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2.
Clin Pharmacol Ther ; 111(3): 614-623, 2022 03.
Article in English | MEDLINE | ID: covidwho-1549189

ABSTRACT

Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. It has been hypothesized that higher-dose anticoagulation, including therapeutic-dose and intermediate-dose anticoagulation, is superior to prophylactic-dose anticoagulation in the treatment of COVID-19. This meta-analysis evaluated the efficacy and safety of higher-dose anticoagulation compared with prophylactic-dose anticoagulation in patients with COVID-19. Ten randomized controlled open-label trials with a total of 5,753 patients were included. The risk of death and net adverse clinical events (including death, thromboembolic events, and major bleeding) were similar between higher-dose and prophylactic-dose anticoagulation (risk ratio (RR) 0.96, 95% CI, 0.79-1.16, P = 0.66 and RR 0.87, 95% CI, 0.73-1.03, P = 0.11, respectively). Higher-dose anticoagulation, compared with prophylactic-dose anticoagulation, decreased the risk of thromboembolic events (RR 0.63, 95% CI, 0.47-0.84, P = 0.002) but increased the risk of major bleeding (RR 1.76, 95% CI, 1.19-2.62, P = 0.005). The risk of death showed no statistically significant difference between higher-dose anticoagulation and prophylactic-dose anticoagulation in noncritically ill patients (RR 0.87, 95% CI, 0.50-1.52, P = 0.62) and in critically ill patients with COVID-19 (RR 1.04, 95% CI, 0.93-1.17, P = 0.5). The risk of death was similar between therapeutic-dose vs. prophylactic-dose anticoagulation (RR 0.92, 95% CI 0.69-1.21, P = 0.54) and between intermediate-dose vs. prophylactic-dose anticoagulation (RR 1.01, 95% CI 0.63-1.61, P = 0.98). In patients with markedly increased d-dimer levels, higher-dose anticoagulation was also not associated with a decreased risk of death as compared with prophylactic-dose anticoagulation (RR 0.86, 95% CI, 0.64-1.16, P = 0.34). Without any clear evidence of survival benefit, these findings do not support the routine use of therapeutic-dose or intermediate-dose anticoagulation in critically or noncritically ill patients with COVID-19.


Subject(s)
Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , Critical Illness , Fibrin Fibrinogen Degradation Products/analysis , Hemorrhage/chemically induced , Humans , Thromboembolism/drug therapy , Thromboembolism/prevention & control , Treatment Outcome
3.
Clin Appl Thromb Hemost ; 27: 10760296211053315, 2021.
Article in English | MEDLINE | ID: covidwho-1523220

ABSTRACT

High rates of thromboembolic events have been described in intensive care unit (ICU) patients. Data regarding thromboembolic events in all hospitalized patients has been less frequently reported, raising concerns that thromboembolic events in non-ICU may be underrecognized. In addition, optimal anticoagulation type and dose is still unsettled at this time. This is a retrospective cohort study of 159 hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia during a 9-month period to determine an association between the frequency of thromboembolic rates and hospitalized patients with COVID-19. Secondary outcomes sought to investigate association of thromboembolic events with relation to place of admission, risk factors, anticoagulation, mortality, hospital length of stay, and discharge disposition. Among the cohort of 159 hospitalized patients who met criteria, 16 (10%) were diagnosed with a thromboembolic event. There were a total of 18 thromboembolic events with 12 venous and 6 arterial. Admission to the ICU was not associated with a higher frequency of thromboembolic events compared with non-ICU patients (37.5% vs 62.5%), p = .71. Patients with a thromboembolic event had a significantly higher mortality compared with those with no thromboembolic event (37.5% vs 13.3%), p = .012. Patients hospitalized with COVID-19 have increased rates of thromboembolic events, both venous and arterial, which contribute to a significant increase in mortality. However, the frequency of thromboembolism in patients admitted to the ICU was similar to events in non-ICU patients. We hope to increase awareness of the increased risk of hypercoagulability in all hospitalized patients with COVID-19 including non-ICU patients.


Subject(s)
COVID-19/complications , Thromboembolism/etiology , Aged , Anticoagulants/therapeutic use , Female , Hospitalization , Humans , Incidence , Intensive Care Units , Male , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Thromboembolism/drug therapy
4.
Int J Mol Sci ; 22(21)2021 Nov 07.
Article in English | MEDLINE | ID: covidwho-1512380

ABSTRACT

Heparin and its derivatives are saving thousands of human lives annually, by successfully preventing and treating thromboembolic events. Although the mode of action during anticoagulation is well studied, their influence on cell behavior is not fully understood as is the risk of bleeding and other side effects. New applications in regenerative medicine have evolved supporting production of cell-based therapeutics or as a substrate for creating functionalized matrices in biotechnology. The currently resurgent interest in heparins is related to the expected combined anti-inflammatory, anti-thrombotic and anti-viral action against COVID-19. Based on a concise summary of key biochemical and clinical data, this review summarizes the impact for manufacturing and application of cell therapeutics and highlights the need for discriminating the different heparins.


Subject(s)
Anticoagulants/chemistry , Cell- and Tissue-Based Therapy/methods , Heparin/analogs & derivatives , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Biocompatible Materials/chemistry , Biocompatible Materials/therapeutic use , Cell Adhesion , Hemorrhage/etiology , Heparin/adverse effects , Heparin/therapeutic use , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Regenerative Medicine , Thromboembolism/drug therapy
5.
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
6.
Open Heart ; 8(2)2021 10.
Article in English | MEDLINE | ID: covidwho-1455738

ABSTRACT

BACKGROUND: COVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population. METHODS: A retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation. RESULTS: 242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation. CONCLUSION: The use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/therapy , Platelet Aggregation Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Blood Coagulation/drug effects , COVID-19/blood , COVID-19/complications , COVID-19/mortality , Female , Hospital Mortality , Humans , Inpatients , Intensive Care Units , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Survival Analysis , Thromboembolism/drug therapy , Thromboembolism/physiopathology , Thrombosis/drug therapy , Thrombosis/physiopathology , Treatment Outcome
7.
Clin Res Cardiol ; 111(3): 322-332, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1427245

ABSTRACT

AIMS: Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients. METHODS AND RESULTS: We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056). CONCLUSIONS: Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , COVID-19/mortality , SARS-CoV-2/drug effects , Thromboembolism/drug therapy , Aged , Blood Coagulation Disorders/virology , Comorbidity , Europe , Female , Humans , Male , Middle Aged , Retrospective Studies , Thromboembolism/virology
8.
Sci Rep ; 11(1): 13325, 2021 06 25.
Article in English | MEDLINE | ID: covidwho-1281739

ABSTRACT

COVID 19 is associated with a hypercoagulable state and frequent thromboembolic complications. For how long this acquired abnormality lasts potentially requiring preventive measures, such as anticoagulation remains to be delineated. We used viscoelastic rotational thrombelastometry (ROTEM) in a single center cohort of 13 critical ill patients and performed follow up examinations three months after discharge from ICU. We found clear signs of a hypercoagulable state due to severe hypofibrinolysis and a high rate of thromboembolic complications during the phase of acute illness. Three month follow up revealed normalization of the initial coagulation abnormality and no evidence of venous thrombosis in all thirteen patients. In our cohort the coagulation profile was completely normalized three months after COVID-19. Based on these findings, discontinuation of anticoagulation can be discussed in patients with complete venous reperfusion.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders , COVID-19 , Thrombelastography , Thromboembolism , Venous Thrombosis , Aged , Blood Coagulation , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/pathology , COVID-19/blood , COVID-19/drug therapy , COVID-19/pathology , Cohort Studies , Female , Humans , Male , Middle Aged , Severity of Illness Index , Thromboembolism/drug therapy , Thromboembolism/pathology , Venous Thrombosis/drug therapy , Venous Thrombosis/pathology
9.
Cell Biol Int ; 45(9): 1832-1850, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1212726

ABSTRACT

December 2019 will never be forgotten in the history of medicine when an outbreak of pneumonia of unknown etiology in Wuhan, China sooner or later prompted the World Health Organization to issue a public health warning emergency. This is not the first nor will it be the last time that a member of ß-coronaviruses (CoVs) is waging a full-scale war against human health. Notwithstanding the fact that pneumonia is the primary symptom of the novel coronavirus (2019nCoV; designated as SARS-CoV-2), the emergence of severe disease mainly due to the injury of nonpulmonary organs at the shadow of coagulopathy leaves no choice, in some cases, rather than a dreadful death. Multiple casual factors such as inflammation, endothelial dysfunction, platelet and complement activation, renin-angiotensin-aldosterone system derangement, and hypoxemia play a major role in the pathogenesis of coagulopathy in coronavirus disease 2019 (COVID-19) patients. Due to the undeniable role of coagulation dysfunction in the initiation of several complications, assessment of coagulation parameters and the platelet count would be beneficial in early diagnosis and also timely prediction of disease severity. Although low-molecular-weight heparin is considered as the first-line of treatment in COVID-19-associated coagulopathy, several possible therapeutic options have also been proposed for better management of the disease. In conclusion, this review would help us to gain insight into the pathogenesis, clinical manifestation, and laboratory findings associated with COVID-19 coagulopathy and would summarize management strategies to alleviate coagulopathy-related complications.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , COVID-19/pathology , Blood Coagulation Disorders/etiology , Blood Platelets/cytology , Blood Platelets/metabolism , COVID-19/complications , COVID-19/virology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Inflammation/etiology , SARS-CoV-2/isolation & purification , Thromboembolism/drug therapy , Thromboembolism/etiology
10.
Fam Med Community Health ; 9(2)2021 04.
Article in English | MEDLINE | ID: covidwho-1195851

ABSTRACT

OBJECTIVES: To review the pathophysiology of COVID-19 disease, potential aspirin targets on this pathogenesis and the potential role of aspirin in patients with COVID-19. DESIGN: Narrative review. SETTING: The online databases PubMed, OVID Medline and Cochrane Library were searched using relevant headlines from 1 January 2016 to 1 January 2021. International guidelines from relevant societies, journals and forums were also assessed for relevance. PARTICIPANTS: Not applicable. RESULTS: A review of the selected literature revealed that clinical deterioration in COVID-19 is attributed to the interplay between endothelial dysfunction, coagulopathy and dysregulated inflammation. Aspirin has anti-inflammatory effects, antiplatelet aggregation, anticoagulant properties as well as pleiotropic effects on endothelial function. During the COVID-19 pandemic, low-dose aspirin is used effectively in secondary prevention of atherosclerotic cardiovascular disease, prevention of venous thromboembolism after total hip or knee replacement, prevention of pre-eclampsia and postdischarge treatment for multisystem inflammatory syndrome in children. Prehospital low-dose aspirin therapy may reduce the risk of intensive care unit admission and mechanical ventilation in hospitalised patients with COVID-19, whereas aspirin association with mortality is still debatable. CONCLUSION: The authors recommend a low-dose aspirin regimen for primary prevention of arterial thromboembolism in patients aged 40-70 years who are at high atherosclerotic cardiovascular disease risk, or an intermediate risk with a risk-enhancer and have a low risk of bleeding. Aspirin's protective roles in COVID-19 associated with acute lung injury, vascular thrombosis without previous cardiovascular disease and mortality need further randomised controlled trials to establish causal conclusions.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Aspirin , COVID-19 , Thromboembolism , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/administration & dosage , Aspirin/adverse effects , Aspirin/therapeutic use , COVID-19/complications , COVID-19/physiopathology , COVID-19/therapy , Humans , Inflammation , Middle Aged , Practice Guidelines as Topic , Thromboembolism/drug therapy , Thromboembolism/etiology , Thromboembolism/prevention & control
11.
Postgrad Med J ; 98(1159): 395-402, 2022 May.
Article in English | MEDLINE | ID: covidwho-1183381

ABSTRACT

Rising incidence of thromboembolism secondary to COVID-19 has become a global concern, with several surveys reporting increased mortality rates. Thrombogenic potential of the SARS-CoV-2 virus has been hypothesised to originate from its ability to produce an exaggerated inflammatory response leading to endothelial dysfunction. Anticoagulants have remained the primary modality of treatment of thromboembolism for decades. However, there is no universal consensus regarding the timing, dosage and duration of anticoagulation in COVID-19 as well as need for postdischarge prophylaxis. This article seeks to review the present guidelines and recommendations as well as the ongoing trials on use of anticoagulants in COVID-19, identify discrepancies between all these, and provide a comprehensive strategy regarding usage of these drugs in the current pandemic.


Subject(s)
COVID-19 , Thromboembolism , Venous Thromboembolism , Aftercare , Anticoagulants/therapeutic use , Humans , Patient Discharge , SARS-CoV-2 , Thromboembolism/drug therapy , Thromboembolism/etiology , Thromboembolism/prevention & control , Venous Thromboembolism/etiology
12.
Thromb Haemost ; 121(12): 1684-1695, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1171416

ABSTRACT

Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels. Conflicting data have yet to elucidate optimal thromboprophylaxis dosing. HEP-COVID (NCT04401293) is a phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low-molecular-weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality 30 ± 2 days post-enrollment. Eligible patients have COVID-19 diagnosis by nasal swab or serologic testing, requirement for supplemental oxygen per investigator judgment, and Dd >4 × upper limit of normal (ULN) or sepsis-induced coagulopathy score ≥4. Subjects are randomized to enoxaparin 1 mg/kg subcutaneous (SQ)/two times a day (BID) (creatinine clearance [CrCl] ≥ 30 mL/min) or 0.5 mg/kg (CrCl 15-30 mL/min) versus local institutional prophylactic regimens including (1) UFH up to 22,500 IU (international unit) daily (divided BID or three times a day), (2) enoxaparin 30 and 40 mg SQ QD (once daily) or BID, or (3) dalteparin 2,500 IU or 5,000 IU QD. The principal safety outcome is major bleeding. Events are adjudicated locally. Based on expected 40% relative risk reduction with treatment-dose compared with prophylactic-dose prophylaxis, 308 subjects will be enrolled (assuming 20% drop-out) to achieve 80% power. Distinguishing design features include an enriched population for the composite endpoint anchored on Dd >4 × ULN, stratification by intensive care unit (ICU) versus non-ICU, and the ability to capture asymptomatic proximal deep venous thrombosis via screening ultrasonography prior to discharge.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Enoxaparin/administration & dosage , Thromboembolism/drug therapy , Anticoagulants/adverse effects , COVID-19/complications , COVID-19/diagnosis , Clinical Trials, Phase III as Topic , Enoxaparin/adverse effects , Humans , Pragmatic Clinical Trials as Topic , Prospective Studies , Risk Assessment , Risk Factors , Thromboembolism/diagnosis , Thromboembolism/etiology , Time Factors , Treatment Outcome , United States , Venous Thromboembolism/diagnosis , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
13.
Aging (Albany NY) ; 13(7): 9225-9242, 2021 03 26.
Article in English | MEDLINE | ID: covidwho-1170595

ABSTRACT

AIM: Coronavirus disease 2019 (COVID-19) has been associated with increased mortality and morbidity from thromboembolism, especially venous thromboembolism. There are more limited data for systemic thromboembolism. The present study aimed to investigate the prevalence of systemic and venous thromboembolism as well as major bleeding and mortality in relation to underlying risk factors and the impact of anticoagulation use in hospitalized patients with COVID-19. METHODS AND RESULTS: Patients with COVID-19 admitted to Union Hospital, Wuhan, Hubei, China between January 08, 2020 and April 7, 2020 were enrolled in this retrospective study. Cox proportional hazard models were utilized to determine associated risk factors for clinical events, adjusting for the severity of COVID-19 infection, drug therapies, comorbidities, surgery, and use of antithrombotic drugs. There were 1125 patients (49.9% male; mean age 58 years (standard deviation, SD, 15 years)) with a mean follow-up of 21 (SD 13) days. Approximately 25 (30%) patients with thromboembolism also suffered bleeding events. Age was an independent risk factor for thromboembolism, bleeding events, and death (all p<0.05). After adjusting for the severity of COVID-19 infection, comorbidities, surgery, antiviral drugs, immunomodulators, Chinese herbs, and antithrombotic drugs, low lymphocyte counts (hazard ratio, HR, 95% confidence interval (CI), 1.03, 1.01-1.05, p=0.01) and surgery (HR 2.80, 1.08-7.29, p=0.03) independently predicted the risk for major bleeding, whereas liver dysfunction (HR 4.13, 1.30-13.1, p=0.02) was an independent risk factor for patients with both thromboembolism and bleeding events. CONCLUSIONS: Patients with COVID-19 were at high risk for thromboembolic and bleeding events as well as mortality. The use of anticoagulants, especially parenteral anticoagulants, significantly reduced the risk for composite outcomes of thromboembolism, bleeding events, and death. The presence of AF was a contributor to systemic thromboembolism in COVID-19 patients.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Thromboembolism/drug therapy , Thromboembolism/etiology , Adult , Aged , Anticoagulants/adverse effects , Antiviral Agents/therapeutic use , COVID-19/drug therapy , China/epidemiology , Female , Hemorrhage/chemically induced , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology
14.
Cardiovasc Hematol Disord Drug Targets ; 21(1): 23-29, 2021.
Article in English | MEDLINE | ID: covidwho-1133783

ABSTRACT

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS- CoV-2) is our latest pandemic and has turned out to be a global public health crisis. One of the special characteristics of this disease is that it may predispose patients to thrombotic disease both in the venous and arterial circulation. We review arterial and venous thromboembolic complications in patients with COVID-19, epidemiology, pathogenesis, hematologic biomarkers, and current antithrombotic strategies. Future perspectives and clinical trials are ongoing to determine the best thromboprophylaxis strategies in the hospitalized patients with severe COVID-19.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Thromboembolism/etiology , Thromboembolism/physiopathology , Biomarkers , Dose-Response Relationship, Drug , Fibrinolytic Agents/therapeutic use , Humans , Pandemics , SARS-CoV-2 , Thromboembolism/drug therapy , Thromboembolism/prevention & control
15.
Diagnosis (Berl) ; 7(4): 357-363, 2020 Nov 18.
Article in English | MEDLINE | ID: covidwho-1021710

ABSTRACT

Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized as a systemic disorder inducing a prothrombotic state. The molecular mechanisms underlying the hypercoagulable state seen in patients with COVID-19 is still incompletely understood, although it presumably involves the close link between inflammatory and hemostatic systems. The laboratory coagulation monitoring of severely ill COVID-19 patients is mandatory to identify those patients at increased thrombotic risk and to modulate thromboprophylaxis accordingly. In this review, we summarize the current understanding on the pathogenesis, epidemiology, clinical and laboratory features and management of coagulopathy associated with COVID-19.


Subject(s)
Betacoronavirus/genetics , Blood Coagulation Disorders/etiology , Coronavirus Infections/diagnosis , Pneumonia, Viral/complications , Anticoagulants/therapeutic use , Blood Coagulation Disorders/prevention & control , Blood Coagulation Disorders/virology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Humans , Inflammation/complications , Inflammation/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index , Thromboembolism/drug therapy , Thromboembolism/etiology , Thromboembolism/prevention & control , Thrombosis/epidemiology , Thrombosis/prevention & control
16.
Trends Cardiovasc Med ; 31(3): 143-160, 2021 04.
Article in English | MEDLINE | ID: covidwho-978447

ABSTRACT

Coronavirus disease of 2019 (COVID-19) is the respiratory viral infection caused by the coronavirus SARS-CoV2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite being a respiratory illness, COVID-19 is found to increase the risk of venous and arterial thromboembolic events. Indeed, the link between COVID-19 and thrombosis is attracting attention from the broad scientific community. In this review we will analyze the current available knowledge of the association between COVID-19 and thrombosis. We will highlight mechanisms at both molecular and cellular levels that may explain this association. In addition, the article will review the antithrombotic properties of agents currently utilized or being studied in COVID-19 management. Finally, we will discuss current professional association guidance on prevention and treatment of thromboembolism associated with COVID-19.


Subject(s)
COVID-19/complications , Fibrinolytic Agents/therapeutic use , SARS-CoV-2/pathogenicity , Thrombosis/drug therapy , Thrombosis/virology , Anticoagulants/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , Humans , Thromboembolism/drug therapy , Thromboembolism/virology , Thrombosis/diagnosis
17.
J Am Coll Cardiol ; 76(16): 1815-1826, 2020 10 20.
Article in English | MEDLINE | ID: covidwho-849705

ABSTRACT

BACKGROUND: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings. OBJECTIVES: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies. METHODS: This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding. Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission. Thromboembolic disease was contextualized by premortem AC among consecutive autopsies. RESULTS: Among 4,389 patients, median age was 65 years with 44% women. Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively). When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC. CONCLUSIONS: AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.


Subject(s)
Anticoagulants , Autopsy/statistics & numerical data , Coronavirus Infections , Hospitalization/statistics & numerical data , Pandemics , Pneumonia, Viral , Post-Exposure Prophylaxis , Thromboembolism , Aged , Anticoagulants/classification , Anticoagulants/therapeutic use , Betacoronavirus/isolation & purification , Blood Coagulation , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Female , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Hospital Mortality , Humans , Male , New York City/epidemiology , Outcome and Process Assessment, Health Care , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Post-Exposure Prophylaxis/methods , Post-Exposure Prophylaxis/statistics & numerical data , Risk Adjustment/methods , SARS-CoV-2 , Thromboembolism/drug therapy , Thromboembolism/mortality , Thromboembolism/prevention & control , Thromboembolism/virology
18.
Ann Hematol ; 99(9): 1953-1965, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-704271

ABSTRACT

In October 2019, a viral infectious disease appeared in the city of Wuhan in China. A new betacoronavirus, SARS-CoV-2, has been recognized as the responsible pathogen in this infection. Although coronavirus disease is principally expressed as a pulmonary infection, critical SARS-CoV-2 infection is frequently complicated with coagulopathy, and thromboembolic events are recognizable in several patients. Dehydration, acute inflammatory condition, protracted immobilization during disease, existence of multiple cardiovascular risk factors such as diabetes, obesity or hypertension, previous coronary artery disease, ischemic stroke, peripheral artery disease are frequent comorbidities in SARS-CoV-2 hospitalized subjects, which possibly augment thrombo-embolic risk. However, other causal factors can still be identified such as unrestricted angiotensin II action, the use of immunoglobulins, an increased production of adhesion molecules able to induce vascular inflammation and endothelial activation, complement stimulation, excessive production of neutrophil extracellular traps (NETs), and increased platelet count. Low-molecular-weight heparin should be chosen as early treatment because of its anti-inflammatory action and its ability to antagonize histones and so defend the endothelium. However, several therapeutic possibilities have also been proposed such as fibrinolytic treatment, drugs that target NETs, and complement inhibition. Nevertheless, although the violence of the pandemic may suggest the use of heroic treatments to reduce the frightening mortality that accompanies SARS-CoV-2 infection, we believe that experimental treatments should only be used within approved and controlled protocols, the only ones that can provide useful and specify information on the validity of the treatments.


Subject(s)
Betacoronavirus , Blood Coagulation Disorders/blood , Coronavirus Infections/blood , Disease Management , Pneumonia, Viral/blood , Thromboembolism/blood , Anti-Inflammatory Agents/therapeutic use , Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Thromboembolism/drug therapy , Thromboembolism/etiology
19.
Clin Radiol ; 75(11): 804-810, 2020 11.
Article in English | MEDLINE | ID: covidwho-693338

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a newly emerging human infectious disease that has quickly become a worldwide threat to health, mainly causing severe acute respiratory syndrome. In addition to the widely described respiratory syndrome, COVID-19 may cause life-treating complications directly or indirectly related to this infection. Among these, thrombotic complications have emerged as an important issue in patients with COVID-19 infection, particularly in patients in intensive care units. Thrombotic complications due to COVID-19 are likely to occur due to a pro-coagulant pattern encountered in some of these patients or to a progressive endothelial thrombo-inflammatory syndrome causing microvascular disease. In the present authors' experience, from five different hospitals in Italy and the UK, imaging has proved its utility in identifying these COVID-19-related thrombotic complications, with translational clinical relevance. The aim of this review is to illustrate thromboembolic complications directly or indirectly related to COVID-19 disease. Specifically, this review will show complications related to thromboembolism due to a pro-coagulant pattern from those likely related to an endothelial thrombo-inflammatory syndrome.


Subject(s)
Anticoagulants/administration & dosage , Coronavirus Infections/complications , Pneumonia, Viral/complications , Pulmonary Embolism/etiology , Severe Acute Respiratory Syndrome/complications , Thromboembolism/drug therapy , Thromboembolism/etiology , Adult , Aged , Brain Ischemia/diagnostic imaging , Brain Ischemia/etiology , Brain Ischemia/mortality , COVID-19 , Cause of Death , Communicable Diseases, Emerging/epidemiology , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Female , Humans , Italy , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/drug therapy , Pulmonary Embolism/mortality , Radiography, Thoracic/methods , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/mortality , Survival Analysis , Thromboembolism/diagnostic imaging , Thromboembolism/mortality , Thromboplastin/metabolism , Tomography, X-Ray Computed/methods
20.
J Thromb Thrombolysis ; 51(2): 308-312, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-645217

ABSTRACT

BACKGROUD: COVID-19 coagulopathy linked to increased D-dimer levels has been associated with high mortality (Fei Z et al. in Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (London, England) 395(10229):1054-62, 2020). While D-dimer is accepted as a disseminated intravascular coagulation marker, rotational thromboelastometry (ROTEM) also detects fibrinolysis (Wright FL et al. in Fibrinolysis shutdown correlates to thromboembolic events in severe COVID-19 infection. J Am Coll Surg (2020). Available from https://pubmed.ncbi.nlm.nih.gov/32422349/ [cited 14 Jun 2020]; Schmitt FCF et al. in Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care 9(1):19, 2019). We describe the ROTEM profile in severely ill COVID-19 patients and compare it with the standard laboratory coagulation test. METHODS: Adult patients diagnosed with COVID-19 admitted to the ICU were prospectively enrolled after Ethics Committee approval (HCB/2020/0371). All patients received venous thromboembolism prophylaxis; those on therapeutic anticoagulation were excluded. The standard laboratory coagulation test and ROTEM were performed simultaneously at 24-48 h after ICU admission. Sequential organ failure assessment (SOFA), disseminated intravascular coagulation (DIC) and sepsis-induced coagulopathy (SIC) scores were calculated at sample collection. RESULTS: Nineteen patients were included with median SOFA-score of 4 (2-6), DIC-score of 1 (0-3) and SIC-score of 1.8 (0.9). Median fibrinogen, D-dimer levels and platelet count were 6.2 (4.8-7.6 g/L), 1000 (600-4200 ng/ml) and 236 (136-364 109/L), respectively. Clot firmness was above the normal range in the EXTEM and FIBTEM tests while clot lysis was decreased. There was no significant correlation between ROTEM or D-dimer parameters and the SOFA score. CONCLUSION: In COVID-19 patients, the ROTEM pattern was characterized by a hypercoagulable state with decreased fibrinolytic capacity despite a paradoxical increase in D-dimer levels. We suggest that, in COVID-19 patients, the lungs could be the main source of D-dimer, while a systemic hypofibrinolytic state coexists. This hypothesis should be confirmed by future studies.


Subject(s)
Anticoagulants/administration & dosage , COVID-19 , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinolysis , SARS-CoV-2/metabolism , Thromboembolism , Aged , COVID-19/blood , COVID-19/drug therapy , Female , Humans , Male , Middle Aged , Retrospective Studies , Thrombelastography , Thromboembolism/blood , Thromboembolism/drug therapy
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