Risk Of Venous Thromboembolic Disease Research Articles

A randomised, two-arm (1:1 ratio), double blind, placebo controlled phase III trial to assess the efficacy, safety, cost and cost-effectiveness of Rituximab in treating de novo or relapsing NS in patients with MCD/FSGS (TURING)

BackgroundMinimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are a spectrum of disease causing the nephrotic syndrome (NS), characterised by proteinuria with debilitating oedema, as well as a high risk of venous thromboembolic disease and infection. Untreated, 50–60% patients with FSGS progress to end stage kidney disease after 5 years. These diseases respond to immunosuppression with high dose glucocorticoids, but 75% will relapse as the glucocorticoids are withdrawn, leading to significant morbidity associated with prolonged use. In children, the B cell depleting monoclonal antibody rituximab reduces relapse risk, but this drug has not been tested in randomised controlled trial in adults.Methods130–150 adults with new or relapsing MCD/FSGS, from UK Renal Units, are being randomised to receive either rituximab (two 1 g infusions two weeks apart) or placebo. Partipicipants are recruited when they present with nephrosis, and all are treated with glucocorticoids as per KDIGO guidelines. Once in remission, prednisolone is withdrawn according to a pre-specified regimen. If in remission at 6 months, participants receive a further dose of trial drug. If they relapse, they are unblinded, and if they have received placebo, they are offered open label rituximab with protocolised prednisolone as in the main phase of the trial. The primary end point is time from remission to relapse. A number of secondary endpoints will be assessed including the effect of rituximab on: (1) NHS and societal resource use and hence cost: (2) safety: (3) other measures of efficacy, such as achievement of partial and complete remission of NS and the preservation of renal function: (4) health status of participant.Trial RegistrationTURING received ethical approval on 14 Jun 2019 - REC reference: 19/LO/0738. It is registered on EudraCT, with ID number: 2018-004611-50, with a start date of 2019-06-14.

An analysis of risk factors for venous thromboembolism in primary versus revision total joint arthroplasty

BackgroundOne of the most serious complications after primary or revision lower extremity total joint arthroplasty (TJA) is venous thromboembolism disease (VTE). Identifying patients at high risk for VTE allows tailoring of prophylactic anticoagulation regimens to those most vulnerable. This study aimed to identify risk factors for VTE in primary and revision lower extremity TJA. MethodsThe Electronic Medical Record was queried from a single academic institution for all patients who underwent a lower extremity TJA between 2007 and 2020. Demographics, comorbid conditions, perioperative characteristics, and postoperative complications were identified. An Elastic Net Multiple Logistic Regression Model was used to assess 49 covariates and predict those associated with a significant risk of VTE. ResultsWe identified 4900 primary and revision total knee arthroplasty (TKA) and total hip arthroplasty (THA) patients. There was no significant difference between primary and revision THA. Primary TKA had a higher rate of VTE than revision TKA. Significant risk factors identified for VTE in THA patients include histories of deep vein thrombosis (DVT), pulmonary embolism (PE), metastatic tumors, hemiplegia, and Hispanic ethnicity. Risk factors for VTE in TKA patients include histories of DVT, PE, metastatic tumors, and postoperative warfarin and heparin use. In all patients, age was a significant predictor of VTE risk. ConclusionOur work identifies many risk factors for VTE following TJA. While the increased rate of VTE in some populations may represent selection bias, it also highlights the incomplete understanding of the etiology and prevention of this complication in the joint arthroplasty population and requires further study.

PB1488 Risk of Venous Thromboembolic Disease and Adequacy of Thromboprophylaxis at a Teaching Hospital and Incidence of VTE in the Three Months after Admission

PB1488 Risk of Venous Thromboembolic Disease and Adequacy of Thromboprophylaxis at a Teaching Hospital and Incidence of VTE in the Three Months after Admission

PB1498 Risk of Venous Thromboembolic Disease and Adequacy of Prophylaxis in Hospitalized Cancer Patients in Uruguay

PB1498 Risk of Venous Thromboembolic Disease and Adequacy of Prophylaxis in Hospitalized Cancer Patients in Uruguay

Comparison of Medical and Mental Health Sequelae Following Hospitalization for COVID-19, Influenza, and Sepsis

People who survive hospitalization for COVID-19 are at risk for developing new cardiovascular, neurological, mental health, and inflammatory autoimmune conditions. It is unclear how posthospitalization risks for COVID-19 compare with those for other serious infectious illnesses. To compare risks of incident cardiovascular, neurological, and mental health conditions and rheumatoid arthritis in 1 year following COVID-19 hospitalization against 3 comparator groups: prepandemic hospitalization for influenza and hospitalization for sepsis before and during the COVID-19 pandemic. This population-based cohort study included all adults hospitalized for COVID-19 between April 1, 2020, and October 31, 2021, historical comparator groups of people hospitalized for influenza or sepsis, and a contemporary comparator group of people hospitalized for sepsis in Ontario, Canada. Hospitalization for COVID-19, influenza, or sepsis. New occurrence of 13 prespecified conditions, including cardiovascular, neurological, and mental health conditions and rheumatoid arthritis, within 1 year of hospitalization. Of 379 366 included adults (median [IQR] age, 75 [63-85] years; 54% female), there were 26 499 people who survived hospitalization for COVID-19, 299 989 historical controls (17 516 for influenza and 282 473 for sepsis), and 52 878 contemporary controls hospitalized for sepsis. Hospitalization for COVID-19 was associated with an increased 1-year risk of venous thromboembolic disease compared with influenza (adjusted hazard ratio, 1.77; 95% CI, 1.36-2.31) but with no increased risks of developing selected ischemic and nonischemic cerebrovascular and cardiovascular disorders, neurological disorders, rheumatoid arthritis, or mental health conditions compared with influenza or sepsis cohorts. In this cohort study, apart from an elevated risk of venous thromboembolism within 1 year, the burden of postacute medical and mental health conditions among those who survived hospitalization for COVID-19 was comparable with other acute infectious illnesses. This suggests that many of the postacute consequences of COVID-19 may be related to the severity of infectious illness necessitating hospitalization rather than being direct consequences of infection with SARS-CoV-2.

Do polycystic ovary syndrome and endometriosis increase risk of venous thrombo-embolic disease?

Do polycystic ovary syndrome and endometriosis increase risk of venous thrombo-embolic disease?

Inflammatory Bowel Disease and Pregnancy

Inflammatory Bowel Disease and Pregnancy

Abstract No. 553 Influence of immune checkpoint inhibitor use on the risk of venous thromboembolic disease in cancer patients

Abstract No. 553 Influence of immune checkpoint inhibitor use on the risk of venous thromboembolic disease in cancer patients

PICO Questions and DELPHI Methodology for the Management of Venous Thromboembolism Associated with COVID-19.

Patients with coronavirus disease 2019 (COVID-19) have a higher risk of venous thromboembolic disease (VTE) than patients with other infectious or inflammatory diseases, both as macrothrombosis (pulmonar embolism and deep vein thrombosis) or microthrombosis. However, the use of anticoagulation in this scenario remains controversial. This is a project that used DELPHI methodology to answer PICO questions related to anticoagulation in patients with COVID-19. The objective was to reach a consensus among multidisciplinary VTE experts providing answers to those PICO questions. Seven PICO questions regarding patients with COVID-19 responded with a broad consensus: 1. It is recommended to avoid pharmacological thromboprophylaxis in most COVID-19 patients not requiring hospital admission; 2. In most hospitalized patients for COVID-19 who are receiving oral anticoagulants before admission, it is recommended to replace them by low molecular weight heparin (LMWH) at therapeutic doses; 3. Thromboprophylaxis with LMWH at standard doses is suggested for COVID-19 patients admitted to a conventional hospital ward; 4. Standard-doses thromboprophylaxis with LMWH is recommended for COVID-19 patients requiring admission to Intensive Care Unit; 5. It is recommended not to determine D-Dimer levels routinely in COVID-19 hospitalized patients to select those in whom VTE should be suspected, or as a part of the diagnostic algorithm to rule out or confirm a VTE event; 6. It is recommended to discontinue pharmacological thromboprophylaxis at discharge in most patients hospitalized for COVID-19; 7. It is recommended to withdraw anticoagulant treatment after 3 months in most patients with a VTE event associated with COVID-19. The combination of PICO questions and DELPHI methodology provides a consensus on different recommendations for anticoagulation management in patients with COVID-19.

Venous thromboembolic disease in adults admitted to hospital in a setting with a high burden of HIV and TB.

Background HIV and tuberculosis (TB) independently cause an increased risk for venous thromboembolic disease (VTE): deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Data from high HIV and TB burden settings describing VTE are scarce. The Wells’ DVT and PE scores are widely used but their utility in these settings has not been reported on extensively. Objectives To evaluate new onset VTE, compare clinical characteristics by HIV status, and the presence or absence of TB disease in our setting. We also calculate the Wells’ score for all patients. Methods A prospective cohort of adult in-patients with radiologically confirmed VTE were recruited into the study between September 2015 and May 2016. Demographics, presence of TB, HIV status, duration of treatment, CD4 count, viral load, VTE risk factors, and parameters to calculate the Wells’ score were collected. Results We recruited 100 patients. Most of the patients were HIV-infected (n=59), 39 had TB disease and 32 were HIV/TB co-infected. Most of the patients had DVT only (n=83); 11 had PE, and 6 had both DVT and PE. More than a third of patients on antiretroviral treatment (ART) (43%; n=18/42) were on treatment for <6 months. Half of the patients (51%; n=20/39) were on TB treatment for <1 month. The median (interquartile range (IQR)) DVT and PE Wells’ score in all sub-groups was 3.0 (1.0 - 4.0) and 3.0 (2.5 - 4.5), respectively. Conclusion HIV/TB co-infection appears to confer a risk for VTE, especially early after initiation of ART and/or TB treatment, and therefore requires careful monitoring for VTE and early initiation of thrombo-prophylaxis.

History of COVID-19 infection is not associated with increased D-dimer levels and risk of deep-vein thrombosis in total joint arthroplasty.

IntroductionIn the acute phase of COVID-19, elevated d-dimer levels indicate a hypercoagulable state putting the patients at increased risk for venous thromboembolic disease (VTE). It is unclear, if prior COVID-19 disease increases the risk for VTE after total joint arthroplasty (TJA) and if d-dimer levels can be used to identify patients at risk.Materials and methodsd-Dimer levels of 313 consecutive SARS-CoV-2 IgG-positive and 2,053 -negative patients undergoing TJA between 05/20 and 12/20 were evaluated. d-Dimer levels were divided into three groups: < 200 ng/ml, 200–400 ng/ml, and > 400 ng/ml d-dimer units (DDU). 277 SARS-CoV-2 IgG-positive patients underwent a Doppler ultrasound to rule out deep-vein thrombosis (DVT) 4–6 weeks after TJA.Resultsd-Dimer levels did not differ significantly between SARS-CoV-2 IgG-positive and -negative patients (p value 0.53). Among SARS-CoV-2 IgG-negative patients, 1687 (82.17%) had d-dimer levels < 200 ng/ml, 256 (12.47%) between 200 and 400 ng/ml, and 110 (5.36%) > 400 ng/ml. Of the SARS-CoV-2 IgG-positive patients, 257 (83.71%) had d-dimer levels < 200 ng/ml, 34 (11.07%) between 200 and 400 ng/ml, and 16 (5.21%) > 400 ng/ml. A postoperative DVT was detected in nine patients (2.9%) in the SARS-CoV-2 IgG-positive group and a PE in one patient (0.3%). 7/229 patients with < 200 ng/ml (3.1%), 1/28 patients (3.6%) with 200–400 ng/ml and 1/9 patients (11.1%) with d-dimer levels > 400 ng/ml had a DVT or PE (p = 0.43).ConclusionsThe findings of this investigation suggest there is no difference in d-dimer levels between SARS-CoV-2 IgG-positive and -negative patients undergoing TJA. Although there is a trend for increased VTE rates with increased d-dimer levels, routine d-dimer testing is not recommended based on the current data. SARS-CoV-2 IgG-positive patients have a low risk of VTE in the current study.

Exome Sequencing Studies Identify Mutations in STAB2 As a Genetic Risk for Venous Thromboembolic Disease

Deep vein thrombosis and pulmonary embolism, collectively referred to as venous thromboembolism (VTE), are the third leading cause of cardiovascular death in the United States. Genetic factors account for 50-60% of VTE risk and a recent meta-analysis of genome-wide association studies confirmed that common variants in F5, ABO, F2 and seven other very low effect size loci are associated with VTE. Rare mutations in the anticoagulant genes PROC (protein C), PROS1 (protein S) and SERPINC1 (antithrombin III) have been linked to highly penetrant VTE risk in family studies but no genome-wide study of rare variants has been reported to date.We performed whole exome sequencing (WES) in 373 unrelated individuals of European ancestry with well characterized unprovoked VTE and compared results to a previously genome sequenced control cohort of 5784 unrelated Europeans. We then identified single nucleotide variants, small insertion or deletions that were present at allele frequencies less than 0.005% in ExAC and had equal sequencing coverage between groups. Using a dominant model and a collapsing association analysis, we looked for genes that were more likely to harbor “knockout” (frame shift, nonsense, splice site and damaging missense) mutations in cases versus controls. Strikingly, ranked by p-value, among 17,395 genes tested, the top 4 genes were PROS1 (P= 2.01E-09, odds ratio: 11.8), STAB2 (P=2.70E-7, odds ratio 3.37), PROC (P=3.24E-05, odds ratio 11.0) and SERPINC1 (P=1.10E-04, odds ratio 8.5), Figure. These findings suggest that heterozygous deficiency for the STAB2 encoded protein, stabilin-2, confers VTE susceptibility similar to the previously well described phenotypes of heterozygous protein C, protein S and antithrombin III deficiency.Stabilin-2 is a single transmembrane glycoprotein scavenger receptor expressed on venous endothelium of liver sinusoids and spleen. We detected damaging STAB2 mutations in 29 (7%) VTE cases versus 141 (2%) of controls. Common and uncommon variants in STAB2 have been associated with elevated plasma von Willebrand factor (VWF) and coagulation factor VIII levels, which are known risk factors for VTE. Stabilin-2 is implicated as a clearance receptor for VWF, so that haploinsufficiency of stabilin-2 may increase plasma VWF half-life. To test this hypothesis, we examined 1162 individuals in the Twins UK Study (VTE status unknown) with available whole genome sequencing data and measured their plasma VWF levels by AlphaLISA. VWF levels were adjusted by log transformation and ABO blood type tagging SNPs. We identified 38 individuals (3.2%, all heterozygous) with rare damaging variants in STAB2. VWF levels were significantly higher in individuals (N=30) with rare STAB2 variants compared to those without (N=1016) (Mann-Whitney, P= 0.0046).To further examine stabilin-2 function in vivo, we compared Stab2 deficient mice (Stab2 -/-) to wild type (Stab2 +/+) controls. Stab2 -/- mice had elevated plasma levels of factor VIII:C (118%, p=0.0006), but no differences in VWF (p=0.58). Next, we examined thrombosis in a mouse model where venous blood clotting was induced by inferior vena cava stenosis. Thrombi were weighed and longitudinal sections were analyzed by quantitative immunohistochemistry 24 hours post-stenosis. Stab2 -/- mice developed significantly larger thrombi than Stab2 +/+ mice (194%, n=19, p=0.003) but no difference in DVT incidence (64% vs 61%, P= 0.85). Despite equivalent hematocrit (P= 0.91) and white type thrombus (P> 0.05), thrombi from Stab2 -/- mice were comprised of more red type thrombus (185%, P= 0.004).Through an unbiased analysis of whole exome sequencing in 6,157 individuals, this studyconfirms the role of haploinsufficiency of PROC, PROS1 and SERPINC1 for VTE susceptibility and identifies STAB2 deficiency as a potential new risk factor. Analysis of an independent human cohort of 1162 Europeans demonstrates that STAB2 haploinsufficiency is associated with elevated VWF levels, a known risk factor for VTE. Finally, a mouse model of Stab2 deficiency demonstrates enhanced thrombosis, though without an association with elevated VWF levels. Taken together, these results suggest that rare genetic variants in STAB2 collectively play a role in individuals with unprovoked VTE by prolonging the plasma half-life of procoagulant factors such as VWF, adding an important new gene to the short list of known risk factors for this common disease. [Display omitted] DisclosuresReitsma:Leiden University Medical Center; VarmX B.V.: Equity Ownership, Patents & Royalties: co-inventor on a patent application related to this abstract.

Anti-Xa Monitoring of Low-Molecular-Weight Heparin during Pregnancy: A Systematic Review.

Low-molecular-weight heparin (LMWH) is commonly used for preventing or treating venous thromboembolic disease (VTE) during pregnancy. The physiological changes in maternal metabolism have led to discussions on optimal LMWH dosing strategy and possible need for monitoring. The aim of this systematic review is to summarize and discuss whether LMWH dose adjustment according to anti-Xa provides superior effectiveness and safety compared with weight adjusted or fixed dosed LMWH in pregnant women. A systematic literature search was performed in PubMed, Embase, and Scopus on September 26, 2020. The study is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Effectiveness was defined as episodes of thrombosis and safety as bleeding episodes. In total, 33 studies were included: 4 randomized controlled studies and 29 cohort studies. Prophylactic dosing strategies employing weight dosed, fixed dosed, or anti-Xa adjusted LMWH dosing performed equal in effectiveness and safety. In pregnant women with VTE or high thromboembolic risk, therapeutic weight-adjusted LMWH and weight plus anti-Xa-adjusted LMWH provided equal results in terms of effectiveness and safety. Pregnant women with mechanical heart valves (MHVs) received therapeutic anti-Xa-adjusted LMWH with four out of seven studies presenting mean peak anti-Xa within target ranges. Still, pregnant women with MHV experienced both thrombosis and bleeding with anti-Xa in target. Based on the results of this systematic review, current evidence does not support the need for anti-Xa monitoring when using LMWH as thromboprophylaxis or treatment during pregnancy. Nonetheless, the need for anti-Xa monitoring in pregnant women with MHV may need further scrutiny.

Maternal thrombin generation and D-dimer levels in obesity and pregnancy: results from the maternal thrombin generation in obesity and pregnancy (MaTOPs) study.

Venous thromboembolic disease (VTE) risk increases five-fold antenatally and 14-fold during the puerperium. Obesity significantly increases this risk. The D-dimer assay and more novel Calibrated Automated Thrombogram (CAT) assay laboratory tests display potential for use in VTE risk stratification in pregnancy, although to date, research in the performance characteristics of these tests in obese and nonobese pregnant populations is limited. The aim of this study was to compare D-dimer and thrombin generation levels in obese and nonobese pregnant women. Pregnant women were recruited and categorised, as obese (BMI ≥30) or nonobese (BMI 18.5-25). Blood was collected at 26-28 weeks' gestation, 36-40 weeks' gestation and 6-12 weeks postpartum and D-dimer concentrations and endogenous thrombin potential (ETP) were determined. Student's t-test was used to analyse differences in mean D-dimer and ETP. At 36-40 weeks, obese pregnant women had higher D-dimer concentrations (P = 0.001) but lower ETP levels compared with nonobese women (P = 0.044). D-dimer was higher in nonobese than in obese women at 6-12 weeks postpartum (P = 0.026). There was no difference in mean D-dimer (P = 0.825) and mean ETP (P = 0.424) between obese and nonobese women at 26-28 weeks. No difference was observed in mean ETP at 6-12 weeks postpartum (P = 0.472). ETP was lower in both obese and nonobese women postpartum than during pregnancy. D-dimer was lower in obese women but not in nonobese women postpartum. D-dimer concentrations and ETP were not significantly different during multiple time points in pregnancy and postpartum between obese and nonobese pregnant women suggesting limited utility in VTE risk assessment in obese pregnant women.

Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period.

Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period.

Conocimiento de la tromboprofilaxis-COVID-19 en los profesionales sanitarios en España

IntroductionPatients suffering from coronavirus infection have an increased risk of venous thromboembolic disease (VTE) associated with COVID-19, which confers a higher risk of mortality. For this reason, it is necessary to analyze the knowledge and the different actions in the management of thromboprophylaxis in work environments. Material and methodsObservational, descriptive and cross-sectional study with data collection through a Google® form with 19 questions for professionals involved in the care of COVID-19. 414 surveys were received. The quantitative variables were represented with means and standard deviation and the qualitative variables with percentages and confidence intervals. Results414 surveys analyzed. 58.2% were women. The most participatory age group was 56-65 years. 95.2% stated that COVID-19 patients had a higher risk of VTE and peripheral arterial microthrombosis. 93.6% considered that outpatient COVID-19 patients should receive thromboprophylaxis. 60.5% of the physicians did not know any protocol for the evaluation of thrombotic risk in these patients. Low molecular weight heparin was considered the main treatment for thromboprophylaxis. ConclusionsThe majority of doctors consider that COVID-19 patients have a higher risk of suffering VTE and peripheral arterial microthrombosis than the general population, however more than a third do not assess the thrombotic risk and a significant percentage claim not to know protocols to evaluate said risk. The survey highlights the training needs of our professionals in thromboprophylaxis so that our patients receive healthcare with the highest possible quality.

Rare and Underestimated Association of Pulmonary Embolism and Olanzapine Therapy; Report of Two Cases.

Venous thromboembolic disease (VTD) is a very common and severe pathological condition in which there are many predisposing factors. Olanzapine is a drug frequently used in psychiatric practises; it is thought to increase the risk of VTD. Here, we report two cases, a young man and a woman, with a medical history of schizophrenia treated by olanzapine who developed pulmonary embolism and we did not find any aetiologies of VTD in them. Due to the link between olanzapine and pulmonary embolism, which has been previously described, olanzapine is considered responsible for this problem. Two mechanisms have been reported in the literature in this regard; significant weight gain and lethargy, which are very common side effects of olanzapine. So far, no direct effect of olanzapine on platelet aggregation or coagulation has been found. In patients developing VTD while being treated with olanzapine, discontinuation of olanzapine as a treatment option must be done with an adjustment of antipsychotic treatment and regular monitoring of psychic symptoms. Since the diagnosis of pulmonary embolism is not easy to make in a schizophrenic patient, clinicians should take that in consideration when prescribing these drugs and when facing clinical situations where VTD is suspected.

Unicompartmental knee arthroplasty and revision total knee arthroplasty have a lower risk of venous thromboembolism disease at 30\u2009days than primary total knee arthroplasty

BackgroundWhile multiple studies have demonstrated a lower venous thromboembolism disease (VTED) risk for unicompartmental knee arthroplasty (UKA) compared to primary total knee arthroplasty (TKA), recent reports have shown that revision TKA also had a lower VTED risk compared to primary TKA, an unexpected finding because of its theoretical increased risk. Given the paucity of up-to-date comparative studies, our goal was to perform a high-powered VTED risk comparison study of UKA and revision TKA to primary TKA using recent data.MethodsThe National Surgical Quality Improvement Program (NSQIP) database was queried between 2011 and 2018, and we identified 213,234 patients for inclusion: 191,810 primary TKA, 9294 UKA, and 12,130 revision TKA. Demographics, medical comorbidities, and possible VTE risk factors were collected. Thirty-day outcomes, including deep vein thrombosis (DVT), pulmonary embolism (PE), and all-cause VTED were compared between knee arthroplasty types.ResultsOn multivariate analysis, UKA was significantly associated with lower rates of DVT [OR 0.44 (0.31–0.61); P < 0.001], PE [OR 0.42 (0.28–0.65); P < 0.001], and all-cause VTED [OR 0.42 (0.32–0.55); P < 0.001] when compared to primary TKA. Revision TKA was significantly associated with lower rates of PE [OR 0.62 (0.47–0.83); P = 0.002], and all-cause VTED [OR 0.82 (0.70–0.98); P = 0.029] when compared to primary TKA.ConclusionsUtilizing recent data from a nationwide patient cohort and controlling for confounding variables, our results showed that both revision TKA and UKA had a lower risk of VTED compared to primary TKA, corroborating the results of recent investigations. Additional prospective investigations are needed to explain this unexpected result.

Thromboprophylaxis for patients with newly diagnosed vs. recurrent cancers: a post-hoc analysis of the avert trial.

Venous thromboembolic disease (VTE) is a common complication among patients with cancer. Data reporting risk of VTE among patients receiving chemotherapy for recurrent cancer compared to those with newly diagnosed tumors is scarce. Furthermore, it is unclear if thromboprophylaxis is beneficial and safe in these specific patient populations. Post-hoc analysis of the AVERT trial which was a randomized, placebo-controlled, double-blind trial comparing apixaban therapy to placebo for VTE prophylaxis among cancer patients who were intermediate-to-high risk for VTE and who were initiating chemotherapy. The HRs for recurrent VTE and major bleeding episodes in patients with newly diagnosed and recurrent cancers were calculated using a Cox regression model controlling for age, gender, and center. Of the 563 included patients 469 and 93 patients had newly diagnosed and recurrent cancers, respectively. Patients with recurrent cancer have a higher risk of VTE (Hazard ratio (HR): 1.53 (95% CI 1.0 to 2.33; p = 0.047) and major bleeding episodes (HR 2.89 (95% CI 1.52 to 5.49; p = 0.001) compared to those with newly diagnosed cancer. In patients with newly diagnosed cancers, the use of apixaban was associated with a significantly lower risk of VTE (HR 0.45; 95% CI 0.27-0.76; p = 0.002) and a higher rate of major bleeding (HR 2.10; 95% CI 1.09-4.08; p = 0.028). In patients with recurrent cancer, apixaban was associated with a significant lower rate of VTE (HR 0.26; 95% CI 0.13-0.53; p < 0.001) without an associated significantly increased risk of major bleeding (HR 1.82; 95% CI 0.36-9.15; p = 0.466). Patients with recurrent cancer seem to be at higher risk of recurrent VTE and major bleeding complications compared to those with newly diagnosed tumors. Apixaban appears to be safe and effective in these patient populations.

A case series of Factor V Leiden mutation in pregnancy

Background. Pregnant patients with Factor V Leiden (FVL) mutation are at an increased risk of venous thromboembolic disease (VTED) and placental-mediated complications. Thromboprophylaxis with low-molecular-weight heparin (LMWH) can potentiallymitigate these risks. Objective. To describe the clinical course of a cohort of patients with FVL mutation with different underlying genotypes. Methods. The pregnancy outcomes, occurrence of VTED events and laboratory test results of pregnant women with FVL mutation managed at a quaternary medical centre over a period of 18 years in Johannesburg, South Africa, were analysed. Results. Over the period of analysis, 25 pregnant women with FVL mutation were referred to the haematology department for management. Ten patients (40%) had a family history, and 15 patients (60%) a personal history of VTED. The majority of provoked VTED events (90%) were secondary to combined oral contraceptive exposure. Previous pregnancy loss occurred in 4 (16%) patients, of whom 3 (75%) suffered recurrent losses. All women received prophylactic anti-Factor Xa (anti-FXa) dose-adjusted LMWH during anteand postnatal periods. All pregnancies resulted in live births with 1 VTED event recorded. Conclusion. Patients with FVL mutation show phenotypical heterogeneity in terms of pregnancy outcomes, VTED events and placentalmediated complications. Confounders contributing to the heterogeneity are not completely defined and deciding on appropriate treatment is not fully standardised but the live birth rate is encouraging.