Therapeutic Enoxaparin Research Articles

Finding individualised treatment in obese needing enoxaparin (FIT ONE): a multicentre study of therapeutic enoxaparin and the role of anti-factor Xa monitoring.

Enoxaparin is dosed according to actual body weight in treatment of arterial and venous thrombosis. Due to its hydrophilic nature, it distributes according to lean body mass which may be problematic when dosing obese patients as this may increase the risk of bleeding events in this population. The aimwasto evaluate current therapeutic enoxaparin dosing strategies, including Antifactor Xa (AFXa) level monitoring, in obese patients and to identify factors that contribute to treatment failure and excess anticoagulation. A retrospective cohort study was conducted reviewing patients administered therapeutic enoxaparin between May 2020 and April 2021. Data were collected on patient characteristics, enoxaparin therapy, AFXa monitoring, and outcomes. Regression models were constructed to assess variables of interest to estimate any association with AFXa levels. In total 762 patients were included in the analysis. The mean initial weight-based dose was 0.95mg/kg twice daily (SD: ± 0.12, IQR 0.92-1.01) and 1.04mg/kg once daily (SD: ± 0.26, IQR 0.93-1.12) and 14.4% of patients had AFXa monitoring. Treatment failure was experienced by 2.2%, 5% experienced bleeding. There was no association between the mean actual milligram per kilogram weight-based twice daily doses and subtherapeutic, therapeutic and supratherapeutic AFXa levels(P = 0.135). Obesity was not includedin the final regression models due to lack of significance. At a mean therapeutic enoxaparin dose of 0.95mg/kg twice daily and 1.04mg/kg once daily no excess in treatment failure or bleeding events were observed in obese patients compared to the product information. Obesity was not an independent variable that affected the achievement of target AFXa levels.

Therapeutic Enoxaparin Dosing in Obesity.

This review aims to systematically summarize the available data on efficacy and safety of therapeutic enoxaparin in obese patients and to identify gaps to guide future research. Medline and Embase were systematically searched for eligible studies (last searched December 20, 2023). Studies were included if they reported on therapeutic dosing regimens, adverse bleeding, thrombotic outcomes, or antifactor Xa (AFXa) monitoring in obese adult patients. The systematic review management tool Covidence was used to manage the study selection and data extraction process. The reference list from eligible studies was screened to determine any additional eligible studies. Sixteen studies were included in the analysis. Studies used a variety of doses, indications, and study designs making comparison difficult. Twelve studies reported the incidence of thrombotic events (median = 1.3% [interquartile range [IQR] = 0.3%-2.3%]) and all studies reported the incidence of bleeding events (median = 5.7% [IQR = 2.4%-14.5%]). Two of the 8 studies analyzing the influence of weight/body mass index (BMI) or dose per kg on AFXa levels reported statistically significant results. One study concluded that BMI did not affect achievement of target AFXa levels. However, the second study found that dosing using actual body weight was an independent predictor of supratherapeutic AFXa levels in the obese population. This is the first comprehensive review with a focus on therapeutic dosing of enoxaparin in obesity and has been conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. Seven of the included studies were published since 2018 indicating that new evidence on this topic is emerging. There was inadequate evidence to support an optimal dosing strategy in obese patients due to the heterogeneity of the studies. The AFXa monitoring may be appropriate to guide dosing in this population. Further research is required to determine a suitable dosing regimen.

Early Diagnosis of Upper Extremity Deep Venous Thrombosis Using Emergency Department Point-of-Care Ultrasound: A Case Report

Introduction: Upper extremity deep vein thrombosis (UEDVT) is a serious condition associated with fatal complications. It necessitates careful consideration and prompt intervention. Despite the proven effectiveness of point-of-care ultrasonography (POCUS) in detecting UEDVT, it is rarely utilized in the Emergency Department (ED). Purpose: To highlight the role of POCUS in the early diagnosis of UEDVT in the ED. Case Summary: A 65-year-old female, actively undergoing chemotherapy via a right subcutaneous port for known left breast cancer, presented to the ED exhibiting throat irritation, facial swelling, and itchiness. These symptoms surfaced the day after her latest chemotherapy session. She typically experienced similar reactions post-chemotherapy, managed by routine oral antihistamines and steroids, yet this instance persisted despite medication. On examination, she appeared flushed, with a plethoric and erythematous face, accompanied by swelling extending from her neck to the left arm, along with tender left axillary lymph nodes. A POCUS of the left upper arm revealed soft tissue edema, a non-compressible brachial vein, and a hypoechoic floating luminal lesion (Figure 1). Subsequent computed tomography (CT) confirmed upper limb deep venous thrombosis extending into the left subclavian and internal jugular vein, partially non-occlusive in the proximal superior vena cava (Figure 2. A & B). Notably, she had a known contrast allergy, requiring pre-treatment with steroid and diphenhydramine before contrast injection. Based on CT findings, therapeutic enoxaparin was initiated in the ED and patient was admitted under oncology care, subsequently discharged on rivaroxaban. Discussion: Based on previous studies, the reliance on radiologists' availability for vascular imaging to diagnose UEDVT within the ED led to significant delays, extending up to two hours. Notably, the utilization of POCUS by Emergency Physicians resulted in a marked reduction in both diagnosis and intervention times. Furthermore, insights from six prospective studies confirm the accuracy of color-Doppler sonographic imaging in diagnosing UEDVT, showcasing sensitivity ranging between 78% to 100% and specificity from 82% to 100%. This compelling evidence strongly advocates for the broader integration of POCUS in EDs, emphasizing its credibility in enhancing diagnostic accuracy and expediting timely intervention for UEDVT. Applying these findings to this specific patient case, reliance on POCUS could have avoided the risks associated with radiation and contrast exposure Conclusion: Integrating POCUS into the ED's diagnostic protocol for UEDVT enables early detection and intervention, and mitigates risks associated with contrast agents and excessive radiation exposure.

Abstract 16013: Non-Bacterial Thrombotic Endocarditis and Recurrent Cerebrovascular Accidents in Immune Checkpoint Inhibitor Myocarditis

Background: Nonbacterial thrombotic endocarditis (NBTE) is a rare condition associated with cancer, hypercoagulable state, and systemic emboli including stroke. This report presents a case of NBTE associated with metastatic lung adenocarcinoma and recurrent strokes despite anticoagulation for prior pulmonary embolism (PE) and highlights the challenges in management of NBTE. Case: 66-year-old man with stage IV non-small cell lung adenocarcinoma treated with pembrolizumab complicated by immune checkpoint inhibitor (ICI) myocarditis treated with high dose steroids and PE treated with rivaroxaban, presented with diplopia and gait instability. MRI brain revealed a left corona radiata infarct and rivaroxaban was switched to apixaban. Three weeks later, the patient developed left internal carotid artery (ICA) occlusion, and underwent emergent thrombectomy. A transesophageal echocardiogram revealed a new 1.8 cm mass on the mitral valve with negative blood cultures. Anticoagulation was switched to therapeutic enoxaparin. Cardiothoracic surgery was consulted, though patient opted for palliative care. Decision making: Patient presented with recurrent multifocal strokes despite treatment with multiple direct oral anticoagulants (DOACs), just weeks after ICI myocarditis. The challenges here were approach to anticoagulation in a patient with recurrent strokes despite anticoagulation, the risk of hemorrhagic conversion of stroke, and the mechanism of stroke. The mitral valve mass was presumed to be NBTE, due to his metastatic malignancy and negative blood cultures. However, a recent history of ICI-myocarditis raised the possibility of an immune mediated mechanism of NBTE, given the growing association of auto-immune diseases and NBTE. Conclusion: NBTE is a rare complication of metastatic disease that can commonly lead to stroke and is treated with optimal anticoagulation and addressing the underlying malignancy. However, this case highlights the failure of multiple oral anticoagulants to treat NBTE and raises the question of additional mechanisms of NBTE beyond malignancy and hypercoagulable state. Further studies are required to elucidate a common immune mediated mechanism of NBTE and ICI myocarditis.

Abstract 14891: Time to Therapeutic Range for Patients With Acute Pulmonary Embolism Undergoing Mechanical Thrombectomy

Introduction: Anticoagulation therapy is the mainstay for the management of patients with acute pulmonary embolism (PE) and achieving a timely time to therapeutic range (TTR) is important. We sought to determine the TTR in patients with acute PE referred for mechanical thrombectomy (MT) and the proportion of patients with therapeutic activated clotting time (ACT) at the time of MT. Methods: This single center retrospective study included all patients who underwent percutaneous MT at a large academic public hospital from January 2020 through April 2023. Therapeutic anticoagulation was defined as an ACT >200 seconds or if the patient received enoxaparin within 6 hours prior to MT. Results: A total of 63 patients (average age 58 years, 43% female) with intermediate or high-risk PE were included in the analysis. The median time from the diagnosis of PE or clot-in-transit (CIT) to MT was 15 (IQR 6.1-23.2) hours. Fifteen patients (23.8%) were initiated on enoxaparin at the diagnosis of acute PE or CIT. Among these patients, 5 (7.9%) were on enoxaparin only and 10 (15.9%) patients were initiated on enoxaparin and then transitioned to a heparin infusion prior to MT. One patient was initiated on argatroban, while the remaining 47 patients were initiated on a heparin infusion at time of diagnosis (77.6% received heparin bolus). In patients who received a heparin infusion, the median ACT in the cath lab was 134 (IQR 118-159) seconds. Only a total of 9/63 (14.3%) were therapeutic by ACT at the time of MT or received therapeutic enoxaparin within 6 hours of MT. Excluding patients who received enoxaparin initially, 34/48 (70.8%) patients reached a therapeutic anti-Xa or partial thromboplastin time (PTT) levels. The median time to reach a therapeutic anti-Xa or aPTT was 5.6 (IQR 3.3-8.2) hours (Figure). Conclusion: In patients with acute PE referred for MT, only a minority of patients had therapeutic ACT prior to mechanical thrombectomy.

Risk Stratification for Supratherapeutic Peak Anti-Xa Levels in Adult Patients on Therapeutic Enoxaparin.

The American Society of Hematology Guidelines for the management of venous thromboembolism recommend against the use of anti-Xa monitoring for assessing enoxaparin dosing based on a low level of evidence associating supratherapeutic levels with an increased risk of bleeding. However, institutions still utilize anti-Xa levels in select patient populations with altered volume of distribution and/or excretion to monitor and adjust therapy. The primary objective of this study was to identify risk factors associated with supratherapeutic peak anti-Xa levels (≥1.10 IU/mL) for patients receiving therapeutic enoxaparin. This was a retrospective single-center study performed at an academic tertiary care hospital. Patients who received enoxaparin at 1 mg/kg twice daily and peak anti-Xa monitoring were separated into supratherapeutic and therapeutic/subtherapeutic cohorts. A total of 436 patients were screened, and 215 were included, with a mean age of 62 years. There were 108 in the therapeutic/subtherapeutic cohort and 107 in the supratherapeutic cohort. Acute kidney injury (AKI), body mass index (BMI), weight, female sex, intensive care unit (ICU) service, Sequential Organ Failure Assessment (SOFA) score ≥4, and creatinine clearance at the time of peak anti-Xa level collection were associated with supratherapeutic anti-Xa levels in univariate models. Adjusted logistic regression models were created and identified BMI in the 30 to 34.9 kg/m2 (odds ratio [OR] 4.35; 95% confidence interval [CI] 1.70-11.13, P < 0.005) and ≥35 kg/m2 (OR 6.75; 95% CI 3.05-14.94, P < 0.005) and AKI (OR 2.62; 95% CI 1.04-6.62, P = 0.042) as significant risk factors for supratherapeutic anti-Xa levels. Our study identified BMI ≥ 30 kg/m2, AKI, female sex, ICU service, SOFA score ≥4, and creatinine clearance as risk factors for supratherapeutic anti-Xa levels in patients receiving 1 mg/kg twice daily dosing of enoxaparin. Further research should be done to provide evidence for the association between anti-Xa levels and bleeding risk.

The Effect of Warfarin Use on Postoperative Outcomes after Femoral Neck Surgery

Introduction: Anticoagulation use in the elderly is common for patients undergoing femoral neck hip surgery. However, its use presents a challenge to balance it with associated comorbidities and benefits for the patients. As such, we attempted to compare the risk factors, perioperative outcomes, and postoperative outcomes of patients who used warfarin preoperatively and patients who used therapeutic enoxaparin. Methods: From 2003 through 2014, we queried our database to determine the cohorts of patients who used warfarin preoperatively and the patients who used therapeutic enoxaparin. Risk factors included age, gender, Body Mass Index (BMI) > 30, Atrial Fibrillation (AF), Chronic Heart Failure (CHF), and Chronic Renal Failure (CRF). Postoperative outcomes were also collected at each of the patients' follow-up visits, including number of hospitalization days, delays to theatre, and mortality rate. Results: The minimum follow-up was 24 months and the average follow-up was 39 months (range: 24-60 months). In the warfarin cohort, there were 140 patients and 2055 patients in the therapeutic enoxaparin cohort. Number of hospitalization days (8.7 vs. 9.8, p = 0.02), mortality rate (58.7% vs. 71.4%, p = 0.003), and delays to theatre (1.70 vs. 2.86, p < 0.0001) were significantly longer for the anticoagulant cohort than the therapeutic enoxaparin cohort. Warfarin use best predicted number of hospitalization days (p = 0.00) and delays to theatre (p = 0.01), while CHF was the best predictor of mortality rate (p = 0.00). Postoperative complications, such as Pulmonary Embolism (PE) (p = 0.90), Deep Vein Thrombosis (DVT) (p = 0.31), and Cerebrovascular Accidents (CVA) (p = 0.72), pain levels (p = 0.95), full weight-bearing status (p = 0.08), and rehabilitation use (p = 0.34) were similar between the cohorts. Conclusion: Warfarin use is associated with increased number of hospitalization days and delays to theatre, but does not affect the postoperative outcome, including DVT, CVA, and pain levels compared to therapeutic enoxaparin use. Warfarin use proved to be the best predictor of hospitalization days and delays to theatre while CHF predicted mortality rate.

Blue toe syndrome secondary to multiple spontaneous aortic thrombi following pneumonia

A 65-year-old man presented with bilateral ischaemic toes 11 days following hospital discharge for pneumonia. His initial admission was complicated by atrial fibrillation requiring rivaroxaban on discharge. A thromboembolic cause of his toe ischaemia was suspected. An echocardiogram demonstrated only moderate atherosclerosis. However, repeat echocardiogram revealed five thrombi within the descending aorta. Medical management included therapeutic enoxaparin, aspirin, atorvastatin and a five-day course of iloprost. Subsequent right 5th toe amputation was required for osteomyelitis, but otherwise the patient made a full recovery and was asymptomatic at 12 months.

May-Thurner Syndrome: a case of unilateral left lower limb deep vein thrombosis

The May–Thurner Syndrome (MTS) is a rare anatomical condition in which the compression of the left common iliac vein by the right common iliac artery causes an outflow obstruction, presenting frequently as chronic venous insufficiency or deep venous thrombosis (DVT). This variant is rarely considered when investigating DVT, especially in patients with other risk factors. MTS requires careful workup and management to avoid complications such as chronic venous insufficiency, post-thrombotic syndrome, and primary lymphedema. The authors present a 63-year-old woman admitted to the emergency department with a 24-hour history of left lower limb pain and edema. Initial assessment, with computed tomography of the lower left limb and pelvis, showed compression of the left common iliac vein with an extensive thrombus of the left common iliac and external iliac veins, as well as femoral and popliteal left veins, consistent with MTS. Therapeutic enoxaparin initially implemented, was then switched to oral anticoagulation. At 6 months reevaluation, venous duplex ultrasound showed only partial recanalization of the femoral vein. Investigation for May-Thurner Syndrome in patients with left lower limb venous thrombotic events, regardless of risk factors, should always be present since the establishment of an effective therapeutic plan and eventually, endovascular treatment can minimize the long-term sequelae of deep vein thrombosis.

Iatrogenic Reversible Hypofibrinogenemia in the Setting of Using a Direct Thrombin Inhibitor for Treatment for Recurrent Deep Vein Thrombosis

Fibrinogen is an essential and abundant peptide synthesized by the liver. It is required for clot formation while providing a matrix and mesh network essential for clot strength. It is used in the diagnosis and monitoring of multiple coagulopathies. The gold standard for measuring fibrinogen is the Clauss method which uses citrated plasma to which thrombin is added, and the clot formation time is recorded via spectroscopic analysis. Hypofibrinogenemia is defined as fibrinogen of less than 150 mg/dL and is primarily treated with supplementation with cryoprecipitate, or a fibrinogen concentrate. Acquired hypofibrinogenemia may occur due to disseminated intravascular coagulopathy (DIC), liver failure, after cardiac surgery or after massive transfusions. There have also been reports of hypofibrinogenemia associated with the use of direct thrombin inhibitors and tPA. We present a case of acquired hypofibrinogenemia while being treated for recurrent deep vein thrombosis (DVT) which was able to be reversed with the cessation of the direct thrombin inhibitor. A 28-year-old female presented to the emergency department with left lower extremity pain, swelling and cyanosis. She was diagnosed with an extensive DVT of the left lower extremity and started on a heparin infusion. She subsequently underwent mechanical thrombectomy, IVC filter placement and iliac vein stenting due to extensive clot burden. She was transitioned to weight-based therapeutic enoxaparin and discharged home. However, despite her compliance, she continued to have worsening left lower extremity pain and swelling and was found to have a persistent DVT. She was then tried on apixaban but failed therapy and required a repeat thrombectomy due to clinical worsening of her lower extremity exam. Her initial hypercoagulability workup for anti-phospholipid syndrome was unremarkable. She then underwent catheter-directed tPA and was started on an argatroban infusion. She remained on the argatroban infusion for 7 days. While on argatroban infusion therapy, routine blood work noted her fibrinogen levels to be less than 50 mg/dL. Despite the initial concern for DIC, the hypofibrinogenemia was ultimately attributed to prolonged argatroban exposure after literature review. The decision was made to not replace the fibrinogen, but instead to transition the argatroban to fondaparinux. The repeat fibrinogen level one day after discontinuing argatroban was back to normal limits at 351 mg/dL and the patient was subsequently discharged on fondaparinux with subsequent clinical improvement. Multiple studies advocate for maintaining fibrinogen levels with supplementation for acquired coagulopathies. However, in this clinical situation, removing the offending agent was the key to correcting the patient's fibrinogen level. With the patient's history of recurrent DVTs, giving her fibrinogen replacement may have led to worsening thrombosis and adverse events. It is imperative that clinicians be aware of the many causes of hypofibrinogenemia. Before reflexively replacing fibrinogen, a physician must consider all reversible causes and make an informed clinical decision.

Bivalirudin vs. Enoxaparin in Intubated COVID-19 Patients: A Pilot Multicenter Randomized Controlled Trial.

(1) Background: In COVID-19 patients, the occurrence of thromboembolic complications contributes to disease progression and mortality. In patients at increased risk for thrombotic complications, therapeutic enoxaparin should be considered. However, critically ill COVID-19 patients could develop resistance to enoxaparin. Bivalirudin, a thrombin inhibitor, may be an alternative. This pilot multicenter randomized controlled trial aims to ascertain if bivalirudin may reduce the time spent under invasive mechanical ventilation, as compared to enoxaparin. (2) Methods: Intubated COVID-19 patients at risk for thrombo-embolic complications were randomized to receive therapeutic doses of enoxaparin or bivalirudin. We ascertained the time spent under invasive mechanical ventilation during the first 28 days from Intensive Care Unit (ICU) admission. A standardized weaning protocol was implemented in all centers. In addition, we assessed the occurrence of thromboembolic complications, the number of patients requiring percutaneous tracheostomy, the gas exchange, the reintubation rate, the ICU length of stay, the ICU and 28-days mortalities. (3) Results: We enrolled 58 consecutive patients. Bivalirudin did not reduce the time spent under invasive mechanical ventilation as compared to enoxaparin (12 [8; 13] vs. 13 [10; 15] days, respectively; p = 0.078). Thrombotic (p = 0.056) and embolic (p = 0.423) complications, need for tracheostomy (p = 0.423) or reintubation (p = 0.999), the ICU length of stay (p = 0.076) and mortality (p = 0.777) were also similar between treatments. Patients randomized to bivalirudin showed a higher oxygenation at day 7 and 15 after randomization, when compared to enoxaparin group. (4) Conclusions: In intubated COVID-19 patients at increased risk for thromboembolic complications, bivalirudin did not reduce the time spent under invasive mechanical ventilation, nor improved any other clinical outcomes.

Atypical Presentation of Traumatic Pediatric Carotid Artery Dissection: A Case Report.

IntroductionCarotid artery dissection is a rare but serious condition manifesting with signs and symptoms that closely overlap with other more benign medical diagnoses. This vascular injury, however, can result in debilitating sequelae, including thromboembolic cerebrovascular accidents.Case ReportWe describe the atypical presentation of a healthy eight-year-old male who presented to the emergency department (ED) with generalized abdominal pain and non-bloody, non-bilious emesis. These symptoms occurred nine days after he sustained blunt head trauma after a non-syncopal fall from standing while playing hockey. He was initially diagnosed with gastroesophageal reflux disease and constipation and was discharged home. The following day he developed an acute headache followed shortly by gait ataxia, prompting a return visit to the ED. Imaging of the head and neck revealed a left internal carotid artery dissection. The patient was started on intravenous unfractionated heparin and admitted to the hospital. He was later discharged symptom-free on therapeutic enoxaparin for eight weeks, followed by daily aspirin therapy.ConclusionPediatric trauma patients, especially those sustaining insult to the head and cervical spine, are at risk for craniocervical arterial injuries. This rare but dangerous pathology often manifests in a non-specific, delayed fashion making it a challenging diagnosis for physicians to make on the initial medical encounter.1,2 Maintaining a high clinical suspicion for carotid artery dissection is required to make this diagnosis and should guide a thorough history, physical examination, and appropriate imaging in order to improve patient morbidity and mortality. This case emphasizes key clinical features and risk factors of this disease that may help emergency clinicians promptly recognize and treat this entity.

A Case of Spontaneous Calf Hematoma with Simultaneous Deep Venous Thrombosis

Patients with active cancer may also have a state of hypercoagulability that increases their risk of venous thromboembolism (VTE). Enoxaparin is a low-molecular weight heparin (LMWH) that is indicated for the prevention and treatment of VTE and is the preferred agent for patients with cancer because of its lower risk of bleeding events and less drug interactions. Bleeding events such as muscular hematomas have been reported with the use of enoxaparin. The risk of hematoma is increased in those with certain risk factors that are frequently present in patients with active malignancy. Coagulation parameters are typically normal in patients with hematoma and there are no accepted criteria to predict which hematomas may become life-threatening. As hematomas present similarly to deep venous thrombosis (DVT), imaging is needed to distinguish them from one another as the treatment for one can worsen the other. Here we present a case of a woman with ovarian cancer and increasing clot burden of chronic diffuse VTE who developed a right calf hematoma while on chronic therapeutic enoxaparin.

A UNIQUE CASE OF PURE ASYMPTOMATIC PERICARDITIS IN COVID-19

TYPE: Case Report TOPIC: Cardiovascular Disease INTRODUCTION: Acute pericarditis in COVID-19 pneumonia (PNA) can present during PNA, after PNA, or even as the main presentation. Chest pain and EKG changes should raise suspicion for pericarditis and be immediately addressed. CASE PRESENTATION: A 43 y/o male with no relevant medical history, presented with respiratory symptoms 20 days with COVID RT-PCR positive 17 days before admission. He was admitted for COVID PNA due to persistent productive cough, increasing dyspnea and decreased exercise tolerance. No chest pain with normal vitals, sat 98% on RA but complained of orthopnea. Labs: Troponin negative x4, potassium 5.1, and D-dimer 2388. He was started on therapeutic enoxaparin and given sodium zirconium cyclosilicate. EKG: diffuse ST segment elevations across precordial leads and lead I with reciprocal ST segment depression in aVR. TTE: small pericardial effusion. This would indicate 2/4 pericarditis diagnosis criteria. CXR and CTPE: b/l patchy and scattered ground-glass opacities. Ibuprofen 600 mg was started; however, colchicine was not initiated. ST segment elevations improved and he was discharged with ibuprofen and apixaban without complications. DISCUSSION: There are few reports on patients who developed pericarditis and pericardial effusions with COVID-19 infection. Most have been associated with myocardial involvement with increasing troponin. Treatment is an on-going debate, but consensus is that corticosteroids and colchicine are safe. CONCLUSIONS: This is a unique case of COVID-19 PNA complicated with troponin negative pericarditis. DISCLOSURE: Nothing to declare. KEYWORD: covid pericarditis

P400 CLINICAL IMPACT OF PROPHYLACTIC ANTICOAGULANT TREATMENT WITH ENOXAPARIN IN CORONAVIRUS DISEASE 2019 (COVID–19)ELDERLY PATIENTS

IntroductionCOVID–19 patients are at increased risk of venous thromboembolism. The WHO/ISSrecommends daily prophylactic anticoagulation therapy with low–molecular weight heparins in COVID–19 patients. Our study evaluated the efficacy of a prophylactic therapy with enoxaparin on clinical outcomes in COVID–19 patients.MethodsThis is a retrospective analysis of 125 SARS–CoV–2 patients hospitalized from 16 MARCH 2020 to MAY 7th, 2021. In this phase of COVID–19 pandemic, man and woman in–patients and out–patients received enoxaparin either at prophilattics or therapeutic dosage. Based on these criteria, we examined 85 patients who received PROPHILATTICenoxaparin (group E, Enoxaparin) and 40 subjects undergone THERAPEUTIC Enoxaparin (group T, Therapeutic). Of them, 95 patients were hospitalized after Sars–Cov2 positive swab and 30 received prophilatic dosage at home.ResultsAfter applying a propensity score matching for age and gender, considering hospitalized patients, there were no significant differences between the two groups (E, T). During hospitalization, a significantly higher percentage of patients of E group developed ARDS (37 vs 13, p = 0.0001) and needed for non–invasive ventilation No significative difference between the two groups was found about incidence of intubation (20 in E vs. 19 in T group; p = 0.4) and pulmonary embolism (17 vs 5, p = 0.4). In–hospital death occurred in 17 E group patients and in 10 T group patients (p = 0.251). No difference on 30–days mortality was found between two groups (p = 0.287). N. 15 patients of T group experienced emorragic events and interrupted enoxaparin therapy. N. 17 of them experienced adverse events (mailny thrombocitopenia).ConclusionsAmong patients with SARS–CoV–2 infection, a therapeutic dose of enoxaparin is not associated with prognostic benefit and did not affect in–hospital and 30–days mortality. A risk–adapted approach to reduce the dose of anticoagulation agent should be considered in selected COVID–19 patients with evidence of coagulopathy. In summary, current data suggest the use of therapeutic–dose LMWH to reduce VTE, it, may increase bleeding, and should be avoided in hospitalized patients with severe COVID–19 in critical care settings.. Lastly, randomized trials in this patient population are still ongoing and novel antithrombotic strategies in critically ill COVID–19 patients are needed.

A single-center experience of anterior accessory saphenous vein endothermal ablation demonstrates safety and efficacy

ObjectiveEndothermal ablation is well-established for the treatment of the great and small saphenous veins. Data are lacking for treatment of the anterior accessory saphenous vein (AASV). The purpose of this study was to evaluate the safety and efficacy of AASV treatment using endothermal ablation. MethodsThis retrospective review included 314 limbs at a single academic institution from 2016 to 2018 using the institutional Vascular Quality Initiative database. All limbs had documented AASV reflux. Baseline characteristics were evaluated including age; sex; ethnicity; clinical, etiology, anatomy, pathophysiology classification; Venous Clinical Severity Score (VCSS); and vein diameter. Outcomes relating to procedure safety and efficacy included treatment modality and length, successful ablation on postoperative imaging, postprocedural clinical outcomes, incidence of endothermal heat-induced thrombosis (EHIT), and any postprocedural complication. ResultsA total of 314 consecutive limbs were identified from 2016 to 2018. The preprocedure VCSS scores were available for 312 limbs and averaged 6.13 ± 3.33. A history of varicose veins were reported in all limbs with 49.4% (n = 155) having previously undergone a procedure. The most common presenting symptom was mild edema in 52.5% (n = 165). Vein diameter and assessment of reflux were obtained by venous duplex ultrasound (DUS) examination. The largest AASV diameter was available for 304 limbs, averaging 7.93 ± 2.69 mm. Treatment modalities included radiofrequency ablation (RFA) in 59.2% (n = 186), endovenous laser ablation (EVLA) in 37.9% (n = 119), and isolated microphlebectomy in 2.9% (n = 9). In all, 38.5% (n = 121) of limbs underwent concomitant microphlebectomy at the time of EVLA. The total treatment length was obtained in 297 limbs, averaging 23.0 cm ± 12.0. Postoperatively, 94.6% of limbs (n = 297) were prescribed compression stockings. Postoperative DUS examination was performed in 312 limbs, revealing successful ablation in 96.5% (n = 303) with 2 limbs (0.6%) developing an EHIT, both treated with therapeutic enoxaparin for 1 week. Repeat DUS examination revealed thrombus resolution in one limb; the other patient was lost to follow-up. VCSS scores after the procedure were available for 145 limbs and averaged 4.45 ± 2.31. This was a statistically significant decrease from preprocedure VCSS scores (P < .01). Average duration of follow-up was 2.2 years, with two limbs lost to follow-up. Of the nine limbs (3.5%) whose initial procedure failed, five (56%) were treated using RFA and four (44%) were treated using EVLA. There were no other postoperative complications. ConclusionsOur experience over a 3-year period for treating the AASV shows it to be safe and effective in a broad range of disease severity with an improvement in VCSS and a low incidence of EHIT. Additionally, RFA and EVLA exhibit similar treatment efficacy. Long-term follow-up data are needed.

A prospective cohort study of catheter-related thrombosis in cancer patients treated with 1 month of anticoagulation after catheter removal.

The duration of anticoagulation in patients with catheter- related thrombosis (CRT) is not standardized. This is a multiinstitutional prospective pilot study in patients with cancer and upper extremity CRT. Patients received therapeutic enoxaparin for 1 month after catheter removal. Incidence of recurrent thrombosis, hemorrhage, and postthrombotic syndrome (PTS) using the modified Villalta scale, and functional limitation using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire were assessed at months 1, 3, and 6 after catheter removal. Clopper-Pearson exact 95% confidence intervals (CI), Pearson correlations, and Skillings-Mack, and Wilcoxon signed ranks tests were done. Twenty-seven patients from three institutions were enrolled. Feasibility outcomes were not met. Seventy percent (n = 19) of the cohort had hematologic malignancies. Excluding two patients who were still on enoxaparin at study withdrawal, the median total duration of therapeutic enoxaparin was 32 [interquartile range (IQR) 30-52] days in the remaining 25 patients. During the 6 months after catheter removal, the incidence of recurrent thrombosis was 0% (n = 0/20, 95% CI 0-17%) and major hemorrhage was 5% (n = 1/20, 95% CI 0.13-25%). One patient (5%, 95% CI 0.13-25%) had PTS in the affected arm at any visit, and none had severe PTS. Higher PTS scores were associated with higher DASH scores. DASH scores at month 6 were significantly lower compared with month 1 (P = 0.0066). No deaths occurred. A multicenter pilot study of treatment with anticoagulation for 1 month after catheter removal did not meet feasibility outcomes but we found no recurrent thrombosis and a low incidence of PTS.

Abstract 17234: Cisplatin Induced Coronary Artery Atherosclerosis Leading To St-elevation Myocardial Infarction: A Case Report

Introduction: Cisplatin-based chemotherapeutic regimen (CBCR) is known for increasing risk of venous thromboembolic (TE) disease. We report a unique case of STEMI associated with CBCR which we believe was caused by coronary artery thrombosis. Case description: A 31-yo man with a past history of germ cell tumor presented with chest pain radiating to back and left arm. It started this morning and intensity did not worsen with exertion. He denied any dyspnea, diaphoresis or palpitations. He was non-smoker and non-obese. He denied any family history of premature coronary artery disease. He had undergone unilateral orchiectomy a year ago, and was currently receiving chemotherapy with bleomycin, etoposide and cisplatin; the last dose of his 3 rd cycle was given the day before. EKG showed ST elevation in leads I, aVL, V4 and V5. Troponin I was high to 6.9 ng/ml (ULN 0.045 ng/ml). He received intravenous infusion of thrombolytic. An angiogram done the next day showed moderate mid-LAD disease with residual clot. A CT scan and an echocardiogram later showed left ventricular thrombus (LVT). He was kept on therapeutic enoxaparin along with aspirin. Follow up echocardiogram showed resolution of the thrombus. His chemotherapy was stopped, and he has been kept on active surveillance since then. Discussion: Most cases of CBCR-associated myocardial infarction that have been reported have been seen in the older population with other risk factors for coronary artery disease. Cases where angiographic data was available, coronary artery vasospasm appeared to be the culprit rather than a true plaque rupture. While the presence of LVT raises possibility of thromboembolism to coronaries causing MI, the angiographic findings support accelerated plaque formation to be the cause of infarction. In earlier reports, elevated pre-treatment level of von Willebrand factor has been postulated to have some role in the disease pathogenesis. Other possible mechanisms for pathogenesis include endothelial cell damage, platelet activation, and imbalance between thromboxane-prostacyclin levels. This case emphasizes the need to keep cardiac etiologies of chest pain in the differential when evaluating patients on CBCR as timely intervention is life saving and prevent morbidity.

Intravenous immunoglobulin therapy for COVID-19 ARDS

Intravenous immunoglobulin therapy for COVID-19 ARDS

Challenges in Steroid and Anticoagulant Therapy in Severe COVID-19 Pneumonia: A Prospective Study.

Background: As COVID-19 has neither a standard treatment protocol nor guidelines, there are many treatment protocols for anti-inflammatory corticosteroids and anti-coagulations for severe COVID-19 pneumonia patients. This study aimed to assess the most suitable modality in this high-risk group. Methods: A prospective, experimental study design was adopted that included 123 severe COVID-19 pneumonia patients admitted at Assiut University Hospital. Patients were divided into three groups according to a combined corticosteroid and anticoagulants therapy protocol. Group A included 32 patients, group B included 45 patients, and group C included 46 patients. Assessment of cases was conducted according to the treatment type and duration, weaning duration from oxygen therapy, length of hospital and ICU stay, and complications during treatment. Three months follow-up after discharge was performed. Results: the three patient groups showed significant differences regarding the 3-month outcome, whereas Group C showed the highest cure rate, lowest lung fibrosis, and lowest mortality rate over the other two groups. The in-hospital outcome, the development of pulmonary embolism, bleeding, hematoma, acute kidney disease, and myocardial infarction showed a significant difference between groups (p values < 0.05). Mortality predictors among severe COVID-19 patients by multivariable Cox hazard regression included treatment modality, history of comorbid diseases, increased C reactive protein, high neutrophil-lymphocyte ratio, and shorter ICU and hospital stay. Conclusion: the use of combined methylprednisolone and therapeutic Enoxaparin, according to a flexible protocol for COVID-19 patients with severe pneumonia, had two benefits; the prevention of disease complications and improved clinical outcome.