Effectiveness Of Thromboprophylaxis Research Articles

Anticoagulation in COVID-19 patients – An updated systematic review and meta-analysis

BackgroundThromboembolic events are common complications of COVID-19. Clinical study results on safety and efficacy of anticoagulation in COVID-19 are controversial. Material and methodsThis report is the second update of our systematic review with meta-analysis on randomized controlled trials (RCTs) comparing standard thromboprophylaxis, intermediate or therapeutic dose anticoagulation or no anticoagulation in COVID-19 in- and outpatients. We searched eligible studies up to 5 October 2023. Certainty of evidence was assessed using GRADE. ResultsFor this update we included fourteen new RCTs and a total of 27 RCTs with 16,789 patients. Certainty of evidence ranged from very low to high depending on outcome and comparison. Standard thromboprophylaxis with low dose anticoagulation may have little or no effect for COVID-19 outpatients compared to no anticoagulation. In inpatients with moderate or severe COVID-19, intermediate dose anticoagulation may decrease any thrombotic events or death, but may increase major bleeding compared to standard thromboprophylaxis. Therapeutic dose anticoagulation decreases thrombotic events or deaths in inpatients with moderate COVID-19, but probably has little or no effect in patients with severe COVID-19 compared to standard thromboprophylaxis with low or intermediate dose anticoagulation. With therapeutic dose anticoagulation, the risk of major bleeding probably increases regardless of COVID-19 severity. We are uncertain on the effect of thromboprophylaxis with low dose anticoagulation compared to no anticoagulation in the post-discharge setting. ConclusionsHospitalized, moderately-ill COVID-19 patients may benefit from intermediate or therapeutic dose anticoagulation, while critically ill patients may not. Risk of major bleeding must be considered.

Application Areas of Intermittent Pneumatic Compression in the Prevention of Deep Vein Thrombosis During Dixon Surgery: A Randomized, Controlled Trial

PurposeDeep vein thrombosis (DVT) is common in the lithotomy position after laparoscopic surgery. Intermittent pneumatic compression (IPC) plays an important role in DVT prevention. However, few studies have compared the different compression areas of IPC application. It was hypothesized that the location of the compression sleeves could have an impact on the effects of thromboprophylaxis. MethodsIn this randomized, controlled trial performed from August 2020 to March 2021, 164 patients scheduled to undergo laparoscopic Dixon surgery were randomly assigned to one of four groups, based on the bilateral placement of compression sleeves during surgery: feet, calves, thighs, or control (no IPC). Both lower extremities were monitored for DVT on days 1 and 7 after surgery, using ultrasonographic assessment of mean blood velocity, blood flow volume, and diameter of the common femoral veins. Thrombosis-related hematologic analysis was performed. FindingsOn day 1 after surgery, IPC of the feet or calves was associated with a reduced prevalence of DVT compared with controls (both: P = 0.024; OR = 0.09; 95% CI, 0.01–0.72), while IPC of the thighs had no significant benefit (P = 0.781; OR = 0.86; 95% CI, 0.29–2.55). The prevalence of DVT in the left extremity was lower with IPC of the feet and calves compared with controls (both, P = 0.048). The mean blood velocity in the common femoral vein was significantly increased after surgery with IPC of the left and right feet (P = 0.006 and 0.007, respectively) and calves (P = 0.011 and P = 0.026, respectively) compared with controls. Similarly, the volume of blood flow in the left common femoral vein was greater with IPC of the feet and calves (P = 0.03 and 0.027, respectively). However, on day 7 after surgery, the between-group differences in the prevalences of DVT and hematologic indicators of thrombosis were not significant. ImplicationsOn day 1 after surgery, IPC application at the feet or calves facilitated venous return and, hence, reduced the prevalence of DVT, especially in the left extremities. However, there were no significant differences in the prevalences of DVT or thrombosis-related hematologic indicators among the four groups on the day 7 after surgery. Chinese Clinical Trial Registration identifier: ChiCTR2000035325.

Effectiveness of thromboprophylaxis with low molecular weight heparin in critically ill patients with COVID-19. An observational prospective, multicenter study.

COVID-19 induces coagulopathy associated with an increase of thromboembolic events. Due to the lack of agreement on recommendations for thromboprophylactic management, the aim of this study was to study the dosages of LMWH used in critically ill COVID-19 patients assessing the effect on their outcome. We evaluated data of the Reg-COVID19. According to LMWH dose two groups were analyzed: prophylaxis and treatment. Primary outcome was the relationship of LMWH dosage with mortality. Secondary outcomes included the incidence of thrombotic and bleeding events, length of ICU stay, invasive mechanical ventilation, and thrombotic and inflammatory parameters. Data of 720 patients were analyzed, 258 in the prophylaxis group and 462 in the treatment group. C Reactive Protein, invasive mechanical ventilation, tocilizumab and corticosteroid treatments were related with the choice of LMWH dose. Hemorrhagic events (66/720, 9.2%) and thrombotic complications (69/720, 9.6%) were similar in both groups (p = .819 and p = .265), as was the time course of the thrombotic events, earlier than hemorrhagic ones (9 [3-18] and 12 [6-19] days respectively). Mortality was lower in prophylaxis group (25.2% versus 35.1%), but once an inverse probability weighting model was applied, we found no effect of LMWH dose. We found no benefit or harm with the administration of therapeutic or prophylactic LMWH dose in COVID19 critically ill patients. With a similar rate of hemorrhagic or thrombotic events, the LMWH dose had no influence on mortality. More studies are needed to determine the optimal thromboprophylaxis protocol for critically ill patients.

PROPHYLAXIS WITH RIVOROXABAN OF CATHETER ASSOCIATED THROMBOSIS IN CANCER PATIENTS (CAT-RIVO TRIAL): MAIN DATA AND INTERMEDIATE RESULTS OF PROSPECTIVE MULTICENTER STUDY

Central venous catheters (CVCs), such as the tunneled catheters and the totally implanted ports, play a major role in general medicine and oncology. Thrombosis associated with CVCs is a common complication in cancer patients. Thus, in order to more widely study the problem of catheter-associated thrombosis in cancer patients, we initiated a study for 2022-2023 within one region. Purpose. Evaluation of the efficacy and safety of thromboprophylaxis of catheter-associated thrombosis with rivaroxaban in cancer patients. Material and methods. Prospective multicenter study, conducted since 01/05/2022 and planned to be completed by the end of 2022, on the basis of three centers. The subjects are divided into 2 groups to randomize 60 participants in each. The first group: receive DOACs (rivaroxaban) at a dosage of 20 mg per day the day before the inserting of the CVC. Second group: treatment of the underlying disease without the use of DOACs. Results. None of the patients developed submassive or massive pulmonary embolism. There were no cases of CAT in the thromboprophylaxis group compared to the non-thrombotic prophylaxis group (0% vs 15.7%). The relative risk of developing CAT is 0.86, which indicates the effectiveness of thromboprophylaxis with rivaroxaban. Conclusion. Our interim results show the efficacy of rivaroxaban at a dosage of 20 mg per day in cancer patients. The final results are planned to be published at the end of the study

Acute and long-term toxicity in patients undergoing induction chemotherapy followed by thermoradiotherapy for advanced cervical cancer

Objectives To determine rates of vascular toxicity, acute kidney injury (AKI), chronic kidney disease (CKD) and survival in high-risk cervical cancer patients treated with platinum-based induction chemotherapy followed by thermoradiotherapy. Methods Between January 1999 and April 2017, patients with large primary tumors (>6cm) and/or para-aortic lymph node (LN) metastases >1 cm and/or para-iliac LN >2 cm were included. Patient and tumor characteristics, Common Toxicity Criteria v4.03 scores, laboratory tests and treatment data were retrieved from patient records. CT scans were reviewed for the presence of thrombo-embolic events (TEE). The study protocol was approved by the Medical Ethics Review Committee of Erasmus MC, Rotterdam (MEC2017-133). Results The 105 included patients had a mean age of 47.9 years (range 22–79) and a median follow-up time of 43 months (IQR 14–72). Median tumor size was 6.0 cm (range 2.6–11.5), 30% had a clinical FIGO stage ≥ IIIB and 42% had enlarged para-aortic LN. Cisplatin-based therapy was started in 86 patients (82%), of whom 30 (35%) switched to carboplatin and 47% of patients completed six cycles of platinum-based chemotherapy. All patients received external beam radiotherapy as planned, 98 patients (93%) underwent brachytherapy as planned or received an external boost, and 95 patients (90%) completed all five planned hyperthermia treatments. During cisplatin chemotherapy, 34 patients experienced AKI (39%). At last follow-up, 35% of patients had chronic renal toxicity (GFR 59 − 15/min/1.73 m2). At presentation, a TEE was present in 10 (10%) and another 23 (22%) patients experienced a TEE (18% venous, 4% arterial) during chemotherapy. Five-year overall survival was 58% (95% CI 47.8–68.6 SE 0.053). Conclusion Achieving a five-year overall survival of 58%, platinum-based induction chemotherapy followed by thermoradiotherapy is an effective treatment for advanced-stage high-risk cervical cancer. However, treatment is accompanied by an unacceptably high prevalence of chemotherapy-associated TEE and acute kidney injury, as well as chronic kidney disease. Future studies should investigate the role of carboplatin in reducing toxicity and the effect of thromboprophylaxis in high-risk patients.

Thromboembolic Events During Treatment with Cisplatin-based Chemotherapy in Metastatic Testicular Germ-cell Cancer 2000–2014: A Population-based Cohort Study

BackgroundCisplatin-based chemotherapy (CBCT) in testicular cancer (TC) is associated with elevated venous thromboembolism (VTE) risk, but trials evaluating the safety and efficacy of thromboprophylaxis are lacking. ObjectiveTo evaluate the arterial thromboembolism (ATE) and VTE incidence and risk factors during first-line CBCT for metastatic TC, and the effect of thromboprophylaxis on VTE and bleeding. Design, setting, and participantsIn a population-based study, 506 men administered first-line CBCT during 2000–2014 at three university hospitals in Norway were included. Clinical variables were retrieved from medical records. Outcome measurements and statistical analysisPatients with ATE and VTE diagnosed at initiation of or during CBCT until 3 mo after completion were registered. Age-adjusted logistic regression was performed to identify possible VTE risk factors. Results and limitationsOverall, 69 men (13.6%) were diagnosed with 70 thromboembolic events. Twelve men (2.4%) experienced ATE. Overall, 58 men (11.5%) experienced VTE, of whom 13 (2.6%) were prevalent at CBCT initiation, while 45 (8.9%) were diagnosed with incident VTE. Age-adjusted logistic regression identified retroperitoneal lymph node metastasis >5 cm (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01–3.91), central venous access (OR 2.84, 95% CI 1.46–5.50), and elevated C-reactive protein (>5 mg/l; OR 2.38, 95% CI 1.12–5.07) as incident VTE risk factors. Thromboprophylaxis (n = 84) did not influence the risk of VTE (VTE incidence with or without prophylaxis 13% vs 8%, p = 0.16). The incidence of bleeding events was significantly higher among those who received thromboprophylaxis than among those without thromboprophylaxis (14.5% vs 1.1%, p < 0.001). ConclusionsWe found a high rate of thromboembolism incidence of 13.6%. Thromboprophylaxis did not decrease the risk of VTE but was associated with an increased risk of bleeding. Patient summaryWe found a high rate of thromboembolism (13.6%) during cisplatin-based chemotherapy for metastatic testicular cancer. Prophylactic treatment against thromboses did not reduce the thrombosis frequency, but it resulted in a high incidence of bleeding events.

Thromboprophylaxis in critically ill patients: balancing on a tightrope.

Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a common and potentially fatal complication in the Intensive Care Unit (ICU). Critically ill patients have some special characteristics that increase the risk for VTE and complicate risk stratification and diagnosis. Given the positive effect of thromboprophylaxis on main outcomes, its use is mandatory in these patients, which is documented by various studies and recommended by all published guidelines. However, anticoagulation management is not an easy issue in clinical practice, as the critical patient may be at high risk for thrombosis or, conversely, at increased risk of bleeding or may balance between thrombotic and bleeding risk. Thrombotic and bleeding risk scoring should be evaluated daily in order to select the appropriate form of thromboprophylaxis. The selection depends on the degree of bleeding risk and the subgroup of ICU patients involved, such as patients with sepsis, acute brain injury, major trauma or COVID-2019. If there is no bleeding risk or other contraindication, the patient should receive pharmacologic thromboprophylaxis with unfractionated heparin or low molecular weight heparins, weighing the advantages of each agent. If the patient is at high risk of bleeding or there is a contraindication to pharmacologic prophylaxis, he should receive mechanical thromboprophylaxis mainly with intermittent pneumatic compression or graduated compression stockings. Thromboprophylaxis compliance with the guidelines is a prerequisite for moving from theory to practice. Direct oral anticoagulants have been studied in ICU patients and have no place at present in VTE prophylaxis requiring further research.

Thromboprophylaxis decreases the risk of pulmonary embolism in COVID-19

Aim: Pulmonary embolism caused by micromboli and microthrombuses might be associated with increased mortality and morbidity in Covid-19. Routine thromboprophylaxis application might contribute to clinical recovery by reducing the risk of pulmonary embolism. In this study, the effects of thromboprophylaxis on clinical outcomes were investigated by examining the rates of computed tomographic angiography requests for the differential diagnosis of pulmonary embolism in the patients with Covid-19. &#x0D; Materials and Methods: Patients who underwent computed tomography (CT) between 10 March and 25 May 2020 in our hospital were retrospectively analysed. Patients who received simultaneous PCR tests during CT examination were included in the study. In the follow-up of these patients, rates of pulmonary CT angiography request with the suspicion of pulmonary embolism and it’s were investigated. &#x0D; Results: During the study period, thorax CT was performed in 11142 patients and pulmonary CT angiography was performed in 161 (1.4%) of them. Ninety-nine patients who were performed CT angiography and PCR test during the hospitalization period were included in the study. PCR test was positive in 22% (n = 21) of the patients (22%) and pulmonary embolism was detected in 6 of them (6.3%). PCR test was negative in 74 patients (78%) and 17 (17.9%) had pulmonary embolism.&#x0D; Conclusion: Routine thromboprophylaxis contributes to the treatment of Covid-19 by preventing the development of microthrombosis and thrombotic complications in the respiratory system.

Thromboprophylaxis in primary shoulder arthroplasty does not seem to prevent death: a report from the Norwegian Arthroplasty Register 2005–2018

Background and purpose — There is still no consensus on whether to use thromboprophylaxis as a standard treatment in shoulder replacement surgery. We investigated the use of thromboprophylaxis reported to the Norwegian Arthroplasty Register (NAR). The primary endpoint was early mortality after primary shoulder arthroplasty with and without thromboprophylaxis. Secondary endpoints included revisions within 1 year and intraoperative complications. Patients and methods — This observational study included 6,123 primary shoulder arthroplasties in 5,624 patients reported to the NAR from 2005 to 2018. Cox regression analyses including robust variance analysis were performed with adjustments for age, sex, ASA score, diagnosis, type of implant, fixation, duration of surgery, and year of primary surgery. An instrumental variable Cox regression was performed to estimate the causal effect of thromboprophylaxis. Results — Thromboprophylaxis was used in 4,089 out of 6,123 shoulder arthroplasties. 90-day mortality was similar between the thromboprophylaxis and no thromboprophylaxis groups (hazard ratio (HR) = 1.1, 95% CI 0.6–2.4). High age (> 75), high ASA class (≥ 3), and fracture diagnosis increased postoperative mortality. No statistically significant difference in the risk of revision within 1 year could be found (HR = 0.6, CI 0.3–1.2). The proportion of intraoperative bleeding was similar in the 2 groups (0.2%, 0.3%). Interpretation — We had no information on cause of death and relation to thromboembolic events. However, no association of reduced mortality with use of thromboprophylaxis was found. Based on our findings routine use of thromboprophylaxis in shoulder arthroplasty can be questioned.

Evaluating the effectiveness of using enoxaparin to prevent venous thromboembolism in hip replacement patients: A retrospective cohort study

Introduction: Our research aims to evaluate the effectiveness of thromboprophylaxis using enoxaparin in patients undergoing hip replacement.&#x0D; Methods: A retrospective cohort study was conducted based on medical records of patients aged 40 years and older undergoing hip replacement. Exclusion criteria included patients who had used anticoagulants to prevent other diseases, patients with a history of chronic renal failure, liver failure, cancer or allergy to anticoagulants, and patients with indicated mechanical prophylaxis. In our study, 65 patients were randomized into 2 groups - the control group and the venous thromboembolism (VTE) prophylaxis group (receiving subcutaneous enoxaparin 40 mg daily for 7 - 14 days). Preventive effectiveness was evaluated based on the comparison of VTE incidence after surgery between the groups.&#x0D; Results: In our study, most of the patients were over 60 years old (79.2%). No case of pulmonary embolism was recorded. There were 11 patients in the control group (17.2%) who developed deep venous thrombosis (DVT) versus 2 patients in the prophylaxis group (3.1%). After adjusting for postoperative hospital stay, use of enoxaparin reduced the risk of DVT by 89.7% (OR 0.103, 95% confidence interval 0.019-0.569, p=0.009), especially in patients over 60 years old (OR 0.147, 95% confidence interval 0.026 - 0.822, p = 0.029).&#x0D; Conclusion: This study demonstrates that using enoxaparin significantly reduces the incidence of DVT in patients undergoing hip replacement, especially in patients over 60 years old.

Inadequate prophylactic effect of low-molecular weight heparin in critically ill COVID-19 patients.

PurposeThe aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on thromboelastography (TEG) and anti-factor Xa in critically ill COVID-19 patients.Material and MethodsWe conducted a prospective study in 31 consecutive adult intensive care unit (ICU) patients. TEG with and without heparinase and anti-factor Xa analysis were performed. Standard thromboprophylaxis was given with dalteparin (75–100 IU/kg subcutaneously).ResultsFive patients (16%) had symptomatic thromboembolic events. All patients had a maximum amplitude (MA) > 65 mm and 13 (42%) had MA > 72 mm at some point during ICU stay. Anti-factor Xa activity were below the target range in 23% of the patients and above target range in 46% of patients. There was no significant correlation between dalteparin dose and anti-factor Xa activity.ConclusionsPatients with COVID-19 have hypercoagulability with high MA on TEG. The effect of LMWH on thromboembolic disease, anti-factor Xa activity and TEG was variable and could not be reliably predicted. This indicates that standard prophylactic doses of LMWH may be insufficient. Monitoring coagulation and the LMWH effect is important in patients with COVID-19 but interpreting the results in relation to risk of thromboembolic disease poses difficulties.

New Oral Anticoagulants for Thromboprophylaxis in Patients with Cancer Receiving Chemotherapy: An Economic Evaluation in a Chinese Setting.

Recent trials showed that thromboprophylaxis with new oral anticoagulants (NOACs) is effective and safe in patients with cancer initiating chemotherapy. However, the cost effectiveness of NOACs is unknown. The objective of this study was to compare the cost effectiveness of preventing venous thromboembolism with NOACs with no thromboprophylaxis for patients with cancer initiating systemic chemotherapy from the perspective of the Chinese healthcare system. A decision analytical model consisting of both acute and chronic venous thromboembolism complications was used to assess the cost effectiveness of thromboprophylaxis with NOACs vs no thromboprophylaxis. The key clinical data were derived from the CASSINI and AVERT trials. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for the two strategies. Scenario and sensitivity analyses were performed. Compared with no thromboprophylaxis, NOACs gained 0.072 QALY at an incremental cost of $US930, leading to an ICER of 12,919/QALY in patients with Khorana scores ≥ 2 by pooling the data from the CASSINI and AVERT trials. Among patients confirmed with no deep-vein thrombosis before thromboprophylaxis (the CASSINI trial) and patients without deep-vein thrombosis screening before thromboprophylaxis (the AVERT trial), the ICERs were $70,897/QALY and $87,204/QALY, respectively. The probability of NOACs being cost effective was 42% at a willingness to pay of $10,276/QALY. The ICER was sensitive to the relative risks of death and asymptomatic venous thromboembolism between NOACs and no thromboprophylaxis and the cost of NOACs. Thromboprophylaxis with NOACs is not likely to be cost effective in patients initiating chemotherapy in the Chinese context. The decision about thromboprophylaxis should be tailored based on the survival of patients with cancer, the risks of venous thromboembolism, and major bleeding.

Effect of thromboprophylaxis on the incidence of venous thromboembolism in surgical patients with colorectal cancer: a meta-analysis.

This study evaluates the role of thromboprophylaxis in venous thromboembolism (VTE) incidence in colorectal cancer (CRC) surgical patients. Literature search was conducted in electronic databases and studies (randomized controlled trials, or prospective/retrospective cohorts) were selected if they reported the incidence of VTE in CRC patients who underwent any type of open or laparoscopic surgery. Random-effects meta-analyses were performed to obtain pooled incidence estimates; or odds ratios (OR) of incidence between prophylaxis and no-prophylaxis groups; or between VTE and non-VTE patients to identify risk factors. Twenty-four studies (804,003 patients) were included. Prophylaxis was performed mainly with low molecular weight heparins. Odds of VTE were significantly lower in prophylactic than in non-prophylactic patients (OR 0.42 [95% CI: 0.28, 0.63]; P<0.00001). Incidence of radiological and symptomatic VTE in patients with prophylaxis was 9.7% [95% CI: 8.6, 10.8] and 1.3% [95% CI: 0.7, 2.0] respectively. Odds of bleeding were higher in patients with prophylaxis (OR: 3.37 [95% CI: 1.05, 10.8]; P=0.04). Incidence of bleeding in patients with and without prophylaxis was 4.3% [95% CI: 3.2, 5.4] and 1.2% [95% CI: 0.02, 2.4] respectively. Operative time, anesthesia duration, and hospital stay were longer in patients with VTE. Obesity, disseminated cancer, chemotherapy, steroid use, emergency case status, advanced stage cancer, hypoalbuminemia, postoperative infection/sepsis, and history of VTE are identified as important risk factors for VTE incidence. Thromboprophylaxis reduces the incidence of VTE in CRC surgical patients but may increase the chances of bleeding. Several risk factors can influence VTE incidence.

Clinical risk assessment model to predict venous thromboembolism risk after immobilization for lower-limb trauma

BackgroundPatients with lower-limb trauma requiring immobilization have an increased risk of venous thromboembolism (VTE). While thromboprophylaxis for all patients seems not effective, targeted thromboprophylaxis in high risk patients may be an appropriate alternative. Therefore, we aimed to develop and validate a risk assessment model for VTE risk: the TRiP(cast) score (Thrombosis Risk Prediction following cast immobilization). MethodsIn this prediction model study, for development, data were used from the MEGA study (case-control study into the etiology of VTE) and for validation, data from the POT-CAST trial (randomized trial on the effectiveness of thromboprophylaxis following cast immobilization) were used. Model discrimination was calculated by estimating the Area Under the Curve (AUC). For model calibration, observed and predicted risks were assessed. FindingsThe TRiP(cast) score includes 14 items; one item for trauma severity (or type), one for type of immobilization and 12 items related to patients’ characteristics. Validation analyses showed an AUC of 0.74 (95%CI 0.61–0.87) in the complete dataset (n = 1250) and 0.72 (95%CI 0.60–0.84) in the imputed data set (n = 1435). The calibration plot shows the degree of agreement between the observed and predicted risks (intercept 0.0016 and slope 0.933). Using a cut-off score of 7 points in the POT-CAST trial (incidence 1.6%), the sensitivity, specificity, positive and negative predictive values were 76.1%, 51.2%, 2.5%, and 99.2%, respectively. InterpretationThe TRiP(cast) score provides a helpful tool in daily clinical practice to accurately stratify patients in high versus low-risk categories in order to guide thromboprophylaxis prescribing. To accommodate implementation in clinical practice a mobile phone application has been developed. FundingZonMW VIMP grant:17110200011.

Тест генерации тромбина в оценке адаптационных возможностей системы гемокоагуляции у пациентов с дегенеративно-дистрофическими заболеваниями суставов

Введение. Поиски методов оценки функционального состояния системы гемокоагуляции у пациентов, которые ожидают выполнения эндопротезирования крупных суставов нижних конечностей, обоснованы высокой частотой встречаемости у них тромбоэмболических осложнений. Цель исследования: изучение теста генерации тромбина (ТГТ) с позиции оценки адаптационных возможностей системы гемокоагуляции у больных с дегенеративнодистрофическими заболеваниями крупных суставов нижних конечностей. Материалы и методы. Обследован 141 больной с дегенеративнодистрофическими поражениями тазобедренных и коленных суставов (35 мужчин, 106 женщин), средний возраст 62,6 9,9 лет. Контрольную группу составили 30 условно здоровых доноров, средний возраст 49,7 6,5 лет. Исследовали коагуляционные свой ства крови рутинными методами и регистрировали кривую процесса тромбинообразования в ТГТ, анализируя параметры: tlag латентное время тромбинообразования, ttpeak время достижения максимума тромбина, peak максимальное количество тромбина, VI индекс скорости тромбинообразования, AUC площадь под кривой. Больные были разделены на 2 группы в зависимости от характера изменения временных параметров ТГТ в ответ на инициацию тромбиногенеза активаторами с концентрацией тканевого фактора 2 пмоль/мл (активатор RB) и 5 пмоль/мл (активатор RClow). Результаты. В 1й группе значения параметров tlag и ttpeak в ответ на действие активатора RClow были меньше, чем на действие активатора RB, реакцию системы гемокоагуляции расценивали как адекватную. Во 2й группе значения tlag и ttpeak при использовании активатора RClow превышали величины аналогичных параметров при инициации тромбообразования активатором RB, а корреляционный анализ отразил ослабление связей между параметрами ТГТ, что свидетельствовало об адаптационной перестройке системы на фоне высокого тромбогенного потенциала и повышенном риске развития гемокоагуляционных осложнений у больных 2й группы. Заключение. ТГТ с использованием активаторов RB и RClow ерспективный инструмент выявления больных с высоким риском развития послеоперационных гемокоагуляционных осложнений. Introduction. The search of methods for assessing of hemocoagulation functional state in patients that are waiting endoprosthesis replacement of large joints of lower extremities is justified by the high incidence of thromboembolic complications. Aim: to study thrombin generation assay (TGA) for assessment of hemocoagulation adaptive potential in patients with degenerativedystrophic diseases of the large joints of lower extremities. Materials and methods. We examined 141 patients with degenerativedystrophic lesions of hip and knee joints (35 men, 106 women), average age was 62.6 9.9 years. Control group consisted of 30 relatively healthy donors, average age was 49.7 6.5 years. We investigated blood coagulation properties by routine methods and recorded the curve of thrombin formation by TGA. We analyzed next parameters: tlag is the latent time of thrombin formation, ttpeak is the time to reach the maximum of thrombin, peak is the maximum amount of thrombin, VI is the index of thrombin formation speed, AUC is the area under the curve. Patients were divided into 2 groups according TGA parameters in response to thrombinogenesis initiation by activators with different tissue factor concentrations 2 pmol/ml (RB activator) and 5 pmol/ml (RClow activator). Results. In the 1st group, tlag and ttpeak values in TGA with RClow activator were less than with RB activator, the hemocoagulation response was regarded as adequate. In the 2nd group, tlag and ttpeak values with RClow activator were higher than with RB activator and correlation analysis revealed the weakening of the relationships between TGA parameters. This indicated about system adaptation at a time of high thrombogenic potential and about increased risk of developing hemocoagulation complications in patients of the 2nd group. Conclusion. TGA with RB and RClow activators is a promising tool for identifying patients with a high risk of postoperative hemocoagulation complications.

Performance of Risk Assessment Models for Peripartum Thromboprophylaxis

There is no consensus on which risk stratification approach to use for thromboprophylaxis in pregnancy, and most available risk assessment models (RAMs) for venous thromboembolism (VTE) events have not been validated in pregnancy. Our objective was to compare the performance of some of the most commonly used VTEs RAMs in our patient population in the peripartum period. This is a retrospective cohort of women who delivered at our institution in 2015 and 2016. We excluded patients with history of prior or current VTEs or those already receiving anticoagulants. Antepartum, intrapartum, and postpartum records were reviewed. Data were collected on known risk factors for VTEs in order to calculate scores for 3 RAMs on admission for delivery: Padua, Caprini, and Royal College of Obstetricians and Gynaecologists (RCOG). The primary objective was to the estimate the performance of the various RAMs in preventing postpartum VTEs. We calculated the proportion of women who would have been high risk, determined the number of VTEs cases within high- and low-risk categories, as well as calculated the number needed to treat (NNT) for each RAM. We performed analyses using different RAM scores cutoffs, VTEs outcome rates, and effectiveness of anticoagulation to prevent VTEs. The P value <.05 was considered statistically significant. A total of 6094 women were included. Three women had VTEs for an overall rate of 0.04% (N = 3; 95% confidence interval [CI]: 0.01-0.15). The proportion of women categorized as high risk for VTEs were 62% (95% CI: 61-64) for RCOG, 0.8% (95% CI: 0.6-1.0) for Padua, and 94% (95% CI: 94-95) for Caprini. Of the 3 VTEs, the RCOG model classified 1 woman as high risk and Padua model classified 3 women as high risk; whereas the Caprini did not identify any women as high risk. Assuming 100% effectiveness of thromboprophylaxis, the observed NNT was 3838 using RCOG, not able to calculate using Padua (no VTEs cases occurred in the high-risk group, thus none were prevented), and 1927 using Caprini. The rates of VTEs in pregnancy are very low and the available RAMs do not identify most of them. The RCOG and Caprini RAMs would categorize a large proportion of women as high risk and are associated with high NNTs. The Padua RAM appears to have the lowest NNT but missed all the VTEs in our cohort.

Thromboprophylaxis in breast microvascular reconstruction: a review of the literature

Microsurgical breast reconstruction patients are at an increased risk for venous thromboembolism (VTE) due to numerous risk factors. A meta-analysis focusing on anti-thrombotics in breast microsurgery has yet to be completed. We aimed to perform a systematic review of the literature to examine the effects of thromboprophylaxis in breast microsurgical reconstruction with a focus on patient and flap complications. A PubMed, Cochrane, and Medline database search was conducted with the following keywords: “venous thrombosis, thromboprophylaxis, mechanical, pneumatic compression, aspirin, heparin, dextran, ketorolac, toradol, warfarin, and coumadin.” Results were combined with the terms “breast microsurgery” and “breast free flap.” All articles that resulted were analyzed. The reference list for each included article was analyzed for other applicable articles. Only articles that addressed pre-operative or post-operative anti-coagulation were included. For data analysis, if the article reported that there were no flap complications, it was assumed there were no operative hematomas, vessel thrombosis, or flap loss. Two hundred and fifty-seven studies were screened from the abovementioned search results and 17 fit inclusion criteria. The majority of included studies were retrospective chart reviews and the type of thromboprophylaxis and its effect on complications was rarely the primary end point. Due to lack of reporting on patient and flap characteristics that could impact outcomes, subgroup analysis was impossible. There has yet to be a consensus on the most effective way to prevent VTE in women undergoing microsurgical breast reconstruction without increasing the risk of hematoma and flap compromise. Studies published to date vary in their thromboprophylatic regimens and rarely include a control or comparison group to allow for intra- or inter-group analysis. There is a need for well-done, randomized, controlled trials in order to determine the best approach to thromboprophylaxis in these patients.

Thromboembolic events in advanced pancreatic cancer: A systematic review.

461 Background: Pancreatic ductal adenocarcinoma (PDA) is highly associated with thromboembolic events (TEs). There is no consensus for prophylaxis of TEs across thromboprophylactic guidelines in ambulatory patient settings. Published ASCO (2014) and ESMO (2011) guidelines recommend use of primary thromboprophylaxis in pancreatic cancer outpatients at high risk of TEs. This systematic review investigated TE rates and prophylaxis among advanced PDA patients. Methods: A literature review identified clinical trials and observational studies reporting TE rates with and without thromboprophylaxis in PDA patients undergoing chemotherapy. A search was conducted using electronic databases including Medline, Medline In-Process, and Embase; limited to English language and publication between 1990 and April 2017. Retrieved articles were cross-referenced and scrutinized to identify additional publications. Results: Seven studies were identified; 2 randomized clinical trials (RCTs) and 5 observational/retrospective studies met the stated criteria. The TE rate in PDA in the 5 observational studies without prophylaxis ranged from 9.6% to 36.0%. Thromboprophylaxis was used in the 2 RCTs and was associated with lower TE rates. Conclusions: This comprehensive literature review shows that PDA patients face a substantial risk of TE after chemotherapy. The high rates of TEs in PDA, and the effectiveness of thromboprophylaxis in patients with PDA, highlight the importance of having consensus for prophylaxis of TEs across thromboprophylactic guidelines in ambulatory patient settings as a critical early preventive measure during the treatment of patients with advanced PDA. [Table: see text]

Effect of thromboprophylaxis with anticoagulant drugs on the incidence of arterial thrombotic events in medical inpatients: a systematic review.

Pharmacological prophylaxis of venous thromboembolism (VTE) is recommended for medical inpatients. Since arterial thrombosis (AT) shares some risk factors with VTE, it would be reasonable to assess the efficacy of thromboprophylaxis by considering both VTE and AT as outcome events. We performed a systematic review and meta-analysis of phase III RCTs on thromboprophylaxis in medical inpatients, to evaluate the quality of reporting and the incidence of AT, and the effect of thromboprophylaxis with anticoagulants on AT incidence. Studies were identified by a combined search strategy until May 2015. Differences in outcomes among groups were expressed as pooled odds ratios (OR) and 95 % confidence intervals (CI). Statistical heterogeneity was assessed by I (2) statistic. Twenty phase III RCTs, encompassing 54,742 patients, were included; of these, 3 (15 %) reported on AT as a pre-defined secondary outcome and 8 (40 %) on at least one AT outcome. Raw-unweighed incidence of fatal MI in the three RCTs is 0.37 % in patients receiving unfractionated heparin or enoxaparin, and 0.38 % in controls (OR 0.97, 95 % CI 0.62-1.52; I (2) = 0 %). A non-statistically significant increase in AT is reported in patients on enoxaparin compared to control (OR 1.95, 95 % CI 0.89-4.27; I (2) = 13 %). AT is underreported in RCTs on VTE prophylaxis in medical inpatients. Published data suggest that incidence of fatal MI in these patients may be clinically relevant. Insufficient data are available to draw firm conclusions on the effects of thromboprophylaxis with anticoagulants on AT incidence in this setting.

Effects of thromboprophylaxis on mesenchymal stromal cells during osteogenic differentiation: an in-vitro study comparing enoxaparin with rivaroxaban

BackgroundLow-molecular-weight heparins (e.g. Enoxaparin) are widely used to prevent venous thromboembolism after orthopaedic surgery, but there are reports about serious side effects including reduction in bone density and strength. In recent years new oral antithrombotic drugs (e.g. direct Factor Xa-inhibitor, Rivaroxaban) have been used to prevent venous thromboembolism. However, there is lack of information on the effects of these new drugs on human mesenchymal stromal cells during osteogenic differentiation and, therefore, effects during postoperative bone healing.MethodsWe evaluated the effects of Rivaroxaban and Enoxaparin on the proliferation, mRNA and surface receptor expression as well as differentiation capacity of primary human mesenchymal stromal cells during their osteogenic differentiation.ResultsEnoxaparin, but not Rivaroxaban treatment significantly increased human mesenchymal stromal cell (hMSC) proliferation during the first week of osteogenic differentiation while suppressing osteogenic marker genes, surface receptor expression and calcification.ConclusionsThis is the first paper to demonstrate that Rivaroxaban had no significant influence on hMSC differentiation towards the osteogenic lineage, indicating a less affected bone healing process compared with Enoxaparin in vitro. Based on these findings Rivaroxaban seems to be superior to Enoxaparin in early stages of bone healing in vitro.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-0966-2) contains supplementary material, which is available to authorized users.