ID: 219407 The Cardiac Patient and Neuromodulation, When Anticoagulation Dictates the Intervention

Introduction: Patients with cardiac comorbidities present unique challenges for undergoing interventional pain procedures. Consensus guidelines on safe anticoagulation management are categorized by procedure, patient specific bleeding risk factors, and class of anticoagulation (Table 1, Table 2).1 Specifically, some procedures occur in close proximity to the spinal cord, require large gauge needles and styletted leads, while others are in compressible locations with minimal tissue disruption. Further, pain-induced hypercoagulation increases the risk of thrombo-vascular events.1 This accentuates the importance of interdisciplinary perioperative coordination with the prescribing cardiologist. Case: A 71-year-old male with past-medical-history of CABG, bilateral femoral-popliteal bypass, atrial fibrillation on apixaban and ticagrelor, and multiple cardiac stents presented with intermittent shooting axial back pain radiating to right buttock, lateral thigh, and calf, worsened with activity. MRI demonstrated thoracic myelomalacia, multi-level lumbar disc herniation, and moderate central canal stenosis. An initial multi-model treatment approach utilizing pharmacologic agents, physical therapy, ESI's, and RFA failed to alleviate symptoms. After extensive discussion with his cardiologist, he was scheduled for a three-day SCS trial. Ticagrelor and apixaban were held throughout the 3-day trial and for 5 and 3 days prior, respectively, while ASA was maintained. Successful trial with tip placement at T6 significantly improved function and pain scores (Figure 1). Upon planned percutaneous implant, the cardiologist recommended against surgical implantation and holding anticoagulation. Alternatively, the patient underwent bilateral lumbar medial branch PNS implant with sustained improvement in lower back symptoms. However, he contracted COVID, resulting in delayed lead explanation (>60 days) without complication. Conclusion(s): Interventional pain practice advisories are well established for anticoagulation use in the perioperative period.1,2 However, there is limited high-quality research on the appropriate length to hold anticoagulation prior to surgery for high thrombotic risk patients. Collegial decision making with the cardiologist was required to avoid deleterious procedural complications. However, they may be unfamiliar with the nuances between interventions or between trial and implant. Prospective studies have shown that low risk procedures, such as the PNS, may not require holding anticoagulants.3 Other case data has demonstrated post-SCS epidural hematoma with ASA use after being held for 1-week prior to surgery. Our patient was unable to undergo SCS implant and instead elected for a lower risk procedure with excellent efficacy. 4 However, delayed PNS lead extraction due to COVID19 hospitalization presented further risk of infection and lead fracture.5 PNS may prove to be an appropriate treatment option for patients who are anticoagulated and are not SCS candidates. Disclosure: Elliot Klein, MD,MPH: None, Clarence Kong, MD: None, Shawn Sidharthan, MD: None, Peter Lascarides, DO: None, Yili Huang, DO: NoneCopyright © 2023

The 'Tic'king Bleeder: A Rare Case of Bleeding Dieulafoy's Lesion in a Jejunal Diverticulum

Introduction: Dieulafoy lesion (DL) is a relatively rare and arguably under-recognized condition, accounting for 1-2% of acute GI bleeding. Most bleeding DLs occur in the stomach, followed by the small intestine, with less than 1% occurring in the jejunum. Bleeding DL on a jejunal diverticulum is even more rare, with a handful cases described in the literature. Here we present a rare case of a bleeding DL in a jejunal diverticulum with its endoscopic management. Case Description/Methods: A 65-year-old female with history of COVID-19 infection one month prior to presentation treated with steroids and therapeutic anticoagulation presented to the ED after having multiple episodes of coffee-ground emesis and two episodes of syncope at home. Last dose of Apixaban was 12 hours prior to admission. Physical exam revealed BP of 90/60 on Norepinephrine infusion, HR of 96, abdominal exam was soft and nontender, DRE revealed melena. Hemoglobin/hematocrit was significantly decreased at 3.6/12.8. Patient was appropriately resuscitated with blood products and fluids, and she was scheduled for an EGD. Initial EGD did not identify a clear source of her bleeding, and she was scheduled for colonoscopy. Colonoscopy with deep cannulation of the terminal ileum up to 40cm revealed significant amounts of fresh blood all throughout the colon and terminal ileum. Decision was made for push enteroscopy, which revealed a jejunal diverticulum containing a Dieulafoy lesion with an overlying clot (Image A). The lesion was first injected with epinephrine at 2 sites followed by a clot removal overlying the lesion using 13-0 circular snare. A clear stigma of recent bleeding was noticed from the lesion after clot removal (Image B), after which 2 metallic clips were placed over the lesion to achieve hemostasis (Image C). The patient had no further episodes of bleeding and was follow up in clinic eventually, recovering well. Discussion(s): Because of the life-threatening nature of Dieulafoy lesions, identification is of paramount importance for treatment purposes. Jejunal DLs are a rare entity but should be considered in cases with negative bidirectional endoscopies. In our case, push enteroscopy helped identify the bleeding lesion. DL in a diverticulum can pose a challenge to the endoscopist due to difficulty of access to the lesion. Epinephrine injection followed by mechanical clipping showed a positive outcome in our case which can be considered while approaching bleeding DLs in a diverticulum. (Figure Presented).

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.

Drug-induced pericarditis

Though not common, drug-induced pericarditis is a serious condition, since pericardial tamponade, should it develop, may be life-threatening. As the number of drugs is constantly expanding, so does the proportion of those capable of causing pericarditis. The authors reviewed the relevant literature in the PubMed database and complemented it with information from the VigiBase database. In their article, the authors present current knowledge about the mechanisms of origin and level of risk of drug-induced pericarditis and discuss relevant information on individual drugs divided into 7 classes. Some medicines are associated with a high risk of developing pericarditis, a fact to be taken into account when treating patients with these agents. © 2022 Czech Society of Cardiology Z.S. All rights reserved.

Desensitization to Pfizer-BioNTech Covid-19 mRNA-based vaccine in patients with severe hypersensitivity to PolyEthylene Glycol and/or Polysorbate 80

Background: Covid-19 viral infection affects strongly the populations in the world by the level of morbidity, mortality and the economic impact. A worldwide vaccination program was developed since the end of 2020 to limit the propagation of the virus and the development of variants. In USA and Europe the risk of an allergic reaction is estimated to be 1.31 (95 % CI, 0.90-1.84) per million vaccine dose. The excipients are considered to be the most probable cause of IgE-mediated allergic reactions: PolyEthylene Glycol (PEG) for the Moderna and the Pfizer-BioNTech vaccines and Polysorbate 80 (P80) for the Astra Zeneca and the Johnson & Johnson. P80 presents clinical cross-reactivity with PEG. Patients with a history of severe allergic reaction to PEG or P80 should avoid the vaccination. However, some of them strongly wanted to be vaccinated because their accumulated risk factors for severe infection. Method(s): To 4 severely PEG/P80 allergic patients (grade 3 of anaphylaxis), we proposed a desensitization protocol (7 steps in 90 min + 60 min of observation) with the Pfizer-BioNTech vaccine. Each injection was performed alternately in the deltoid muscle (SC for 2 treated by apixaban) every 15 min. Two patient received all the injections in the same arm due to insufficient lymphatic drainage post mastectomy. The protocol was repeated 1 month and once again 6 months later for the second and the booster doses respectively. One patient didn't received the last one because she was meanwhile moved in palliative treatment. We followed the modification of their immunological status. All patients took a premedication with bilastine 20 mg and montelukast 10 mg (without PEG/P80) 24 h and 3 h before each protocol. Result(s): No patient developed adverse nor allergic reaction after the successive vaccinations. Conclusion(s): We c an p ropose adesensitization protocol to the COVID-19 Pfizer-BioNTech vaccine to patients with severe hypersensitivity to PEG/P80. The desensitization is well tolerated and followed by an increase of specific antibodies and an evolution of antibody level like patients who received the total dosis (0.3 ml) in one injection. (Figure Presented).

Development of a multivariate model with desirability-based optimization for simultaneous determination of five co-administrated drugs for the management of COVID-19 infection in their dosage forms via validated RP-HPLC method

More than 2.9 million people have died as a result of the global demographic impact of the coronavirus illness of 2019 (COVID-19). Numerous antiviral and anti-inflammatory medications have FDA approval to treat COVID-19 patients. For the simultaneous determination of COVID-19 utilized medications (Remdesivir, Moxifloxacin, Dexamethasone, Apixaban, and paracetamol) in their dosage forms, a sensitive technique has been developed and validated. The aforementioned medications were separated and quantified with the help of experimental design. The Box-Behnken design was used in the experiment to optimize the chromatographic method's analytical parameters. It employed RP-HPLC with a UV detector. An INERTSIL ODS-3 C18 column (5 µm, 250 × 4.6 mm) with mobile phase composed of acetonitrile: 30 mmoL potassium dihydrogen phosphate buffer (pH = 7.5) (50:50, v/v), at room temperature was employed to separate the aforementioned drugs. Paracetamol was linear over the concentration range (1–50 µg/mL), Moxifloxacin (5–70 µg/mL), Apixaban (5–70 µg/mL), Dexamethasone (1–100 µg/mL), and Remdesivir (5–100 µg/mL). According to ICH guidelines, the new approach underwent thorough validation. Between the proposed method's results and those from the reference or reported methods, there was no significant difference. The technique is simple to use in research of the cited medications in their dosage forms for quality control aspects.

Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19.

BACKGROUND: Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. OBJECTIVES: We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19. METHODS: Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit-level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group. RESULTS: Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent. CONCLUSIONS: Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID [FREEDOM COVID Anticoagulation Strategy]; NCT04512079).

Possible immune reaction to COVID-19 vaccination - a case report

Introduction Side effects may occur after vaccination against COVID-19. Temporary reactions such as redness, swelling and pain at the injection site, high temperature, fever, tiredness, etc. may be signs of the body's response to the vaccine. Such reactions usually develop within two days after vaccination and last for a few days. With the growing number of vaccinations against SARSCoV- 2 a rising number of reports also showed serious side effects. In some of the most severe cases, life-threatening thrombotic events may develop. We present a case that shows further symptoms that may be due to an immune reaction to the vaccine. Method In this case report a 67 male smoker presented to our outpatient clinic in April 2022. A few days after vaccination against SARS-CoV-2 with an mRNA vaccine the patient developed pain at all finger tips. The clinical examination showed cool and livid discoloration of all fingers to different degrees;toes were not involved. The symptoms developed progressively over the following weeks into a severe form with progressive fingertip skin necrosis. Results The blood test showed a CRP of 9.18 mg/l (reference range: 0-3 mg/l) as well as an increased fibrinogen and factor VIII activity. D-dimers were only slightly increased to 290 ng/ml (reference range: < 230 ng/ml) during initial examination. Cold agglutinins, cryoglobulin and cryofibrinogen were tested negative. Angiologic examination revealed small multiple thrombi in the ulnar and digital arteries. Furthermore, the resting ECG showed no dilated ventricles and no indication of a hemodynamically relevant defect. The assessment revealed a good cardiac function overall with no evidence of embolism. Therapy was started with Nifidipine (gold standard in Raynaud's disease), Eliquis 5 mg 1-0-1, and diclofenac following hospital admission. In the further course, the therapy regimen was changed to Ilomedin IV for 4 days once a month. After two weeks, symptoms significantly improved and the signs of necrosis at the fingers disappeared. Conclusion In summary, a circulatory perfusion disorder associated with microthrombotic events may be a possible side effect of SARS CoV-2 vaccination. A combination of Nifidipine, DOAC and pain therapy has been shown to be an effective treatment of "COVID-fingers" in this case report.

Frequent need for apixaban dose adjustment for atrial fibrillation in an unselected acute medical admission population during the COVID 19 pandemic

Background: During the COVID-19 pandemic, systematic switching patients of eligible patients with atrial fibrillation from warfarin to direct oral anticoagulants (DOACs) was encouraged to simplify drug dosing and obviate the need for regular monitoring. Regional exclusions to switching included mechanical heart valves, moderate to severe mitral stenosis and stage 5 chronic kidney disease (estimated glomerular filtration rate [eGFR]< 15ml/min/1.73m2). However, each DOAC requires dose adjustment depending on renal function and other patient factors. Purpose(s): Failure to dose reduce when indicated leads to excessive serum drug concentration and increased risk of major haemorrhage, particularly in patients who are acutely unwell. We thus quantified the likelihood of need for dose adjustment in an unselected acute medical admission population. Method(s): While on call, a single investigator prospectively identified all patients admitted on the acute medical or cardiology take-in between 1/ 12/21 and 1/2/22 who were taking apixaban for atrial fibrillation. Apixaban was selected as the study DOAC as it was the most commonly used DOAC but had the most complex dose adjustment algorithm and hence risk of dose error. In order to determine the appropriate drug dosage, patient age, weight, serum creatinine and eGFR were recorded. Dose reduction to 2.5mg was required if the patient meet 2 of the following 3 criteria of [age>80 years, weight <60kg, serum creatinine >133umol/l], or a single criterion, had an eGFR <30ml/min/1.73m2. Drug discontinuation was required if eGFR was <15ml/min/1.73m2. Result(s): All patients identified (n=50) had a CHA2DS2-VASc score of >=2. Patients with active COVID-19 infection were excluded. Mean age was 77.2 years (range 46-102). Mean weight was 78kg (range 52-101). Mean serum creatinine was 212umol/l (range 62-595). Mean eGFR was 33ml/min/1.73m2 (range 8 to >60). Of the 50 patients, 24 (48%) were taking the appropriate apixaban dose on admission which did not require dose adjustment (18 of whom were appropriately taking 5mg bd and 6 were taking 2.5mg bd). Dose reduction from 5mg bd to 2.5mg bd was required in 17 (34%) patients. Stopping treatment, at least temporarily due to eGFR<15ml/min/1.73m2, was indicated in 9 (18%) of patients. No patient required an increase in drug dose. (Graph 1) Conclusion(s): Over half of acute medical or cardiology patients admitted within a COVID-19 setting and taking apixaban for atrial fibrillation required at least temporary drug dose adjustment or discontinuation. Clinicians should expect that adjustment of apixaban dose may be required during acute admission.

Acute Transcatheter Aortic Valve Replacement Failure Secondary to Covid-19 Infection

Background Valve thrombosis is a documented cause of prosthetic valve failure. Common features include increased cusp thickness, reduced cusp mobility, and increased transvalvular gradient. Case reports have been published of prosthetic valve thrombosis secondary to COVID-19 infection, but this may represent the first documented case of bioprosthetic transcatheter aortic valve replacement (TAVR) thrombosis in the setting of COVID-19. Case A 90 year-old female with atrial fibrillation on apixaban and severe aortic stenosis status-post TAVR with normal valve function on recent echocardiogram presented in clinic with acute chest pain. She was found to have COVID-19 infection and severe bioprosthetic valvular regurgitation with leaflet thickening, abnormal cusp mobility, and elevated transvalvular gradient. [Formula presented] Decision-making Given the time course of valve failure, COVID-19 infection, and echocardiographic features, the patient was diagnosed with bioprosthetic valve thrombosis secondary to COVID-19. She was optimized with diuresis and continued on apixaban before undergoing valve-in-valve TAVR with resolution of valvular dysfunction. Conclusion This case contributes to a body of literature describing thrombotic complications in patients with valve replacement and COVID-19 infection despite concurrent anticoagulation. Increased vigilance and investigations are warranted to better characterize thrombotic risk and optimal antithrombotic strategies in this patient populace.Copyright © 2023 American College of Cardiology Foundation

"Two in One": Rare Case of Dual Left Anterior Descending Artery

Background Coronary artery anomalies are rare with an incidence of 0.3 to 1.3%. Here we are describing an extremely rare anomaly of the left anterior descending artery (LAD) Case A 55-year-old female with covid-related chronic hypoxemic respiratory failure, pulmonary embolism on apixaban and IgG deficiency on IVIG therapy presented with dyspnea and increased oxygen requirement. EKG had no ischemic changes. Troponins were negative. CTPE was negative. TTE showed normal EF with no valvular or wall motion abnormalities. Right ventricular systolic pressure wasn't calculated due to insufficient TR. Decision-making Left and right heart catheterization was negative for coronary artery disease, bridging or pulmonary hypertension but revealed a dual LAD system and an interesting right coronary anatomy as seen below. These findings were confirmed with a coronary CT angiogram (done in the past that we reviewed again). Stress test was negative for ischemia of the apical anterior wall. The patient reported undergoing coronary angiograms multiple times at other institutions before for recurrent chest pains but has not been diagnosed with anomalous coronary artery until current admission. Conclusion This is a rare anomaly that has been not described before (upon our literature review). It is important to recognize dual LAD system as Inability to visualize the additional vessel, especially when the long LAD originates from the right coronary sinus, can be misinterpreted for mid-LAD occlusion. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

Primary Cardiac Lymphoma with an Aggressive Hostile Take-Over

Background Primary cardiac lymphoma (PCL) is an extranodal lymphoma involving only the heart and/or pericardium. PCL accounts for 2% of primary cardiac tumors and 0.5% of extranodal lymphomas. Its diagnosis is usually delayed due to rarity and non-specific findings. Case A 77-year-old man with Alzheimer dementia, atrial fibrillation on apixaban, and COVID-19 illness 3-weeks prior, who presented to the hospital with diffuse abdominal discomfort, fatigue, anorexia, and hypoactivity. Patient was tachycardic and normotensive with pronounced jugular venous distention, non-collapsing with respiration. ECG revealed sinus tachycardia, first degree atrioventricular (AV) block and chronic LBBB. Cardiac troponins were mildly elevated without significant delta. An abdominopelvic CT revealed an incidental, large pericardial effusion (PE). Bedside echocardiogram confirmed a large hemodynamically significant PE as well as a mass-like echogenicity encasing and infiltrating the pericardium and myocardium at the basal aspect of the right ventricle free wall. Decision-making In view of recent COVID-19 infection, he was started on indomethacin and colchicine for suspected viral or neoplastic pericarditis. Pericardiocentesis drained 900ml of amber to serosanguineous fluid with quick hemodynamic improvement. Fluid analysis was non-diagnostic for neoplasia. Subsequently, he developed symptomatic bradycardia with an intermittent complete AV block with junctional escape rhythm, transitioning to a second-degree AV block after removal of beta-blocker. Awaiting permanent pacemaker implant, he developed ventricular fibrillation with sudden cardiac death that required prolonged unsuccessful ACLS. Autopsy revealed an extensive infiltrative tumor, predominantly right-sided, consistent with primary cardiac B-cell lymphoma. Conclusion PCL should be part of the working diagnosis in patients presenting with a pericardial effusive process in combination with a right sided myocardial mass. Early cardiac MRI/PET scan or biopsy should be considered when the diagnosis is not certain. Prompt diagnosis could allow for treatment that potentially prolongs survival.Copyright © 2023 American College of Cardiology Foundation

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.

Catastrophic Antiphospholipid Crisis Triggered by Anticoagulant Switch

Case report - Introduction: The COVID-19 pandemic led to drastic changes for some patients on warfarin for venous thromboembolic (VTE) disease and atrial fibrillation. Warfarin monitoring necessitates frequent interaction with healthcare workers, which is sufficiently risky for COVID-19 transmission. As a result, selected patients were swapped over to novel oral anticoagulants (NOACs). Our patient was changed without investigating for antiphospholipid syndrome (APLS);it later transpired he was triple antibody positive. He presented in a crisis and we describe his narrative. Patients on warfarin due to presumed unprovoked venous thromboembolic disease should not be swapped to NOACs without completing, or checking, previous antiphospholipid antibody testing. Case report - Case description: A 73-year-old gentleman presented locally in August 2020 with erythema over the anterolateral surface of his left leg. He was initially treated with antibiotics for presumed cellulitis. Within a few days this lesion became necrotic and rapidly spread. At this point, he was transferred to a tertiary rheumatology centre. Within days to weeks, he developed several necrotic lesions affecting his trunk and limbs, with facial sparing noted. Approximately 30-35% of his whole-body surface became involved. He soon developed an oxygen requirement, with CTPA demonstrating lymphocytic interstitial pneumonitis without evidence of pulmonary emboli (PE). Throughout his admission, he had several other pathologies such as hyponatraemia that required level 2 care and severe noninfectious diarrhoea. Skin biopsy identified thrombotic vasculopathy. Serology confirmed triple positive antiphospholipid antibody status and a dsDNA titre of>400 iU/mL. This was the first-time serology had been undertaken despite a history of three deep vein thrombosis (DVT) episodes and two PE incidents. He had no history of SLE symptoms. His initial management for vasculitis secondary to APLS at the point of limited necrosis consisted of IV methylprednisolone followed by rituximab and PO prednisolone. While there was some delay in the progression of his disease, new areas of necrosis arose, leading to the patient receiving cyclophosphamide. Low molecular weight heparin was used for anticoagulation. This gentleman later developed proteinuria and neurological symptoms, fulfilling the criteria for catastrophic antiphospholipid syndrome. He received plasma exchange, without an improvement. He developed complications from his disease and treatment, including poor wound healing. It became apparent his condition would not improve and active treatments were stopped. He passed away 6 weeks after initial presentation. Prior to his admission to hospital, his warfarin was swapped to a NOAC. This is thought to have been the trigger behind catastrophic thrombosis. Case report - Discussion: After excluding other conditions such as necrotising fasciitis, this gentleman was rapidly started on IV methylprednisolone to halt any further progression. This is because glucocorticoids have the greatest evidence base for managing this poorly understood acute disease manifestation. After this failed to manage his condition, he was given a further immunosuppressive agent in the form of rituximab. This was used after his serology confirmed triple antibody status. It was hoped this would stop any further immunological mediated disease progression. Oral prednisolone was started at 40mg at this stage and kept under review with a tapering schedule. Cyclophosphamide was given within a few days of rituximab, with hope of a quicker onset of action. A careful MDT decision was made on these drug choices, particularly regarding their combined use and appreciating their side effect profiles. Cyclophosphamide has evidence behind its use, especially for those with APLS associated with lupus. While he did not develop any infections related to treatment, his condition progressed. Case reports suggest that plasma exchange can be useful in the management of catastrophic antiphospholipid syndrome, so the team recommen ed this. Consent at this stage became tricky due to his altered mental status, but it was felt he did demonstrate capacity for this specific decision. As his condition did not improve after this level of immunosuppression, the team reached the decision that no other treatments would likely change the outcome. He remained on oral steroids for the remainder of his admission. The other management facet of APLS crises pertains to anticoagulation. Low molecular weight heparin was recommended by the haematologists. His NOAC was stopped after the diagnosis was confirmed. Warfarin was restarted later in his admission given he had been well on this for years. Case report - Key learning points: This fascinating case exemplifies the importance of completing an antiphospholipid antibody screen for patients who present with unprovoked venous thromboembolic disease. NOACs are commonly used anticoagulant medications. Several case reports have demonstrated that patients with antiphospholipid syndrome experience breakthrough thromboembolic events when treated with NOACs. The highest risk is associated with history of arterial thrombosis and those with triple positive antibody status. Three clinical trials have either been completed or are in the process of investigating whether NOACs sufficiently prevent thromboembolic disease in these patients. The TRAPS study compared rivaroxaban to warfarin in those with triple antibody positive antiphospholipid syndrome. The study was terminated early given that higher adverse events were observed in the rivaroxaban arm (19%, n11/59) versus warfarinised patients (3%, n2/61). The RAPS study found no difference in thromboembolic risk and results from the ASTRO-APS study looking into apixaban are awaited. There is insufficient evidence to suggest that NOACs prevent VTE in a similar fashion to warfarin, so many still advocate the use of warfarin. The optimal immune management of this acute complication is not well elucidated, with a shortfall in mechanistic pathological understanding. The conference will generate discussion on this subject matter in detail. During the COVID-19 pandemic, it has been observed for patients to change anticoagulation from warfarin to NOACs. Given NOACs do not require monitoring, this medication change reduces the number of interactions patients have with healthcare services. We postulate this change triggered the crisis in our patient, where we suggest continuation of warfarin would have been ideal. This is due to the history of several unprovoked thromboembolic events without a prior antiphospholipid screen being completed. Dissemination of learning points from this case are imperative to ensure decision-making encompasses patients who may have undiagnosed antiphospholipid syndrome.

Development of a multivariate model with desirability-based optimization for simultaneous determination of five co-administrated drugs for the management of COVID-19 infection in their dosage forms via validated RP-HPLC method

More than 2.9 million people have died as a result of the global demographic impact of the coronavirus illness of 2019 (COVID-19). Numerous antiviral and anti-inflammatory medications have FDA approval to treat COVID-19 patients. For the simultaneous determination of COVID-19 utilized medications (Remdesivir, Moxifloxacin, Dexamethasone, Apixaban, and paracetamol) in their dosage forms, a sensitive technique has been developed and validated. The aforementioned medications were separated and quantified with the help of experimental design. The Box-Behnken design was used in the experiment to optimize the chromatographic method's analytical parameters. It employed RP-HPLC with a UV detector. An INERTSIL ODS-3 C18 column (5 µm, 250 × 4.6 mm) with mobile phase composed of acetonitrile: 30 mmoL potassium dihydrogen phosphate buffer (pH = 7.5) (50:50, v/v), at room temperature was employed to separate the aforementioned drugs. Paracetamol was linear over the concentration range (1–50 µg/mL), Moxifloxacin (5–70 µg/mL), Apixaban (5–70 µg/mL), Dexamethasone (1–100 µg/mL), and Remdesivir (5–100 µg/mL). According to ICH guidelines, the new approach underwent thorough validation. Between the proposed method's results and those from the reference or reported methods, there was no significant difference. The technique is simple to use in research of the cited medications in their dosage forms for quality control aspects. [ FROM AUTHOR]

Green fitted second derivative synchronous spectrofluorometric method for simultaneous determination of remdesivir and apixaban at Nano gram scale in the spiked human plasma.

Remdesivir and apixaban have been included in the treatment guidelines of several countries for severe COVID-19 infections. To date, no analytical method has been developed for the determination of remdesivir and apixaban in plasma matrix. The main objective of this work was to develop a highly sensitive, green-adapted spectrofluorometric method for the determination of remdesivir and apixaban at the Nanoscale. Remdesivir and apixaban showed overlapping fluorescence emission spectra at 403 nm and 456 nm when excited at 246 nm and 285 nm, respectively. This overlap was resolved in two steps. The first step was synchronous fluorescence scanning of remdesivir and apixaban, and the second step was manipulation of the second-order derivative for the obtained spectra. These steps allowed complete resolution of the overlapping fluorescence spectra and selective determination of remdesivir and apixaban at 410 and 469 nm, respectively. The variables affecting the synchronous scanning of the aforementioned drugs were optimized in terms of sensitivity parameters and principles of green analytical chemistry. The described method allowed sensitive determination of remdesivir and apixaban over the concentration range of 5-200 ng/mL and 50-3000 ng/mL, respectively. The described method was validated and successfully applied for the simultaneous determination of the mentioned drugs in pure form and in spiked human plasma.

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.

Native heart valve thrombosis associated with COVID-19 - a report of 4 cases.

Native heart valve thrombosis (NHVT) is a rare valvular pathology, usually associated with prothrombotic state or disturbed intracardiac blood flow related to structural valve abnormalities. While different venous and arterial thromboembolic complications of COVID-19 have been widely described, so far NHVT has not been reported in the context of the disease. The authors describe 4 cases of NHVT associated with COVID-19, revealed on aortic, mitral (2 patients) and tricuspid valve. In a 29-yearold male with mild pneumonia, large thrombus developed on bicuspid aortic valve (BAV), which resulted in fatal brain emboli. In a 76-yearold male with a history of rheumatoid arthritis (RA) being in a recovery period after COVID-19, central retinal artery occlusion (CRAO) was the first sign of mitral valve thrombus, which disappeared after 3 weeks, during apixaban use. Such therapy was also successful in a 46-yearold female with multiple cardiovascular risk factors in whom mitral valve thrombus was found in a routine echocardiography after she got COVID-19 the third time. In a 75-year-old man with moderate COVID-19 pneumonia and bacterial coinfection, coexistent transient focal LV dysfunction and tricuspid valve thrombus were observed. The patient was treated with apixaban as well; however, in this case only reduction in the thrombus size was seen after 4 months therapy. The authors indicate that in patients with COVID-19 and NHVT, other prothrombotic conditions can usually be found. This complication may involve different valves and occur irrespective of COVID-19 severity. Interdisciplinary evaluation of such patients is necessary.