Elevated INR in a COVID-19 patient after concomitant administration of azvudine and anticoagulants.

Background: Azvudine (FNC) is a promising treatment candidate for managing coronavirus disease 2019 (COVID-19). However, drug interactions with azvudine have been poorly studied, especially with no reported cases of azvudine with anticoagulants such as warfarin and rivaroxaban. Case summary: The patient was diagnosed with lower limb venous thrombosis and took warfarin regularly. The international normalized ratio (INR) was stable (2.0-3.0). However, the INR increased to 7.52 after administering azvudine. The patient had no other factors justifying this change. This increase in INR occurred again with the administration of azvudine in combination with rivaroxaban, and the INR increased to 18.91. After azvudine administration was stopped, the INR did not increase when rivaroxaban was used alone. Conclusion: Azvudine, warfarin, and rivaroxaban might have previously unidentified drug interactions that increased the INR. Therefore, the INR must be closely monitored when they are concomitantly administered in COVID-19 patients.

A Case Report of Ivermectin-Induced Liver Failure

Introduction: Ivermectin is an antiparasitic medication that is primarily metabolized by the liver. During the COVID-19 pandemic, researchers demonstrated that Ivermectin successfully inhibited the replication of SARS-COV-2 in vivo, but current research has failed to demonstrate clinical benefit for treatment of COVID-19. Despite this, misinformation campaigns have misled patients to ingest Ivermectin at concentrations meant for domestic animals. Here, we present a case of acute liver failure secondary to the use of Ivermectin. Case Description/Methods: A 61-year-old man with medical history of ischemic cardiomyopathy with last echocardiogram showing ejection fraction at 21%, atrial fibrillation on warfarin for oral anticoagulation, and previously treated Hepatitis C presented with generalized weakness and yellowish discoloration of the skin worsening over the last two weeks. The patient denied significant alcohol use, acetaminophen use, or illicit drugs. He admitted to injecting himself with two doses of weight-based horse ivermectin, for COVID prophylaxis, two weeks prior to his presentation. Physical exam was pertinent for scleral icterus and hepatomegaly with no abdominal tenderness. Initial labs revealed elevated liver chemistries in a mixed pattern (Figure 1). Acute hepatitis panel, HSV, and CMV were negative. Hepatitis C antibodies were positive, but the patient was in sustained virologic response. Full workup for chronic liver disease was unremarkable. Ultrasound revealed hepatosplenomegaly with patent portal and hepatic vasculature. Subsequently, the patient developed hepatic encephalopathy along with his coagulopathy, raising concern for acute hepatic failure. The patient was transferred to the ICU and started on NAcetylcysteine, rifaximin, and supportive care. The patient recovered well and fortunately did not require liver transplant. Discussion(s): While the FDA recommends against the use of Ivermectin for COVID-19, many continue to inappropriately consume it. Ivermectin-induced liver failure is a rare but deadly side effect. Given our patient's rapid onset of symptoms post-self injection of Ivermectin, his liver injury was presumed to be related to Ivermectin. The drug interaction between Ivermectin and warfarin had worsened the patients coagulopathy. Physicians should be aware of the ways Ivermectin overdose may clinically present to avoid delayed treatment. This case demonstrates the detriments of perpetuation of medical misinformation to care.

A Case of Primary Biliary Cirrhosis With New Onset Hyperthyroidism and Supratherapeutic INR

Introduction: Hyperthyroidism is known to increase catabolism of vitamin-K-dependent clotting factors (II, VII, IX, X) and increase the response of vitamin K antagonists, usually warfarin. Primary biliary cirrhosis (PBC) has been associated with thyroid dysfunction (TD), especially with autoimmune thyroid disease. In the below case, a patient with known PBC on warfarin is found to have severely elevated INR related to new-onset hyperthyroidism with clinical consequences of hemorrhage including upper GI bleed. Case Description/Methods: A 64-year-old female with PBC and antiphospholipid antibody syndrome on warfarin was admitted for hemorrhagic epiglottitis requiring emergency intubation and supratherapeutic INR. Her PBC was diagnosed as stage II on biopsy 23 years ago and has remained clinically stable on ursodiol therapy. On presentation, the patient was tachycardic, tachypneic, and had O2 saturations <90% on HFNC prior to intubation. Physical exam significant for larger goiter with diffuse upper airway swelling. She was admitted and found to have COVID-19 infection, INR .16.0 and PT>200.0 (limit of lab), WBC of 22.8, and lactate of 2.5. LFTs WNL aside from albumin of 2.0. TSH was <0.0017 (limit of lab) and free T4 of 3.4, free T3 of 5.3. TSH receptor antibody (TRAB) and thyroid stimulating immunoglobulin (TSI) levels were normal. Her last TSH was normal a year ago. CTA chest found a 5.7cm heterogeneous, partially calcified superior mediastinal mass consistent with multinodular thyroid goiter. Patient was initially given prothrombin complex concentrate and vitamin K with correction of INR over the following few days. She was extubated and started on methimazole. During the hospital course, she was found to have coffee ground emesis for which an EGD was done with findings of non-bleeding gastric ulcer (Forrest Class IIc) and LA Grade D esophagitis with adherent clot and bleeding for which hemostatic spray was applied. Patient was discharged a few days later following resumption of warfarin and on pantoprazole and methimazole. Discussion(s): The above case demonstrates a rare case of PBC and new-onset hyperthyroidism due to multinodular thyroid goiter causing significantly elevated INR in the setting of warfarin use with hospital course complicated by GI bleed. PBC is associated with TD - hyperthyroidism, hypothyroidism, and thyroid cancer. Hyperthyroidism is less commonly associated with PBC compared to other TDs but should be considered especially with a finding of elevated INR.

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.

Telemonitoring of older anticoagulant users during the COVID-19 pandemic

The COVID-19 pandemic brought challenges to the monitoring of anticoagulant users, especially older adults, making telemonitoring an alternative to provide continuity of care for these patients. The present study aimed to describe the experience of telemonitoring of older anticoagulant users during the COVID-19 pandemic. This is a descriptive study concerning the telemonitoring pharmaceutical service for older adults (>= 60 years old) using oral anticoagulants in a private geriatric outpatient clinic (Belo Horizonte). Older people had parameters of effectiveness and safety of anticoagulants monitored monthly by telephone (Apr-Dec/2021). Identified problems generated interventions for the patient or the multidisciplinary team. A total of 425 older adults were included in the service. Most used apixaban (189;41.9%), rivaroxaban (146;34.4%) and warfarin (47;11.1%). There was a mean age of 82.1 years, mostly female (65.2%), most at high risk of vulnerability (69%), and an incidence of 9.9% of COVID-19. There were 219 interventions related to warfarin (average of 4.6 interventions/patient);including requests for an INR test (57.5%), health guidelines (19.6%), dosage change (reduction -10.5%;increase -5.9%;suspension -0.6%), or referral (5.9%). Users of other anticoagulants did not show alterations in the monitored parameters. Eleven older adults suffered falls and 10 required hospitalizations due to thromboembolic or hemorrhagic events. There was no statistically significant difference in hospitalization rates between users of warfarin or other anticoagulants (p=0.314). Monitoring older anticoagulant users is important, especially considering the high level of frailty identified and the thromboembolic and non-thromboembolic risks that COVID-19 brings. Telemonitoring was important, allowing for multiple interventions to be performed.

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.

Cirrhosis and COVID-19: Diffuse venous thrombosis and its clinical implication

A 60-year-old woman with Hepatitis C infection, cirrhosis, recurrent hepatic hydrothorax, and hepatocellular carcinoma was hospitalized with Coronavirus disease-2019 (COVID-19). After her initial discharge, she was re-admitted three weeks later with decompensated liver disease. Imaging revealed extensive thrombosis in the portal vein, superior mesenteric vein, splenic vein and bilateral brachial veins. Given the acute onset and extent of the thrombosis, the patient received therapeutic anticoagulation despite elevated prothrombin time/ international normalized ratio, thrombocytopenia and low fibrinogen. Cirrhotic patients with COVID-19 maybe at high risk of thrombosis, which can present with significant hepatic decompensation.Copyright © 2022 The Author(s)

Myocardial infarction with non-obstructive coronary arteries (MINOCA) complicating myocarditis

Myocarditis can lead to myocardial infarction in the absence of coronary artery obstruction. We report a case of probable myocarditis, complicated by myocardial infarction with non-obstructive coronary arteries. A 19-year-old man presented with chest pain typical of myocarditis. He was a smoker but was otherwise well. Electrocardiogram revealed diffuse ST-elevation and echocardiography revealed a thin, akinetic apex. Troponin-T levels on admission were raised leading to an initial diagnosis of myocarditis being made. However, late gadolinium enhancement study on cardiac magnetic resonance imaging demonstrated transmural enhancement typical of ischaemia. Coronary angiogram was normal, leading to a likely diagnosis of myocardial infarction with non-obstructive coronary arteries. It is important to highlight that coronary assessment remains important when working up for myocarditis, as myocardial infarction with non-obstructive coronary arteries can often complicate myocarditis in cases of normal angiography. Another important lesson was on how cardiac magnetic resonance imaging provided vital evidence to support underlying ischaemia despite normal coronary angiogram, leading to a diagnosis of myocardial infarction with non-obstructive coronary arteries. Myocardial infarction with non-obstructive coronary arteries remains a broad 'umbrella' term and cardiac magnetic resonance imaging, as well as more invasive coronary imaging techniques during angiography, can further assist in its diagnosis. Our case provides a reminder that myocardial infarction with non-obstructive coronary arteries, although increasingly recognised, remains under-diagnosed and can often overlap with peri-myocarditis, highlighting the need to employ multi-modality imaging in guiding management.Copyright © The Author(s) 2021.

Prosthetic valve thrombosis: literature review and two case reports

Prosthetic heart valve thrombosis is one of the most dangerous prosthetic valve complications. Proper monitoring and management of these patients help to prevent this complication. Fluoroscopy is advantageous in cases of thrombosis to assess the function of the prosthetic valve by measuring opening and closing angles. We describe two cases of aortic mechanical valve thrombosis with different mechanisms of thrombus formation. The first case was a 48-year-old woman admitted to the hospital because of shortness of breath during minimal exertion and significantly reduced exercise tolerance. Due to rheumatic heart disease the patient underwent aortic and mitral mechanical prosthesis and has been using warfarin in therapeutic norms. During echocardioscopy aortic prosthesis obstruction and severe tricuspid valve regurgitation were observed. The patient was scheduled for aortic root and TV prosthesis surgery. The second patient also had aortic mechanical valve due to severe aortic stenosis caused by rheumatism and presented with organizing pneumonia and progressing respiratory failure as complications of the COVID-19 infection and was admitted with dyspnea, cough, and weakness. Aortic prosthetic valve thrombosis was diagnosed despite optimal treatment and therapeutic INR.Copyright © 2023, CKS.

Acute ischemic stroke due to floating thrombus of ascending aorta: An acute and subacute complication of SARS-CoV-2 infection

Objective: To describe ischemic stroke due to floating thrombus of ascending aorta occurring as acute and subacute complication of SARS-CoV-2 infection. Material(s) and Method(s): consecutive identification in clinical practice of ischemic strokes secondary to aortic arch thrombosis and history of acute or recent Covid-19 infection. Result(s): two patients had ischemic stroke with evidence of aortic arch thrombosis. The first case had concomitant acute Covid-19 infection, the second had recent Covid-19 infection. Both patients underwent intravenous thrombolysis, and subsequent anticoagulation. One patient died due to cerebral hemorrhage. Discussion and Conclusion(s): aortic arch thrombosis can be an incidental finding in acute ischemic stroke in patients with concomitant and recent COVID-19 disease. However, the infection may lead to thrombosis in non-atherosclerotic vessels and to cerebral embolism. Our findings support active radiological search for aortic thrombosis during acute stroke in patients with acute or recent COVID-19 disease.Copyright © 2022

Appraising SARS-CoV-2 infections after full mRNA COVID-19 vaccination in patients with systemic lupus erythematosus (SLE)

The 2019 Coronavirus disease (COVID-19) vaccine is a major weapon in the fight against the severe acute respiratory syndrome brought about by coronavirus 2 (SARS-CoV-2). The vaccine significantly reduces the risk and severity of infection by SARS-CoV-2. Patients with systemic lupus erythematosus (SLE) need protection from vaccine-preventable diseases including COVID-19. SLE patients have higher rates of severe infections due to immunosuppressive therapies and multiple immunologic defects - both of which are capable of blunting the immune responses after vaccination. In the management of COVID-19, recommendations have been developed to guide adjustments and/or continuation of immunosuppressive therapies for an effective immune response following vaccination with mRNA-based or viral vector-delivered vaccines. Monoclonal antibodies have also become available since December 2021. Here we present three cases of SLE patients who contracted COVID-19 after vaccination. One was managed in ambulatory settings and two required inpatient hospital admission.Copyright © 2022

A Controversy: Warfarin Failure in Covid-19 with Supratherapeutic Inr

Background COVID-19 has been previously associated with thromboembolism. We present a unique case of a patient who was compliant with warfarin and yet developed breakthrough Deep Venous Thrombosis after recently being diagnosed with COVID-19. Case A 49-year-old female with past medical history of rheumatic fever complicated with mitral stenosis and treated with mechanical mitral valve replacement in 2003, presented with right-sided leg swelling, warmth, and pain for the past 1 week. She tested positive for COVID-19 almost 2 weeks ago but was not hospitalized or treated due to minimal symptoms. She had been on warfarin for the last 19 years due to underlying mechanical valve with an INR (international normalized ratio) goal of 2.5-3.5. On examination, the right calf was swollen and tender to palpation. Homan sign was positive. INR was elevated to 9.88 (a month ago it was within the therapeutic range of 2.5-3.5). The rest of the lab work up including fibrinogen levels, PT, aPTT, CBC, and CMP was unremarkable. A lower extremity venous duplex was performed that came back remarkable for acute right popliteal DVT. Decision-making Warfarin was held considering elevated risk of bleeding. INR was repeated daily and once it was below 2.5, therapeutic dose of enoxaparin 1mg/kg twice daily was started for 3 months. Due to limited anticoagulation options, a shared decision was made to place the patient back on warfarin, since she was out of the window of COVID-19 infection. She was not a candidate for DOAC's considering her mechanical valvular heart disease history and patient did not want to consider invasive interventions as well. Conclusion Our case study is the first ever reporting warfarin failure with supratherapeutic INR due to COVID-19 infection. It also raises concerns if warfarin is safe to use in COVID-19 patients, which might need further research studies to have clear answers. In patients with mechanical heart valves and supratherapeutic INR who present with concerns of warfarin failure, treatment options are limited. Recommended management is holding warfarin to achieve therapeutic INR levels, switch to enoxaparin temporarily, and eventually placement of IVC filter.Copyright © 2023 American College of Cardiology Foundation

Unusual Stroke: Left Ventricular Non-Compaction Causing an Embolic Cerebrovascular Accident

Background Left Ventricular Non-Compaction Cardiomyopathy (LVNC) is a rare genetic, developmental disorder when the left apical chamber of the heart contains bundles or pieces of muscle that extend into the chamber called trabeculations. These trabeculations are a sponge-like network of muscle fibers that typically become compacted to transform heart muscle to become smooth and solid during a normal development process. Those who have LVNC most commonly are asymptomatic. Those who are symptomatic present with syncope, palpitations, dizziness, dyspnea, fatigue and/or unexplained weight gain or swelling. LVNC has also been suggested as a rare cause of embolic stroke, in our patient's case, "due to sluggish blood flow in deep intertrabecular recesses." Case We present a 29 year old African American female, G2P0011, with a history of cleft palate repair, and recent pregnancy complicated by COVID-19 who reported to ED after having a fall the day before, leg weakness and numbness, unable to walk, headache and a left facial droop on day of admission. No family history of SCD or other cardiac disease was noted. On assessment, was found to have NIHSS of 7 with rate lateral gaze palsy, left facial palsy, and decreased strength and sensation of LUE and LLE. TPA was not given due to being outside the therapeutic window. CT head and MRI brain were consistent with acute right MCA stroke. Secondary stroke workup with TTE revealed reduced LVEF 15-20%, loosely arranged myocardium with suspected LVNC and RV apical thrombus. Cardiac MRI showed increased trabeculations consistent with LVNC. Decision-making Currently, there are no ACC/AHA guidelines on anticoagulation in the setting of LVNC. Cardiology and Neurology had an extensive multidisciplinary discussion on the need for anticoagulation specifically with Warfarin. The patient was educated extensively on the need for medical adherence with anticoagulation and guideline directed medical therapy. Conclusion The patient was started on guideline directed medical therapy for cardiomyopathy and was started on Warfarin after bridging from Lovenox. She continued with physical therapy and was noted to have improvement in residual deficits at her outpatient follow up.Copyright © 2023 American College of Cardiology Foundation

Clinico-Epidemiological Profile of Cutaneous Adverse Drug Reactions at Rural Tertiary Care Centre

Background: Cutaneous adverse drug reactions (CADRs), also known as toxidermia, are skin manifestations resulting from systemic drug administration and it constituted 10%-30% among all reported adverse drug reactions (ADRs). These reactions range from mild morbilliform drug rash to much more severe reactions. Material(s) and Method(s): A retrospective observational study was conducted at dermatology outpatient department of rural based tertiary care center for a duration of 03 years from August 2019 to July 2022, a total of 211 patients who had been clinically diagnosed or were suspected to have drug reactions were studied. Result(s): In this observation there was male preponderance (59.72%) and majority of patients were in their 3rd and 4th decade (40.28%) with maculopapular drug rash (33.17%) being most common clinical profile of CADRs, followed by urticaria (23.70%). Less frequently seen CADRs were acneiform eruptions (21), hair Loss (9), photodermatitis (9), generalised pruritus (7), erythroderma (2), pityriasis rosea (2), Stevens Johnson Syndrome-Toxic Epidermal Necrolysis (SJS-TEN) (4), lichenoid drug eruptions (3), Vasculitis (1) and pustular drug eruption (1). The most common group of drugs causing CADRs were antibiotics (40.28%), followed by NSAIDs (28.43%). Conclusion(s): Cutaneous Adverse Drug Reactions (CADRs) are price we pay for the benefits of modern drug therapy;knowledge of these reactions is important for treating physician as prompt recognition and treatment can prove lifesaving.Copyright © 2022 Academic Medicine and Pharmacy

Extensive bowel necrosis in a case of COVID-19 disease despite warfarin toxicity: a paradoxical event

Background: Coronavirus disease 2019 (COVID-19) involves multiple organs, including the gastrointestinal tract. It also causes frequent thromboembolic events because of its thrombogenicity. This study reports a COVID-19 case of extensive bowel necrosis despite using warfarin. Case Presentation: A 52-year-old homeless addict male was brought via Emergency Medical Services with a chief complaint of abdominal pain for two days and loss of consciousness since the day before. He had a history of cough and dyspnea for seven days and had been using warfarin after mitral valve replacement three years earlier. On admission, he had low oxygen saturation, tachycardia, and fever. Because of his respiratory signs and symptoms, a chest CT scan was performed, and evidence of COVID-19 infection was detected. He had nausea, and on abdominal examination, there was generalized tenderness, rebound tenderness, and guarding. Following physical examination and abnormal laboratory test results, he underwent an emergent laparotomy. Extensive necrosis made surgical intervention impossible, and he died shortly after the surgery. Conclusion: COVID-19-associated coagulopathy raises many challenges nowadays, and according to the present case, even using anticoagulants may not prevent it.

Comparison of the prophylactic antithrombotic effect of indobufen and warfarin in patients with nephrotic syndrome: a randomized controlled trial.

PURPOSE: The risk of thromboembolic events is elevated in patients with nephrotic syndrome, and warfarin use has been associated with an increased risk of bleeding. Indobufen, a selective cyclooxygenase-1 inhibitor, is currently being evaluated for the prevention of thromboembolic events in nephrotic syndrome. This study aimed to compare the efficacy and safety of indobufen with that of warfarin in patients with nephrotic syndrome. MATERIALS AND METHODS: This multicenter, randomized, three-arm, open-label, parallel controlled trial involved a total of 180 adult patients with nephrotic syndrome from four centers in China. Patients were randomly assigned to receive 100 mg indobufen (bid), 200 mg indobufen (bid), and 3 mg warfarin (qd) daily for 12 weeks. The primary endpoints included thromboembolic and bleeding events, while laboratory results and adverse events constituted secondary endpoints. RESULTS: No thromboembolic events occurred in the high-/low-dose indobufen and warfarin groups. Moreover, the use of a low dose of indobufen significantly reduced the risk of minor bleeding events compared with warfarin use (2% versus 18%, p < .05). Finally, adverse events were more frequent in warfarin-treated patients. CONCLUSIONS: This study found that indobufen therapy provided equivalent effects in preventing thromboembolic events compared with warfarin therapy, while low dose of indobufen was associated with a reduced risk of bleeding events, thus it should be recommended for the prevention of thromboembolic events in clinical practice in patients with nephrotic syndrome. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17013428.

Interaction between warfarin and molnupiravir in a patient with coronavirus disease 2019 infection.

Molnupiravir is a novel antiviral agent for coronavirus disease 2019 (COVID-19) treatment. Warfarin is an oral anticoagulation agent with difficult management due to drug interactions. Here, we describe a case of international normalized ratio (INR) prolongation in a patient who administrated warfarin with molnupiravir for COVID-19. An increased INR at 3.80, enough to discontinue warfarin, was observed on the fifth day of molnupiravir therapy, although the warfarin dose and INR were stable at 4 mg/day and approximately 2.0 before the molnupiravir initiation, respectively. Factors that affect the INR, such as severe COVID-19, cytokine, diet, liver dysfunction, and the concomitant use of medications other than molnupiravir, were unlikely in this patient. This case suggests that healthcare physicians should be aware of the possibility of drug interaction between molnupiravir and warfarin.

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.

Potential Drug Interaction Between Favipiravir and Warfarin in Patients With COVID-19: A Real-World Observational Study.

Favipiravir is one of the most used antiviral agents for the treatment of coronavirus disease 2019 infection in many countries, including Thailand. This study aimed to investigate the effect of favipiravir-warfarin interaction in terms of changes in international normalized ratio (INR) of patients. Medication charts of all inpatients in a hospital in Thailand between April 2021 and March 2022 were reviewed. Patients who received either warfarin with standard care or warfarin with favipiravir were included. The INR levels of patients were monitored at baseline and the earliest date following treatment, as well as other laboratory parameters. There were 43 and 53 patients in the warfarin-favipiravir and the warfarin-only groups, respectively. Baseline characteristics, such as sex, age, body mass index, and warfarin dose, were not significantly different between the 2 groups. The results showed that the mean INR of patients using favipiravir and warfarin was increased from 2.14 to 3.88 (P < .001), while the patients using warfarin alone had no increase in the mean INR (1.93 vs 1.91; P = .906). Other parameters were not significantly changed, including white blood cell count, red blood cell count, hemoglobin, hematocrit, and liver function. However, an increase in platelet count was observed in the favipiravir-warfarin group, but not in the control group. This real-world study highlighted a significant increase in the INR levels of patients who used favipiravir together with warfarin, compared to patients who used only warfarin. However, the interaction did not affect other laboratory parameters, except an increase in platelet count.

Paediatric Aps - Children Are Not Just Small Adults

Introduction/Background: Antiphospholipid syndrome (APS) is a rare autoimmune multisystem disease characterised by thrombosis and pregnancy morbidity in the presence of persistently elevated titres of: lupus anticoagulant, anticardiolipin and/or anti-glycoprotein 1. It may be primary (occurring alone) or secondary (in combination with another disease, most commonly systemic lupus erythematosus (SLE)). Recent publications highlighted clinical criteria limitations for children and raised awareness of the burden and prevalence of non-criteria manifestations in this population. This case report adds further weight to the need to raise multi-specialty awareness of non-criteria manifestations to aid recognition and treatment of this rare condition with potentially severe sequelae. Description/Method: 13-year-old female with SLE diagnosed aged 8 in India with bilateral optic neuritis occurring two months later. ANA positive at diagnosis with low complement and thrombocytopenia. Treated with prednisolone and hydroxychloroquine. Patient moved to the UK aged 9;initial abnormal bloods: mildly positive ANA (ENA negative), thrombocytopenia, strong lupus anticoagulant. As serology not strongly suggestive and optic neuritis rare in lupus diagnosis questioned. Ophthalmology review confirmed bilateral optic atrophy without evidence of previous vasculitis. There was debate whether the postretinal demyelination was due to antiphospholipid syndrome or a primary demyelinating condition. Hydroxychloroquine stopped and azathioprine started. Following normal neurology investigations (brain, spine MRI/MRV/MRA) concluded if patient developed new APSrelated symptoms or worsening visual evoked potentials anticoagulation would be discussed. Patient remained stable over four years with chronic thrombocytopenia and ESR persistently elevated. Azathioprine changed to Mycophenolate mofetil (MMF) due to side effects. Routine medication monitoring bloods in 2022 showed ESR 97, CRP 78, Platelets 61. Review identified vasculitic rash on soles of both feet with palpable nodules and normal pulses. Further investigation confirmed antiphospholipid antibody triple positivity. Aspirin commenced, hydroxychloroquine restarted, MMF dose increased and rituximab administered. Left foot rash settled but right progressed with toe discolouration and numbness. Skin biopsy considered but not performed due to skin integrity concerns. Foot pulses remained present and normal. Bilateral lower limb doppler reported as normal;increased symptoms resulted in CT angiogram which revealed bilateral non-occlusive popliteal thrombus and left pulmonary embolus. Subsequent echocardiogram was normal. Patient was anticoagulated with low molecular weight heparin followed by warfarin. Vascular surgical team advocated medical management and patient received seven infusions of Iloprost followed by Sildenafil. She achieved near total resolution of skin changes to toes with only minimal loss of skin over tip of right great toe. Patient will now require long-termanticoagulation. Discussion/Results: APS was considered in initial differential diagnosis but patient did not meet current clinical criteria as no past evidence of thrombosis. Lupus anticoagulant was consistently strongly positive and anticardiolipin repeatedly negative. As anti-B2 glycoprotein 1 antibody is not routinely tested and must be verbally requested, it was only checked once (negative) prior to discovery of triple positivity. ANA reported as strongly positive at time of SLE diagnosis but reviewing original notes from India titre was 1:100 and therefore not highly convincing. ENA negative and complement and white cell count normal on repeat testing since. Therefore, it is probable that this patient has primary APS as opposed to secondary APS in association with SLE. However, it is possible that this patient may develop more symptoms of SLE over time. When this patient presented with foot rash there were high numbers of children presenting with varying severity of painful, itchy toes coined 'covid toes' due to suspected lin to SARS-CoV-2 infection. Patient had exposure history, and COVID antibody serology was difficult to interpret due to recent vaccination. Dermatology found appearance to be consistent with 'covid toes' and advised supportive treatment. The triple APS antibody positivity result provided probable aetiology. Providing evidence of thrombus was problematic with false reassurance from apparently normal lower limb arterial doppler when actually popliteal arteries were not checked in view of the presence of normal flow proximally at the groin and distally in the feet. This case highlights the need to continue to search for thrombus in presence of high titres antiphospholipid antibodies and particularly in the case of triple positivity as although patient presented with colour change to toes, she was entirely asymptomatic from her PE and her left foot improved spontaneously despite a left popliteal thrombus also being present. Key learning points/Conclusion: Non-criteria manifestation of thrombocytopenia (occurs in 25% paediatric APS patients) was present throughout and patient had past history of haematuria (a recognised renal non-criteria manifestation). A paediatric specific APS criteria including these may have resulted in earlier detection of triple antiphospholipid antibody positivity and thus earlier treatment escalation and possible avoidance of thrombus. It has been reported that a high proportion of children with positive antiphospholipid antibodies don't develop a thrombus. However, it is interesting that our patient was entirely asymptomatic from her pulmonary embolus which was an incidental finding on her CT angiogram. This prompts a discussion about how much imaging should be performed in those with high levels of persistent positive antiphospholipid antibodies. Rituximab resulted in normalisation of platelet count and ESR for the first time since initial presentation. Anticardiolipin antibodies normalised, lupus anticoagulant decreased from strong to moderate and anti- B2 glycoprotein levels decreased but remained positive. Rituximab is a recognised treatment for catastrophic antiphospholipid syndrome (CAPS) but not routinely used in APS. The consistently raised ESR in an apparently clinically well patient is a reminder to continue to search for causes of inflammation. As the CRP was largely in normal range, this demonstrates the unique value of the ESR. In view of anti-B2 glycoprotein 1 antibody requiring to be verbally requested, discussions are ongoing with the laboratory department regarding the possibility of electronic request and a comment with recommendation to check other two antiphospholipid antibodies following one positive antibody result. As a result of this case, a plan will be put in place to ensure annual screening of antiphospholipid antibodies in all juvenile SLE patients in our care. It is hoped that this case report promotes discussion amongst the paediatric rheumatology community regarding further research required for development of paediatric specific APS criteria and management.