The influence of perioperative enoxaparin on bleeding after TORS oropharyngectomy.

Perioperative enoxaparin is often avoided in patients undergoing transoral robotic (TORS) oropharyngectomy. Our goal was to quantify the risk of postoperative hemorrhage (POH) in patients receiving enoxaparin after TORS oropharyngectomy. This was a retrospective database cohort study set up in 89 separate healthcare organizations. The TriNetX electronic database was queried for patients with OPSCC who underwent TORS oropharyngectomy. Propensity-score matching was used to create two cohorts, one receiving and one not receiving perioperative enoxaparin. Outcome measures were the POH rate within 1 day of surgery ("primary") and POH rate within 2-30 days of surgery ("secondary"). 1109 patients undergoing TORS for OPSCC were identified, 400 of which received perioperative enoxaparin. One-to-one propensity score matching resulted in 310 patients per cohort. After matching, the primary POH rates between patients receiving and not receiving enoxaparin were 3.23% for both cohorts (OR 1.000, 95% CI 0.410 to 2.438). The secondary POH rates between those receiving and not receiving enoxaparin were 5.47% vs. 3.54% (OR 1.577, 95% CI 0.726 to 3.424). The number needed to harm (NNH) with perioperative enoxaparin use for secondary POH after TORS was 53; no difference was found in primary POH rates. While not statistically significant, the use of perioperative enoxaparin after TORS is associated with increased odds of secondary POH with a NNH of 53; no difference was found in rates of primary POH. For patients undergoing TORS, enoxaparin use requires careful weighing of the risks and benefits.

Warfarin dosage in a postpartum woman while breastfeeding: A case report.

Warfarin is the only oral anticoagulant recommended in women who are breastfeeding. Although warfarin is a compatible and recommended agent in the postpartum period and during lactation, little is known regarding changes to warfarin dose requirements in this patient population. Here, we report the case of a 40-year-old woman who transitioned from enoxaparin monotherapy back to warfarin at 2 months postpartum, while she was breastfeeding. Despite resuming warfarin at her previously therapeutic dose, her international normalized ratio (INR) remained subtherapeutic and required multiple dose increases. She ultimately required a 100% increase in her warfarin dose postpartum, compared to pre-pregnancy, to achieve a therapeutic INR. This case suggests patients may require higher warfarin doses postpartum, compared to pre-pregnancy, especially if breastfeeding. Clinicians should closely monitor these patients and adjust warfarin doses as necessary.

Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.

PURPOSE: Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. METHODS: A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. RESULTS: The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. CONCLUSIONS: The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.

Comparison of the safety and efficacy for different regimens of pharmaco-prophylaxis among severely burned patients: a randomized controlled trial.

PURPOSE: Venous thromboembolism (VTE) is a common complication in critically ill patients, including severe burn cases. Burn patients respond differently to medications due to pharmacokinetic changes. This study aims to assess the feasibility and safety of different VTE pharmaco-prophylaxis in patients admitted to the ICU with severe burns. METHODS: A pilot, open-label randomized controlled trial was conducted on ICU patients with severe burns (BSA ≥ 20%). By using block randomization, patients were allocated to receive high-dose enoxaparin 30 mg q12hours (E30q12), standard-dose enoxaparin 40 mg q24hours (E40q24), or unfractionated heparin (UFH) 5000 Units q8hours. In this study, the primary outcomes assessed were the recruitment and consent rates, as well as bleeding or hematoma at both the donor and graft site. Additionally, secondary measures were evaluated to provide further insights. RESULTS: Twenty adult patients out of 114 screened were enrolled and received E30q12 (40%), E40q24 (30%), and UFH (30%). The recruitment rate was one patient per month with a 100% consent rate. Donor site bleeding occurred in one patient (16.7%) in the UFH group. On the other hand, graft site bleeding was only reported in one patient (12.5%) who received E30q12. Major bleeding happened in two patients, one in E30q12 and one in the UFH group. Five patients (25.0%) had minor bleeding; two patients (25.0%) received E30q12, two patients E40q24, and one patient UFH. RBC transfusion was needed in four patients, two on E30q12 and two on UFH. Only one patient had VTE, while four patients died in the hospital. CONCLUSION: The study observed a low recruitment rate but a high consent rate. Furthermore, there were no major safety concerns identified with any of the three pharmacologic prophylaxis regimens that were evaluated. TRIAL REGISTRATION NUMBER: NCT05237726.

Prophylactic anticoagulation after minimally invasive hysterectomy for endometrial cancer: a cost-effectiveness analysis.

OBJECTIVE: To determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging surgery for endometrial cancer. METHODS: All patients with newly diagnosed endometrial cancer who underwent minimally invasive staging surgery from January 1, 2017 to December 31, 2020 were identified retrospectively, and clinicopathologic and outcome data were obtained through chart review. Event probabilities and utility decrements were obtained through published clinical data and literature review. A decision model was created to compare 28 days of no post-operative pharmacologic prophylaxis, prophylactic enoxaparin, and prophylactic apixaban. Outcomes included no complications, deep vein thrombosis (DVT), pulmonary embolism, clinically relevant non-major bleeding, and major bleeding. We assumed a willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained. RESULTS: Three of 844 patients (0.36%) had a VTE following minimally invasive staging surgery for endometrial cancer. In this model, no pharmacologic prophylaxis was less costly and more effective than prophylactic apixaban and prophylactic enoxaparin over all parameters examined. When all patients were assigned prophylaxis, prophylactic apixaban was both less costly and more effective than prophylactic enoxaparin. If the risk of DVT was ≥4.8%, prophylactic apixaban was favored over no pharmacologic prophylaxis. On Monte Carlo probabilistic sensitivity analysis for the base case scenario, no pharmacologic prophylaxis was favored in 41.1% of iterations at a willingness-to-pay threshold of $100 000 per QALY. CONCLUSIONS: In this cost-effectiveness model, no extended pharmacologic anticoagulation was superior to extended prophylactic enoxaparin and apixaban in clinically early-stage endometrial cancer patients undergoing minimally invasive surgery. This model supports use of prophylactic apixaban for 7 days post-operatively in select patients when the risk of DVT is 4.8% or higher.

Efficacy and safety of salvianolate and enoxaparin in the prevention of perioperative deep venous thrombosis in gastrointestinal surgery.

OBJECTIVE: In this study, the efficacy and safety of salvianolate were compared with enoxaparin in the prevention of perioperative deep vein thrombosis in gastrointestinal surgery. METHODS: From October 2017 to September 2019, 563 patients who underwent gastrointestinal surgery were collected. Based on the inclusion and exclusion criteria, 119 patients were divided into two groups: enoxaparin group (n = 65) and salvianolate group (n = 54). Comparisons were made regarding the outcomes: prothrombin time (PT), prothrombin activity (PTA), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-dimer level (D-D), platelet count (PLT), hematokrit (HCT), and incidence of deep vein thrombosis (DVT). RESULTS: The main outcomes showed no significance between enoxaparin group and salvianolate group (p > .05). The incidence of DVT in salvianolate group was 1.85%, significantly lower than that in enoxaparin group (12.3%) (p < .05). No serious adverse reactions occurred in the two groups during treatment. CONCLUSION: Compared with enoxaparin, salvianolate has an advantage in the prevention of perioperative thrombosis in gastrointestinal surgery with a lower incidence of DVT.

Superior ophthalmic vein and cavernous sinus thrombosis associated with COVID-19: a case report / Trombose de veia oftálmica superior e seio cavernoso associada à COVID-19: relato de caso

ABSTRACT Cavernous sinus and superior ophthalmic vein thrombosis is a rare clinical condition, and little described in the literature. The clinical presentation is nonspecific and highly variable, and symptoms may include red eye, ophthalmoplegia, coma, and death. The main etiology results from infection of the paranasal sinuses. The final diagnosis must be made through imaging tests such as magnetic resonance imaging. We describe a case of cavernous sinus and superior ophthalmic vein thrombosis after COVID-19 infection in a 64-year-old patient with persistent ocular hyperemia and pain on eye movement. Ophthalmological examination showed preserved visual acuity, conjunctival hyperemia, dilation of episcleral vessels and retinal vascular tortuosity in the right eye. Magnetic resonance imaging confirmed the diagnosis. The association with the COVID-19 was raised, excluding other infectious causes. Enoxaparin and Warfarin were started with significant improvement in the ocular clinical presentation and maintenance of initial visual acuity after 12 months of follow-up.

RESUMO A trombose de seio cavernoso e veia oftálmica superior é uma condição clínica rara e pouco descrita na literatura. A apresentação clínica é inespecífica e altamente variável. Os sintomas podem incluir olho vermelho, oftalmoplegia, coma e morte. A etiologia principal resulta da infecção dos seios paranasais. O diagnóstico final deve ser efetuado por meio de exames de imagem, como ressonância magnética. Descrevemos um caso de trombose de seio cavernoso e veia oftálmica superior após COVID-19 em paciente de 64 anos e com quadro de hiperemia ocular persistente e dor à movimentação ocular. Ao exame oftalmológico, observou-se acuidade visual preservada, hiperemia conjuntival, dilatação de vasos episclerais e tortuosidade vascular retiniana em olho direito. A ressonância confirmou o diagnóstico. A associação com a COVID-19 foi levantada, excluindo-se demais causas infecciosas. Prescrevemos enoxaparina e varfarina, com melhora do quadro clínico ocular e manutenção da acuidade visual inicial após 12 meses de acompanhamento.

Rabdomiossarcoma de ovário em paciente jovem: Relato de caso / Ovarian rhabdomyosarcoma in a young patient: report of case

O sarcoma de partes moles mais comum na infância é o rabdomiossarcoma. Entretanto a localização ovariana é extremamente rara. Acredita-se que este tumor se origina de células imaturas destinadas a compor o músculo esquelético, porém pode surgir em locais onde tipicamente não há músculo esquelético. O diagnóstico do Rabdomiossarcoma primário de ovário pode causar um dilema entre os clínicos, cirurgiões e patologistas, por se tratar de um tumor muito raro. Após o diagnóstico, é necessária a investigação de possíveis metástases. Este caso trata de uma paciente de 17 anos, submetida a parto cesáreo e, no intraoperatório, foi observado aumento de volume, inespecífico, de ovário direito sendo optado por não abordar naquele momento. De antecedentes pessoais, apresentava ooforectomia esquerda aos 13 anos, por Tumor de células da granulosa juvenil e lobectomia inferior esquerda por malformação adenomatosa cística aos 7 anos. Deu entrada no Pronto Socorro 17 dias após dar à luz com queixa de febre, vômitos e dor abdominal. Foi realizada ultrassonografia de urgência, onde foi visualizada massa sólida em fossa ilíaca direita medindo 14,0 x 11,2 x 10,8 cm. Realizada laparotomia exploradora com anexectomia direita e cito-redução subótima do tumor. O resultado anátomo-patológico demonstrou neoplasia maligna fusocelular com áreas de necrose em ovário. A complementação com o estudo imunohistoquímico concluiu rabdomiossarcoma embrionário. Ela voltou a procurar atendimento no Pronto Socorro dois meses após a abordagem com queixa de vômitos biliosos e epigastralgia. Realizou tomografia computadorizada que identificou recidiva do tumor. Durante a internação, evoluiu com quadro de tromboembolismo pulmonar agudo. Diante disso, foi iniciada terapia com enoxaparina em dose plena e quimioterapia com esquema VAC (Vincristina, Doxorrubicina e Ciclofosfamida). Entretanto, ela apresentou insuficiência de múltiplos órgãos, que culminou com o óbito da paciente. O curso clínico desse caso mostra a rápida progressão e letalidade dessa neoplasia. Além da histopatologia, a idade, o tamanho do tumor, a ressecabilidade, o subtipo histopatológico, a presença de metástase no momento do diagnóstico e a invasão linfonodal influenciam no curso clínico da doença. Palavras-chave: Neoplasias ovarianas. Rabdomiossarcoma. Ovário.

Tromboprofilaxis precoz y evolución en embarazadas con COVID-19 / Early thromboprophylaxis and evolution in pregnant women with COVID-19

Introducción: en marzo del año 2020 se declara Pandemia, por la aparición de un nuevo Coronavirus, el SARS-CoV2 (COVID-19). Las mujeres embarazadas presentan un riesgo mayor de presentar procesos tromboembólicos, por lo que se recomienda utilizar de manera profiláctica heparina, para prevención de procesos tromboembólicos durante la infección por SARS-CoV2. Objetivo: Describir la evolución de las embarazadas con infección por SARS-CoV2 con la utilización de heparina de bajo peso molecular, Enoxaparina, ajustada al peso de manera precoz. Metodología: estudio descriptivo prospectivo, observacional, de corte transversal. Resultados: en la evolución de 30 mujeres embarazadas con infección por SARS-CoV2, las edades más frecuentes corresponden a 31 a 35 años, mayor número de infectadas en el segundo trimestre del embarazo, el índice de masa corporal predominante en rango de sobrepeso y obesidad, la dosis de enoxaparina utilizada fue de 40 mg/día, ya que se ajustó al peso de la embarazada, las comorbilidades más frecuentes correspondieron al sobrepeso y obesidad, enfermedad hipertensiva del embarazo y diabetes gestacional, la sintomatología resultó muy variada, debido a las distintas variantes del virus, con más frecuencia la rinorrea, congestión nasal, tos, anosmia, disgeusia, cefalea, fiebre y dificultad respiratoria, y la mayoría de las embarazadas no estaban vacunadas. Conclusiones: ninguna de las 30 embarazadas que recibieron heparina de bajo peso molecular (Enoxapina), ajustada al peso, y de manera precoz, con infección por SARS.CoV2, falleció, ni requirió internación en Unidad de Terapia Intensiva. Una embarazada, fue internada por disnea moderada y saturación de oxígeno menor a 95%. Las restantes embarazadas tuvieron buena evolución en su domicilio, sin ninguna complicación

Introduction: in March 2020, a Pandemic was declared, due to the appearance of a new Coronavirus, SARS-CoV2 (COVID-19). Pregnant women have a higher risk of presenting thromboembolic processes, so it is recommended to use heparin prophylactically, to prevent thromboembolic processes during SARS-CoV2 infection. Objective: to describe the evolution of pregnant women with SARS-CoV2 infection with the early use of Enoxaparin, adjusted to the weight of low molecular weight heparin. Methodology: prospective, observational, cross-sectional descriptive study. Results: in the evolution of 30 pregnant women with SARS-CoV2 infection, the most frequent ages correspond to 31 to 35 years, the highest number of infected in the second trimester of pregnancy, the predominant body mass index in the range of overweight and obesity. , the dose of enoxaparin used was 40 mg/day, since it was adjusted to the weight of the pregnant woman, the most frequent comorbidities were overweight and obesity, hypertensive disease of pregnancy and gestational diabetes, the symptoms were highly varied, due to the different variants of the virus, more frequently rhinorrhea, nasal congestion, cough, anosmia, dysgeusia, headache, fever and respiratory distress, and most of the pregnant women were not vaccinated. Conclusions: none of the 30 pregnant women who received low molecular weight heparin (Enoxapine), adjusted for weight, and early, with SARS.CoV2 infection, died or required admission to the Intensive Care Unit. A pregnant woman was hospitalized due to moderate dyspnea and oxygen saturation less than 95%. The remaining pregnant women had a good evolution at home, without any complications

Síndrome inflamatorio multisistémico asociado a COVID-19: a propósito de un caso clínico con fenotipo shock e íleo paralítico / Multisystem inflammatory syndrome associated with COVID-19: clinical case with shock phenotype and paralytic ileus / Síndrome inflamatória multissistêmica associada à COVID-19: relato de caso com fenótipo de choque e íleo paralítico

La enfermedad por coronavirus 2019 (COVID-19) causada por la infección por SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) se ha extendido por todo el mundo desde diciembre de 2019. Luego de la primera ola de COVID-19, se reporta por primera vez en mayo de 2020 en el Reino Unido un estado hiperinflamatorio asociado temporalmente a la infección por SARS-CoV-2 en un grupo de niños ingresados a unidades de cuidado intensivo pediátrico. Este nuevo fenotipo, con características similares a la enfermedad de Kawasaki y al síndrome del shock tóxico, se ha denominado síndrome inflamatorio multisistémico en niños (MIS-C). Es fundamental la sospecha y el reconocimiento tempranos de esta entidad, con el fin de ofrecer un tratamiento médico oportuno, para prevenir la muerte y el desarrollo de secuelas. Presentamos el caso de una preescolar de 5 años, en la que se realizó diagnóstico de MIS-C con un fenotipo shock e íleo paralítico.

The coronavirus disease 2019 (COVID-19) caused by the infection by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has spread worldwide since December 2019. After the first wave of COVID-19, a hyperinflammatory condition temporarily associated with SARS-CoV-2 infection appeared in a group of children admitted to pediatric intensive care units and reported for the first time in May 2020 in the United Kingdom. This new phenotype shared characteristics with the Kawasaki disease and toxic shock syndrome and has been called multisystem inflammatory syndrome in children (MIS-C). Early suspicion and recognition of this condition is key in order to offer timely medical treatment to prevent death and the development of sequelae. We present the case of a 5-year-old child, in which diagnosis of MIS-C with a shock phenotype and paralytic ileus.

A doença de coronavírus 2019 (COVID-19) causada pela infecção por SARS-CoV-2 (síndrome respiratória aguda grave coronavírus 2) se espalhou pelo mundo desde dezembro de 2019. Após a primeira onda de COVID-19, houve relatos pela primeira vez em maio de 2020 no Reino Unido duma doença hiperinflamatória temporariamente associada à infecção por SARS-CoV-2 num grupo de crianças internadas em unidades de terapia intensiva pediátrica. Esse novo fenótipo com características semelhantes à doença de Kawasaki e a síndrome do choque tóxico foi chamado de síndrome inflamatória multissistêmica em crianças (MIS-C). A suspeita precoce e o reconhecimento dessa entidade são essenciais, a fim de oferecer tratamento médico oportuno, para prevenir a morte e o desenvolvimento de sequelas. Apresentamos o caso de uma menina pré-escolar de 5 anos que foi diagnosticada com MIS-C com fenótipo de choque e íleo paralítico.

Venous thromboembolism risk assessment and prophylaxis in hospitalised medical patients in the Cape Town metropole, South Africa.

BACKGROUND: Venous thromboembolism (VTE) is regarded as the most preventable cause of inpatient death in hospital settings globally. VTE can be prevented through the provision of non-pharmacological and/or pharmacological thromboprophylaxis following individualised risk screening. The Caprini risk assessment model (RAM) offers a validated and well-established approach for VTE risk assessment in medical inpatients. Literature findings describe a trend towards inappropriate and under-prescribing of thromboprophylaxis in this population. Together with concerns regarding clinicians' perceived importance of VTE risk assessment, the need to clarify these aspects of practice is evident. OBJECTIVES: To describe VTE risk assessment and prophylaxis practices of medical practitioners in public sector hospitals in Western Cape Province, South Africa (SA). METHODS: A retrospective, cross-sectional study design was employed in the medical wards of two district hospitals and one regional hospital in the Cape Town metropole, Western Cape. Medical folders of adult medical inpatients admitted between January and July 2020 were reviewed to assess VTE risk using the Caprini RAM. Thromboprophylaxis therapy prescribed and contraindications to chemoprophylaxis were also evaluated. RESULTS: Of 380 patients included in the review, 51.6% were female, and the average age was 52.1 years (range 18 - 96); 21.3% had their weight recorded, while none had their height documented. Infectious disease was the predominant diagnosis (49.2%) detected in the sample. Common VTE risk factors identified included bed rest/restricted mobility for <72 hours (76.3%) and serious infection (67.4%). A total of 97.1% of patients (n=369) were found to be at moderate or higher risk of VTE (Caprini score ≥2). Of this at-risk group, 24.1% were eligible to receive chemoprophylaxis, yet no prescription for thromboprophylaxis was identified. Seventy percent of patients (n=266) were prescribed chemoprophylaxis, with enoxaparin accounting for 98.5% of regimens. Contraindications to chemoprophylaxis were recorded in 13.4% of patients. CONCLUSIONS: Although rates of VTE prophylaxis in medical inpatients may be improving, thromboprophylaxis still remains critically underutilised in this population. This study highlighted a consequence of this trend, with inappropriate chemoprophylaxis prescribing becoming more evident. Mechanical prophylaxis prescribing in medical inpatients is lacking, despite the associated benefits. RAMs should be adapted for the SA setting, where infectious diseases are prevalent. Future research should assess RAM use by clinicians, as this could provide insight into improving RAM uptake and thromboprophylaxis prescribing.

Rationale and Design of the H-REPLACE Study: Safety and Efficacy of LMWH Versus Rivaroxaban in ChinEse Patients HospitaLized with Acute Coronary SyndromE.

BACKGROUND: Acute coronary syndrome (ACS) is a serious and life-threatening condition. Anticoagulation during the acute phase of ACS is effective in reducing ischemic events. The most widely used parenteral anticoagulation agent in ACS patients is enoxaparin. Rivaroxaban is a novel oral anticoagulant with potent anti-Xa activity, which might be an attractive alternative drug to enoxaparin. In fact, rivaroxaban was consistently shown to be non-inferior to enoxaparin therapy in terms of reduction of recurrent venous thromboembolism events. OBJECTIVE: This prospective, randomized, open-label, active-controlled, multicenter study is designed to compare the safety and efficacy of rivaroxaban versus enoxaparin in patients with ACS, who missed the primary reperfusion therapy window and before selective revascularization. METHODS AND RESULTS: Up to 2055 participants receiving background treatment of aspirin plus clopidogrel or ticagrelor will be randomly assigned to either oral rivaroxaban 2.5 mg twice daily or rivaroxaban 5 mg twice daily or subcutaneous enoxaparin 1 mg/kg twice daily until hospital discharge for a maximum of 8 days or 12 h before revascularization therapy. The primary safety endpoint is the International Society on Thrombosis and Hemostasis definition of bleeding events [minor, clinically relevant non-major and major bleeding]. The primary efficacy endpoint is a composite of major adverse cardiac events (MACE), including cardiac death, myocardial infarction, re-revascularization or stroke, and major bleeding events. Secondary endpoints include cardiac-related rehospitalization and all-cause death. Patients will be followed for 12 months after randomization. CONCLUSIONS: The H-REPLACE trial offers an opportunity to assess clinical outcomes of rivaroxaban versus enoxaparin during the acute phase of ACS and may provide an alternative anticoagulation strategy for ACS patients, who missed the primary reperfusion therapy window and before selective revascularization. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03363035.

Enoxaparin titrated by anti-Xa levels reduces venous thromboembolism in trauma patients.

BACKGROUND: Trauma is a major risk factor for the development of a venous thromboembolism (VTE). After observing higher than expected VTE rates within our center's Trauma Quality Improvement Program data, we instituted a change in our VTE prophylaxis protocol, moving to enoxaparin dosing titrated by anti-Xa levels. We hypothesized that this intervention would lower our symptomatic VTE rates. METHODS: Adult trauma patients at a single institution meeting National Trauma Data Standard criteria from April 2015 to September 2019 were examined with regards to VTE chemoprophylaxis regimen and VTE incidence. Two groups of patients were identified based on VTE protocol-those who received enoxaparin 30 mg twice daily without routine anti-Xa levels ("pre") versus those who received enoxaparin 40 mg twice daily with dose titrated by serial anti-Xa levels ("post"). Univariate and multivariate analyses were performed to define statistically significant differences in VTE incidence between the two cohorts. RESULTS: There were 1698 patients within the "pre" group and 1406 patients within the "post" group. The two groups were essentially the same in terms of demographics and risk factors for bleeding or thrombosis. There was a statistically significant reduction in VTE rate (p = 0.01) and deep vein thrombosis rate (p = 0.01) but no significant reduction in pulmonary embolism rate (p = 0.21) after implementation of the anti-Xa titration protocol. Risk-adjusted Trauma Quality Improvement Program data showed an improvement in rate of symptomatic pulmonary embolism from fifth decile to first decile. CONCLUSION: A protocol titrating prophylactic enoxaparin dose based on anti-Xa levels reduced VTE rates. Implementation of this type of protocol requires diligence from the physician and pharmacist team. Further research will investigate the impact of protocol compliance and time to appropriate anti-Xa level on incidence of VTE. LEVEL OF EVIDENCE: Therapeutic/care management, Level IV.

Nebulization with alkaline hipertonic ibuprofen induces a rapid increase in platelets circulating in COVID-19 patients but not in healthy subjects.

We analyze changes in circulating platelets in COVID-19 positive patients who received conventional treatment Dexamethasone and Enoxaparin (Dexa-Enoxa) compared to patients treated with conventional therapy plus nebulization with alkaline hypertonic ibuprofenate (AHI). Results show that after 24 h of nebulization with AHI, circulating platelets shows an increase about 40% at 24 h and reach 65% at 96 h. In patients with platelets content below 200,000 by microliter the increase was 49% and 79% at 24 and 96 h respectively. In patients with platelets above 200,000 by microliter the increase was 24% and 31% at 24 and 96 h, respectively. The increase of platelets via AHI was similar in both, men and women.To evaluate whether this action of AHI was related to platelets from COVID-19 positive patients or also for healthy people, two controls were included: one of them with 10 healthy volunteers and another one with COVID-19 positive patients hospitalized and treated only with Dexa-Enoxa. Results show that, in healthy volunteers, the number of circulating platelets remains unchanged even after 7 days of treatment with AHI. In COVID-19 positive patients treated only with Dexa-Enoxa for 4 days, platelets increased only 16%.

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

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

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial.

BACKGROUND: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. METHODS: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. RESULTS: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). CONCLUSION: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

Time is of the Essence: Impact of a More Aggressive Chemical Venous Thromboembolism Prophylaxis Regimen on Trauma Patients.

BACKGROUND: Trauma patients are at high risk for venous thromboembolism (VTE). Opportunity for chemical VTE prophylaxis improvement was identified and practice was altered to start chemoprophylaxis on admission in most patients. The purpose of this study was to determine if early VTE prophylaxis is safe and reduces VTE. METHODS: The trauma registry was queried over a 12-month period for patients admitted greater than 1 day for traumatic injury. The study spanned 6 months on either side of instituting aggressive chemoprophylaxis. Patients were risk adjusted on demographics, Injury Severity Score, transfusions, procedure type, length of stay, and mortality. Pre-intervention patients were then compared to patients in the aggressive cohort with the primary outcome of VTE. Secondary outcomes included transfusions, mortality, and length of stay (LOS). RESULTS: 1597 patients were identified over the study period with 754 (47%) patients in the aggressive period. There were no differences in age, sex, Injury Severity Score, transfusions, procedures, or LOS between cohorts. Pre-algorithm patients were more likely to have penetrating mechanism (9.3% vs 6.6%; P = .009) and longer time to VTE prophylaxis (23.3 vs 13.9 hours; P < .001). No differences were noted in anticoagulant, VTE rate (2.0% vs 1.2%; P = .195), or mortality. Linear regression analysis identified time to chemical prophylaxis as significant predictor of VTE (ß = 43.9, P < .001). CONCLUSIONS: Early aggressive chemical VTE prophylaxis is safe without increasing transfusions. Venous thromboembolism rates were decreased, but did not reach statistical significance.

Mechanisms of COVID-19-induced kidney injury and current pharmacotherapies.

The COVID-19 pandemic created a worldwide debilitating health crisis with the entire humanity suffering from the deleterious effects associated with the high infectivity and mortality rates. While significant evidence is currently available online and targets various aspects of the disease, both inflammatory and noninflammatory kidney manifestations secondary to COVID-19 infection are still largely underrepresented. In this review, we summarized current knowledge about COVID-19-related kidney manifestations, their pathologic mechanisms as well as various pharmacotherapies used to treat patients with COVID-19. We also shed light on the effect of these medications on kidney functions that can further enhance renal damage secondary to the illness.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.