Thromboprophylactic Treatment Research Articles

Predictive model for deep venous thrombosis caused by closed lower limb fracture after thromboprophylactic treatment.

Currently, there are still no convincing clinical models predicting closed lower extremity fracture-associated deep vein thrombosis in patients treated through thromboprophylactic methods. We aimed at using two retrospective cohorts to develop and externally verify a clinical prediction model for deep vein thrombosis in patients treated with anticoagulants after suffering closed lower extremity fractures. We evaluated the patients' pre- and post-operatively, to accurately determine the predictive power of the biomarkers and clinical risk factors. Two retrospective cohorts were used for the development and external verification of a pre-operative clinical prediction model (development: n = 2,253; verification: n = 833) and post-operative clinical prediction model (development: n = 1,422; verification: n = 449), respectively. The C-indices were used to show the predicted incidence of objective thrombosis at the pre- and post-operative stage, which were then compared with the observed incidence of thrombosis in both cohorts. Biomarkers and clinical indicators were included in pre- and post-operative nomograms, which were adequately calibrated in both cohorts. The cross-validated C-indices of the pre- and post-operative clinical prediction models in the verification cohort were 0.706 (95% Cl, 0.67-0.74) and 0.875 (95% Cl, 0.84-0.91), respectively. We present our findings of novel pre- and post-operative nomograms for the prediction of deep venous thrombosis in patients who received thromboprophylaxis after suffering closed lower extremity fractures.

Prevention of venous thromboembolic events in patients with lower leg immobilization after trauma: Systematic review and network meta-analysis with meta-epsidemiological approach.

BackgroundLower limb trauma requiring immobilization is a significant contributor to overall venous thromboembolism (VTE) burden. The clinical effectiveness of thromboprophylaxis for this indication and the optimal agent strategy are still a matter of debate. Our main objective was to assess the efficacy of pharmacological thromboprophylaxis to prevent VTE in patients with isolated temporary lower limb immobilization after trauma. We aimed to estimate and compare the clinical efficacy and the safety of the different thromboprophylactic treatments to determine the best strategy.Methods and findingsWe conducted a systematic review and a Bayesian network meta-analysis (NMA) including all available randomized trials comparing a pharmacological thromboprophylactic treatment to placebo or to no treatment in patients with leg immobilization after trauma. We searched Medline, Embase, and Web of Science until July 2021. Only RCT or observational studies with analysis of confounding factors including adult patients requiring temporary immobilization for an isolated lower limb injury treated conservatively or surgically and assessing pharmacological thromboprophylactic agents or placebo or no treatment were eligible for inclusion. The primary endpoint was the incidence of major VTE (proximal deep vein thrombosis, symptomatic VTE, and pulmonary embolism-related death). We extracted data according to Preferred Reporting Items for Systematic Reviews and Meta-analyses for NMA and appraised selected trials with the Cochrane review handbook. Fourteen studies were included (8,198 patients). Compared to the control group, rivaroxaban, fondaparinux, and low molecular weight heparins were associated with a significant risk reduction of major VTE with an odds ratio of 0.02 (95% credible interval (CrI) 0.00 to 0.19), 0.22 (95% CrI 0.06 to 0.65), and 0.32 (95% CrI 0.15 to 0.56), respectively. No increase of the major bleeding risk was observed with either treatment. Rivaroxaban has the highest likelihood of being ranked top in terms of efficacy and net clinical benefit. The main limitation is that the network had as many indirect comparisons as direct comparisons.ConclusionsThis NMA confirms the favorable benefit/risk ratio of thromboprophylaxis for patients with leg immobilization after trauma with the highest level of evidence for rivaroxaban.Trial registrationPROSPERO CRD42021257669.

Platelet dysfunction after trauma: From mechanisms to targeted treatment.

Platelet dysfunction after trauma: From mechanisms to targeted treatment.

Effect of lower‐leg trauma and knee arthroscopy on procoagulant phospholipid‐dependent activity

BackgroundLower‐leg injury and knee arthroscopy are both associated with venous thromboembolism (VTE). The mechanism of VTE in both situations is unknown, including the role of procoagulant microparticles. This may provide useful information for individualizing thromboprophylactic treatment in both patient groups. ObjectiveWe aimed to study the effect of (1) lower‐leg trauma and (2) knee arthroscopy on procoagulant phospholipid‐dependent (PPL) activity plasma levels. MethodsPOT‐(K)CAST trial participants who did not develop VTE were randomly selected for the current study. Plasma was collected shortly after lower‐leg trauma or before and after knee arthroscopy. For aim 1, samples of 67 patients with lower‐leg injury were compared with control samples (preoperative samples of 74 patients undergoing arthroscopy). Linear regression was used to obtain mean ratios (natural logarithm retransformed data), adjusted for age, sex, body mass index, infections, and comorbidities. For aim 2, pre‐ and postoperative samples of 49 patients undergoing arthroscopy were compared using paired t tests. PPL activity was measured using modified activated factor X–dependent PPL clotting assay. ResultsFor aim 1, PPL activity levels were almost threefold higher in patients with lower‐leg injury compared with controls, that is, mean ratio, 2.82 (95% confidence interval [CI], 1.98‐4.03). For aim 2, postoperative PPL activity levels did not change significantly, that is, mean change, −0.72 mU/mL (95% CI, −2.03 to 0.59). ConclusionLower‐leg trauma was associated with increased plasma levels of PPL activity, in contrast to knee arthroscopy. Lower‐leg trauma triggers the release of procoagulant microparticles.

Effectiveness and safety of dual antiplatelet therapy in coronary aneurysms caused by Kawasaki disease in children: study protocol for a multicenter randomized clinical trial.

BackgroundMedium or large coronary artery aneurysm (CAA) is a serious complication of Kawasaki disease (KD) and may cause thrombosis, coronary artery stenosis, and even myocardial infarction at different stages of the disease. Dual antiplatelet therapy (aspirin plus clopidogrel) is considered for prophylaxis of coronary thrombosis in KD presenting with more than medium CAAs based on adult coronary artery disease experience and expert consensus. This paper describes the study protocol for a randomized controlled trial that measures the clinical effectiveness and safety of dual antiplatelet therapy in the thromboprophylactic treatment of KD.MethodsThe present study is a multicenter, open-label, randomized controlled trial (RCT) with a 12-month follow-up. KD patients with medium or large CAAs (Z-value ≥5), evaluated by echocardiogram and clinicians before treatment, are randomized in a 1:1 ratio and assigned to aspirin therapy alone (Control group), or dual antiplatelet (aspirin plus clopidogrel) therapy (Experimental group). Antiplatelet therapy is given to the KD patients from the time of diagnosis until the coronary artery returns to normal. Weekly or monthly follow-up visits are conducted to record compliance, recovery, and biochemical indicators and continue for one year. The primary outcome is the incidence of thrombus throughout the disease and the effective of dual antiplatelet. The secondary outcomes are the safety of dual antiplatelet drugs, platelet-related indicators, inflammatory indicators, biochemical indexes and drug-related indicators during the study period. Patients who do not meet the inclusion criteria of the RCT trial or those unwilling to provide informed consent enter the registration trial.DiscussionThis is the first study to evaluate the effectiveness and safety of dual antiplatelet therapy in coronary aneurysms caused by Kawasaki disease in children. It is hoped that this study will play an important and significant role in improving the prognosis and long-term quality of life for children with KD complicated by CAAs.Trial registrationChinese Clinical Trial Registry, ChiCTR1800019181. Registered on Oct 30, 2018.

Pulmonary Embolism in Adipsic DI: Can Desmopressin Be a Contributing Factor?

Background: Adipsic DI (ADI) is a rare disease associated with various morbidities. One of them is venous thromboembolism (VTE). In literature there are less than 10 reported cases and scarce management orientations. Classically, in ADI, VTE risk is due to dehydration and acute hypernatremia. Desmopressin should also be considered as it has a known role in blood coagulation such as increasing platelet cohesion and promoting von Willebrand factor release. Clinical Case: A 51-year woman with past medical history of obesity class 3 and a craniopharyngioma surgically intervened 8 months before, underwent a second craniotomy due to recurrent lesion. Postoperatively the patient developed an ADI, hypopituitarism and impairement of higher brain functions namely short-term memory and sleep-wake cycles impairment. She was discharged on desmopressin 0.35mg/day, levetiracetam 1500mg/day, hidrocortisone 15mg/day, levothyroxine 75mcg/day and quetiapine 25mg/day. Two weeks after discharge, the patient was admitted to the emergency room with anorexia and malaise. Tests were consistent with PE: elevated D-dimmer levels and CT angiography revealing bilateral PE. Treatment with enoxaparin was initiated. There was no hemoconcentration or polycythemia; kidney and liver function were normal, and sodium of 148 mEq/L (135-145 mEq/L). Three days before she had normal sodium levels. Respiratory insufficiency, deep vein thrombosis and infection were excluded. The patient did not present signs of dehydration. Brain CT did not show acute alterations. There was no personal history of smoking or family history of thrombosis and the patient was not on bed rest in the previous couple of weeks. During hospital stay abdominal and pelvic CT did not reveal malignancies. The patient was discharged on enoxaparin and posteriorly underwent a mammogram and colonoscopy; both exams without relevant alterations. At the last follow-up visit, she remained hypocoagulated and with desmopressin, with no further episodes of thrombosis. Conclusion: We report for the first time a case of PE in an obese patient with ADI treated with desmopressin and without overt hypernatremia or dehydration. All previously published cases of VTE in ADI have occurred in patients presenting with moderate to severe hypernatremia (sodium 157-181 mEq/L) and some degree of dehydration at the time of the event. Obesity and a recent hospitalization may have contributed to the development of VTE but desmopressin should also be taken into consideration due to its known effects on coagulation. Thromboprophylactic treatment after pituitary surgery and during acute episodes of hypernatremia and dehydration is already warranted in ADI but we additionally suggest considering at least short-term thromboprophylaxis in obese patients with recent ADI diagnosis treated with desmopressin as they might have this additional increased thrombotic risk.

High risk of venous thromboembolism after orthopedic surgery in patients with thrombophilia

ObjectiveThis study aimed at evaluating the effect of thrombophilia on the risk of venous thromboembolism (VTE) in patients undergoing any type of orthopedic surgery. BackgroundPatients undergoing orthopedic surgery are at high risk for VTE. Although patients with thrombophilia have an increased risk of VTE, it is currently unclear whether there is a synergetic effect in patients with thrombophilia who undergo orthopedic surgery. MethodsData from a large population‐based case–control study (the Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis study) were used. Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for age, sex, and body mass index (BMI) (ORadj) were calculated for patients undergoing any orthopedic intervention. ResultsOf 4721 cases and 5638 controls, 263 cases and 94 controls underwent orthopedic surgery. Patients who had any orthopedic intervention in the year before the index date were at higher risk of VTE (ORadj 3.7; 95% CI, 2.9‐4.8) than those who did not undergo any orthopedic surgery. There was an additionally increased risk in patients with factor V Leiden (OR 17.5, 95% CI, 4.1‐73.6), non‐O blood group (OR 11.2; 95% CI, 3.4‐34.0), or elevated plasma levels of factor VIII (OR 18.6; 95% CI, 7.4‐46.9) all relative to patients without these defects, not undergoing orthopedic surgery. ConclusionsPatients with factor V Leiden, high levels of factor VIII, or blood group non‐O were found to have a high risk of VTE after orthopedic surgery. Identification of these patients may enable individualized thromboprophylactic treatment to efficiently reduce VTE risk.

Coagulopathie associée au COVID-19 : les éléments essentiels pour l’anesthésiste-réanimateur

RésuméLes perturbations de la coagulation sont fréquemment observées chez les patients atteints de COVID-19 ainsi que les événements cliniques thrombotiques. Ces évènements augmentent le risque de décès au cours de la maladie. Parmi les évènements biologiques, on observe une augmentation des D-Dimères (> 3 μg/L), du fibrinogène (> 8 g/L) et une thrombopénie qui caractérisent le syndrome et sont associées à un mauvais pronostic. Ces marqueurs devraient être surveillés régulièrement au cours de l’hospitalisation des patients en réanimation. Le diagnostic d’embolie pulmonaire peut être difficile dans le contexte mais doit être évoqué en cas d’aggravation inexpliquée de l’hypoxémie ou d’insuffisance cardiaque droite. Le risque thromboembolique doit être stratifié pour adapter la thrombo-prophylaxie en prenant compte la fonction rénale et le surpoids des patients.

Single stage bilateral total hip arthroplasty - 10 years of experience

Background/Aim. Coxarthrosis is a chronic degenerative joint disorder which occurs in approximately 4% of population, and bilateral occurrence is estimated at 42%. Patients with bilateral coxarthrosis can undergo bilateral hip replacement in one or two stage procedure. Aim of this article was to present our experience in simultaneous bilateral hip arthroplasty, and to recommend it in patients with adequate indications. Methods. We processed data for 113 patients of both genders, operated at the Clinic for Orthopedic Surgery and Traumatology of the Military Medical Academy in Belgrade, Serbia from 2005 until 2015 where single stage bilateral hip arthroplasty was performed. Identical operative technique was applied in all patients as well as standard antibiotic and thromboprophylactic treatment. Follow-up period was 30 days postoperatively. Results. Mean age of patients was 56 ? 10.2 years, whereby 45 (39.8%) of them were males and 68 (60.2%) females. Primary coxarthrosis was etiologic factor for the majority of patients, 69 (61.1%). Postoperative hospitalization duration was 10.3 days on average (range from 3 to 34 days). We noticed the following complications: one luxation of the endoprosthesis, one deep infection and one thrombosis of the leg. There was no mortality. Majority of operated patients were grouped as the American Society of Anesthesiologists (ASA) scores 1-3. Mean blood transfusion was 1,275 mL (range from 300 to 2,830 mL). Conclusion. One stage bilateral hip arthroplasty can be performed routinely and safely in facilities with possibility for interdisciplinary approach and adequate selection of patients. Data from our study which indicate significantly increased need for blood substitution, emphasize the need to introduce contemporary perioperative blood loss management principles. The rate of complications observed in our study was within rates published in the literature concerning hip arthroplasty.

Venous thromboembolism risk and prophylaxis prescription in surgical patients at a tertiary hospital in Eastern Cape Province, South Africa.

Venous thromboembolism (VTE) is a common complication during and after hospitalisation, and is regarded as the most common cause of preventable death in hospitalised patients worldwide. Despite its importance, there are few data on VTE risk and adherence to prophylaxis prescription guidelines in surgical patients from the South African (SA) public sector, especially from low-resource environments such as Eastern Cape Province. To evaluate the risk and prescription of VTE prophylaxis to surgical patients at a tertiary government hospital in the Eastern Cape. A cross-sectional clinical audit of general surgical inpatients was performed on two dates during July and August 2017. Patients' VTE risk was calculated by using the Caprini risk assessment model (RAM) and thromboprophylaxis prescription evaluated accordingly. A total of 179 patients were included in the study, of whom 56% were male and 44% female. The average age was 45 (range 18 - 83) years. Of the total number of participants, 33% were elective cases and 67% were emergency admissions. With application of RAM, 77% of patients were at risk of VTE (Caprini score ≥2), with 81% of elective and 74% of emergency patients being at risk. The most prevalent risk factors for VTE were major surgery (34%), age 41 - 60 years (30%), age 61 - 74 years (20%) and sepsis during the previous month (27%). A contraindication to chemoprophylaxis was recorded in 30% of patients, with the most prevalent being renal dysfunction (40%), peptic ulcer disease (34%), active bleeding (17%), liver dysfunction (17%), coagulopathy (6%) and recent cerebral haemorrhage (6%). With regard to VTE risk profile and contraindications to chemoprophylaxis, the correct thromboprophylactic treatment was prescribed to 26% of at-risk patients, with 21% of elective and 27% of emergency admission patients receiving the correct therapy. Despite a high proportion of patients being at risk of VTE, the rate of adequate thromboprophylaxis prescription for surgical inpatients at Frere Hospital, East London, SA is very low. Increased availability of mechanical prophylaxis, as well as interventions to improve the rate of adequate prophylaxis prescription, needs to be evaluated for feasibility and effect in this hospital and other SA public hospitals.

No effectiveness of anticoagulants for thromboprophylaxis after non-major knee arthroscopy: a systemic review and meta-analysis of randomized controlled trials.

Arthroscopic knee surgery is the most commonly performed orthopedic procedure worldwide and whether thromboprophylaxis should be undertaken after knee arthroscopy is still controversial. To evaluate the efficacy of thromboprophylaxis for deep venous thrombosis (DVT) and venous thromboembolism (VTE) after knee arthroscopic surgery. A meta-analysis was conducted using data from eight randomized trials (4148 patients) to compare thromboprophylaxis with placebo or no prophylactic treatment in patients undergoing knee arthroscopy. The benefits and harms of thromboprophylaxis were evaluated, including the incidence of asymptomatic DVT, symptomatic VTE, pulmonary embolism and anti-coagulation related adverse events. Thromboprophylaxis significantly decreased the incidence of DVT (95% CI 0.07-0.64, P = 0.006) and symptomatic VTE in patients undergoing knee arthroscopy (95% CI 0.23-0.76, P = 0.004), but not significantly decreased the incidence of pulmonary embolism (n.s.). Regarding to non-major knee arthroscopy surgery (simple surgical procedures without ligament reconstruction), no significant difference of the incidence of DVT or symptomatic VTE was noted between thromboprophylactic group and control group (n.s.). Thromboprophylactic treatment showed higher incidence rate of anti-coagulation related adverse events compared with the control group (95% CI 1.12-1.90, P = 0.005). There was no significant difference of the incidence of clinically relevant major bleeding between the two groups (n.s.). This meta-analysis indicates no effectiveness of thromboprophylaxis for preventing DVT or symptomatic VTE in patients undergoing non-major knee arthroscopy. Regarding to patient undergoing knee ligament construction, the thromboprophylactic strategy should mainly take into account the patient's risk factors.

Video-assisted Thoracoscopic surgery (VATS) lobectomy for lung cancer does not induce a procoagulant state

BackgroundChanges in the coagulation system in patients undergoing surgery for lung cancer have been sparsely investigated and the impact of the surgical trauma on the coagulation system is largely unknown in these patients. An increased knowledge could potentially improve the thromboprophylaxis regimes. The aim of this study was to assess the coagulation profile evoked in patients undergoing curative surgery by Video-Assisted Thoracoscopic Surgery (VATS) lobectomy for primary lung cancer.MethodsThirty-one patients diagnosed with primary lung cancer undergoing VATS lobectomy were prospectively included. The coagulation profile was assessed preoperatively and in the first two days postoperatively using a wide range of standard coagulation tests, dynamic whole blood coagulation measured by rotational thromboelastometry (ROTEM®) and thrombin generation evaluated by calibrated automated thrombography. Patients did not receive thromboprophylactic treatment. Data was analyzed using repeated measures one-way ANOVA.ResultsThe standard coagulation parameters displayed only subtle changes after surgery and the ROTEM® and thrombin generation results remained largely unchanged.ConclusionsPatients undergoing VATS lobectomy are normocoagulable in the preoperative state and a VATS lobectomy does not significantly influence the coagulation.Trial registrationThe trial is registered at ClinicalTrials.gov (Identifier: NCT01741506) and at EudraCTno. 2012–002409-23. Registered December 2012.

P3582Increased thromboprophylactic treatment of patients with atrial fibrillation after the introduction of NOACs - an analysis of sex and gender differences

P3582Increased thromboprophylactic treatment of patients with atrial fibrillation after the introduction of NOACs - an analysis of sex and gender differences

Sex and Gender Differences in Thromboprophylactic Treatment of Patients With Atrial Fibrillation After the Introduction of Non–Vitamin K Oral Anticoagulants

To examine sex differences in thromboprophylaxis in patients with atrial fibrillation before and after the introduction of non-vitamin K oral anticoagulants, we performed a cross-sectional registry study based on anonymized individual-level patient data of all individuals with a diagnosis of nonvalvular atrial fibrillation (International Classification of Diseases, Tenth Revision code I48) in the region of Stockholm, Sweden (2.2 million inhabitants), in 2011 and 2015, respectively. Thromboprophylaxis improved considerably during the period. During 2007 to 2011, 23,198 men and 18,504 women had an atrial fibrillation diagnosis. In 2011, more men than women (53% men vs 48% women) received oral anticoagulants (almost exclusively warfarin) and more women received aspirin only (35% women vs 30% men), whereas there was no sex difference for no thromboprophylaxis (17%). During 2011 to 2015, 27,237 men and 20,461 women had a diagnosis of atrial fibrillation. Compared with the earlier time period, a higher proportion used oral anticoagulants (71% women vs 70% men), but fewer women ≥80 years received anticoagulants (67% women vs 72% men), more women received aspirin (15% women vs 13% men), and fewer women had no thromboprophylaxis (15% women vs 17% men). Patients with co-morbidities potentially complicating oral anticoagulant use used more oral anticoagulant in 2015 compared with 2011. The sex differences observed in 2011 with fewer women using oral anticoagulants had disappeared in 2015 except in women 80 years and older and in patients with complicated co-morbidity.

Interrelation of blood coagulation and hemorheology in cancer.

Cancer progression is associated with activation of blood coagulation. Blood coagulation process, platelet hemostasis and hemorheological properties were evaluated in patients with solid tumors (n = 27) before and after surgery and in healthy control (n = 20). The main features of blood coagulation process in cancer patients were elevated intensity and shortened period of contact phase of coagulation and inhibited fibrinolysis stage. Such prothrombotic state was fixed before surgery as well as in early postoperative period in spite of preventing thromboprophylactic treatment. Platelets depletion within the high level of spontaneous and ADP-induced platelet aggregation was fixed in cancer. The main cause of blood viscosity decrease in cancer patients was dramatic fall of Hct, because blood viscosity adjusted by Hct 40% was increased owing to the rise of plasma viscosity and substantially worsened RBC microrheological properties. The results of our study indicated close correlation between hemorheological and hemostasis parameters; these interrelations were more numerous and strong in cancer. In cancer patients the combination of a high aggregation activity of platelets, reduced number of erythrocytes (Hct), an increase of RBC aggregation and plasma viscosity caused impairment of blood oxygen transportation efficacy that provoke hypoxia in the microcirculation favoring thrombosis, settlement of tumor and metastasis.

Determination of dabigatran and rivaroxaban by ultra-performance liquid chromatography-tandem mass spectrometry and coagulation assays after major orthopaedic surgery

Major orthopaedic surgery is associated with an increased risk of venous thromboembolism. Direct oral anticoagulants (DOACs) are recommended as thromboprophylactic agents after orthopaedic surgery. Although routine monitoring of DOACs in general is not required, measuring DOAC concentration may be necessary in clinical settings. The effects of DOACs on routine coagulation assays in spiked material are studied extensively, however, few data are available on DOAC concentration in patients after major orthopaedic surgery.We measured trough and peak DOAC concentrations with UPLC-MS/MS and routine coagulation tests in a prospective study including 40 patients receiving thromboprophylactic treatment with dabigatran 220mg od and 40 patients receiving rivaroxaban 10mg od after major orthopaedic surgery.For rivaroxaban, the median trough concentration with UPLC-MS/MS was 17.1ng/mL and median peak concentration was 149ng/mL. The anti-Xa assay displayed a good correlation, but a positive bias in comparison to the reference method. Furthermore, trough levels were mostly below the LOD of the anti-Xa assay. For dabigatran, the median trough concentration with UPLC-MS/MS was 12.1ng/mL, and median peak level was 80.8ng/mL. A positive bias was found when results from coagulation assays were compared to UPLC-MS/MS data. However, the addition of glucuronidated metabolites to dabigatran concentration UPLC-MS/MS data generally resolved most of this bias. Age was found to have a significant influence on dabigatran pharmacokinetics, irrespective of kidney function, whereas no effect of age was found during rivaroxaban treatment. In both treatment groups, female subjects displayed faster pharmacokinetics in comparison to male subjects, although not reaching significance.We conclude that UPLC-MS/MS is the method of choice to measure trough concentrations of DOACs in patients after orthopaedic surgery. Current coagulation assays are not suited for this purpose. We found large heterogeneity in both peak and trough concentrations of DOACs, and showed that pharmacokinetics of novel oral anticoagulants may be influenced by age and gender. Whether patients with high or low trough concentrations are at increased risk for bleeding or thromboembolic events respectively remains to be established.

The overuse of thromboprophylaxis in medical patients: main clinical aspects

Overuse of thromboprophylaxis is not an infrequent behavior in internal medicine. However, differently from underuse, overuse of thromboprophylaxis is rarely taken into account, and only few studies have addressed this issue. The purpose of our study was to try to understand the reasons behind this phenomenon. Using data from the TEVERE study, we evaluated 279 patients hospitalized in 21 hospitals of the Lazio Region in Italy. Only patients who were negative to major risk scores as established in the scientific literature were included. We assessed the frequency of thromboprophylaxis in acutely ill medical patients hospitalized in emergency and internal medicine wards, and we performed a comparative analysis for each risk factor among patients who received or not received thromboprophylaxis. Forty-seven patients (16.5%) with negative risk scores were given thromboprophylaxis during hospitalization. On backward stepwise logistic regression analysis, severe infection (odds ratio [OR] 2.31; 95% confidence interval [CI] 1.25-4.35) and chronic venous insufficiency (OR 3.02; 95% CI 1.96-4.67) were found to be the strongest predictors of the use of thromboprophylactic treatment with heparin. The subgroup of patients who did not exhibit risk factors was also analyzed, and age was found to be the main factor in the decision-making process regarding heparin administration in the absence of other risk factors (74.9 ± 11.8 vs 63.7 ± 18.1, p=0.002). Our findings suggest that thromboprophylaxis is associated with considerable uncertainty, which results in its overuse. Further research is needed to better understand thromboembolic risk factors in hospitalized medical patients.

A Phase II Multicenter Trial With Rivaroxaban in the Treatment of Livedoid Vasculopathy Assessing Pain on a Visual Analog Scale.

BackgroundLivedoid vasculopathy is an orphan skin disease characterized by recurrent thrombosis of the cutaneous microcirculation. It manifests itself almost exclusively in the ankles, the back of the feet, and the distal part of the lower legs. Because of the vascular occlusion, patients suffer from intense local ischemic pain. Incidence of livedoid vasculopathy is estimated to be around 1:100,000. There are currently no approved treatments for livedoid vasculopathy, making off-label therapy the only option. In Europe, thromboprophylactic treatment with low-molecular-weight heparins has become widely accepted.ObjectiveThe aim of this trial is the statistical verification of the therapeutic effects of the anticoagulant rivaroxaban in patients suffering from livedoid vasculopathy.MethodsWe performed a therapeutic phase IIa trial designed as a prospective, one-armed, multicenter, interventional series of cases with a calculated sample size of 20 patients. The primary outcome is the assessment of local pain on the visual analog scale (VAS) as an intraindividual difference of 2 values between baseline and 12 weeks.ResultsEnrollment started in December 2012 and was still open at the date of submission. The study is expected to finish in November 2014.ConclusionsLivedoid vasculopathy is associated with increased thrombophilia in the cutaneous microcirculation and the continuous use of anticoagulants helps improve the symptoms. The causes of cutaneous infarctions are heterogenous, but ultimately follow the known mechanisms of the coagulation cascade. Rivaroxaban affects the coagulation cascade and inhibits the factor Xa–dependent conversion of prothrombin to thrombin, thereby considerably reducing the risk of thrombosis.Trial RegistrationTrial Registration EudraCT Number: 2012-000108-13-DE; https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000108-13 (Archived by WebCite at http://www.webcitation.org/6UCktWVCA); German Clinical Trials Register (DRKS): DRKS00004652; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004652 (Archived by WebCite at http://www.webcitation.org/6UCIAKyCS).

Inflammatory bowel disease: epidemiology, pathology and risk factors for hypercoagulability.

Hypercoagulability observed in patients with inflammatory bowel diseases (IBD) may lead to thromboembolic events (TE), which affect the venous and arterial systems alike and are an important factor in patients' morbidity and mortality. The risk of TE in IBD patients has been demonstrated to be approximately three-fold higher as compared to the general population. The pathogenesis of thrombosis in IBD patients is multifactorial and not fully explained. The most commonly listed factors include genetic and immune abnormalities, disequilibrium between procoagulant and anticoagulant factors, although recently, the role of endothelial damage as an IBD-triggering factor is underlined. Several studies report that the levels of some coagulation enzymes, including fibrinogen, factors V, VII, VIII, active factor XI, tissue factor, prothrombin fragment 1 + 2 and the thrombin-antithrombin complex, are altered in IBD patients. It has been demonstrated that there is a significant decrease of tissue plasminogen activator level, a marked increase of plasminogen activator inhibitor type 1 and thrombin-activable fibrinolysis inhibitor, a significantly lower level of antithrombin III and tissue factor pathway inhibitor. IBD patients have been also observed to produce an increased amount of various anticoagulant antibodies. Hyperhomocysteinemia, which is a potential risk factor for TE was also observed in some IBD patients. Further studies are necessary to assess the role of coagulation abnormalities in IBD etiology and to determine indications for thromboprophylactic treatment in patients at high risk of developing TE.

Risk of cardiovascular disease in inflammatory bowel disease.

Abundant scientific evidence supporting an association between inflammatory bowel disease (IBD) and venous thromboembolic events, caused by an IBD related hypercoagulability, is acknowledged and thromboprophylactic treatment strategies are now implemented in the management of IBD patients. In contrary, the risk of arterial thromboembolic disease, as ischemic heart disease, cerebrovascular events, and mesenteric ischemia in patients with IBD remains uncertain and the magnitude of a potentially increased risk is continuously debated, with ambiguous risk estimates among studies. The evident role of inflammation in the pathogenesis of atherosclerosis forms the basis of a biological plausible link; the chronic systemic inflammation in IBD patients increases the risk of atherosclerosis and thereby the risk of thrombotic events. Further, studies have shown that the burden of traditional risk factors for atherosclerosis, such as obesity, diabetes mellitus, and dyslipidemia is lower in IBD populations, thus further strengthen the role of non-traditional risk factors, as chronic inflammation in the linking of the two disease entities. Likewise, mortality from cardiovascular disease in IBD remains questioned. The aim of the current review is to give an up-date on the existing evidence of the possible association between IBD and cardiovascular disease and to discuss traditional and non-traditional risk factors.