High Risk Of Thromboembolic Events Research Articles

Impaired plasma clot lysis and its determinants in patients with obstructive sleep apnea syndrome.

Evidence indicates that hypercoagulability and impaired fibrinolysis have been observed in patients with obstructive sleep apnea syndrome (OSAS). It is unclear which factors determine prolonged fibrin clot lysis in OSAS. One hundred and sixty-five consecutive patients suspected of OSAS underwent overnight polysomnography. Prior to polysomnography, we determined plasma clot lysis time (CLT), plasminogen activator inhibitor (PAI)-1 antigen, activated thrombin-activatable fibrinolysis inhibitor (TAFIa), plasmin, and antiplasmin. OSAS was diagnosed in 110 (66.7%) patients, including 35 (31.8%) with severe OSAS, 26 (23.6%) with moderate OSAS, and 49 (44.6%) mild OSAS. Compared with 55 (33.3%) individuals in whom OSAS was not confirmed, OSAS patients had prolonged CLT (+12.8%), associated with higher PAI-1 antigen (+18.1%) (after adjustment for age, diabetes, and body mass index; both P < 0.01) and similar levels of TAFIa, plasmin, or antiplasmin. PAI-1, TAFIa, and CLT correlated positively with apnea/hypopnea index, which reflects the severity of OSAS (R = 0.66, P < 0.001; R = 0.29, P = 0.002; R = 0.55, P = 0.001, respectively), and with other polysomnography parameters, with the most potent correlations observed for desaturation index. Regression analysis adjusted for potential confounders showed that in OSAS, CLT was independently predicted by apnea/hypopnea index (B = 0.29, P = 0.002), PAI-1 (B = 0.42, P < 0.001), and TAFIa (B = 0.81, P = 0.044), whereas both PAI-1 and TAFIa were predicted only by desaturation index (B = 0.24, P = 0.002; and B = 0.14, P = 0.001, respectively). The severity of OSAS is closely associated with hypofibrinolysis measured in a global plasma-based assay, driven largely by PAI-1. Attenuated fibrinolysis might contribute to high risk of thromboembolic events in this disease.

Fondaparinux for Heparin-Induced Thrombocytopenia

Patients with suspected heparin-induced thrombocytopenia (HIT) are at high risk for thromboembolic events and require anticoagulant therapy. The

Predicting and preventing thromboembolic events in patients receiving cisplatin-based chemotherapy for germ cell tumours

BackgroundPatients with germ cell tumours (GCT) receiving cisplatin-based chemotherapy are at high risk of thromboembolic events (TEE). Previously, we identified serum lactate dehydrogenase (LDH) and body surface area (BSA) as independent predictive factors for TEE.The aim of this study was to validate these predictive factors and to assess the impact of thromboembolism prophylaxis in patients at risk of deep venous thrombosis (DVT). MethodsBetween 2001 and 2014, 295 patients received first-line cisplatin-based chemotherapy for GCT. Preventive anticoagulation with low-molecular-weight heparin (LMWH) was progressively implemented in patients with predictive factors. Sixteen patients with evidence of TEE before starting chemotherapy were excluded from the analysis. ResultsAmong 279 eligible patients, a TEE occurred in 38 (14%) consisting of DVT (n = 26), arterial thrombosis (n = 2), and superficial thrombophlebitis (n = 10). DVT occurred in 26 (12.7%) of 204 patients with risk factors versus two (2.6%) of 75 patients with no risk factors (p = 0.01).After a prevention protocol was progressively implemented from 2005, primary thromboprophylaxis was administered to 104 patients (68%) with risk factors. Among patients at risk (n = 151), the incidence of DVT decreased by roughly half when they received a LMWH: 9/97 (9.2%) and 9/54 (16.6%), respectively (p = 0.23). ConclusionPatients with GCT who receive cisplatin-based chemotherapy are at risk of developing a TEE which can be predicted by elevated serum LDH. To our knowledge this is the first study exploring LMWH as thromboprophylaxis in GCT patients. A prospective trial testing prophylactic anticoagulation is warranted.

Potential of a Pharmacogenetic-Guided Algorithm to Predict Optimal Warfarin Dosing in a High-Risk Hispanic Patient: Role of a Novel NQO1*2 Polymorphism.

Deep abdominal vein thrombosis is extremely rare among thrombotic events secondary to the use of contraceptives. A case to illustrate the clinical utility of ethno-specific pharmacogenetic testing in warfarin management of a Hispanic patient is reported. A 37-year-old Hispanic Puerto Rican, non-gravid female with past medical history of abnormal uterine bleeding on hormonal contraceptive therapy was evaluated for abdominal pain. Physical exam was remarkable for unspecific diffuse abdominal tenderness, and general initial laboratory results—including coagulation parameters—were unremarkable. A contrast-enhanced computed tomography showed a massive thrombosis of the main portal, splenic, and superior mesenteric veins. On admission the patient was started on oral anticoagulation therapy with warfarin at 5 mg/day and low-molecular-weight heparin. The prediction of an effective warfarin dose of 7.5 mg/day, estimated by using a recently developed pharmacogenetic-guided algorithm for Caribbean Hispanics, coincided with the actual patient’s warfarin dose to reach the international normalized ratio target. We speculate that the slow rise in patient’s international normalized ratio observed on the initiation of warfarin therapy, the resulting high risk for thromboembolic events, and the required warfarin dose of 7.5 mg/day are attributable in some part to the presence of the NQO1*2 (g.559C>T, p.P187S) polymorphism, which seems to be significantly associated with resistance to warfarin in Hispanics. By adding genotyping results of this novel variant, the predictive model can inform clinicians better about the optimal warfarin dose in Caribbean Hispanics. The results highlight the potential for pharmacogenetic testing of warfarin to improve patient care.

Atrial fibrillation and stroke: risk factors, anticoagulation, and left atrial appendage occluders.

![Graphic][1] Atrial fibrillation is one of the most common arrhythmias. Its incidence and prevalence increase with age, particularly in patients with hypertension and heart failure.1,2 Although by itself not a particularly dangerous arrhythmia, atrial fibrillation is associated with a considerable risk of stroke. Of note, patients with atrial fibrillation and heart failure have a higher risk of thrombo-embolic events and overall mortality compared with those with atrial fibrillation without heart failure as reflected by the CHA2DS2-VASc score.3,4 Importantly, the prevalence of atrial fibrillation increases with the severity of heart failure. Anticoagulation with vitamin K antagonists is more unstable in patients with concomitant atrial fibrillation and heart failure, which is an independent risk factor for reduced time under the therapeutic range. Thus the clinical review ‘ Antithrombotic therapy in heart failure patients with and without atrial fibrillation: update and future challenges ’ by Joao Pedro Ferreira and colleagues from the Centre Hospitalier Universitaire de Nancy in France is a timely update for the clinician.5 Of importance in this context, non-vitamin K antagonist oral anticoagulants, the so-called NOACs,6,7 have emerged as therapeutic alternatives for stroke prevention in patients with non-valvular atrial fibrillation, as they are at least as efficacious and safe, with less intracranial bleeding events, compared with vitamin K antagonists. The subgroup analyses of the NOAC trials in patients with atrial fibrillation and heart failure revealed that the efficacy and safety of these agents are likely to be similar to those observed in patients with atrial fibrillation without heart failure. However, many gaps in evidence exist, since heart failure has been neither consistently defined nor used as an … [1]: /embed/inline-graphic-1.gif

¿Están correctamente anticoagulados nuestros pacientes con fibrilación auricular no valvular?

IntroductionAtrial fibrillation is one of the most important health problems in the world due to its high prevalence, morbidity and mortality, and because it is a frequent cause of hospital admission and the main indicator for anticoagulation therapy in primary care. ObjectiveThe motivation of our study was to define the percentage of patients with non-valvular atrial fibrillation treated with oral anticoagulants and their clinical characteristics, calculating risks for embolisms and bleeding in this type of patients and their appropriate therapeutic approach. Patients and methodsDescriptive, cross-sectional, retrospective study in patients of a primary care centre with three primary care quotas with a diagnosis of non-valvular atrial fibrillation. Variables: demographic data, personal history (arterial hypertension, diabetes mellitus, dyslipidemia, alcohol addiction, smoking habit, ischemic heart disease, heart failure, cerebrovascular disease, kidney failure, peripheral artery disease and systemic embolism), CHA2DS2-VASc and HAS-BLED scores. ResultsOut of 4,626 patients, 99 (2.15%) were found to have non-valvular atrial fibrillation. Average age 77±10 years, 52.5% women and 47.5% men. 33% are not receiving any anticoagulation therapy, 53% takes acenocoumarol and the rest (13%) a new oral blood-thinning drug (dabigatran, apixaban or rivaroxaban).97% of patients present a CHA2DS2-VASc ≥2 risk (high for embolism), of which 30% are not receiving any anticoagulation therapy. 80% of patients present HAS-BLED ≥ 3 risk (high for bleeding), of which 55% is taking acenocoumarol, 25% showing international normalized ratio out of the therapeutic range. ConclusionNon-valvular atrial fibrillation is one of the main causes of cerebrovascular accidents in our patients. It is shown that anticoagulation therapy in patients with high risk of embolism reduces cerebrovascular accidents by 64% and mortality by 26%. In our field, most patients diagnoses with non-valvular atrial fibrillation have this risk, but 33% are not taking anticoagulants and 25% are poorly controlled with acenocoumarol (a total of 46% of patients). All this implies that 50% of our patients with non-valvular atrial fibrillation develop a high risk for thromboembolic events due to lack or inadequacy of the treatment.

Is DVT prophylaxis necessary after oncology lower limb surgery? A pilot study

Background Deep vein thrombosis (DVT) has been independently associated with both malignant diseases and orthopaedic surgery. Therefore, orthopaedic oncology patients may be at a high risk for thromboembolic events. However, less emphasis is given to this group of patients compared to the patients undergoing total hip and knee replacement. The objective of this study is to determine the incidence of DVT and their risk factors in patients undergoing orthopaedic oncology lower limb surgery without prophylaxis.Questions/purposes(1) What is the incidence of DVT in patients who underwent orthopaedic oncology surgery for the lower limb? (2) What are the risk factors related to DVT in patients who underwent oncology surgery of the lower limb surgery? (3) This is a pilot study to determine if further trial is warranted.MethodsThis is a prospective study. All sequential patients undergoing orthopaedic oncology operations from the period of 1st October 2013 till 30th September 2014 were recruited for the study with their consent. Their demographic data, diagnosis and surgery were documented. Thirty-eight patients who underwent lower limb surgeries for orthopaedic oncology indications were included in the study. No tourniquet was used in these lower limb surgeries. There were 24 men and 14 women with a mean age of 36 years (11–75). All potential risk factors were also identified and documented. All patients were not given any form of DVT prophylaxis (mechanical and chemical) before and after operation as this is a standard protocol in our center and a Medical Ethics Committee approval was taken for this study. DVT surveillance was performed 1 day before operation and 2 weeks after operation with ultrasound Doppler. Patients diagnosed with DVT via ultrasound Doppler were subsequently scheduled for CTPA to look for pulmonary embolism (PE).ResultsDVT was detected in two patients (5 %). Both patients were asymptomatic and they both had proximal thrombosis. One patient (2.6 %) was diagnosed with non-fatal PE and was asymptomatic. PE was detected incidentally by staging computed tomography scan and the patient had negative ultrasound Doppler of the operated and non-operated limb for DVT. We did not carry out a statistical analysis as the study population with DVT and pulmonary embolism is small.ConclusionsThe incidence of DVT in patients after undergoing orthopaedic oncology lower limb surgery was low even without prophylaxis at our center. Further investigation with larger sample size is needed to validate our results and identify the risk factors.Level of evidenceLevel III descriptive study.

Antithrombotic therapy in heart failure patients with and without atrial fibrillation: update and future challenges.

Atrial fibrillation (AF) and heart failure (HF) often coexist, and patients with AF and HF have a higher risk of thromboembolic events and overall mortality compared with those with AF without HF. Additionally, the prevalence of AF increases with the severity of HF. The use of vitamin K antagonists is more unstable in patients with concomitant AF and HF, which is an independent risk factor for reduced time under therapeutic range. More recently, non-vitamin K antagonists oral anticoagulants (NOACs) have emerged as therapeutic alternatives for stroke prevention in patients with non-valvular AF, as they have been shown to be at least as efficacious and safe, with less intracranial bleeding events, compared with vitamin K antagonists. The subgroup analyses of the NOAC trials in patients with AF and HF show that the efficacy and safety of these agents are likely to be similar to those observed in patients with AF and no HF. However, many gaps in evidence exist, since HF has not been consistently defined nor used as an endpoint in these trials. In patients with HF and sinus rhythm, the risk of stroke and other thrombotic events is high, and the use of warfarin has not, to date, been shown to confer outcome benefit. The benefit of the NOAC, rivaroxaban, is being investigated in HF without AF in the ongoing COMMANDER-HF trial. This review aims to provide an insightful perspective on the use of antithrombotic treatments in patients with both AF and HF, and in patients with HF and sinus rhythm, with particular attention to the NOACs, and provides background for therapeutic, outcome and trial improvement.

Patrón tromboelastográfico en pacientes anticoagulados con rivaroxabán por fibrilación auricular

IntroductionAtrial fibrillation is the most common arrhythmia, and it is associated with a higher risk of thromboembolic events requiring anticoagulation therapy. Nowadays there is no test that allows monitoring the therapeutic range when using new anticoagulants. MotivationTo describe thromboelastographic patterns in patients with atrial fibrillation who are taking anticoagulants with rivaroxaban in the Cardiology Department at the University Hospital Fundación Santa Fe de Bogotá. Material and methodsThe present cross-sectional study collected data relating to 30 patients with atrial fibrillation who received anticoagulation therapy with rivaroxaban between July 10th 2013 and January 6th 2015.General characteristics of the sample, as well as paramametres obtained from the thromboelastography, and they were compared to the thromboelastographic patterns according to the anticoagulant dose. ResultsAverage age was 75.8 years and the main indication for anticoagulation therapy was paroxysmal atrial fibrillation (56.67%). In more than 60% of patients a prolonged reaction time and low coagulation index was obtained. The remaining parametres from the thromboelastography were located within the normal range in most cases. No statistically significant differences were found in thromboelastographic patterns when comparing the 15mg versus 20mg rivaroxaban dose. ConclusionThromboelastographic patterns obtained in most study participants were characterized by a high reaction time and low coagulation index, possibly due to the effect of the factor Xa inhibitor.

Khorama score as a predictive tool for thromboembolic events in high risk patients

There is an established relation between cancer and the development of thromboembolic venous disease. Khorana et al developed a predictive score using clinical characteristics and laboratory values to stratify patients according to their risk. To characterize using Khorana score, patients with active cancer and a diagnosis of thromboembolic disease during hospitalization in an oncology hospital. Review of records of the pharmacy of the hospital, selecting patients who received heparin in therapeutic doses during their hospitalization. Using laboratory values available in the medical records, the Khorama score was calculated. Twenty seven patients with thromboembolic events, aged 60 ± 2 years (56% males) were selected for the study. Eighty percent of them were catalogued in the intermediate and high risk group according to Khorana score. Khorana score is a simple scale that might be useful to establish early prophylactic measures in patients with high risk for thromboembolic events, especially those with cancer.

Young Male Patients with Atrial Fibrillation and CHA2DS2-VASc Score of 1 May Not Need Anticoagulants: A Nationwide Population-Based Study.

BackgroundIt is unclear whether oral anticoagulants are beneficial for atrial fibrillation (AF) patients with low CHA2DS2-VASc score. Age could be important in determining the risk of thromboembolism in low risk AF patients (CHA2DS2-VASc score of 1 for male or 2 for female).MethodsThe Taiwan National Health Insurance Research Database (NHIRD) was used and 27,521 AF patients with CHA2DS2-VASc score of 1 (male) or 2 (female) not receiving anticoagulants were acquired as the study cohort, which were classified into three age groups: 20–49, 50–64, and 65–74 years. The clinical endpoint was the occurrence of ischemic thromboembolism within one year of follow up.ResultsDuring the follow-up of 0.94 ± 0.19 years, 385 (2.19%) male patients experienced ischemic thromboembolism, with annual rate of 2.32%. The annual risk ranged from 1.29%, 2.43% to 2.77% for male patients aged 20–49, 50–64 and 65–74 years respectively. Of the female patients, 218 (2.20%) experienced clinical event with annual rate of 2.32%. The annual risk increased from 1.87%, 2.28% to 2.64% for female patients aged 20–49, 50–64 and 65–74 years respectively. There was no difference in risk between the male patients aged 20–49 years with CHA2DS2-VASc score of 1 and overall male patients with CHA2DS2-VASc score of 0. (P = 0.631) The female patients aged 20–49 years with CHA2DS2-VASc score of 2 was associated with a higher risk of thromboembolic events than overall female patients with CHA2DS2-VASc score of 1 (HR = 1.93; P = 0.008).ConclusionsAge is important in determining the risk of thromboembolism in AF patients with single risk factor. In male patients <50 years old with CHA2DS2-VASc score of 1, the risk of ischemic thromboembolism was low. Considering the benefits and the risk of bleeding, oral anticoagulation therapy may not be favorable in these patients.

The Periprocedural Management of Anticoagulation and Platelet Aggregation Inhibitors in Endoscopic Interventions.

In Germany, more than half a million persons, most of them elderly, are under long-term treatment with anticoagulants. The approval of new oral anticoagulants and platelet aggregation inhibitors, as well as new data on periprocedural bridging with heparins, have introduced marked complexity to the management of treatment with anticoagulants and platelet aggregation inhibitors for endoscopic interventions in visceral surgery. This review is based on pertinent publications retrieved by a selective literature search in PubMed, as well as on the relevant guidelines. Robust data are available on the management of vitamin K antagonists (VKA) and platelet aggregation inhibitors for endoscopic procedures; on the other hand, the data on the periprocedural management of non-VKA oral anticoagulants (NOAC) are still inadequate. Endoscopic procedures that carry a low risk of bleeding can be performed under treatment with anticoagulants or platelet aggregation inhibitors. Before any procedure with a high risk of bleeding (≥ 1.5%) oral anticoagulants of any type and P2Y12 inhibitors should generally be discontinued. Patients in whom VKA are temporarily discontinued for this reason need bridging treatment with heparin only if they are at high risk of thromboembolic events (≥ 10% per year). For patients who are anticoagulated with NOAC, timely discontinuation of the drug depending on renal function is of key importance, and bridging is usually unnecessary. Adequate scientific evidence supports the current recommendations and treatment algorithms for the periprocedural management of oral anticoagulants and platelet aggregation inhibitors in endoscopic procedures. Larger-scale studies are still needed to provide a sound basis for the corresponding recommendations about NOAC.

Incidence and Risk Factors of Thromboembolism with Multiple Myeloma in the Presence of Death as a Competing Risk: An Empirical Comparison of Statistical Methodologies

Multiple myeloma (MM) has an inherent high risk of thromboembolic events associated with patient as well as disease- and treatment-related factors. Previous studies have assessed the association of MM-related thromboembolism using “traditional” Kaplan–Meier (KM) and/or Cox proportional hazard (PH) regression. In the presence of high incidence of death, as would be the case in cancer patients with advanced age, these statistical models will produce bias estimates. Instead, a competing risk framework should be used. This study assessed the baseline patient demographic and clinical characteristics associated with MM-related thromboembolism and compared the cumulative incidence and the measures of association obtained using each statistical approach. The cumulative incidence of thromboembolism was 9.2% using the competing risk framework and nearly 12% using the KM approach. Bias in the measures of covariate risk associations was highest for factors related to risk of death such as increased age (75% bias) and severe liver disease (50%) for the Cox PH model compared to the competing risk model. These results show that correct specification of statistical techniques can have a large impact on the results obtained.

Risks of thromboembolic events among patients diagnosed with metastatic pancreatic ductal adenocarcinoma treated with chemotherapy.

380 Background: Clinical trials suggest that patients with metastatic pancreatic ductal adenocarcinoma (mPDA) are at a high risk of thromboembolic events (TEs) as a result of both disease and treatment. Real-world data on TE rates are limited for patients with mPDA. Methods: Using a retrospective cohort design, patients with mPDA aged ≥ 65 years and treated with chemotherapy during 2007-2012 were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients enrolled in Medicare parts A, B, and D were followed from the start of first-line chemotherapy (index date) to the earliest of disenrollment from Medicare, death, or 12/31/2012. The baseline (BL) period was defined as 12 months prior to the index date. The incidence of TEs was calculated as the number of events per 100 person-years (PY) of follow-up (F/U) among patients without a BL TE. Anticoagulant use during F/U was categorized as preventive (before first TE, if any) and treatment (on or after first TE date) among patients with no BL TE. Results: Of 1,308 patients meeting the selection criteria, the mean age was 74 years, and 56% were female. The prevalence of TEs during the study period (BL or F/U) was 58% (n = 755). Excluding the 427 patients (33%) with TEs during BL, 328/881 (37%) of patients had a first TE during F/U, for an incidence rate of 85/100PY, including 29/100PY arterial and 59/100PY venous events. In the full study cohort, only 467/1,308 (36%) had a claim for any anticoagulant during the study period, although inpatient anticoagulant use is likely under-reported. Among patients receiving anticoagulants, 287/467 (61%) received low molecular weight heparin (LMWH). Preventive anticoagulant use was observed in 74/881 (8%) of patients without a BL TE; anticoagulation treatment was observed for 159/328 (48%) patients with a first TE during F/U. Conclusions: Real-world mPDA patients face a significant risk of TEs both before and after starting chemotherapy. Although inpatient use of anticoagulants including LMWH is incomplete in this database, it is clear that use of anticoagulants for treatment, and for prevention, of TEs is sub-optimal.

Heart Disease in WomenNandaNavin C., KeserNurgul, 513 pages. New Delhi, India: Jaypee Brothers Medical Publishing Ltd. 2015. $184.00, ISBN-13: 978-9351522942

Navin C. Nanda, Nurgul Keser, 513 pages. New Delhi, India: Jaypee Brothers Medical Publishing Ltd. 2015. $184.00, ISBN-13: 978-9351522942 Heart disease is the leading cause of death among women. In comparison with men, women have greater cardiovascular mortality, report more morbidity, and have greater reductions in quality of life. Furthermore, sex disparities in cardiovascular health exist among women of all ages, socioeconomic backgrounds, and racial subgroups, which likely reflect both lingering diagnostic and treatment disparities, and underlying biological sex differences, as well. For example, there is a largely female predominance of stress-induced (Takotsubo) cardiomyopathy after menopause, a greater occurrence of heart failure with preserved ejection fraction, particularly in elderly women, and a higher incidence of rheumatic mitral stenosis among women in developing countries. In addition, after 55 years of age, hypertension is more prevalent in women than in men, particularly in black women. Clinical outcomes also differ by sex. Women with atrial fibrillation have a higher risk of thromboembolic events in comparison with men, and, among individuals younger than 55 years of age, the rate of acute myocardial infarction in the past decade has declined in men, but not in women. As the importance and impact of cardiovascular disease in women is increasingly recognized, we are learning how heart disease is distinct between the sexes, both in its pathophysiology and in our ability to diagnose and treat women. To better understand and appreciate sex differences in cardiovascular disease, there needs to be a compilation of current knowledge and an accessible tool that …

Hemorrhagic stroke and oral anticoagulants: What is to be done?

Hemorrhagic stroke (HS) is associated with high mortality and disability rates. Due to the introduction of the current guidelines for the prevention of systemic thromboembolic events in patients with atrial fibrillations and to an increase in the number of older patients, there has been a rise in the incidence of intracranial hemorrhage (ICH) associated with the use of oral anticoagulants. The paper discusses medical treatment in patients with HS during therapy with vitamin K antagonists (warfarin) and novel oral anticoagulants (dabigatran. rivaroxaban, apixaban), as well as an anticoagulant resumption policy after prior ICH in patients at high risk for thromboembolic events.

Comparing the Efficacy of Aspirin or Low Molecular Weight Heparin or Vitamin K Antagonists in the Risk of Thromboembolic Events in Patients with Multiple Myeloma Treated with Lenalidomide-Based Therapy

BackgroundMalignancy is a well-recognized risk factor for venous thromboembolism (VTE). In multiple myeloma the incidence of VTE varies between 3% and 10%. Immunomodulatory drugs (IMiDs) play a crucial role in the treatment of myeloma and are known to be associated with an increased risk of arterial and venous thromboembolic events (TE). It appears that patients with newly diagnosed multiple myeloma (NDMM) are at higher risk for TE compared to patients with relapsed or refractory myeloma (RRMM) at the start of IMiD therapy.Lenalidomide is a second-generation IMiD which in combination to dexamethasone has shown to be an effective and well-tolerated therapy for patients with NDMM or RRMM. However, studies have consistently demonstrated the need for TE prophylaxis in patients receiving the combination lenalidomide-dexamethasone which leads to a 4.4-fold increased risk for VTE compared to dexamethasone alone in the absence of prophylactic anticoagulants.Panel consensus from the International Myeloma Work Group has agreed that the choice of thromboprophylaxis depends on the individual risk of TE, as determined by patient and treatment-related factors, such as obesity, prior VTE, central venous catheter, immobilization, recent surgery, comorbidities, use of erythropoietin stimulating agents and myeloma therapy. Aspirin (ASA) is recommended for patients with one or no risk factors, and LMWH for those with more than one risk factor. However, the optimal approach to thromboprophylaxis has not yet been established.In this study we sought to compare the efficacy of ASA or low molecular weight heparin (LMWH) or vitamin K Antagonists (VKA) in the prevention of VTE or arterial thromboembolism (ATE) in patients with myeloma using lenalidomide-based therapy.MethodsWe performed a retrospective chart review in 2 centres (London, Canada; and Salamanca, Spain) on patients with NDMM or RRMM multiple myeloma receiving lenalidomide-based therapy. We collected data from january 2010 to December2014.We included adult patients diagnosed with NDMM or RRMM receiving lenalidomide-based therapy. We did not include who received lenalidomide but refused or had contra-indication to thromboprophylaxis; or used single agent lenalidomide.ResultsWe included 168 patients with multiple myeloma receiving lenalidomide-based therapy. 14 (8%) were NDMM and 154 (92%) had RRMM. Median age was 68 (31-89) and 106 (63%) were males. On average patients with RRMM had 1.6 previous treatments (range:1-11). 104 (62%) patients were low risk and 64 (38%) were high risk for TE. 140 (83%) patients received prophylaxis with ASA, 32 (19%) LMWH and 6 (4%) VKA. 10 patients started with prophylactic LMWH for an average of 2 months then were empirically switched over to ASA. In total, there were 18 (10.7%) TE of which, 16 (9.5%) were VTE: 3 PE, 12 DVT, 1 both. The relative risk for TE was the same regardless of risk stratification [RR=1.27 (95%CI 0.524 - 3.059; p=0.599)]. At TE diagnosis, 16 patients were on ASA, 1 on LMWH and 1 on VKA. The relative risk of TE was significantly higher for patients on ASA compared to LMWH or VKA [RR= 2.17 (0.522 - 9.03; p= 0.286).After the TE, all patients changed anticoagulation strategy: 15 of 16 (94%) patients with VTE switched to therapeutic LMWH and 1 who was on VKA had ASA added. In the 2 patients with ATE, 1 started on full dose LMWH and the other one continued on ASA. 16 of 18 patients with a TE continued on lenalidomide-based therapy. There was no recurrent arterial or venous TE within the first 6 months of anticoagulation after the TE. Univariate analysis suggested that BMI, use of ASA and sex could be potential predictors of TE; but the logistic regression was not statistically significant (Table).ConclusionsIn patients with multiple myeloma on lenalidomide-based therapy the preferred TE prophylactic approach is low dose ASA irrespective of patients' risk assessment for thromboembolism. However, VTE risk in these patients is not negligible (9.5%) and low dose ASA may not be the best prophylactic strategy for them. It appears that patients on ASA, obese and males are at higher risk for TE. Future studies are needed to confirm these assumpations.Table 1Multivariate Analysis of the TE risk for patients with myeloma on lenalidomide-based therapyOdds RatioVariablePoint Estimate95% CIp -valueSex2.3160.8546.2780.0989BMI1.7050.5015.8040.3935ASA3.8700.48630.7960.2010 DisclosuresLouzada:Celegene: Consultancy, Other: advisory board and expert opinion; pfizer: Consultancy, Other: advisory board and expert opinion; janssen: Consultancy, Other: advisory board and expert opinion. Mateos:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ocio:Array BioPharma: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy; Mundipharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; MSD: Research Funding; Pharmamar: Consultancy, Research Funding; Janssen: Honoraria. Porras:Celgene: Consultancy, Honoraria.

Higher risk of thromboembolic events with IVIg therapy

Higher risk of thromboembolic events with IVIg therapy

Prognostic value of CHA2DS2-VASc score in patients with ‘non-valvular atrial fibrillation’ and valvular heart disease: the Loire Valley Atrial Fibrillation Project

The CHA2DS2VASc score is a clinical risk stratification tool which estimates the risk of stroke and thromboembolism in non-valvular atrial fibrillation (AF). We aimed to establish the value of this score for risk evaluation in patients with non-valvular AF and valvular heart disease. Among 8053 patients with non-valvular AF (ESC guidelines definition), patients were categorized into Group 1 (no valve disease, n = 6851; 85%) and Group 2 (valve disease with neither rheumatic mitral stenosis nor valve prothesis, n = 1202; 15%). After follow-up of 868 ± 1043 days, 627 stroke/ thromboembolic (TE) events were recorded. Group 2 was significantly older, had a higher CHA2DS2VASc score and had a higher risk of thromboembolic events [hazard ratio (HR) 1.39; 95% CI 1.14-1.69, P = 0.001] compared with Group 1. Severe valve disease was not associated with worse prognosis for stroke/TE events. In the two groups, stroke/TE risk increased with a higher CHA2DS2VASc score. Factors independently associated with increased risk of stroke/TE events were older age (HR 1.25, 95% CI 1.14-1.36 per 10-year increase, P < 0.0001) and higher CHA2DS2VASc score (HR 1.33, 95% CI 1.23-1.45, P < 0.0001). The predictive value (c-statistic) of the CHA2DS2VASc score was similar in the two groups. In patients with non-valvular AF, left-sided valvular heart disease (excluding mitral stenosis and protheses) was associated with an increased risk of stroke/TE events. A higher CHA2DS2VASc score in these patients is likely to explain these results.

EP News: Clinical

Steinberg et al (Eur Heart J 2015;36:288, PMID 2520959) evaluated the risk of thromboembolism on the basis of the category of atrial fibrillation (AF) in patients randomized to rivaroxaban or warfarin. Thromboembolic events, bleeding, and death were analyzed. Of 14,062 patients, 11,548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF had higher rates of stroke or systemic embolism (2.18 vs 1.73 events per 100-patient-years; P = .048) and all-cause mortality (4.78 vs 3.52; P = .006). Rates of major bleeding were similar (3.55 vs 3.31; P = .77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs warfarin, P = 0.6). The authors conclude that in patients with AF receiving anticoagulation, those with persistent AF have a higher risk of thromboembolic events and worse survival than those with paroxysmal AF.