Dose Of Enoxaparin Research Articles

Clinical evaluation of the safety and efficacy of enoxaparin in patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), increases thrombotic risk in hospitalised patients. The rate of thrombosis in patients with COVID-19 is unclear. The role of heparin, frequently used in the management of hospitalised patients, also needs to be clarified. In this study, we investigated the efficacy and safety of enoxaparin given at prophylactic or therapeutic dose in hospitalised patients with COVID-19, and evaluated its role in the development of disease in terms of mortality, and incidence of thrombotic and bleeding events. We included 141 patients with SARS-CoV-2 infection, admitted to five different wards (one intensive care unit, 2 sub-intensive care units, and 2 general infectious disease units) of Cotugno Hospital, a tertiary care hospital in Naples, Italy, between March and May 2020. Over a median time of 17 days (IQR 11-25), enoxaparin was given to 90/141 patients (63.8%) of whom 65 took a prophylactic and 25 a therapeutic dose. We documented 14 episodes of thrombosis (9.9%); almost all were cases of pulmonary embolism. No significant difference in terms of thromboembolic prevention was found between those patients not receiving anticoagulants and those on prophylactic or therapeutic dose of enoxaparin. Five episodes of major bleeding occurred (3.5%); therapeutic dose of enoxaparin was associated with a greater bleeding risk than prophylactic dose (p=0.002). During follow-up, 31 patients (22%) died; these were mostly elderly men with two or more comorbidities at admission. No advantages of enoxaparin, either as prophylaxis or at high doses, in terms of mortality were observed. At multivariate analysis, low estimated glomerular filtration rate, and high total bilirubin and fasting hyperglycaemia were independently associated with a higher mortality. We did not observe advantages in terms of either thromboembolic prevention or mortality of enoxaparin, which however was more frequently used in patients with more severe disease. Prophylactic enoxaparin was not seen to be associated with bleeding risk.

542 Ceftriaxone-induced Kounis syndrome in the time of COVID-19

A 53 years old male subject with diabetes mellitus, hypertension, dyslipidaemia, obesity, and history of perianal abscess was admitted to the local hospital for generalized maculopapular rash on his trunk and limbs, which was accompanied by intense itching, sweating, hypotension, and severe chest pain. The rash and the accompanying signs/symptoms appeared 10 min after the administration of ceftriaxone (2 g) as antibiotic therapy for the perianal abscess. The patient had no clinical history for any type of allergy. At the first medical contact, an urgent electrocardiogram was taken showing ST-segment elevation in the anterior–lateral leads. The patient was still then treated with methylprednisolone and adrenalin i.v. as an anaphylactic shock was suspected. Afterwards, the patient was admitted in the emergency department, where he showed flu-like symptoms, chills, and fever. An echo-fast showed left ventricular wall motion abnormalities with hypokinesia of the anterior and posterior wall and moderate mitral regurgitation with normal EF. Laboratory tests showed increased levels of high-sensitivity cTnT (32.8 ng/l; NV < 14), white blood cells (13.74 × 103/μl; NV 5.2–12.4 × 103), IL-6 (10.54 pg/ml; NV < 7), C-reactive protein (PCR) (29.3 mg/l; NV 0–3). As for the cutaneous manifestations, flu-like symptoms, and blood test results (elevation of IL-6 and PCR despite an increase of white cell count) a SARS COV-2 swab was done. As recently noted in several preliminary studies, COVID-19 patients indeed show erythematous rash, and localized or widespread urticaria as initial manifestations in acute severe cases along with the humoural acute-phase response. The latter made it complicated to distinguish viral infection vs. drug administration as the underlying cause of the event. In the meantime, the patient started the treatment for an acute coronary syndrome and acetylsalicylic acid 100 mg, clopidogrel 300 mg orally, and enoxaparin dose subcutaneously were administered. Chest pain disappeared 30 min later and the ECG returned to normal 40 min after drug administration. Subsequently, the swab test result turned to be negative for SARS-CoV-2 and the patient was transferred to our centre for an emergency coronary angiography that revealed proximal subocclusive thrombotic stenosis and middle 70–80% thrombotic stenosis of the left anterior descending (LAD) coronary artery and a 80% thrombotic stenosis of the distal portion of the circumflex. Both vessels’ respective stenoses were treated with PCIs. When considering all together the anamnestic, laboratory, and instrumental/invasive findings, a case of Kounis Syndrome (KS) was suspected. Kounis syndrome (KS) has been indeed defined as cardiovascular symptoms that occur secondary to allergic or hypersensitivity insults mainly elicited by specific medications in male patients. KS involves the following three recognized variants: Type 1: the acute coronary event is secondary to spasm; Type 2: coronary thrombosis is the main culprit, and Type 3: the coronary event occurs secondary to drug-eluting stent thrombosis. Therefore, the patient was finally discharged with the diagnosis of ST-elevated MI likely secondary to a type II KS.

Different doses of enoxaparin in the prevention of postoperative abdominal adhesions. Experimental study

BackgroundPostoperative abdominal adhesions (PAAs) are present in more than 90% of patients undergoing abdominal surgery. They are a cause of chronic pain, hospitalizations, multiple surgeries, and infertility in women of reproductive age. The participation of three processes have been recognized: coagulation, fibrinolysis, and inflammation. The usefulness of subcutaneous enoxaparin in their prevention has been established. The objective is to establish the safest and most efficient dose for PAA prevention by testing five different doses of subcutaneous enoxaparin (0.25, 0.5, 1, 1.5, and 2 mg/kg/day) given in one dose/day for seven days. Material and methodsFifty Sprague-Dawley rats were studied, 10 in each group. Adhesions were induced through controlled rubbing of the cecum and suturing of an incision in the terminal ileum. Two independent observers recorded the degree of adhesion formation at 14 days and histologically studied the adhesions. Statistical analysisANOVA compared group averages. The nonparametric Kruskal-Wallis test was used to identify group differences. ResultsThe 0.5 mg/kg/day group had greater formation of adhesions (p < 0.001). There was no significant difference between the 1.5 and 2 mg/kg/day groups, though the latter group had an incidence of 27.2% of bleeding in the abdominal cavity. The degree of adhesions in the histological sections coincided with the macroscopic findings. The interobserver agreement was kappa = 0.88 (very good). ConclusionThe safe and effective dose of subcutaneous enoxaparin to prevent PAA formation was 0.5–1.5 mg/kg/day for seven days.

Giant compressive emphysema: a rare complication of COVID-19

BackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a new ribonucleic acid (RNA) beta-coronavirus, responsible for a worldwide pandemic. Very few cases of SARS-COV-2-related emphysema have been described, except among patients with chronic obstructive pulmonary disease. The thoracic CT scan is the key examination for the diagnosis and allows to evaluate the severity of the pulmonary involvement. The prognosis of the patient with giant emphysema (GE) on coronavirus disease 2019 (COVID-19) in critical or severe form remains poor. We report an original case of COVID-19 pneumonia, critical form, complicated by a giant compressive left emphysema of 22.4 cm in a young subject without respiratory comorbidities.Case presentationA 34-year-old man was hospitalized for left laterothoracic pain. He had no prior medical history. The physical examination revealed tympany on percussion of the left lung. The CT scan confirmed COVID-19 pneumonia with 95% lung involvement. Also, the presence of a voluminous left sub pleural emphysema of 22.4 cm with compression of the ipsilateral pulmonary parenchyma as well as the mediastinal structures towards the right side. The diagnosis COVID-19 pneumonia, critical form, complicated by a compressive left giant emphysema was made. He was put on oxygen, a dual antibiotic therapy, a corticotherapy, and curative doses of enoxaparin. A thoracic drainage surgery was performed at 24th day of hospitalization, which confirmed the giant emphysema. The patient remains on long-term oxygen therapy.ConclusionThe COVID-19 has polymorphic manifestations, pneumonia is the most important one. There are relatively few reports associating COVID-19 and emphysema; furthermore, reports associating COVID-19 and giant emphysema are extremely scarce. CT scans can confirm the diagnosis and differentiate it from a pneumothorax. The pulmonary prognosis of the association of COVID-19 in its severe or critical form with giant emphysema remains poor.

Abstract 13331: Case Report Of Transient Right Bundle Branch Block With S1q3t3 Pattern In Acute Pulmonary Embolism

69 year old woman with hypertension, sleep apnea and who had a recent knee replacement, was brought in to the emergency room (ER) for syncope. She had her physiotherapy session earlier in the day and became symptomatic with dizziness and shortness of breath and passed out. In the ER she had a systolic blood pressure (SBP) of 90mmHg and an oxygen saturation (O2 sat) of 80% on room air. She was given fluid bolus with improvement of SBP to 110mmHg. O2 sat improved to 99% with 10L of oxygen. Treatment was started with full dose of Enoxaparin subcutaneously. A 12-lead electrocardiogram (EKG) showed sinus tachycardia (ST) at 117 beats per minute (BPM), right bundle branch block (RBBB) and S1Q3T3 pattern. A bedside echocardiogram showed right ventricular (RV) distension. A CT-angiogram showed bilateral main stem pulmonary emboli (PE) with signs of RV strain. Patient was admitted and remained hemodynamically stable. A repeat EKG done the following day showed ST at 110 BPM with resolution of RBBB. An echocardiogram done now showed normal RV size and function. Patent was eventually discharged home on full dose apixaban. Q3S1T3 Figure 1 - ST, RBBB, S1Q3T3 pattern Figure 2 - ST Discussion: The patient presented with new RBBB (Figure 1) due to RV strain from acute PE as shown by the CT-angiogram and bedside echocardiogram. The EKG also showed S1Q3T3 pattern. With the resolution of the RV strain the following day, as noted on the subsequent echocardiogram, the 12 lead EKG showed the resolution of the RBBB and the QRS complex became narrow (Figure 2). RBBB is thought to be caused by acute RV overload and dilatation, accompanied by subendocardial ischemia in the right bundle. The S1Q3T3 pattern is historically considered as a “classic” EKG pattern associated with acute PE, even though it is neither sensitive nor specific for acute PE. Conclusion: The RBBB along with the S1Q3T3 pattern and its resolution with improvement of RV hemodynamics, is the first reported case in the literature.

Carotid Artery Stenting in Patients with Atrial Fibrillation: Direct Oral Anticoagulants, Brief Double Antiplatelets, and Testing Strategy.

Carotid endarterectomy is usually preferred over carotid artery stenting (CAS) for patients with atrial fibrillation (AF). We present our experience with short-course periprocedural triple antithrombotic therapy in 32 patients aged >18 years with nonvalvular AF undergoing CAS. There were no deaths, cardiac events, embolic strokes, hyperperfusion syndrome, intracranial hemorrhage, or stent thrombosis within 30 days. Transient intraprocedural hemodynamic instability in 15/32 (47%) and prolonged instability in 4/32 (13%) was managed conservatively. At a mean 16-month follow-up, there were no new neurological events or deterioration. Mean stenosis was reduced from 78.0% ± 9.7% to 17.3% ± 12.2%. This retrospective study included patients AF who were symptomatic (minor stroke (NIHSS ≤ 5)/TIA) with ICA stenosis >50%, or asymptomatic under DOAC therapy with carotid stenosis >80%, who underwent CAS from 6/2014–10/2020. Patients received double antiplatelets and statins. Antiplatelet therapy effectiveness was monitored. Stenting was performed when P2Y12 reaction units (PRU) were <150. DOACs were discontinued 48 h before angioplasty; one 60 mg dose of subcutaneous enoxaparin was administered in lieu. DOAC was restarted 12–24 h after intervention. Patients were discharged under DOAC and one nonaspirin antiplatelet. 32 patients on DOAC were included (26 male, mean age 71). 19 (59.4%) presented with stroke (ICA stenosis-related in 14); 13 (40.6%) were asymptomatic. Stents were deployed under filter protection following pre-angioplasty; post-angioplasty was performed at least once in 12 patients (37.5%). Our experience suggests that CAS can be safely performed in selected patients with CAS and AF requiring DOAC. The role of CAS in AF patients under DOAC warrants study in rigorous trials.

Antithrombin III Supplementation in a Premature Infant: Is There a Target Antithrombin Level?

The optimal antithrombin (AT) activity for low-molecular-weight heparin efficacy and the benefits of antithrombin III (ATIII) supplementation in premature infants diagnosed with venous thromboembolism are unknown. Currently, there are no neonatal-specific guidelines directing the appropriate target AT activity during supplementation. This case report describes a critically ill premature infant with a progressive, occlusive inferior vena cava thrombus who received supplemental ATIII during enoxaparin treatment. The patient did not achieve therapeutic anti-Xa levels despite increasing enoxaparin dosing to 3 mg/kg every 12 hours. ATIII supplementation sufficient to attain an AT activity of >40%, in combination with an enoxaparin dosing of >2 mg/kg every 12 hours, was needed to achieve therapeutic anti-Xa levels. Future large studies are needed to determine if there is an optimal target AT activity for critically ill premature infants.

An Inpatient COVID-19 Prophylaxis Protocol and Its Outcomes: Adherence and Efficacy

Introduction: Patients with coronavirus disease 2019 (COVID-19) have an increased risk for venous thromboembolic events. Thrombotic events contribute to the morbidity and mortality associated with COVID-19 infection, and have prompted investigation into strategies for mitigating thrombosis risk in patients hospitalized with COVID-19 infection. Our team reviewed the charts of patients hospitalized with COVID-19 pneumonia at a tertiary hospital in metropolitan Phoenix Arizona between 2020-2021, to assess frequency and efficacy of utilizing a VTE prophylaxis algorithm designed to prevent thrombosis in patients infected with COVID-19.Methods: A total of 846 patients were retrospectively evaluated to determine if they were treated with guideline-appropriate anticoagulation while hospitalized with COVID-19, as well as if they developed venous or arterial thrombotic events, or major or minor bleeds. 317 patients were excluded for taking therapeutic anticoagulation prior to admission, or for having a COVID-19 diagnosis >7 days after admission. Appropriate anticoagulation was determined by an institutionally designed COVID-19 thromboprophylaxis algorithm, based on platelet count, d-dimer, bleeding risk, and level of medical care required. Regimen options included: no anticoagulation, prophylactic enoxaparin (40 mg SQ daily) or heparin in the setting of kidney dysfunction, weight-based dosing of enoxaparin (40 mg SQ BID if BMI>40), intermediate intensity enoxaparin without thrombus (30 mg BID if BMI<40, or 40 mg BID if BMI>40), and therapeutic anticoagulation (for example enoxaparin 1 mg/kg BID) with thrombus.Demographics: Demographic data and clinical characteristics were collected for 529 patients. Average age was 59 years old, and the majority were men (58.4%). Most patients were White (58.3%), followed by Hispanic (17.8%), or Native American (15.7%). Fewer patients had a normal BMI (21.3%; BMI 18.5 - 24.9) compared to those who were overweight (31.2%; BMI 25-29.9) or obese (43.1% BMI > 30). Other comorbidities included Type 1 or Type 2 diabetes mellitus (N= 172, 32.5%), hypertension (N = 271, 51.2%), and hyperlipidemia (N = 176, 33.3%).Results: A total of 42 patients (8%), were diagnosed with a venous thrombosis during hospitalization. Patients admitted to the ICU were significantly more likely to have a thrombotic event of any type compared to non-ICU patients (21.6% to 5.7%; p < 0.001). Specifically, critically ill patients had higher incidences of deep vein thrombosis (9.5% to 0.7%), pulmonary emboli (8.1% to 4.8%), and superficial thrombi (2.7% to 0.2%). Only 1.1% of patients (6/529) experienced any bleeding, of which 3 were classified as a major bleed.Discussion: Among patients hospitalized at our institution with COVID-19, the majority were anticoagulated appropriately according to the COVID-19 thromboprophylaxis algorithm. Overall incidence of thrombosis in the study population was 8%. A significantly higher percent of critically ill patients had thrombi, supporting reports of correlation between severity of illness and thrombosis risk. The two regimens of anticoagulation least adhered to were weight-based and intermediate-based dosing, likely reflecting a departure from the hospital's thromboprophylaxis regimens prior to COVID-19 pandemic. Further studies are needed to characterize whether identifiable risk factors correlate with the incidence of thrombosis, and whether treatment with lower than recommended doses of anticoagulation, based on the COVID-19 thromboprophylaxis algorithm, were associated with thrombosis. DisclosuresNo relevant conflicts of interest to declare.

O21 A case of thromboembolic ischaemic cardiomyopathy and intracardiac thrombus in a patient with antiphospholipid syndrome

Abstract Case report - Introduction Commonly found in association with lupus, antiphospholipid syndrome (APLS) is a potentially life-threatening disease of which an understanding is essential for rheumatologists. In addition to well-recognised sequelae such as pulmonary embolism and obstetric complications, APLS can provoke thrombi ranging from microscopic to massive in size in a wide range of arterial and venous territories. We present the case of a young woman with APLS who suffered significant morbidity as a result of intracardiac and coronary thromboembolism shortly after becoming pregnant and switching anticoagulant therapy, highlighting the importance of vigilance and investigation for rarer thromboses in APLS patients. Case report - Case description A 34-year-old woman with known APLS and 5 weeks pregnant was admitted to hospital with a history of headache, nausea/vomiting and mild photophobia followed by fever, shortness of breath, confusion, pleuritic chest pain and lower limb swelling. She had commenced enoxaparin in place of warfarin on becoming pregnant. Examination was suggestive of cardiac failure. Troponin and NTproBNP were markedly elevated, without ischaemic ECG changes. A brain CT venogram was reported as normal, but echocardiogram revealed a dilated LV with reduced ejection fraction (39%), inferior and lateral wall hypokinesia and possible LV thrombus. She was treated initially for myocarditis (presumed viral or autoimmune) and received antibiotics given her raised WCC and CRP. Treatment dose enoxaparin was continued. Bloods revealed anaemia, thrombocytopenia, and positive immunology: cardiolipin IgG 123U/ml, IgM 612, anti-B2GP1 IgG 19/IgM 607, ANA (1/320) and RNP 70. C3 was normal (0.8) and C4 low (0.03). A livedoid rash consistent with APLS was present on the trunk, but there were no other clinical manifestations of connective tissue disease. Repeat CT venogram performed after the patient reported worsening headaches revealed a small tentorial subdural haematoma, resulting in the reversal of enoxaparin with protamine. Later review of these images suggested a stable 5mm haematoma that was present on the earlier scan, and enoxaparin was recommenced. Cardiac MRI revealed extensive infarct with contained LV wall rupture. Coronary angiography showed normal vessels. LVEF on repeat echocardiogram fell to 28%. Surgical pregnancy termination was performed in accordance with patient wishes, with subsequent reversion to warfarin anticoagulation. Repeat MRI showed thinned anterior/lateral LV walls, evidence of transmural myocardial fibrosis and residual laminar thrombus, and bubble echo demonstrated no PFO. The patient was ultimately managed for presumed microembolic myocardial infarction with resulting heart failure, and has been referred to a cardiac transplant centre. Case report - Discussion This case highlights the potential risk associated with a relatively common scenario: anticoagulant switching in females with APLS at the start (or in anticipation) of pregnancy. In this case our patient started enoxaparin 80mg BD 48 hours after discontinuing warfarin, developing symptoms consistent with intracerebral thrombosis shortly afterwards, followed by those of heart failure. The possible diagnoses on the basis of the patient’s initial presentation were numerous, and she was appropriately investigated in the first instance for a possible cerebral thrombotic event with cranial CT and venogram. On development of cardiorespiratory symptoms, there was a delay in requesting investigations (troponin, BNP) that may have pointed towards myocardial pathology, and once these investigations were noted to be abnormal the patient was managed as a probable myocarditis in keeping with most other patients of her age without a significant past medical history. Perhaps insufficient diagnostic weight was given to her known thrombophilia and recent medication change, which may have prompted closer review of her brain imaging leading to earlier detection of the subdural haematoma. It may also have led to more rapid investigation for possible thrombus elsewhere via earlier echo, CTPA or cardiac MRI. The latter investigation was ultimately crucial in definitively showing myocardial injury to be the result of infarction rather than inflammation, where prior ECGs had not suggested ischaemia. The subsequent unremarkable coronary angiogram added weight to the likely thromboembolic nature of the infarction, potentially via multiple microemboli being thrown off the LV thrombus. The precise timing of the presumed embolisation to our patient’s coronary circulation is unclear, and the absence of overt ischaemic cardiac symptoms suggests this may have been a relatively prolonged, subacute process. Earlier recognition of the thrombotic nature of this event may have prevented myocardial injury if embolic showers continued into her inpatient stay. Case report - Key learning points

Incidence of Venous Thromboembolic Events with Long Term Enoxaparin in Patients Undergoing Robotic Surgery for Endometrial Cancer

<h3>Study Objective</h3> To determine the incidence of venous thromboembolic (VTE) events in patients undergoing robotic surgery for endometrial cancer who receive postoperative enoxaparin for 28 days starting before surgery versus those receiving only a single dose of preoperative prophylaxis with enoxaparin. <h3>Design</h3> Retrospective cohort study. <h3>Setting</h3> University hospital. <h3>Patients or Participants</h3> All patients undergoing robotic assisted surgical staging between 1/2017 to 8/2020 for endometrial intraepithelial neoplasia (EIN), endometrial adenocarcinoma (EAC), uterine serous carcinoma (USC), and uterine carcinosarcoma (MMMT). Exclusion criteria included a history of a prior thromboembolic event prior to surgery (i.e., DVT, PE), thrombophilia, history of a prior CVA, or use of anti-coagulant therapy prior to surgery. <h3>Interventions</h3> N/A. <h3>Measurements and Main Results</h3> A total of 190 patients had robotic assisted surgical staging for endometrial cancer by two attending surgeons at a single gynecologic oncology practice during the study period. One hundred fifty-nine patients met inclusion criteria. In this cohort, 35 (22%) patients received 28-days of prophylactic enoxaparin postoperatively and 124 (78%) patients did not receive postoperative enoxaparin. There was no significant difference between the 2 groups with respect to age, BMI, tobacco use, aspirin use, and ASA classification. There was no significant difference between the 2 groups with respect to postoperative diagnosis, tumor grade, and stage. There was no significant difference between length of stay and postoperative complications. The rate of clinical VTE diagnosed within 30 days postoperatively was 0 (0%) in the group receiving 28-days of enoxaparin postoperative and 1 (0.81%) in the group receiving no prophylactic enoxaparin (p= 1.0). <h3>Conclusion</h3> In our patient population, no significant increase in rate of clinical VTE was observed in patients who did not receive 28-days of postoperative enoxaparin compared to those receiving one dose of preoperative enoxaparin who were undergoing robotic surgery for endometrial cancer.

Supraprophylactic Anti–Factor Xa Levels Are Associated with Major Bleeding in Neurosurgery Patients Receiving Prophylactic Enoxaparin

Prior studies demonstrated reduced risk for venous thromboembolism (VTE) in neurosurgical patients secondary to prophylaxis with both heparin and low-molecular-weight heparin. The ability to monitor low-molecular-weight heparin by obtaining anti-factor Xa (anti-Xa) serum levels provides an opportunity to evaluate safety and efficacy. The aim of this study was to describe characteristics of patients who have anti-Xa levels outside of the goal range (0.2-0.4/0.5 IU/mL) and investigate incidence of major bleeding and VTE. A single-center, retrospective, observational study was conducted on neurosurgical patients receiving enoxaparin for VTE prophylaxis between August 2019 and December 2020. Significance testing was conducted via Fisher exact test and independent samples t test. The study included 85 patients. Patients were less likely to have an anti-Xa level in the goal range if they were male, had a higher weight, or were morbidly obese. Three neuroendovascular patients (3.5%) experienced a major bleed. Serum anti-Xa levels were significantly higher in patients who experienced major bleeds compared with patients who did not (0.45 ± 0.16 IU/mL vs. 0.28 ± 0.09 IU/mL, P= 0.003). Patients with a supraprophylactic anti-Xa level (>0.5 IU/mL) were more likely to experience a major bleed (P= 0.005). One VTE event occurred: the patient experienced a pulmonary embolism with anti-Xa level at goal. Anti-Xa-guided enoxaparin dosing for VTE prophylaxis in neurosurgical patients may help prevent major bleeding. These data suggest that a higher anti-Xa level may predispose patients to major bleeding. Further evaluation is needed to identify the goal anti-Xa level for VTE prophylaxis in this population.

Anticoagulant profile of supplementary-dose enoxaparin in patients undergoing prolonged percutaneous coronary intervention

Abstract Background Enoxaparin 0.75 mg/kg, with either a staged-dose regimen (0.5+0.25 mg/dl) or a single-dose regimen (0.75 mg/dl) achieves target anticoagulation for 90 min in patients undergoing percutaneous coronary intervention (PCI). In patients with prolonged procedures (&amp;gt;90 min), a supplementary-dose enoxaparin (0.375 mg/kg) needs to be given at 90 min to maintain target anticoagulation for additional 90 min. However, the actual anticoagulant profile of this supplementary-dose regimen remains unknown because it is recommended only based on pharmacokinetic simulations. Purpose This study directly assessed the anticoagulant profile of supplementary-dose enoxaparin (0.375 mg/kg) in troponin-negative patients undergoing prolonged elective trans-radial PCI who received a total dose of enoxaparin 0.75 mg/kg during the first 90 min of their procedures. Methods In 33 patients with prolonged procedures, 15 patients received enoxaparin 0.5 mg/kg at the beginning of coronary angiography and additional enoxaparin 0.25 mg/kg before PCI (Staged-dose regimen); while, 18 patients received enoxaparin 0.75 mg/kg at the beginning of coronary angiography without additional dose before PCI (Single-dose regimen). A supplementary-dose enoxaparin (0.375 mg/kg) was administered at 90 min after the first dose was given, and every 90 min thereafter until the end of PCI. Anti-Xa levels were assessed at 0 min (immediately before), 10 min and 90 min after each supplementary dose was given (S_0min, S_10min, and S_90min, respectively). Target anticoagulation was defined as anti-Xa level of 0.5–1.8 IU/ml. Results In patients who received only one supplementary dose (n=28), the anti-Xa levels were S1_0min: 0.87±0.19 IU/ml, S1_10min: 1.44±0.21 IU/ml, and S1_90min: 1.10±0.21 IU/ml. In patients who received two supplementary doses (n=5), the anti-Xa levels were S1_0min: 0.86±0.07 IU/ml, S1_10min: 1.27±0.27 IU/ml, and S1_90min: 1.03±0.23 IU/ml, as well as S2_0min: 1.03±0.23 IU/ml, S2_10min: 1.56±0.28 IU/ml, and S2_90min: 1.28±0.18 IU/ml, respectively. No patient received more than two doses of supplementary enoxaparin. All anti-Xa levels were within the range of target anticoagulation except for two patients receiving one supplementary dose (S1_10min: 1.96 IU/ml and 1.81 IU/ml, respectively) and another one receiving two supplementary doses (S2_10min: 1.87 IU/ml). Conclusions In patients undergoing prolonged PCI who received a total dose of enoxaparin 0.75 mg/kg during the first 90 min of their procedures, a supplementary-dose enoxaparin (0.375 mg/kg), which was administered at 90 min and every 90 min thereafter, maintained target anticoagulation for additional 90 min each time it was given. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Peking Union Medical College Hospital (PUMCH) Science Fund for Junior Faculty

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Anticoagulant profile of subcutaneous enoxaparin in healthy dogs.

Our study objective was to identify a subcutaneous enoxaparin dosage that provided a consistent anticoagulant intensity in dogs. Our hypotheses were that a dose of 0.8mg/kg would provide inconsistent anticoagulation, a higher dose would provide consistent anticoagulation over a greater duration of time, and viscoelastometry would effectively monitor the anticoagulant status. Six healthy dogs received two subcutaneous enoxaparin doses (0.8 and 2mg/kg) for anti-Xa activity determinations and pharmacokinetic modeling. Based on calculations derived from these results, 1.3mg/kg, SC, q8h was administered for seven doses. Target ranges for anticoagulant intensity were defined as anti-Xa activity of 0.5-1U/ml, and change from baseline of two viscoelastometric parameters: activated clotting time (ΔACT; ≥40s), and clot rate (CRpost; ≤20U/min). Following an initial injection at 1.3mg/kg, anti-Xa activity of 5/6 dogs reached or exceeded the target range. Following the final dose, anti-Xa activity reached or exceeded the target range in all dogs, and ΔACT and CRpost values exceeded target for 2-6 and 4-12h, respectively. At an enoxaparin dosage of 1.3mg/kg, SC, q8h, anti-Xa activity was consistently above the minimum threshold of the target range; however, the safety of this dosage remains to be determined.

Anticoagulation is the answer in treating noncritical COVID-19 patients.

All autopsy studies demonstrated widespread thrombosis and alveolar-capillary microthrombi as the cause of death among patients with COVID-19. The autopsy studies are the gold-standard for diagnostic accuracy and therapeutic strategies for any clinical scenarios. The author initially observed that patients already taking therapeutic dose of oral direct factor Xa inhibitors for an unrelated reason, have significantly better survival rates than those not taking any anticoagulants. This influenced the author to conduct a retrospective chart review of the hospitalized patients in Jackson Hospital (Alabama) to evaluate the effect of variable doses of anticoagulation among COVID-19 patients. The study found that serum inflammatory bio-marker D-dimer trends are associated with changes in oxygen requirement among patients with COVID-19, if patients present at an early stage, and titration of Enoxaparin (anticoagulation) dose based on D-dimer trends leads to increased patient survival.

COVID-19 INFECTION IN A PATIENT WITH HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: As we navigate through the Covid pandemic, there is emerging evidence of cardiac injury related to Covid-19 infection such as myocardial ischemia, arrhythmia and pericardial effusion. Studies have associated Covid-19 related cardiac injury with a 5-fold increase in the risk of mechanical ventilation and 14 times higher mortality rate(1). In the presence of cardiac co-morbidities, Covid-19 related all-cause mortality rate increases. We present a case of Covid-19 infection in a patient with Hypertrophic Obstructive Cardiomyopathy (HCM) intending to discuss its sequelae. CASE PRESENTATION: A 72-year old male presented to ER with 2 days history of non-productive cough and dyspnea. Six months ago, he was hospitalized for 8 days with respiratory failure secondary to Covid-19 pneumonia. He was treated with remdesivir, ceftriaxone, azithromycin and dexamethasone. His past history was significant for HCM status post AICD placement, chronic diastolic heart failure with ejection fraction of 55% and hypertension.On presentation, he was hypotensive at 83/50, with a heart rate of 58 and saturation of 94% on room air. His WBC count was elevated at 12.2. Chest x-ray revealed right basal infiltrate with bilateral small pleural effusions. His presentation ECG revealed new onset atrial fibrillation (AF). Covid PCR test was negative. He was admitted to intensive care unit for vasopressor support for management of septic shock secondary to pneumonia.Therapeutic dose of enoxaparin was initiated in view of AF with CHA2DS2VASC score of 3. Echocardiogram showed mild concentric left ventricular hypertrophy with ejection fraction of 55-60%. Significant left ventricular outflow tract gradient consistent with HCM was noted. Due to worsening of bilateral pleural effusions, bilateral thoracocentesis was performed separately draining 650ml of hemorrhagic fluid on the left and 800ml of hemorrhagic fluid on the right. Pleural fluid (PF) analysis was exudative and cytology was negative. Re-accumulation of PF warranted bilateral chest drain placement. PF culture remained negative. Unfortunately, patient had recurrent hypovolemic shock and he opted for comfort care measures. DISCUSSION: ACE2 receptor in the respiratory epithelium serves as the entry portal for the SARS-CoV-2 virus. In patients with HCM, there is up-regulation of ACE2 expression causing a 5-fold increase in ACE2 protein in sarcomeres, thereby increasing susceptibility to cardiac complications (2). Our patient in discussion had new onset AF, on the background of HCM. CONCLUSIONS: Reports indicate an increased incidence of cardiac complications in HCM patients with Covid-19 infection such as arrhythmia, as in our patient. AF in the setting of underlying HCM, can be explained by ACE2 protein up-regulation. Physicians managing HCM patients should well be aware of increased risk of such complications. REFERENCE #1: Toloui A, Moshrefiaraghi D, Madani Neishaboori A, Yousefifard M, Haji Aghajani M. Cardiac Complications and Pertaining Mortality Rate in COVID-19 Patients;a Systematic Review and Meta-Analysis. Arch Acad Emerg Med. 2021 Feb 13;9(1):e18. doi: 10.22037/aaem.v9i1.1071. PMID: 33870205;PMCID: PMC8035700. REFERENCE #2: Bos JM, Hebl VB, Oberg AL, Sun Z, Herman DS, Teekakirikul P, Seidman JG, Seidman CE, Dos Remedios CG, Maleszewski JJ, Schaff HV, Dearani JA, Noseworthy PA, Friedman PA, Ommen SR, Brozovich FV, Ackerman MJ. Marked Up-Regulation of ACE2 in Hearts of Patients With Obstructive Hypertrophic Cardiomyopathy: Implications for SARS-CoV-2-Mediated COVID-19. Mayo Clin Proc. 2020 Jul;95(7):1354-1368. doi: 10.1016/j.mayocp.2020.04.028. Epub 2020 Apr 28. PMID: 32448590;PMCID: PMC7186205. DISCLOSURES: No relevant relationships by Khushdeep Chahal, source=Web Response No relevant relationships by Sangeetha Isaac, source=Web Response No relevant relationships by Kavitha Juvvala, source=Web Response No relevant relationships by Eileen Montalvan, source=Web Response No relevant relationships by Utibe Ndebbio, source=Web Response No relevant relationships by Mohammed Afraz Pasha, source=Web Response

HEART HALF FULL

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: COVID-19 is associated with arterial and venous thrombosis with incidence of 2.3-22% in severe cases and 0-6% in mild cases. Very few case reports exist about cardiac thrombus in COVID-19 patients with Myocardial infarction (MI) but our patient purely had increased thromboembolic risk from COVID-19 without MI. CASE PRESENTATION: A 49-year-old male with a history of HTN, IDDM, CKD stage 3, and asthma presented to the hospital with six days of progressive dyspnea with fever, fatigue, and cough. He tested positive for COVID-19 two days prior. He was hypoxic at 83% on room air. Pertinent physical exam revealed coarse breath sounds bilaterally and no murmurs. Lab work showed creatinine 1.93 mg/dl, troponin 0.357 ng/ml, B-natriuretic peptide (BNP) 275 pg/ml. D-dimer 1,369 ng/ml, Ferritin 1,569 ng/ml, and CRP >8 mg/dl. Chest x-ray showed bilateral patchy nodular opacities. CTA chest showed pneumonia and bilateral effusions without pulmonary embolism. The patient was started on oxygen supplementation, dexamethasone, and enoxaparin 30 mg every 12 hours. On day 2, Remdesivir was initiated as kidney function had improved. The enoxaparin dose was increased to 0.5mg/kg (60 mg every 12 hours) due to worsening D-dimer at 2268 ng/ml. On day 3, he had worsening respiratory failure and was transitioned to a high flow respiratory system on 60L. Repeat BNP increased to 475.4 pg/ml and D-dimer to >7650 ng/ml. Troponin plateaued at 0.3 ng/ml. He was switched to a low-intensity heparin protocol of 10 units/kg/hr. A trans-thoracic echocardiogram (TTE) showed an ejection fraction of 57% with a questionable apical clot and without wall motion abnormality. A TTE with contrast showed a spherical echogenic mass 1.87 x 1.64 cm, consistent with left ventricular (LV) thrombus attached to the septum. He was then switched to a high-intensity heparin protocol of 15 units/kg/hr and then transitioned to warfarin with a plan for outpatient cardiac MRI. On day 11, he was discharged home on 2L of oxygen. DISCUSSION: Thromboembolic disease is a well-known complication of COVID-19. The pathophysiology of thromboembolism in COVID-19 is multifactorial including platelet dysfunction, viral-mediated endothelial inflammation, hypercoagulability, and acquired antiphospholipid antibodies.LV thrombus is a known complication of MI and dilated cardiomyopathy but our patient did not have associated MI. His only apparent predisposing factor was hypercoagulability due to COVID-19. TTE with contrast increases the visibility of the thrombus. But, cardiac MRI with contrast remains the gold standard for its diagnosis. Anticoagulation is the mainstay of treatment as it reduces the major adverse cardiac events (MACE) and overall mortality. CONCLUSIONS: Cardiac thrombus is a rare thromboembolic phenomenon that needs to be considered in COVID-19 patients with or without MI. Immediate parenteral anticoagulation is key for reducing complications. REFERENCE #1: Roberts KA, Colley L, Agbaedeng TA, Ellison-Hughes GM, Ross MD. Vascular Manifestations of COVID-19 – Thromboembolism and Microvascular Dysfunction. Front Cardiovasc Med. 2020;7:598400. doi:10.3389/fcvm.2020.598400 REFERENCE #2: Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432 REFERENCE #3: Jadhav KP, Jariwala P. Intra-Cardiac Thrombus in COVID-19 pandemic – Case Series and Review. Eur J Cardiovasc Med. Published online November 23, 2020. doi:10.5083/ejcm20424884.180 DISCLOSURES: No relevant relationships by Tundun babalola, source=Web Response No relevant relationships by Francis Jenkins, source=Web Response No relevant relationships by Nirvi Shah, source=Web Response No relevant relationships by Shraddha Tongia, source=Web Response

Failure of Therapeutic Enoxaparin to Prevent Massive Deep Vein Thrombosis and Cerebral Venous Sinus Thrombosis in a Pregnant Patient with Combined Factor V Leiden Mutation and Antithrombin III Deficiency

Women with combined inherited thrombophilia are at high risk of developing thrombotic events, especially when they are pregnant. Low-molecular-weight (LMW) heparins are the preferable agents for anticoagulation during pregnancy. Despite the fact that they have been proven to be effective in the treatment and prevention of venous thromboembolism, thrombotic events can still happen. Here, we report a case of a 40-year-old white pregnant woman with combined factor V Leiden mutation and antithrombin III deficiency who developed massive deep vein thrombosis and cerebral venous sinus thrombosis despite being on therapeutic doses of enoxaparin.

THE LEAKY LUNG: A CASE OF COVID-19 PNEUMONIA COMPLICATED BY LUNG ABSCESS, BRONCHOPLEURAL FISTULA, AND PNEUMOTHORAX

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Lung abscesses develop when necrosis of lung tissue caused by underlying infections form cavitary spaces of the lung parenchyma. A bronchopleural fistula (BPF) is a complication of cavitary lesions where a sinus tract forms between the bronchus and pleural space. We present the first reported case of a patient with severe COVID-19 who developed a lung abscess with a BPF and spontaneous pneumothorax requiring video-assisted thoracoscopic surgery (VATS). CASE PRESENTATION: A 60-year-old male with a history of hypertension and dyslipidemia presented to the hospital with shortness of breath after a recent diagnosis of COVID-19. The patient was hypoxic on room air and his chest x-ray (CXR) revealed bilateral infiltrates. The patient was admitted to the medical floors and treated with methylprednisolone, Remdesivir, piperacillin/tazobactam and DVT prophylaxis doses of enoxaparin. Methylprednisolone was increased to higher doses over the next few days in response to worsening inflammatory markers and hypoxia, as high as 125mg IV 4 times a day and was subsequently tapered to 160mg IV daily in divided doses for 30 days. On day 40, a new cavitary lesion of the right middle lobe (RML) was seen on CXR, and blood cultures grew methicillin sensitive staphylococcus aureus (MSSA) for which linezolid, meropenem and micafungin were started. On day 42, the patient developed a right sided pneumothorax which required chest tube insertion. On day 47 the patient developed respiratory distress and worsening pneumothorax, the pleural drainage system demonstrated continuous air leak and the patient was subsequently intubated due to worsening respiratory failure. VATS was performed which revealed a RML abscess; the procedure was converted to open thoracotomy with RML wedge resection. Histopathological analysis showed organizing pneumonia, interstitial fibrosis, alveolar damage and a BPF. Cultures taken from the abscess grew MSSA. On day 49, the patient became hypotensive and required the initiation of vasopressors. In the following days he developed a new air leak noted on the pleural drainage system. He remained in the ICU for several days and did not exhibit clinical improvement, thus his family transitioned him to comfort measures and he passed away soon after. DISCUSSION: High dose corticosteroids are used to treat severe COVID-19 with the goal of preventing cytokine storm and subsequent ARDS. Immunosuppression is a complication of prolonged treatment with high dose corticosteroids and may result in bacterial superinfection. Lung abscesses are typically treated conservatively with broad spectrum antibiotics. In cases such as those with BPF and pneumothorax, treatment with surgical intervention may be required. CONCLUSIONS: While corticosteroids have been used widely in the treatment of COVID-19, clinicians should be cautious in the consequences of prolonged utilization and should monitor for related complications. REFERENCE #1: Kuhajda, I., Zarogoulidis, K., Tsirgogianni, K., Tsavlis, D., Kioumis, I., Kosmidis, C., . . . Kuhajda, D. (2015, August). Lung abscess-etiology, diagnostic and treatment options. Retrieved April 29, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543327/ REFERENCE #2: Salik, I. (2020, August 27). Bronchopleural fistula. Retrieved April 29, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK534765/ DISCLOSURES: No relevant relationships by Arslan Chaudhry, source=Web Response No relevant relationships by Rajapriya Manickam, source=Web Response No relevant relationships by Christopher Millet, source=Web Response No relevant relationships by Sushant Nanavati, source=Web Response No relevant relationships by Sherif Roman, source=Web Response No relevant relationships by Anish Samuel, source=Web Response

PULMONARY EMBOLISM CASES WHICH OCCURRED UNDER ENOXAPARIN SODIUM 4000 IU PROPHYLAXIS

TOPIC: Pulmonary Vascular Disease TYPE: Global Case Reports INTRODUCTION: Some surgical based guidelines recommends standart 4000 IU Enoxaparin for VTE prophylaxis. However fixed dose enoxaparin will often fail to achieve therapeutic levels, since for therapeutic anticoagulation, enoxaparin is dosed based on weight (1mg/kg). To draw attention to this issue, we presented 3 cases who developed PE while receiving 4000 IU Enoxaparin prophylaxis. CASE PRESENTATION: Cases Case 1:A 27-year-old, 72 kilogram male patient, who had no known chronic disease history, was using Enoxaparin sodium 4000 international units (IU) regularly once a day after the meniscus operation. Complaints of back pain and shortness of breath developed two weeks after the operation In the computed tomography pulmonary angiography(CTPA), filling defects in the middle and lower lobar branches of the right lung and extending to the lingular segment of the upper lobe of the left lung were seen. The patient was followed up in our department with the diagnosis of bilateral lobar pulmonary embolism (PE).Case 2:An 80-year-old 65-kilogram female patient with a known chronic obstructive pulmonary disease, atrial fibrillation (AF), hypertension, was using a new generation oral anticoagulant (NOAC) due to AF. NOAC was discontinued upon the development of ecchymotic lesions in the body, and Enoxaparin sodium 4000 IU was added to the treatment once a day.. Three weeks after the treatment change, the patient was admitted to the emergency department with the complaint of dyspnea, and a thrombus extending from the distal of both main pulmonary arteries to the bilateral lower and upper lobe bronchial artery was detected in the CTPA, and he was followed up in our service with the diagnosis of massive PE. DISCUSSION: Case 3: An 81 years old, 67-kilogram female patient with a diagnosis of hypertension and Alzheimer's disease admitted to the hospital with complaints of shortness of breath and swelling in the legs for a week. Seven months ago, Enoxaparin sodium 4000 IU was planned twice a day in an external center due to pulmonary embolism. The patient continued to use LMWH 4000 IU once a day after the 3rd month of his own request. CTPA revealed filling defects in the right pulmonary artery upper lobe posterior and lower lobe posterobasal segments. Lower extremity venous Doppler ultrasonography revealed deep vein thrombus (DVT). When compared with previous examinations, it was observed that pulmonary embolism had newly developed and the patient was followed up with segmental PE + DVT diagnoses. CONCLUSIONS: Although low-dose LMWH treatment is recommended in some guidelines and drug package insert for PE prophylaxis, the cases we have presented suggest that it would be safer to consider the patient's weight when administering LMWH prophylaxis. REFERENCE #1: Prophylactic Enoxaparin Dosing in Obese Orthopedic Patients: A Literature SearchVan N Tran 1, Ilya Varfolomeev 2, Geoff Hill 3 DISCLOSURES: No relevant relationships by MELTEM GUNDUZ, source=Web Response No relevant relationships by H.Canan Hasanoglu, source=Web Response