Supratherapeutic INR Research Articles

Supratherapeutic INR During Treatment With Nirmatrelvir/Ritonavir and Warfarin and Acute Illness With COVID-19: A Case Report

Background: Several studies have examined INR fluctuations using pharmacokinetic (PK) models or post-hoc INR values after completing nirmatrelvir/ritonavir, but further study of the effects of the drug interaction with warfarin during treatment is necessary. Case Summary: Nirmatrelvir/ritonavir is largely utilized in the outpatient setting so data regarding INR trends in hospitalized patients on warfarin is limited. However, many who receive nirmatrelvir/ritonavir outpatient experience difficulty with presenting to clinic for INR checks due to feeling acutely ill along with isolation precautions. We present the case of a patient receiving warfarin and utilizing home INR testing for monitoring. After diagnosis of coronavirus disease of 2019 (COVID-19), she was started on nirmatrelvir/ritonavir on day five after testing positive. Most recent INR prior to the start of therapy was 2.7 and had been stable on the same dose for months prior to infection. On day two of nirmatrelvir/ritonavir, her INR rose to 4.0 on home point of care INR testing. Despite reducing her dose of warfarin by 15%, her INR remained supratherapeutic the day after completing nirmatrelvir/ritonavir (4.0) and for several checks after. One month after completion of therapy, her INR returned to therapeutic levels. Practice Implications: While PK models and case series have hypothesized both potential increases or decreases in INR with the nirmatrelvir/ritonavir and warfarin interaction, COVID-19 infection itself can cause several pharmacodynamic changes which can increase INR, including decreased appetite and, in severe cases, organ dysfunction. This case provides real-world insight into the drug interaction between nirmatrelvir/ritonavir and the drug-disease state interaction between warfarin and COVID-19.

Case report on Pharmacogenetic guided warfarin dosing in a postoperative valve replacement patient

Patient underwent mitral valve replacement with mechanical valve and was initiated on oral anticoagulation with standard dose of warfarin. She developed supra therapeutic INR levels. Genotyping of CYP2C9 and VKORC1 encoding genes revealed homozygous variation of CYP2C9*3*3 and heterozygous variation of VKORC1 G>A making her hypersensitive to warfarin. Based on this study result and Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline, a low dose of warfarin (0.5mg per day) was prescribed, to achieve a therapeutic INR of 2.5 to 3.5 and adverse drug effects were avoided.

Practical Suggestions for an Optimal Management of Vitamin K Antagonists: Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies (FCSA) Position Paper.

In the era of direct oral anticoagulants, vitamin K antagonists retain a clinically relevant role in thrombotic disorders. In Italy, approximately 20% of the patients on anticoagulant therapies receives a VKA, in most cases warfarin. The optimal management of this drug is challenging and cannot disregard its intricate and unpredictable pharmacokinetic properties and patient's thrombotic and bleeding risk. Several clinical issues encountered during warfarin treatment are still unanswered and are tentatively addressed by physicians. In this regard, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) provides some experience-based good clinical practice's suggestions on the following topics: (1) how to start the anticoagulant treatment with warfarin and warfarin induction regimen; (2) how to manage a subtherapeutic INR value; (3) how to manage a supratherapeutic INR value in asymptomatic patients; and (4) how to manage the association of warfarin with interfering drugs.

The impact of child-specific characteristics on warfarin dosing requirements

BackgroundThe influence of child characteristics on warfarin dosing has been reported; however, there is no consensus on the nature and extent of this effect. ObjectivesTo investigate the impacts of the demographic and clinical characteristics of children on the warfarin dose required to achieve a therapeutic international normalization ratio (INR). MethodsThis retrospective cohort study included children aged 3 months to 14 years old who were prescribed warfarin for 3 months or longer with a “stable INR.” The primary outcome was the total daily dose (TDD) and total weekly dose of warfarin required to achieve a therapeutic INR target. ResultsWe included 127 patients with a mean age of 7.7 ± 3.7 years and a median weight of 22 (IQR, 16-33) kg. Of the sample, 55 patients (43.3%) required a TDD of ≤0.1 mg/kg. The TDD for children younger than 5 years, 5 to 10 years, and older than 10 years were 0.14 ± 0.06 mg/kg, 0.12 ± 0.05 mg/kg, and 0.096 ± 0.04 mg/kg, respectively (P = .002). Overweight and obese children required a smaller TDD than normal-weight children: 0.09 ± 0.05 vs 0.13 ± 0.05 mg/kg (P = .004), which was similar for underweight children. A lower body surface area (<0.5 m2) required a higher dose. All the other variables did not affect warfarin doses. The incidence of a subtherapeutic or supratherapeutic INR was independent of demographic or clinical variables. ConclusionThe study confirmed that the patient demographics affect the daily warfarin dose required to achieve the INR target. However, they do not have any predictive value for the incidence of out-of-range-INR.

The effect of COVID-19 vaccination on anticoagulation stability in adolescents and young adults using vitamin K antagonists

IntroductionThe European Medicine Agency has authorized COVID-19 vaccination in adolescents and young adults (AYAs) from 12 years onwards. In elderly vitamin K antagonist (VKA) users, COVID-19 vaccination has been associated with an increased risk of supra- and subtherapeutic INRs. Whether this association is also observed in AYAs using VKA is unknown. Our aim was to describe the stability of anticoagulation after COVID-19 vaccination in AYA VKA users. Materials and methodsA case-crossover study was performed in a cohort of AYAs (12–30 years) using VKAs. The most recent INR results before vaccination, the reference period, were compared with the most recent INR after the first and, if applicable, second vaccination. Several sensitivity analyses were performed in which we restricted our analysis to stable patients and patients without interacting events. Results101 AYAs were included, with a median age [IQR] of 25 [7] years, of whom 51.5 % were male and 68.3 % used acenocoumarol. We observed a decrease of 20.8 % in INRs within range after the first vaccination, due to an increase of 16.8 % in supratherapeutic INRs. These results were verified in our sensitivity analyses. No differences were observed after the second vaccination compared to before and after the first vaccination. Complications after vaccination occurred less often than before vaccination (9.0 vs 3.0 bleedings) and were non-severe. Conclusionsthe stability of anticoagulation after COVID-19 vaccination was decreased in AYA VKA users. However, the decrease might not be clinically relevant as no increase of complications nor significant dose adjustments were observed.

Supra-therapeutic Anticoagulation with Warfarin: A Cross-sectional Study.

To identify the extent and associated factors for patients with prolonged prothrombin time, international normalized ratio (PT-INR), and the dosage modifications were carried out with warfarin. Studies evaluating patients on warfarin with supratherapeutic anticoagulation are limited. It is vital to understand the management strategies for patients receiving warfarin who are bleeding and those with only supratherapeutic PT-INR. To evaluate the factors associated with supratherapeutic anticoagulation without bleeding with warfarin. A cross-sectional study was carried out on patients receiving long-term warfarin with at least one PT-INR value > 3.2. Percent time in therapeutic range (TTR) was calculated and National Institute for Health and Care Excellence (NICE) guidelines were adhered to defining anticoagulation control into good (> 65%) and poor (< 65%). One hundred and forty-four patients were recruited. Nearly half of the study population had PT-INR values between 3.2 and 3.9. On average, individuals had at least 4 times PT-INR values in the supratherapeutic range. Elderly patients were observed with a significant trend of supratherapeutic INR. Duration of therapy was significantly correlated with the risk of PT-INR > 4. Lower TTR was observed in patients with frequent PT-INR > 4 and those patients had significantly poor anticoagulation control. Duration of warfarin therapy and HAS-BLED scores were observed to be significant predictors of supratherapeutic INR. Large variations were observed in the modifications of warfarin dose carried out at various supratherapeutic INR values and consequently PTINR values. We observed that the majority of patients with supratherapeutic INR had their INR values between 3.2 and 3.9. Elderly patients, with higher HAS-BLED scores and prolonged duration of warfarin therapy, were observed with an increased risk of supratherapeutic anticoagulation. Careful dosage modifications are needed particularly in high-risk categories as mentioned above.

Warfarin Related Kidney Damage: A Confusing Case of Thrombophlebitis Masquerading as Infection.

Anticoagulant-related nephropathy (ARN) is a rare, newly recognized cause of acute kidney injury and significant but underdiagnosed complication of anticoagulation therapy. ARN occurs in patients taking oral anticoagulant therapy most often warfarin or a novel oral anticoagulant (NOAC). It is a potentially devastating disorder with serious renal consequences and increased all-cause mortality. Anticoagulant-related nephropathy presents as an acute kidney injury (AKI) in the setting of a supratherapeutic INR with profuse glomerular hemorrhage seen as renal tubules filled with red cells and red cell casts on renal biopsy. Being that millions of Americans are on warfarin, a thorough understanding and awareness of the clinical presentation, diagnosis, and therapeutic interventions are crucial to protecting the renal function, lowering all-cause mortality and optimizing treatment. Our goal is to provide education on a newly recognized form of AKI and significant but underdiagnosed complication of anticoagulation therapy.

Gastrointestinal bleeding during anticoagulation with direct oral anticoagulants compared to vitamin K antagonists.

Aim: Patients receiving oral anticoagulants with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) have an increased risk of gastrointestinal bleeding (GIB). We compared cases of GIB associated with VKAs and DOACs in terms of risk factors, scores, timing, location, severity, and outcome. Methods: Data from patients treated at a university hospital in Switzerland for GIB under VKA and DOACs between 2012 and 2018 were analyzed in this investigator-driven, retrospective, single-center study. Results: A total of 248 patients (110 males; median age, 80years; 134 VKA, 114 DOAC) were included. No significant differences in age, weight or sex were observed. The propensity of the VKA group for risk factors such as comorbidities, interacting medications, or a high risk for bleeding (HAS-BLED score) was higher than that of the DOAC group. 56% of the VKA-treated patients had a supratherapeutic INR, and 25% in the DOAC group received an unlicensed dose. Significantly more patients in the DOAC group were not formally overdosed with OAC whilst receiving amiodarone compared to the VKA group (57% vs. 18%, respectively, p=0.03). Latency between the documented start of oral anticoagulation and GIB was shorter in the DOAC group (median 3 months) than in the VKA group (median 23.5 months, p¡0.001). There were no differences in terms of location and severity of the GIB, length of hospitalization, or mortality. Conclusion: Patients taking VKAs displayed more risk factors for GIB than those taking DOACs. Treatment with DOACs was associated with early GIB and calls for increased vigilance during the first months after commencement. Co-medication with amiodarone appeared to be a risk factor for GIB in patients taking DOACs.

A Difficult Task: Determining Oral Anticoagulation Efficacy (OAC) in Patients with HIT Type II

Since 1937, heparin has remained the anticoagulant of choice for a wide variety of clinical scenarios. There remains a relatively high prevalence of heparin-induced thrombocytopenia (HIT), an immune-mediated syndrome in which antibodies (most frequently IgG) bind to a complex of heparin and platelet factor IV, resulting in platelet destruction and the release of prothrombotic platelet derived microparticles. Serious complications include thrombocytopenia (usually occurring between 6-12 days after initiating therapy) and thrombosis. The risk of thrombosis in patients with HIT is estimated at 30% and mortality rates have been reported as high as 20-30%. In cases of HIT type II when patients require continuous anticoagulation, such as following implantation of mechanical heart valves, alternative anticoagulants such as direct thrombin inhibitors can be used. The difficulty of using drugs such as argatroban for bridging therapy to warfarin is that they have been found to elevate both the aPTT as well as INR. Therefore, is it difficult to assess whether patients will maintain therapeutic INRs when argatroban is held and they are continued on warfarin monotherapy. The standard treatment regimen calls for argatroban to be started until INR reaches some therapeutic level at which time argatroban is held and INR is rechecked 4-6 hours later. The risk of major bleeding associated with supra-therapeutic INR's is substantial, and as such patients should be continued on bridging therapy to the lowest INR level that is still found to be therapeutic once argatroban is held. Previous research has examined the efficacy of transitioning from argatroban to warfarin in patients with HIT type II. This case report reviews the care of a patient following a diagnosis of HIT, the methods used to measure the efficacy of oral anticoagulation (OAC), and the complications that arose with management. The patient is a 51-year-old woman who received a mechanical mitral valve replacement for mitral valve regurgitation. Two weeks later, she returned to the hospital with lower extremity swelling. On admit, the patient's INR was sub-therapeutic at 1.2. Enoxaparin was initiated with plans to bridge to warfarin until the INR reached 2.5-3.5. Within four days of enoxaparin initiation, platelets decreased from 238,000/uL to 114,000/uL. On day four, a new non-occlusive right internal jugular thrombus was found. A serotonin release assay (SRA) and HIT antibody with reflex were ordered. While labs were in process, enoxaparin was held and argatroban initiated. The PTT was checked and found to be 62.6 seconds, and it was determined that the patient was adequately anticoagulated. A 4-T score of 6 indicated a ~64% probability of HIT with the patient requiring indefinite anticoagulation due to the mechanical mitral valve. When the patient's INR reached 2.5 argatroban was held, however the following INR was found to be subtherapeutic at 1.3. Argatroban was restarted with plans to continue argatroban therapy until INR>4, at which time argatroban was to be held and INR rechecked in 4-6 hrs. If the INR remained therapeutic off argatroban then it was determined that the patient was appropriately anticoagulated. When the INR reached 4.9 and argatroban was held, the recheck 5 hours later was 3.1. Using this algorithm, the patient ultimately achieved a therapeutic INR with platelet counts of >300,000/uL at time of discharge without any major bleeding events or other serious complications. For patients in whom HIT is diagnosed, immediate discontinuation of heparin infusions and elimination of heparin from all flushes and ports is a necessity as the first step of treatment. Argatroban may be used as a bridging agent, but OAC efficacy cannot be monitored solely using the parameter of INR due to argatroban's INR-elevating effect. By trending the aPTT to monitor anticoagulation status and only utilizing the INR once argatroban therapy was removed, we ensured that the patient had achieved OAC efficacy prior to discharge. In our patient an INR of 5 did not result in any major bleeding incident; however, by initially discontinuing prematurely at an INR of 2.5, the patient's hospital stay was extended. The chromogenic factor X assay has shown some accuracy in predicting INR free of argatroban influence by measuring the amount of vitamin x, but further studies are warranted to establish an optimal method by which to convert patients from argatroban to warfarin. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Skin Necrosis in a Patient with Protein S Deficiency, Warfarin Anticoagulation, and Acute COVID-19 Infection: A Case Report

Abstract Introduction/Objective Although thrombotic complications from COVID are well documented, the pathophysiology remains poorly understood, especially in patients with comorbid hypercoagulable risk factors and anticoagulant medication use. COVID has several dermatologic manifestations that may occur due to alterations in hemostasis. We present a case of skin necrosis in a patient with protein S deficiency, warfarin anticoagulation, and acute COVID infection. Methods/Case Report A 48-year-old female, BMI &amp;gt;50, heterozygous Protein S (PS) deficiency, Factor V Leiden, and history of recurrent venous thromboembolic events on warfarin, tested positive for COVID. Her only symptom was fatigue. Several days later, the patient developed painful ecchymoses and erythematous blisters on her breast, arm, and abdomen. Laboratory results showed INR 3.6, fibrinogen 675-1054 gm/dL, WBC 15k with absolute neutrophilia, and D-dimer 2274 ug/L DDU. The patient confirmed compliance with her maintenance warfarin dose. Biopsy showed thrombotic vasculopathy without leukocytoclastic vasculitis. Wound cultures were negative. Results (if a Case Study enter NA) NA. Conclusion The patient’s history and presentation were concerning for warfarin induced skin necrosis. However, the patient had taken warfarin for &amp;gt; 20 years and had an INR of 3.6 which substantiated that warfarin was not discontinued or missed. A retrospective review of INR results during acute COVID infection showed a decrease in time in therapeutic range and an increase in supratherapeutic INRs, suggesting COIVD patients may require decreased warfarin doses. Additionally, PS levels decline in patients with COVID; a similar effect is seen with HIV and Varicella infections. It is theorized that this may be mediated by an increase in C4b binding protein, an acute phase reactant that regulates the complement cascade and binds PS. With an infectious source ruled out and the patients’ known comorbid conditions, an acute exacerbation of the patients underlying hypercoagulable state is the likely driver of the patient’s skin necrosis with COVID as the probable precipitator. In summary, inherited and acquired hypercoagulable risk factors should be included in the differential diagnosis as a cause of skin changes in patients with COVID infection. Although histology may be helpful in diagnosing the cause of skin changes with COVID, laboratory results and clinical correlation are key in identifying a etiology.

S1687 A Case of Primary Biliary Cirrhosis With New Onset Hyperthyroidism and Supratherapeutic INR

S1687 A Case of Primary Biliary Cirrhosis With New Onset Hyperthyroidism and Supratherapeutic INR

Iatrogenic pseudoaneurysm of the middle meningeal artery during embolization of bilateral chronic subdural hematomas.

Summary/AbstractMiddle meningeal artery embolization has become an important treatment option for chronic subdural hematomas. While the treatment is safe, we present a unique case of development of an iatrogenic middle meningeal artery pseudoaneurysm during endovascular embolization with use of a dual-lumen balloon catheter used for injection of a liquid embolic agent. A 62-year-old man on Coumadin for portal vein thrombosis presented to the hospital with headache and supratherapeutic INR. Imaging revealed bilateral acute on chronic subdural hematomas. Given his medical comorbidities he underwent endovascular middle meningeal artery embolization. During the embolization, angiography revealed a pseudoaneurysm of the middle meningeal artery related to use of a dual-lumen balloon catheter. This pseudoaneurysm was successfully treated with ethylene vinyl alcohol embolization. Intracranial pseudoaneurysm related to balloon catheter use is a rare cause of iatrogenic pseudoaneurysm and could lead to life-threatening intracranial bleeding. Therefore, recognition and timely treatment are important.

Mechanical thrombectomy of COVID-19 DVT with congenital heart disease leading to phlegmasia cerulea dolens: a case report

BackgroundCOVID-19 and Fontan physiology have each been associated with an elevated risk of venous thromboembolism (VTE), however little is known about the risks and potential consequences of having both.Case presentationA 51 year old male with tricuspid atresia status post Fontan and extracardiac Glenn shunt, atrial flutter, and sinus sick syndrome presented with phlegmasia cerulea dolens (PCD) of the left lower extremity in spite of supratherapeutic INR in the context of symptomatic COVID-10 pneumonia. He was treated with single session, catheter directed mechanical thrombectomy that was well-tolerated.ConclusionsThis report of acute PCD despite therapeutic anticoagulation with a Vitamin K antagonist, managed with emergent mechanical thrombectomy, calls to attention the importance of altered flow dynamics in COVID positive patients with Fontan circulation that may compound these independent risk factors for developing deep venous thrombosis with the potential for even higher morbidity.

The Immediate Effect of COVID-19 Vaccination on Anticoagulation Control in Patients Using Vitamin K Antagonists

Background: In January 2021, the Dutch vaccination programme against SARS-CoV-2 was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications.Aims: To investigate whether the BNT162b2 vaccine affects anticoagulation control in outpatients using Vitamin K antagonists (VKAs).Methods: A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. INR results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination.Results: A total of 3148 outpatient VKA users were included, with a mean age (standard deviation (SD)) of 86.7 (8.7) years, of whom 43.8% were male, 67.0% used acenocoumarol and 33.0% phenprocoumon. We observed a decrease of 8.9% of INRs within range in the standard intensity group (target INR 2.0-3.0). There was both an increased risk of supratherapeutic [OR=1.34 (95% CI 1.08-1.67)] and subtherapeutic levels [OR=1.40 (95% CI 1.08-1.83)] after first vaccination. In the high-intensity group (target INR 2.5-3.5), the risk of a supratherapeutic INR was 2.3 times higher after first vaccination [OR=2.29 (95% CI 1.22-4.28)] and 3.3 times higher after second vaccination [OR 3.25 (95% CI 1.06-9.97).Conclusion: BNT162b2 was associated with an immediate negative effect on anticoagulation control in patients treated with vitamin K antagonists, so it is advisable to monitor the INR short after vaccination, even in stable patients. [Display omitted] DisclosuresKruip: Daiichi Sankyo: Research Funding; Bayer: Honoraria, Research Funding.

LEFT ATRIAL THROMBUS AND COVID-19-ASSOCIATED COAGULOPATHY

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: COVID-19 (Coronavirus Disease of 2019) is a global pandemic caused by the rapidly spreading SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). Although COVID-19 primarily affects the respiratory system, evidence suggests a strong predisposition for pro-thrombotic states with COVID-19 infection, manifesting as both venous and arterial thromboembolism. COVID-19 associated coagulopathy and its varying complications contribute to a significant portion or morbidity and mortality in addition to respiratory failure. CASE PRESENTATION: A 75-year-old woman with stage IV colorectal carcinoma, rheumatic mitral valve stenosis status-post recent balloon valvulotomy, and atrial fibrillation on warfarin presented with fever, cough, anosmia, ageusia, dyspnea, generalized weakness, and anorexia. She was admitted for neutropenic fever, acute hypoxic respiratory failure, and sepsis in the context of COVID-19 pneumonia. Computed tomography angiogram (CTA) of the chest showed bilateral infiltrates consistent with COVID-19 pneumonia, as well as a more unusual finding of a large 7 x 4 x 7 cm left atrial mass (Figure 1), consistent in appearance with a thrombus. Comparison with CTA chest one month prior confirmed that the thrombus was acute. On admission, the patient also had a supratherapeutic INR of 4. Echocardiography confirmed the suspicion for thrombus and redemonstrated restricted mitral valve leaflets consistent with rheumatic valvular stenosis. The patient was treated with supplemental oxygen, remdesivir, vancomycin, cefepime and filgrastim. She responded well and had resolution of her neutropenia, sepsis, and hypoxia. Because she formed the thrombus while on warfarin, decision was made to discontinue warfarin and transition to enoxaparin for anticoagulation. She was subsequently discharged home on hospice. DISCUSSION: Although venous thromboembolism is commonly encountered with COVID-19 patients, to our knowledge this case represents the first report of COVID-19 associated left atrial thrombus. Rheumatic mitral valve disease is a known risk factor for left atrial thrombus formation and colorectal carcinoma may have also contributed to hypercoagulability. However, the patient in our vignette had a supratherapeutic INR at the time of thrombus formation. Furthermore, the absence of thrombus on imaging one month prior confirms a temporal association with COVID-19 infection. As such, evidence suggests that hypercoagulability secondary to COVID-19 contributed to the formation of her left atrial thrombus. CONCLUSIONS: This case adds to the growing body of literature surrounding the profound hypercoagulability provoked by SARS-CoV-2 infection and reiterates the role of anticoagulation in the management of COVID-19 patients during the ongoing pandemic. REFERENCE #1: Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020;109:102433. REFERENCE #2: Incidence of thrombotic complications in critically ill ICU patients with COVID-19. lok FA, Kruip MJHA, van der Meer NJM, et al. Thromb Res. 2020;191:145–147. REFERENCE #3: Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–847. DISCLOSURES: No relevant relationships by Nikhila Janakiram, source=Web Response No relevant relationships by Eva Ma, source=Web Response No relevant relationships by Andreas Mauer, source=Web Response

SARCOIDOSIS WITH SUPERIMPOSED SARS-COV-2 LEADING TO HIGHER PREVALENCE OF CAPA?

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: The recent SARS-CoV-2 pandemic has immensely affected individuals worldwide leading to a serious global emergency. It has the capability to end in post-infection complications and critical outcomes due to significant pro-inflammatory conditions. The role of SARS-CoV-2 in patients with immune disorders, such as sarcoidosis, and the specific interaction between these two diseases remains unclear. Here we present a case of a 65-year-old female with sarcoidosis who got infected with SARS-CoV-2 complicated by pulmonary embolism (PE) and COVID associated pulmonary aspergillosis (CAPA) CASE PRESENTATION: A 60-year-old African American female with a PMH of Sarcoidosis, Chronic thromboembolic pulmonary hypertension (CTEPH) on Riociguat, Macitentan, and Warfarin presented with cough, SOB, and fever for 1-week duration. Upon arrival to the ED, vital signs were significant for tachypnea and hypoxemia. COVID-19 PCR was positive. Initial chest CT revealed bilateral ground-glass opacities (GGOs) with multilobar chronic airspace disease. She was treated with Remdesivir and dexamethasone. During the hospital course, warfarin was held due to supratherapeutic INR. However, before discharge her respiratory parameters decompensated and she required HFNC to maintain her saturation. CT pulmonary angiogram revealed PE in the right distal segmental branch with significant bilateral patchy infiltrates more severe in the distribution of lower lobe suggestive of multilobar pneumonia with bilateral GGOs with crazy paving. Beta galactomannan came back positive and Voriconazole was started empirically with significant improvement in respiratory symptoms. Later fungal culture from sputum confirmed aspergillosis. DISCUSSION: SARS-CoV-2 activates the immune system which results in a release of inflammatory cytokines and leads to cytokine storms. But it remains unknown how the interaction differs in patients with an altered immune system, especially in cases of impairment of the T-cell immunity and granuloma formation, such as sarcoidosis. Some authors suggested that constitutional defects of the regulation of macroautophagy in sarcoidosis could lead to a more severe outcome from the novel SARS-CoV-2 infection. literature review showed that alveolar damage, dysfunctional mucociliary clearance, and altered immune system further facilitates fungal invasion. We, therefore, hypothesize that SARS-CoV-2 in a patient with underlying sarcoidosis may lead to increased risk for pulmonary aspergillosis. CONCLUSIONS: The role of infection from the novel coronavirus in patients having sarcoidosis is still largely unknown however clinicians should be aware that it has the risk of serious complications and clinical deterioration including further destruction of lung architecture, hypervascular response, hypercoagulability, and superinfection like CAPA. REFERENCE #1: https://www.lung.org/lung-health-diseases/lung-disease-lookup/sarcoidosis/learn-about-sarcoidosis REFERENCE #2: https://www.hopkinsmedicine.org/health/conditions-and-diseases/pulmonary-sarcoidosis REFERENCE #3: https://www.nature.com/articles/s41379-020-00661-1#citeas DISCLOSURES: No relevant relationships by Danilo Enriquez, source=Web Response No relevant relationships by SM Hossain, source=Web Response No relevant relationships by Tahmina Jahir, source=Web Response No relevant relationships by Ruby Risal, source=Web Response No relevant relationships by Marie Frances Schmidt, source=Web Response No relevant relationships by Binav Shrestha, source=Web Response No relevant relationships by Sabbena Uppal, source=Web Response

Single Centre Retrospective Analysis of Patients Who Underwent Emergency Reversal of Warfarin Anticoagulation

IntroductionWarfarin is used in the treatment and prevention of thromboembolic disorders, with the risk of bleeding ranging from 1% to 3% per year resulting in hospitalisation or death. Emergency reversal of warfarin is indicated when warfarin therapy is complicated by bleeding, prior to emergency procedures / surgeries, and in patients who have supra-therapeutic INR with high risk of bleeding. Launceston General Hospital is a 330-bed hospital in regional Australia and we practise warfarin reversal in accordance with the national guidelines. Prothrombinex-VF (PTx-VF) is a 3-factor prothrombin complex concentrate (PCC) used in Australia, which contains factors II, IX, and X mainly. Due to low factor VII levels in PTx-VF, addition of 1 unit of FFP with PTx-VF is generally recommended, however there is lack of supportive evidence. There are a few reports of successful use of 3-factor PCC without the use of FFP. Hence in our hospital, the addition of FFP to PTx-VF for warfarin reversal is based on clinician's preference.Aim of studyTo study the clinical, laboratory, therapeutic and outcome data on patients who underwent emergency reversal of warfarin anticoagulation, and to compare the warfarin reversal (INR values) after administration of PTx-VF vs PTx-VF + FFP.MethodsWe performed a retrospective study of patients who underwent emergency reversal of warfarin in our hospital between January 2011 and December 2013. All the patients who underwent emergency reversal of warfarin with PTx-VF +/- FFP were captured from the blood bank database. Patients who received PTx-VF for indications other than emergency warfarin reversal and those with insufficient data were excluded from the study. The clinical, laboratory and transfusion data of these patients and the warfarin reversal strategies and clinical outcomes across different clinical settings were analysed. Non-parametric statistical analysis was used to compare the differences in post-treatment INR values in the PTx-VF vs PTx-VF + FFP groups and statistical significance was assumed at a P value of less than 0.05.ResultsA total number of 125 patients who underwent emergency warfarin reversal were included in the study. The median age was 77 years (range: 28 - 95) with 78 males (62%) and 48 females (38%). Table-1 presents clinical characteristics of the patients. Three clinical subgroups were identified - major bleeding in 61 patients (49%), emergency surgery in 54 patients (43%) and supra-therapeutic INR with high risk of bleeding in 10 patients (8%). Table-2 compares the clinical, laboratory, management and outcome characteristics in these subgroups. According to clinicians' preference, 56% of patients received PTx-VF alone, while 44% received PTx-VF + FFP. Statistically there were no differences in median INR values performed within 6 - 12 hours after administration of PTx-VF vs PTx-VF + FFP in all patients (P = 0.10), bleeding subgroup (P = 0.08) and emergency surgery subgroup (P = 0.24); and the number of patients in the supra-therapeutic INR subgroup was very small for evaluation. Overall 4 patients died due to warfarin-related complications, all of them in the bleeding subgroup.ConclusionIn our study majority (64%) of patients were above 75 years and the most common (69%) reason for warfarin anticoagulation was atrial fibrillation, which were similar in other studies. We observed that GI bleeding was the most common cause for warfarin reversal. Rapid INR correction with good clinical haemostasis occurred in most of the patients after administration of PTx-VF +/- FFP. The mortality rate in our cohort was 3% (4 of 125), and intracranial bleeding accounted for 75% (3 of 4) deaths. Among 14 patients who experienced intracranial bleeding, either spontaneous or induced by trauma, three (21%) died. There were no significant differences in the post-treatment INR values with PTx-VF alone when compared to PTx-VF + FFP, overall and also in the clinical subgroups. The major advantage of warfarin over DOACs is the rapid reversibility in emergency settings and we demonstrated that our 3-factor PCC (PTx-VF) was effective in emergency reversal of warfarin, without the need for FFP. There are a few limitations in this study since it is retrospective and observational. Hence prospective studies are required for better evaluation of the clinical characteristics, and the efficacy of 3-factor PCC without FFP in emergency reversal of warfarin anticoagulation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Anticoagulation Champion — Efficacy of Warfarin Anticoagulation in a Resident Based Primary Care Clinic

INTRODUCTION: Warfarin is still anticoagulant of choice for many patients.Therapeutic time in range (TTR) is used to assess quality of warfarin anticoagulation. A TTR of above approximately 60% has been show to improve mortality and reduce risk of complications.Our hypothesis was the creation of a resident Anticoagulation Champion (AC) would be more efficacious than individual provider driven anticoagulation in a primary care resident clinic.METHODS: To be the AC residents were given a lecture on warfarin anticoagulation and assigned to the AC role for 2 week intervals. Duties included monitoring the anticoagulation book, calling patient's for appointment reminders, education, following up INR's and prescribing. There were a total of 56 patient charts which were reviewed from April 2014- March 2016. Three were excluded for not having INR values recorded during the time period. Of the 53 patients included, 5 patients had INR goals of 2.5-3.5 and 48 patients INR goal was 2-3. When calculating TTR, this range was extended to 1.95-3.04 and 2.45-3.54 as dosage would not be adjusted at these values. Patients were classified as not therapeutic with sub therapeutic and supra therapeutic INR's. Data was then split into 2 time periods: pre-resident based (April 2014-March 2015) and with AC (April 2015-March 2016). We calculated TTR using the traditional method. We compared TTR by month, age and sex. Comparisons were analyzed with a t-test.RESULTS: Of the subjects included, 57% were male. Mean and Median ages of patients were 60.94 and 60.5 respectively with range from 31 to 90 years old. Twenty patients were >65 years. The highest and lowest INR's in this study were 6.22 and 0.92 respectively. A total of 415 INR values were recorded. Pre- AC there was 37 values and with AC 378 values. TTR for males was 56% and females 49%. Average TTR by age was 53.47% for those <65yo and 57.25% for >65 years old. 11 patients had data before and with AC. The TTR pre-AC was 49.52% and with AC was 55.83%. The p value was 0.37. TTR by month ranged from 37-74%.CONCLUSIONS: There was a dramatic improvement in frequency of INR monitoring with the initiation of AC as shown by an increase of INR values during this time period. There was also a trend of improvement in the TTR with AC, however it was not statistically significant likely secondary to the low sample size.CLINICAL IMPLICATIONS: This suggests warfarin anticoagulation could be more efficacious with implementation of an Anticoagulation Champion in resident based primary care clinics. DisclosuresNo relevant conflicts of interest to declare.

Ventricular Assist Device Driveline Infection and Development of Intracranial Hemorrhage: A Case Series.

Durable left ventricular assist devices (LVAD) are frequently complicated by driveline infection. The objective of this case series was to examine whether an association exists between driveline infection and intracranial hemorrhage. This retrospective case series included patients at a single tertiary care hospital on durable LVAD support who developed intracranial hemorrhage. Physical examination data, vital signs, and laboratory markers of sepsis including blood cultures and imaging of driveline sites were reviewed. A total of nine patients were included in the case series. At the time of hemorrhagic event, five patients had active driveline infection, and five patients were found to be bacteremic. All bacteremic patients were found to have supratherapeutic INR at the time of presentation. Although five patients experienced subarachnoid hemorrhage, only one patient was found to have a cerebral aneurysm. This case series highlights a possible association between LVAD driveline infection and intracranial hemorrhage, and the need for further research to better understand the pathophysiology driving this association.

Characteristics of strokes associated with centrifugal flow left ventricular assist devices

Stroke is a devastating complication of left ventricular assist device (LVAD) therapy. Understanding the characteristics, risk factors and outcomes of strokes associated with the centrifugal flow LVADs is important to devise better strategies for management and prevention. This is a retrospective cohort study at a single US academic medical center. The cohort includes patients who received a first time Heartmate 3 (HM3) or Heartware (HVAD) LVAD between September 2009 through February 2018 and had a stroke while the LVAD was in place. Descriptive statistics were used when appropriate. A logistic regression analysis was used to determine predictors of poor outcome. Out of a total of 247 patients, 12.1% (N = 30, 24 HVAD and 6 HM3) had a stroke (63% ischemic) and 3 of these patients had pump thrombosis. Events per patient year (EPPY) were similar for HVAD and HM3 patients (0.3 ± 0.1). INR was subtherapeutic in 47.4% of ischemic stroke patients and supratherapeutic in 18.2% of hemorrhagic stroke patients. Concurrent infections were more common in the setting of hemorrhagic stroke than ischemic stroke (45.4% vs 5.3%, p = 0.008). Strokes were severe in most cases, with initial NIH stroke scale (NIHSS) higher in HM3 patients compared to HVAD patients (mean 24.6 vs 16) and associated with high in-patient mortality (21.1% of ischemic stroke vs. 88.8% of hemorrhagic stroke). Predictors of death within 30 days and disability at 90 days included creatinine at stroke onset, concurrent infection, hemorrhaghic stroke, and initial stroke severity (NIHSS). A score derived from these variables predicted with 100% certainty mortality at 30 days and mRS ≥ 4 at 90 days. For patients with centrifugal flow LVADs, ischemic strokes were more common but hemorrhagic strokes were associated with higher in-patient mortality and more frequently seen in the setting of concurrent infections. Infections, sub or supratherapeutic INR range, and comorbid cardiovascular risk factors may all be contributing to the stroke burden. These findings may inform future strategies for stroke prevention in this population.