Heparin Thromboprophylaxis Research Articles

26. Does anticoagulant thromboprophylaxis increase bleeding complications in spinal surgery and spinal cord injury? A systematic review and meta-analysis

BACKGROUND CONTEXT The routine use of anticoagulants for the prevention of venothromboembolism in spinal patients is controversial and the risk benefit analysis is poorly described. PURPOSE The objective of this systematic review and meta-analysis is to collate the current evidence and quantify the risk of bleeding associated with anticoagulant thromboprophylaxis in the spinal patient, both in the elective and trauma settings. STUDY DESIGN/SETTING Spinal surgery and trauma inpatients. PATIENT SAMPLE A total of 92,406 patients. OUTCOME MEASURES Outcomes of interest were the number of patients with spinal epidural hematoma or wound hemorrhagic complications that were associated with neurological symptoms or required treatment, including either operative or nonoperative intervention. METHODS MEDLINE, EMBASE, Cochrane Trial Register databases and the grey literature were searched. Data were pooled via a meta-analysis from randomized trials and cohort studies comparing the rates of spinal epidural hematoma and wound hemorrhagic complications in spinal surgery patients receiving low molecular weight and low dose unfractionated heparin (LMWH/UFH) thromboprophylaxis and those not anticoagulated. The risk of bias within individual studies and across all the studies was assessed using the Cochrane risk of bias tools and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool, respectively. RESULTS The meta-analysis included 11 studies of 92,406 patients with 1,007 relevant bleeding complications. A significant increase in the risk of extra-spinal wound hemorrhage was found in patients receiving perioperative LMWH/UFH thromboprophylaxis compared to controls (OR 1.56, 95% CI 1.18 - 2.06, p=0.002, I2=8%). The same comparison revealed no significant increase in the risk of spinal epidural hemorrhage (OR 1.20, 95% CI 0.65 - 2.22, p=0.56, I2=0%). The quality of evidence for both outcomes was low. There was insufficient data to conclude about the risk of hemorrhagic complications in spinal trauma and in patients receiving nonheparin thromboprophylaxis agents. CONCLUSIONS Our results raise concern about a possible increased risk of extraspinal wound hemorrhage associated with LMWH/LDUFH thromboprophylaxis in spinal surgery. FDA DEVICE/DRUG STATUS low molecular weight heparin (Approved for this indication), low dose unfractionated heparin (Approved for this indication)

DVT incidence and risk factors in critically ill patients with COVID-19

Few data are available on the incidence of deep vein thrombosis (DVT) in critically ill COVID-19 with thrombosis prophylaxis. This study retrospectively included 88 patients in the ICU with critically ill COVID-19 at Jinyintan Hospital in Wuhan, China. All patients underwent compression ultrasonography for identifying DVT. Firth logistic regression was used to examine the association of DVT with sex, age, hypoalbuminemia, D-dimer, and SOFA score. The median (interquartile range [IQR]) age and SOFA score of 88 patients were 63 (55–71) years old and 5 (4–6), respectively. Despite all patients receiving guideline-recommended low-molecular-weight heparin (LMWH) thromboprophylaxis, the incidence of DVT was 46% (95% CI 35–56%). Proximal DVT was recognized in 9% (95% CI 3–15%) of the patients, while 46% (95% CI 35–56%) of patients had distal DVT. All of the proximal DVT combined with distal DVT. Risk factors of DVT extension occurred in all distal DVT patients. As Padua score ≥ 4 or IMPROVE score ≥ 2, 53% and 46% of patients had DVT, respectively. Mortality was higher in patients with acute DVT (30%) compared with non-DVT (17%), but did not reach statistical significance. Hypoalbuminemia (odds ratio [OR], 0.17; 95% CI 0.06–0.05, P = 0.001), higher SOFA score (OR per IQR, 2.07; 95% CI 1.38–3.39, P = 0.001), and elevated D-dimer (OR per IQR, 1.04; 95% CI 1.03–1.84, P = 0.029) were significant DVT risk factors in multivariable analyses. High incidence of DVT was identified in patients with critically ill COVID-19, despite the use of guideline-recommended pharmacologic thromboprophylaxis. The presence of hypoalbuminemia, higher SOFA score, and elevated D-dimer were significantly independent risk factors of DVT. More effective VTE prevention and management strategies may need to be addressed.

COVID19 coagulopathy in Caucasian patients.

SummaryAlthough the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung‐centric coagulopathy may play an important role. Elevated D‐dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies. Critically however, ethnicity has major effects on thrombotic risk, with a 3–4‐fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African‐Americans. In this study, we investigated COVID19 coagulopathy in Caucasian patients. Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity. Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC). In rare COVID19 cases where DIC does develop, it tends to be restricted to late‐stage disease. Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary‐specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC. Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality.

Extended versus inpatient thromboprophylaxis with heparins following major open abdominopelvic surgery for malignancy: a systematic review of efficacy and safety

BackgroundPatients undergoing open abdominopelvic procedures for malignancy are at high risk of postoperative venous thromboembolism (VTE). This risk can be mitigated with prophylaxis; however, optimum duration in this population remains unknown. Our objective was to conduct a systematic review of contemporary literature on the use of heparin thromboprophylaxis following major open pelvic surgery for malignancy, comparing the efficacy and safety of extended duration to inpatient treatment.MethodsA study protocol describing search strategy and inclusion and exclusion criteria was developed and registered with PROSPERO. A literature review was conducted in accordance with the protocol.ResultsLiterature review identified only 4 studies directly comparing extended and inpatient duration prophylaxis, with a combined population of 3198 and 3135 patients for VTE rate and bleeding events, respectively. Despite many studies reporting lower VTE rates in patients receiving extended prophylaxis, no statistically significant difference in rates of postoperative VTE (p = 0.18) or bleeding complications (p = 0.43) was identified between patients receiving extended duration prophylaxis and those receiving inpatient only prophylaxis.ConclusionOn the review of contemporary literature, no significant difference was found in rates of postoperative VTE or bleeding complications between patients receiving extended duration heparin VTE prophylaxis and those receiving inpatient prophylaxis after open abdominopelvic surgery for malignancy.This raises the question of how extended duration prophylaxis has become common practice in this population, and whether this needs to be re-evaluated.

Are We Missing Treatment Standards for Thromboprophylaxis of the Obese and Super-Obese Patient Population? A Prospective Systematic Cohort Study.

Venous thromboembolism (VTE) is the most frequent 30-day complication in patients with morbid obesity undergoing bariatric surgery. Therefore, there is a need for optimized low molecular weight heparin (LMWH) thromboprophylaxis dosing strategies in order to avoid VTE-associated morbidity and mortality in this patient population. The primary goal was to evaluate if a pre-specified enoxaparin dosing regimen in patients undergoing bariatric surgery reaches anti-factor Xa (aFXa) levels in the defined target range (0.2-0.4U/ml). Second, we aimed to identify biometric and laboratory parameters that might influence the aFXa value. A prospective database of 236 patients with obesity who received thromboprophylaxis with enoxaparin was established. These patients were divided into two weight-adjusted groups (group 1 < 150kg, group 2 ≥ 150kg). Enoxaparin was administered twice daily; dosing was determined by weight (group 1, 2 × 40mg/day; group 2, 2 × 60mg/day). In both groups, the peak aFXa serum level was evaluated 3days after initiating the thromboprophylaxis. In group 1 (body mass index (BMI) 42.94 ± 6.84kg/m2, weight of 121.7 ± 17.49kg), seventy-one of the included 124 patients (57.25%) reached the aFXa target range of 0.2 to 0.4U/m. In group 2 (BMI 63.21 ± 10.05kg/m2, weight of 191.66 ± 33.37kg), 68 of 112 (60.71%) patients scored prophylactic aFXa range. Multiple regression of the biometric and laboratory parameters showed significance for weight, waist-to-hip ratio, glomerular filtration rate (GFR), creatinine, and HbA1c exclusively in group 1. There was no case of VTE within 3months after surgery and no case of severe perioperative bleeding in those patients who underwent surgery. Measurement of the aFXa level helps to define the real prophylactic thromboprophylaxis status in patients with obesity, especially in those with a weight above 150kg. In patients at risk, the measurement of aFXa should be considered in routine clinical practice.

Pulmonary embolism in cases of COVID-19.

Emerging reports indicate a high incidence of venous thromboembolism in patients hospitalised for SARS-CoV-2pneumonia during the spring 2020pandemic. The pronounced pulmonary and systemic inflammatory responses observed in these patients may contribute to a transient hypercoagulable state. In this setting, pulmonary embolism may cause further respiratory distress and clinical deterioration. We describe the clinical course of three patients admitted with SARS-CoV-2 infection and respiratory distress, where pulmonary embolism was detected during the course of the hospitalisation. Two of the cases occurred despite early institution of standard dosage of low molecular weight heparin thromboprophylaxis, and in one case, pulmonary embolism was diagnosed during the convalescent phase of an otherwise benign COVID-19 disease course. These cases highlight the importance of awareness of the potentially increased incidence of venous thromboembolism in COVID-19 disease. Further research is required to establish appropriate clinical management guidelines for prevention of thromboembolic complications in COVID-19.

227: Factors associated with women's adherence to postpartum thromboprophylaxis: a prospective cohort study

Postpartum low-molecular-weight heparin (LMWH) thromboprophylaxis is indicated for a substantial proportion of women. We assessed women's adherence to postpartum thromboprophylaxis and the factors associated with adherence. This prospective cohort study was conducted at a university hospital during 2018. Parturients for whom a recommendation for LMWH prophylaxis was given at discharge from the maternity ward were contacted at the end of the recommended post-discharge course of LMWH, and were invited to participate in a telephone survey. The main outcome measures were optimal (>80%) and suboptimal adherence (< 80%) to LMWH administration, reasons for nonadherence, and views regarding LMWH, as assessed by an adapted Beliefs about Medication Questionnaire. Overall, 250 women completed the questionnaire. The median recommended duration of post-discharge LMWH was 7 [5-8] days. Suboptimal adherence was reported by 82 (32.8%); 45 (18.0%) women did not administer any LMWH dose following discharge and only 147 (58.8%) completed the full LMWH course. In multivariate analysis, optimal adherence was positively associated with patients' perceptions of the necessity of LMWH (odds ratio [95% CI]: 3.50 (2.12, 9.53), P=0.002) and of the adequacy of explanation given prior to discharge regarding LMWH technical administration (odds ratio [95% CI]: 5.0 (2.33, 11.11), P< 0.001). Nearly one-third of women prescribed postpartum LMWH thromboprophylaxis reported suboptimal adherence. Patients' perceptions of the necessity of the treatment and their opinion of the adequacy of explanation regarding LMWH technical administration were identified as predictors of treatment compliance, and thus represent potential areas for improvement.

Safety and Efficacy of High-Dose Unfractionated Heparin Versus High-Dose Enoxaparin for Venous Thromboembolism Prevention in Morbidly Obese Hospitalized Patients

Venous thromboembolism is a cause of morbidity and mortality in hospitalized patients, and morbid obesity increases this risk. Various prophylaxis dosing strategies have been investigated. However, it is unclear if high-fixed dose enoxaparin or high-fixed dose unfractionated heparin thromboprophylaxis is optimal for minimizing the incidence of major bleeding and reducing hospital-acquired venous thromboembolism. A single-center retrospective observational study was conducted in hospitalized patients who were morbidly obese (body mass index ≥40 kg/m2) and who received either high-fixed dose enoxaparin (40 mg every 12 hours) or unfractionated heparin (7500 units every 8 hours) for venous thromboembolism prophylaxis. Co-primary outcomes included incidence of major bleeding and venous thromboembolism diagnosed during hospitalization. Predictors of major bleeding were evaluated by multivariable regression. In the 305 patients included (n=190 unfractionated heparin, n=115 enoxaparin), the incidence of major bleeding was significantly higher in the unfractionated heparin group (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.07-3.13; P=0.025), with no significant difference in the incidence of venous thromboembolism diagnosed during hospitalization. The only independent predictors of major bleeding were intensive care acuity (OR 3.32, 95% CI 1.91-5.78; P <0.001) and selection of unfractionated heparin rather than enoxaparin for venous thromboembolism prophylaxis (OR 2.16, 95% CI 1.22-3.82; P=0.008). High-fixed dose unfractionated heparin for venous thromboembolism prophylaxis may lead to a higher risk of major bleeding events compared with high-fixed dose enoxaparin in patients who are morbidly obese.

The risk and prevention of venous thromboembolism in the pregnant traveller.

The average risk of venous thromboembolism (VTE) in long haul travellers is approximately 2.8 per 1000 travellers, which is increased in the presence of other VTE risk factors. In pregnant long-haul travellers, little is known in terms of the absolute risk of VTE in these women and, therefore, there is limited consensus on appropriate thromboprophylaxis in this setting. This review will provide guidance to allow practitioners to safely minimize the risk of travel-related VTE in pregnant women. The suggestions provided are based on limited data, extrapolated risk estimates of VTE in pregnant travellers and recommendations from published guidelines. We found that the absolute VTE risk per flight appears to be <1% for the average pregnant or postpartum traveller. In pregnant travellers with a prior history of VTE, a potent thrombophilia or strong antepartum risk factors (e.g. combination of obesity and immobility), the risk of VTE with travel appears to be >1%. Postpartum, the risk of VTE with travel may be >1% for women with thrombophilias (particularly in those with a family history) and other transient risk factors and in women with a prior VTE. Based on our findings, we recommend simple measures be taken by all pregnant travellers, such as frequent ambulation, hydration and calf exercises. In those at an intermediate risk, we suggest a consideration of 20-30mmHg compression stockings. In the highest risk group, we suggest careful consideration for low-molecular-weight heparin thromboprophylaxis. If there are specific concerns, we advise consultation with a thrombosis expert at the nearest local centre.

Factors associated with women’s adherence to postpartum thromboprophylaxis

Postpartum low-molecular-weight heparin (LMWH) thromboprophylaxis is indicated for a substantial proportion of women. We assessed women's adherence to postpartum thromboprophylaxis and the factors associated with adherence. This retrospective cohort study was conducted at a university hospital during 2018. Parturients for whom a recommendation for LMWH prophylaxis was given at discharge from the maternity ward were contacted at the end of the recommended post-discharge course of LMWH, and were invited to participate in a telephone survey. The main outcome measures were optimal (> 80%) and suboptimal adherence (< 80%) to LMWH administration, reasons for nonadherence, and views regarding LMWH, as assessed by an adapted Beliefs about Medication Questionnaire. Overall, 250 women completed the questionnaire. The median recommended duration of post-discharge LMWH was 7 [5-8] days. Suboptimal adherence was reported by 82 (32.8%); 45 (18.0%) women did not administer any LMWH dose following discharge and only 147 (58.8%) completed the full LMWH course. In multivariate analysis, patients' perceptions of the necessity of LMWH [odds ratio (95% CI): 3.50 (2.12, 9.53), P = 0.002] and of the adequacy of the explanation given prior to discharge regarding LMWH technical administration [odds ratio (95% CI): 5.0 (2.33, 11.11), P < 0.001] were positively associated with optimal adherence. Nearly one-third of women prescribed postpartum LMWH thromboprophylaxis reported suboptimal adherence. Patients' perceptions of the necessity of the treatment and their opinion of the adequacy of explanation regarding LMWH technical administration were identified as predictors of treatment compliance, and thus represent potential areas for improvement.

Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis

BackgroundWhether adjunctive intermittent pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis would result in a lower incidence of deep-vein thrombosis than pharmacologic thromboprophylaxis alone is uncertain.MethodsWe randomly assigned patients who were considered adults according to the local standards at the participating sites (≥14, ≥16, or ≥18 years of age) within 48 hours after admission to an intensive care unit (ICU) to receive either intermittent pneumatic compression for at least 18 hours each day in addition to pharmacologic thromboprophylaxis with unfractionated or low-molecular-weight heparin (pneumatic compression group) or pharmacologic thromboprophylaxis alone (control group). The primary outcome was incident (i.e., new) proximal lower-limb deep-vein thrombosis, as detected on twice-weekly lower-limb ultrasonography after the third calendar day since randomization until ICU discharge, death, attainment of full mobility, or trial day 28, whichever occurred first.ResultsA total of 2003 patients underwent randomization — 991 were assigned to the pneumatic compression group and 1012 to the control group. Intermittent pneumatic compression was applied for a median of 22 hours (interquartile range, 21 to 23) daily for a median of 7 days (interquartile range, 4 to 13). The primary outcome occurred in 37 of 957 patients (3.9%) in the pneumatic compression group and in 41 of 985 patients (4.2%) in the control group (relative risk, 0.93; 95% confidence interval [CI], 0.60 to 1.44; P=0.74). Venous thromboembolism (pulmonary embolism or any lower-limb deep-vein thrombosis) occurred in 103 of 991 patients (10.4%) in the pneumatic compression group and in 95 of 1012 patients (9.4%) in the control group (relative risk, 1.11; 95% CI, 0.85 to 1.44), and death from any cause at 90 days occurred in 258 of 990 patients (26.1%) and 270 of 1011 patients (26.7%), respectively (relative risk, 0.98; 95% CI, 0.84 to 1.13).ConclusionsAmong critically ill patients who were receiving pharmacologic thromboprophylaxis, adjunctive intermittent pneumatic compression did not result in a significantly lower incidence of proximal lower-limb deep-vein thrombosis than pharmacologic thromboprophylaxis alone. (Funded by King Abdulaziz City for Science and Technology and King Abdullah International Medical Research Center; PREVENT ClinicalTrials.gov number, NCT02040103; Current Controlled Trials number, ISRCTN44653506.)

Long-term outcome of open surgery in CVI patients concerning postoperative complications, perioperative hemodynamics and clinical efficacy, Part I

Chronic venous disease (CVD) is extremely common worldwide. The prevalence is increasing with age and is associated with a reduced quality of life, particularly in relation to pain, physical function and mobility. Symptomatic chronic venous insufficiency (CVI) with venous ulcer at its' endpoint, indicates interventional surgery to cure venous reflux therewith promoting wound healing and preventing recurrence. To our knowledge up to now no coherent study has been undertaken in patients with CVI who underwent an open venous surgery concerning complications, venous hemodynamics and perioperative symptomology in one study population. This was undertaken in our retrospective, single-centre, consecutive case-control study in a single patient population of a university clinic in northern Germany. Part I covers postoperative complications in relation with co-morbidities, co-medication and clinical presentation. Part II will focus on pre- and postoperative hemodynamics and evolution of symptoms. Records of n = 429 (467 extremities) patients from 2009-2013 treated with open surgery were analysed. Number and type of complication were evaluated with regards to demographic parameters, co-existing medical conditions and procedure related aspects. Complications were grouped as no events (NE), neglectable adverse events (NAE), non-neglectable adverse events (NNAE) and severe (life-threatening) adverse events (SAE). In 467 extremities of 429 patients with CVI 130 (27,84%) postoperative complications were observed after open surgery, thereof 64 (13,7%) NAE, 66 (14,14%) NNAE and 0 SAE. 29 (6,76%) patients developed a postoperative surgical site infection, thereof 4 (0,9%) with consecutive septicaemia. Except one case with nerval lesion and paraesthesia and hypoesthesia not resolving after 12 months all complications resolved within surveillance time span of 12 months. Patients developing NAE had a higher BMI (p = 0.003), were more likely to have diabetes mellitus (p < 0.001), and co-morbidities leading to the intake of anti-platelet or anticoagulation drugs (p < 0.001). Metabolic syndrome (p < 0.001) and anti-platelet or anticoagulation (p < 0.001) could be defined as independent risk factors for the development of complications. Patients receiving open surgery of small saphenous veins had 8 times higher risk of calf muscle venous thrombosis (p = 0.001). Patients with a metabolic syndrome or receiving anti-platelet therapy or anticoagulation medication should undergo open venous surgery under hospital conditions with routine postinterventional surveillance visits. Patients undergoing an open surgery of SSV are definite candidates for postoperative subcutaneous heparin thromboprophylaxis. In general stripping below knee increases the risk of postoperative sensory deficit. This resolves in almost all patients within one year.

Rivaroxaban for prevention and treatment of venous thromboembolism.

Until recently, heparins and vitamin K antagonists (VKAs) were the cornerstones for prevention and treatment of venous thromboembolism (VTE). This situation changed with the introduction of the direct oral anticoagulants, which are now replacing low-molecular-weight heparin for thromboprophylaxis after elective hip or knee arthroplasty and VKAs for VTE treatment. Rivaroxaban, an oral factor Xa inhibitor, was the first direct oral anticoagulant licensed for VTE prevention and treatment. This paper provides the rationale for factor Xa as a target for anticoagulants, describes the development of rivaroxaban, reviews its pharmacological profile, discusses the clinical trials with rivaroxaban for VTE prevention and treatment and highlights areas of uncertainty.

Safety and efficacy of adjusted-dose enoxaparin in pregnant patients with increased risk for venous thromboembolic disease.

To assess the efficacy and safety of anti-Xa guided dose-adjusted low molecular weight heparin (LMWH) thromboprophylaxis in at-risk pregnant women. This single-center retrospective study was conducted at a quaternary hospital in Johannesburg, South Africa. We analyzed clinical and laboratory data for pregnant patients referred between January 1, 1999, and May 1, 2017, with an increased risk of venous thromboembolic disease (VTED) and treated with prophylactic LMWH adjusted according to anti-Xa levels. The efficacy endpoint was pregnancy-related VTED and/or pregnancy loss despite anti-Xa guided dose-adjusted LMWH thromboprophylaxis. We reviewed data for 113 consecutive pregnant patients with 151 pregnancies referred for prophylactic LMWH. Prevalence of pregnancy-related VTED was 1.3% (95% confidence interval [CI] 0.1-4.7), which is lower than that reported in the literature for fixed-dose thromboprophylaxis in similar at-risk groups. One venous thromboembolism event occurred in the antenatal period (despite adequate prophylaxis) and the second in the postpartum period (related to prolonged labor). Prevalence of pregnancy-related bleeding was 2% (95% CI 0.4-5.7) with all bleeding events considered to be minor and unrelated to LMWH therapy. This study demonstrated the efficacy and safety of anti-Xa dose-adjusted LMWH thromboprophylaxis in at-risk pregnant patients.

Thromboprophylaxis following cesarean section – a nation-wide survey from Germany

Objective: Our study aimed to assess current practice related to thromboprophylaxis following cesarean section (c.s.) among obstetricians in Germany taking account of the German and international guidelines.Study design: A nation-wide survey using a structured 22-item questionnaire was conducted in Germany. The questionnaire was sent to head of all registered departments of obstetrics and gynecology in Germany, followed by a single reminder followed 3 weeks after the first return deadline. The respondents’ answers were related to the different levels of care (1–4) of German perinatal centers.Results: In total 726 obstetric departments were invited to participate. Questionnaires were returned by 389 (54%) of departments. Of the respondents 162 (41%) stated to undertake risk assessment for venous thromboembolism (VTE) using a structured checklist or interview. Compared to level 4 centers risk assessment was significantly more often performed by perinatal centers level 1 (47 versus 35%, p = .05). The majority of responding hospitals preferred universal heparin thromboprophylaxis following elective and emergency caesarean section, regardless of additional risk factors (n = 362; 93%). The “usual” prophylactic dose of heparin was given by the majority of hospitals (n = 280, 72%), while 98 (25%) hospitals used heparin doses adjusted to patients’ body weight. In women at increased risk for VTE (e.g. previous VTE) there was a considerable variation in the recommended doses; 140 responding hospitals (36%) used 50–75% of the therapeutic heparin dose, 139 hospitals (36%) the “usual” prophylactic dose, and 97 hospitals (25%) preferred a therapeutic dose. In women at low risk for VTE 64% (n = 248) of hospitals recommended heparin thromboprophylaxis only during the hospital stay, 16% (n = 62) for at least 7 days after c.s., 4% (n = 15) for 10 days, 6% (n = 23) for 2–5 weeks, and 3% (n = 14) for 6 weeks postpartum. In women at increased risk level 1 centers prescribed heparin for VTE prophylaxis significantly more often for 6–8-week postpartum compared to level 4 centers (p = .02) whereas Level 4 centers used prophylactic heparin significantly more often <6 weeks (p = .01).Conclusion: Our survey reveals that the vast majority of hospitals (93%) used heparin prophylaxis after any c.s., irrespective of individual risk factors and the mode of c.s. (elective or emergency). This is in remarkable contrast to the recommendations from the German and other international guidelines. As well, we found a wide variation among respondents in dosing and duration of heparin related to the risk profile of VTE. This demonstrates, that there is little awareness and/or adherence to the German and other guideline recommendations which mirrors the inconsistencies between current guidelines. There is an urgent need to clarify optimal prophylaxis strategies after c.s. and the true magnitudes of benefits and harms associated with heparin prophylaxis by randomized controlled trials with sufficient statistical power.

Extended thromboprophylaxis with low-molecular weight heparin (LMWH) following abdominopelvic cancer surgery.

Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Certain abdominopelvic cancer surgeries are associated with a six to 14-fold increased risk of DVT versus surgeries for benign disease, and extended thromboprophylaxis using perioperative LMWHs may further reduce VTE rates over standard duration administration. This review assesses the value of extended low molecular weight heparin (LMWH) thromboprophylaxis as a recommended strategy after abdominopelvic cancer surgery. Six eligible randomized controlled trials (RCTs), seven meta-analyses (MAs), and five non-randomized cohort studies were identified evaluating extended versus standard thromboprophylaxis following abdominopelvic cancer surgery. Available evidence showed significantly reduced rates of VTE for extended versus standard LMWH thromboprophylaxis following abdominopelvic cancer surgery, with some studies showing trends toward reduced rates of symptomatic VTE events. Many of these studies showed significantly reduced rates of proximal DVT and some showed trends toward reduced PE, suggesting potentially important clinical benefits.

Low-Molecular-Weight Heparin for the Prevention of Venous Thromboembolism in Patients Undergoing Knee Arthroscopic Surgery and Anterior Cruciate Ligament Reconstruction: A Meta-analysis of Randomized Controlled Trials

Background: Low-molecular-weight heparin (LMWH) thromboprophylaxis is widely used for reducing the risk of thrombosis after major orthopaedic surgery. However, the effect and safety on knee arthroscopic surgery are still controversial. Purpose: To assess the efficacy and safety of LMWH for the prevention of symptomatic venous thromboembolism (VTE) after knee arthroscopic surgery and anterior cruciate ligament reconstruction (ACLR) by conducting a meta-analysis of randomized controlled trials (RCTs). Study Design: Meta-analysis. Methods: The authors searched the electronic databases of MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Web of Science for all studies from inception to June 30, 2017. All selected studies were categorized into 2 subgroups: simple knee arthroscopic surgery and ACLR. The primary effect and safety endpoint were the incidence of major VTE and major bleeding events (BEs), respectively. The secondary effect and safety endpoint were the incidence of all VTE and all BEs, respectively. Relative risks (RRs) with 95% CIs were calculated using Review Manager 5.3. Results: Eight RCTs with 4113 patients were included. For patients undergoing simple knee arthroscopic surgery, LMWH prophylaxis did not bring a significant reduction in the risk of major VTE (RR, 1.00 [95% CI, 0.37-2.67]; P > .99) and all VTE (RR, 0.63 [95% CI, 0.31-1.29]; P = .21) and did not increase the risk of major BEs (RR, 0.98 [95% CI, 0.06-15.72]; P = .99) but did have a higher risk of all BEs (RR, 1.64 [95% CI, 1.18-2.28]; P = .003) in comparison with non-LMWH prophylaxis. For patients undergoing ACLR, LMWH prophylaxis was associated with a significantly lower rate of major VTE (RR, 0.23 [95% CI, 0.12-0.43]; P < .001) and all VTE (RR, 0.22 [95% CI, 0.06-0.73]; P = .01) but no increase in major BEs (RR, 1.80 [95% CI, 0.19-17.25]; P = .61) and all BEs (RR, 1.12 [95% CI, 0.72-1.74]; P = .61) in comparison with non-LMWH prophylaxis. Conclusion: Compared with non-LMWH treatment, LMWH had no significant efficacy in preventing VTE in patients undergoing simple knee arthroscopic surgery but increased the risk of BEs. However, LMWH had significant efficacy in preventing VTE for patients mainly undergoing ACLR and did not increase the risk of BEs.

ГЕМОСТАЗИОЛОГИЧЕСКИЕ МАРКЕРЫ ПРОГНОЗИРОВАНИЯ РЕОККЛЮЗИИ ПОСЛЕ ТРОМБОЛИТИЧЕСКОЙ ТЕРАПИИ У ПАЦИЕНТОВ С КАРДИОЭМБОЛИЧЕСКИМ ИНСУЛЬТОМ

Цель работы: определить прогностическую значимость гемостазиологических параметров в развитии реокклюзии после тромболитической терапии у пациентов с кардиоэмболическим инсультом. Материалы и методы. Проанализировано лечение 52 пациентов с кардиоэмболическим типом ишемического инсульта, тяжесть которого по шкале NIHSS составляла 10-17 баллов. Данные пациенты попадали в терапевтическое окно, и согласно национальным рекомендациям им был проведен системный тромболизис. Ретроспективно больные были разделены на 2 группы: с эффективным тромболизисом (n = 36) и с признаками реокклюзии (n = 14). Результаты. Через 3 часа после тромболитической терапии у пациентов, у которых впоследствии развилась реокклюзия, в ответ на тромболитическую терапию наблюдалась мощная активация системы гемостаза, проявляющаяся существенным повышением уровня Д-димера и формированием патологически плотного сгустка на тромбоэластограмме. По данным ROC-анализа выявлена хорошая прогностическая точность в отношении развития реокклюзии со стороны концентрации Д-димера (AUROC = 0,766; точка отсечения – значения Д-димера ≥ 0,75 нг/мл) и отличная прогностическая точность со стороны параметра МА тромбоэластограммы (AUROC = 0,903; точка отсечения – значения МА ≥ 48 мм). Заключение. Для выделения когорты пациентов, которым в связи с высоким риском реокклюзии показано назначение антикогулянтов (антиагрегантов) сразу же после тромболизиса, необходимы дальнейшие исследования. Aim: to determine the prognostic significance of hemostasiological parameters in the development of reocclusion after thrombolytic therapy in patients with cardioembolic stroke. Materials and methods. The treatment of 52 patients with cardioembolic type of ischemic stroke (the severity – 10-17 points according NIHSS scale) was analyzed. These patients received systemic thrombolysis according to national guidelines. Retrospectively patients were divided into 2 groups: with effective thrombolysis (n = 36) and with signs of reocclusion (n = 14). Results. Three hours after thrombolytic therapy in patients with further developed reocclusion powerful hemostasis activation was observed that manifested by a significant increasing of D-dimer level and formation of a pathologically dense clot on thromboelastogram. According to ROC analysis good prognostic accuracy of reocclusion development for D-dimer level (AUROC = 0,766; cut-off point – D-dimer ≥ 0,75ng/ml) and excellent prognostic accuracy for parameter MA of thromboelastogram (AUROC = 0,903; cut-off point – МА ≥ 48 mm) were revealed. Conclusion. Further studies are needed for identification of patients with high risk of reocclusion who are prescribed the appointment of anticoagulants (antiaggregants) immediately after thrombolysis.

Venous Thromboembolic Complications to Hysterectomy for Benign Disease: A Nationwide Cohort Study

Study ObjectiveTo estimate the risk of venous thromboembolic complications after abdominal, laparoscopic, and vaginal hysterectomy when performed for benign disorders. DesignA nationwide cohort study (Canadian Task Force classification II-2). SettingData from Danish national registers on all women undergoing hysterectomy for benign conditions from 1996 to 2015. PatientsWomen aged 18 years and older who underwent hysterectomy for benign disease were stratified into 3 groups according to the hysterectomy approach: abdominal, laparoscopic, or vaginal. InterventionsHysterectomy. Measurements and Main ResultsEighty-nine thousand nine hundred thirty-one women met the inclusion criteria. Venous thromboembolism (VTE) as a diagnosis or cause of death was identified. The risk of postoperative VTE was examined with Cox proportional hazard models adjusting for age, surgical approach, and relevant comorbidities. The mean age was 49.9, 47.9, and 54.3 years for women with abdominal, laparoscopic, and vaginal hysterectomy, respectively. The crude incidences of VTE within 30 days after hysterectomy were 0.24% (n = 142), 0.13% (n = 12), and 0.10% (n = 21). The most important predictors of VTE were the approach to hysterectomy and a history of thromboembolic disease. In the multivariable analysis, the risk of VTE was significantly reduced with laparoscopic hysterectomy (hazard ratio [HR] = 0.51; 95% confidence interval [CI], 0.28–0.92; p = .03) and vaginal hysterectomy (HR = 0.39; 95% CI, 0.24–0.63; p < .001) when compared with the abdominal procedure. Data on postoperative heparin thromboprophylaxis were available in 53 566 patients, and the adjusted HR was 0.63 (95% CI, 0.42–0.96; p = .03) in patients receiving heparin thromboprophylaxis. ConclusionThe 30-day cumulative incidence of VTE after hysterectomy for benign conditions was low overall (0.19%). Laparoscopic hysterectomy and vaginal hysterectomy carry a lower risk than the abdominal procedure. Postoperative heparin thromboprophylaxis significantly reduces the risk of VTE and should be considered, especially if risk factors are present.

Plasma anti-FXa concentration after continuous intravenous infusion and subcutaneous dosing of enoxaparin for thromboprophylaxis in critically ill patients. A randomized clinical trial

IntroductionIn intensive care unit (ICU) patients, subcutaneous low-molecular weight heparin thromboprophylaxis results in lower plasma anti-factor Xa (anti-FXa) levels compared to general ward patients. The aim of this study was to examine whether enoxaparin thromboprophylaxis given as a continuous intravenous infusion (CII) results in more constant and predictable anti-FXa concentration than standard subcutaneous bolus (SCB) administration. Materials and methodsThis was a prospective, single-blind, multicenter, randomized controlled trial where ICU patients requiring thromboprophylaxis received enoxaparin either 40mg as a SCB once daily or 40mg as a CII over 24h for three consecutive days.The primary outcome was maximum serum anti-FXa concentration (Cmax24h) within the first 24h; the secondary outcome was anti-FXa area under the curve (AUC)(0–24h). Trough level was measured at 72h. ResultsThirty-nine patients were included in the intention to treat analysis. The median anti-FXa Cmax24h was 0.05 (interquartile range, IQR, 0.05–0.18) IU/ml in the CII group and 0.18 (IQR, 0.12–0.33) IU/ml in the SCB group (p=0.05). Median anti-FXa AUC(0–24h) was 1.20 (IQR, 0.98–2.88) in the CII and 1.54 (IQR, 1.22–4.12) in the SCB group (p=0.095). After 72h, 66.7% of patients in the CII group had a detectable anti-FXa concentration of >0.1IU/ml, compared with 16.7% in the SCB group (p=0.019). ConclusionsContinuous infusion of enoxaparin led to lower anti-FXa Cmax24h than standard SCB administration. No difference in anti-FXa AUC0–24h was detected.