Dose Of Enoxaparin Research Articles

Outcomes of Catheter-Related Arterial and Venous Thrombosis After Enoxaparin Therapy in Neonates and Infants With Congenital Heart Disease.

Outcomes of catheter-related arterial and venous thrombosis after enoxaparin therapy in neonates and infants with congenital heart disease. A single-center retrospective cohort study. Cardiac ICU. Patients under 1 year old cared for in the cardiac ICU at Nicklaus Children's Hospital from January 2015 to January 2019 and treated with enoxaparin for central vascular catheter-related arterial and venous thrombosis. None. One-hundred fifty-six events of central catheter-related arterial and venous thrombosis were included in the study. Arterial thrombi accounted for 109 (69.9%) and venous thrombi for 47 (30.1%) of the events. Femoral vessels were the most commonly affected site (88.5%). Therapeutic outcomes were analyzed in 106 events, excluding those without follow-up imaging. The analysis was stratified by age into neonates and infants and catheter types into arterial and venous catheter groups. Therapeutic dose of enoxaparin was higher in neonates (median 1.8 mg/kg/dose) compared with infants (1.6 mg/kg/dose; p = 0.001). Complete resolution was seen in 68%, partial resolution in 19%, nonresolution in 13% of the events. The complete resolution was higher for arterial than venous (85% vs 65.6%; p = 0.032) thrombi with a shorter duration of enoxaparin treatment (23 vs 43 d; p = 0.014). Complete resolution was lowest in neonates with venous thrombosis (42.9%). The median time to complete resolution by Kaplan-Meier analysis was 24.9 days in the overall cohort, 34.3 days in neonates, 24.9 days in infants, 20 days in arterial, and 44.9 days in venous catheter group. A high proportion of vascular catheter-related thrombi identified in infants with congenital heart disease resolve with enoxaparin treatment. In all patients with thrombosis, arterial versus venous thrombosis is associated with greater odds of resolution.

Optimal enoxaparin dosing strategies for venous thromboembolism prophylaxis and treatment of high body weight patients

ObjectiveObesity is a risk factor for developing venous thromboembolism (VTE). Optimal dosage of enoxaparin has not been established in the obese population. We aimed to study clinical outcomes and complications with enoxaparin in obese patients. MethodsA retrospective, single centre observational study of obese patients treated with enoxaparin for VTE (n = 47) using a body mass index (BMI)-stratified dosing, thromboprophylaxis (n = 46), and non-obese controls (n = 20) was performed. Anti-Xa was used to measure enoxaparin efficacy. ResultsPatients with a median BMI of 36.3 kg/m2 (range 30–52.7) with a median weight of 136 kg (range 68–240) received therapeutic enoxaparin at median 120 mg BID (range 60–200). A median targeted anti-Xa level of 0.79 (95% CI 0.72–1.03) IU/mL was achieved in 58% of patients. Dose reduction, or increase was needed in 25%, and 16% patients respectively. Mild or major haemorrhage, or VTE occurred in 10%, 2% and 2% patients respectively.Patients with a median weight of 160 kg (range 130–245) received thromboprophylaxis with 40 mg BID enoxaparin. Targeted median anti-Xa of 0.22 IU/mL (95% CI 0.19–0.24) was achieved in 59% patients. Mild haemorrhage was seen in 2%, while none developed major haemorrhage or VTE.Control patients who received enoxaparin 40 mg daily did not develop VTE; 5% had minor bleeding events. ConclusionsBMI-stratified therapeutic enoxaparin dosing regimen is safe and effective therapy in obese patients. Fixed dosing without monitoring may not be appropriate. Thromboprophylaxis with 40 mg BID in obese patients was efficacious in preventing VTE without excess bleeding compared to control patients.

Two Weeks of Low Molecular Weight Heparin for Isolated Symptomatic Distal Vein Thrombosis (TWISTER study)

BackgroundTreatment of low-risk patients with isolated symptomatic distal deep vein thrombi (IDDVT) is uncertain. Objective: assess whether two weeks of therapeutic anticoagulation is efficacious/safe for IDDVT. Primary outcome: symptomatic three-month venous thromboembolism (VTE) incidence in the two-week anticoagulation group. Secondary outcomes included post-thrombotic syndrome (PTS) and bleeding. MethodsProspective multicentre cohort study. Consecutive low-risk IDDVT patients enrolled within 72 h of diagnosis and treated with therapeutic dose enoxaparin or rivaroxaban. At two weeks, patients had repeat complete whole leg compression ultrasound (CUS)/clinical review. If resolution of leg symptoms AND no radiological evidence of thrombus extension, anticoagulation was stopped. If ongoing symptoms and/or radiographic extension within distal veins, anticoagulation was continued for four more weeks. Patients with extension into the popliteal vein on two-week ultrasound were treated off-study. Patients were reviewed at three and six months. Findings/interpretation241 eligible patients received ≥2 weeks anticoagulation. 167/241 (69%) were assigned to the 2-week anticoagulation group; 71/241 (30%) to the six-week anticoagulation group; 3/241 patients (1%) had extension into the popliteal vein on two-week CUS.Two patients in the two-week anticoagulation group had symptomatic IDDVT recurrence in ≤3 months; VTE recurrence 2/156; 1.3%(95% CI 0.05–4.85%). 69% of patients had complete resolution of symptoms within two weeks. Six-month PTS rates were 8/184, 4.4%(95% CI 2.1–8.5%). No major bleeding was reported.Our findings suggest it's safe/efficacious to stop therapeutic anticoagulation at two weeks in low-risk IDDVT patients with resolution of symptoms/no extension on ultrasound.This could replace 6–12 weeks of anticoagulation for ambulatory, low-risk IDDVT patients. Trial registrationClinicalTrials.govNCT01252420

Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID‐19: A multi‐center, open‐label, randomized controlled trial

BackgroundCoronavirus disease 2019 (COVID‐19) is associated with coagulopathy but the optimal prophylactic anticoagulation therapy remains uncertain and may depend on COVID‐19 severity. ObjectiveTo compare outcomes in hospitalized adults with severe COVID‐19 treated with standard prophylactic versus intermediate dose enoxaparin. MethodsWe conducted a multi‐center, open‐label, randomized controlled trial comparing standard prophylactic dose versus intermediate dose enoxaparin in adults who were hospitalized with COVID‐19 and admitted to an intensive care unit (ICU) and/or had laboratory evidence of coagulopathy. Patients were randomly assigned in a 1:1 ratio to receive standard prophylactic dose enoxaparin or intermediate weight‐adjusted dose enoxaparin. The primary outcome was all‐cause mortality at 30 days. Secondary outcomes included arterial or venous thromboembolism and major bleeding. ResultsA total of 176 patients (99 males and 77 females) underwent randomization. In the intention‐to‐treat population, all‐cause mortality at 30 days was 15% for intermediate dose enoxaparin and 21% for standard prophylactic dose enoxaparin (odds ratio, 0.66; 95% confidence interval, 0.30–1.45; P = .31 by Chi‐square test). Unadjusted Cox proportional hazards modeling demonstrated no significant difference in mortality between intermediate and standard dose enoxaparin (hazard ratio, 0.67; 95% confidence interval, 0.33–1.37; P = .28). Arterial or venous thrombosis occurred in 13% of patients assigned to intermediate dose enoxaparin and 9% of patients assigned to standard dose enoxaparin. Major bleeding occurred in 2% of patients in each arm. ConclusionIn hospitalized adults with severe COVID‐19, standard prophylactic dose and intermediate dose enoxaparin did not differ significantly in preventing death or thrombosis at 30 days.

Comparison of the injection of low molecular weight heparin in arterial or venous bloodline for preventing extracorporeal circuit clotting during hemodialysis

Low molecular weight heparins (LMWH) are widely used for preventing clotting during hemodialysis (HD). Although injection in venous bloodline (VBL) is recommended to avoid initial loss of LMWH through the dialyzer, LMWH is still frequently administered in the arterial blood line (ABL) at the start of dialysis. The aim of this study was to compare the efficacy and safety of same enoxaparin dose administered through VBL or ABL. We also evaluated antifactor Xa (aXa) activity according to the injection route and dialysis modalities: high-flux (HF) HD, medium cut-off (MCO) HD and on-line hemodiafiltration (OL-HDF). This open, single-center prospective study was conducted at the Poitiers university Hospital HD unit. Forty-three patients were studied over 18 consecutive dialysis sessions using a fixed enoxaparin dose (20 or 40 mg) first administered through ABL bolus and then through VBL for another 18 sessions. Compared to ABL, VBL bolus resulted in significant increase in median post-dialysis aXa activity: 0.16 (0.1–0.6) IU/mL vs. 0.31 (0.1–1.3) IU/mL, respectively, P = 0.006. After ABL bolus of enoxaparin 40 mg, median post-dialysis aXa activity was significantly lower with OL-HDF compared to HF-HD: 0.14 (0.1–0.35) vs. 0.32 (0.15–0.49), P = 0.02. A trend for lower clotting within lines and bubble trap using VBL bolus was observed. In conclusion, VBL enoxaparin injection is safe in OL-HDF patients. However, in HF-HD and MCO-HD, VBL injection of enoxaparin 40 mg may increase overdosing risk. Thus, aXa activity should be monitored in HF-HD and MCO-HD patients at risk of bleeding and/or on vitamin K antagonists, and careful surveillance is required when administering enoxaparin dose 40 mg through the VBL route.

Application of thromboelastography in comparing coagulation difference of rivaroxaban and enoxaparin for thromboprophylaxis after total hip arthroplasty.

Purpose: The purpose of this study was to compare the coagulation difference in patients with either rivaroxaban or enoxaparin as thromboprophylaxis after total hip arthroplasty (THA) regarding thromboelastography (TEG) and routine coagulation tests. Patients and methods: Two hundred and twenty-eight patients undergoing primary THA were recruited in this study. They were divided into two groups according to a computer-generated random sequence. Patients in the rivaroxaban group received 10mg of rivaroxaban orally once daily. Patients in the enoxaparin group received 4000 AxaIU (0.4mL) of enoxaparin subcutaneously once daily. Rivaroxaban and enoxaparin were started 6-8h after surgery. The administration of the anticoagulant prophylaxis was lasted for a minimum of 14days. TEG and routine coagulation tests were performed on the day before the operation and 1day and 7days after the operation. Results: No difference was observed in the incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE) between the two groups. There was no significant difference with regard to prothrombin time (PT), activated partial thromboplastin time (PTT), international normalized ratio (INR), and thrombin time (TT) between the two groups. However, while considering TEG, R time of the rivaroxaban group was significantly higher than that of the enoxaparin group (p = 0.003), whereas the maximum amplitude (MA) (p = 0.036) value and coagulation index (CI) (p = 0.002) value were significantly lower than those of the enoxaparin group. Conclusion: With regard to TEG analysis, there was coagulation difference in patients with rivaroxaban and those with enoxaparin as thromboprophylaxis after THA. Under recommended dose of rivaroxaban and enoxaparin, patients undergoing THA were in hypercoagulability on 7days postoperative.

Venous Thromboembolism Chemoprophylaxis in Trauma and Emergency General Surgery Patients: A Systematic Review.

Appropriate venous thromboembolism (VTE) chemoprophylaxis in trauma and emergency general surgery (EGS) patients is crucial. The purpose of this study is to review the recent literature and offer recommendations for VTE chemoprophylaxis in trauma and EGS patients. We conducted a literature search from 2000 to 2021 for articles investigating VTE chemoprophylaxis in adult trauma and EGS patients. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Our search resulted in 34 articles. Most studies showed low-molecular-weight heparin (LMWH) is similar to unfractionated heparin (UFH) for VTE prevention; however, LMWH was more commonly used. Adjusted chemoprophylaxis dosing did not change the VTE rate but the timing did. Direct oral anticoagulants (DOACs) have been shown to be safe and effective in trauma and traumatic brain injury (TBI)/spinal cord injury (SCI). Studies showed VTE prophylaxis in EGS can be inconsistent and improves with guidelines that lower VTE events. There may be no benefit to receiving LMWH over UFH in trauma patients. In addition, different drugs under the class of LMWH do not change the incidence of VTE. Adjusted dosing of enoxaparin does not seem to affect VTE incidence. The use of DOACs in the trauma TBI and SCI setting has been shown to be safe and effective in reducing VTE. One important consideration with VTE prophylaxis may be the timing of prophylaxis initiation, specifically as it relates to TBI, with a higher likelihood of developing VTE as time progresses. EGS patients are at a high risk of VTE. Improved compliance with clinical guidelines in this population is correlated with decreased thrombotic events.

Abstract MP03: Histone-mediated Platelet Activation And Microvesicle-induced Thrombin Generation In COVID-19

Background: Severe COVID-19 leads to inflammation and coagulopathy with progression to multiple organ failure. Several prothrombotic mechanisms have been proposed, including NETosis with release of citrullinated histones, platelet hyperactivation, and generation of procoagulant microvesicles. Aims: We hypothesized that histones derived from NETosis promote platelet activation and release of microvesicles that mechanistically contribute to thrombin generation and thrombosis in COVID-19. Methods: Platelet poor plasma (PPP) was prepared from 136 COVID-19 patients enrolled in a multicenter randomized clinical trial comparing standard prophylactic dose to intermediate dose enoxaparin in hospitalized patients with COVID-19 (NCT04360824). We also prepared PPP and washed platelets from 53 healthy subjects. We measured citrullinated histone H3 (H3Cit) by ELISA, microvesicles by flow cytometry, and thrombin generation using the Calibrated Automated Thrombogram. Ex vivo platelet adhesion and thrombus growth on collagen was measured in a microfluidic chamber. Results: Compared to healthy subjects, COVID-19 patients had elevated plasma levels of H3Cit and platelet-derived microvesicles. When PPP was triggered with exogenous tissue factor and phospholipids, higher endogenous thrombin potential, peak thrombin, and velocity index were observed in COVID-19 patients compared to healthy subjects. Increased thrombin generation with COVID-19 PPP was evident even when triggered without added phospholipids, suggesting the presence of procoagulant microvesicles in COVID-19 plasma. Enhanced thrombin generation also was observed after transfer of microvesicles isolated from COVID-19 patient plasma to control PPP. Incubation of control platelets with PPP from COVID-19 patients but not healthy subjects caused increased platelet-dependent thrombin generation and larger platelet-thrombi under venous shear stress. These effects of COVID-19 plasma on platelet-dependent thrombin generation and platelet-thrombi formation were inhibited by a histone aptamer. Conclusions: We conclude that histone-mediated platelet activation promotes thrombosis in COVID-19 in part via increased thrombin generation driven by microvesicles.

Standard Dose Prophylaxis Application and Venous Thromboembolism Findings in Patients Who Had Bariatric Surgery

Aim: Venous thromboembolism (VTE) events covering deep vein thrombosis (DVT) and pulmonary embolism (PE) constitute the most important morbidity-mortality cause in obesity surgery. The objective of this study was to assessment of thromboembolism results in patients who underwent bariatric surgery with standard dose prophylaxis. Patients and Methods: The patients who were operated for morbid obesity in our clinic between 2015 and 2019 were retrospectively examined. Cases that had laparoscopic sleeve gastrectomy and were applied standard dose Enoxaparin prophylaxis were included in the study. Demographic data, preoperative preparation and postoperative antiembolic treatment conditions of the patients were registered. Results: Eighty-seven patients who had laparoscopic sleeve gastrectomy were included in the study. 66 (%75,8) of the patients were female and 21 (%24,1) were male. The mean age was 38.7 (18-55). Mean hospitalization duration was 6.6 (3-69) days. Four patients (% 4,5) had postoperative complication. PE developed in two patients while leak-related mediastinitis and incisional hernia (%1,1) developed in one case each. Conclusion: Despite available prophylaxis methods, VTE constitutes an important morbidity and mortality cause in patients who had bariatric surgery. While high-dose low-molecular weight heparin (LMWH) use may cause bleeding, the possibility of VTE increases with using low-dose LMWH. This situation appears as a limitation of LMWHs. New studies are needed for increased dose at early period and standard dose application after discharge.

The Impact of Risk-Adjusted Heparin Regimens on the Outcome of Patients with COVID-19 Infection. A Prospective Cohort Study.

Background. According to recent guidelines, all hospitalized patients with COVID-19 should receive pharmacological prophylaxis for venous thromboembolism (VTE), unless there are specific contraindications. However, the optimal preventive strategy in terms of intensity of anticoagulation for these patients is not well established. Objectives. To investigate the impact of individualized regimens of enoxaparin on the development of VTE and on the risk of major bleeding complications during hospitalization in patients with COVID-19 infection. Methods. All consecutive patients admitted to the medical wards of six Italian hospitals between 15 September and 15 October 2020 with COVID-19 infection of moderate severity were administered enoxaparin in subcutaneous daily doses adjusted to the Padua Prediction Score stratification model: No heparin in patients scoring less than 4, 4000 IU daily in those scoring 4, 6000 IU in those scoring 5, and 8000 in those scoring six or more. Objective tests were performed in patients developing clinical symptoms of deep vein thrombosis and/or pulmonary embolism. Bleeding complications were defined according to the ISTH classification. Results. From the 154 eligible patients, enoxaparin was administered in all: 4000 IU in 73 patients, 6000 IU in 53, and 8000 IU in the remaining 28. During the course of hospitalization, 27 patients (17.5%) died. VTE developed in 14 of the 154 patients (9.1%; 95% CI, 4.6% to 13.6%), and was fatal in 1. Major bleeding complications developed in 35 patients (22.7%; 95% CI, 16.1% to 29.3%), and were fatal in 8. Conclusions. Despite the use of risk-adjusted doses of enoxaparin, the rate of VTE events was consistent with that reported in contemporary studies where fixed-dose low-molecular-weight heparin was used. The unexpectedly high risk of bleeding complications should induce caution in administering enoxaparin in doses higher than the conventional low ones.

Effectiveness and Tolerability of Fondaparinux vs Enoxaparin in a Population of Indian Patients with Symptomatic Deep Vein Thrombosis: A Retrospective Real-World Study.

BackgroundFondaparinux is the first approved anticoagulant drug among factor Xa inhibitors, with proven effectiveness and safety in preventing deep vein thrombosis. However, limited data are available supporting the benefit-risk profile of fondaparinux vs enoxaparin in a real-world group of Indian patients with deep vein thrombosis.ObjectiveTo compare the effectiveness and tolerability of fondaparinux vs enoxaparin in patients with symptomatic deep vein thrombosis in a long-term real-world setting.MethodsData from the electronic medical records of adult patients diagnosed with deep vein thrombosis prescribed fondaparinux (n = 503) or enoxaparin (n = 508) as monotherapy were analyzed. Effectiveness was analyzed in terms of recurrence, duration, and type of deep vein thrombosis event, and tolerability as bleeding events at initial hospitalization and follow-up visits up to 3 months duration. Appropriate statistical methods were used to determine the significance (p < 0.05) between the two groups.ResultsThe deep vein thrombosis recurrence in the fondaparinux group was non-inferior (2.78%) when compared with enoxaparin (3.76%), with a mean duration of 47 and 48 days, respectively. The number of events and mean duration of events (in days) were not significant (p > 0.05). Major bleeding events were higher in the enoxaparin group at 3.17% than the fondaparinux group at 2.19%, and the difference was not statistically significant (p > 0.05).ConclusionsThe weight-based, once-daily subcutaneous fondaparinux dose showed non-inferior effectiveness and a comparable tolerability profile when compared with the twice-daily enoxaparin dose for the management of symptomatic deep vein thrombosis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-021-00273-4.

Effects of Changing Anticoagulation with Unfractionated Heparin into Enoxaparin in Hemodialysis Patients:Prospective Non Randomized Unicentre Study

Background: Maintaining the patency of the extracorporeal circuit (ECC) is required. The cost and long-term effect of anticoagulants on hemodialysis (HD) patients' parameters are still matters of concern. We aimed to study the effect of shifting to enoxaparin instead of unfractionated heparin (UFH) during HD and evaluate its efficacy, safety, and benefits.&#x0D; Design and methodology: This study was conducted at Arar hospital, Kingdom of Saudi Arabia (KSA), and included 86 end-stage renal disease (ESRD) patients on HD for six months starting from October 2017. All patients had been on UFH as an anticoagulant during hemodialysis sessions before they were shifted to equivalent doses of enoxaparin sodium (Clexan®) as a therapeutic upgrade to start with. The patients’ files were examined retrospectively for the period of UFH therapy and then all patients were observed prospectively for at least 6 months while on Clexane. The occurrence of clotting in the dialysis sets were recorded and the need for urgent HD for each patient and the reasons. &#x0D; Results: There was a reduction of filter clots even with the reduction of enoxaparin dose. There was a significant reduction of mean cholesterol, calcium, phosphorus, sodium, chloride, and serum osmolality. We found a significant reduction of pre-dialysis potassium among those who presented with a pre-dialysis potassium of higher than 5.5 mg/dl during the enoxaparin phase. Patients, who had thrombocytopenia while on UFH; showed improvement in platelet count after the shift to enoxaparin. However, patients who had platelet count lowered than 150000/mm3 6 months after having been shifted to enoxaparin; many of them received HD through a permanent catheter. No patients had a three-fold increase of normal values (3ULN) of liver function tests whether being on heparin or enoxaparin.&#x0D; Conclusion: Low molecular weight heparin (LMWH) could be more efficacious and safe than UFH with the improvement of some variables in HD patients.

Common iliac vein stenting for May-Thurner syndrome and subsequent pregnancy

BackgroundFor women with left common iliac vein compression (ie, May-Thurner syndrome) who undergo venous stenting and subsequently become pregnant, concerns have been raised regarding a possible compromise of stent patency due to compression from the gravid uterus and the hypercoagulability induced by pregnancy. Only a small body of literature exists on this subject, and limited management guidelines are available. The present study was designed to evaluate the safety of iliac vein stenting for May-Thurner syndrome (MTS) with subsequent pregnancy. MethodsFemale patients who had undergone common iliac vein stenting at our center who were aged 18 to 45 years and had subsequently become pregnant were identified. A retrospective medical record review of eight eligible patients was conducted, recording the demographics, procedural characteristics, and anticoagulation strategies. The primary outcome evaluated was stent patency. ResultsAll eight patients had undergone left common iliac vein stenting for MTS. A total of eight stents were placed, and all demonstrated duplex ultrasound patency throughout pregnancy and postpartum. Seven patients delivered healthy pregnancies, and one experienced a stillbirth. The clinical CEAP (clinical, etiologic, anatomic, pathophysiologic) class remained unchanged or improved from pregnancy to postpartum for all patients. The average age at stent placement was 31 ± 5 years, and the average interval from stent placement to pregnancy was 28 ± 19 months. One patient developed nonobstructive deep vein thrombosis (DVT) of the left femoral vein during pregnancy and was treated with therapeutic enoxaparin. The nonobstructive DVT did not compromise the iliac vein stent. Two patients received low-dose aspirin and prophylactic doses of enoxaparin, one for a history of DVT and factor V Leiden and one for a recent history of fertility treatment. The five remaining patients received no anticoagulation, three received low-dose aspirin, and two received no antiplatelet therapy. ConclusionsCommon iliac vein stent patency was not compromised by subsequent pregnancy in our eight patients with MTS. Furthermore, the stents remained patent throughout pregnancy in patients receiving a wide range of anticoagulation and antiplatelet treatments, suggesting that no uniform therapeutic threshold exists and treatment should be individualized. For most patients, low-dose aspirin alone or no treatment was adequate. This could have implications for counseling women who require intervention for MTS and are of child-bearing age.

Factor Xa Levels in Patients Receiving Prophylactic Enoxaparin Sodium in the Intensive Care Unit of an Academic Hospital.

ABSTRACTBackground: The aim of this study was to determine the anti-factor Xa levels in patients receiving enoxaparin sodium for venous thromboembolism prophylaxis in the intensive care unit (ICU).Patients and methods: Using a cross-sectional study methodology, 73 ICU patients receiving 40 mg enoxaparin sodium daily were enrolled in this study. Anti-factor Xa levels were measured following the second dose. Prophylactic and subprophylactic groups of patients were compared for age, sex, weight, body mass index, total bilirubin, serum albumin, and APACHE II score.Results: Anti-factor Xa levels were prophylactic (0.2–0.6 IU/mL) in 44 (60.3%) patients and subprophylactic (<0.2 IU/mL) in 29 (39.7%) patients. The mean (SD) actual delivered dose of enoxaparin per kilogram body weight was significantly higher, at 0.59 (0.11) mg/kg in the prophylactic group compared to 0.53 (0.13) mg/kg in the subprophylactic group (p = 0.043). The subprophylactic group had significantly lower serum albumin levels compared to the prophylactic group. The total bilirubin levels were not found to be significantly different between the two groups (p = 0.110).Conclusion: A fixed prophylactic 40 mg dose of enoxaparin was associated with a high proportion of subprophylactic anti-factor Xa levels. Weight-based dose and serum albumin level were independent predictors of achieving the prophylactic target range.How to cite this article: Baloo MM, Scribante J, Perrie H, Calleemalay D, Omar S. Factor Xa Levels in Patients Receiving Prophylactic Enoxaparin Sodium in the Intensive Care Unit of an Academic Hospital. Indian J Crit Care Med 2021;25(8):917–919.

Effective use of weight-based enoxaparin for deep vein thrombosis chemoprophylaxis in patients with traumatic brain injury

BackgroundEnoxaparin is the recommended agent for deep vein thrombosis (DVT) chemoprophylaxis in trauma patients. Current literature suggests weight-based dosing is superior to standard dosing for adequate chemoprophylaxis. Literature regarding the use of weight-based enoxaparin in the setting of traumatic brain injury (TBI) however is limited. MethodsA retrospective analysis of adult trauma patients admitted between January 1, 2018 to February 28, 2019 was performed. Sixty-six patients with TBI receiving weight-based enoxaparin met inclusion criteria. Incidence of intracranial hemorrhage (ICH) expansion was the primary endpoint. Newly diagnosed venous thromboembolism (VTE) and death were secondary endpoints. ResultsTwo patients, out of sixty-six, had progression of their TBI requiring surgical intervention. Newly diagnosed VTE occurred in one patient. No deaths were due to ICH expansion or VTE. ConclusionsUse of weight-based enoxaparin dosing in the setting of TBI shows promise without an increased incidence of ICH expansion when compared to other studies.Level of Evidence and Study Type: Level IV, Therapeutic.

A Research of the Factors Associated with Mortality of the Patients with COVID-19 in the Intensive Care Unit

Aim: The aim of this retrospective study is to investigate the clinical and laboratory factors associated with mortality of the patients with COVID-19 in the Intensive Care Unit. Methods: The patients with COVID-19 who were under follow-up and treat in the Anesthesia Intensive Care Unit between March and May 2020 were retrospectively analyzed. The patients were divided into two groups as Survival Group and Mortal Group. Age, gender, body mass index (BMI), comorbidities, laboratory values such D-dimer, ALT, AST, CRP, ferritin, troponin, IL-6, bicarbonate and lactate, intubation and ventilation, all treatments, coagulopathies, duration of ventilation and stay in the ICU, nosocomial infections and complications were compared between the two groups. Results: Body Mass Index (BMI), any comorbidity such hypertension and cardiovascular disease, APACHE II scores, oxygen saturation, and PaO2/FiO2 rate were significant different between the Survival and Mortal groups. As laboratory markers; D-dimer, ALT, AST, CRP, ferritin, troponin, IL-6, bicarbonate and lactate values higher in Mortal group. Full dose of enoxaparin and vasopressor using were associated with mortality. As complications, ARDS, cardiac injury, cardiac arrest and sepsis were more in the Mortal group. Conclusion: On admission higher BMI, APACHE II scores and some comorbidity such hypertension and cardiovascular disease, and lower PaO2/FiO2 rate were associated with mortality. In addition, higher levels of D-dimer, ALT, AST, CRP, ferritin, troponin, IL-6, bicarbonate and lactate values, and full dose of enoxaparin and vasopressor using, and the development of ARDS, cardiac injury and sepsis is also associated with high mortality in the patients with COVID-19 in ICU follow-up.

Abstracts of the 30th Annual Pediatric Pharmacy Association (PPA) Meeting April 21 to 25, 2021

Abstracts of the 30th Annual Pediatric Pharmacy Association (PPA) Meeting April 21 to 25, 2021

Recognizing the Existence of Heparin Induced Thrombocytopenia and Thrombosis in the Setting of High-Dose Melphalan and Autologous Stem Cell Transplantation: A Single Institution Case Series

Background: Heparin induced thrombocytopenia and thrombosis (HIT/HITT) is a disorder characterized by transient hypercoagulability, with increased risk of venous or arterial thrombosis, related to the development of antibodies directed against the heparin-PF4 complex. HIT can occur in any patient receiving heparin but has rarely been described in the setting of high dose melphalan and autologous stem cell transplantation (HDM/SCT) so the true incidence in this population is unknown. Clinical suspicion of HIT in this setting is often clouded by the increased frequency of thrombocytopenia due to stem cell collection or high dose chemotherapy, as well as the increased risk of thrombosis in hematologic malignancies. We report five such cases, with clinically apparent and laboratory confirmed HIT that were diagnosed while undergoing treatment with high dose melphalan and autologous stem cell transplantation.Results: Five patients pursuing treatment with HDM/SCT were diagnosed with HIT during a five year period at our institution. Four patients were being treated for AL amyloidosis and one for multiple myeloma. The average patient age was 64 years (range, 59 to 69), including four males and 1 female. At the time of HIT diagnosis one patient was receiving prophylactic doses of enoxaparin due to a history of line-associated deep vein thrombosis. The other four patients had only been exposed to heparin as part of standard practice for central line placement, line flushes, or stem cell collection. Suspicion of HIT arose in all cases when the patient had delayed platelet recovery during the days following stem cell collection. Only one patient had proceeded with melphalan treatment before HIT was diagnosed. The average platelet nadir was 29, with a range of 6 to 68 x 109/L (Table 1). In two patients the development of thrombosis prompted the work-up for HIT: one with an internal jugular thrombosis and the other with limb threatening aortoiliac thrombosis requiring aortoiliac and femoral artery embolectomy with fasciotomy. All five patients had confirmation of diagnosis with heparin-PF4 antibody (optical density range, 0.5 to 3.3) and a positive serotonin release assay (SRA). Four patients were started on anticoagulation with fondaparinux or argatroban with appropriate platelet recovery in all patients. Three patients proceeded with HDM/SCT, while the remaining two patients received alternative therapies because the previously collected stem cells had been processed with heparin and could not be given to the patients.Conclusions: Herein we have describe five cases of HIT confirmed by the presence of a heparin-PF4 antibody and SRA testing. In all five cases the cause of thrombocytopenia was initially thought to be related to stem cell collection, which is known to cause a decline in platelets. It is notable that the platelet nadir in these patients, was frequently much lower than the nadir that is typically expected in HIT (50 to 80 x 109/L). Despite the development of thrombosis in two patients and the known increase in mortality in patients with HIT, the long term outcome in each of these patients was favorable. This is potentially attributable to rapid diagnosis, cessation of heparin, and initiation of alternative anticoagulation. In reaction to the initial cases, our institution has changed practices to eliminate heparin in the processing of stem cells so that all patients are able to receive their collected stem cells even in the setting of HIT. These cases highlight the existence of HIT during the process of HDM/SCT and the need for increased diligence in monitoring for unexpected thrombocytopenia or sluggish platelet recovery, in particular immediately after stem cell collection. Clinicians should have a low threshold to send diagnostic testing, begin alternative anticoagulation and postpone high dose chemotherapy in order to prevent life threatening complications. [Display omitted] DisclosuresSloan:Molecular Templates, Inc.: Consultancy; Stemline Pharmaceuticals: Consultancy.

Does Venous Thromboembolism Prophylaxis Policy Have Any Impact on Clot Risk Reduction in Hospitalized Solid Tumor Patients at Princess Margaret Cancer Centre: A Longitudinal Study?

BackgroundWe continued to witness a strong associations between cancer and the development of blood clots in the in-patient hospital setting. Patients are being treated for a venothromboembolism (VTE) event at any given time. The primary objective of this retrospective study is to determine the safety and efficacy impact of VTE prophylaxis (Prx.) by measuring the incidences of VTE before and after implementation of our prophylaxis policy over a span of 9 years, in order to gauge the clinical impact of this policy.MethodDischarged Abstract Database (DAD) was used to extract post admitted PE and DVT events based on patients' primary diagnosis of solid tumor identified by the ICD-10-CA diagnosis codes. DAD identified the number of total patients or visits admitted to the in-patient units during the fiscal years of 2007 to 2016. Post-Admit VTE bleeding and death while on prophylaxis anticoagulant was also documented. From the pharmacy generated reports over the same period, the medication profile for each patient was cross-referenced with the DAD documented VTE events for accuracy. The timing of anticoagulant ordering for a given VTE event was checked against the information documented in the radiology/imaging section of the electronic patient record. Patients who came in with a full anticoagulant treatment regimen were removed from analysis. Similarly, patients who began anticoagulation treatment during the first 48 hours of hospital admission were also removed from analysis. The resulting vetted patient list containing only those who developed VTE 48 hours post-admission during their hospital stay, and receiving prophylaxis was the target population for analysis. The patients then were divided into two groups; pre-policy 2007-2012 and post-policy 2012-2016, policy implementation date was Sept. 2012. Each of these patient groups was analyzed and categorized by VTE risk according to the in-patient Padua risk score. When available, any information on bleeding in the presence of anticoagulation was reported. The proportion of patient population (*) receiving VTE prophylaxis was evolving in an increasing trend over the study period (from 2007 to policy 2012). The rate of Prx. post policy was close to 100%.ResultsTable 1. Comparisons between pre- and post- policy period in those received Prx. vs. no Prx., as well as risk scores and incidences of VTE within the two groups of patients with or without Prx.ConclusionThe VTE Prx. policy in the in-patient setting has demonstrated positive impact in reducing the absolute number of incidence over the study period (p=0.0020). The bleeding incidence was low in the both pre- and post- periods. The documented 3 deaths in the pre- period was attributable to PE and none of these patients received Prx. Although VTE events in both pre- and post- periods were similar (18 and 20 respectively), these patients received routine Prx. The breakthrough VTE cases while on Prx. may be explained by the high Padua risk scores. In addition to cancer, obesity (Ave. wt. 77 kg, med. Wt. 75kg in pre- and Ave. Wt. 75.5kg, med Wt. 71kg in post-period), reduce mobility, acute infection and hormonal treatments (glucocortico-steroid) may have accounted for the significant VTE risks. Standard dose of enoxaparin 40mg once daily provided VTE prevention in the majority of our hospitalized patients, however a weight-based dosing schema may be needed for higher risk patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Use of Thromboelastography in Monitoring Coagulation Status for Patients Treated with Low Molecular Weight Heparin, Warfarin, Apixaban, and Rivaroxaban

Introduction: Thromboelastography (TEG) is used to rapidly assess global coagulation status. A few studies in the literature have explored a possible role for TEG in anticoagulant monitoring, with conflicting observations. We wondered if TEG might be used adjunctively with traditional markers of anticoagulation as a measure of anticoagulant efficacy. We hypothesized that some of these variations might be due to changes in certain coagulation factor levels.Methods: Blood samples were collected from patients on therapeutic doses of warfarin, low molecular weight heparin (LMWH, enoxaparin or dalteparin), or an anti-Xa direct oral anticoagulant (DOAC, apixaban or rivaroxaban) due to a history of thrombosis. TEG was performed on all samples with and without addition of heparinase; R time, K time, alpha-angle, maximum amplitude, and percent of clot lysis after 30 minutes were measured. Standard anticoagulation parameters were obtained at the same time as TEG values [prothrombin time (PT) and activated partial prothrombin time (PTT) for warfarin- and DOAC-treated patients; anti-Xa level for LMWH-treated patients]. For each patient, pertinent medical history was recorded including: age, medical comorbidities, and thrombotic history. Von Willebrand factor (vWF) antigen level, factor VIII (fVIII) activity, anti-Xa, and R time were examined in a follow-up cohort of enoxaparin-treated patients. Correlation between TEG and anticoagulation parameters was analyzed using Spearman correlation coefficient (r).Results: Forty-six patients participated in this study. Median age was 52 years (range, 20-83). The most common indication for anticoagulation was deep venous thrombosis or pulmonary embolism (N = 33); 5 subjects had active cancer at the time of anticoagulation testing (all on LMWH). Among warfarin-treated patients (N = 19), INR was significantly correlated with R time (Figure 1, p=0.005), with 4 patients demonstrating a prolonged R time of over 10 min. Among patients on LMWH (enoxaparin, N = 13; dalteparin, N = 1), 5 had a prolonged R time, but there was no correlation between anti-Xa level and R time, R time ratio or R time difference with or without heparinase, or any other measured TEG parameter when analyzing all LMWH patients or only enoxaparin-treated patients as a function of total daily enoxaparin dose. Among DOAC patients (apixaban, N = 6; rivaroxaban, N = 8), R time was not elevated in any of the samples, but there was a significant correlation between PTT and R time (p=0.006). Four study patients had recurrent thrombotic events (1 with antithrombin deficiency, chronic liver disease, and bowel resection, on warfarin; 1 with May-Thurner syndrome, on LMWH; 2 with metastatic cancer and Trousseau's syndrome, also on LMWH) in spite of therapeutic INR or anti-Xa levels; these patients were all found to have normal R times on TEG. In a follow-up analysis of 8 enoxaparin-treated patients, 6 had normal and 2 had prolonged R times. All 6 with normal R times had elevations in vWF and/or fVIII, while the 2 with prolonged R times had normal levels of vWF and fVIII.Conclusion:TEG R time is significantly correlated with INR in patients on warfarin. TEG R time is also correlated with PTT in patients on DOACs. For both DOACs and warfarin, TEG could be useful in rapidly assessing the coagulation status of patients who present with emergent bleeding and may benefit from reversal agents. In patients on LMWH, TEG R time is affected by circulating levels of vWF and fVIII. For select patients on LMWH, TEG may be helpful as an adjunctive measure of anticoagulant activity in cases where anti-Xa monitoring may not be accurate. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.