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1.
Rinsho Ketsueki ; 63(5): 471-480, 2022.
Article in Japanese | MEDLINE | ID: covidwho-1879649

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 and is known to have thrombotic complications. Various-sized thrombosis occurs in the arteries and veins, especially in lung tissue. The prevention and treatment of thrombosis is an important issue that is directly linked to its prognosis. Additionally, the drastic fibrinolytic enhancement and lethal bleeding in some severe COVID-19 are important issues. The efficacy of antiplatelet for COVID-19 is controversial. Thus, warfarin or tranexamic acid alone should be avoided. Heparin is effective for mild to moderate COVID-19 but is ineffective in severe cases since the anticoagulant activity of heparin is insufficient or heparin increases major bleeding. In severe COVID-19 cases with drastic fibrinolytic enhancement, heparin and nafamostat combination therapy may avoid lethal bleeding. In COVID-19 clinical practice, not only the coagulation activation was evaluated but also the fibrinolytic activation to consider treatment strategies.


Subject(s)
COVID-19 , Thrombosis , Anticoagulants/therapeutic use , COVID-19/complications , Fibrinolytic Agents/therapeutic use , Hemorrhage/drug therapy , Heparin , Humans , SARS-CoV-2 , Thrombosis/drug therapy , Thrombosis/etiology , Thrombosis/prevention & control
2.
N Engl J Med ; 386(21): 1986-1997, 2022 05 26.
Article in English | MEDLINE | ID: covidwho-1864788

ABSTRACT

BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).


Subject(s)
Antifibrinolytic Agents , Tranexamic Acid , Antifibrinolytic Agents/adverse effects , Antifibrinolytic Agents/therapeutic use , Canada , Hemorrhage/etiology , Hemorrhage/prevention & control , Humans , Surgical Procedures, Operative , Thrombosis/chemically induced , Thrombosis/drug therapy , Tranexamic Acid/adverse effects , Tranexamic Acid/therapeutic use
3.
BMJ Case Rep ; 15(4)2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1854260

ABSTRACT

A transgender man in his late teens presented with signs of multisystem disease, including hepatitis, mucositis and bone marrow suppression. He later developed dyspnoea, leucocytosis and bilateral pulmonary infiltrates on chest radiograph. He was treated for community-acquired pneumonia. After several days of treatment, he developed hypoxaemic respiratory failure due to bronchoscopy-confirmed diffuse alveolar haemorrhage (DAH). The differential diagnosis and workup were extensive, and he was ultimately treated with intravenous steroids and five sessions of plasmapheresis for a presumed autoimmune aetiology. Investigations were remarkable only for elevated IgM and IgG to Mycoplasma pneumoniae (MP). This case represents a rare presentation of multisystem disease secondary to MP in adults. Clinicians should consider Mycoplasma infection in cases of multisystem disease and observe for DAH even after initiation of appropriate therapy.


Subject(s)
Community-Acquired Infections , Lung Diseases , Adolescent , Adult , Bronchoscopy , Hemorrhage/etiology , Hemorrhage/therapy , Humans , Lung Diseases/diagnosis , Lung Diseases/etiology , Male , Mycoplasma pneumoniae
5.
BMJ Open ; 12(5): e051971, 2022 05 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
6.
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
7.
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
8.
J Thromb Thrombolysis ; 53(4): 766-776, 2022 May.
Article in English | MEDLINE | ID: covidwho-1820966

ABSTRACT

This study describes demographics, thrombotic and bleeding events, mortality, and anticoagulant use among hospitalized patients with COVID-19 in the United States. Premier Healthcare Database data were analyzed to identify inpatients with a discharge diagnosis for COVID-19 (ICD-10-CM code: U07.1) from April 1, 2020 to March 31, 2021, and matched historical controls without COVID-19 (inpatients discharged between April 1, 2018 and March 31, 2019). Thrombotic [including venous thromboembolism (VTE)] and bleeding events were based on ICD-10-CM discharge diagnosis codes. Of the 546,656 patients hospitalized with COVID-19, 20.1% were admitted to the ICU, 62.8% were aged ≥ 60 years, 51.5% were male, and 31.0% were non-white. Any thrombotic event was diagnosed in 10.0% of hospitalized and 20.8% of ICU patients with COVID-19 versus (vs) 11.5% and 24.4% for historical controls, respectively. More VTE events were observed in hospitalized and ICU patients with COVID-19 than historical controls (hospitalized: 4.4% vs 2.7%, respectively; ICU: 8.3% vs 5.2%, respectively; both P < 0.0001). Bleeding events were diagnosed in 10.2% of hospitalized and 21.8% of ICU patients with COVID-19 vs 16.0% and 33.2% for historical controls, respectively. Mortality among hospitalized (12.4%) and ICU (38.5%) patients with COVID-19 was higher vs historical controls (2.4%, P < 0.0001 and 9.4%, P < 0.0001, respectively) and higher in hospitalized patients with COVID-19 who had thrombotic events (29.4%) vs those without thrombotic events (10.8%, P < 0.0001). VTE and mortality were higher in hospitalized and ICU patients with COVID-19 vs historical controls. The presence of thrombotic events was associated with worse outcomes.


Subject(s)
COVID-19 , Thrombosis , Venous Thromboembolism , Anticoagulants/adverse effects , COVID-19/complications , Female , Hemorrhage/chemically induced , Humans , Male , Retrospective Studies , Thrombosis/chemically induced , United States/epidemiology , Venous Thromboembolism/chemically induced , Venous Thromboembolism/epidemiology
9.
Minerva Anestesiol ; 88(3): 107-109, 2022 03.
Article in English | MEDLINE | ID: covidwho-1818989
10.
Am Heart J ; 249: 76-85, 2022 07.
Article in English | MEDLINE | ID: covidwho-1803370

ABSTRACT

BACKGROUND: Screening for atrial fibrillation (AF) is attractive because AF independently raises the risk of ischemic stroke, this risk is largely reversible by long-term oral anticoagulant therapy (OAC), and many patients with AF remain undiagnosed and untreated. Recent trials of one-time brief screening for AF have not produced a significant increase in the proportion of patients diagnosed with AF. Trials of longer-term screening have demonstrated an increase in AF diagnoses, primarily paroxysmal AF. To date, however, no trials have demonstrated that screening for AF results in lower rates of stroke. Clinical practice guidelines conflict in their level of support for screening for AF. METHODS: The GUARD-AF individually randomized trial is designed to test whether screening for AF in individuals age 70 years or greater using a 2-week single-lead electrocardiographic patch monitor can identify patients with undiagnosed AF and lead to treatment with OAC, resulting in a reduced rate of stroke in the screened population. The trial's efficacy end point is hospitalization for stroke (either ischemic or hemorrhagic) and the trial's safety end point is hospitalization for a bleeding event. End points will be ascertained via Medicare claims or electronic health records at 2.5 years after study start. Enrollment is based in primary care practices and the OAC decision for screen-detected cases is left to the patient and their physician. The initial planned target sample size was 52,000, with 26,000 allocated to either screening or to usual care. RESULTS: Trial enrollment was severely hampered by the novel coronavirus disease 2019 (COVID-19) pandemic and stopped at a total enrollment of 11,931 participants. Of 5,965 randomized to the screening arm, 5,713 patients (96%) returned monitors with analyzable results. Incidence of screen-detected and clinically detected AF and associated stroke and bleeding outcomes will be ascertained. CONCLUSIONS: GUARD-AF is the largest AF screening randomized trial using a longer-term patch-based continuous electrocardiographic monitor. The results will contribute important information on the yield of patch-based AF screening, the "burden" of AF detected (percent time in AF, longest episode), and physicians' OAC decisions as a function of AF burden. GUARD-AF's stroke and bleed results will contribute to pooled trial analyses of AF screening, thereby informing future studies and guidelines.


Subject(s)
Atrial Fibrillation , COVID-19 , Stroke , Aged , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Electrocardiography , Hemorrhage/chemically induced , Humans , Medicare , Risk Factors , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , United States
11.
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
12.
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
13.
J Cardiothorac Vasc Anesth ; 36(8 Pt B): 2961-2967, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1795642

ABSTRACT

OBJECTIVES: To compare heparin-based anticoagulation and bivalirudin-based anticoagulation within the context of critically ill patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: An observational study. SETTING: At the intensive care unit of a university hospital. PARTICIPANTS AND INTERVENTIONS: Critically ill patients with a SARS-CoV-2 infection receiving full anticoagulation with heparin or bivalirudin. MEASUREMENTS AND MAIN RESULTS: Twenty-three patients received full anticoagulation with bivalirudin and 60 with heparin. Despite patients in the bivalirudin group having higher mortality risk scores (SAPS II 60 ± 16 v 39 ±7, p < 0.001) and a higher need for extracorporeal support compared to the heparin group, hospital mortality was comparable (57% v 45, p = 0.3). No difference in thromboembolic complications was observed, and bleeding events were more frequent in patients treated with bivalirudin (65% v 40%, p = 0.01). Similar results were confirmed in the subgroup analysis of patients undergoing intravenous anticoagulation; in addition to comparable thrombotic complications occurrence and thrombocytopenia rate, however, no difference in the bleeding rate was observed (65% v 35%, p = 0.08). CONCLUSIONS: Although heparin is the most used anticoagulant in the intensive care setting, bivalirudin-based anticoagulation was safe and effective in a cohort of critically ill patients with SARS-CoV-2. Bivalirudin may be given full consideration as an anticoagulation strategy for critically ill patients with SARS-CoV-2, especially in those with thrombocytopenia and on extracorporeal support.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Thrombocytopenia , Anticoagulants , Antithrombins/therapeutic use , COVID-19/complications , Critical Illness/therapy , Extracorporeal Membrane Oxygenation/methods , Fibrinolytic Agents , Hemorrhage/chemically induced , Heparin/adverse effects , Hirudins , Humans , Recombinant Proteins/therapeutic use , Retrospective Studies , SARS-CoV-2 , Thrombocytopenia/chemically induced
14.
Phlebology ; 37(5): 326-337, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1784999

ABSTRACT

INTRODUCTION: COVID-19 associated VTE is a new disease entity with high morbidity and mortality. The aim of this paper is to review contemporary emerging literature on the incidence, pathophysiology, predictive prognostic indicators, and management consensus for Covid-19 related thrombotic complications, in particular DVT and PE. METHODS: A literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. All searches were done via PubMed. References of review articles were further screened according to the exclusion criteria. RESULTS: In total, 154 records were identified and 20 duplicates were removed. A final 68 articles were included in the qualitative analysis. COVID-19 related thrombosis can affect multiple organs of the body, presenting in the form of arterial or venous thrombosis such as ischemic stroke, myocardial infarction, mesenteric ischemia, limb ischemia, DVT, or PE. DVT and PE has an overall incidence of 6-26%, and severely ill COVID-19 patients have even higher incidence of thromboembolism. On the other hand, incidence of arterial thromboembolism is much lower with incidence of 0.7%-3.7%. D-dimer is found to be an independent risk factor, and IMPROVE score, Caprini score, and Padua score have all been used as predictors. International guidelines suggest the use of low molecular weight heparin (LMWH) or fondaparinux for prophylaxis of VTE, and therapeutic dosage of weight adjusted LMWH for treatment if confirmed diagnosis. CONCLUSIONS: Contemporary rapidly evolving evidence shows that COVID-19 associated thrombosis was a novel clinical entity, especially in severely ill COVID-19 patients. There are multiple society-driven guidelines only, but without any level 1 evidence for management regimen. The ideal dose for prophylaxis is not established and may vary depending on balance of bleeding and thrombosis risk. The risk of bleeding may be increased in patients in intensive care unit.


Subject(s)
COVID-19 , Pulmonary Embolism , Thrombosis , Venous Thromboembolism , Anticoagulants , COVID-19/complications , Hemorrhage/chemically induced , Heparin, Low-Molecular-Weight , Humans , Pulmonary Embolism/epidemiology , Thrombosis/epidemiology , Thrombosis/etiology , Venous Thromboembolism/prevention & control
15.
Intern Med ; 61(12): 1869-1876, 2022 Jun 15.
Article in English | MEDLINE | ID: covidwho-1779845

ABSTRACT

A 73-year-old man receiving hemodialysis and antiplatelets was admitted with a mild case of COVID-19. Heparin was added, and iliopsoas hemorrhage developed. He was successfully treated by interventional radiology. A 76-year-old man receiving hemodialysis and antiplatelets was admitted with mild COVID-19. Heparin was added, and iliacus hemorrhage developed. Despite heparin discontinuation, he died of worsening pneumonia. A 74-year-old man undergoing hemodialysis was admitted with severe COVID-19. Gastrointestinal bleeding developed during continuous hemodiafiltration with heparin. Upon switching to nafamostat and increasing the dose, iliopsoas hemorrhage developed. Despite interventional radiology, he died of infectious complications. Attention to hemorrhagic complications is therefore needed in patients with COVID-19.


Subject(s)
COVID-19 , Aged , Anticoagulants/adverse effects , COVID-19/complications , Hemorrhage/drug therapy , Heparin/therapeutic use , Humans , Male , Renal Dialysis/adverse effects
16.
BMJ ; 377: o817, 2022 04 06.
Article in English | MEDLINE | ID: covidwho-1779338
17.
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
18.
J Cardiothorac Vasc Anesth ; 36(8 Pt B): 3193-3196, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1778657

ABSTRACT

Venovenous extracorporeal membrane oxygenation (VV-ECMO) has become a mainstay treatment modality for a select patient population who do not respond to conventional medical therapy suffering from severe acute respiratory distress syndrome (ARDS) due to COVID-19. This therapy necessitates the utilization of anticoagulation, whether unfractionated heparin or bivalirudin, to prevent thrombotic complications. Scarce are reports of VV-ECMO implementation leading to acute hemorrhage mandating cessation of anticoagulation in a patient suffering from COVID-19 ARDS. Herein, the authors report a case of a successful outcome in a COVID-19 ARDS patient who suffered an acute hemorrhagic complication leading to pre-emptive termination of systemic anticoagulation. The authors believe this to be one of the first such cases in the literature.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Anticoagulants , COVID-19/complications , COVID-19/therapy , Hemorrhage , Heparin , Humans , Respiratory Distress Syndrome/therapy
19.
Front Immunol ; 13: 839844, 2022.
Article in English | MEDLINE | ID: covidwho-1775672

ABSTRACT

Mesenchymal stromal cells (MSCs) possess profound immunomodulatory and regenerative properties that are of clinical use in numerous clinical indications with unmet medical need. Common sources of MSCs include among others, bone marrow (BM), fat, umbilical cord, and placenta-derived decidua stromal cells (DSCs). We here summarize our more than 20-years of scientific experience in the clinical use of MSCs and DSCs in different clinical settings. BM-MSCs were first explored to enhance the engraftment of autografts in hematopoietic cell transplantation (HCT) and osteogenesis imperfecta around 30 years ago. In 2004, our group reported the first anti-inflammatory use of BM-MSCs in a child with grade IV acute graft-versus-host disease (GvHD). Subsequent studies have shown that MSCs appear to be more effective in acute than chronic GvHD. Today BM-MSC-therapy is registered for acute GvHD in Japan and for GvHD in children in Canada and New Zeeland. MSCs first home to the lung following intravenous injection and exert strong local and systemic immunomodulatory effects on the host immune system. Thus, they were studied for ameliorating the cytokine storm in acute respiratory distress syndrome (ARDS). Both, MSCs and DSCs were used to treat SARS-CoV-2 coronavirus-induced disease 2019 (COVID-19)-induced ARDS. In addition, they were also used for other novel indications, such as pneumomediastinum, colon perforation, and radiculomyelopathy. MSC and DSCs trigger coagulation and were thus explored to stop hemorrhages. DSCs appear to be more effective for acute GvHD, ARDS, and hemorrhages, but randomized studies are needed to prove superiority. Stromal cell infusion is safe, well tolerated, and only gives rise to a slight fever in a limited number of patients, but no major side effects have been reported in multiple safety studies and metaanalysis. In this review we summarize current evidence from in vitro studies, animal models, and importantly our clinical experience, to support stromal cell therapy in multiple clinical indications. This encloses MSC's effects on the immune system, coagulation, and their safety and efficacy, which are discussed in relation to prominent clinical trials within the field.


Subject(s)
COVID-19 , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Animals , COVID-19/therapy , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hemorrhage/etiology , Humans , Mesenchymal Stem Cell Transplantation/adverse effects , Pregnancy , SARS-CoV-2
20.
Am J Obstet Gynecol MFM ; 4(4): 100636, 2022 07.
Article in English | MEDLINE | ID: covidwho-1773079

ABSTRACT

BACKGROUND: Although the increased risk for severe illness and adverse pregnancy outcomes associated with SARS-CoV-2 infection during pregnancy is well described, the association of infection with severe maternal morbidity has not been well characterized. OBJECTIVE: This study aimed to evaluate the risk for severe maternal morbidity associated with SARS-CoV-2 infection during pregnancy. STUDY DESIGN: This was a multicenter retrospective cohort study of all pregnant patients who had a SARS-CoV-2 test done and who delivered in a New York health system between March 1, 2020 and March 1, 2021. Patients with missing test results were excluded. The primary outcome of severe maternal morbidity, derived from the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine example list of diagnoses and complications, was compared between the following 2 groups: patients who tested positive for SARS-CoV-2 during pregnancy and patients who tested negative. Secondary outcomes included subgroups of severe maternal morbidity. Multivariable logistic regression was used to adjust for potential confounders such as maternal demographics, neighborhood socioeconomic status, hospital location, and pregnancy-related complications. A subanalysis was performed to determine if the risk for severe obstetrical hemorrhage and hypertension-associated or neurologic morbidity differed based on the timing of SARS-CoV-2 infection between those who tested positive for SARS-CoV-2 at their delivery hospitalization (ie, active infection) and those who tested positive during pregnancy but negative at their delivery hospitalization (ie, resolved infection). RESULTS: Of the 22,483 patients included, 1653 (7.4%) tested positive for SARS-CoV-2 infection. Patients with SARS-CoV-2 infection were more commonly Black, multiracial, Hispanic, non-English speaking, used Medicaid insurance, were multiparous, and from neighborhoods with a lower socioeconomic status. Patients with SARS-CoV-2 infection were at an increased risk for severe maternal morbidity when compared with those without infection (9.3 vs 6.5%; adjusted odds ratio, 1.52; 95% confidence interval, 1.21-1.88). Patients with SARS-CoV-2 infection were also at an increased risk for severe obstetrical hemorrhage (1.1% vs 0.5%; adjusted odds ratio, 1.78; 95% confidence interval, 1.04-2.88), pulmonary morbidity (2.0% vs 0.5%; adjusted odds ratio, 3.90; 95% confidence interval, 2.52-5.89), and intensive care unit admission (1.8% vs 0.5%; adjusted odds ratio, 3.29; 95% confidence interval, 2.09-5.04) when compared with those without infection. The risk for hypertension-associated or neurologic morbidity was similar between the 2 groups. The timing of SARS-CoV-2 infection (whether active or resolved at time of delivery) was not associated with the risk for severe obstetrical hemorrhage or hypertension-associated or neurologic morbidity when compared with those without infection. CONCLUSION: SARS-CoV-2 infection during pregnancy was associated with an increased risk for severe maternal morbidity, severe obstetrical hemorrhage, pulmonary morbidity, and intensive care unit admission. These data highlight the need for obstetrical unit preparedness in caring for patients with SARS-CoV-2 infection, continued public health efforts aimed at minimizing the risk for infection, and support in including this select population in investigational therapy and vaccine trials.


Subject(s)
COVID-19 , Hypertension , Pregnancy Complications, Infectious , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Female , Hemorrhage , Humans , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Retrospective Studies , SARS-CoV-2 , United States
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