Previous Venous Thromboembolic Events Research Articles

Abstract #1403021: HIV Status in a Patient on Testosterone Therapy: Confounder or Modifier to Venous Thromboembolism?

The association between venous thromboembolic events (VTE) and testosterone therapy has been controversial. Some studies showed an increased risk of VTE with testosterone use, while few studies showed none. Furthermore, some data suggest HIV can also predispose patients to a hypercoagulable state due to immune dysregulation. A 60-year-old male presented with right leg pain and dyspnea. He was on an aromatase inhibitor and testosterone replacement therapy (TRT) for aromatase excess syndrome, and on bictegravir, emtricitabine and tenofovir alafenamide for HIV infection with normal CD4 count and undetectable viral load. Hospital course revealed right mid-femoral deep vein thrombosis and right-sided pulmonary embolism. He was managed conservatively with IV heparin and eventually discharged on a direct oral anticoagulant. Existing literature on the correlation between VTE and TRT is inconclusive. A case-control study in the USA showed no increased risk of VTE in those on TRT. However, another population-based case-control study in the UK showed that TRT had an increased incidence of VTE compared to general population, with peak risk noted at 6 months. Possible reasons for the higher risk of VTE in patients requiring TRT included increased hematocrit, platelet aggregation, and blood viscosity. A recent case-crossover study that included more VTE-exposed cases showed that TRT patients had greater short-term risk of VTE, especially in the immediate period after initiation of therapy. Another important factor to consider in this patient’s predisposition to VTE is his HIV status which promotes a prothrombotic state and predisposes patients to venous and arterial thromboembolism. Likely due to immune dysregulation secondary to chronic inflammation and immune activation. It usually happens in patients with low CD4 counts and high viral loads. But, in HIV patients with well-controlled viral load and CD4 counts, data suggests that VTE incidence is close to that of general population. In our patient, who was on TRT chronically with no previous VTE, it is hard to assess if his current HIV status was a confounder to his hypercoagulable state or a modifier to an existing risk. With subgroups of TRT-using patients like the transgender population having an increased incidence of HIV, concurrent infection may heighten clinical risk. It is essential to further explore the confounding versus modifying effect that HIV may have on VTE incidence. Currently, there are no large-scale clinical trial data available to identify the true association of VTE with TRT.

Factors Affecting Residual Stump Length Following Endovenous Laser Ablation.

Current instruction for endovenous laser ablation (EVLA) recommends that the laser fibre tip should be at least 2cm caudal to the saphenofemoral or saphenopopliteal junction. This is to reduce risk of deep vein thrombosis (DVT) whilst ensuring that the Great Saphenous Vein (GSV)/Short saphenous vein (SSV) occlusion (residual stump) is close to the SFJ/SPJ to reduce recurrence rates. Our aim was to primarily assess the effects of pre-operative junction distance of the laser fibre on stump length but also look at other factors affecting this. This was a retrospective analysis of an electronic collected database performing EVLA of the GSV and SSV under local anaesthesia. Patients with previous venous thromboembolic events and incomplete data were excluded. Patients were reviewed at 6weeks with venous Duplex scan to assess for the residual stump distance and DVT. Multivariable logistic regression was used to account for confounders. Between 2012 and 2018, 2341 patients underwent EVLA and complete data were available on 825 (35.2%) patients. All patients were scanned 6weeks after procedure. Sixty-nine patients (8.4%) had flush occlusion, 3 patients (.4%) had extension into femoral or popliteal vein but not considered to be a DVT and 1 patient had a DVT. High BMI and increasing length of the pre-operative junction was associated with lower incidence of flush occlusion; higher rates of flush occlusions were noted in patients undergoing short saphenous vein (SSV) EVLT (OR 4.11, 95% CI 2.34-7.20; P < .001). Consideration should be given to increase the intra-procedure laser tip junction to more than 2cm particularly in patients undergoing SSV treatment to ensure that residual stump is sufficiently distal to SPJ and SFJ reducing risks of thrombus into the femoral or popliteal veins. Lower BMI may be associated with higher risk of this though the reasons for this are unclear.

Systematic search for the UBA1 mutation in men after a first episode of venous thromboembolism: A monocentric study

Systematic search for the UBA1 mutation in men after a first episode of venous thromboembolism: A monocentric study

Pregnancy after Combined Oral Contraceptive-Associated Venous Thromboembolism: An International Retrospective Study of Outcomes.

Few data are available on thrombotic outcomes during pregnancy and puerperium occurring after an initial provoked venous thromboembolic (VTE) event. To describe thrombotic outcomes during pregnancy after a first combined oral contraceptive (COC)-associated VTE and the factors associated with recurrence. This was an international multicentric retrospective study on patients referred for thrombophilia screening from January 1, 2010 to January 1, 2021 following a first COC-associated VTE, including women with neither inherited thrombophilia nor antiphospholipid antibodies and focusing on those who had a subsequent pregnancy under the same thromboprophylaxis treatment. Thrombotic recurrences during pregnancy and puerperium as well as risk factors for recurrence were analyzed. We included 2,145 pregnant women. A total of 88 thrombotic events, 58 antenatal and 29 postnatal, occurred, mostly during the first trimester of pregnancy and the first 2 weeks of puerperium. Incidence rates were 49.6 (37-62) per 1,000 patient-years during pregnancy and 118.7 (78-159) per 1,000 patient-years during puerperium. Focusing on pulmonary embolism, incidence rates were 1.68 (1-4) per 1,000 patient-years during pregnancy and 65.5 (35-97) per 1,000 patient-years during puerperium.Risk factors for antenatal recurrences were maternal hypercholesterolemia and birth of a very small-for-gestational-age neonate. A risk factor for postnatal recurrence was the incidence of preeclampsia. Our multicentric retrospective data show significant rates of VTE recurrence during pregnancy and puerperium in women with a previous VTE event associated with COC, despite a unique low-molecular-weight heparin-based thromboprophylaxis. These results may provide benchmarks and valuable information for designing future randomized controlled trials.

Risk Factors for Venous Thromboembolism in Severe COVID-19: A Study-Level Meta-Analysis of 21 Studies.

Venous thromboembolism (VTE) in patients with COVID-19 in intensive care units (ICU) is frequent, but risk factors (RF) remain unidentified. In this meta-analysis (CRD42020188764) we searched for observational studies from ICUs reporting the association between VTE and RF in Medline/Embase up to 15 April 2021. Reviewers independently extracted data in duplicate and assessed the certainty of the evidence using the GRADE approach. Analyses were conducted using the random-effects model and produced a non-adjusted odds ratio (OR). We analysed 83 RF from 21 studies (5296 patients). We found moderate-certainty evidence for an association between VTE and the D-dimer peak (OR 5.83, 95%CI 3.18–10.70), and length of hospitalization (OR 7.09, 95%CI 3.41–14.73) and intubation (OR 2.61, 95%CI 1.94–3.51). We identified low-certainty evidence for an association between VTE and CRP (OR 1.83, 95% CI 1.32–2.53), D-dimer (OR 4.58, 95% CI 2.52–8.50), troponin T (OR 8.64, 95% CI 3.25–22.97), and the requirement for inotropic drugs (OR 1.67, 95% CI 1.15–2.43). Traditional VTE RF (i.e., history of cancer, previous VTE events, obesity) were not found to be associated to VTE in COVID-19. Anticoagulation was not associated with a decreased VTE risk. VTE RF in severe COVID-19 correspond to individual illness severity, and inflammatory and coagulation parameters.

Thromboembolism in Muscle-Invasive Bladder Cancer. A Population-based Nationwide Study.

Routine VTE prophylaxis within 30 days of radical cystectomy (RC) for urinary bladder cancer (UBC) is used to protect from venous thromboembolism (VTE). However, randomized studies and nationwide population-based studies are lacking. To study VTE and risk factors for VTE in muscle-invasive UBC in a nationwide population-based series, with a focus on the association with RC with and without chemotherapy. We studied all patients with clinical stage T2-T4 UBC diagnosed 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe). Previous VTE events and risk factors for VTE were registered from 1987. Cox regression analyses and Kaplan-Meier curves were performed to study risk factors for VTE and cumulative incidence of VTE. In 9720 patients (71%males) with a median age of 74 years 546 (5.6%) had VTE after diagnosis. In Cox analyses controlling for patient's and tumour characteristics, and risk factors for VTE, VTE after diagnosis and first treatment date were associated with chemotherapy with or without RC. Cumulative incidence of VTE increased during 24 months after diagnosis and first treatment date. VTE were less common in patients with previous cardiovascular disease. VTE was commonly observed after 30 days from diagnosis and from first treatment date in patients with T2-T4 UBC, particularly after chemotherapy. The findings suggest that long-term intervention studies of benefit and possible harms of VTE prophylaxis after UBC should be undertaken.

Aggressive lymphoma subtype is a risk factor for venous thrombosis. Development of lymphoma - specific venous thrombosis prediction models.

Venous thromboembolic events (VTE) are a frequent complication of lymphoma. We conducted a retrospective analysis to compare VTE risk in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Subjects were randomly assigned to training and validation sets to identify risk factors of VTE and evaluate risk model performance, including the Khorana score. A group of 790 patients were diagnosed from 2002 to 2014 (DLBCL = 542, FL = 248). Median follow- up was 49 months. We observed 106 VTE, with higher incidence in DLBCL (5-year cumulative incidence = 16.3% vs 3.8% in FL patients). Five-year OS for patients with VTE was 51.4% vs 73.1% in patients without VTE (P < .001). Baseline VTE risk factors identified in the training cohort included lymphoma subtype, previous VTE, ECOG performance status ≥2, decreased albumin, increased calcium, elevated WBC, absolute lymphocyte count or monocyte count, and presence of bulky disease. Addition of new variables to the Khorana score improved its performance measured by Akaike information criterion and Concordance index. A new risk model including lymphoma subtype, albumin, WBC count, and bulky disease was validated in time-based ROC analyses. These findings were confirmed in the validation cohort. Lymphoma subtypes have different VTE risk. The effect of lymphoma subtype was independent from disease burden and the use of systemic therapy. The Khorana risk-score was validated in time to event analyses, and a more robust lymphoma-specific VTE risk score is proposed. These findings suggest lymphoma patients with highest VTE risk can be identified with baseline parameters.

The Pro-Adhesive and Reduced Angiogenic Properties of Endothelial Colony Forming Cells (ECFC) from JAK2V617F MPN Patients Are Not Related to the Expression of the JAK2 mutation in These Cells: A Potential Role of ADAM17

INTRODUCTION: JAK2V617F mutation is independently associated with a higher risk of venous thromboembolic events (VTE) in myeloproliferative neoplasms (MPN). We have previously shown that endothelial colony-forming cells (ECFCs) from JAK2V617F MPN patients do not express this mutation but exhibit a pro-adhesive phenotype with a lower in vitro angiogenic potential. Here, we explore the mechanisms through which ECFCs from JAK2V617F MPN patients behave differently from ECFCs from healthy individuals. METHODS: We selected 38 patients with newly or previously diagnosed MPN, regardless of current or prior hydroxyurea therapy, with or without a history of VTE. Plasma levels of ADAMTS13, P-selectin, soluble VCAM, soluble ICAM, PDGF-AA, PDGF-AB/BB, IL-8, IL-1β, and soluble CD40 ligand were measured through the use of a multiplex assay. We then tried to isolate ECFCs from 20 of the JAK2V617F patients as well as 14 healthy individuals. Successfully isolated ECFCs were then submitted to co-culture with red blood cells (RBC), after which RNA was extracted from ECFCs. ADAMTS13, P-selectin, sVCAM, and sICAM were measured in the supernatant from ECFCs and RBC co-culture with multiplex assay. ECFCs' surface expression of P-selectin, VCAM, ICAM, and E-selectin was measured with the use of flow cytometry. Gene expression in RNA from co-cultured ECFCs was assessed with two 84-gene RT-PCR arrays for endothelial cell biology and signal transduction pathways (RT2 Profiler PCR array, Qiagen®). RESULTS: Recruited patients had polycythemia vera (PV) (n=17), primary myelofibrosis (PMF) (n=7) and essential thrombocythemia (ET) (n=14); 34% of them had had a previous VTE (6/17 PV; 3/14 ET and 4/7 PMF). Median age was 59 years (26-88), 23% were male. Compared with JAK2wt, JAK2V617F MPN patients (n=29) showed higher median concentrations of sVCAM (1063 vs. 786.5 ng/ml, p=0.0315), sCD40L (339 vs. 166.4 ng/ml, p=0.0065), PDGF-AA (430.6 vs. 136.5 ng/ml, p=0.03) and PDGF-AB/BB (1068 vs. 365.8 ng/ml, p=0.004). Success in ECFC isolation was 9/20 (45%) in JAK2V617F MPN patients and 8/14 (57%) in healthy individuals. None of the ECFCs from JAK2V617F MPN patients expressed this mutation. In comparison with ECFCs from healthy individuals, ECFCs from JAK2V617F MPN patients did not show a higher expression of either VCAM1, ICAM, P-selectin, and E-selectin, as measured by flow cytometry after co-culture with RBCs. Multiplex assay on the supernatant of this co-culture did not show any difference in the levels of ADAMTS13, sVCAM, sICAM, and sP-selectin. RNA PCR array from the ECFCs after co-culture with RBCs showed no difference in the expression of adhesion molecules when compared with ECFCs from healthy individuals, except for the increased expression of ADAM17 (fold regulation: 5.46, p=0.006), a metalloprotease involved in the shedding of adhesion molecules, among them VCAM1. ECFCs from MPN patients did not show higher activation of the JAK-STAT pathway but had a lower expression of WNT5 (fold regulation: -2.22, p=0.03), indicating a reduced activation of the Hedgehog pathway, suitable with the reduced in vitro angiogenesis capacity of these cells. CONCLUSIONS: JAK2V617F MPNs are associated with an increase in circulating adhesion molecules, such as sVCAM, and platelet activation markers. The pro-adhesive phenotype and lower angiogenic potential of ECFCs JAK2V617F MPN patients are not related to this mutation, which is not expressed in these cells and might be related to an increased expression of ADAM17 and reduced activation of the Hedgehog pathway. Disclosures Ozelo: BioMarin: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Novo Nordisk: Research Funding; Roche: Research Funding.

Fasting plasma glucose, oral glucose tolerance test, and the risk of first-time venous thromboembolism. A report from the VEINS cohort study.

IntroductionIt remains unclear whether high plasma glucose levels are associated with venous thromboembolism (VTE). This study investigated the association between fasting plasma glucose (FPG), oral glucose tolerance test (two-hour post-load plasma glucose (2HPG)), diabetes, and VTE. Materials and methodsThe population-based, prospective Venous thromboEmbolism In Northern Sweden (VEINS) cohort study included 108,025 residents of Västerbotten County in northern Sweden. The participants were aged 30 to 60 years and had no previous VTE events. They were included from 1985 onwards and were followed until a VTE event, death, emigration, or the study end on September 5, 2014. All underwent a health examination that measured weight, height, FPG, and 2HPG and included a questionnaire regarding smoking, education level, and history of diabetes. Potential VTE events were identified by an extensive diagnosis registry search and were validated by reviewing medical records and radiology reports. ResultsAn objectively verified first-time VTE event was experienced by 2054 participants during 1,496,669 person-years of follow-up. In univariable analysis, there were associations between FPG, 2HPG, diabetes, and the risk of VTE. These associations disappeared after adjustment for potential confounders (age, sex, body mass index, cancer at inclusion, education level, smoking, and hypertension). The adjusted hazard ratios were 1.01 (95% confidence interval 0.83–1.23) for diabetes, 1.01 for each standard deviation of FPG (95% confidence interval 0.97–1.05), and 0.96 for each standard deviation of 2HPG (95% confidence interval 0.91–1.00). ConclusionsThere were no independent associations between FPG, 2HPG, diabetes, and future risk of VTE.

The prevalence and clinical manifestation of hereditary thrombophilia in Korean patients with unprovoked venous thromboembolisms.

BackgroundHereditary thrombophilia (HT) is a genetic predisposition to thrombosis. Asian mutation spectrum of HT is different from Western ones. We investigated the incidence and clinical characteristics of HT in Korean patients with unprovoked venous thromboembolism (VTE).MethodsAmong 369 consecutive patients with thromboembolic event who underwent thrombophilia tests, we enrolled 222 patients diagnosed with unprovoked VTE. The presence of HT was confirmed by DNA sequencing of the genes that cause deficits in natural anticoagulants (NAs). Median follow-up duration was 40±38 months.ResultsAmong the 222 patients with unprovoked VTE, 66 (29.7%) demonstrated decreased NA level, and 33 (14.9%) were finally confirmed to have HT in a genetic molecular test. Antithrombin III deficiency (6.3%) was most frequently detected, followed by protein C deficiency (5.4%), protein S deficiency (1.8%), and dysplasminogenemia (1.4%). The HT group was significantly younger (37 [32–50] vs. 52 [43–65] years; P < 0.001) and had a higher proportion of male (69.7% vs. 47%; P = 0.013), more previous VTE events (57.6% vs. 31.7%; P = 0.004), and a greater family history of VTE (43.8% vs. 1.9%; P < 0.001) than the non-HT group. Age <45 years and a family history of VTE were independent predictors for unprovoked VTE with HT (odds ratio, 9.435 [2.45–36.35]; P = 0.001 and 92.667 [14.95–574.29]; P < 0.001).ConclusionsAbout 15% of patients with unprovoked VTE had HT. A positive family history of VTE and age <45 years were independent predictors for unprovoked VTE caused by HT.

OC-01 - Clinical history of cancer patients with isolated distal deep vein thrombosis: a multicenter cohort study

Isolated distal deep vein thrombosis (IDDVT) accounts for one-fourth to one-half of all deep vein thrombosis (DVT) of the leg. Patients with IDDVT are frequently treated for a shorter period of time compared to patients with proximal DVT and/or pulmonary embolism (PE) due to a perceived lower risk of recurrence. About 10-20% of patients with venous thromboembolic events (VTEs) have concomitant cancer. Guidelines recommend long-term anticoagulant treatment in this group of patients due to their high risk of VTE recurrence. Unfortunately, information on the clinical history of IDDVT patients is limited and, to date, no study has evaluated the long-term risk of VTE recurrence in IDDVT patients with cancer. To provide information on the clinical history of IDDVT patients with active cancer. A multicenter, cohort study including active-cancer patients with an objective diagnosis of IDDVT (between January 2011 and September 2014) was conducted. Information on baseline characteristics, thrombosis location and extension, concomitant risk factors, type and duration of treatment was collected. All patients were followed for a minimum of 12 months and up to 24 months. During follow-up, VTE recurrence, major bleeding episodes and death were registered. Potential risk factors for VTE recurrence were evaluated. 308 patients (mean age 66.2±13.2 years, female 57.1%) in 13 centers were included, Table1; 261 patients had solid cancer and 47 patients hematologic cancer. At the time of IDDVT diagnosis, the disease was metastatic in 148 patients (48.1%); 99.0% of patients received anticoagulant treatment: 288 patients (93.5%) were initially treated with low molecular weight heparin, 15 with fondaparinux (5.2%) and 1 with unfractionated heparin; vitamin K antagonists were used in 46 patients (14.9%) only. Total follow-up was 389 patient-years, mean follow-up 15.2 months. Mean duration of treatment was 4.2 months. During the study period there were 47 episodes of VTE recurrence (36 proximal DVT or PE) for a incidence rate of 13.2 events per 100 patient-years; 7 patients had major bleeding (2.3%) and 137 died (44.5%). At multivariate analysis, previous VTE was associated with an increased risk of recurrence (OR 2.10; 95% 1.06, 4.14), whereas patients with gastrointestinal cancer had a lower risk of recurrence (OR 0.26; 95% CI 0.08, 0.86). Cancer patients with IDDVT have a high risk of VTE recurrence. Other studies are warranted to address the adequate management of these patients.

Incidence and risk factors for symptomatic venous thromboembolism following cholecystectomy.

The benefit of thromboembolism prophylaxis in cholecystectomy is controversial. This population-based study report on the incidence of and risk factors for symptomatic venous thromboembolism (VTE) after cholecystectomy. All cholecystectomies registered in the Swedish Register of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) between 2006 and 2011 were reviewed. By linking patient data to the Swedish National Patient Register (NPR), the 30-day postoperative incidence of VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) was identified. Age- and gender-standardized incidence ratio (SIR) for deep venous thrombosis (DVT) and pulmonary embolism (PE) were calculated. Multivariable analysis determined risk factors for VTE by calculating odds ratio (OR). Altogether 62,488 procedures were registered and postoperative VTE was seen in 154 (0.25%) patients. DVT was seen in 36 (0.06%) patients and PE in 25 (0.04%) patients within 30 days after surgery. The SIR for DVT was 22.2 (95% confidence interval (CI) 13.1-31.3) and for PE 5.6 (95% CI 2.3-8.9). Risk factors for VTE within 30 days after cholecystectomy were age >70 years (odds ratio [OR] = 2.69; 95% confidence interval [CI] 1.68-4.30), open cholecystectomy (OR = 1.95; CI 1.31-2.92), operation time >120 min (OR = 1.66; CI 1.18-2.35), acute cholecystitis (OR = 1.69; CI 1.18-2.42), and previous history of VTE (OR = 50.5; CI 27.3-92.8). Thromboembolism prophylaxis (TP) increased the risk for postoperative bleeding (OR = 1.72; 1.44-2.05). The incidence of VTE after cholecystectomy is low and thromboembolism prophylaxis (TP) increases the risk for postoperative bleeding. Patients with previous VTE events should be given TP when undergoing cholecystectomy.

Prevalence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Prevalence of CTEPH after pulmonary embolism.

Chronic thromboembolic pulmonary hypertension (CTEPH) has been estimated to occur in 0.1-0.5% of patients who survive a pulmonary embolism (PE), but more recent prospective studies suggest that its incidence may be much higher. The absence of initial haemodynamic evaluation at the time of PE should explain this discrepancy. We performed a prospective multicentre study including patients with PE in order to assess the prevalence and to describe risk factors of CTEPH. Follow-up every year included an evaluation of dyspnea and echocardiography using a predefined algorithm. In case of suspected CTEPH, the diagnosis was confirmed using right heart catheterisation (RHC). Signs of CTEPH were searched on the multidetector computed tomography (CT) and echocardiography performed at the time of PE. Of the 146 patients analysed, eight patients (5.4%) had suspected CTEPH during a median follow-up of 26 months. CTEPH was confirmed using RHC in seven cases (4.8%; 95%CI, 2.3 - 9.6) and ruled-out in one. Patients with CTEPH were older, had more frequently previous venous thromboembolic events and more proximal PE than those without CTEPH. At the time of PE diagnosis, patients with CTEPH had a higher systolic pulmonary artery pressure and at least two signs of CTEPH on the initial CT. After acute PE, the prevalence of CTEPH appears high. However, initial echocardiography and CT data at the time of the index PE suggest that a majority of patients with CTEPH had previously unknown pulmonary hypertension, indicating that a first clinical presentation of CTEPH may mimic acute PE.

The new guides for deep venous thromboembolic event prophylaxis in elective hip and knee replacement surgery. Are we nearer or further away from a consensus?

Venous thromboembolism events (VTEs) prophylaxis after elective hip or knee replacement surgery is a subject of controversy. Three sets of guidelines (National Institute for Health and Clinical Excellence (NICE), American College of Chest Physicians (ACCP) and American Academy of Orthopaedic Surgeons (AAOS)) on this topic have recently been updated.The guidelines have points in common: prophylaxis is necessary; it is recommended to combine mechanical and pharmacological prophylaxis in patients who have suffered a previous VTE, isolated mechanical measures and low molecular weight heparins (LMWH) are effective; the new oral anticoagulants (NOAC) and fondaparinux are effective drugs. There is some consensus in recommending regional anaesthesia, in advising against echography studies in asymptomatic patients, and in the promotion of early mobilisation of the patient.There is controversy over the most suitable pharmacological treatment and the time of starting, and the duration of this, as well as on vena cava filters (VCF), antiplatelet (AP) drugs, and VTE or bleeding risk factors.

Las nuevas guías de profilaxis de enfermedad tromboembólica venosa en artroplastia de cadera y rodilla electivas: ¿Nos acercamos o nos alejamos del consenso?

Venous thromboembolism events (VTE) prophylaxis after elective hip or knee replacement surgery is a subject of controversy. Three sets of guidelines (NICE, ACCP and AAOS) on this topic have recently been updated.The guidelines have points in common: prophylaxis is necessary, it is recommended to combine mechanical and pharmacological prophylaxis in patients who have suffered a previous VTE, isolated mechanical measures and low molecular weight heparins are effective, the new oral anticoagulants and fondaparinux are effective drugs. There is some consensus in recommending regional anaesthesia, in advising against echography studies in asymptomatic patients, and in the promotion of early mobilisation of the patient.There is controversy over the most suitable pharmacological treatment and the time of starting, and the duration of this, as well as on vena cava filters, antiplatelet drugs, and VTE or bleeding risk factors.

Anticoagulation-induced severe bleeding in a patient receiving bevacizumab therapy

A 56-year-old female with heavily pretreated stage 4 nonsmall cell lung cancer metastatic to brain, lungs and bone who had been diagnosed with a lower extremity deep vein thrombosis and started on low molecular weight heparin in the previous week presented to the emergency department with severe bilateral flank pain, denied fever, trauma, dysuria or gastrointestinal bleeding. The patient had just finished receiving her second cycle of a clinical trial involving erlotinib, cetuximab and bevacizumab. Restaging imaging studies performed 3 days prior to presentation showed a 43% decrease in the size of her primary lung lesion, and did not show intra-abdominal metastatic disease. Physical exam revealed a chronic diffuse cetuximabinduced rash and new sacral, lumbar, and bilateral flank hematomas (Fig. 1a–c). Hemoglobin was 7.5 g/dL, decreased from 11.5 g/dL, platelets were 120 K/uL, which were at baseline, and coagulation studies, including activated partial thromboplastin time (APTT), international normalized ratio (INR), and fibrinogen, were normal. A computed tomography (CT) of the abdomen showed collections of fluid in the left paravertebral area, bilateral paraspinal regions, and adjacent to the left psoas, likely representing hematomas (Fig. 1d). The patient was transfused with packed red blood cells resulting in normalization of hemoglobin, anticoagulation was stopped, and an inferior vena cava (IVC) filter was placed. Major bleeding has been reported to affect less than 1% of patients receiving anticoagulation. Bevacizumab has been associated with venous thromboembolic events (VTE), and bleeding in patients receiving anticoagulation after a first VTE while receiving bevacizumab-based therapy, leading to temporary or permanent discontinuation of treatment. Some known toxicities of bevacizumab include hypertension, wound healing impairment, thrombosis, bleeding, and gastrointestinal perforation, which have been hypothesized to be related to the action of this monoclonal antibody against vascular endothelial growth factor (VEGF). The concomitant use of an anticoagulant and bevacizumab may have induced such massive hemorrhage in our patient, as no alternative causes were found after a thorough analysis of the bleeding event. The use of bevacizumab together with anticoagulants will inevitably rise, as bevacizumab is increasingly being used in cancer patients, who already have an inherent predisposition to VTE due to their malignancy-induced hypercoagulability state. We should, therefore, exercise caution regarding bevacizumab-induced bleeding in patients who are already receiving anticoagulation due to a previous VTE.

Risk factors for symptomatic deep-vein thrombosis in patients after total ankle replacement who received routine chemical thromboprophylaxis

The aim of this study was to identify the incidence of post-operative symptomatic deep-vein thrombosis (DVT), as well as the risk factors for and location of DVT, in 665 patients (701 ankles) who underwent primary total ankle replacement. All patients received low-molecular-weight heparin prophylaxis. A total of 26 patients (3.9%, 26 ankles) had a symptomatic DVT, diagnosed by experienced radiologists using colour Doppler ultrasound. Most thrombi (22 patients, 84.6%) were localised distally in the operated limb. Using a logistic multiple regression model we identified obesity, a previous venous thromboembolic event and the absence of full post-operative weight-bearing as independent risk factors for developing a symptomatic DVT. The incidence of symptomatic DVT after total ankle replacement and use of low-molecular-weight heparin is comparable with that in patients undergoing total knee or hip replacement.

Efficacy of obstetric thromboprophylaxis and long-term risk of recurrence of venous thromboembolism

To study the efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) in pregnant women with one previous venous thromboembolic event (VTE). Secondary aims were to study the long-term risk of secondary recurrence, bleeding and obstetric complications. A prospective national study of long-term LMWH thromboprophylaxis in Sweden. All hospitals in Sweden during January 1998-December 2002, Pregnant women with one previous VTE and controls drawn from the Swedish Medical Birth Registry. The women were cross-matched with the Swedish Hospital Discharge Register to identify all recurrences and to ascertain the annual risk of recurrence. Recurrence of VTE, bleeding complications at delivery and obstetric complications. 326 of 393 registered women could be evaluated. The relative risk reduction in VTE was 88%. There was an absolute increased risk of VTE during the thromboprophylaxis period: 1.2% compared to 0.2% among controls (p<0.001). The risk during the immediate post-treatment period (43-100 days post-partum) was increased 28-fold. The annual incidence of VTE after delivery was 1%. The risk of hematoma and major blood loss at delivery was increased during thromboprophylaxis (p<0.001). There were no differences in the incidences of preeclampsia, intrauterine growth restriction or placental abruption. The relative risk reduction in VTE during thromboprophylaxis was 88%. After pregnancy, the annual long-term risk of recurrence was 1%. The risk was most pronounced in the post-treatment period. There was an increased risk of bleeding complications among women given LMWH, but there was no effect on obstetric complications.

Influence of Sickle Cell Trait on the Risk of Venous Thromboembolism In Pregnancy and the Postpartum

AbstractAbstract 1628 Background:Evidence suggests a disparity in the incidence of venous thromboembolic events (VTE) amongst racial groups, with blacks purported to have a higher occurrence of VTE than whites. In contrast, Hispanics and Asians have been observed to have a lower occurrence of VTE. Sickle cell anemia is a known prothrombotic state and recent studies contend that sickle cell trait (SCT) may also predispose to VTE. We hypothesized that SCT might play a role in the increased VTE risk for blacks. To this end, we conducted a study to investigate whether pregnant/postpartum women with SCT have a higher VTE incidence than controls without SCT. Methods:Patient information was obtained using our hospital database spanning the eleven years 1998–2008. All pregnant women seen in our large urban medical center had hemoglobin (Hb) electrophoresis screening on their first clinic visit; demographic data was obtained from the patient at registration. Using prospectively-collected data, three patient cohorts were identified. Group A included women with SCT as identified by %HbS of 30–45% on Hb electrophoresis. To ensure exclusion of patients with sickle cell disease who were post-transfusion, subjects who at any time in their medical record had %HbS >45% were excluded from analysis. HbAA black (Group B) and white (Group C) cohorts were included if %HbA was ≥95.5%. Women who self-identified themselves as Hispanic, multiracial, “declined”, “not available” or “not applicable” were also excluded. VTE cases were identified using ICD-9 codes from hospital, ER or outpatient visit discharges during the pregnancy or postpartum period (294 days before delivery or 56 days after delivery). All charts of VTE indexed cases were reviewed (by SP) to ensure accuracy of reporting. Results:The prevalence of SCT was found to be high (11.1%) in our Group A population as compared to 8.3% in the general pregnant/postpartum non-white population that included Hispanics, multiracial and unavailable individuals. We identified 679 black subjects with SCT, 5465 black subjects with HbAA and 1162 white subjects with HbAA. VTE incidence was 0.44% in Group A (SCT), in 0.49% in Group B (Black AA) and in 0.26% in Group C (White AA). The rate of VTE did not significantly differ between these groups. When patients were included who had been thromboprophylaxed secondary to previous VTEs, the incidence of VTE in Black AA was 0.6%, still not significantly different from the white AA group (p=0.13). Age was a more important factor: patients with VTE were significantly older than non-VTE pregnant patients (mean 32.2 vs. 27.6 years, p=0.0002). As expected, the majority of VTE occurred in the postpartum period (61%). Conclusion:Our results suggest that there is a nonsignificant trend toward a higher incidence of VTE in black HbAA (Group B) as compared to white women with HbAA (Group C) in the pregnant/postpartum period. We could not detect a difference in VTE incidence between black SCT (Group A) and black HbAA (Group B). The role of sickle cell trait as an inherited prothrombotic mutation remains unclear. Even a mild increase in age appears to constitute a prothrombotic risk. However, as VTE remains one of the major causes of maternal mortality, further studies will be needed to better identify risk factors of VTE in pregnancy. Prospective studies identifying such patients may help characterize the true impact of sickle cell trait on venous thromboembolism in pregnancy and postpartum. Disclosures:No relevant conflicts of interest to declare.

Prolonged travel and venous thromboembolism findings from the RIETE registry

There is a lack of information on clinical risk factors for venous thromboembolism (VTE) development following prolonged traveling. Clinical characteristics and additional risk factors for VTE in travelers were analyzed in RIETE, an ongoing registry of patients with symptomatic, confirmed acute VTE. Of 26,172 patients enrolled in RIETE as of May 2009, 2% developed VTE in association with recent traveling. Travelers were ten years younger, had significantly more previous VTE events (20% vs. 16%; OR: 1.4; 95%CI: 1.1-1.7) and their body mass index (BMI) was 28.4 ± 5.1 vs. 27.7 ± 5.2 in other patients from the registry (P = 0.004). 115 (20%) of recent travelers had previous VTE compared to 16% among others patients (OR: 1.4; 95%CI: 1.1-1.7). Recent travelers used hormones significantly more frequently (8.7% vs. 3.7%; OR: 2.5; 95% CI: 1.8-3.3) and more often had a positive thrombophilia test (16% vs. 8.7%; OR: 2; 95%CI: 1.6-2.6). Travelers used LMWH prophylaxis significantly less frequently than other patients in the registry (2.4% vs. 13%; OR 0.2; 95%CI: 0.1-0.3). There were differences in VTE risk in professional drivers compared to passengers. The current study demonstrates four risk factors for VTE development after long traveling: high BMI, previous VTE, hormone use and thrombophilia. Studies of prophylactic antithrombotic therapy in high risk travelers are warranted.