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.

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.

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.

Cefazolin-Associated INR Elevation: A Case Report.

PURPOSE: To describe a case of significantly elevated international normalized ratio (INR) in a patient on apixaban receiving treatment with intravenous cefazolin in the setting of coronavirus disease 2019 (COVID-19) infection and malnutrition. SUMMARY: A 74-year-old male patient on apixaban receiving cefazolin for osteomyelitis in the setting of COVID-19 and poor nutritional intake presented with internal jugular tunneled catheter site bleeding and an INR of greater than 22.5. Laboratory abnormalities and bleeding concerns were successfully managed with vitamin K and changing antimicrobial therapy from cefazolin to daptomycin. Follow-up labs one week later demonstrated a sustained improvement in coagulopathy. CONCLUSION: INR prolongation believed to be secondary to cefazolin can be effectively managed with administration of vitamin K and conversion of antimicrobial therapy to an alternative agent.