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1.
BMJ Open ; 12(5): e051971, 2022 May 02.
Article in English | MEDLINE | ID: covidwho-1832439

ABSTRACT

OBJECTIVES: Coagulation changes associated with COVID-19 suggest the presence of a hypercoagulable state with pulmonary microthrombosis and thromboembolic complications. We assessed the dynamic association of COVID-19-related coagulation abnormalities with respiratory failure and mortality. DESIGN: Single-centre, prospective cohort study with descriptive analysis and logistic regression. SETTING: Tertiary care hospital, North India. PARTICIPANTS: Patients with COVID-19 pneumonia requiring intensive care unit (ICU) admission between August 2020 and November 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: We compared the coagulation abnormalities using standard coagulation tests like prothrombin time, D-dimer, platelet count, etc and point-of-care global coagulation test, Sonoclot (glass beaded(gb) and heparinase-treated(h)). Incidence of thromboembolic or bleeding events and presence of endogenous heparinoids were assessed. Cox proportional Hazards test was used to assess the predictors of 28-day mortality. MEASUREMENT: All patients underwent Sonoclot (glass beaded) test at admission apart from the routine investigations. In patients at risk of thromboembolic or bleeding phenomena, paired tests were performed at day 1 and 3 with Sonoclot. Activated clotting time (ACT) <110 s and peak amplitude >75 units were used as the cut-off for hypercoagulable state. Presence of heparin-like effect (HLE) was defined by a correction of ACT ≥40 s in h-Sonoclot. RESULTS: Of 215 patients admitted to ICU, we included 74 treatment naive subjects. A procoagulant profile was seen in 45.5% (n=5), 32.4% (n=11) and 20.7% (n=6) in low-flow, high-flow and invasive ventilation groups. Paired Sonoclot assays in a subgroup of 33 patients demonstrated the presence of HLE in 17 (51.5%) and 20 (62.5%) at day 1 and 3, respectively. HLE (day 1) was noted in 59% of those who bled during the disease course. Mortality was observed only in the invasive ventilation group (16, 55.2%) with overall mortality of 21.6%. HLE predicted the need for mechanical ventilation (HR 1.2 CI 1.04 to 1.4 p=0.00). On multivariate analysis, the presence of HLE (HR 1.01; CI 1.006 to 1.030; p=0.025), increased C reactive protein (HR 1.040; CI 1.020 to 1.090; p=0.014), decreased platelet function (HR 0.901; CI 0.702 to 1.100 p=0.045) predicted mortality at 28days. CONCLUSION: HLE contributed to hypocoagulable effect and associated with the need for invasive ventilation and mortality in patients with severe COVID-19 pneumonia. TRIAL REGISTRATION: NCT04668404; ClinicalTrials.gov.in. Available from https://clinicaltrials.gov/ct2/show/NCT04668404.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Anticoagulants/therapeutic use , COVID-19/complications , Fibrin Fibrinogen Degradation Products , Hemorrhage , Heparin/therapeutic use , Humans , Point-of-Care Systems , Prospective Studies
2.
Surgery ; 171(5): 1422-1426, 2022 May.
Article in English | MEDLINE | ID: covidwho-1829571

ABSTRACT

BACKGROUND: To determine the impact of COVID-19 infection in patients with chronic limb-threatening ischemia, mainly the limb salvage estimates rate and the overall survival. METHODS: This was a retrospective, consecutive cohort study of chronic limb-threatening ischemia in patients with COVID-19 infection. RESULTS: Overall, 35 patients with chronic limb-threatening ischemia and COVID-19 infection were evaluated. The mean age of the patients was 72.51 years, and most of them were male (60%), with arterial hypertension (85.7%), followed by diabetes mellitus (80%) and tobacco user (71.4%). There was a higher prevalence of wound, ischemia and foot infection (WIfI) classification 4 with 58.8% and Rutherford grade 5 (74.3%). The factors related to overall mortality rate were: D-dimer >1,000 mg/dL (hazard ratio = 22.7, P < .001, confidence interval = 10.49-26.52), respiratory symptoms (hazard ratio = 16.6, P < .001, confidence interval = 9.87-20.90), chest computed tomography compromising higher than 50% of the pulmonary tract (hazard ratio = 16,0, P < .001, confidence interval = 10.41-20.55), acute kidney failure (hazard ratio = 21.58, P < .001, confidence interval = 16.5-30.5), chronic kidney disease (hazard ratio = 4.4, P = .036, confidence interval = 1.45-10.1), therapeutic anticoagulation (hazard ratio = 8.37, P = .004, confidence interval = 1.35-8.45), and WIfI classification (hazard ratio = 5.28, P = .022, confidence interval = 1.34-10.01). The following were related to limb loss: D-dimer >1,000 mg/mL (hazard ratio = 5.47, P = .02, confidence interval = 1.94-10.52), respiratory symptoms (hazard ratio = 5.42, P = .02, confidence interval = 1.87-10.90), and WIfI classification (hazard ratio = 4.44, P = .035, confidence interval = 1.34-8.01). CONCLUSION: This study concluded that COVID-19 has a catastrophic impact among patients with chronic limb-threatening ischemia. The main factors related to overall mortality were D-dimer >1,000 mg/dL, respiratory symptoms, chest computed tomography compromising higher than 50% of the pulmonary tract, acute kidney failure, chronic kidney disease, therapeutic anticoagulation, and WIfI classification. The factors related to limb loss were WIfI classification, D-dimer >1,000 mg/mL and respiratory symptoms.


Subject(s)
COVID-19 , Peripheral Arterial Disease , Wound Infection , Aged , Amputation , Anticoagulants , COVID-19/complications , Cohort Studies , Female , Humans , Ischemia/surgery , Kaplan-Meier Estimate , Limb Salvage , Male , Peripheral Arterial Disease/surgery , Predictive Value of Tests , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Wound Healing , Wound Infection/diagnosis , Wound Infection/surgery
3.
PLoS One ; 17(5): e0266944, 2022.
Article in English | MEDLINE | ID: covidwho-1822269

ABSTRACT

BACKGROUND: Early reports of increased thrombosis risk with SARS-CoV-2 infection led to changes in venous thromboembolism (VTE) management. Real-world data on the prevalence, efficacy and harms of these changes informs best practices. OBJECTIVE: Define practice patterns and clinical outcomes related to VTE diagnosis, prevention, and management in hospitalized patients with coronavirus disease-19 (COVID-19) using a multi-hospital US sample. METHODS: In this retrospective cross-sectional study of 1121 patients admitted to 33 hospitals, exposure was dose of anticoagulant prescribed for VTE prophylaxis (standard, intensified, therapeutic), and primary outcome was VTE (pulmonary embolism [PE] and deep vein thrombosis [DVT]); secondary outcomes were PE, DVT, arterial thromboembolism (ATE), and bleeding events. Multivariable logistic regression models accounting for clustering by site and adjusted for risk factors were used to estimate odds ratios (ORs). Inverse probability weighting was used to account for confounding by indication. RESULTS: 1121 patients (mean age 60 ± 18, 47% female) admitted with COVID-19 between February 2, 2020 and December 31, 2020 to 33 US hospitals were included. Pharmacologic VTE prophylaxis was prescribed in 86%. Forty-seven patients (4.2%) had PE, 51 (4.6%) had DVT, and 23 (2.1%) had ATE. Forty-six patients (4.1%) had major bleeding and 46 (4.1%) had clinically relevant non-major bleeding. Compared to standard prophylaxis, adjusted odds of VTE were 0.67 (95% CI 0.21-2.1) with no prophylaxis, 1.0 (95% CI 0.06-17) with intensified, and 3.0 (95% CI 0.89-10) with therapeutic. Adjusted odds of bleeding with no prophylaxis were 5.6 (95% CI 3.0-11) and 5.3 (95% CI 3.0-10) with therapeutic (no events on intensified dosing). CONCLUSIONS: Therapeutic anticoagulation was associated with a 3-fold increased odds of VTE and 5-fold increased odds of bleeding. While higher bleeding rates with high-intensity prophylaxis were likely due to full-dose anticoagulation, we conclude that high thrombosis rates were due to clinical concern for thrombosis before formal diagnosis.


Subject(s)
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , Adult , Aged , Anticoagulants , Cross-Sectional Studies , Female , Hemorrhage/epidemiology , Hospitals , Humans , Male , Middle Aged , Pulmonary Embolism/drug therapy , Pulmonary Embolism/epidemiology , Pulmonary Embolism/prevention & control , Retrospective Studies , SARS-CoV-2 , Venous Thromboembolism/drug therapy , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control
4.
J Cardiothorac Surg ; 17(1): 108, 2022 May 07.
Article in English | MEDLINE | ID: covidwho-1822197

ABSTRACT

INTRODUCTION: Extracorporeal circulation (ECC) in cardiac surgery is performed under systemic heparinization. Adequacy of heparin therapy and anticoagulation during ECC is assessed by activated clotting time (ACT), although there are concerns regarding the reliability of this measure. The ACT can be affected by factors other than heparin anticoagulation. A novel factor that should be considered is the influence of a COVID-19 infection. More than half of the hospitalized COVID-19 patients develop coagulation abnormalities with dysregulated coagulation test results. Patients recently recovered from COVID-19 may still demonstrate some forms of coagulation disorder affecting the ACT. This case describes an inaccurate point-of-care ACT testing in a patient with previous COVID-19 infection undergoing cardiac surgery with ECC and the alternative coagulation testing performed. CASE PRESENTATION: A 77-years-old Caucasian male presented with symptomatic severe mitral valve regurgitation for which he underwent surgery. Medical history revealed a COVID-19 infection one month before surgery. Pre-operative hematological lab results were normal and baseline ACT during surgery was 100 s. To achieve an adequate ACT of > 400 s, multiple doses of heparin were needed and after administration of a triple dose (75,000 IE heparin in total) this adequate ACT was achieved. In the meanwhile we measured anti-Xa level and APTT, which were at adequate levels when ACT was still < 400 s. DISCUSSION: This case emphasizes the need of alternative methods for monitoring heparin therapy in case ACT does not respond adequately. Another point to highlight in this case is the poorly correlated relation between ACT and APTT and anti-Xa in light of the recent COVID-19 infection. Although studies have shown that COVID-19 infection can cause coagulopathy and altered hemostatic parameters, ACT has never been investigated in COVID-19 patient. Understanding the correlation between ACT, APTT and anti-Xa in COVID-19 patients is mandatory.


Subject(s)
COVID-19 , Cardiopulmonary Bypass , Aged , Anticoagulants/therapeutic use , Heparin/therapeutic use , Heparin, Low-Molecular-Weight , Humans , Male , Point-of-Care Systems , Reproducibility of Results , Whole Blood Coagulation Time
5.
J Thromb Haemost ; 20(5): 1056-1066, 2022 05.
Article in English | MEDLINE | ID: covidwho-1822054

ABSTRACT

Venous thromboembolism is a very common and costly health problem worldwide. Anticoagulant treatment for VTE is imperfect: all have the potential for significant bleeding, and none prevent the development of post thrombotic syndrome after deep vein thrombosis or chronic thromboembolic pulmonary hypertension after pulmonary embolism. For these reasons, alternate forms of therapy with improved efficacy and decreased bleeding are needed. Selectins are a family (P-selectin, E-selectin, L-selectin) of glycoproteins that facilitate and augment thrombosis, modulating neutrophil, monocyte, and platelet activity. P- and E-selectin have been investigated as potential biomarkers for thrombosis. Inhibition of P-selectin and E-selectin decrease thrombosis and vein wall fibrosis, with no increase in bleeding. Selectin inhibition is a promising avenue of future study as either a stand-alone treatment for VTE or as an adjunct to standard anticoagulation therapies.


Subject(s)
Pulmonary Embolism , Thrombosis , Venous Thromboembolism , Venous Thrombosis , Anticoagulants/therapeutic use , E-Selectin , Hemorrhage , Humans , Pulmonary Embolism/drug therapy , Selectins , Venous Thromboembolism/drug therapy , Venous Thrombosis/prevention & control
6.
BMJ Open ; 12(4): e059383, 2022 Apr 26.
Article in English | MEDLINE | ID: covidwho-1816767

ABSTRACT

INTRODUCTION: COVID-19 induces venous, arterial and microvascular thrombosis, involving several pathophysiological processes. In patients with severe COVID-19 without macrovascular thrombosis, escalating into high-dose prophylactic anticoagulation (HD-PA) or therapeutic anticoagulation (TA) could be beneficial in limiting the extension of microvascular thrombosis and forestalling the evolution of lung and multiorgan microcirculatory dysfunction. In the absence of data from randomised trials, clinical practice varies widely. METHODS AND ANALYSIS: This is a French multicentre, parallel-group, open-label, randomised controlled superiority trial to compare the efficacy and safety of three anticoagulation strategies in patients with COVID-19. Patients with oxygen-treated COVID-19 showing no pulmonary artery thrombosis on computed tomography with pulmonary angiogram will be randomised to receive either low-dose PA, HD-PA or TA for 14 days. Patients attaining the extremes of weight and those with severe renal failure will not be included. We will recruit 353 patients. Patients will be randomised on a 1:1:1 basis, and stratified by centre, use of invasive mechanical ventilation, D-dimer levels and body mass index. The primary endpoint is a hierarchical criterion at day 28 including all-cause mortality, followed by the time to clinical improvement defined as the time from randomisation to an improvement of at least two points on the ordinal clinical scale. Secondary outcomes include thrombotic and major bleeding events at day 28, individual components of the primary endpoint, number of oxygen-free, ventilator-free and vasopressor-free days at day 28, D-dimer and sepsis-induced coagulopathy score at day 7, intensive care unit and hospital stay at day 28 and day 90, and all-cause death and quality of life at day 90. ETHICS AND DISSEMINATION: The study has been approved by an ethical committee (Ethics Committee, Ile de France VII, Paris, France; reference 2020-A03531-38). Patients will be included after obtaining their signed informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04808882.


Subject(s)
COVID-19 , Anticoagulants/therapeutic use , Blood Coagulation , Humans , Microcirculation , Multicenter Studies as Topic , Quality of Life , Randomized Controlled Trials as Topic
7.
Intern Med J ; 52(5): 717-723, 2022 May.
Article in English | MEDLINE | ID: covidwho-1816561

ABSTRACT

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare, but serious, syndrome characterised by thrombocytopenia, thrombosis, a markedly raised D-dimer and the presence of anti-platelet factor-4 (PF4) antibodies following COVID-19 adenovirus vector vaccination. VITT occurs at a rate of approximately 2 per 100 000 first-dose vaccinations and appears exceedingly rare following second doses. Our current understanding of VITT pathogenesis is based on the observations that patients with VITT have antibodies that bind to PF4 and have the ability to form immune complexes that induce potent platelet activation. However, the precise mechanisms that lead to pathogenic VITT antibody development remain a source of active investigation. Thrombosis in VITT can manifest in any vascular bed and affect multiple sites simultaneously. While there is a predilection for splanchnic and cerebral venous sinus thrombosis, VITT also commonly presents with deep vein thrombosis and pulmonary embolism. Pillars of management include anticoagulation with a non-heparin anticoagulant, intravenous immunoglobulin and 'rescue' therapies, such as plasma exchange for severe cases. VITT can be associated with a high mortality rate and significant morbidity, but awareness and optimal therapy have significantly improved outcomes in Australia. A number of questions remain unanswered, including why VITT is so rare, reasons for the predilection for thrombosis in unusual sites, how long pathological antibodies persist, and the optimal duration of anticoagulation. This review will provide an overview of the presentation, diagnostic workup and management strategies for patients with VITT.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Anticoagulants/adverse effects , COVID-19 Vaccines/adverse effects , Humans , Platelet Factor 4/adverse effects , SARS-CoV-2 , Thrombocytopenia/chemically induced , Thrombosis/chemically induced , Thrombosis/complications , Vaccines/adverse effects
9.
Front Cell Infect Microbiol ; 12: 861703, 2022.
Article in English | MEDLINE | ID: covidwho-1809353

ABSTRACT

Many discharged COVID-19 patients affected by sequelae experience reduced quality of life leading to an increased burden on the healthcare system, their families and society at large. Possible pathophysiological mechanisms of long COVID include: persistent viral replication, chronic hypoxia and inflammation. Ongoing vascular endothelial damage promotes platelet adhesion and coagulation, resulting in the impairment of various organ functions. Meanwhile, thrombosis will further aggravate vasculitis contributing to further deterioration. Thus, long COVID is essentially a thrombotic sequela. Unfortunately, there is currently no effective treatment for long COVID. This article summarizes the evidence for coagulation abnormalities in long COVID, with a focus on the pathophysiological mechanisms of thrombosis. Extracellular vesicles (EVs) released by various types of cells can carry SARS-CoV-2 through the circulation and attack distant tissues and organs. Furthermore, EVs express tissue factor and phosphatidylserine (PS) which aggravate thrombosis. Given the persistence of the virus, chronic inflammation and endothelial damage are inevitable. Pulmonary structural changes such as hypertension, embolism and fibrosis are common in long COVID. The resulting impaired lung function and chronic hypoxia again aggravates vascular inflammation and coagulation abnormalities. In this article, we also summarize recent research on antithrombotic therapy in COVID-19. There is increasing evidence that early anticoagulation can be effective in improving outcomes. In fact, persistent systemic vascular inflammation and dysfunction caused by thrombosis are key factors driving various complications of long COVID. Early prophylactic anticoagulation can prevent the release of or remove procoagulant substances, thereby protecting the vascular endothelium from damage, reducing thrombotic sequelae, and improving quality of life for long-COVID patients.


Subject(s)
COVID-19 , Thrombosis , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Humans , Hypoxia , Inflammation/complications , Quality of Life , SARS-CoV-2 , Thrombosis/etiology , Thrombosis/prevention & control
10.
JAMA ; 327(13): 1247-1259, 2022 04 05.
Article in English | MEDLINE | ID: covidwho-1801957

ABSTRACT

Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Interventions: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Results: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). Conclusions and Relevance: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.


Subject(s)
COVID-19 , Critical Illness , Platelet Aggregation Inhibitors , Venous Thromboembolism , Adult , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Aspirin/adverse effects , Aspirin/therapeutic use , Bayes Theorem , COVID-19/complications , COVID-19/drug therapy , COVID-19/mortality , COVID-19/therapy , Critical Illness/mortality , Critical Illness/therapy , Female , Hemorrhage/chemically induced , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Purinergic P2Y Receptor Antagonists/adverse effects , Purinergic P2Y Receptor Antagonists/therapeutic use , Respiration, Artificial , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology
11.
J Med Invest ; 69(1.2): 148-151, 2022.
Article in English | MEDLINE | ID: covidwho-1799016

ABSTRACT

INTRODUCTION: Early prophylactic administration of anticoagulants is recommended in patients with coronavirus disease 2019 (COVID-19). A case of retroperitoneal hemorrhage during inpatient treatment for COVID-19 is reported. CASE PRESENTATION: A 69-year-old man was diagnosed with COVID-19 6 days after symptom onset. After admission for difficulty of breathing, he was treated with steroid pulse therapy, remdesivir, and heparin sodium. On day 16 after admission, his hemoglobin and blood pressure dropped. Computed tomography showed a left retroperitoneal hematoma and multiple areas of extravasation in bilateral iliopsoas muscles. Anticoagulation therapy was stopped, and blood transfusion therapy was chosen by considering poor general condition caused by severe pneumonia. On day 19, the hemoglobin and blood pressure improved, and blood transfusion was stopped. However, he died on day 25 due to pneumonia. CONCLUSION: When retroperitoneal hemorrhage occurs as a complication of COVID-19, appropriate treatment decision, transcatheter arterial embolization or conservative treatment, should be chosen based on patient's condition. J. Med. Invest. 69 : 148-151, February, 2022.


Subject(s)
COVID-19 , Aged , Anticoagulants/therapeutic use , COVID-19/complications , Hemoglobins , Hemorrhage/etiology , Hemorrhage/therapy , Heparin , Humans , Male
12.
Viruses ; 14(4)2022 Apr 14.
Article in English | MEDLINE | ID: covidwho-1792420

ABSTRACT

Critically ill COVID-19 patients are at high risk for venous thromboembolism (VTE), namely deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and death. The optimal anticoagulation strategy in critically ill patients with COVID-19 remains unknown. This study investigated the ante mortem incidence as well as postmortem prevalence of VTE, the factors predictive of VTE, and the impact of changed anticoagulation practice on patient survival. We conducted a consecutive retrospective analysis of postmortem COVID-19 (n = 64) and non-COVID-19 (n = 67) patients, as well as ante mortem COVID-19 (n = 170) patients admitted to the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Baseline patient characteristics, parameters related to the intensive care unit (ICU) stay, and the clinical and autoptic presence of VTE were evaluated and statistically compared between groups. The occurrence of VTE in critically ill COVID-19 patients is confirmed in both ante mortem (17%) and postmortem (38%) cohorts. Accordingly, comparing the postmortem prevalence of VTE between age- and sex-matched COVID-19 (43%) and non-COVID-19 (0%) cohorts, we found the statistically significant increased prevalence of VTE in critically ill COVID-19 cohorts (p = 0.001). A change in anticoagulation practice was associated with the statistically significant prolongation of survival time (HR: 2.55, [95% CI 1.41-4.61], p = 0.01) and a reduction in VTE occurrence (54% vs. 25%; p = 0.02). In summary, in the autopsy as well as clinical cohort of critically ill patients with COVID-19, we found that VTE was a frequent finding. A change in anticoagulation practice was associated with a statistically significantly prolonged survival time.


Subject(s)
COVID-19 , Venous Thromboembolism , Anticoagulants/therapeutic use , Autopsy , COVID-19/epidemiology , Critical Illness , Humans , Retrospective Studies , Risk Factors , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology
13.
Pol Merkur Lekarski ; 50(296): 118-123, 2022 Apr 19.
Article in English | MEDLINE | ID: covidwho-1790558

ABSTRACT

COVID-19 patients, particularly those with severe pulmonary involvement, are at an increased thromboembolic risk related, among various causes, to the cytokine storm and excessive activation of the coagulation cascade and platelets. Different intensity of anticoagulation for them is proposed, mainly with low molecular weight heparins (LMWHs); in a confirmed pulmonary embolism (PE) the therapeutic dose of LMWH is routinely used. Some authors suggest that hemorrhagic complications in COVID-19 patients are rare. At the same time, one can find reports on internal bleeding, including retroperitoneal hematoma (RPH) and other abdominal hematomas. CASE REPORTS: The authors describe 5 cases (3 of those aged more than 80 years) with giant RPHs and with moderate/severe COVID-19 pneumonia, treated before RPH diagnosis with different enoxaparin doses. The therapeutic dose was given to the male with verified PE limited to the segmental/subsegmental pulmonary arteries and initially to the female in whom echocardiography was strongly suggestive of PE, yet this diagnosis was excluded on CT angiography. In one patient, the enoxaparin dose was escalated from 40 mg bd to 60 mg bd after the D-dimer increase. Two patients had bleeding complications despite the enoxaparin dose restricted to 40 mg/daily or bd. Two males had a coexistent psoas hematoma while in only one female there was a coexistent femoral hematoma. RPHs occurred between day 4 and 14 of hospitalization and all were treated conservatively. Three patients who died were particularly charged, so their deaths were not merely directly associated with RPH, which was closely analyzed in one autopsy performed. The authors underline that the choice of anticoagulation intensity in patients with COVID-19 pneumonia without venous thromboembolism seems sometimes difficult but recent publications indicate the low prophylactic enoxaparin dose as an optimal option. Anticoagulation dose escalation based only on the D-dimer level may not be appropriate for certain patients; moreover, the D-dimer increase is commonly observed during internal bleeding.


Subject(s)
COVID-19 , Pulmonary Embolism , Adult , Aged , Aged, 80 and over , Anticoagulants , COVID-19/complications , Enoxaparin/adverse effects , Enoxaparin/therapeutic use , Female , Hematoma/chemically induced , Hematoma/drug therapy , Heparin, Low-Molecular-Weight/adverse effects , Humans , Male , Middle Aged , Pulmonary Embolism/drug therapy
14.
Kardiologiia ; 62(3): 21-27, 2022 Mar 31.
Article in Russian, English | MEDLINE | ID: covidwho-1789754

ABSTRACT

Aim      To evaluate the incidence and features of left atrial appendage (LAA) thrombosis in patients with persistent atrial fibrillation (AF) after novel coronavirus infection (COVID-19).Material and methods  Percutaneous echocardiography (pcEchoCG) was performed for 128 patients with persistent AF prepared for cardioversion, 36 (28.1 %) of whom had had COVID-19. In 3 (8.3 %) patients, the lung lesion area was 50-75 %; in 31 (86.1 %) patients, 25-50 %; in 1 (2.8 %) patient, less than 25 %. One patient had no lung lesion. Median time from the onset of COVID-19 to the patient enrollment in the study was 76.5 days. At the time of enrollment, the polymerase chain reaction test for SARS-CoV-2 was negative in all patients.Results Patients after COVID-19 and those who had not had COVID-19 were comparable by age (62.5±9.2 and 62.4±9.1 years, respectively; р=0.956), gender (men 52.8 and 59.8 %, respectively; р=0.471), and risk of stroke (score 2.19±1.28 and score 1.95±1.35, respectively; р=0.350). Duration of the last arrhythmia episode was longer for patients after COVID-19 than for the comparison group (76.5 and 45.0 days, respectively; р=0.011). All patients received oral anticoagulants. 55.6 % of COVID-19 patients received rivaroxaban, whereas 62.0% of patients who had not had COVID-19 were treated with apixaban. Median duration of the anticoagulant treatment was longer for COVID-19 patients than for the comparison group (61.5 and 32.0 days; р=0.051). LAA thrombus was detected in 7 (19.4 %) patients after COVID-19 and in 6 (6.5 %) patients of the comparison group (р=0.030). In COVID-19 patients, the thrombus adhered to LAA wall over the entire thrombus length whereas in patients who had not have COVID-19, the thrombus had a free part that formed a sharp angle with LAA walls. In the presence of LAA thrombus, the LAA blood flow velocity was considerably higher for COVID-19 patients than for the comparison group (31.0±8.9 and 18.8±4.9 cm/sec, respectively; p=0.010). At the follow-up examination performed at 24.0 days on the average, the thrombus was found to be dissolved in 80 and 50% of patients after and without COVID-19, respectively (р=0.343).Conclusion      In patients with persistent AF after the novel coronavirus infection, LAA thrombosis was detected more frequently than in patients who had never had COVID-19; it was characterized by mural localization and was not associated with a decrease in LAA blood flow velocity.


Subject(s)
Atrial Appendage , Atrial Fibrillation , COVID-19 , Heart Diseases , Thrombosis , Aged , Anticoagulants/therapeutic use , Atrial Appendage/diagnostic imaging , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , COVID-19/complications , Echocardiography, Transesophageal/adverse effects , Heart Diseases/complications , Humans , Male , Middle Aged , SARS-CoV-2 , Thrombosis/diagnosis , Thrombosis/epidemiology , Thrombosis/etiology
17.
Ann Palliat Med ; 11(4): 1317-1325, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1786443

ABSTRACT

BACKGROUND: There currently exists a paucity of data on whether pre-admission anticoagulants use may have benefits among COVID-19 patients by preventing COVID-19 associated thromboembolism. The aim of this study was to assess the association between pre-admission anticoagulants use and COVID-19 adverse outcomes. METHODS: We conducted a population-based cohort studying using the Health Insurance Review and Assessment Service (HIRA) claims data released by the South Korean government. Our study population consisted of South Koreans who were aged 40 years or older and hospitalized with COVID-19 between 1 January 2020 through 15 May 2020. We defined anticoagulants users as individuals with inpatient and outpatient prescription records in 120 days before cohort entry. Our primary endpoint was a composite of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Individual components of the primary endpoint were secondary endpoints. We compared the risk of endpoints between the anticoagulants users and non-users by logistic regression models, with the standardized mortality ratio weighting (SMRW) adjustment. RESULTS: In our cohort of 4,349 patients, for the primary endpoint of mortality, mechanical ventilation and ICU admission, no difference was noted between anticoagulants users and non-users (SMRW OR 1.11, 95% CI: 0.60-2.05). No differences were noted, among individual components. No effect modification was observed by age, sex, history of atrial fibrillation and thromboembolism, and history of cardiovascular disease. When applying the inverse probability of treatment weighting (IPTW) and SMRW with doubly robust methods in sensitivity analysis, anticoagulants use was associated with increased odds of the primary endpoint. CONCLUSIONS: Pre-admission anticoagulants were not determined to have a protective role against severe COVID-19 outcomes.


Subject(s)
COVID-19 , Thromboembolism , Anticoagulants/therapeutic use , Humans , Prognosis , SARS-CoV-2 , Thromboembolism/chemically induced
18.
Viruses ; 14(4)2022 Apr 07.
Article in English | MEDLINE | ID: covidwho-1786073

ABSTRACT

(1) Background: It is well-established that coronavirus disease-2019 (COVID-19) is highly pro-inflammatory, leading to activation of the coagulation cascade. COVID-19-induced hypercoagulability is associated with adverse outcomes and mortality. Current guidelines recommend that hospitalized COVID-19 patients should receive pharmacological prophylaxis against venous thromboembolism (VTE). (2) INTERACT is a retrospective, phase IV, observational cohort study aiming to evaluate the overall clinical effectiveness and safety of a higher than conventionally used prophylactic dose of anticoagulation with tinzaparin administered for VTE prevention in non-critically ill COVID-19 patients with moderate disease severity. (3) Results: A total of 705 patients from 13 hospitals in Greece participated in the study (55% men, median age 62 years). Anticoagulation with tinzaparin was initiated immediately after admission. A full therapeutic dose was received by 36.3% of the participants (mean ± SD 166 ± 33 IU/Kgr/day) and the remaining patients (63.9%) received an intermediate dose (mean ± SD 114 ± 22 IU/Kgr/day). The median treatment duration was 13 days (Q1-Q3: 8-20 days). During the study (April 2020 to November 2021), 14 thrombotic events (2.0%) were diagnosed (i.e., three cases of pulmonary embolism (PE) and 11 cases of deep venous thrombosis, DVT). Four bleeding events were recorded (0.6%). In-hospital death occurred in 12 patients (1.7%). Thrombosis was associated with increasing age (median: 74.5 years, Q1-Q3: 62-79, for patients with thrombosis vs. 61.9 years, Q1-Q3: 49-72, p = 0.0149), increased D-dimer levels for all three evaluation time points (at admission: 2490, Q1-Q3: 1580-6480 vs. 700, Q1-Q3: 400-1475, p < 0.0001), one week ± two days after admission (3510, Q1-Q3: 1458-9500 vs. 619, Q1-Q3: 352-1054.5, p < 0.0001), as well as upon discharge (1618.5, Q1-Q3: 1010-2255 vs. 500, Q1-Q3: 294-918, p < 0.0001). Clinical and laboratory improvement was affirmed by decreasing D-dimer and CRP levels, increasing platelet numbers and oxygen saturation measurements, and a drop in the World Health Organization (WHO) progression scale. (4) Conclusions: The findings of our study are in favor of prophylactic anticoagulation with an intermediate to full therapeutic dose of tinzaparin among non-critically ill patients hospitalized with COVID-19.


Subject(s)
COVID-19 , Thrombosis , Venous Thromboembolism , Aged , Anticoagulants/adverse effects , COVID-19/drug therapy , Female , Hospital Mortality , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Tinzaparin , Venous Thromboembolism/drug therapy , Venous Thromboembolism/prevention & control
19.
BMJ ; 377: e069590, 2022 04 06.
Article in English | MEDLINE | ID: covidwho-1779333

ABSTRACT

OBJECTIVE: To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19. DESIGN: Self-controlled case series and matched cohort study. SETTING: National registries in Sweden. PARTICIPANTS: 1 057 174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants. MAIN OUTCOMES MEASURES: Self-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event). RESULTS: Compared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after covid-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after covid-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after covid-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical covid-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with covid-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding. CONCLUSIONS: The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19.


Subject(s)
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , Venous Thrombosis , Anticoagulants/adverse effects , COVID-19/complications , COVID-19/epidemiology , Cohort Studies , Hemorrhage/chemically induced , Hemorrhage/etiology , Humans , Pulmonary Embolism/epidemiology , Pulmonary Embolism/etiology , Pulmonary Embolism/prevention & control , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/chemically induced , Venous Thrombosis/chemically induced , Venous Thrombosis/etiology
20.
Am J Ther ; 29(1): e43-e49, 2021 Nov 26.
Article in English | MEDLINE | ID: covidwho-1778979

ABSTRACT

BACKGROUND: Therapeutic doses of anticoagulation have been administered to patients with coronavirus-19 disease (Covid-19) without thromboembolism, although there is a lack of robust evidence supporting this practice. STUDY QUESTION: To compare outcomes between patients admitted to the hospital for Covid-19 who received full-dose anticoagulation purely for the indication of Covid-19 and patients who received prophylactic doses of anticoagulation. STUDY DESIGN: This is a multicenter retrospective cohort study, including 7 community hospitals in Michigan. Patients were >18 years of age, confirmed positive for Covid-19 by polymerase chain reaction, and admitted to the hospital between March 10 and May 3, 2020. Exposed group: Patients receiving therapeutic dose anticoagulation for Covid-19 for any duration excluding clinically evident venous thromboembolism, atrial fibrillation, and myocardial infarction; control group: Patients receiving prophylactic anticoagulation. Propensity score matching was used to adjust for the nonrandomized nature of the study. MEASURES AND OUTCOMES: The primary endpoint: 30-day in-hospital mortality. Secondary endpoints: intubation, length of hospital stay, and readmissions in survivors. RESULTS: A total of 115 exposed and 115 control patients were analyzed. Rates of 30-day in-hospital mortality were similar (exposed: 33.0% vs. control: 28.7%). Controlling for institution, there was no significant association between treatment and 30-day in-hospital mortality (hazard ratio: 0.63; 95% confidence interval: 0.37-1.06). Survivors had statistically similar length of hospital stay and readmission rates. CONCLUSIONS: We found no difference in mortality in patients with Covid-19 without clinically evident venous thromboembolism, atrial fibrillation, and myocardial infarction who received therapeutic versus prophylactic doses of anticoagulation.


Subject(s)
COVID-19 , Venous Thromboembolism , Anticoagulants/adverse effects , Humans , Propensity Score , Retrospective Studies , SARS-CoV-2
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