Dose Of Low Molecular Weight Heparin Research Articles

#949 Factor XIIa inhibitory antibody does not provide sufficient anticoagulation in ex vivo hemodialysis

Abstract Background and Aims Unfractionated heparin (UFH) and low molecular-weight heparin (LMWH) are the most commonly used anticoagulants in haemodialysis (HD). While effective in preventing clotting, they are also associated with complications including increased risk of bleeding and heparin induced thrombocytopenia. The contact activation system is commonly assumed to be the main trigger of coagulation during HD, through autoactivation of factor (F)XII upon contact with the dialyser. FXII deficient individuals do not have an increased risk of bleeding which makes activated FXII (FXIIa) an attractive drug target as it has the potential to inhibit clotting without disrupting haemostasis. The aim of the study was to evaluate the efficacy of CSL312, a monoclonal, humanized IgG4 antibody against activated FXII (FXIIa), in preventing intradialytic coagulation. Method An ex vivo haemodialysisis model was used to test the efficacy of CSL312 as an anticoagulant. CSL312 (400 µg/mL) was compared to standard doses of UFH, LMWH and citrate anticoagulation. The antibody was provided by CSL Limited. Anticoagulant-free haemodialysisis was used as control. Whole-blood was collected from 12 healthy adult donors in blood-transfer bags containing citrate to prevent clotting before dialysis. Each donor provided blood for two HD-sessions, using different anticoagulants. The blood was dialyzed for one hour through paediatric polysulfone high-flux dialysers. Right before the start of HD, calcium was added to reverse the anticoagulant effect of citrate, except in the citrate group. Blood was sampled before and at 5, 15, 30 and 60 minutes after HD start. To quantify the activity of the contact system, the concentrations of enzyme-inhibitor complexes of antithrombin (AT) or C1-inhibitor (C1INH) in conjunction with FXIIa, FXIa, kallikrein, MASP-1, MASP-2 and thrombin were measured in plasma using enzyme-linked immunosorbent assays. Results Using CSL312 to inhibit FXIIa protease activity (n = 5), clotting occurred in all tests (at 30, 31, 36, 49 and 50 minutes) with a mean clotting time of 39.2 minutes compared to 17 and 30 minutes using no anticoagulation (n = 2). No clotting was evident with other anticoagulants. Using CSL312, the plasma concentration of FXIIa-C1INH at 15 minutes was significantly higher than at baseline (mean 26.2 (SD 9.08) vs mean 17.6 (SD 10.6) µg/mL, p = 0.011). Conclusion FXIIa inhibition using a monoclonal antibody does not provide sufficient anticoagulation during HD. This suggests that the contact system may not be solely responsible for clotting during HD.

Primary prevention of venous thromboembolism with low molecular weight heparins in surgical patients – 2024: Council of Experts resolution

On March 15, 2024, in Moscow, the Russian Phlebological Association and the National Association of Specialists in Thrombosis, Clinical Hemostasiology and Hemorheology organized a meeting of the Council of Experts during the Russian Forum on Thrombosis and Hemostasis on the acute issues of venous thromboembolism (VTE) primary prevention using low molecular weight heparins (LMWH) in surgical patients with different body weight. The participants reviewed the relevance and prevalence of this problem in surgical practice, discussed risk factors and the frequency of VTE development, including bleeding in the postoperative period, and the Caprini risk score for complications. The discussion also focused on standard and personalized LMWH doses for primary prophylaxis of VTE in the perioperative period in surgical patients, depending on body weight, and the role of laboratory tests, including assessment of LMWH anti-Xa activity for monitoring the efficacy and safety of VTE primary prevention in clinical practice.

The treatment of COVID-19 associated venous thromboembolism (VTE); an evidence review investigating the efficacy of different low-molecular weight heparin doses for VTE prophylaxis in COVID-19 patients

The treatment of COVID-19 associated venous thromboembolism (VTE); an evidence review investigating the efficacy of different low-molecular weight heparin doses for VTE prophylaxis in COVID-19 patients

Weight-Based Dosing for Low-Molecular-Weight Heparin (Enoxaparin) Administration to Achieve Optimal VTE Prophylaxis in Trauma Patients.

Patients admitted after traumatic injuries are at high risk for developing venous thromboembolism (VTE). Low-molecular-weight heparin (LMWH) is commonly used to prevent VTE in this patient population; however, the optimal dosing strategy has yet to be determined. To address this question, a fixed-dosing strategy of LMWH was compared to a weight-based dosing strategy of LMWH for VTE prophylaxis. A retrospective, pre-post implementation cohort study compared a fixed vs a weight-based dosing strategy of LMWH for VTE prophylaxis. Patients admitted to our level 1 trauma center were included if they had an estimated glomerular filtration rate >30mL/min/1.73m2, received at least 3 doses of LMWH, and had an appropriately drawn anti-Xa level on their initial dosing regimen. Patients in the pre-cohort received 30mg LMWH subcutaneously twice daily as the initial dosing regimen. Patients in the post-cohort received .5mg/kg (max 60mg) LMWH subcutaneously every 12h as the initial dosing regimen. A goal anti-Xa of .2-.4 IU/mL was targeted for prophylaxis. There were 817 patients in the fixed-dosing group (FDG) and 874 patients in the weight-based dosing group (WBDG). In the FDG, 42.8% of the patients achieved the goal initial anti-Xa level, with 54.1% and 3.1% reaching sub- and supratherapeutic doses, respectively. In the WBDG, 66.5% of patients reached goal initial anti-Xa levels, with 23.5% and 10.1% at sub- and supratherapeutic levels. The distribution of dose ranges was significantly different between the dosing strategies (P-value <.001). There was no difference in the number of patients who received blood products (39.1% vs 41.7%. P-value = .299). In our study, weight-based dosing of LMWH yielded a significantly higher proportion of patients who achieved goal prophylactic anti-Xa levels than fixed-dosing of LMWH. Larger-scale studies are needed to assess the risk of VTE events and bleeding with these dosing strategies.

Is early bilateral compression ultrasonography and D-dimer monitoring appropriately for prophylaxis and diagnosis of deep venous thrombosis after cesarean section women: a single-center observation study of Chinese Han population

BackgroundVenous thromboembolism (VTE) is most prevalent among parturients following a cesarean section (CS). The objective of this study was to assess the practical utility of bilateral compression ultrasonography (CUS) of the lower limbs, coupled with D-dimer monitoring, in the early diagnosis of VTE within the Han Chinese population.MethodsOur prospective observational study included 742 women who underwent CUS and D-dimer testing on the first day post-CS. Subsequently, telephone or outpatient follow-ups were conducted until 42 days postpartum. States of hypercoagulation and thrombosis, as indicated by CUS, were classified as CUS abnormal. A D-dimer level ≥ 3 mg/l was considered the D-dimer warning value. Early ambulation and mechanical prophylaxis were universally recommended for all parturients post-CS. A sequential diagnostic strategy, based on the 2015 RCOG VTE risk-assessment tool, was employed. Therapeutic doses of low-molecular-weight heparin (LMWH) were administered for the treatment of thromboembolic disease. Prophylactic doses of LMWH were given for VTE prophylaxis in parturients with hypercoagulative status accompanied by D-dimer levels ≥ 3 mg/l. All high-risk women (RCOG score ≥ 4 points) were additionally treated with preventive LMWH. Statistical analyses were conducted using the R statistical software, with a two-sided P value < 0.05 considered statistically significant.ResultsFifteen cases of VTE and 727 instances without VTE were observed. The overall VTE rate post-CS was 2.02% (15/742), with 66.7% (10/15) being asymptomatic. Eleven patients received a VTE diagnosis on the first postpartum day. Among the 41 parturients exhibiting hypercoagulation ultrasound findings and D-dimer levels ≥ 3 mg/l, despite receiving pharmacological VTE prophylaxis with LMWH, 4.88% (2/41) in the high-risk group were eventually diagnosed with VTE. A total of 30.86% (229/742) exhibited normal ultrasound findings and D-dimer levels < 3 mg/l on the first day post-CS, with no VTE occurrences in the postpartum follow-up. According to RCOG’s recommendation, 78.03% (579/742) of cesarean delivery women should receive prophylactic anticoagulation, while only 20.62% (153/742) met our criterion for prophylactic anticoagulation.ConclusionThe strategy of timely routine bilateral CUS and D-dimer monitoring is conducive to the early diagnosis and treatment of VTE, significantly reducing the use of LMWH in the Chinese Han population.

Evaluation of anticoagulant effect and predicted dose of low molecular weight heparin in hemodialysis by anti-Ⅹa factor activity

The purpose of this study was to explore the reasonable dose of low molecular weight heparin (LMWH) in hemodialysis (HD) and the strategy of preventing extracorporeal circuit coagulation (ECC). A retrospective case-control study included patients who used LMWH for anticoagulation during maintenance hemodialysis (MHD) in the Hemodialysis Center of Beijing Hospital from December 2020 to January 2021. Basic data such as weight, height, basic kidney disease, dialysis age and anti-Ⅹa factor activity before, during and after dialysis were collected. A total of 46 patients were enrolled in this study, including 5 patients in coagulation group (10.9%) and 41 patients in non-coagulation group (89.1%). The anti-Ⅹa factor activity reached its peak at 0.5 h after the start of HD. The level of anti-Ⅹa factor was incorporated into the receiver operating characteristic curve (ROC curve). The results showed that the area under the ROC curve (AUC) was 0.802 (95% confidence interval: 0.651-0.54, P=0.029), and the cutoff was 0.31 IU/ml (sensitivity 1, specificity 0.683). It is suggested that the body surface area should be used as the basis to estimate the anticoagulant dose of LMWH in HD, and the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml, which is of diagnostic value for ECC. In addition, the results of binary logistic regression analysis showed that dialysis age was an independent risk factor for ECC (OR value 1.319, 95%CI 1.052-1.654, P=0.017). In summary, this study reveals that dialysis age may be a risk factor for ECC and that the activity of HD 4 h anti-Ⅹa factor ≤0.31 IU/ml can be used as a potential diagnostic cut-off point for ECC in HD patients, which provides a scientific basis for monitoring strategies to prevent blood coagulation in HD filters.

Infrequent transition to direct oral anticoagulants in patients with cancer.

Pharmacokinetic drug-drug interactions (DDIs) are challenging aspects of direct oral anticoagulant (DOAC) therapy in patients with cancer. We evaluated the prevalence of potential DOAC/antineoplastic agent DDIs and the one-year cumulative incidence of switching from low-molecular-weight heparin (LMWH) to a DOAC in patients with cancer. Patients with cancer and an indication of LMWH were included from Herlev and Gentofte Hospital, Denmark, in the 2014-2019 period. Follow-up was initiated when the first dose of LMWH was dispensed. Data were obtained from electronic medical records. One-year cumulative incidence of switching from LMWH to DOAC was estimated using the Aalen-Johansen estimator. Potential DDIs were evaluated using a report from the European Heart Rhythm Association (EHRA) and a review by Hellfritzsch et al. RESULTS. A total of 161 patients were included with a median age of 70.8 (interquartile range: 64.2-76.1) years. The one-year cumulative incidence of switching from LMWH to DOAC was 32% (95% confidence intervals: 21-43%) in patients eligible for DOACs. Using the EHRA report, a total of 24% of antineoplastic agents were not identified. This percentage decreased to 8% using data from Hellfritzsch et al. CONCLUSIONS. In patients with cancer, the one-year cumulative incidence of switching from LMWH to DOAC was less-t 35% in patients eligible for DOAC, revealing a potential for improved anticoagulant treatment. Furthermore, contemporary data elaborated on potential DDIs between DOACs/antineoplastic agents. "Helsefonden" (21-B-0350) and the "Karen Elise Jensens Fonden" (29-4-2021) funded the study. Not relevant.

Anticoagulation for people receiving long-term haemodialysis.

Haemodialysis (HD) requires safe and effective anticoagulation to prevent clot formation within the extracorporeal circuit during dialysis treatments to enable adequate dialysis and minimise adverse events, including major bleeding. Low molecular weight heparin (LMWH) may provide a more predictable dose, reliable anticoagulant effects and be simpler to administer than unfractionated heparin (UFH) for HD anticoagulation, but may accumulate in the kidneys and lead to bleeding. To assess the efficacy and safety of anticoagulation strategies (including both heparin and non-heparin drugs) for long-term HD in people with kidney failure. Any intervention preventing clotting within the extracorporeal circuit without establishing anticoagulation within the patient, such as regional citrate, citrate enriched dialysate, heparin-coated dialysers, pre-dilution haemodiafiltration (HDF), and saline flushes were also included. We searched the Cochrane Kidney and Transplant Register of Studies up to November 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating anticoagulant agents administered during HD treatment in adults and children with kidney failure. Two authors independently assessed the risk of bias using the Cochrane tool and extracted data. Treatment effects were estimated using random effects meta-analysis and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach (GRADE). We included 113 studies randomising 4535 participants. The risk of bias in each study was adjudicated as high or unclear for most risk domains. Compared to UFH, LMWH had uncertain effects on extracorporeal circuit thrombosis (3 studies, 91 participants: RR 1.58, 95% CI 0.46 to 5.42; I2 = 8%; low certainty evidence), while major bleeding and minor bleeding were not adequately reported. Regional citrate anticoagulation may lower the risk of minor bleeding compared to UFH (2 studies, 82 participants: RR 0.34, 95% CI 0.14 to 0.85; I2 = 0%; low certainty evidence). No studies reported data comparing regional citrate to UFH on risks of extracorporeal circuit thrombosis and major bleeding. The effects of very LMWH, danaparoid, prostacyclin, direct thrombin inhibitors, factor XI inhibitors or heparin-grafted membranes were uncertain due to insufficient data. The effects of different LMWH, different doses of LMWH, and the administration of LMWH anticoagulants using inlet versus outlet bloodline or bolus versus infusion were uncertain. Evidence to compare citrate to another citrate or control was scant. The effects of UFH compared to no anticoagulant therapy or different doses of UFH were uncertain. Death, dialysis vascular access outcomes, blood transfusions, measures of anticoagulation effect, and costs of interventions were rarely reported. No studies evaluated the effects of treatment on non-fatal myocardial infarction, non-fatal stroke and hospital admissions. Adverse events were inconsistently and rarely reported. Anticoagulant strategies, including UFH and LMWH, have uncertain comparative risks on extracorporeal circuit thrombosis, while major bleeding and minor bleeding were not adequately reported. Regional citrate may decrease minor bleeding, but the effects on major bleeding and extracorporeal circuit thrombosis were not reported. Evidence supporting clinical decision-making for different forms of anticoagulant strategies for HD is of low and very low certainty, as available studies have not been designed to measure treatment effects on important clinical outcomes.

Surveillance reports to identify duplicate anticoagulant prescribing

Abstract Introduction A number of patients admitted to hospital on direct oral anticoagulants (DOACs) are often switched to low molecular weight heparin (LMWH) for a limited period of time as part of their clinical management. Electronic prescribing systems (EPMA) allow DOACs to be suspended temporarily and then re-started when clinically indicated. However the system does not generate an alert when DOACs are re-started, leading to unintentional co-prescribing of LMWH which could lead to severe patient harm.1,2 Aim To determine whether anticoagulation surveillance reports reduce the number of inappropriate duplicate anticoagulation prescriptions. Methods A retrospective review of duplicate anticoagulation errors was carried out between September 2017 and March 2022 across the 3 main Royal Cornwall hospital sites. Data on all anticoagulant administrations and the administration time was collected from EPMA via Crystal Reporting pre and post intervention with each period covering 831 days. Data was analysed using Excel. As part of the intervention, surveillance reports were set up in December 2019 to identify patients who were prescribed both LMWHs and DOACs. Reports were generated twice a day, 7 days a week and reviewed for patients who were prescribed both LMWHs and DOACs. The ward pharmacists were then alerted of co-prescribing to complete the necessary interventions. As this project falls under the definition of a service evaluation, according to UK NHS Research Ethics Committees, formal ethical approval was not required. This project was registered on the hospital’s clinical audit database. Results 948,036 doses of LMWH and DOACs were administered (September 2017 to March 2022) with 817 duplicate prescribing identified, a 0.09% error rate. The longest time on duplicate therapy was dramatically reduced pre and post intervention from 322 hrs to 36 hrs with mean number of hours reduced from 14.03 to 8.07. The number of patients receiving more than two doses of co-prescribed LMWH and DOAC before the error was rectified, also reduced from 56 (pre-intervention) to 30 (post-intervention). Likewise, the average duration of more than 2 doses of co-prescription reduced from 48.3 to 18.7 hours before the error was corrected. Discussion/Conclusion Some limitations of the study are that staffing is more limited on weekends which may have prevented pharmacists actioning these alerts over weekends. Data will only include anticoagulants prescribed on EPMA so excludes some infusions such as unfractionated heparin. Timestamps associated with administrations on EPMA are user-entered so may not be exact to the time given. Although EPMA generates an alert when patients on DOACs are prescribed LMWHs, it does not provide a similar alert when suspended DOACs are re-started. EPMA providers are planning to develop alerts to correct this. In the interim we have shown that surveillance reports capture co-prescribing of DOACs and LMWH at an earlier stage preventing potential serious patient harm. It also allows for pharmacists to educate prescribers on risks of anticoagulation co-prescribing. This report is now routine practice, including additional monitoring - patients on warfarin, fondaparinux, LMWH prescribed twice daily and INR levels. We will re-evaluate to include new parameters.

Platelet-Based Dose-Adjusted Low Molecular Weight Heparin Treatment Is Efficacious and Safe in Newly Diagnosed Acute Leukemia Patients with Catheter-Related Thrombosis

Introduction: Catheter-related thrombosis (CRT) is a major complication in patients with acute leukemia. Severe thrombocytopenia related to either the concomitant disease or therapy underscores the challenge of CRT management, resulting in the use of suboptimal anticoagulation, potentially leading to high rates of short-term complications, including recurrent thromboembolism and hemorrhage. Due to the paucity of data regarding the impact of reduced-dose anticoagulation on this clinical setting, the current study aimed to assess the safety and efficacy of this treatment approach to CRT management in this challenging patient population. Methods: In this retrospective, case-control study, all adult (age ≥18 years) acute leukemia patients, who had arrived at the Rambam Health Care Campus (RHCC, Haifa, Israel) between 1.11.2004-30.6.2022 to receive anti-leukemia therapy via a peripherally inserted central catheter (PICC) line were screened. The inclusion criteria were: patients with acute myeloid, promyelocytic and lymphoid leukemia (AML, APL, and ALL, respectively) and CRT confirmed by Doppler ultrasound within 3 months of leukemia diagnosis. Patients were divided into full- (i.e., 1 mg/kg bid) vs. partial-dose low molecular weight heparin (LMWH) groups. The LMWH dose was based on the platelet count with a cutoff of 50K/L, distinguishing between the selected doses. Primary endpoints: A record of venous thromboembolism (VTE; including pulmonary embolism (PE), deep vein thrombosis (DVT), and catheter-related thrombosis (CRT) recurrence within 12 months as well as a major hemorrhage (including intracranial, retinal and gastrointestinal hemorrhage) within 6 months. Secondary endpoints: blood product requirement (unit/day) before and after the CRT diagnosis (from leukemia diagnosis till CRT identification and 90 days or death (if prior) from the event, respectively) assessed in a self-controlled case series manner. Data were collected from the hospital electronic medical records. Chi-square and paired samples Wilcoxon tests were utilized for statistical analysis. Results: Overall,195 patients [aged 54±15 years; 103 (53%) males], diagnosed with CRT were included. The most frequent leukemia diagnosis was AML (n=149; 76%), with ALL and APL established in 23 (12%) patients each. CRT was diagnosed in the left upper limb in 136 (70%) patients, with 99 (46%) patients suffering from DVT. Eighty-eight (45%) patients were treated with full-dose LMWH. Recurrent VTE was identified in 11(12.5%) patients treated with full-dose LMWH vs. 9 (8.4%) receiving partial-dose LMWH (p-value 0.484), while major hemorrhage was diagnosed in 12 (13.6%) patients from the former group vs. 14 (13.0%) patients from the latter group (table 1). Similar results were documented upon stratification to deep vs. superficial CRT, and the leukemia type. The packed red blood cell (RBC) administration rate was lower in the post-CRT phase (0.12 units/day, IQR 0.06-0.20) compared to the pre-CRT phase (0.20 units/day, IQR 0-0.36; p-value &amp;lt;0.0001). Platelet utilization rates were similar in both the pre-CRT and post-CRT phases (0.05 units/day, IQR 0-0.24 and 0.06 units/day, IQR 0.01-0.16, respectively; p-value 0.126). Comparable results were observed in both full and partial-dose LMWH groups. Conclusion: LMWH dose adjustment based on platelet counts, in newly diagnosed acute leukemia patients with CRT, is not associated with higher rates of VTE recurrence. Moreover, this strategy does not result in major hemorrhagic complications even in patients with severe thrombocytopenia. Notably, RBC infusion requirements were lower in the post-CRT diagnosis phase, while platelet transfusion was similar during the pre- and post-CRT phases. This analysis, including a large number of patients, demonstrates that the adjusted therapy is safe and efficient in this challenging clinical scenario.

Thromboprophylaxis with Intermediate Dose Low Molecular Weight Heparin in Adults Undergoing Induction with L-Asparaginase for Acute Lymphoblastic Leukemia

Introduction Adolescents and young adults (AYA, defined as age 15-39 years) with acute lymphoblastic leukemia (ALL) have a poorer prognosis than their pediatric counterparts. To replicate the success of ALL treatment in children, pediatric-inspired regimens have been incorporated into the treatment of AYA and often include the use of L-asparaginase. Rates of thrombosis in adults receiving L-asparaginase for treatment of ALL have been reported to be as high as 34%, compared to only about 5% in pediatric patients. The risk of thrombosis is elevated primarily during the induction phase of treatment. Several strategies have been studied in adults, including antithrombin III replacement, fresh frozen plasma replacement, and prophylactic dosing of anticoagulation, however no clear guidelines exist on how to prevent thrombosis in these high-risk patients. To prevent L-asparaginase-induced thrombotic events, our institution implemented a standard practice of 1mg/kg/day of low molecular weight heparin (LMWH), a dose in-between prophylactic and therapeutic dosing, administered to all adults with ALL who were treated with L-asparaginase during induction chemotherapy. In this current study, we report data from patients who have been treated with this strategy from 2012 to present, focusing on the antithrombotic efficacy and safety of 1mg/kg/day LMWH in this population. Methods This retrospective chart review included 62 patients who received prophylactic anticoagulation with the LMWH enoxaparin (1mg/kg/day) while undergoing induction chemotherapy with L-asparaginase for ALL at the Oregon Health &amp; Science University from 2012 to present. Anticoagulation with enoxaparin was initiated with the first dose of L-asparaginase and continued until the day of discharge or day 30 of induction. The primary outcome was the incidence of thrombosis within the first 30 days of L-asparaginase administration. Minor and major bleeding events, as defined by the International Society of Thrombosis and Haemostasis (ISTH), were recorded. Statistical analysis with univariate regression models was performed to evaluate the association of thrombotic events with demographic, disease and treatment variables. Results Sixty-two patients received 1mg/kg/day LMWH prophylaxis during ALL induction between January 2012 and June 2023 (43 with B-ALL and 19 with T-ALL). Median age at induction was 25.7 years (range 18-39 years). A majority of patients (83.9%) received the maximum dose of 2500mg/m 2 of L-asparaginase. Four patients (6.5%; 95% CI 1.8%-15.7%) experienced a thrombotic event within the first 30 days of induction with L-asparaginase; 3 of the events were catheter-associated and were treated supportively or with catheter removal, and 1 patient developed a distal lower extremity deep vein thrombosis related to myositis. Median time to thrombosis was 13.5 days (range 11-22 days). There were no significant associations between development of thrombotic events with age, gender, B- or T-cell precursor, or dose of L-asparaginase. No thrombosis-related deaths or major bleeding events occurred. Conclusions Prophylactic anticoagulation with intermediate dose 1mg/kg/day LMWH in adults with ALL undergoing induction chemotherapy with L-asparaginase is a safe and an effective strategy to prevent serious thrombotic events. Our institutional rate of 6.5% of patients experiencing thrombotic events during induction with L-asparaginase, with all of the events being clinically low risk, compares favorably to historically reported rates in adults and approaches the low rates reported in children. Further prospective research is warranted.

Thrombosis Rates and Use of Thromboprophylaxis after Discharge from Gynecologic Cancer-Related Surgery

Background: Cancer and major abdominopelvic surgeries pose significant thrombosis risks, making cancer-related surgery highly susceptible to venous thromboembolism (VTE) despite prophylaxis. Without post-operative thromboprophylaxis (TPX), VTE risk can reach 29% in the weeks following major surgeries. National Comprehensive Cancer Network (NCCN) guidelines recommend anticoagulation for up to 4 weeks after such surgeries, primarily using low molecular weight heparin (LMWH) for 28 days postoperatively. This study aimed to determine VTE rates linked to various gynecologic cancer-related surgeries and explore TPX utilization in a large cancer-center cohort. Additionally, we sought to further understand the necessity for post-discharge TPX in this setting. Methods: Patients (pts) diagnosed with gynecologic cancer between January 1st, 2012, through September 15th, 2022, at our institution were identified through our tumor registry. Using an in-house automated text search tool from our electronic medical record (Epic®), combined with natural language processing review, venous thromboembolism (VTE) events were identified, with secondary adjudication by the study leader (GAS). VTE was defined as either lower extremity deep vein thrombosis (DVT), or pulmonary embolism (PE) diagnosed from the day of surgery until 90 days after the first day of surgery. Logistic regression was performed on binary outcomes for the presence of VTE and TPX use at discharge. Kaplan-Meier curves and Cox regression were used for overall survival analysis. Results: 801 pts who underwent gynecologic cancer-related surgeries were identified. Patient demographics and surgery types are described in Table 1. VTE occurred in 1.9% (n=15) of the overall population but was unequally distributed. The number of VTE in those undergoing minimally invasive surgery (MIS), vulvovaginal surgery, and biopsies collectively was low (0.57%, n=3), even when considering that only 11.1% of those pts received TPX at discharge. VTE was more commonly diagnosed in patients who underwent open surgery (4.3%, n=12), with 5 pts (1.8%) diagnosed before discharge and 7 pts (2.5%) after discharge. In multivariable logistic regression analysis, during the full study period, open procedures were associated with a higher risk of thrombosis, (relative risk 7.5, p &amp;lt; 0.001) and higher use of post-discharge TBX (RR 4.55, p &amp;lt; 0.001). Notably, only 50% (139 of 279) of pts who underwent open surgery received TPX at the time of discharge. Within the open surgery cohort, the rate of post-discharge VTE correlated with the use of post-discharge TPX. Of pts on TPX, 0.7% (n=1) were diagnosed with VTE compared to 4.3% (n=6) of pts who did not receive TPX (RR=0.17, p= 0.12). There was no difference in overall survival in pts who received TPX and those who did not after open surgery up to 36 months after the surgery. Conclusions: Our findings suggest a tiered risk of post-operative VTE after gynecologic cancer surgery, with a clinically relevant risk observed only in women undergoing open surgery. Our gynecologic oncology practice already reflects this, as post-operative TPX is not routinely prescribed for lower-risk procedures. In patients who underwent open surgery, TPX at discharge showed a trend towards a protective effect, although this result did not reach statistical significance, probably due to sample size, it supports the need for a targeted prospective study. If this trend towards benefit holds in a prospective study, the number needed to treat to avoid one clinically detected post-operative VTE would be 28 pts. The relatively high fraction of post-op VTE events during the inpatient hospital stay also supports efforts for early TPX, as has been done with a prophylactic dose of pre-operative unfractionated heparin or LMWH in other high-risk cancer surgery settings (Selby et al, J Am Coll Surg. 2016). The limitations of this study include being conducted at a single institution, retrospective and non-randomized.

The Impact of Laboratory Sample Request Evaluation and the Use of Probability Testing for HIT By Trained Physician on the Decrease of Unnecessary Tests and Increase the Likelihood of Positivity

Introduction: Heparin-induced thrombocytopenia (HIT) is an extremely serious and potentially fatal condition that can develop in patients taking heparin-based medications, such as unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). The laboratory tests for diagnosis of HIT is expensive and time consuming. Clinical assessment (4Ts) followed by testing for Heparin/platelet factor 4 antibody in intermediate and high risk patients is the standard algorithm of pretest for (HIT) which can be later confirmed by serotonin releasing assay if available. Materials and methods: We conducted a retrospective analysis of laboratory practice of pretest evaluation of samples submitted for HIT testing in a cohort of patients treated in a tertiary hospital in Saudi Arabia who had a clinical suspicion of HIT. The 4 T score was a pretest requisite to proceed for electronic request for HIT. It had to be performed by the requesting physicians of different medical specialties. The request then been evaluated by hematopathologist before proceeding. The test will be cancelled if: the 4T score calculated by attending physician is &amp;lt; 4 or if platelet count is normal with no evidence of significant drop in the last 4 days from request or the test was performed at least 2 days before the new request. Additional exercise was performed by two physicians in training after train them to standardize the calculation of the 4T scores without re evaluation by the hematopatologist. The sample proceeded for testing if it met the testing criteria of 4T score &amp;gt; 3 and passed the evaluation by the hematopathologist. All tested sample were performed by immunoglobulin G (IgG) antibodies via an ELISA (Asserachrom HPIA-IgG, Stago Diagnostica STA®) and Optic density ( OD) and was evaluated and considered positive if OD &amp;gt;0.39 with sub classification to low positive 0.4-1, moderate 1-2 and strong if &amp;gt;2. Over a period of 2 years, we received 449 samples for patients who were admitted to our hospital, received prophylactic or therapeutic doses of LMWH or UFH, and underwent an HIT test due to clinical suspicion ( &amp;gt; 50% drop in platelet count from baseline, or ≥ 2 consecutive platelet counts &amp;lt; 150,000 per mm 3 and was defined as possible HIT). The 4 T score was calculated in the hospital system by attending physicians referred to as (system 4T score) and recalculated by trained two physicians and referred to (re calculated 4T score). Descriptive statistics, paired samples statistics, correlations, and analysis of variance (ANOVA) were performed. Results: The test was labeled by the laboratory physician ( hematopathologist ) as not indicated and test was not performed in 156 (35%) for various reasons including low 4 T score &amp;lt;3 in 90 (57%), Normal platelet count &amp;gt; 150 at time of test ( and wrong calculated 4T score) in 28 (18%), duplication of test order in 10 (6.4%%), There was clear other cause of thrombocytopenia in 15 (10%), Bad sample quality 5 (3.2%%) and 8 (5%) for other reasons. The samples for HIT test were for 231(51%) males and 220 (49%) females with mean age 56.3 (1-102) years. The mean platelet count at time of request was 82.9 (2-384) per mm 3. Out of the total cohort 422 (95.1%) patients had received UFH and only 22 (4.9%) received LMWH. There is only 69/449 (15.4%) agreement between the two calculations (system and re calculated score) . Out of the tested samples 293, total positive tests 19 (6.5%), were 11 (3.8%) had low positive for HIT test, moderate positive in 6 (2%) and only 2 strongly positive for HIT. The calculated (system 4T score) of &amp;lt; 4 were 142 (32%) samples while the (re calculated 4T score) were 136 (30%) of which 60 ( 38%) of the cancelled tests by hematopathologist, of which 68 (23%) of tested samples were negative and 7 (37%) of positive tests could have been missed based on this calculation. There were 12 out of 19 had moderate and high score by calculation and positive HIT while there were 17 out of 19 had moderate and high score by system calculation. Conclusion: We are reporting improved detection of HIT and confirmed the value of applying the 4 T score for HIT testing with added value of pre test screening to exclude low probability and cancel samples with no clear indication of HIT due to presence of other causes of thrombocytopenia.The retrospective re calculation even with more trained physicians did not add a value compared to pretest evaluation and screening by hematopathologist which had resulted in cancelation or more than third of the requested tests.

Thromboprophylaxis strategies in patients undergoing endovenous thermal ablation: a UK survey

Introduction: It remains unclear whether patients undergoing endovenous thermal ablation (EVTA) for superficial venous incompetence (SVI) should receive pharmacological thromboprophylaxis. A survey was conducted to assess current thromboprophylaxis practices across the UK in patients undergoing EVTA for SVI. Methods: To examine the thromboprophylaxis practices of clinicians performing EVTA for SVI in the UK, an online survey was developed using the Qualtrics online survey tool. The survey link was circulated via email to members of the multidisciplinary collaborative Vascular and Endovascular Research Network (VERN) and promoted through social media. The primary focus of the survey was to gather information regarding venous thromboembolism (VTE) prophylaxis during EVTA for SVI. Results: A total of 32 vascular surgeons and one vascular nurse specialist based in the UK participated in the survey. All respondents reported routine prescription of compression therapy in the immediate postoperative period. Of all the respondents, 67% (n=22) reported routine prescription of pharmacological thromboprophylaxis during the peri-procedural period. Extended prophylaxis was routinely offered by 15% (n=5) of all respondents. Among those who provided extended prophylaxis, the majority (80%, n=4) used low molecular weight heparin (LMWH), while 20% (n=1) opted for a direct-acting oral anticoagulant (DOAC). Conclusion: The findings from this survey indicate that a significant proportion of patients undergoing EVTA for SVI routinely receive pharmacological thromboprophylaxis, with a single perioperative dose of LMWH being the prevailing practice. However, there is a notable lack of robust high-quality evidence to substantiate this practice. Grade A evidence is required to assess the potential benefit of pharmacological thromboprophylaxis in the context of EVTA to guide the development of clinically relevant guidelines. Should pharmacological thromboprophylaxis prove to offer no additional benefit for this specific patient population, this could result in cost savings for the NHS and enable patients to avoid unwanted side effects associated with anticoagulation therapy.

Maternal and Newborn Characteristics-A Comparison between Healthy and Thrombophilic Pregnancy.

A thrombophilic woman is more likely to experience difficulties during pregnancy, difficulties that will also affect the development of the newborn. This study aims to compare maternal and newborn characteristics between healthy and thrombophilic pregnancy. The following characteristics were analysed: maternal characteristics (BMI- body mass index, haemostasis parameters, thrombophilia-specific treatment) and newborn characteristics (gestational period, birth weight, the Apgar score). This follow-up study spanning five years, from 2018 to 2022, focuses on a cohort of 500 women who underwent delivery hospitalization in the western region of Romania. The maternal characteristics influence the newborn: the greater the weight of the mother with thrombophilia, the more the chances that the fetus will have a lower birth weight; increasing the dose of LMWH (low molecular weight heparin), connected with the necessity to control the homeostasis parameters, the more likely the fetus will be born with a lower birth weight. A pregnant woman with thrombophilia, treated appropriately, having a normal weight, and not presenting other risk factors independent of thrombophilia, will have a newborn with characteristics similar to a healthy pregnant woman.

PB0943 Results of a Clinical Audit of Intermediate Dose Low Molecular Weight Heparin for Thromboprophylaxis in Newly Diagnosed Multiple Myeloma Patients

PB0943 Results of a Clinical Audit of Intermediate Dose Low Molecular Weight Heparin for Thromboprophylaxis in Newly Diagnosed Multiple Myeloma Patients

Anti-factor Xa level monitoring of low-molecular-weight heparin for prevention of venous thromboembolism in critically ill patients (AXaLPE): protocol of a randomised, open-label controlled clinical trial

IntroductionWhether and when to monitor the amount of anti-factor Xa (aFXa) activity in critically ill patients with complex diseases to prevent venous thromboembolism (VTE) remain unclear. This study is a...

P09 A catastrophic decline: a significant skin rash in a patient presenting with catastrophic antiphospholipid syndrome

P09 A catastrophic decline: a significant skin rash in a patient presenting with catastrophic antiphospholipid syndrome

Moderate LMWH Anticoagulation Improves Success Rate of Hind Limb Allotransplantation in Mice.

The mouse hind limb model represents a powerful research tool in vascularized composite tissue allotransplantation, but its applicability is limited due to poor graft survival (62%-83%). Vascular thrombosis and massive hemorrhage are the major causes for these drop-outs. We hypothesize that because of better anticoagulation effect and lower risk of thrombocytopenia, application of low molecular weight heparin (LMWH) will minimize vascular complications and enhance graft and animal survival. Fifty allogeneic hind limb transplantations were performed (C57BL/6 to DBA/2 mice) using five different anticoagulation protocols. Bleeding and thromboembolic events were recorded macroscopically by postoperative hemorrhage and livid discoloration of the graft, respectively. Graft perfusion and survival were monitored daily by capillary-refill-time of graft toes within 2-3 seconds. Vascular congestion and tissue necrosis were examined by histological evaluation of hematoxylin-eosin-stained tissue sections. All transplantations were technically successful. Increase in thromboembolic events and a concomitant decrease in bleeding events were observed with the decreasing concentration of heparin in the perfusion solution. Although treatment of donor and recipient with low dose of LMWH could not reduce thromboembolic events, moderate dose effectively reduced these events. Compared with the poor outcome of graft perfusion with heparin alone, additional treatment of donor and recipient with low dose of LMWH improved graft and animal survival by 18%. Interestingly, animals treated with moderate dose of LMWH demonstrated 100% graft and animal survival. Treatment of donor and recipient mice with a moderate dose of LMWH prevents vascular complications and improves the outcome of murine hind limb transplants.

Is There a Role for Anti-factor Xa Activity Assay in Venous Thromboembolism Prophylaxis Management Among Orthopaedic Trauma Patients? Systematic Review and Meta-analysis.

To determine the effect of anti-factor Xa assay dosing of low-molecular-weight heparin (LMWH) on rates of venous thromboembolism (VTE), deep vein thrombosis (DVT), pulmonary embolism (PE), bleeding, and mortality among orthopaedic trauma patients. PubMed/MEDLINE, Embase, Ovid, Cochrane Central Register of Controlled Trials (CENTRAL), clinicaltrials.gov , and Scopus were systematically searched from inception of the database to 2021. Prospective, retrospective, and randomized controlled trial studies were included if they compared rates of VTE, DVT, PE, bleeding, and/or mortality between orthopaedic trauma patients receiving anti-factor Xa-based LMWH dosing and those receiving standard dosing. Two independent reviewers screened titles and abstracts for eligibility. Study characteristics including study design, inclusion criteria, and intervention were extracted. Meta-analysis was performed using pooled proportion of events (effect size) with 95% confidence intervals. A random-effects model was used. Heterogeneity was quantified by Higgins I 2 . Heterogeneity and variability between subgroups indicated differences in the pooled estimate represented by a P -value. Six hundred eighty-five studies were identified, and 10 studies including 2870 patients were included. In total, 30.3% and 69.7% received an adjusted and nonadjusted dose of LMWH, respectively. The rate of VTE and DVT were significantly lower in the anti-factor Xa-adjusted cohort, whereas there was no statistically significant difference in rates of PE, bleeding, or mortality between the cohorts. This systematic review and meta-analysis demonstrates that anti-factor Xa activity assay dosing of LMWH among orthopaedic trauma patients leads to a reduction in overall DVT rates, although not PE rates, without an increased risk of bleeding events. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.