Unfractionated Heparin Group Research Articles

Unfractionated heparin versus enoxaparin for venous thromboembolism prophylaxis in intensive care units: a propensity score adjusted analysis.

Venous thromboembolism (VTE) is a common complication in hospitalized patients. Pharmacologic prophylaxis is used in order to reduce the risk of VTE events. The main purpose of this study is to compare the prevalence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients admitted to the intensive care unit (ICU) who received unfractionated heparin (UFH) versus enoxaparin as VTE prophylaxis. Mortality was evaluated as a secondary outcome. This was a Propensity Score Adjusted Analysis. Patients admitted to neurology, surgical, or medical ICUs and screened with venous doppler ultrasonography or computed tomography angiography for detection of VTE were included in the analysis. We identified 2228 patients in the cohort, 1836 (82.4%) patients received UFH and 392 (17.6%) patients received enoxaparin. Propensity score matching yielded a well-balanced cohort of 950 (74% UFH, 26% enoxaparin) patients. After matching, there was no difference in prevalence of DVT (RR 1.05; 95% CI 0.67-1.64, p = 0.85) and PE (RR 0.76; 95% CI, 0.44-1.30, p = 0.31). No significant differences in location and severity of DVT and PE between the two groups were detected. Hospital and intensive care unit stay was similar between the two groups. Unfractionated heparin was associated with a higher rate of mortality, (HR 2.04; 95% CI, 1.13-3.70; p = 0.019). The use of UFH as VTE prophylaxis in ICU patients was associated with a similar prevalence of DVT and PE compared with enoxaparin, and the site and degree of occlusion were similar. However, a higher mortality rate was seen in the UFH group.

Intraoperative unfractionated heparin before femoral component cementation should be avoided in femoral neck fracture treated with hybrid total hip arthroplasty.

To compare the incidence of perioperative thromboembolic events in femoral neck fracture (FNF) patients treated with hybrid total hip arthroplasty (THA) with intraoperative unfractionated heparin (UFH) versus a control group without intraoperative UFH before femoral component cementation. We compared 139 cases without UFH (group A) versus 134 who received 10 UI/kg UFH (group B). Indication of UFH before cementation depended on the preferences of the anaesthesiologists in each case. We assessed intraoperative bone cement implantation syndrome (BCIS) and 30-day thromboembolic events, and 90-day and 1-year mortality. BCIS was classified as per Donaldson et al.'s classification according to the degree of hypotension, arterial desaturation or loss of consciousness. BCIS was observed in 51 (18%) cases, including 37 (13%) grade 1 and 14 (5%) grade 2. Forty-seven BCISs (35%) were observed in group B and 4 (3%) in group A (p < 0.001). Multivariate regression showed that intraoperative UFH (OR = 18, CI 95% 6-52) and consumption of oral anticoagulants (OR = 3.3, CI 95% 1-10) increased the risk of BCIS. Five patients further developed a 30-day pulmonary embolism in group B, while 2 presented this complication in group A (p = 0.231). No association between BCIS and 30-day thromboembolic events was found (p = 0.62). 90-day (1% each, p = 0.98) and 1-year (2% vs. 3%, p = 0.38) mortality were similar. BCIS was a frequent finding in FNF patients treated with hybrid THA. We found a paradoxically significant increase in BCIS with the use of UFH. Heparin did not seem to prevent BCIS, other thromboembolic events and mortality in this group of patients.

Low-dose thrombolytic therapy versus unfractionated heparin in patients with intermediate-high risk pulmonary embolism.

Patients with intermediate-high risk pulmonary embolism (PE) who have acute right ventricular dysfunction and myocardial injury without overt hemodynamic compromise may be candidates for thrombolytic therapy (TT). In this study, we aimed to compare the clinical outcomes of low-dose prolonged TT and unfractionated heparin (UFH) in intermediate-high risk PE patients. This study enrolled 83 (female: 45 [54.2%], mean age: 70.07±10.7 years) retrospectively evaluated patients with the diagnosis of acute PE who were treated with low-dose and slow-infusion of TT or UFH. The primary outcomes of the study were de-fined as a combination of death from any cause and hemodynamic decompensation, and severe or life-threatening bleeding. Secondary endpoints were recurrent PE, pulmonary hypertension, and moderate bleeding. The initial management strategy of intermediate-high risk PE was TT in 41 (49.4%) patients and UFH in 42 (50.6%) cases. Low-dose prolonged TT was successful in all patients. While the frequency of hypotension decreased significantly after TT (22 vs. 0%, P<0.001), it did not decrease after UFH (2.4 vs. 7.1%, p=0.625). The proportion of hemodynamic decompensation was significantly lower in the TT group (0 vs. 11.9%, p=0.029). The rate of secondary endpoints was significantly higher in the UFH group (2.4 vs. 19%, P=0.016). Moreover, the prevalence of pulmonary hypertension was significantly higher in UFH group (0 vs. 19%, p=0.003). Prolonged TT regimen with low dose, slow infusion of tissue plasminogen activator was found to be associated with a lower risk of hemodynamic decompensation and pulmonary hypertension in patients with acute intermediate-high-risk PE compared to UFH.

Venous Thromboembolism Prophylaxis with Enoxaparin Versus Unfractionated Heparin in Patients with Low Body Weight

Background Although reduced doses of enoxaparin have been studied in low body weight patients, no study has directly compared enoxaparin to unfractionated heparin for venous thromboembolism (VTE) prophylaxis in this population. Objective To determine the most safe and efficacious parenteral venous thromboembolism prophylaxis regimen for low body weight patients. Design Retrospective cohort. Methods Hospitalized patients weighing &lt; 55 kg receiving either enoxaparin or unfractionated heparin for VTE prophylaxis over a period of two and a half years were evaluated. Primary outcomes included rates of VTE and overall bleeding events. Secondary outcomes included rates of major and clinically relevant minor bleeding. Dosing regimens were analyzed to determine associations between dose, weight, creatinine clearance, VTE, and bleeding events. Primary and secondary outcomes were evaluated using Chi squared and Fischer's Exact tests. Results Three hundred and sixty-one patients contributed 400 episodes of VTE prophylaxis. Most patients were female (88%), had a Padua score ≥ 4 (82%) and were admitted to medical/surgical units (76%). VTE rates were 0.4% in patients receiving enoxaparin and 2.5% in patients receiving unfractionated heparin ( P = 0.334). Bleeding rates were 12% and 11% in the enoxaparin and unfractionated heparin groups, respectively ( P = 1). Patients receiving enoxaparin 30 mg daily had bleeding rates of 7.6% compared to 14.7% in patients receiving 40 mg daily ( P = 0.134). Patients receiving heparin twice daily had no bleeding events compared to 12.9% of patients receiving heparin three times daily ( P = 0.222). Conclusion Overall, no difference in VTE or bleeding rates were found between patients weighing &lt; 55 kg receiving enoxaparin versus unfractionated heparin, and there was no difference in bleeding or VTE events in the patients receiving enoxaparin 30 mg daily. Due to this, empirically reducing the dose of enoxaparin for VTE prophylaxis appears reasonable and safe in patients weighing &lt; 55 kg.

Comparison between unfractionated heparin (UFH) and fondaparinux on platelets and D-dimer level in COVID-19 patients with hypercoagulation

Introduction: This study aimed to compare the clinical effects between UFH and fondaparinux in COVID-19 patients with hypercoagulation. Material and methods: This was a prospective cohort study. Samples were taken consecutively from hospitalized COVID-19 patients with hypercoagulation who received UFH or fondaparinux based on the standardized guidelines. A total of 71 patients met the inclusion criteria. Patients were evaluated for platelet and D-dimer values before and after administration of UFH or fondaparinux. Results: Although there was no difference in D-dimer reduction between the two groups (p = 0.44), fondaparinux showed a greater reduction, 26% against 22% for UFH. While on platelets, there was a significant difference (p = 0.04) between fondaparinux and UFH. Fondaparinux showed a reduced thrombocytopenia impact, as seen by an increase in pre- and post-therapy platelets of up to 50%, compared to 16% in UFH. In regard to the incidence of Heparin-Induced Thrombocytopenia (HIT), there was no significant difference between post-UFH therapy and post-fondaparinux therapy (p = 0.361). Conclusion: Fondaparinux did not reduce platelet levels as much as UFH, but there was no difference between the fondaparinux group compared to the UFH group in the effect of decreasing D-dimer levels and the sign of HIT.

779: FACTOR XA INHIBITORS IN PATIENTS WITH ACUTE KIDNEY INJURY

Introduction: Data is lacking regarding the safety and efficacy of factor Xa inhibitors in patients with acute kidney injury (AKI). The goal of this study is to compare bleeding and thromboembolic events in patients receiving therapeutic doses of apixaban or rivaroxaban versus unfractionated heparin (UFH) in patients with AKI. Methods: This retrospective, observational study evaluated hospitalized adult patients who received therapeutic doses of either apixaban, rivaroxaban, or UFH for at least 24 hours in the setting of AKI as defined by AKIN criteria. Patients were excluded if they met any of the following criteria: non-FDA approved factor-Xa inhibitor indication; COVID admission; major bleeding or clinically relevant non-major bleeding (CRNMB) on admission, embolic event within 30 days of admission; coagulopathy; receipt of a contraindicated medication, or ESRD. Bleeding events were evaluated in accordance with International Society on Thrombosis and Hemostasis criteria. The primary outcome was defined as composite major and clinically relevant non-major bleeding events. Secondary outcomes included comparison of the individual components of the composite bleeding endpoint and thromboembolic events. Results: A total of 500 patients met inclusion criteria, with 250 patients included in the UFH group and factor Xa inhibitor group. AKIN Stage I was most prevalent in the overall study population; patients with AKIN stage III were more likely to be transitioned to UFH (p< 0.01). Surgical patients were more likely to be transitioned to UFH (p< 0.01). Patients transitioned to IV heparin were more likely to undergo a procedure (p< 0.01). After adjusting for confounding factors, patients who received a factor Xa inhibitor experienced a lower risk of composite major bleeding and CRNMB events as compared to UFH (OR: 0.57, 95% CI: 0.34-0.94; p = 0.03). This was driven by a decreased risk of CRNMB in the factor Xa inhibitor group (OR: 0.55, 95% CI: 0.33-0.91, p = 0.02). No significant differences in major bleeding or VTE were noted. Conclusions: Continuation of factor Xa inhibitor therapy in the setting of AKI was associated with a reduced incidence of bleeding events compared to patients transitioned to UFH in accordance with package insert recommendations.

809: ANTICOAGULATION IN ADULT ECMO: PERCENTAGE OF TIME IN THERAPEUTIC RANGE WITH HEPARIN OR BIVALIRUDIN

Introduction: There is debate regarding optimal anticoagulation strategies in adults receiving extracorporeal membrane oxygenation (ECMO). While unfractionated heparin (UFH) is most utilized, there is increasing use of alternate anticoagulants. This investigation examined the efficacy and safety of UFH versus bivalirudin. Methods: This retrospective, observational study examined adult (age >= 18 years) ECMO patients who received UFH or bivalirudin for systemic anticoagulation in a health system between January 1, 2015 and November 30, 2020. Demographics, lab values, ECMO type, anticoagulation strategy, and clinical outcomes were collected. The primary outcome was percentage of time spent in the therapeutic range, defined by coagulation labs. Secondary outcomes included time to reach therapeutic goal and clinical events. Univariable and multivariable comparisons, controlling for ECMO type and admission period, were performed. Impact of admission period between 2015-2017 and 2018-2020 was analyzed due to changes in anticoagulation practices. Results: There were 118 patients, of whom 39% (n=46) received UFH and 61% (n=72) received bivalirudin. Demographics were similar between groups. More VV ECMO patients were in the bivalirudin group (65%) than in the UFH group (24%) (p< 0.001). Bivalirudin treated patients reached therapeutic range sooner than UFH treated patients (median time 9.3 vs. 16.5 hours, p= 0.0236) although this difference was not significant when controlling for ECMO type and admission period. Bivalirudin treated patients spent a greater percentage of time in therapeutic range compared to UFH treated patients (median 80% vs 24%, p < .0001), an effect that persisted after controlling for ECMO type and admission period (66% vs 39%, p=0.0002). There were no differences between groups in length of stay, days on ECMO, safety outcomes, or inpatient mortality. In multivariable modeling, UFH treated patients received more red blood cell transfusions per ECMO day compared to bivalirudin treated patients (1.40 vs 0.90, p=0.048). Conclusions: A bivalirudin strategy offered more time spent in therapeutic range and fewer blood product transfusions compared to UFH in adult ECMO patients and had similar clinical and safety outcomes. Bivalirudin is a viable anticoagulant for adult patients receiving ECMO.

Standard dosing of enoxaparin versus unfractionated heparin in critically ill patient with COVID-19: a multicenter propensity-score matched study.

Thrombotic events are common in critically ill patients with COVID-19 and have been linked with COVID-19- induced hyperinflammatory state. In addition to anticoagulant effects, heparin and its derivatives have various anti-inflammatory and immunomodulatory properties that may affect patient outcomes. This study compared the effectiveness and safety of prophylactic standard-doses of enoxaparin andunfractionated heparin (UFH) in critically ill patients with COVID-19. METHODS: A multicenter, retrospective cohort study included critically ill adult patients with COVID-19 admitted to the ICU between March 2020 and July 2021. Patients were categorized into two groupsbased on the type of pharmacological VTE thromboprophylaxis given in fixed doses (Enoxaparin 40mg SQevery 24hours versus UFH 5000 Units SQevery 8hours) throughout their ICU stay.The primary endpoint was all cases of thrombosis. Other endpoints were considered secondary. Propensity score (PS)matching was used to match patients (1:1 ratio)between the two groups based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analysis were used as appropriate. RESULTS: A total of 306 patients were eligible based on the eligibility criteria; 130 patients were included after PS matching (1:1 ratio). Patients who received UFH compared to enoxaparin had higher all thrombosis events at crude analysis (18.3% vs. 4.6%; p-value = 0.02 as well in logistic regression analysis (OR: 4.10 (1.05, 15.93); p-value = 0.04). Although there were no significant differences in all bleeding cases and major bleeding between the two groups (OR: 0.40 (0.07, 2.29); p-value = 0.31 and OR: 1.10 (0.14, 8.56); p-value = 0.93, respectively); however, blood transfusion requirement was higher in the UFH group but did not reach statistical significance (OR: 2.98 (0.85, 10.39); p-value = 0.09). The 30-day and in-hospital mortality were similar between the two groups at Cox hazards regression analysis. In contrast, hospital LOS was longer in the UFH group; however, it did not reach the statistically significantdifference (beta coefficient: 0.22; 95% CI: -0.03, 0.48; p-value = 0.09). Prophylactic enoxaparin use in critically ill patients with COVID-19 maysignificantly reduce all thrombosis cases with similar bleeding risk compared to UFH.

Application of argatroban in patients receiving extracorporeal membrane oxygenation support: a case-control study

To evaluate the safety and efficacy of argatroban applied as alternative anticoagulant in critical illness patients underwent extracorporeal membrane oxygenation (ECMO) with contraindications of unfractionated heparin (UFH), and to further explore the effective dose of argatroban. From July 1, 2013 to February 28, 2022, there were 14 patients who admitted in the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital received ECMO and used argatroban for anticoagulation (argatroban group). Two of them received argatroban as the initial anticoagulant. The remaining 12 patients used UFH at first, and then switched to argatroban. UFH group included 28 patients who received UFH for anticoagulation after matching the demographic characteristics. Primary endpoint was the prevalence of ECMO-related thrombotic events. Secondary endpoints included the type of thrombotic events, prevalence of ECMO-related major bleeding events, bleeding sites, ICU mortality, mortality during ECMO, liver and kidney function, thrombelastogram, blood transfusion, dosage of argatroban, the dynamic changes of coagulation variables 4 days before and 7 days after argatroban treatment. In argatroban group, there were 8 patients received veno-venous ECMO (VV-ECMO), 2 patients with veno-arterial ECMO (VA-ECMO), and 4 patients with veno-arterio-venous ECMO (VAV-ECMO). In UFH group, VV-ECMO was applied in 23 patients, VA-ECMO and VAV ECMO was established in 3 patients and 2 patients, respectively. In endpoint events, the incidence of ECMO related thrombotic events in argatroban group was slightly higher than that in UFH group (28.6% vs. 21.4%). The ECMO running time in argatroban group was slightly longer than that in UFH group [days: 16 (7, 21) vs. 13 (8, 17)]. The incidence of ECMO-related bleeding events (28.6% vs. 32.1%) and mortality during ECMO (35.7% vs. 46.4%) in argatroban group were slightly lower than those in UFH group. However, the differences were not statistically significant (all P < 0.05). The platelet transfusion in argatroban group was significantly higher than that in UFH group [U: 7.7 (0, 10.0) vs. 0.8 (0, 1.0)]. The coagulation reaction time (R value) in thrombelastography in argatroban group was significantly longer than that in UFH group [minutes: 9.3 (7.2, 10.8) vs. 8.8 (6.3, 9.7)]. The maximum width value [MA value, mm: 48.4 (40.7, 57.9) vs. 52.6 (45.4, 61.5)] and blood clot generation rate [α-Angle (deg): 54.1 (45.4, 62.0) vs. 57.9 (50.2, 69.0)] in the argatroban group were significantly lower than those in the UFH group (all P < 0.05). The activated partial thromboplastin time (APTT) was prolonged after changing from UFH to argatroban in the argatroban group [seconds: 63.5 (58.4, 70.6) vs. 56.7 (53.1, 60.9)]. The PLT level showed a decreasing trend during UFH anticoagulation therapy, and gradually increased after changing to argatroban. D-dimer level was 19.1 (7.0, 28.7) mg/L after switching to argatroban, and then no longer showed an increasing trend. The level of fibrinogen (FIB) showed a decreasing trend during the anticoagulant therapy of UFH (the lowest was 23.6 g/L), and fluctuated between 16.8 and 26.2 g/L after changing to argatroban. The median initial dose of argatroban was 0.049 (0.029, 0.103) μg×kg-1×min-1, which the highest dose was in VV-ECMO patients of [0.092 (0.049, 0.165) μg×kg-1×min-1]. The initial dose of VAV-ECMO was the lowest [0.026 (0.013, 0.041) μg×kg-1×min-1], but without significant difference (P > 0.05). The maintenance dose of argatroban was 0.033 (0.014, 0.090) μg×kg-1×min-1, VV-ECMO patients was significantly higher than those in VA-ECMO and VAV-ECMO patients [μg×kg-1×min-1: 0.102 (0.059, 0.127) vs. 0.036 (0.026, 0.060), 0.013 (0.004, 0.022), both P < 0.05]. Argatroban appears to be a feasible, effective and safety alternative anticoagulant for patients with contraindications to UFH who undergoing ECMO support.

Meta-Analysis Comparing Bivalirudin Versus. Unfractionated Heparin in Adult Patients With Extracorporeal Membrane Oxygenation

Introduction: Unfractionated heparin (UFH) has traditionally been the agent of choice in patients on extracorporeal membrane oxygenation (ECMO). However, direct thrombin inhibitors (DTI) have recently garnered more attention in ECMO because of their advantages over UFH. Given the heterogeneous results of multiple recent published studies, we performed a meta-analysis to describe pooled outcomes between bivalirudin and UFH anticoagulation in patients on ECMO. Methods: Relevant studies were identified from MEDLINE and Google Scholar database searches through April 23, 2022. The primary efficacy outcome was thromboembolism (TE), and secondary efficacy outcomes included all-cause mortality and circuit thrombosis. The primary safety outcome was major bleeding. Results: A total of 6 studies were included in the meta-analysis. Bivalirudin use was associated with significantly lower risk of TE (OR 0.61; 95% CI 0.38-.99; P = .05; I2 = 0%) and circuit thrombosis (OR 0.51; 95% CI .32-.80; P = .004; I2 = 0%) compared with UFH. There was no significant difference in all-cause mortality risk (OR 0.75; 95% CI .52−1.09; P = .13; I2 = 30%) between the bivalirudin and UFH groups. No significant difference in the risk of major bleeding between 2 groups was found (OR 0.67; 95% CI 0.25−1.81; P = .43; I2 = 80%). Conclusion: These data support that bivalirudin is a reasonable alternative to UFH in patients on ECMO. Randomized controlled trials are needed to confirm bivalirudin’s efficacy and safety results compared with UFH.

Unfractionated Heparin Protects Microcirculation in Endotoxemic Rats by Antagonizing Histones

IntroductionLevels of extracellular histones are highly increased in sepsis and may facilitate microcirculatory dysfunction. Unfractionated heparin (UFH) binds histones and neutralizes their cytotoxicity. We investigated the effect of UFH on microcirculatory dysfunction by interacting with extracellular histones in endotoxemic rats. MethodsTwenty-four Wistar rats were randomly divided into three groups: control, lipopolysaccharide (LPS) group, and LPS + UFH group. In the LPS and LPS + UFH groups, 10 mg/kg LPS was injected to induce endotoxemia, and 100 IU/kg/h UFH was administered intravenously in the LPS + UFH group. The rats underwent midline laparotomy, and then intestinal microcirculation was evaluated using an incident dark field microscope. Circulating histones and microstructures of the rat intestinal microvascular endothelium were also detected. Additionally, the antagonistic effect of UFH on histone-induced cytotoxicity was investigated in human intestinal microvascular endothelial cells. ResultsUFH protected the microcirculation of the intestinal serosa and mucosa in endotoxemic rats, as evidenced by increased total vessel density, perfused vessel density, and proportion of perfused vessels of both the serosa and mucosa, and increased microcirculatory flow index of the mucosa in the LPS + UFH group. UFH treatment decreased the levels of circulating histones and alleviated intestinal microvascular endothelial injuries in endotoxemic rats. Furthermore, UFH inhibited histone cytotoxicity in vitro. ConclusionsUFH attenuated microcirculatory dysfunction in endotoxemic rats by antagonizing extracellular histones, thereby providing a potential therapeutic strategy for sepsis.

Comparison of the hepatotoxicity of low-molecular-weight versus unfractionated heparin for anticoagulation therapy after digital replantation

Purpose: Unfractionated heparin (UFH) is more commonly used as an anticoagulant after digital replantation than low-molecular-weight heparin (LMWH). We compared the success and complication rates of these two anticoagulants, since only a few studies have made this comparison directly. Methods: Forty-four patients who underwent digital replantation for complete or incomplete digital amputation in the past 7 years at a single institution were included. The patients were divided into LMWH and UFH groups according to the anticoagulant administered. The success rates for each group were obtained, and the postoperative serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels were analyzed to compare the complication rates.Results: All patients, except one, had successful recovery of circulation after replantation, and the success rate did not show a statistically significant difference between the two groups. The statistical analysis showed that the proportion of patients with abnormal serum AST or ALT levels in the LMWH group was significantly lower than that in the UFH group.Conclusion: Although there was no significant difference in the success rate between the two groups, the risk of hepatotoxicity was significantly lower in the LMWH group than in the UFH group. Considering the advantages of LMWH, its extensive use is highly recommended for anticoagulation therapy in patients after digital replantation.

Enoxaparin versus Unfractionated Heparin for the Perioperative Anticoagulant Therapy in Patients with Mechanical Prosthetic Heart Valve Undergoing Non-Cardiac Surgery.

Background and Objectives: Immediate postoperative anticoagulation regimens in patients with mechanical prosthetic valves undergoing non-cardiac surgery are clear only for unfractionated heparin (UH), whereas the few low-molecular-weight heparin (LMWH) trials available to date concern the use of Enoxaparin in general/orthopedic surgery. We performed a single-center real-world data study comparing the efficacy and safety of LMWH—Enoxaparin (E)— and UH during the perioperative period in non-cardiac surgical procedures in patients with mechanical prosthetic valve replacement in the mitral, aortic, or tricuspid positions. Materials and Methods: We enrolled 380 patients, who received E or UH together with oral anticoagulation with antivitamin K (acenocoumarol) until they achieved an optimal International Normalized Ratio (INR). Objective assessment of E efficacy included the following: normal value for all the parameters of ultrasound prosthetic functioning, no early thrombosis of the prosthesis, and rapid achievement of target INR with a decreased period of subcutaneous anticoagulation. Subjective assessment included the following: clinical improvement with decreased immobilization and in-hospital stay, fewer gluteal ulcerations, and fewer postoperative depression and anxiety episodes. Results: Comparing with UH, anticoagulation with E was more effective (p < 0.0001 and p = 0.02). The probability of death was smaller in the E group compared with the UH group. No major hemorrhagic event was reported. Mild bleeding episodes and thrombocytopenia were more common in the UH group. Patient’s compliance and quality of life were better with E due to shortened hospitalization, decreased need for testing of coagulation (every 6 h for UH), better dosing (SC every 12 h for E versus continuous infusion for UH), shortened immobilization during the immediate postoperative period with subsequent improvement in the psychological status, as well as due to lack of significant side effects. Conclusions: Taking into consideration the improved efficiency and safety, as well as all the supplementary advantages, such as no need for anticoagulation monitoring, the ease of administration, and reduced duration of hospitalization, E should be seen as an attractive alternative for anticoagulation which deserves further investigation.

Evaluation of Efficacy of Heparin in Patients with Cellulitis

Abstract Introduction Heparin is useful in inflammatory conditions for amelioration of symptoms by altering the microcellular environment. This study was aimed at evaluation of the role of heparin in patients with cellulitis on antibiotics. Methodology In our prospective nonrandomized comparative study, the subjects were divided into two groups: group A treated with subcutaneous injection of unfractionated heparin plus antibiotics and group B with antibiotics alone. Comparison was done in terms of improvement in clinical parameters like erythema (cellulitis area), edema (measuring limb girth), pain (visual analog scale), total leucocyte count, and duration of hospital stay. Results Total of 96 patients were divided into two groups of 48 each. In the experimental group, there was improvement in mean area of cellulitis with decrease of 32.36% compared with 10.99% in controls treated with antibiotics at day 5 (p &lt; 0.001). There was 26.27% decrease in edema compared with 12.87% (p &lt; 0.001). There was 45.36% decrease of pain compared with 38.02% (p &lt; 0.001). There was 29.18% drop in total leucocyte counts compared with 25.87% (p &lt; 0.001). There was reduced duration of stay at 7.15 days compared with 9.23 days in controls. Conclusion The addition of heparin with antibiotic therapy in cellulitis hastens recovery with faster amelioration of symptoms and shorter hospital stay.

Comparison of Bivalirudin Versus Unfractionated Heparin for Anticoagulation in Adult Patients on Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) contributes to coagulopathy, necessitating systemic anticoagulation to prevent thrombosis. Traditionally, unfractionated heparin (UFH) has been the anticoagulant of choice, however, due to many inadequacies new evidence suggests benefit with the use of direct thrombin inhibitors. This retrospective cohort sought to evaluate the safety and efficacy of bivalirudin compared to UFH in ECMO patients. Primary endpoints included incidence of bleeding and thrombosis. Percent time in therapeutic range (TR), time to achieve TR and number of dose titrations required to maintain TR were calculated to assess efficacy of institutional protocols. Overall incidence of thrombosis was low, with one event in the bivalirudin group and no events in the UFH group. No difference was found in rates of bleeding between groups (6% vs . 10%, P = 0.44). Bivalirudin yielded higher percent time in TR (86% vs. 33%, P < 0.001), faster time to TR (2 vs . 18 hr, P < 0.001) and required fewer dose adjustments to maintain TR (2 vs . 11, P < 0.001) compared to UFH. These results suggest bivalirudin and UFH are associated with similar rates of bleeding and thrombosis in patients requiring ECMO support. Our results demonstrate the favorable pharmacokinetic profile of bivalirudin, and its ability to consistently maintain TR when compared to UFH.

Heparin for patients with coronavirus disease 2019 and hypercoagulation complications: A cohort study

BackgroundThrombotic complications of coronavirus disease 2019 (COVID-19) are a worrisome aspect of the disease due to their high incidence in critically ill patients and their poor clinical outcomes. The aim of this study was to compare the effectiveness of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) (fondaparinux) in hospitalized COVID-19 patients with hypercoagulable complications. Material and methodsThe study design used a retrospective cohort approach incorporating pre- and post-tests via secondary data extracted from the medical records of inpatients with confirmed COVID-19. ResultsAmong the 98 individuals studied (52% women; 30.6% at >60 years of age), 35 patients received UFH, while the remaining 63 patients received LMWH (fondaparinux). The greatest decrease in the D-dimer value (0.01 ± 0.5 g fibrinogen equivalent units/mL) was observed in 12 (34.3%) and 15 (23.8%) patients in the UFH and LMWH (fondaparinux) groups, respectively. Most inpatients with confirmed COVID-19 were aged 50–59 years and were women. ConclusionThere was a tendency toward increased D-dimer, normal prothrombin time, normal activated partial thromboplastin clotting time, and increased fibrinogen values in each COVID-19 patient. The results demonstrated a significant relationship between the D-dimer and prothrombin time parameter in confirmed COVID-19 inpatients.

Delayed Cranial Decompression Rates After Initiation of Unfractionated Heparin versus Low-Molecular-Weight Heparin in Traumatic Brain Injury

Both unfractionated heparin (UH) and low-molecular-weight heparin (LMWH) are routinely used prophylactically after traumatic brain injury (TBI) to prevent deep vein thrombosis (DVT). Their comparative risk for development or worsening of intracranial hemorrhage necessitating cranial decompression is unclear. Furthermore, the absence of a specific antidote for LMWH may lead to UH being used more often for high-risk patients. This study aims to compare the incidence of delayed cranial decompression occurring after initiation of prophylactic UH versus LMWH using the National Trauma Data Bank. Cranial decompression procedures included craniotomy and craniectomy. Multiple imputation was used for missing data. Propensity score matching was used to account for selection bias between UH and LMWH. The 1:1 matched groups were compared using logistic regression for the primary outcome of postprophylaxis cranial decompression. A total of 218,594 patients with TBI were included, with 61,998 (28.3%) receiving UH and 156,596 (71.7%) receiving LMWH as DVT prophylaxis. The UH group had higher patient age, body mass index, comorbidity rates, Injury Severity Score, and worse motor Glasgow Coma Scale score. After the UH and LMWH groups were matched for these factors, logistic regression showed lower rates of postprophylaxis cranial decompression for the LMWH group (odds ratio, 0.13; 95% confidence interval, 0.11-0.16; P < 0.001). Despite the absence of a specific antidote, LMWH was associated with lower rates of need for post-DVT-prophylaxis in craniotomy/craniectomy. This finding questions the notion of UH being safer for patients with TBI because it can be readily reversed. Randomized studies are needed to elucidate causality.

The Safety and Efficacy of Low-Molecular-Weight Heparin in Pregnant Women With Rheumatic Heart Disease and Valves Replacement.

Background: In patients with rheumatic heart disease (RHD) and prosthetic valve replacement, the risk of thromboembolic complications is the highest during and immediately after pregnancy. Therapeutic anticoagulation during this period is crucial to minimize the risk of thromboembolic complications. The use of low-molecular-weight heparin (LMWH) remains an off-label indication. The type of anticoagulants used, dosing regimens, target anti-Xa levels, and frequency of anti-Xa monitoring are highly variable in the pregnant population and have been derived from pilots, observational studies, and empirical evidence. Herein, in a real-world setting, we sought to examine the efficacy and safety of variable anticoagulation options with a focus on LMWH in the management of RHD-related valvular disease in pregnant women.Methods: This study is a retrospective study conducted at a large university-affiliated tertiary care center (King Saud University Medical City) between January 2011 and February 2020. All pregnant women with RHD who had heart valve replacements were reviewed. Patient data were extracted for demographic information, baseline characteristics, anticoagulation type, and primary outcomes. Primary endpoints were thromboembolic events, hemorrhagic complications, and fetal outcomes.Results: A total of 744 pregnancies in 149 women were identified. The mean age ± SD of the women was 43.8 ± 12 years. A total of 86 women (58%) were on the LMWH regimen, 35 women (23%) were on LMWH and warfarin regimen, and 28 women (19%) were on unfractionated heparin (UFH) and warfarin regimen. Overall, thromboembolic events developed in five (0.7%) pregnancies. Of those, two were in the LMWH group, two were in the LMWH and warfarin group, and one was in the UFH and warfarin group. In addition, significant hemorrhagic complications occurred in five pregnancies. Of these, two occurred in the LMWH group, two in the LMWH and warfarin group, and one in the UFH and warfarin group. No adverse maternal and fetal outcomes were noted.Conclusion: This study presents the largest retrospective study of variable anticoagulation options in pregnant women with RHD and prosthetic valve replacement. LMWH is both safe and effective in preventing major thromboembolic complications compared to other forms of anticoagulation used during pregnancy.

118 Delayed Cranial Decompression Rates After Initiation of Unfractionated Heparin Versus Low-Molecular-Weight Heparin in Traumatic Brain Injury

INTRODUCTION: Both unfractionated heparin (UH) and low-molecular weight heparin (LMWH) are routinely used prophylactically after traumatic brain injury (TBI) to prevent deep vein thrombosis. Their comparative risk for intracranial hemorrhage (ICH) development or worsening necessitating cranial decompression after prophylaxis initiation is unclear. Furthermore, the absence of a specific antidote for LMWH may lead to UH being used more often for high-risk patients. METHODS: We compared the incidence of delayed cranial decompression occurring after initiation of prophylactic UH vs. LMWH using the National Trauma Data Bank. Cranial decompression procedures included craniotomy, craniectomy, and external ventricular drain placement. Multiple imputation was utilized for missing data. To account for selection bias between UH and LMWH, we conducted propensity score matching using factors that were significantly different between the two groups. The matched UH and LMWH groups were then compared using logistic regression for the primary outcome of post-prophylaxis cranial decompression. RESULTS: A total of 218,594 TBI patients were included, with 61,998 (28.3%) receiving UH and 156,596 (71.7%) receiving LMWH as DVT prophylaxis. The UH group had significantly higher patient age, BMI, comorbidity rates, injury severity score, and worse motor Glasgow coma scale. After matching the UH and LMWH groups for these factors, logistic regression demonstrated lower rates of post-prophylaxis cranial decompression for the LMWH group (OR 0.13, 95% CI 0.11-0.16, P &lt; 0.001). CONCLUSION: Despite the absence of a specific antidote, LMWH was associated with substantially lower rates of post-DVT-prophylaxis cranial decompression. This indicates that UH may not be the safer alternative in TBI patients at high risk for intracranial hemorrhagic complications.

Efficacy and safety of fondaparinux versus unfractionated heparin in patients hospitalised with severe COVID-19 pneumonia and coagulopathy: a randomised, open-label clinical trial

Funding AcknowledgementsType of funding sources: Public hospital(s). Main funding source(s): Syarifah Ambami Rato Ebu General Hospital, Bangkalan, East Java, IndonesiaBackgroundThe use of unfractionated heparin (UFH) has been renowned to reduce mortality in COVID-19. There are no data about the efficacy and safety of fondaparinux (FPX) in COVID-19.PurposeTo evaluate the efficacy and safety of FPX as compared to UFH in patients hospitalised with severe COVID-19 and coagulopathy.MethodsThis was a single-center, open-label, equally randomised, parallel-group study conducted between April 1st and July 15th, 2021. Eligible and consenting patients were randomly assigned (1:1 ratio) to receive either FPX or UFH, in prophylactic and therapeutic dose. The primary efficacy endpoint was 28-day all-cause mortality; and secondary efficacy endpoints were episode of acute myocardial infarction (MI), objectively confirmed venous (VTE) or arterial thromboembolism (ATE), progression to non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), progression to ARDS, sepsis, acute kidney injury (AKI) and acute lung oedema (ALO). The primary safety endpoint was major bleeding (MB); and secondary safety endpoint was clinically relevant non-major bleeding (CRNMB). All composite endpoints were analysed on a 28-day intention-to-treat basis. All patients received guideline-driven therapy throughout the study.ResultsDuring allocated period, 250 (71%) of 352 patients were eligible and were assigned to either FPX or UFH group. The baseline characteristics were well-matched between the two groups (all p > 0.05). FPX compared with UFH revealed no significant difference in 28-day all-cause mortality (35.2% vs. 39.2%, hazard ratio [HR] 0.88, p = 0.59). FPX exhibited no significant difference in the trend of thromboembolic events i.e. acute MI (16.8% vs. 16.8%, HR 0.78, p = 0.53); VTE (2.4% vs. 3.2%, HR 0.49, p = 0.42); and ATE (1.6% vs. 1.6%, HR 0.94, p = 0.95) compared to UFH. Among those not on NIV or IMV at randomisation, FPX showed no significant difference in the proportion of patients meeting the composite endpoint of progression to NIV/IMV (33.6% vs. 35.2%, HR 0.91, p = 0.74) or ARDS (25.6% vs. 24.8%, HR 0.91, p = 0.77). FPX group demonstrated no significant difference in the progression to septic shock (24% vs. 24.8%, HR 0.97, p = 0.92), AKI (19.2% vs. 16%, HR 1.01, p = 0.98), and ALO (10.4% vs. 12%, HR 1.19, p = 0.79) than UFH. Allocation to FPX had no significant effect on the proportion of patients discharged from hospital within 28 days (64% vs. 59.2%, HR 0.72, p = 0.43). Regarding safety, there was no significant difference between FPX and UFH group in terms of major bleeding (1.6% vs. 1.6%, HR 0.88, p = 0.88) or CRNMB (8% vs. 8.8%, HR 0.74, p = 0.53) at 28 days. Our prespecified sub-analysis comparing patients who received the respective therapeutic or prophylactic dose revealed that the efficacy and safety outcomes at 28 days did not differ between the FPX and UFH group (all p > 0.05).ConclusionIn patients hospitalised with severe COVID-19 and coagulopathy, FPX was associated with similar efficacy and safety as compared to UFH. Figure. Baseline characteristics of study groups Figure. Allocation of FPX on composite endpoints