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1.
Clin Appl Thromb Hemost ; 27: 10760296211051712, 2021.
Article in English | MEDLINE | ID: covidwho-1495925

ABSTRACT

BACKGROUND: Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic, there have been many reports of increased incidence of venous thromboembolism and arterial events as a complication. OBJECTIVE: To determine the incidence of symptomatic thrombotic events (TEs) in patients hospitalized for SARS-CoV2 disease (coronavirus 19 [Covid-19]). METHODS: A retrospective single-center cohort study with adult patients with a positive reverse transcriptase-polymerase chain reaction (rt-PCR) for SARS-CoV2, included from the date of diagnosis of Covid-19 and followed for 90 days or until death. RESULTS: A total of 1621 patients were included in this study. The median age was 73 years (interquartile range25th-75th [IQR] 53-87 years) and 57% (913) were female. Overall mortality was 21.6% (348). The overall incidence of symptomatic TEs within 90 days of diagnosis was 1.8% (30 of 1621) occurring in 28 patients, including an incidence of pulmonary embolism of 0.9% (15, 95% confidence interval [CI] 0.60%-1.6%), deep venous thrombosis of 0.61% (10, 95% CI 0.2%-1%), ischemic stroke of 0.25% (4, 95% CI 0.09%-0.65%), and ischemic arterial events of 0.06% (1, 95% CI 0.008%-0.43%). No acute coronary syndrome events were recorded. The incidence of symptomatic TEs was significantly lower in the general ward than in intensive care units (1.2% vs 5.7%; p < .001). The median time since positive rt-PCR for SARS-CoV2 to symptomatic TE was 22.5 days (IQR 19-43 days). There was no significant difference in the proportion of patients receiving (53.6%) and not receiving thromboprophylaxis (66.5%) and the development of TEs. CONCLUSION: The overall incidence of symptomatic TEs among these patients was lower than the incidence previously reported.


Subject(s)
Arterial Occlusive Diseases/epidemiology , COVID-19/epidemiology , Pulmonary Embolism/epidemiology , Thromboembolism/epidemiology , Venous Thrombosis/epidemiology , Aged , Aged, 80 and over , Argentina/epidemiology , Arterial Occlusive Diseases/blood , Arterial Occlusive Diseases/diagnosis , COVID-19/blood , COVID-19/diagnosis , Female , Humans , Incidence , Ischemic Stroke/blood , Ischemic Stroke/diagnosis , Ischemic Stroke/epidemiology , Male , Middle Aged , Patient Admission , Pulmonary Embolism/blood , Pulmonary Embolism/diagnosis , Retrospective Studies , Thromboembolism/blood , Thromboembolism/diagnosis , Time Factors , Venous Thrombosis/blood , Venous Thrombosis/diagnosis
2.
J Hematol Oncol ; 14(1): 172, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1477441

ABSTRACT

BACKGROUND: Thromboembolism has been reported as a consequence of severe COVID-19. Although warfarin is a commonly used anticoagulant, it acts by antagonising vitamin K, which is low in patients with severe COVID-19. To date, the clinical evidence on the impact of regular use of warfarin on COVID-19-related thromboembolism is lacking. METHODS: On behalf of NHS England, we conducted a population-based cohort study investigating the association between warfarin and COVID-19 outcomes compared with direct oral anticoagulants (DOACs). We used the OpenSAFELY platform to analyse primary care data and pseudonymously linked SARS-CoV-2 antigen testing data, hospital admissions and death records from England. We used Cox regression to estimate hazard ratios (HRs) for COVID-19-related outcomes comparing warfarin with DOACs in people with non-valvular atrial fibrillation. We also conducted negative control outcome analyses (being tested for SARS-CoV-2 and non-COVID-19 death) to assess the potential impact of confounding. RESULTS: A total of 92,339 warfarin users and 280,407 DOAC users were included. We observed a lower risk of all outcomes associated with warfarin versus DOACs [testing positive for SARS-CoV-2, HR 0.73 (95% CI 0.68-0.79); COVID-19-related hospital admission, HR 0.75 (95% CI 0.68-0.83); COVID-19-related deaths, HR 0.74 (95% CI 0.66-0.83)]. A lower risk of negative control outcomes associated with warfarin versus DOACs was also observed [being tested for SARS-CoV-2, HR 0.80 (95% CI 0.79-0.81); non-COVID-19 deaths, HR 0.79 (95% CI 0.76-0.83)]. CONCLUSIONS: Overall, this study shows no evidence of harmful effects of warfarin on severe COVID-19 disease.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/epidemiology , Thromboembolism/drug therapy , Thromboembolism/virology , Warfarin/therapeutic use , Administration, Oral , Adolescent , Adult , Aged , Aged, 80 and over , Anticoagulants/pharmacology , COVID-19/blood , COVID-19/drug therapy , COVID-19/virology , Cohort Studies , England/epidemiology , Humans , Middle Aged , SARS-CoV-2/isolation & purification , Thromboembolism/blood , Thromboembolism/epidemiology , Treatment Outcome , Young Adult
4.
Cells ; 10(10)2021 09 29.
Article in English | MEDLINE | ID: covidwho-1444117

ABSTRACT

Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of numerous factors in vivo, including the induction of other stem cells' differentiation. In vitro, the culture media supernatant is named secretome and contains soluble molecules and extracellular vesicles that retain potent biological function in tissue regeneration. MSCs are considered safe for human treatment; their use does not involve ethical issues, as embryonic stem cells do not require genetic manipulation as induced pluripotent stem cells, and after intravenous injection, they are mainly found in the lugs. Therefore, these cells are currently being tested in various preclinical and clinical trials for several diseases, including COVID-19. Several affected COVID-19 patients develop induced acute respiratory distress syndrome (ARDS) associated with an uncontrolled inflammatory response. This condition causes extensive damage to the lungs and may leave serious post-COVID-19 sequelae. As the disease may cause systemic alterations, such as thromboembolism and compromised renal and cardiac function, the intravenous injection of MSCs may be a therapeutic alternative against multiple pathological manifestations. In this work, we reviewed the literature about MSCs biology, focusing on their function in pulmonary regeneration and their use in COVID-19 treatment.


Subject(s)
COVID-19/blood , COVID-19/therapy , Lung/physiology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Regeneration/physiology , Animals , COVID-19/drug therapy , Cell Differentiation , Cell- and Tissue-Based Therapy , Culture Media , Extracellular Vesicles , Humans , Inflammation , Mice , Mice, SCID , Phenotype , Pneumonia/blood , Pneumonia/immunology , Pneumonia/therapy , Respiratory Distress Syndrome , SARS-CoV-2 , Thromboembolism/blood , Thromboembolism/immunology , Thromboembolism/therapy
5.
Transfus Apher Sci ; 60(6): 103237, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1366698

ABSTRACT

SARS-CoV-2 attaches to the angiotensin-converting enzyme 2 (ACE-2) receptor on human cells. The virus causes hypercytokinemia, capillary leak, pulmonary edema, acute respiratory distress syndrome, acute cardiac injury, and leads to death. Mesenchymal stem cells (MSCs) are ACE-2 negative cells; therefore, can escape from SARS-CoV-2. MSCs prevent hypercytokinemia and help the resolution of the pulmonary edema and other damages occurred during the course of COVID-19. In addition, MSCs enhance the regeneration of the lung and other tissues affected by SARS-CoV-2. The case series reported beneficial effect of MSCs in COVID-19 treatment. However, there are some concerns about the safety of MSCs, particularly referring to the increased risk of disseminated intravascular coagulation, and thromboembolism due to the expression of TF/CD142. Prospective, randomized, large scale studies are needed to reveal the optimum dose, administration way, time, efficacy, and safety of MSCs in the COVID-19 treatment.


Subject(s)
COVID-19 , Lung/physiology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Regeneration , SARS-CoV-2/metabolism , COVID-19/blood , COVID-19/epidemiology , COVID-19/therapy , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Humans , Peptidyl-Dipeptidase A/metabolism , Prospective Studies , Risk Factors , Thromboembolism/blood , Thromboembolism/etiology , Thromboplastin/biosynthesis
6.
Biomed Res Int ; 2021: 2013371, 2021.
Article in English | MEDLINE | ID: covidwho-1358934

ABSTRACT

BACKGROUND: This study was aimed at revealing neuroimaging findings in COVID-19 patients and at discussing their relationship with epidemiological data and some laboratory parameters. Materials and Method. This study included 436 cases of COVID-19 and 40 cases of non-COVID-19 acute/subacute thromboembolism who underwent at least one neuroimaging procedure due to neurological symptoms between April 2020 and December 2020. The group of COVID-19-positive acute/subacute thromboembolism cases was compared with both the group of normal brain imaging cases and the non-COVID-19 acute/subacute thromboembolism group in terms of demographic data and laboratory parameters. RESULTS: When the acute/subacute thromboembolism group and neuroimaging findings were compared in terms of negative group, presence of comorbid disease, D-dimer level, and lymphocyte count in COVID-19 patients, a statistically significant difference was found (p = 0.047, 0.014, and <0.001, respectively). COVID-19-positive and COVID-19-negative acute/subacute thromboembolism cases that were compared in terms of gender, neuroimaging reason, C-reactive protein, D-dimer level and lymphocyte count, a statistically significant difference was found (p = 0.003, <0.001, 0.005, 0.02, and <0.001, respectively). CONCLUSION: Acute thromboembolic events are common in patients with COVID-19 due to a potentially increased procoagulant process. Neurological evaluation and, if necessary, detailed neuroimaging should be performed, especially in cases with high D-dimer levels.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnostic imaging , Neuroimaging/methods , Adolescent , Adult , Aged , Aged, 80 and over , Brain/diagnostic imaging , COVID-19/blood , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Male , Middle Aged , Occipital Lobe/diagnostic imaging , Retrospective Studies , SARS-CoV-2/isolation & purification , Thromboembolism/blood , Thromboembolism/diagnostic imaging , Young Adult
7.
Expert Opin Drug Saf ; 20(11): 1451-1453, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1310857

ABSTRACT

Introduction: Concerns about the increased risk of blood clots associated with the VAXZEVRIA (previously named Oxford-AstraZeneca COVID-19 vaccine) and Johnson & Johnson (Janssen) COVID-19 vaccines raises the question of the thrombotic safety of other COVID-19 vaccines such as Pfizer-BioNTech or Moderna, especially in younger women, who at the early stage of the pandemic was a priority group for vaccination. Methods: Using the US-based Vaccine Adverse Event Reporting System (VAERS) and the FDA Event Reporting System (FAERS), we retrieved cases of thrombosis following vaccinations or hormonal contraceptive use in women aged ≤ 50 years. We used the reporting odds ratio (ROR) as a disproportionality measure. Results: On 19 March 2021, out of 13.6 million women aged ≤ 50 exposed to at least one dose of Pfizer-BioNTech or Moderna COVID-19 vaccines in the US, only 61 cases were reported with a total of 68 thromboembolic events (1 case per 222,951 vaccinated). None of the thromboembolic events included in our analysis were disproportionally reported for the two COVID-19 vaccines. Conclusion: Our results do support that, when compared to hormonal contraceptive use, the mRNA vaccines do not show disproportional reporting of thromboembolic events in younger women.


Subject(s)
COVID-19 Vaccines/adverse effects , Thromboembolism/blood , Vaccination/adverse effects , Adverse Drug Reaction Reporting Systems , Age Factors , COVID-19 Vaccines/administration & dosage , Contraceptives, Oral, Hormonal/adverse effects , Female , Hormonal Contraception/adverse effects , Humans , Middle Aged , Risk Assessment , Risk Factors , Sex Factors , Thromboembolism/diagnosis , Thromboembolism/epidemiology , Treatment Outcome
9.
J Thromb Thrombolysis ; 52(2): 542-552, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1222780

ABSTRACT

Coronavirus 2019 disease (COVID-19) is associated with coagulation dysfunction that predisposes patients to an increased risk for both arterial (ATE) and venous thromboembolism (VTE) and consequent poor prognosis; in particular, the incidence of ATE and VTE in critically ill COVID-19 patients can reach 5% and 31%, respectively. The mechanism of thrombosis in COVID-19 patients is complex and still not completely clear. Recent literature suggests a link between the presence of antiphospholipid antibodies (aPLs) and thromboembolism in COVID-19 patients. However, it remains uncertain whether aPLs are an epiphenomenon or are involved in the pathogenesis of the disease.


Subject(s)
Antibodies, Antiphospholipid/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Thromboembolism/immunology , Animals , Antibodies, Antiphospholipid/blood , Blood Coagulation , COVID-19/blood , COVID-19/complications , Critical Illness , Humans , Thromboembolism/blood , Thromboembolism/complications , Venous Thromboembolism/blood , Venous Thromboembolism/complications , Venous Thromboembolism/immunology
10.
Front Endocrinol (Lausanne) ; 12: 651009, 2021.
Article in English | MEDLINE | ID: covidwho-1190304

ABSTRACT

Introduction: Patients with severe COVID-19 infections have coagulation abnormalities indicative of a hypercoagulable state, with thromboembolic complications and increased mortality. Platelets are recognized as mediators of inflammation, releasing proinflammatory and prothrombotic factors, and are hyperactivated in COVID-19 infected patients. Activated platelets have also been reported in type 2 diabetes (T2D) patients, putting these patients at higher risk for thromboembolic complications of COVID-19 infection. Methods: A case-control study of T2D (n=33) and control subjects (n=30) who underwent a hyperinsulinemic clamp to induce normoglycemia in T2D subjects: T2D: baseline glucose 7.5 ± 0.3mmol/l (135.1 ± 5.4mg/dl), reduced to 4.5 ± 0.07mmol/l (81 ± 1.2mg/dl) with 1-hour clamp; Controls: maintained at 5.1 ± 0.1mmol/l (91.9 ± 1.8mg/dl). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was used to determine a panel of platelet proteins. Results: Prothrombotic platelet proteins were elevated in T2D versus controls: platelet factor 4 (PF4, p<0.05); platelet glycoprotein VI (PGVI p<0.05); P-selectin (p<0.01) and plasminogen activator inhibitor I (PAI-1, p<0.01). In addition, the antithrombotic platelet-related proteins, plasmin (p<0.05) and heparin cofactor II (HCFII, p<0.05), were increased in T2D. Normalization of glucose in the T2D cohort had no effect on platelet protein levels. Conclusion: T2D patients have platelet hyperactivation, placing them at higher risk for thromboembolic events. When infected with COVID-19, this risk may be compounded, and their propensity for a more severe COVID-19 disease course increased. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03102801, identifier NCT03102801.


Subject(s)
Blood Platelet Disorders/blood , Blood Platelet Disorders/etiology , Blood Platelets/chemistry , Blood Proteins/analysis , COVID-19/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Hypoglycemia/blood , Hypoglycemia/complications , Aged , COVID-19/complications , Case-Control Studies , Female , Glucose Clamp Technique , Humans , Lipids/blood , Male , Middle Aged , Platelet Activation , Thromboembolism/blood , Thromboembolism/etiology
11.
J Thromb Thrombolysis ; 52(3): 772-778, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1176387

ABSTRACT

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann-Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13-0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.


Subject(s)
Anticoagulants/therapeutic use , Blood Transfusion , COVID-19/therapy , Heparin, Low-Molecular-Weight/therapeutic use , Thromboembolism/prevention & control , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Blood Transfusion/mortality , COVID-19/blood , COVID-19/diagnosis , COVID-19/mortality , Clinical Decision-Making , Female , Heparin, Low-Molecular-Weight/adverse effects , Hospital Mortality , Hospitalization , Humans , Male , Middle Aged , Protective Factors , Risk Assessment , Risk Factors , Thromboembolism/blood , Thromboembolism/diagnosis , Thromboembolism/mortality , Time Factors , Treatment Outcome
12.
J Thromb Thrombolysis ; 52(3): 914-924, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1137164

ABSTRACT

In this study, we investigated whether the CHA2DS2-VASc score could be used to estimate the need for hospitalization in the intensive care unit (ICU), the length of stay in the ICU, and mortality in patients with COVID-19. Patients admitted to Merkezefendi State Hospital because of COVID-19 diagnosis confirmed by RNA detection of virus by using polymerase chain reaction between March 24, 2020 and July 6, 2020, were screened retrospectively. The CHA2DS2-VASc and modified CHA2DS2-VASc score of all patients was calculated. Also, we received all patients' complete biochemical markers including D-dimer, Troponin I, and c-reactive protein on admission. We enrolled 1000 patients; 791 were admitted to the general medical service and 209 to the ICU; 82 of these 209 patients died. The ROC curves of the CHA2DS2-VASc and M-CHA2DS2-VASc scores were analyzed. The cut-off values of these scores for predicting mortality were ≥ 3 (2 or under and 3). The CHA2DS2-VASc and M-CHA2DS2-VASc scores had an area under the curve value of 0.89 on the ROC. The sensitivity and specificity of the CHA2DS2-VASc scores were 81.7% and 83.8%, respectively; the sensitivity and specificity of the M-CHA2DS2-VASc scores were 85.3% and 84.1%, respectively. Multivariate logistic regression analysis showed that CHA2DS2-VASc, Troponin I, D-Dimer, and CRP were independent predictors of mortality in COVID-19 patients. Using a simple and easily available scoring system, CHA2DS2-VASc and M-CHA2DS2-VASc scores can be assessed in patients diagnosed with COVID-19. These scores can predict mortality and the need for ICU hospitalization in these patients.


Subject(s)
COVID-19/diagnosis , Decision Support Techniques , Hospital Mortality , Hospitalization , Intensive Care Units , Thromboembolism/diagnosis , Adolescent , Adult , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/mortality , COVID-19/therapy , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Length of Stay , Male , Middle Aged , Predictive Value of Tests , Prognosis , Receptors, Immunologic/analysis , Retrospective Studies , Risk Assessment , Risk Factors , Thromboembolism/blood , Thromboembolism/mortality , Thromboembolism/therapy , Time Factors , Troponin I/blood , Turkey , Young Adult
13.
J Thromb Thrombolysis ; 52(3): 782-790, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1111318

ABSTRACT

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000 IU) vs. higher (> 4000 IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400-0.1.792; p = 0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/therapy , Enoxaparin/administration & dosage , Hospitalization , Thromboembolism/prevention & control , Aged , Aged, 80 and over , Anticoagulants/adverse effects , COVID-19/blood , COVID-19/diagnosis , COVID-19/mortality , Enoxaparin/adverse effects , Female , Hospital Mortality , Humans , Italy , Male , Middle Aged , Protective Factors , Respiration, Artificial , Retrospective Studies , Risk Assessment , Risk Factors , Thromboembolism/blood , Thromboembolism/diagnosis , Thromboembolism/mortality , Time Factors , Treatment Outcome
14.
Arterioscler Thromb Vasc Biol ; 40(12): 2975-2989, 2020 12.
Article in English | MEDLINE | ID: covidwho-1105571

ABSTRACT

OBJECTIVE: Pulmonary thrombosis is observed in severe acute respiratory syndrome coronavirus 2 pneumonia. Aim was to investigate whether subpopulations of platelets were programmed to procoagulant and inflammatory activities in coronavirus disease 2019 (COVID-19) patients with pneumonia, without comorbidities predisposing to thromboembolism. Approach and Results: Overall, 37 patients and 28 healthy subjects were studied. Platelet-leukocyte aggregates, platelet-derived microvesicles, the expression of P-selectin, and active fibrinogen receptor on platelets were quantified by flow cytometry. The profile of 45 cytokines, chemokines, and growth factors released by platelets was defined by immunoassay. The contribution of platelets to coagulation factor activity was selectively measured. Numerous platelet-monocyte (mean±SE, 67.9±4.9%, n=17 versus 19.4±3.0%, n=22; P<0.0001) and platelet-granulocyte conjugates (34.2±4.04% versus 8.6±0.7%; P<0.0001) were detected in patients. Resting patient platelets had similar levels of P-selectin (10.9±2.6%, n=12) to collagen-activated control platelets (8.7±1.5%), which was not further increased by collagen activation on patient platelets (12.4±2.5%, P=nonsignificant). The agonist-stimulated expression of the active fibrinogen receptor was reduced by 60% in patients (P<0.0001 versus controls). Cytokines (IL [interleukin]-1α, IL-1ß, IL-1RA, IL-4, IL-10, IL-13, IL, 17, IL-27, IFN [interferon]-α, and IFN-γ), chemokines (MCP-1/CCL2 [monocyte chemoattractant protein 1]), and growth factors (VEGF [vascular endothelial growth factor]-A/D) were released in significantly larger amounts upon stimulation of COVID-19 platelets. Platelets contributed to increased fibrinogen, VWF (von Willebrand factor), and factor XII in COVID-19 patients. Patients (28.5±0.7 s, n=32), unlike controls (31.6±0.5 s, n=28; P<0.001), showed accelerated factor XII-dependent coagulation. CONCLUSIONS: Platelets in COVID-19 pneumonia are primed to spread proinflammatory and procoagulant activities in systemic circulation.


Subject(s)
Blood Platelets/metabolism , COVID-19/blood , Thromboembolism/etiology , Aged , Aged, 80 and over , COVID-19/complications , Cytokines/metabolism , Female , Flow Cytometry , Humans , Male , Middle Aged , Pandemics , Prognosis , Thromboembolism/blood
15.
J Thromb Haemost ; 19(2): 522-530, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1059727

ABSTRACT

BACKGROUND: Multiple investigators have described an increased incidence of thromboembolic events in SARS-CoV-2-infected individuals. Data concerning hemostatic complications in children hospitalized for COVID-19/multisystem inflammatory syndrome in children (MIS-C) are scant. OBJECTIVES: To share our experience in managing SARS-CoV-2-associated pro-coagulant state in hospitalized children. METHODS: D-dimer values were recorded at diagnosis in children hospitalized for SARS-CoV-2-related manifestations. In moderately to critically ill patients and MIS-C cases, coagulation and inflammatory markers were checked at multiple time points and median results were compared. Pro-thrombotic risk factors were appraised for each child and thromboprophylaxis was started in selected cases. RESULTS: Thirty-five patients were prospectively enrolled. D-dimer values did not discriminate COVID-19 of differing severity, whereas were markedly different between the COVID-19 and the MIS-C cohorts. In both cohorts, D-dimer and C-reactive protein levels increased upon clinical worsening but were not accompanied by decreased fibrinogen or platelet values, with all parameters returning to normal upon disease resolution. Six patients had multiple thrombotic risk factors and were started on pharmacological thromboprophylaxis. No deaths or thrombotic or bleeding complications occurred. CONCLUSIONS: COVID-19 pediatric patients show mildly altered coagulation and inflammatory parameters; on the other hand, MIS-C cases showed laboratory signs of an inflammatory driven pro-coagulant status. Universal anticoagulant prophylaxis in hospitalized children with SARS-CoV-2-related manifestations is not warranted, but may be offered to patients with other pro-thrombotic risk factors in the context of a multi-modal therapeutic approach.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation/drug effects , COVID-19/drug therapy , Thromboembolism/prevention & control , Adolescent , Age Factors , Biomarkers/blood , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/etiology , COVID-19/blood , COVID-19/complications , Child , Child, Preschool , Clinical Decision-Making , Female , Hospitalization , Humans , Infant , Infant, Newborn , Italy , Male , Prospective Studies , Risk Factors , Thromboembolism/blood , Thromboembolism/etiology , Time Factors , Treatment Outcome , Young Adult
18.
Ann Saudi Med ; 40(6): 462-468, 2020.
Article in English | MEDLINE | ID: covidwho-976449

ABSTRACT

BACKGROUND: Venous thromboembolism or extensive thrombosis is relatively common in patients with severe COVID-19 infection and has been associated with increased mortality. During the current COVID-19 pandemic, several prophylactic doses and types of low-molecular-weight heparin (LMWH) are being used worldwide; however, there are no high-quality studies or recommendations for an optimal prophylactic LMWH dose. OBJECTIVES: Investigate the relationship between coagulation parameters and the LMWH dose, and mortality and ICU admission in hospitalized patients with severe COVID-19 pneumonia. DESIGN: Retrospective. SETTING: Tertiary care hospital. PATIENTS AND METHODS: Data on clinical features, coagulation parameters and anticoagulant medications of inpatients with severe COVID-19 were collected for the period between 11 March 2020 and 31 April 2020. MAIN OUTCOME MEASURES: Mortality and ICU admission for prophylactic dose LMWH (0.5 mg/kg twice daily) and therapeutic dose LMWH (1 mg/kg twice daily). SAMPLE SIZE: 154 cases. RESULTS: Ninety-eight (63.6%) patients were treated with the LMWH prophylactic dose and 56 (36.4%) patients were treated with the therapeutic dose. Forty-four (44.9%) of 98 patients using the prophylactic dose LMWH died, while 10 (17.9%) of 56 patients using the therapeutic dose LMWH died (P=.001). Mortality was 6.4-fold higher in the prophylactic dose LMWH users than in the therapeutic dose LMWH users (OR=6.5, 95% CI: 2.4-17.6, P<.001). CONCLUSIONS: Therapeutic dosing of LMWH may decrease mortality in patients with severe COVID-19 infected pneumonia. More aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies. LIMITATIONS: Lack of information about bleeding complications. LMWH was not compared with other anticoagulant therapies. There was no comparison between our two groups on the APACHE score. Used different doses of LMWH in different clinics in our hospital. Single-center, retrospective study. CONFLICT OF INTEREST: None.


Subject(s)
COVID-19 , Chemoprevention/methods , Heparin, Low-Molecular-Weight , SARS-CoV-2/isolation & purification , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Blood Coagulation/drug effects , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , COVID-19/therapy , Dose-Response Relationship, Drug , Female , Heparin, Low-Molecular-Weight/administration & dosage , Heparin, Low-Molecular-Weight/adverse effects , Humans , Male , Middle Aged , Mortality , Outcome and Process Assessment, Health Care , Retrospective Studies , Thromboembolism/blood , Thromboembolism/etiology , Thromboembolism/prevention & control , Turkey/epidemiology
19.
Radiographics ; 40(6): 1574-1599, 2020 10.
Article in English | MEDLINE | ID: covidwho-810605

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in coronavirus disease 2019 (COVID-19), which was declared an official pandemic by the World Health Organization on March 11, 2020. The infection has been reported in most countries around the world. As of August 2020, there have been over 21 million cases of COVID-19 reported worldwide, with over 800 000 COVID-19-associated deaths. It has become apparent that although COVID-19 predominantly affects the respiratory system, many other organ systems can also be involved. Imaging plays an essential role in the diagnosis of all manifestations of the disease, as well as its related complications, and proper utilization and interpretation of imaging examinations is crucial. With the growing global COVID-19 outbreak, a comprehensive understanding of the diagnostic imaging hallmarks, imaging features, multisystemic involvement, and evolution of imaging findings is essential for effective patient management and treatment. To date, only a few articles have been published that comprehensively describe the multisystemic imaging manifestations of COVID-19. The authors provide an inclusive system-by-system image-based review of this life-threatening and rapidly spreading infection. In part 1 of this article, the authors discuss general aspects of the disease, with an emphasis on virology, the pathophysiology of the virus, and clinical presentation of the disease. The key imaging features of the varied pathologic manifestations of this infection that involve the pulmonary and peripheral and central vascular systems are also described. Part 2 will focus on key imaging features of COVID-19 that involve the cardiac, neurologic, abdominal, dermatologic and ocular, and musculoskeletal systems, as well as pediatric and pregnancy-related manifestations of the virus. Vascular complications pertinent to each system will be also be discussed in part 2. Online supplemental material is available for this article. ©RSNA, 2020.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/diagnostic imaging , Lung/diagnostic imaging , Pandemics , Pneumonia, Viral/diagnostic imaging , Thromboembolism/diagnostic imaging , Thrombosis/diagnostic imaging , Angiography/methods , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/physiopathology , Disease Progression , Fibrin Fibrinogen Degradation Products/analysis , Humans , Inflammation , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Pulmonary Artery/diagnostic imaging , Receptors, Virus/physiology , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Symptom Assessment , Thromboembolism/blood , Thromboembolism/etiology , Thrombosis/blood , Thrombosis/etiology , Thrombotic Microangiopathies/diagnostic imaging , Thrombotic Microangiopathies/etiology , Tomography, X-Ray Computed/methods , Ultrasonography/methods
20.
Oncologist ; 25(10): e1500-e1508, 2020 10.
Article in English | MEDLINE | ID: covidwho-717626

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a current global pandemic caused by the novel coronavirus SARS-CoV-2. Alongside its potential to cause severe respiratory illness, studies have reported a distinct COVID-19-associated coagulopathy that is characterized by elevated D-dimer levels, hyperfibrinogenemia, mild thrombocytopenia, and slight prolongation of the prothrombin time. Studies have also reported increased rates of thromboembolism in patients with COVID-19, but variations in study methodologies, patient populations, and anticoagulation strategies make it challenging to distill implications for clinical practice. Here, we present a practical review of current literature and uses a case-based format to discuss the diagnostic approach and management of COVID-19-associated coagulopathy. IMPLICATIONS FOR PRACTICE: Coronavirus disease 2019 (COVID-19)-associated coagulopathy is characterized by elevated D-dimer levels, hyperfibrinogenemia, and increased rates of thromboembolism. Current management guidelines are based on limited evidence from retrospective studies that should be interpreted carefully. At this time, all hospitalized patients with suspected or confirmed COVID-19 should receive coagulation test surveillance and standard doses of prophylactic anticoagulation until prospective randomized controlled trials yield definitive information in support of higher prophylactic doses.


Subject(s)
COVID-19/complications , Thrombosis/diagnosis , Thrombosis/therapy , Anticoagulants/therapeutic use , Biomarkers/blood , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/complications , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/therapy , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , SARS-CoV-2 , Thromboembolism/blood , Thromboembolism/diagnosis , Thromboembolism/prevention & control , Thrombosis/blood , Thrombosis/complications
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