Risk and Management of Bleeding Complications with Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Venous Thromboembolism: a Narrative Review.

Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent conditions with a significant healthcare burden, and represent the main indications for anticoagulation. Direct oral anticoagulants (DOACs) are the first choice treatment of AF/VTE, and have become the most prescribed class of anticoagulants globally, overtaking vitamin K antagonists (VKAs). Compared to VKAs, DOACs have a similar or better efficacy/safety profile, with reduced risk of intracerebral hemorrhage (ICH), while the risk of major bleeding and other bleeding harms may vary depending on the type of DOAC. We have critically reviewed available evidence from randomized controlled trials and observational studies regarding the risk of bleeding complications of DOACs compared to VKAs in patients with AF and VTE. Special patient populations (e.g., elderly, extreme body weights, chronic kidney disease) have specifically been addressed. Management of bleeding complications and possible resumption of anticoagulation, in particular after ICH and gastrointestinal bleeding, are also discussed. Finally, some suggestions are provided to choose the optimal DOAC to minimize adverse events according to individual patient characteristics and bleeding risk.

Left Ventricular Thrombosis: Current Perspective and Use of Direct Oral Anticoagulants br

Left ventricular thrombus (LVT) is a serious risk factor for systemic embolism development. Despite the evident danger of this condition, currentguidelines describe management of patients with this potentially fatal complication very briefly. LVT can complicate myocardial infarction where its in-cidence is around 10%, as well as various forms of cardiomyopathies and novel coronavirus infection. According to clinical guidelines vitamin K antag-onists (VKAs) should be used as treatment of choice for thrombus resolution. However, experts point out that this therapy lacks necessary evidentialbase and bears certain difficulties because of pharmacokinetic and pharmacodynamical properties of VKAs. These drawbacks are absent in direct oralanticoagulants (DOACs), the possibility of using which in LVT is being actively studied. As for now, published results of 3 randomised clinical trialshave demonstrated similar safety and efficacy profiles of DOACs and VKAs. Similarly, the majority of retrospective cohort studies did not observesignificant differences between two groups, where some of them have shown superiority of DOACs especially in terms of earlier thrombus resolution.Nevertheless, some studies have found DOACs ineffective and even potentially unsafe regarding systemic embolism. Existing data does not allow toform an unambiguous conclusion about the equivalence of DOACs and VKAs for LVT resolution. Large randomised clinical trials are needed todetermine efficacy and safety of such treatment in these patients.

Acute limb ischemia secondary to vaccine-induced inmune thrombotic thrombocytopenia (VITT) after ChAdOx1 nCoV-19

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a syndrome that resembles to heparin-induced thrombocytopenia (HIT). Platelet factor 4 (PF-4) reacts to a vaccine component resulting formation of immune complex that stimulates an autoimmune reaction triggering platelet consumption causing thrombus formation and producing thrombotic events. When suspected is important to confirm for make a correct anticoagulation management to avoid complications related to unfractioned and low weight heparins use. In this report we describe a case of acute limb ischemia secondary to ChAdOx1 nCoV-19 vaccine (Astrazeneca, Cambridge, UK)Copyright © 2022

Evaluation of a pharmacist-led drive-up anticoagulation clinic during the coronavirus 2019 pandemic

Background: The University of Kentucky HealthCare Anticoagulation Clinic at the Gill Heart and Vascular Institute in Lexington, Kentucky, designed and implemented a drive-up clinic for warfarin management with the goal to minimize person-to-person exposure during the coronavirus disease 2019 (COVID-19) pandemic. Objective: The purpose of this study was to evaluate the effect on warfarin management in a pharmacist-led anticoagulation service when transitioned from an in-person clinic to a drive-up clinic during the COVID-19 pandemic. Methods: This is a retrospective observational cohort study of 68 patients seen in the University of Kentucky HealthCare Anticoagulation Clinic on warfarin therapy for any indication. Patients were included if they had scheduled visits at least 3 times in the period 6 months before, during, and after the initiation of the drive-up clinic. The primary outcome is the difference in time in therapeutic range (TTR) before and during the drive-up clinic. Results: The difference between the mean TTR in period 1 (69.1% ± 23.2%) and period 2 (69.6% ± 19.2%) was not statistically significant (P = 0.882). The mean TTR in period 3 (70.5% ± 20.8%) did not differ in statistical significance from either period 1 (P = 0.688) or period 2 (P = 0.746). Safety outcomes including reported bleeding events and emergency department visits or hospital admissions for bleeding or thrombotic events were consistently low across each period. Conclusion: The results of this study illustrate that a drive-up clinic for warfarin management may be a reasonable alternative approach to providing care for outpatient anticoagulant management and may support nontraditional clinic models for long-term management of anticoagulation and other chronic disease states.

Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study.

BACKGROUND: Early evidence has shown that anticoagulant reduces the risk of thrombotic events in those infected with COVID-19. However, evidence of the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes is limited. AIM: To investigate the association between OACs and COVID-19 outcomes in those with atrial fibrillation and a CHA2DS2-VASc score of 2. DESIGN AND SETTING: On behalf of NHS England, a population-based cohort study was conducted. METHOD: The study used primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. Cox regression was used to estimate hazard ratios (HRs) for COVID-19 outcomes comparing people with current OAC use versus non-use, accounting for age, sex, comorbidities, other medications, deprivation, and general practice. RESULTS: Of 71 103 people with atrial fibrillation and a CHA2DS2-VASc score of 2, there were 52 832 current OAC users and 18 271 non-users. No difference in risk of being tested for SARS-CoV-2 was associated with current use (adjusted HR [aHR] 0.99, 95% confidence interval [CI] = 0.95 to 1.04) versus non-use. A lower risk of testing positive for SARS-CoV-2 (aHR 0.77, 95% CI = 0.63 to 0.95) and a marginally lower risk of COVID-19-related death (aHR, 0.74, 95% CI = 0.53 to 1.04) were associated with current use versus non-use. CONCLUSION: Among those at low baseline stroke risk, people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or unmeasured confounding, including more cautious behaviours leading to reduced infection risk.

Retrospective study of COVID patients diagnosed with VTE

Background: We found that the number of patients diagnosed with PE following COVID began to increase so we wanted to study the trend and triggers In a recent review of our COVID-19 admissions, the incidence of VTE in patients with SARSCoV-2 was 34.5% in imaged patients (119 patients had CT pulmonary angiograms, and 41patients had identified pulmonary thromboembolism (Barnet Hospital, unpublished data, 2020 Kumar el at 2020). Aim(s): To review the number of patients referred to the clinic before and present, make a comparison of number of VTEs before and during COVID pandemic Methods: Retrospective cohort study was conducted from Jan until June 2020. All patients who have confirmed as COVID with VTE were included, suspected COVID were excluded from the study The anticoagulation team all uploaded information to excel and this was analysed and report produced Results: A total of 657 patients were referred to the anticoagulation clinic between Jan to June 2020 Out of them 184 had VTE out of that number 32 were identified as COVID 19. DOAC drug prescribed Total number 32 Apixaban 5 mg BD 20 Rivaroxaban 20 mg 8 Dabigatran 150 mg 0 Edoxaban 60 mg OD 0 LMWH 3 Conclusion(s): Conclusion(s): Most patients did not have any issues related to the VTE but they were still recovering as a result of COVID. They reported feeling tired, short of breath and weak. These are not the usual symptoms reported by VTE patients apart from PE patients We treated them for duration of three months but if these patients were not fully mobile or had on going symptoms we plan to continue the therapy for a total of six months.

FOOD FOR THOUGHT: A CAUTIONARY TALE OF RIVAROXABAN FAILURE IN A MIDDLE-AGED MAN

SESSION TITLE: Rare Cases of Nervous System and Thrombotic Complication Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Rivaroxaban is a dose-dependent inhibitor of factor Xa. It is approved by the FDA to help reduce the risk of blood clots. Although bioavailability is not significantly affected at lower doses (80-100%), bioavailability at higher doses (≥15 mg) is as low as 66% when given without food [1] [3]. Here, we present a patient with poor oral intake who developed deep vein thrombosis (DVT) while on high dose Xarelto. CASE PRESENTATION: Our patient was a 48-year-old male with a history of pulmonary embolism diagnosed two months prior to admission (on 20 mg rivaroxaban daily at home) and morbid obesity who presented with dyspnea, fever, and decreased appetite. His viral PCR was positive for COVID-19, and CT angiogram showed multifocal ground glass opacities but was negative for pulmonary embolism. He was severely hypoxic on room air and required noninvasive ventilatory support in the intensive care unit. He was treated with remdesivir, dexamethasone, and baricitinib. His food intake was extremely poor due to near continuous use of noninvasive ventilation and decreased appetite. A nasogastric (NG) tube was offered, but the patient declined and elected to continue diminished oral feedings. He was able to take all of his home medications including rivaroxaban during this time. On day four, clinical nutrition was consulted because he had 3% loss of body weight. On day seven, the patient developed a fever of 101.6° F. Ultrasound of his lower extremities revealed acute DVTs in his left popliteal vein, posterior tibial vein, and peroneal vein. His anticoagulation was switched to full-dose enoxaparin and a NG tube was placed. On day ten, he was intubated due to worsening hypoxia. Unfortunately, the patient deteriorated into multiorgan failure and died on day seventeen. DISCUSSION: The latest expert guidelines suggest that direct oral anticoagulants (DOAC) should be used over vitamin K antagonists (VKA) in patients with acute venous thromboembolism (VTE) due to lower rates of major bleeding and recurrent VTE as well as convenience. Although VKAs are preferred in situations with extreme weight and renal impairment, DOACs have been proven to be effective for the large majority of patients [2]. Unlike rivaroxaban, the bioavailabilities of other DOACs like apixaban, edoxaban, and dabigatran are all unaffected by food and should be preferred in patients with tenuous oral intake [3]. It is well known that COVID-19 can produce a hypercoagulable state. This factor, combined with our patient's predisposition to blood clots and poor appetite, ended up precipitating new onset VTEs in his left leg despite rivaroxaban therapy. CONCLUSIONS: In patients with decreased oral intake, DOACs other than rivaroxaban should be considered. Patients should be briefed on the importance of taking high dose rivaroxaban with food. Our goal is to bring awareness to providers about this significant pharmacodynamic property of rivaroxaban. Reference #1: Mueck W, Stampfuss J, Kubitza D, Becka M. Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet. 2014 Jan;53(1):1-16. doi: 10.1007/s40262-013-0100-7. PMID: 23999929;PMCID: PMC3889701. Reference #2: Stevens SM, Woller SC, Baumann Kreuziger L, Bounameaux H, Doerschug K, Geersing GJ, Huisman MV, Kearon C, King CS, Knighton AJ, Lake E, Murin S, Vintch JRE, Wells PS, Moores LK. Executive Summary: Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report. Chest. 2021 Dec;160(6):2247-2259. doi: 10.1016/j.chest.2021.07.056. Epub 2021 Aug 2. PMID: 34352279. Reference #3: Lexicomp Online. Copyright © 1978-2022 Lexicomp, Inc. DISCLOSURES: No relevant relationships by Rishika Bajaj No relevant relationships by Ann Hylton No relevant relationships by Roger McSharry No relevant relationships by Krupa Solanki

DURAL VENOUS SINUS THROMBOSIS: A RARE PRESENTING CONSEQUENCE OF COVID-19

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: The severe acute respiratory syndrome coronavirus (SARS-COV2) and its resulting coronary virus 2019 syndrome (COVID-19) has resulted in an unprecedented global pandemic affecting more than 250 million people and resulting in at least 5 million deaths worldwide. Clinical manifestations of the Covid-19 disease process include but are not limited to respiratory dysfunction and failure, coagulopathy, malaise and cytokine storm. We report a case of dural sinus thrombosis (DST) as a sequelae to COVID-19. CASE PRESENTATION: A 26-year-old woman with a history of migraines presented with sudden diffuse headache and photosensitivity. She reported no palpitations, oral ulcers, dizziness, diaphoresis, slurred speech, weakness, paresthesias or recent head trauma. Her presenting vital signs were within normal range. Physical exam was negative for focal neurologic deficits, weakness, or sensory loss. A rapid pregnancy test was negative. D-dimer was 7,200 ng/mL (reference <500 ng/mL). A COVID test was positive. A computed tomography (CT) of the head revealed diffuse hypodensity in the torcula and the transverse sinuses bilaterally extending into the cerebellar folia, suspicious for DST, which was confirmed on magnetic resonance venography. A full hypercoagulable panel resulted negative. It was determined that the patient's coronavirus disease infection resulted in a prothrombotic state and her dural sinus vein thromboses. The patient was started on a high intensity heparin drip for seven days, then transitioned to Dabigatran and Topiramate for management of headache upon discharge. DISCUSSION: COVID-19 typically manifests as fever, hypoxia, and dyspnea. If coagulopathy were to occur, the most common of them are deep vein thromboses. Cerebral thrombotic events, specifically, a DST has been underreported in literature. It is suspected that the burden of cerebral thrombosis in COVID-19 patients is 0.08%. In the same study, it was also identified that 31% of those who developed a cerebral thrombosis also had other hypercoagulable risk factors not present in this patient. Advancement in neuroimaging has allowed these thrombotic issues to be identified, however, early recognition, especially with a lack of risk factors, creates a less straightforward management plan. Our patient manifested a DST in the setting of an active COVID-19 infection. Higher levels of evaluation are required in patients who test positive for Covid-19 when clinically indicated. Such indications include headaches that are new in onset, severe in nature, and diffuse. Delayed diagnosis and management can be permanently damaging. CONCLUSIONS: Dural venous sinus thrombosis is a rare, yet deadly complication of COVID-19. All risk factors and other etiologies of hypercoagulable states should be ruled out followed by early detection based on clinical and physical exam, and accompanied by appropriate imaging followed by prompt intervention. Reference #1: Baldini, T., Asioli, G. M., Romoli, M., Carvalho Dias, M., Schulte, E. C., Hauer, L., Aguiar De Sousa, D., Sellner, J., & Zini, A. (2021). Cerebral venous thrombosis and severe acute respiratory syndrome coronavirus-2 infection: A systematic review and meta-analysis. European journal of neurology, 28(10), 3478–3490. https://doi.org/10.1111/ene.14727 Reference #2: Hemasian, H., & Ansari, B. (2020). First case of Covid-19 presented with cerebral venous thrombosis: A rare and dreaded case. Revue neurologique, 176(6), 521–523. https://doi.org/10.1016/j.neurol.2020.04.013 Reference #3: Thompson, A., Morgan, C., Smith, P., Jones, C., Ball, H., Coulthard, E. J., Moran, E., Szewczyk-Krolikowski, K., & Rice, C. M. (2020). Cerebral venous sinus thrombosis associated with COVID-19. Practical neurology, practneurol-2020-002678. Advance online publication. https://doi.org/10.1136/practneurol-2020-002678 DISCLOSURES: No relevant relationships by Steven Douedi No relevant relationships by slam Elkherpitawy No relevant relationships by Justin Ilagan No relevant relationships by David Kountz No relevant relationships by Anton Mararenko No relevant relationships by Mihir Odak

Anticoagulants: dose control methods and inhibitors

These days, anticoagulants are in great demand. They are used as a prophylaxis for thromboembolic complications in various diseases and conditions in general therapeutic practice, cardiology, neurology, as well as obstetrics to manage high-risk pregnancies. The relevance of anticoagulants competent use has come to the fore in connection with the emergence of a new disease – COVID-19 and its serious complications such as developing thrombotic storm, in which the timely applied anticoagulant therapy is the key to the success of therapy. The risk of bleeding should be considered when using any anticoagulant. Age, impaired renal function and concomitant use of antiplatelet agents are common risk factors for bleeding. Moreover, only vitamin K antagonists and heparin have specific antidotes – vitamin K and protamine, respectively. Inhibitors of other anticoagulants are universal presented as inactivated or activated prothrombin complex concentrate and recombinant factor VIIa. Hemodialysis effectively reduces dabigatran concentration, activated charcoal is effective in the case of recent oral administration of lipophilic drugs. Research on new antidotes of currently available anticoagulants is under way, similar to testing of new types of anticoagulants that are sufficiently effective in preventing and treating thromboembolic complications with minimal risk of hemorrhagic. The main contraindication to anticoagulants use is the doctor's ignorance of the mechanisms of drug action and opportunities for suppressing its effect.

The role of DOACs in anticoagulant treatment in a tertiary Hospital of Thessaloniki, Greece

Introduction: Low molecular weight heparins are used extensively in anticoagulant therapy, due to their safer profile, in comparison to other anticoagulants. Direct Oral AntiCogulants (DOACs) have been initiated in anticoagulant therapy as a safer treatment choice than coumarin derivatives. Objectives: The aim of this study was to investigate the use of oral and injectable anticoagulants, and especially the place of DOACs in anticoagulant treatment, in a tertiary Hospital of Thessaloniki, Greece. Methods: The data were collected by investigating prescriptions from the Hospital Pharmacy of a tertiary Hospital in Thessaloniki, Greece. Prescriptions of oral and injectable anticoagulants for hospitalized patients were collected during the period from June to September 2021. The consumption of the following oral and injectable anticoagulants was recorded in DDDs: acenocumarol, rivaroxaban, apixaban, dabigatran, heparin, enoxaparin, tinzaparin, bemiparin and fondaparinux. Results: The total amount of anticoagulants used was 53,041 DDDs, of which 97,9% were injectable anticoagulants whereas 2,1% were oral anticoagulants. DOACs represented the 1,8% of the anticoagulants used. The consumption of injectable anticoagulants for the hospitalized patients was 51,936 DDDs, of which 63.5% was enoxaparin, 18.5% was tinzaparin, 6.3% was heparin, 6.1% was bemiparin, and 5.6% was fondaparinux. The consumption of acenocumarol was 176 DDDs and the consumption of DOACs was 929 DDDs, with the percentage of rivaroxaban, apixaban, and dabigatran being 46%, 45% and 9% respectively. Indications with the highest prevalence for patients on enoxaparin was COVID 19, heart failure, stroke, angina pectoris, malignancy. Indications with the highest prevalence for patients on tinzaparin was COVID 19, malignancy, stroke. Indications with the highest prevalence for patients on bemiparin was malignancy, COVID 19, aortic valve disease, stroke. Heart failure, stroke and atrial fibrillation were the indications with highest prevalence in patients on DOACs. Acenocumarol was used mainly for heart failure, stroke and aortic valve stenosis. Conclusion: Injectable anticoagulants, and mainly low molecular weight heparins were the treatment of choice in hospitalized patients. Oral anticoagulants represented only a very small proportion (2,1%) of the anticoagulants used. DOACs have replaced coumarin derivatives, representing the 86% of oral anticoagulants in clinical use. Nevertheless, the percentage of DOACs was very low (1.8%) in the total consumption of anticoagulants, with rivaroxaban and apixaban being the most commonly used DOACs. Injectable anticoagulants, especially enoxaparin, are preferred by the clinicians as a safer choice for managing high risk thrombosis in hospitalized patients. DOACs, Direct Oral AntiCogulants, anticoagulants, NOACs.

Cerebral Venous Sinus Thrombosis(CVST) As A Complication Of COVID-19 Infection Presenting As Post COVID-19 Headache

Objective: NA Background: COVID-19 infection has been associated with a state of hypercoagulability. The hypercoagulability typically presents as a Deep Venous thrombus or Pulmonary Embolism but rarely can manifest as CVST even after recovery from the original COVID-19 infection. Case Report: 27-year-old Caucasian female who had a COVID-19 infection 2 weeks prior, presented with 4 days of persistent headaches associated with nausea and vomiting. Patient also had episodes of rightward gaze without loss of awareness. No prior history of seizures. NIHStrokeScale was 0. CT head showed a hyper density within the sylvian fissure and the sulci of the right temporal and right lateral frontal lobes suggestive of subarachnoid hemorrhage(SAH);CTA head showed cerebral venous sinus thrombosis(CVST) involving straight sinus, most of vein of Gale, right transverse and right sigmoid sinuses that was also seen on MR venogram. MRI brain showed illdefined edema in a distribution concerning for venous infarct due to CVST. CTA chest also showed multiple bilateral pulmonary emboli. EEG showed focal slowing in the right hemisphere and no epileptiform discharges. Patient was started on heparin and transitioned to Dabigatran on discharge. Past medical history was remarkable for Wolf-Parkinson-White syndrome (s/p ablation), obesity and depression. Patient has no personal or family history of hypercoagulability or malignancy. Patient reported birth control use which she stopped 3 weeks prior to this presentation. Patient stopped cigarette smoking 5 years ago. Patient has a healthy 2.5-year-old son and has no history of miscarriages. Patient was not vaccinated for COVID. Results: NA Conclusions: This is a case of CVST without major classical predisposing factors for CVST however patient had recent COVID-19 infection which should be considered as a potential risk factor for CVST. Considering MR venogram of the head in patients presenting with persistent post-COVID headaches can help identify this potential life threating condition in a timely manner.

New disposable ion-selective sensors for the determination of dabigatran etexilate: The oral anticoagulant of choice in patients with non-valvular atrial fibrillation and COVID-19 infection

Selective, sensitive, and reproducible ion-selective electrodes containing dabigatran etexilate- phosphotungstate ion pair as a modifier have been fabricated to determine dabigatran etexilate in pure and pharmaceutical dosage form. The modified electrodes ion selective carbon paste electrode and ion selective pencil graphite electrode showed fast and linear responsewithin a concentration range of 1.0 × 10−5to 1.0 × 10−2 M and 1.0 × 10−6to 1.0 × 10−2 M with a detection limit of 4.36 × 10−6 M and 4.26 × 10−7 M by ISCPE and ISGPE, respectively. Electrodes are selective to dabigatran etexilate over common excipients. The present study demonstrated the determination of dabigatran etexilate in pure and pharmaceutical dosage forms with high accuracy and precision.

American Heart Association (AHA) Scientific Sessions-2021 Annual Meeting

The AHA Scientific Sessions, the annual meeting of the Amer-ican Heart Association, highlights the latest cutting-edge basic, translational and clinical research in cardiovascular diseases. This year, the conference took place virtually due to the COVID-19 pandemic and comprised several days of live sessions and on-demand virtual content, including posters and prerecorded presentations.

Dabigatran in patients with atrial fibrillation after COVID-19 hospitalization: an update of the ANIBAL protocol.

COVID-19 increases the risk of atrial fibrillation (AF) and thrombotic complications, particularly in severe cases, leading to higher mortality rates. Anticoagulation is the cornerstone to reduce thromboembolic risk in patients with AF. Considering the risk of hepatotoxicity in patients with severe COVID-19 as well as the risk of drug-drug interactions, drug-induced hepatotoxicity and bleeding, the ANIBAL protocol was developed to facilitate the anticoagulation approach at discharge after COVID-19 hospitalization. However, since the publication of the original algorithm, relevant changes have occurred. First, treatment of COVID-19 pneumonia has been modified with the use of dexamethasone or remdesivir during the first week in patients that require oxygen therapy, and of dexamethasone and/or tocilizumab or baricitinib during the second week in patients that necessitate supplementary oxygen or with a high inflammation state, respectively. On the other hand, metabolic syndrome is common in patients with AF as well as metabolic-associated fatty liver disease, and this could negatively impact the prognosis of patients with COVID-19, including high transaminase levels in patients treated with immunomodulators. The EHRA guidelines update also introduce some interesting changes in drug-drug interaction patterns with the reduction of the level of the interaction with dexamethasone, which is of paramount importance in this clinical context. Considering the new information, the protocol, named ANIBAL II, has been updated. In this new protocol, the anticoagulant of choice in patients with AF after COVID-19 hospitalization is provided according to three scenarios: with/without dexamethasone treatment at discharge and normal hepatic function, transaminases ≤2 times the upper limit of normal, or transaminases >2 times the upper limit of normal.

Appearing and disappearing right-heart thrombus: A case reporto in COVID- 19 patient

Aims: Venous thromboembolism represents frequent complication of patients with severe COVID-19 disease. Several reports about atypical thrombosis are described, rarely it has been described a right venticular thrombus during the course of infection. We report a case of right endoventricular thrombosis in a patient with SARSCov- 2 pneumonia. Methods and results: A 58-year-old man was admitted to our ward for severe respiratory failure in interstitial pneumonia. The nasopharyngeal swab for COVID-19 resulted positive. Steroids and prophylaxis with LMWHwere started, associated to CPAP to maintain good gas exchange. During hospitalization a venous ECD was performed with evidence of left popliteal thrombosis despite the therapy. D-Dimer was 44±3 ng/ml. A new onset AF was documented at the telemetry, without troponin elevation. A cardiac ultrasound was performed showing a right endoventricular lesion of 1.8 cm adhering to the free wall of the right ventricle. A CT-pulmonary angiogram (CTPA) resulted negative for pulmonary embolism and confirmed suspected right ventricular thrombus. Treatment with fondaparinux 7.5mg was started. After 10 days, cardiac ultrasound shown complete resolution of thrombosis, and CT confirmed the disappearing of the mass. Dabigatran 150 mg twice/day was started. Patient clinically improved and he was discharged after 20 days of hospitalization. Conclusions: SARS-CoV-2 infection may cause inflammation with cytokine storm and hypercoagulability leading to venous thromboembolism. Atypical thrombus formation was reported, including right-ventricle free wall. Early caridac ultrasound was critical to make diagnosis and starting prompt treatment, therefore routine cardiac ultrasound is mandatory in severe COVID-19 patients.

In transit thrombosis in CoViD-19 patient

Background: Venous thromboembolism represents frequent complication of patients with severe CoViD-19 disease. The occurrence of venous thromboembolism is mainly in typical district, however several reports about atypical thrombosis are described. We report a case of isolated right endoventricular thrombosis in a patient with SARS-CoV-2 infection. Case Report: A 60-year-old man was admitted to our ward for severe respiratory failure in interstitial pneumonia. The nasopharyngeal swab for CoViD-19 resulted positive. Prophylaxis with LMWH were started associated to CPAP to maintain good gas exchange. During hospitalization a new onset AF was documented at the telemetry and an echocardiogram was performed showing a right endoventricular lesion of 1.8 cm adhering to the free wall. A CTpulmonary angiogram (CTPA) resulted negative for pulmonary embolism. Doppler ultrasound showed left popliteal thrombosis. A treatment with fondaparinux was started. After 10 days, an echocardiogram was repeated showing complete resolution of thrombosis. Another CTPA confirmed the absence of pulmonary embolism. The patient clinically improved and he was discharged with dabigatran. Conclusions: SARS-CoV-2 infection may cause hypercoagulability and inflammation leading to venous thromboembolism and this seems to be related with worse outcome of these patients. For this reason, to monitor the venous thrombosis complication is an important step in the assessment of patients with CoViD-19.

Using Pharmacogenetics of Direct Oral Anticoagulants to Predict Changes in Their Pharmacokinetics and the Risk of Adverse Drug Reactions.

Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.

Thromboelastography utilization for dabigatran reversal in a patient with acute kidney injury.

PURPOSE: This case report describes utilization of thromboelastography (TEG) in the setting of an acute major bleed in a patient on dabigatran who had concomitant acute kidney injury. SUMMARY: An 80-year-old female presented to the emergency department after a fall with complaints of pain in her knee, shoulder, and hip. Her medical history was significant for coronary artery disease, for which she took clopidogrel 75 mg daily, and atrial fibrillation, for which she took dabigatran 150 mg twice daily. The physical exam was remarkable for pain within the shoulder, hip, and knee, which had swelling and ecchymosis that extended into the right thigh. Given the possibility of compartment syndrome with multiple possible etiologies of coagulopathy, TEG and computed tomography angiography (CTa) of the right lower extremity were performed. The initial TEG showed prolonged R time and activated clotting time, indicating clotting factor dysfunction with no additional coagulopathy noted, including antiplatelet effects. On the basis of the TEG and CTa findings, it was decided to reverse dabigatran with 5 grams of idarucizumab. Approximately 1 hour after administration of idarucizumab, the patient was taken to interventional radiology where a limited angiogram of the right lower extremity showed no active extravasation. Because of the patient's renal dysfunction and the possibility of rebound hypercoaguability, repeat TEG tests were ordered at 4 and 8 hours after the initial reversal to ensure clearance of idarucizumab-dabigatran complexes. The repeat TEG values showed complete reversal of the initial coagulopathy noted. During the admission, the patient required no blood transfusions or surgical interventions and all her initial laboratory results improved. CONCLUSION: Serial TEG testing was successful at managing multiple coagulopathies in a patient at risk for trauma-induced compartment syndrome.

Dabigatran, the oral anticoagulant of choice at discharge in patients with non-valvular atrial fibrillation and COVID-19 infection: the ANIBAL protocol.

Atrial fibrillation is a frequent complication among patients with severe coronavirus disease-2019 (COVID-19) infection. Both direct and indirect mechanisms through COVID-19 have been described to explain this relationship. COVID-19 infection increases the risk of developing both arterial and venous thrombotic complications through systemic coagulation activation, leading to increased mortality. Chronic oral anticoagulation is essential to reduce the thromboembolic risk among AF patients. Switching to low-molecular-weight heparin has been recommended during hospitalization for COVID-19 infection. Of note, at discharge, the prescription of direct oral anticoagulants may offer some advantages over vitamin K antagonists. However, oral anticoagulants should only be prescribed after the consideration of drug-drug interactions with antiviral therapies as well as of the risk of hepatotoxicity, which is common among individuals with severe COVID-19 pneumonia. Not all anticoagulants have the same risk of hepatotoxicity; dabigatran has shown a good efficacy and safety profile and could have a lower risk of hepatotoxicity. Furthermore, its metabolism by cytochrome P450 is absent and it has a specific reversal agent. Therefore, dabigatran may be considered as a first-line choice for oral anticoagulation at discharge after COVID-19 infection. In this review, the available information on the antithrombotic management of AF patients at discharge after COVID-19 infection is updated. In addition, a practical algorithm, considering renal and liver function, which facilitates the anticoagulation choice at discharge is presented.