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1.
JAMA ; 326(17): 1703-1712, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1525396

ABSTRACT

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Factor Xa Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Thrombosis/prevention & control , Adult , Aspirin/adverse effects , COVID-19/complications , Dose-Response Relationship, Drug , Double-Blind Method , Early Termination of Clinical Trials , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Hospitalization , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridones/administration & dosage , Pyridones/adverse effects
2.
Open Heart ; 8(2)2021 11.
Article in English | MEDLINE | ID: covidwho-1523054

ABSTRACT

BACKGROUND: Early in the COVID-19 pandemic, the National Health Service (NHS) recommended that appropriate patients anticoagulated with warfarin should be switched to direct-acting oral anticoagulants (DOACs), requiring less frequent blood testing. Subsequently, a national safety alert was issued regarding patients being inappropriately coprescribed two anticoagulants following a medication change and associated monitoring. OBJECTIVE: To describe which people were switched from warfarin to DOACs; identify potentially unsafe coprescribing of anticoagulants; and assess whether abnormal clotting results have become more frequent during the pandemic. METHODS: With the approval of NHS England, we conducted a cohort study using routine clinical data from 24 million NHS patients in England. RESULTS: 20 000 of 164 000 warfarin patients (12.2%) switched to DOACs between March and May 2020, most commonly to edoxaban and apixaban. Factors associated with switching included: older age, recent renal function test, higher number of recent INR tests recorded, atrial fibrillation diagnosis and care home residency. There was a sharp rise in coprescribing of warfarin and DOACs from typically 50-100 per month to 246 in April 2020, 0.06% of all people receiving a DOAC or warfarin. International normalised ratio (INR) testing fell by 14% to 506.8 patients tested per 1000 warfarin patients each month. We observed a very small increase in elevated INRs (n=470) during April compared with January (n=420). CONCLUSIONS: Increased switching of anticoagulants from warfarin to DOACs was observed at the outset of the COVID-19 pandemic in England following national guidance. There was a small but substantial number of people coprescribed warfarin and DOACs during this period. Despite a national safety alert on the issue, a widespread rise in elevated INR test results was not found. Primary care has responded rapidly to changes in patient care during the COVID-19 pandemic.


Subject(s)
Anticoagulants/administration & dosage , Blood Coagulation/drug effects , COVID-19 , Drug Substitution/standards , Factor Xa Inhibitors/administration & dosage , Practice Guidelines as Topic/standards , Practice Patterns, Physicians'/standards , State Medicine/standards , Warfarin/administration & dosage , Aged , Anticoagulants/adverse effects , Blood Coagulation Tests , Drug Monitoring , Drug Prescriptions , Drug Substitution/adverse effects , Drug Utilization/standards , England , Factor Xa Inhibitors/adverse effects , Female , Humans , Male , Middle Aged , Patient Safety , Primary Health Care/standards , Retrospective Studies , Risk Assessment , Risk Factors , Warfarin/adverse effects
3.
Anesthesiology ; 135(6): 1076-1090, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1507118

ABSTRACT

BACKGROUND: Mortality in critically ill COVID-19 patients remains high. Although randomized controlled trials must continue to definitively evaluate treatments, further hypothesis-generating efforts to identify candidate treatments are required. This study's hypothesis was that certain treatments are associated with lower COVID-19 mortality. METHODS: This was a 1-yr retrospective cohort study involving all COVID-19 patients admitted to intensive care units in six hospitals affiliated with Yale New Haven Health System from February 13, 2020, to March 4, 2021. The exposures were any COVID-19-related pharmacologic and organ support treatments. The outcome was in-hospital mortality. RESULTS: This study analyzed 2,070 patients after excluding 23 patients who died within 24 h after intensive care unit admission and 3 patients who remained hospitalized on the last day of data censoring. The in-hospital mortality was 29% (593 of 2,070). Of 23 treatments analyzed, apixaban (hazard ratio, 0.42; 95% CI, 0.363 to 0.48; corrected CI, 0.336 to 0.52) and aspirin (hazard ratio, 0.72; 95% CI, 0.60 to 0.87; corrected CI, 0.54 to 0.96) were associated with lower mortality based on the multivariable analysis with multiple testing correction. Propensity score-matching analysis showed an association between apixaban treatment and lower mortality (with vs. without apixaban, 27% [96 of 360] vs. 37% [133 of 360]; hazard ratio, 0.48; 95% CI, 0.337 to 0.69) and an association between aspirin treatment and lower mortality (with vs. without aspirin, 26% [121 of 473] vs. 30% [140 of 473]; hazard ratio, 0.57; 95% CI, 0.41 to 0.78). Enoxaparin showed similar associations based on the multivariable analysis (hazard ratio, 0.82; 95% CI, 0.69 to 0.97; corrected CI, 0.61 to 1.05) and propensity score-matching analysis (with vs. without enoxaparin, 25% [87 of 347] vs. 34% [117 of 347]; hazard ratio, 0.53; 95% CI, 0.367 to 0.77). CONCLUSIONS: Consistent with the known hypercoagulability in severe COVID-19, the use of apixaban, enoxaparin, or aspirin was independently associated with lower mortality in critically ill COVID-19 patients.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Critical Illness/mortality , Critical Illness/therapy , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anticoagulants/administration & dosage , Antiviral Agents/administration & dosage , Cohort Studies , Factor Xa Inhibitors/administration & dosage , Female , Humans , Male , Middle Aged , Mortality/trends , Retrospective Studies , Treatment Outcome
4.
JAMA ; 326(17): 1703-1712, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1460106

ABSTRACT

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Factor Xa Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Thrombosis/prevention & control , Adult , Aspirin/adverse effects , COVID-19/complications , Dose-Response Relationship, Drug , Double-Blind Method , Early Termination of Clinical Trials , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Hospitalization , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridones/administration & dosage , Pyridones/adverse effects
5.
Clin Appl Thromb Hemost ; 27: 10760296211039288, 2021.
Article in English | MEDLINE | ID: covidwho-1448131

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a systemic disease that can be life-threatening involving immune and inflammatory responses, and that can result in potentially lethal complications, including venous thrombo-embolism (VTE). Forming an integrative approach to thrombo-prophylaxis and coagulation treatment for COVID-19 patients ensues. We aim at reviewing the literature for anticoagulation in the setting of COVID-19 infection to provide a summary on anticoagulation for this patient population. COVID-19 infection is associated with a state of continuous inflammation, which results in macrophage activation syndrome and an increased rate of thrombosis. Risk assessment models to predict the risk of thrombosis in critically ill patients have not yet been validated. Currently published guidelines suggest the use of prophylactic intensity over intermediate intensity or therapeutic intensity anticoagulant for patients with critical illness or acute illness related to COVID-19 infection. Critically ill COVID-19 patients who are diagnosed with acute VTE are considered to have a provoking factor, and, therefore, treatment duration should be at least 3 months. Patients with proximal deep venous thrombosis or pulmonary embolism should receive parenteral over oral anticoagulants with low-molecular-weight heparin or fondaparinux preferred over unfractionated heparin. In patients with impending hemodynamic compromise due to PE, and who are not at increased risk for bleeding, reperfusion may be necessary. Internists should remain updated on new emerging evidence regarding anticoagulation for COVID-19 patients. Awaiting these findings, we invite internists to perform individualized decisions that are unique for every patient and to base them on clinical judgment for risk assessment.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , SARS-CoV-2 , Thrombophilia/drug therapy , Anti-Inflammatory Agents/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Consensus , Critical Illness , Disease Management , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Female , Fibrin Fibrinogen Degradation Products/analysis , Fondaparinux/adverse effects , Fondaparinux/therapeutic use , Hemorrhage/chemically induced , Heparin/adverse effects , Heparin/therapeutic use , Heparin, Low-Molecular-Weight/administration & dosage , Heparin, Low-Molecular-Weight/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Inpatients , Male , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Hematologic/prevention & control , Pregnancy Complications, Infectious/blood , Pulmonary Embolism/drug therapy , Pulmonary Embolism/etiology , Pulmonary Embolism/prevention & control , Risk , Thrombophilia/etiology , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
6.
Am Heart J ; 242: 115-122, 2021 12.
Article in English | MEDLINE | ID: covidwho-1392113

ABSTRACT

BACKGROUND: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis. DESIGN: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria. SUMMARY: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.


Subject(s)
COVID-19/complications , Factor Xa Inhibitors/administration & dosage , Rivaroxaban/administration & dosage , Thrombosis/prevention & control , Adult , Brazil , Drug Administration Schedule , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Humans , Male , Prospective Studies , Pulmonary Embolism/etiology , Pulmonary Embolism/prevention & control , Rivaroxaban/adverse effects , Thromboembolism/etiology , Thromboembolism/prevention & control , Thrombosis/etiology , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
7.
Cardiovasc Diabetol ; 20(1): 176, 2021 09 04.
Article in English | MEDLINE | ID: covidwho-1388767

ABSTRACT

BACKGROUND: It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis. METHODS: A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis. RESULTS: 2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03-1.98; Log-Rank test p = 0.029). CONCLUSION: In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding.


Subject(s)
Ambulatory Care/methods , Anticoagulants/administration & dosage , COVID-19/drug therapy , Heart Diseases/drug therapy , Metabolic Diseases/drug therapy , Vitamin K/antagonists & inhibitors , Administration, Oral , Aged , Aged, 80 and over , Anticoagulants/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Factor Xa Inhibitors/administration & dosage , Female , Follow-Up Studies , Heart Diseases/diagnosis , Heart Diseases/mortality , Hemorrhage/chemically induced , Hemorrhage/mortality , Humans , Intensive Care Units/trends , Male , Metabolic Diseases/diagnosis , Metabolic Diseases/mortality , Middle Aged , Mortality/trends , Treatment Outcome
8.
Neurologist ; 26(3): 108-111, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1214713

ABSTRACT

INTRODUCTION: The coronavirus disease 2019 (COVID-19) has been associated with a hypercoagulable state, increasing the risk for ischemic stroke. In select cases, patients are already on anticoagulation therapy. Such examples highlight the severity of COVID-19's hyperthrombotic state, and raise questions regarding optimal stroke prevention in these patients. CASE REPORT: An 84-year-ool male with past medical history of chronic obstructive pulmonary disease, hypertension, and paroxysmal atrial fibrillation was admitted for respiratory failure secondary to COVID-19 pneumonia. He was continued on his home apixaban 5 mg twice daily. On day 2 of admission, he developed a new aphasia, and right-sided facial droop. Computed tomography (CT) head was unrevealing. CT angiography did not show large vessel occlusion. CT perfusion demonstrated a left middle cerebral artery ischemic penumbra, without core. He was not eligible for thrombolysis or thrombectomy interventions. Later CT head confirmed L middle cerebral artery infarct. The patient's D-dimer was 1,184 ng/mL on day 1 of admission, and increased to 111,574 by day 4. His hypoxia worsened, requiring intubation and transfer to the ICU. He experienced further clinical decline and eventual demise. CONCLUSION: Ischemic stroke in anticoagulated patients with COVID-19 has been previously reported. Such cases emphasize the severity of the coronavirus virus associated hypercoagulable state. A majority of reported cases have occurred in patients continuing their ambulatory therapy. Overall, such cases are likely underreported. There are current trials comparing therapeutic versus prophylactic dose anticoagulation in patients with COVID-19. There are no studies specifically addressing anticoagulation agent failure in these patients. Further research is required this area to determine the optimal therapy for patients with COVID-19.


Subject(s)
COVID-19/complications , Factor Xa Inhibitors/administration & dosage , Ischemic Stroke/etiology , Aged, 80 and over , Atrial Fibrillation/drug therapy , Fatal Outcome , Humans , Hypertension/drug therapy , Male , Pulmonary Disease, Chronic Obstructive/drug therapy , Pyrazoles/administration & dosage , Pyridones/administration & dosage
9.
Int J Lab Hematol ; 43(6): 1284-1290, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1186165

ABSTRACT

INTRODUCTION: Patients with COVID-19 frequently exhibit a hypercoagulable state with high thrombotic risk, particularly those admitted to intensive care units (ICU). Thromboprophylaxis is mandatory in these patients; nevertheless, thrombosis still occurs in many cases. Thus, the problem of assessing an adequate level of anticoagulation in ICU patients becomes evident during the COVID-19 pandemic. The aim of this study was to evaluate the heparin resistance and the efficacy of heparin monitoring using an anti-Xa activity assay. METHODS: Thirty-seven heparin-treated patients admitted to ICU for SARS-CoV-2 pneumonia were retrospectively studied for antifactor Xa activity (anti-Xa), activated partial thromboplastin time (APTT), Antithrombin, Fibrinogen, D-Dimer, Factor VIII, von Willebrand Factor, and the total daily amount of heparin administered. The correlation between APTT and anti-Xa was evaluated for unfractionated heparins (UFH). The correlations between the daily dose of UFH or the dosage expressed as IU/kg b.w. for low molecular weight heparin (LMWH) and anti-Xa were also evaluated. RESULTS: Twenty-one patients received calcium heparin, 8 sodium heparin, and 8 LMWH. A moderate correlation was found between APTT and anti-Xa for UFH. APTT did not correlate with coagulation parameters. 62% of UFH and 75% of LMWH treated patients were under the therapeutic range. About 75% of patients could be considered resistant to heparin. CONCLUSIONS: SARS-COV2 pneumonia patients in ICU have frequently heparin resistance. Anti-Xa seems a more reliable method to monitor heparin treatment than APTT in acute patients, also because the assay is insensitive to the increased levels of fibrinogen, FVIII, and LAC that are common during the COVID-19 inflammatory state.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/blood , Drug Monitoring/methods , Heparin/therapeutic use , Intensive Care Units , Pandemics , SARS-CoV-2 , Thrombophilia/drug therapy , Aged , Anticoagulants/administration & dosage , COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Comorbidity , Diabetes Mellitus/epidemiology , Drug Resistance , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/therapeutic use , Female , Heparin/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Male , Middle Aged , Partial Thromboplastin Time , Respiratory Tract Diseases/epidemiology , Retrospective Studies , Thrombophilia/blood , Thrombophilia/etiology , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control
10.
J Thromb Thrombolysis ; 52(3): 754-758, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1118255

ABSTRACT

As a result of infection control regulations during the coronavirus disease 2019 (COVID-19) pandemic, anticoagulation clinics have been required to adjust their practices in order to continue providing safe and effective services for their patients. In accordance with a guidance document issued by the Anticoagulation Forum, The Brooklyn Hospital Center (TBHC) anticoagulation clinic in Brooklyn, New York implemented measures including telemedicine follow-ups instead of in-person clinic visits, extending the interval of INR testing, and reviewing eligible candidates for transition from warfarin to direct oral anticoagulants. This study describes the outcomes of one hospital-based clinic location in the 3 months before and after COVID-19 became a significant concern in the New York City area. The primary outcome of time-in-therapeutic range (TTR) for patients receiving warfarin was 60.6 % and 65.8 % in the pre-COVID and post-COVID groups, respectively (p = 0.21). For secondary outcomes, there was no difference in percent of therapeutic INRs (51.5 % pre-COVID v. 44.8 % post-COVID, p = 0.75) or percent of INRs ≥ 4.5 (2.3 % pre-COVID v. 4 % post-COVID, p = 0.27). Based on the data reported in this study, the short-term changes implemented at TBHC's anticoagulation clinic did not appear to cause reductions in safety and efficacy of chronic warfarin therapy management.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation/drug effects , COVID-19 , Drug Monitoring , Outpatient Clinics, Hospital , Pharmacists , Telemedicine , Warfarin/therapeutic use , Ambulatory Care , Anticoagulants/adverse effects , Delivery of Health Care, Integrated , Drug Substitution , Factor Xa Inhibitors/administration & dosage , Female , Humans , International Normalized Ratio , Male , Middle Aged , New York , Predictive Value of Tests , Retrospective Studies , Warfarin/adverse effects
11.
BMJ Case Rep ; 13(12)2020 Dec 22.
Article in English | MEDLINE | ID: covidwho-999235

ABSTRACT

Intra-abdominal thromboses are a poorly characterised thrombotic complication of COVID-19 and are illustrated in this case. A 42-year-old man with chronic hepatitis B (undetectable viral load, FibroScan 7.4 kPa) developed fever and cough in March 2020. 14 days later, he developed right upper quadrant pain. After being discharged with reassurance, he re-presented with worsening pain on symptom day 25. Subsequent abdominal ultrasound suggested portal vein thrombosis. CT of the abdomen confirmed portal and mid-superior mesenteric vein thromboses. Concurrent CT of the chest suggested COVID-19 infection. While reverse transcription PCR was negative, subsequent antibody serology was positive. Thrombophilia screen excluded inherited and acquired thrombophilia. Having been commenced on apixaban 5 mg two times per day, he is currently asymptomatic. This is the first case of COVID-19-related portomesenteric thrombosis described in the UK. A recent meta-analysis suggests 9.2% of COVID-19 cases develop abdominal pain. Threshold for performing abdominal imaging must be lower to avoid this reversible complication.


Subject(s)
COVID-19 , Hepatitis B, Chronic/complications , Mesenteric Ischemia , Mesenteric Veins/diagnostic imaging , Portal Vein/diagnostic imaging , Pyrazoles/administration & dosage , Pyridones/administration & dosage , SARS-CoV-2/isolation & purification , Abdominal Pain/diagnosis , Adult , COVID-19/blood , COVID-19/complications , COVID-19/therapy , COVID-19 Serological Testing/methods , Diagnosis, Differential , Factor Xa Inhibitors/administration & dosage , Humans , Male , Mesenteric Ischemia/etiology , Mesenteric Ischemia/physiopathology , Mesenteric Ischemia/therapy , Portography/methods , Tomography, X-Ray Computed/methods , Treatment Outcome , Ultrasonography/methods
12.
BMJ Case Rep ; 13(11)2020 Nov 04.
Article in English | MEDLINE | ID: covidwho-957913

ABSTRACT

A 60-year-old man recently admitted for bipedal oedema, endocarditis and a persistently positive COVID-19 swab with a history of anticoagulation on rivaroxaban for atrial fibrillation, transitional cell carcinoma, cerebral amyloid angiopathy, diabetes and hypertension presented with sudden onset diplopia and vertical gaze palsy. Vestibulo-ocular reflex was preserved. Simultaneously, he developed a scotoma and sudden visual loss, and was found to have a right branch retinal artery occlusion. MRI head demonstrated a unilateral midbrain infarct. This case demonstrates a rare unilateral cause of bilateral supranuclear palsy which spares the posterior commisure. The case also raises a question about the contribution of COVID-19 to the procoagulant status of the patient which already includes atrial fibrillation and endocarditis, and presents a complex treatment dilemma regarding anticoagulation.


Subject(s)
Aspirin/administration & dosage , Atrial Fibrillation , Blindness , Brain Stem Infarctions , Coronavirus Infections , Diplopia , Endocarditis, Bacterial , Ophthalmoplegia , Pandemics , Pneumonia, Viral , Pyrazoles/administration & dosage , Pyridones/administration & dosage , Retinal Artery Occlusion , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Betacoronavirus/isolation & purification , Blindness/diagnosis , Blindness/etiology , Brain Stem Infarctions/diagnostic imaging , Brain Stem Infarctions/drug therapy , Brain Stem Infarctions/physiopathology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Diplopia/diagnosis , Diplopia/etiology , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/physiopathology , Factor Xa Inhibitors/administration & dosage , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Ophthalmoplegia/diagnosis , Ophthalmoplegia/etiology , Platelet Aggregation Inhibitors/administration & dosage , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Retinal Artery Occlusion/diagnostic imaging , Retinal Artery Occlusion/drug therapy , Retinal Artery Occlusion/etiology , Retinal Artery Occlusion/physiopathology , SARS-CoV-2 , Tomography, Optical Coherence/methods , Treatment Outcome
13.
J Clin Pharm Ther ; 46(2): 519-523, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-939769

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with increased risk of venous thromboembolism (VTE). Guidance for VTE prophylaxis continues to evolve, including addressing direct oral anticoagulants (DOACs) continued upon hospitalization. CASE SUMMARIES: We present 5 patients hospitalized for COVID-19 while on DOACs. Four patients had atrial fibrillation and had a previous VTE. Four patients developed acute VTE and one developed stroke-like symptoms. Monitoring D-dimer assisted with the detection of VTE. Three patients died, and two were discharged alive. WHAT IS NEW AND CONCLUSION: Therapeutic failure with DOACs appears to be commonplace in COVID-19. Further research is needed to determine whether there is an underlying cause to this association.


Subject(s)
Atrial Fibrillation , COVID-19 , Factor Xa Inhibitors/administration & dosage , Fibrin Fibrinogen Degradation Products/analysis , Venous Thromboembolism , Aged , Aged, 80 and over , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , COVID-19/blood , COVID-19/complications , COVID-19/drug therapy , COVID-19/physiopathology , Drug Monitoring/methods , Fatal Outcome , Female , Humans , Male , Mortality , Respiration, Artificial/methods , Stroke/diagnosis , Stroke/drug therapy , Stroke/etiology , Treatment Outcome , Venous Thromboembolism/diagnosis , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology
14.
J Thromb Thrombolysis ; 51(4): 947-952, 2021 May.
Article in English | MEDLINE | ID: covidwho-754367

ABSTRACT

Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of thromboembolic complications due to systemic coagulation activation. Little is known about the role of direct anticoagulants (DOACs) in COVID-19 related thrombosis. In this audit we sought to distinguish COVID-19 hospitalised patients with a diagnosis of venous thromboembolism (VTE) and record their outcomes over a period of 3 months (01/02/2020-30/04/2020). A total of 1583 patients were diagnosed with laboratory proven COVID-19 disease. Amongst them, 38 patients (0.82%) suffered VTE (median age 68 years, male/female: 20/18). VTE was the presenting symptom on admission in 71%. Pulmonary embolism was diagnosed in 92% of patients; 5 patients required intensive care and 3 underwent thrombolysis. 27 patients received initial treatment with unfractionated heparin/low molecular weight heparin (LMWH) while 10 were treated with direct anticoagulants (DOACs). After a median follow up of 25 days, 29 (76%) patients were alive while 5 were still hospitalised. Most patients (83%) were discharged on DOACs, no VTE recurrence or bleeding was recorded post-discharge. Our results suggest that direct anticoagulants could be a safe and effective treatment option in selected COVID-19 positive patients who have suffered venous thromboembolism.


Subject(s)
COVID-19 , Factor Xa Inhibitors/administration & dosage , Heparin/administration & dosage , Pulmonary Embolism , Venous Thromboembolism , Aftercare/statistics & numerical data , Aged , COVID-19/blood , COVID-19/complications , COVID-19/drug therapy , COVID-19/epidemiology , Clinical Audit , Critical Care/methods , Critical Care/statistics & numerical data , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolytic Agents/administration & dosage , Humans , Male , Outcome and Process Assessment, Health Care , Pulmonary Embolism/diagnosis , Pulmonary Embolism/drug therapy , Pulmonary Embolism/etiology , SARS-CoV-2/isolation & purification , Thrombolytic Therapy/methods , Thrombolytic Therapy/statistics & numerical data , United Kingdom/epidemiology , Venous Thromboembolism/diagnosis , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology
16.
J Stroke Cerebrovasc Dis ; 29(8): 104982, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-343281

ABSTRACT

We report a case of ophthalmic artery occlusion (OAO) in a young patient with COVID-19 infection that was on therapeutic anticoagulation with apixaban for deep venous thrombosis (DVT). A 48-year-old man with obesity was hospitalized with a severe form of COVID-19 infection, complicated with acute respiratory failure, septic shock, dilated cardiomyopathy and fungemia. Despite treatment with prophylactic enoxaparin (initial D-Dimer 1.14 µg/ml FEU (normal < 0.05 µg/ml FEU), D-Dimer increased to above 20 µg/ml FEU and patient continued to spike high fevers. This prompted further investigations and upper and lower extremities DVTs were confirmed and managed with enoxaparin 1 mg/kg twice daily. D-dimer level decreased to 4.98 µg/ml FEU while on therapeutic anticoagulation. Three weeks later pending hospital discharge, the anticoagulation was switched to oral apixaban 10 mg twice daily. Patient developed acute severe right eye visual loss of no light perception and was diagnosed with incomplete OAO. D-Dimer was elevated at 2.13 µg/ml FEU. Stroke etiological work-up found no embolic sources, resolution of the dilated cardiomyopathy and negative antiphospholipid antibodies. Treatment was changed to enoxaparin and no thrombotic events were encountered to date. Ocular vascular complications have not yet been reported in COVID-19. Controversy exists on the best management algorithm for the hypercoagulable state associated to COVID-19 Either direct oral anticoagulants or low-molecular-weight-heparin are considered appropriate at discharge for patients with venous thromboembolism. The optimum regimen for ischemic stroke prevention and the significance of D-Dimer for anticoagulation monitoring in COVID-19 remain unclear.


Subject(s)
Arterial Occlusive Diseases/etiology , Coronavirus Infections/drug therapy , Factor Xa Inhibitors/administration & dosage , Ophthalmic Artery , Pneumonia, Viral/drug therapy , Pyrazoles/administration & dosage , Pyridones/administration & dosage , Venous Thrombosis/drug therapy , Arterial Occlusive Diseases/diagnostic imaging , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Drug Substitution , Enoxaparin/administration & dosage , Factor Xa Inhibitors/adverse effects , Host Microbial Interactions , Humans , Male , Middle Aged , Ophthalmic Artery/diagnostic imaging , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Pyrazoles/adverse effects , Pyridones/adverse effects , Risk Factors , SARS-CoV-2 , Treatment Outcome , Venous Thrombosis/blood , Venous Thrombosis/diagnosis , Venous Thrombosis/virology
17.
J Thromb Haemost ; 18(6): 1320-1323, 2020 06.
Article in English | MEDLINE | ID: covidwho-116313

ABSTRACT

BACKGROUND: Antiviral drugs are administered in patients with severe COVID-19 respiratory syndrome, including those treated with direct oral anticoagulants (DOACs). Concomitant administration of antiviral agents has the potential to increase their plasma concentration. A series of patients managed in the Cremona Thrombosis Center were admitted at Cremona Hospital for SARS-CoV-2 and started antiviral drugs without stopping DOAC therapy. DOAC plasma levels were measured in hospital and results compared with those recorded before hospitalization. METHODS: All consecutive patients on DOACs were candidates for administration of antiviral agents (lopinavir, ritonavir, or darunavir). Plasma samples for DOAC measurement were collected 2to 4 days after starting antiviral treatment, at 12 hours from the last dose intake in patients on dabigatran and apixaban, and at 24 hours in those on rivaroxaban and edoxaban. For each patient, C-trough DOAC level, expressed as ng/mL, was compared with the one measured before hospitalization. RESULTS: Of the 1039 patients hospitalized between February 22 and March 15, 2020 with COVID-19 pneumonia and candidates for antiviral therapy, 32 were on treatment with a DOAC. DOAC was stopped in 20 and continued in the remaining 12. On average, C-trough levels were 6.14 times higher during hospitalization than in the pre-hospitalization period. CONCLUSION: DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels. In order to prevent bleeding complications, we believe that physicians should consider withholding DOACs from patients with SARS-CoV-2 and replacing them with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge.


Subject(s)
Antithrombins/blood , Antiviral Agents/adverse effects , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Dabigatran/blood , Factor Xa Inhibitors/blood , Pneumonia, Viral/drug therapy , Pyrazoles/blood , Pyridines/blood , Pyridones/blood , Thiazoles/blood , Administration, Oral , Aged , Aged, 80 and over , Antithrombins/administration & dosage , Antithrombins/adverse effects , Antiviral Agents/administration & dosage , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Dabigatran/administration & dosage , Dabigatran/adverse effects , Darunavir/adverse effects , Drug Interactions , Drug Monitoring , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Humans , Italy , Lopinavir/adverse effects , Male , Pandemics , Patient Safety , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridines/administration & dosage , Pyridines/adverse effects , Pyridones/administration & dosage , Pyridones/adverse effects , Risk Assessment , Risk Factors , Ritonavir/adverse effects , SARS-CoV-2 , Severity of Illness Index , Thiazoles/administration & dosage , Thiazoles/adverse effects
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