northern Sweden) studies, that include a random general population sample. Longitudinal data on VTE and diagnoses were obtained from the Swedish National Patient Registry. Associations were analyzed using multivariable Cox regression. ResultsAt inclusion, 46% of the AATD individuals and 53% of the controls were never‐smokers. COPD was present in 46% of the AATD individuals compared with 4% of the controls. During a median follow‐up of 18 years, 116 (7%) of the AATD individuals and 89 (1%) of the control subjects developed VTE, unadjusted hazard ratio 6.5 (95% confidence interval 4.9–8.6). Risk factors for incident VTE were male gender, age, COPD, cancer, and liver disease. Adjusting for these factors, the AATD individuals had a significantly higher risk of incident VTE, adjusted hazard ratio 4.2 (95% confidence interval 2.9–6.2) as compared with the controls. ConclusionSubjects with severe AATD have considerably increased risk of developing VTE compared with the general population, even after accounting for risk factors. This calls for optimized risk factor management and clinical follow‐up of this patient group.

Hormonal contraception and venous thromboembolism

The use of combined hormonal contraceptives (CHC) is a well-established risk factor for venous thromboembolism (VTE). The VTE risk depends on the specific combination of oestrogen and gestagen components. Progestin-only contraceptives with the exception of depot medroxyprogesterone acetate are not associated with a significant VTE risk and can therefore be offered to women with known thrombophilia or a prior VTE. The recent German S3 guideline "Contraception" advises to carefully assess individual VTE risk factors before prescribing CHC. According to recent data there is no evidence suggesting that VTE risk is increased during oral anticoagulation. To reduce the risk of vaginal bleeding complication and the risk of unplanned pregnancy, the use of CHC can be continued under anticoagulation treatment provided that the patient is switched to an oestrogen-free contraception no later than six weeks before the end of anticoagulation. The risk of recurrence is low in women with hormone-associated VTE. Anticoagulation is therefore in general discontinued after 3-6 months. Thromboprophylaxis with low molecular heparin is recommended for women with prior hormone-associated VTE during pregnancy and the postpartum period.

Thrombosis and myeloma: it is time to get the elephant out of the room.

Thrombosis and myeloma: it is time to get the elephant out of the room.

Venous Thromboembolism Prediction in Postoperative Urogynecology Patients: The Utility of Risk Assessment Tools.

The aim of the study was to evaluate the utility of risk assessment tools (Rogers and Caprini Score models) in predicting venous thromboembolism (VTE) in a urogynecology patient population. All surgical patients underwent a procedure in the operating room with 1 of 7 female pelvic medicine and reconstructive surgery.Attendings from January 1 to December 31, 2015, were investigated. Rogers and Caprini Scores were calculated for each patient as well as the occurrence of any VTE in the 30 days after surgery. Patients were then grouped into risk categories based on the American College of Chest Physicians guidelines. A total of 783 patients were identified and included in this study. The average patient age was 58 years (range = 18-89 years). The average operative time was 109 minutes (range = 4-491 minutes). Most patients obtained a Rogers Score of 5 (32%) and a Caprini Score of 4 (34%). Based on Caprini scoring, the American College of Chest Physicians category distribution was as follows: 10% low risk, 61% moderate risk, and 29% high risk. Based on Rogers scoring, this distribution was as follows: 96.8% very low risk, 3.1% low risk, and 0.1% moderate risk. Two VTE events were identified in the cohort. Overall, the incidence of VTE was 0.26%. The standard VTE risk assessment tools grade urogynecology patients very differently. Although the Caprini Scale seems to appropriately differentiate individual patient VTE risk, the Rogers Scale does not adequately stratify this risk, thus potentially limiting its use within this population.

Post-discharge venous thromboembolism after pancreatectomy for malignancy: Predicting risk based on preoperative, intraoperative, and postoperative factors.

Extended chemoprophylaxis is recommended for high-risk patients following pancreatectomy for malignancy. However, quantifying risk remains difficult. We sought to (a) identify factors associated with post-discharge venous thromboembolism (VTE) following pancreatectomy for malignancy and (b) develop a post-discharge VTE risk calculator to identify high-risk patients. Patients who underwent pancreatectomy for malignant histology from 2014 to 2018 were identified from the ACS NSQIP pancreatectomy procedure targeted dataset. Preoperative, intraoperative, and postoperative factors known at hospital discharge were evaluated for association with post-discharge VTE via multivariable logistic regression. A post-discharge VTE risk calculator was developed and validated. Of 19 340 analyzed patients, 280 (1.5%) developed post-discharge VTE. Post-discharge VTE was associated with increasing body mass index (BMI; eg, morbidly obese BMI odds ratio [OR]: 1.99 [95% confidence interval {CI}: 1.30-3.02] vs normal BMI), procedure type (distal pancreatectomy OR: 1.47 [95% CI: 1.02-2.12] vs pancreaticoduodenectomy), pancreatic fistula (OR: 1.59 [95% CI: 1.19-2.13]) and delayed gastric emptying (OR: 1.81 [95% CI: 1.29-2.52]). Patients' predicted probability of post-discharge VTE ranged from 0.7% to 9.0%. Twenty iterations of 10-fold cross-validation demonstrated internal validity. Preoperative, intraoperative, and postoperative factors were associated with post-discharge VTE following pancreatectomy for malignancy. This post-discharge VTE risk calculator allows for quantification of individual post-discharge VTE risk, which ranged from 0.7% to 9.0%.

Management of Venous Thromboembolism in Patients with Hereditary Antithrombin Deficiency and Pregnancy: Case Report and Review of the Literature

Background. Hereditary antithrombin deficiency is a thrombogenic disorder associated with a 50–90% lifetime risk of venous thromboembolism (VTE), which is increased during pregnancy and the puerperium in these patients. We present a case of a woman with antithrombin (AT) deficiency who presented with a VTE despite therapeutic low molecular weight heparin (LMWH). Though the pregnancy was deemed unviable, further maternal complications were mitigated through the combined use of therapeutic anticoagulation and plasma-derived antithrombin concentrate infusions to normalize her functional antithrombin levels. Methods. A review of the literature was conducted for studies on prophylaxis and management of VTE in pregnant patients with hereditary AT deficiency. The search involved a number of electronic databases, using combinations of keywords as described in the text. Only English language studies between 1946 and 2015 were included. Conclusion. Antithrombin concentrate is indicated in pregnant women with hereditary AT deficiency who develop VTE despite being on therapeutic dose anticoagulation. Expert opinion suggests AT concentrate should be used concomitantly with therapeutic dose anticoagulation. However, further high-quality studies on the dose and duration of treatment in the postpartum period are required. Use of AT concentrate for prophylaxis is controversial and should be based on individual VTE risk stratification.

Hypercoaguable Work up : Are We Overtesting ?

BACKGROUNDHypercoaguable states are defined as a group of inherited or acquired conditions associated with predisposition to venous thromboembolism(VTE) , arterial thrombosis or both . Of the inherited thrombophilias , Factor V Leiden mutation(FVL) is the most common, with Prothrombin mutation G20210(PT) being the second most common cause, both being inherited as autosomal dominant.FVL is a single point mutation in the gene that codes for coagulation factor V. It renders factor V resistant to inactivation by activated protein C. Heterozygosity for Factor V Leiden occurs in 3-8% of the general US and European populations, homozygosity being very rare. Approximately 10% of FVL heterozygotes develop VTE over their lifetime. The relative risk for VTE is increased three to six fold in Factor V Leiden heterozygotes. PT is a single point mutation (G to A substitution at nucleotide 20210) in the prothrombin gene. This mutation appears to result in elevated concentration of plasma prothrombin. The overall prevalence is approximately 2%. Risk of VTE in individuals who are heterozygous for PT has been estimated to be increased approximately three- to fourfold. However , the relative risk of having one of these mutations in patients presenting with a first time VTE is 15-20% and 6% for FVL and PT respectively .Although these mutations increases the chances of VTE, its association with arterial thrombosis and obstetric complications( recurrent miscarriages , still birth, Intraueterine fetal demise) are not clear. Therefore testing for these mutations is appropriate only in patients with idiopathic VTE, younger patients and or those with family history , recurrent thrombosis , thrombosis in unusual vascular bed. In our institution ,there was a concern that appropriate selections of patients to test for these mutations was not occurring and the cost of inappropriate testing may be adding to the healthcare costs. We performed a retrospective review of indications for thrombophilia testing and its costs over a period of one year at our tertiary medical center. METHODSAll patients who had testing for FVL and PT from June 2015-June 2016 were identified by screening ordered tests done in the special coagulation laboratory. Inpatients and outpatients were included .The clinical data reviewed included age, sex and indication for the tests ordered.Overall cost was calculated for each group. RESULTSWe evaluated 144 patients . The mean age of patients was 51 years (range :7 Weeks - 88 years)Males constituted 51%(74/144), females were 49%(70/144) of the cohort.Both FVL and PT tests were ordered on all the patients.Of 144 patients , only 3 patients tested positive and were heterozygous for FVL and, 1 positive patient was heterozygous for PT.The cost of the test for FVL was $348 and for PT $267 in a standard laboratory. The following table lists the common indications for the tests ordered*Other included Lung transplant workup 10%, heart transplant work up9% , VAD thrombosis 1%, MI (0.9%) miscarriage 5% and other -10% The number of tests that did not meet the standard criteria for testing were103Only 28 % of testing was done for an appropriate indication (Unprovoked VTE , Recurrent VTE , VTE at an unusal site) Cost associated of unnecessary testing$63,345 CONCLUSIONTesting for inherited risk factors for VTE when not indicated by standard criteria leads to excess costs for patients and healthcare systems .Education of healthcare providers may limit unnecessary testing and ultimately reduce healthcare costs . [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Variation in Definitions of Immobility in Pharmacological Thromboprophylaxis Clinical Trials in Medical Inpatients: A Systematic Review.

Although immobility is a common risk factor for venous thromboembolism (VTE) in medical inpatients, lack of a consistent definition of this term may limit accurate assessment of VTE risk for thromboprophylaxis. To examine various definitions of immobility used in recent pharmacological thromboprophylaxis clinical trials. PubMed and relevant references from articles/reviews from 2008 to 2016 were searched. Randomized controlled trials (RCTs) and other clinical studies involving adult hospitalized medical patients in acute care hospital settings that used the term immobility were selected. Two investigators independently abstracted data in duplicate, and accuracy was checked by a third investigator. Twenty-one clinical studies were included. There was heterogeneity among individual VTE risk factors, with respect to the definition of immobility in medical inpatients in these trials. Thirteen studies utilized objective criteria to define "immobility" including duration (12 studies) and distance or time walked (6 studies). In contrast, 7 studies focused principally on subjective definitions (ie, describing the nature of immobility rather than specifying its quantitative measurement). Three RCTs vaguely defined the level of patient's immobility after hospitalization. Despite the well-known effectiveness of pharmacological thromboprophylaxis for the prevention of VTE in acutely ill medical patients, there is no current consensus on how to define immobility. The heterogeneous nature of definitions of immobility has led to uncertainty about the importance of immobility in VTE risk assessment models. Although clinical studies have incorporated varying definitions of immobility into their inclusion criteria, immobility as a specific VTE risk factor has not been clearly defined.

Modulating thrombotic diathesis in hereditary thrombophilia and antiphospholipid antibody syndrome: a role for circulating microparticles?

Over the past decades, there have been great advances in the understanding of the pathogenesis of venous thromboembolism (VTE) in patients with inherited and acquired thrombophilia [mainly antiphospholipid antibody syndrome (APS)]. However, a number of questions remain unanswered. Prognostic markers capable of estimating the individual VTE risk would be of great use. Microparticles (MPs) are sub-micron membrane vesicles constitutively released from the surface of cells after cellular activation and apoptosis. The effects of MPs on thrombogenesis include the exposure of phopshatidylserine and the expression of tissue factor and MPs have been described in clinical studies as possible diagnostic and prognostic biomarkers for VTE. This review will provide a novel perspective on the current knowledge and research trends on the possible role of MPs in hereditary thrombophilia and APS. Basically, the published data show that circulating MPs may contribute to the development of VTE in thrombophilic carriers, both in mild and severe states. Moreover, the presence of endothelial-MPs and platelet-MPs has been described in antiphospholipid syndrome and seems to be directly linked to antiphospholipid antibodies and not to other underlying autoimmune disorders or the thrombotic event itself. In conclusion, circulating MPs may constitute an epiphenomenon of thrombophilia itself and could be up-regulated in acute particular conditions, promoting a global prothrombotic state up to the threshold of the clinical relevant thrombotic event.