Low-dose Unfractionated Heparin Research Articles

Consumptive coagulopathy: how low-dose unfractionated heparin can prevent bleeding complications during extracorporeal life support.

Consumptive coagulopathy: how low-dose unfractionated heparin can prevent bleeding complications during extracorporeal life support.

Impact of Pharmacist-Led Education on Proper Prophylactic Enoxaparin Dosing in Obese Patients

Background/Purpose: Venous thromboembolism (VTE) is a common cardiovascular complication in middle-aged adults. There is a likelihood a patient may experience VTE when admitted to a hospital. Prophylactic medications such as low-dose unfractionated heparin and enoxaparin are started to prevent VTE. A pharmacist-led health system-wide Grand Rounds promoted prophylactic enoxaparin 40 mg twice daily instead of once daily in patients with a body mass index (BMI) 40 kg/m2 or greater. Methodology: This case-control study was conducted at a Essentia Health – Fargo, in the Upper Midwest. Data of acute care patients were extracted from electronic health records 2 years before and after the pharmacist-led education. Patients in the study were 18 years old or older, hospitalized with a need for prophylactic anticoagulation receiving enoxaparin, and had a BMI 40 kg/m2 or greater. Patients with a diagnosis of COVID-19 and recent bleeding were excluded. Groups were compared to determine the effect of pharmacist-led education. The outcome was the number of patients who received enoxaparin 40 mg twice daily compared to once daily. Results: In the control group, 9 out of 15 hospitalizations received enoxaparin 40 mg subcutaneous twice daily and in the case group 34 out of 70 hospitalizations received the twice daily dosing. The odds ratio of receiving enoxaparin 40 mg twice daily after the pharmacist-led education compared to before the education was OR = .99, 95% CI = .96, 1.02. Conclusions: There was no difference in enoxaparin 40 mg once daily and twice daily dosing after the pharmacist-led education.

Successful Pregnancy and Delivery at Term Following Intravenous Immunoglobulin Therapy with Heparin for Unexplained Recurrent Pregnancy Loss Suspected of Immunological Abnormalities: A Case Report and Brief Literature Review

About 60% of cases of recurrent pregnancy loss have unexplained etiology. Immunotherapy for unexplained recurrent pregnancy loss is still unestablished. A 36-year-old woman, not obese, had a stillbirth at 22 gestational weeks and a spontaneous abortion at 8 weeks. She had been examined for recurrent pregnancy loss at previous clinics with no significant findings. When she visited our clinic, a hematologic test showed a Th1/Th2 ratio imbalance. Ultrasonography, hysteroscopy, and semen analysis showed no abnormalities. She successfully conceived by embryo transfer in hormone replacement therapy cycle. However, she had a miscarriage at 19 weeks. The baby had no deformities, but a chromosomal test was not performed, according to the parents' will. The placenta pathologically suggested hemoperfusion problems. Her and her husband's chromosomal tests showed normal karyotypes. Other examinations revealed a repeated Th1/Th2 ratio imbalance and a high resistance index of uterine radial artery blood flow. She was administered low-dose aspirin, intravenous immunoglobulin, and unfractionated heparin after the second embryo was transferred. Her baby was healthily born by cesarean section at 40 weeks. Intravenous immunoglobulin therapy can be a choice for recurrent miscarriage without risk factors because it has clinically beneficial influences on the patient's immunological aberration.

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.

Safety and efficacy of periprocedural antithrombotics in patients with successful reperfusion after endovascular stroke treatment

ObjectivesWe aimed to evaluate whether the overall harmful effect of periprocedural treatment with aspirin or heparin during endovascular stroke treatment is different in patients with a successful reperfusion after the procedure. Materials and methodsWe performed a post-hoc analysis of the MR CLEAN-MED trial, including adult patients with a large vessel occlusion in the anterior circulation eligible for endovascular treatment (EVT). In this trial, patients were randomized for periprocedural intravenous treatment with aspirin or no aspirin (1:1 ratio), and for moderate-dose unfractionated heparin, low-dose unfractionated heparin or no unfractionated heparin (1:1:1 ratio). We tested for interaction between the post-EVT extended thrombolysis in cerebral infarction (eTICI) score and treatment with periprocedural medication with multivariable regression analyses. The primary outcome was the modified Rankin Scale score at 90 days. Secondary outcomes were final infarct volume, intracranial hemorrhage, and symptomatic intracranial hemorrhage. ResultsOf 534 included patients, 93 (17%) had a post-EVT eTICI score of 0-2a, 115 (22%) a score of 2b, 73 (14%) a score of 2c, and 253 (47%) a score of 3. For both aspirin and heparin, we found no interaction between post-EVT eTICI score and treatment on the modified Rankin Scale score (p=0.76 and p=0.47, respectively). We found an interaction between post-EVT eTICI score and treatment with heparin on the final infarct volume (p=0.01). Of note, this interaction showed a biologically implausible distribution over the subgroups. ConclusionsThe overall harmful effect of periprocedural aspirin and unfractionated heparin is not different in patients with a successful reperfusion after EVT.

Anticoagulants for thrombosis prophylaxis in acutely ill patients admitted to hospital: systematic review and network meta-analysis

ObjectiveTo assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital.DesignSystematic...

Do no harm: the role of perioperative heparin in urethroplasty.

To examine the safety of single modality mechanical venous thromboembolism (VTE) prophylaxis in patients undergoing urethroplasty. VTE is a perioperative complication with significant morbidity. Routine use of peri-operative VTE prophylaxis is common guideline-driven practice across multiple surgical specialties. There is a discrepancy between guideline recommendations and clinical practice in the administration of peri-operative low-dose unfractionated heparin (LDUH) for urethroplasty. Patients were identified from an IRB-approved database of patients undergoing urethral reconstruction by a single surgeon at MedStar Washington Hospital Center from 2012 to 2020. All patients had sequential compression devices (SCD) prior to anesthesia induction. Select patients received LDUH as dual prophylaxis. Primary endpoint was perioperative VTE within 30days. We identified 345 patients who met inclusion criteria. Sixty-nine patients received peri-operative LDUH. One patient had a deep vein thrombosis in the SCD only group. Routine LDUH administration likely overtreats men undergoing urethroplasty. There may be a subset of men in whom dual prophylaxis with LDUH and SCD is beneficial for prevention of VTE. Current guidelines do not offer adequate criteria to identify these men. We offer clinical considerations to help guide further study to identify these patients.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Low-dose unfractionated heparin prophylaxis is a safe strategy for the prevention of hepatic sinusoidal obstruction syndrome after myeloablative adult allogenic stem cell transplant.

Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication after allogeneic stem cell transplantation (allo-HCT). However, there is no uniform consensus on the optimal strategy for SOS prevention. Ursodeoxycholic acid is the most used regimen, even though its administration is challenging in recipients unable to tolerate oral medication. Defibrotide was recently studied in a phase 3 trial, but enrollment was stopped early due to futility. Low dose unfractionated heparin (UFH) is an alternative strategy. However, its efficacy is reputed but unproven increased risk of bleeding has not been fully established. We evaluated 514 adult allo-HCT recipients who received SOS prophylaxis with low dose UFH. Bleeding complications occurred in 12 patients 2.3% of patients of which only 2 (0.4%) had significant grade 3 bleeding. Only 14 patients were diagnosed with hepatic SOS. Univariate analysis showed that day 100 SOS was higher in recipients of unmodified grafts when compared to CD34+ selected ex vivo T-cell depleted grafts (p ≤ 0.001), and patients with hepatitis B and/or C exposure pre-HCT (p = 0.028). Overall, UFH was well tolerated and associated with a low incidence of subsequent hepatic SOS. Low dose UFH prophylaxis can be considered in select patients who cannot tolerate oral ursodiol.

Uninterrupted DOACs Approach for Catheter Ablation of Atrial Fibrillation: Do DOACs Levels Matter?

Most patients present for catheter ablation of atrial fibrillation (CAAF) with residual or full effect of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). In daily practice, it has been observed that the activated clotting time (ACT) was actually poorly sensitive to the effect of DOACs and that patients on DOACs required more unfractionated heparin (UFH) to achieve the ACT target of 300 s during the procedure, leading some authors to worry about potential overdosing. Conversely, we hypothesize that these higher doses of UFH are necessary to achieve adequate hemostasis during CAAF regardless of the residual effect of DOACs. During CAAF, thrombosis is promoted mainly by the presence of thrombogenic sheaths and catheters in the bloodstream. Preclinical data suggest that only high doses of DOACs are able to mitigate catheter-induced thrombin generation, whereas low dose UFH already do so. In addition, the effect of UFH seems to be lower in patients on DOACs, compared to patients on VKAs, explaining part of the differences observed in heparin requirements. Clinical studies could not identify increased bleeding risk in patients on DOACs compared to those on VKAs despite similar efficacy during CAAF procedures. Moreover, targeting a lower ACT was associated with an increased periprocedural thrombotic risk for both DOAC and VKA patients. Therefore, the low sensitivity of the ACT to the residual effect of DOACs should not be a major concern in its use in the interventional cardiology laboratory.

Safety and efficacy of aspirin, unfractionated heparin, both, or neither during endovascular stroke treatment (MR CLEAN-MED): an open-label, multicentre, randomised controlled trial

Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke. We did an open-label, multicentre, randomised controlled trial with a 2 × 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, ≥18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621. Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1·95 [95% CI 1·13-3·35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1·98 [1·14-3·46]). Both aspirin (adjusted common OR 0·91 [95% CI 0·69-1·21]) and unfractionated heparin (0·81 [0·61-1·08]) led to a non-significant shift towards worse modified Rankin Scale scores. Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome. The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.

Equivalent VTE rates after total joint arthroplasty using thromboprophylaxis with aspirin versus potent anticoagulants: retrospective analysis of 4562 cases across a diverse healthcare system

BackgroundGuidelines support aspirin thromboprophylaxis for primary total hip and knee arthroplasty (THA and TKA) but supporting evidence has come from high volume centers and the practice remains controversial.MethodsWe studied 4562 Medicare patients who underwent elective primary THA (1736, 38.1%) or TKA (2826, 61.9%) at 9 diverse hospitals. Thirty-day claims data were combined with data from the health system’s electronic medical records to compare rates of venous thromboembolism (VTE) between patients who received prophylaxis with: (1) aspirin alone (47.3%), (2) a single, potent anticoagulant (29%), (3) antiplatelet agents other than aspirin or multiple anticoagulants (21.5%), or (4) low-dose subcutaneous unfractionated heparin or no anticoagulation (2.2%). Sub-analyses separately evaluating THA, TKA and cases from lower volume hospitals (n = 975) were performed.ResultsThe 30-day VTE incidence was 0.6% (29/4562). VTE rates were equal in patients receiving aspirin and those receiving a single potent anticoagulant (0.5% in both groups). Patients with VTE were significantly older than patients without VTE (mean 76.5 vs. 73.1 years, P = 0.04). VTE rate did not associate with sex or hospital case volume. On bivariate analysis considering age, aspirin did not associate with greater VTE risk compared to a single potent anticoagulant (OR = 2.1, CI = 0.7–6.3) with the numbers available. Odds of VTE were increased with use of subcutaneous heparin or no anticoagulant (OR = 6.4, CI = 1.2–35.6) and with multiple anticoagulants (OR = 3.6, CI = 1.1–11.2). THA and TKA demonstrated similar rates of VTE (0.5% vs. 0.7%, respectively, P = 0.43). Of 975 cases done at lower volume hospitals, 387 received aspirin, none of whom developed VTE.ConclusionsThis study provides further support for aspirin as an effective form of pharmacological VTE prophylaxis after total joint arthroplasty in the setting of a multi-modal regimen using 30-day outcomes. VTE occurred in 0.7% of primary joint arthroplasties. Aspirin prophylaxis did not associate with greater VTE risk compared to potent anticoagulants in the total population or at lower volume hospitals.

Management and Outcomes of Women with Antiphospholipid Antibodies or Antiphospholipid Syndrome during Pregnancy

BackgroundPregnant women with antiphospholipid antibodies (aPLs) or antiphospholipid syndrome have an increased risk for thrombosis. Although a combination of low-dose aspirin and unfractionated heparin (UFH) or low molecular weight heparin (LMWH) are usually prescribed in pregnancy, there is no consensus on optimal dosing of these agents. Despite the use of low-dose aspirin and LMWH, approximately 30% of women with a positive lupus anticoagulant (LA), underlying autoimmune disease, or a previous history of thrombosis have unfavorable outcomes.AimTo describe the management and outcomes of women with either aPLs or APS during pregnancy at a university medical center.MethodsWe conducted a retrospective cohort study of pregnant women with either aPLs or APS seen in our hematology clinic in consultation between January 2006 and August 2021. Data collected included demographics, reason for aPLs testing, personal or family history of thrombosis or autoimmune disease, and presence of other thrombophilias. Antiphospholipid antibodies included the LA, anti-cardiolipin (aCL) and anti-beta-2 glycoprotein 1 (ß2GP1) confirmed on two occasions at least 12 weeks apart. Data was collected on antithrombotic agents used during pregnancy, including aspirin, dose of LMWH, UFH and certolizumab. We recorded the following obstetric outcomes: live births, early delivery, fetal loss, early pregnancy loss <10 weeks gestational age (GA), pre-eclampsia, venous thromboembolic events (VTE), arterial thromboembolism (ATE), and post-partum hemorrhage (PPH). We compared management and outcomes in the presence or absence of LA. Statistical comparisons between groups were conducted with the Fisher's exact test.ResultsThere was a total of 202 pregnancies in 62 women with 11% of pregnancies achieved with assisted reproductive techniques. The most common reasons for aPLs testing were pregnancy loss (35%), VTE (23%), and ATE (8%). Antiphospholipid antibody profiles consisted of 56% triple positive, 8% positive LA plus either aCL or anti- ß2GP1, 13% positive LA alone and 22% with either double positive aCL and anti- ß2GP1 or single aCL or anti- ß2GP1. Twenty-tree percent of women had an additional inherited thrombophilia (Table 1). Of the 202 pregnancies, 52% resulted in live births, 20% in pregnancy loss <10 weeks, 12% in pregnancy loss >10 weeks, and 28% were either electively terminated, resulted on an ectopic pregnancy, or the outcome was unknown due to lost to follow up. Antithrombotic therapy was used in 47% of pregnancies: 26% used aspirin and LMWH, 10% used LMWH alone, and 7% used aspirin alone (Table 2). In 10% of pregnancies, patients were transitioned to UFH prior to delivery. Pre-eclampsia with or without HELLP syndrome occurred in 10% of pregnancies and maternal thromboembolic complications occurred in 6%. On analysis of outcomes stratified by LA status, there was a trend toward a higher rate of preterm births in the presence of a positive LA (Table 3). The rate of live births was increased with the use of antithrombotic therapy (Table 4).ConclusionPatients with antiphospholipid antibodies (aPLs) and antiphospholipid syndrome had elevated rates of complications and adverse outcomes during pregnancy. LA positive status was associated with a trend toward a higher rate of preterm births. Further studies are needed to clarify the factors associated with adverse outcomes and optimal anticoagulation management. [Display omitted] DisclosuresDesancho: Sanofi-Genzyme: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure:Certolizumab with the hypothesis of improving clinical outocomes

Venous Thromboembolic Prophylaxis After Total Hip and Knee Arthroplasty.

The selection of an agent for prophylaxis against venous thromboembolism (VTE) is a balance between efficacy and safety. The goal is to prevent symptomatic VTE while limiting the risk of bleeding. The optimal agent for VTE prophylaxis has not been identified. The American College of Chest Physicians guidelines recommend that, after total hip or total knee arthroplasty, patients receive at least 10 to 14 days of 1 of the following prophylaxis agents: aspirin, adjusted-dose vitamin K antagonist, apixaban, dabigatran, fondaparinux, low-molecular-weight heparin, low-dose unfractionated heparin, rivaroxaban, or portable home mechanical compression. The use of aspirin for VTE prophylaxis has increased in popularity over the past decade because it is effective, and it is an oral agent that does not require monitoring. The true efficacy of aspirin needs to be determined in multicenter randomized clinical trials. Validated risk stratification protocols are essential to identify the safest and most effective regimen for VTE prophylaxis for individual patients. There is no consensus regarding the optimal method for risk stratification; the selection of a prophylaxis agent should be determined by shared decision-making with the patient to balance the risk of thrombosis versus bleeding. Patients with atrial fibrillation being treated with chronic warfarin therapy or direct oral anticoagulants should stop the agent 3 to 5 days prior to surgery. Patients do not typically require bridging therapy prior to surgery.

Low-Dose Unfractionated Heparin Administration Inhibits Pulmonary Growth and Development

Low-Dose Unfractionated Heparin Administration Inhibits Pulmonary Growth and Development

Acute External Iliac Artery Occlusion as an Uncommon Complication Encountered during Coronary Angiography.

A 40-year-old female patient presented to our cardiology department with typical angina of 1 month’s duration. The patient was on a combination of valsartan and hydrochlorothiazide for the treatment of hypertension. Electrocardiography showed a normal sinus rhythm with T-wave negativity in the anterior precordial leads. A cardiovascular stress test with the Bruce protocol revealed 2 mm horizontal ST-segment deviation in the inferior and lateral leads. Therefore, the patient was scheduled to undergo coronary angiography (CAG). Before CAG, she was anxious and stressed; hence, intravenous diazepam was administered. CAG, performed via the right femoral artery, demonstrated an insignificant muscular bridge in the mid-portion of the left anterior descending artery (Figure 1A). Twenty minutes after the procedure, the patient felt numbness in her right lower leg and had difficulties in her movements. On physical examination, there was no pulse in the right lower extremity. Because of the presence of the signs and symptoms of acute lower extremity ischemia, an urgent peripheral angiography via the left femoral artery was performed. It illustrated an acute occlusion in the external iliac artery (EIA) (Figure 1B and Video 1). Afterward, intravenous nitroglycerin and unfractionated heparin (5000 U) were given through the right diagnostic catheter. Following this therapy, antegrade blood flow was achieved in the EIA and the signs and symptoms of acute limb ischemia disappeared (Figure 1C and Video 2). Arterial duplex ultrasonography just after this procedure revealed a retrograde arterial dissection flap without significant stenosis (Figure 1D-E and Video 3). In addition, a triphasic blood-flow pattern was observed in the EIA (Figure 1E). During coronary intensive care, intravenous low-dose nitroglycerin and unfractionated heparin were administered for 48 hours. The in-hospital follow-up of the patient was uneventful, and there were no signs and symptoms of peripheral embolism. Arterial duplex ultrasonography, performed 2 weeks after hospital discharge, showed that there was no residual stenosis and that the dissection flap was sealed.Arterial dissection is an infrequent clinical entity encountered during CAG. Remarkably, even though vasospasm and compression to the access site were other contributing factors, acute EIA occlusion due to retrograde dissection is an extremely rare event. As was shown in our case, medical therapy, including intravenous nitroglycerin and unfractionated heparin, could potentially allow the resolution of the total occlusion of the EIA without necessitating percutaneous transluminal angioplasty or stenting.

Effects of low-dose unfractionated heparin and low molecular weight heparin on early brain injury after subarachnoid hemorrhage in mice.

Effects of low-dose unfractionated heparin and low molecular weight heparin on early brain injury after subarachnoid hemorrhage in mice.

The Role of D-Dimer for Optimal Thromboprophylaxis Strategy in Patients with COVID-19

Background:Novel coronavirus infection (SARS CoV-2 or COVID-19) is associated with a high risk of thrombotic complications, including macro- and micro-thrombi in major organs, leading to increased morbidity and mortality. Anticoagulant use, mainly heparin, which has both anticoagulant and anti-inflammatory properties, has been suggested as potentially beneficial. However, the optimal dose of anticoagulant for patients with COVID-19 is unknown. Establishing the optimal thromboprophylaxis strategy and determining the role of biomarkers for patient risk stratification may help to improve outcomes in COVID-19.Methods:This single-center retrospective cohort study is part of an ongoing Quality Improvement project on the use of an anti-factor Xa-driven heparin protocol, which includes a low-dose intravenous (IV) unfractionated heparin (UFH) option, being conducted at our medical center. Data on the type, dose, and indication for anticoagulation as well as outcomes including thrombosis, bleeding and survival was collected for inpatients diagnosed with COVID-19 between mid-March and June 15, 2020. To address COVID-coagulopathy we developed a d-dimer-based anticoagulation protocol for patients with COVID-19 (Figure 1). We recorded anticoagulant use as either standard prophylactic, escalated prophylactic (low-dose intravenous unfractionated heparin titrated to achieve an anti-factor Xa level of 0.1-0.3 anti-Xa units or enoxaparin 0.5mg/kg subcutaneously every 12 hours) or standard therapeutic dose used during the hospitalization. The primary endpoints assessed were ISTH-defined major and clinically relevant non-major bleeding (CRNMB) events and survival. Secondary endpoints included incidence of breakthrough thrombosis and duration of hospitalization.Results:A total of 263 patients with COVID-19 were reviewed. Of these, 68.44% of patients received prophylactic, 12.55% escalated prophylactic and 19.01% therapeutic dosage. Of total, 129 (49%) were receiving ICU level of care. No major bleeding events were observed. The incidence of CRNMB was 4.56% in the whole cohort, which did not differ significantly between the escalated prophylactic and therapeutic groups (12% and 12.12%, respectively). Patients treated with standard prophylaxis had less CRNMB (1.11%), but this was not statistically significant in a multivariate analysis that included other confounding factors such as age, sex, ethnicity, BMI, comorbidity, HASBLED bleeding risk, and sepsis induced coagulopathy score (SICS).The mortality rate was 12.6% in the whole cohort (7.22%, 21.21% and 26% in prophylactic, escalated prophylactic, and therapeutic dosage, respectively). Factors significantly associated with increased mortality included age and ICU level of care (HR 1.10, 95%CI [1.05, 1.15] and HR 20.42, 95%CI [2.84, 146.72], respectively). The use of therapeutic dose heparin and high-flow nasal cannula demonstrate a survival benefit in multivariate analysis (HR 0.13, 95%CI [0.04,0.44] and HR 0.23, 95%CI [0.07, 0.72], respectively; Figure 2).Breakthrough thrombosis occurred in 7 (2.66%) patients; 1 (0.56%), 1 (3.03%) and 5 (10%)) in prophylactic, escalated prophylactic and therapeutic dosage, respectively but very few diagnostic tests were performed during this time period. Duration of hospitalization was significantly longer in the therapeutic dose group when compared to escalated prophylaxis and standard prophylactic groups.Conclusion:In this cohort of inpatients with COVID-19, there were no major bleeding events related to any dose of heparin or LMWH prophylaxis. By multivariate analysis, implementation of a d-dimer-titrated anticoagulation strategy was not associated with increased CRNMB. Therapeutic dose heparin based on a d-dimer-driven anticoagulation protocol was associated with a survival benefit in COVID19-infected patients. Limitations of this study include the retrospective observational nature and a lack of a uniform diagnostic protocol for patients with suspected VTE. Although no significant difference in bleeding events were observed in our study subgroups, randomized clinical trials are necessary to determine optimal thromboprophylaxis strategy in the COVID-19 population.DisclosuresNo relevant conflicts of interest to declare.

Continuous Low-Dose Heparin Infusion for Catheter-Related Thrombosis Prophylaxis in Critically-Ill Children

Introduction: Central venous catheters (CVC) are often required in critical care settings to provide life-sustaining care. Their usage has improved the quality of care in pediatric patients by providing a secure point of access which minimizes the number of peripheral needle sticks. However, CVC usage is not without risks. Children can experience acute CVC-related complications such as venous thromboembolisms (VTEs) and infections. Over the past 20 years, CVC utilization has increased and its associated complications (VTE, central line associated blood stream infection [CLABSI], catheter dysfunction) result in increased lengths of stay and hospital costs. Clinical studies identify CVCs as the single most important risk for DVT in children. Incidence rates in critically-ill children are widely divergent with historical rates of 2.7-18% and 24.7-32.5 per 1000 catheter days. In addition, other historical rates for another CVC-related complication, CLABSI, are limited but demonstrate a rate of 1.21-6.5% and 14.4 per 1000 catheter days. Prevention of catheter-related thrombosis with prophylactic anticoagulants, such as unfractionated heparin, low molecular weight heparin or warfarin, have been tested in several studies in specific subgroups of patients and the majority of studies in pediatric populations were not able to clearly demonstrate a benefit. Despite this, nearly 50% of surveyed Pediatric Intensive Care Unit (PICUs) utilize various forms and doses of heparin prophylaxis to prevent CVC-associated complications. The Penn State Health Children's Hospital PICU utilizes low dose unfractionated heparin infusions (LDUFHI) at 5-15 units/kg/hr for catheter patency and for the prevention of CVC associated complications. Methods: A retrospective chart review of all CVCs, which include non-tunneled CVC (NT-CVC), tunneled lines (TL) and peripherally inserted central catheters (PICC), utilized in the PICU at The Penn State Health Children's Hospital in 2015 was performed to determine if the usage of LDUFHI in critically ill children to maintain catheter patency results in a lower incidence of VTE and CLABSI without increasing bleeding complications in comparison to historically reported data (Beck et al.,J Pediatr. 1998;133(2):237-241; Faustino et al.,J Pediatr. 2013;162(2):387-391; Krishnaiah et al.,Pediatr Crit Care Med. 2012;13(3):e176-e180.). Results: We identified 178 subjects who had CVC which received LDUFHI in 2015. There were a total of 228 CVCs with the majority being non-tunneled CVCs (54%) followed by tunneled lines (34%) and PICCs (12%). Combined, these catheters resulted in 2086 days of use. There was a total of 5 VTEs events for an overall incidence rate of 2.19% and 2.39 per 1000 catheter days. NT-CVC had the lowest rate (1.63%) followed by TL (2.56%) and PICCs (3.7%). However, PICCs has a slightly lower rate when measuring by catheter days (NT-CVC = 2.2 per 1000 catheter days; TL = 4.01 per 1000 catheter days; PICC = 1.46 per 1000 catheter days). There were 3 CLABSI events for an incidence rate of 1.32% and 1.43 per 1000 catheter days (NT-CVC = 1.63% and 2.2 per 1000 catheter days; TL no events; PICC = 3.7% and 1.46 per 1000 catheter days). There were no episodes of heparin induced thrombocytopenia or major bleeding. Overall, the VTE and CLABSI incidence rates are dramatically lower than historical comparisons (VTE = 2.19% and 2.39 per 1000 catheter days versus 15.8-18% and 24.7-32.5 per 1000 catheter days; CLABSI = 1.32% and 1.43 per 1000 catheter days versus 6.5% and 14.4 per 1000 catheter days). In addition, this study can offer more accurate rates as incidence was also measured as a factor in catheter days. Conclusion: This study used a single tertiary pediatric intensive care site in a non-randomized fashion. These data suggest an overall lower incidence of catheter related VTE and CLABSI in critically-ill children who received LDUFHI when compared to published with comparable pediatric study populations. The incidence of complications such as CLABSI were also lower with LDUFHI usage when compared to published data involving critically ill children. The incidence rates were even lower than recently published data involving non-critically ill children. These findings suggest that a multicenter randomized study should be pursued. Disclosures No relevant conflicts of interest to declare.

Continuous Infusion Low-Dose Unfractionated Heparin for the Management of Hypercoagulability Associated With COVID-19

Introduction: The Coronavirus Disease 2019 (COVID-19) is associated with severe hypercoagulability. There is currently limited evidence supporting the routine use of therapeutic anticoagulation in the setting of COVID-19. Objectives: The primary objective was to compare the incidence of thromboembolic events in adult patients with COVID-19 treated with an unfractionated heparin (UFH) infusion versus prophylactic dose anticoagulation. Secondary objectives included exploration of the efficacy and safety of an UFH infusion through the evaluation of organ function and incidence of minor and major bleeding. Methods: Retrospective observational cohort study with propensity score matching of COVID-19 patients who received an UFH infusion targeting an aPTT between 40 and 60 seconds. Results: Fifty-six patients were included in this study. There was no difference in the composite of thromboembolic events comprised of venous thromboembolism, arterial thrombosis, and catheter-related thrombosis between the UFH and control group (17.9% vs. 3.6%, P = 0.19). There was a significant increase in median D-dimer concentrations from day 1 to day 7 in the control group (475 ng/mL [291-999] vs. 10820 ng/mL [606-21033], P = 0.04). Patients treated with UFH had a higher incidence of minor bleeding (35.7% vs. 0%, P < 0.005) and required more units of packed red blood cell transfusion (0.8 units ± 1.6 vs. 0 units, P = 0.01). Conclusion: Continuous infusion of UFH for patients with COVID-19 infection did not decrease the overall incidence of thromboembolic complications. UFH was associated with stabilization of D-dimer concentrations and increased rates of minor bleeding and transfusions.