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1.
Am Surg ; 86(9): 1062-1066, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33049165

RESUMO

BACKGROUND: Direct oral anticoagulants (DOACs) have overtaken warfarin as the preferred anticoagulants for stroke prevention with atrial fibrillation and for treatment of venous thromboembolism. Despite the increased prevalence of DOACs, literature studying their impact on trauma patients with intracranial hemorrhage (ICH) remains limited. Most DOAC reversal agents have only been recently available, and concerns for worse outcomes with DOACs among this population remain. This study aims to assess the outcomes of patients with traumatic ICH taking DOACs compared with those taking warfarin. METHODS: A retrospective analysis of patients with traumatic ICH over a 5-year period was conducted. Demographics, injury severity, medication, and outcome data were collected for each patient. Patients taking warfarin and DOACs were compared. RESULTS: 736 patients had traumatic ICH over the study period, 75 of which were on either DOACs (25 patients) or warfarin (50 patients). The median age of the anticoagulated patients was 78 years; 52% were female, and 91% presented secondary to a fall. DOACs were reversed at close to half the rate of warfarin (40% vs 77%; P = .032). Despite this, the 2 groups had similar rates of worsening examination, need for operative intervention, and in-hospital mortality. In the follow-up, fewer patients taking DOACs had died at 6-months postinjury compared with those taking warfarin (8% vs 30%; P = .041). DISCUSSION: Despite DOACs being reversed at nearly half the rate of warfarin, patients presenting with traumatic ICH on warfarin had higher 6-month mortality suggesting a potential survival advantage for DOACs over warfarin in this population.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Hemorragia Intracraniana Traumática/complicações , Acidente Vascular Cerebral/prevenção & controle , Varfarina/administração & dosagem , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Coagulação Sanguínea/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Hemorragia Intracraniana Traumática/sangue , Hemorragia Intracraniana Traumática/mortalidade , Masculino , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia
2.
Angiol Sosud Khir ; 26(3): 16-26, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33063748

RESUMO

The routine practice of a vascular surgeon is invariably associated with decreasing the risk of adverse cardiovascular events in patients presenting with either arterial or venous pathology. Antithrombotic therapy is one of the key approaches used to achieve this purpose. However, a wide variety of modern drugs inhibiting platelet aggregation and agents blocking the coagulation cascade, as well as their combinations makes the selection of the most appropriate treatment for a particular patient quite a difficult task. The choice should carefully be made taking into consideration the nosology, aetiology, accompanying diseases and therapy thereof, as well as the balance of the risk of ischaemic and haemorrhagic complications. Therefore, availability of modern antithrombotic drugs favourably contributing to a more personified approach to treatment is of utmost importance. Thus, for example, rivaroxaban, an anticoagulant belonging to the class of direct-acting oral factor Xa inhibitors, provides a possibility to select an optimal dosage and regimen for a particular patient with arterial or vascular pathology in practice of a cardiovascular surgeon.


Assuntos
Anticoagulantes , Inibidores da Agregação de Plaquetas , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/efeitos adversos , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Rivaroxabana/efeitos adversos
4.
Anesth Analg ; 131(5): 1324-1333, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33079850

RESUMO

Patients with coronavirus disease 2019 (COVID-19) frequently experience a coagulopathy associated with a high incidence of thrombotic events leading to poor outcomes. Here, biomarkers of coagulation (such as D-dimer, fibrinogen, platelet count), inflammation (such as interleukin-6), and immunity (such as lymphocyte count) as well as clinical scoring systems (such as sequential organ failure assessment [SOFA], International Society on Thrombosis and Hemostasis disseminated intravascular coagulation [ISTH DIC], and sepsis-induced coagulopathy [SIC] score) can be helpful in predicting clinical course, need for hospital resources (such as intensive care unit [ICU] beds, intubation and ventilator therapy, and extracorporeal membrane oxygenation [ECMO]) and patient's outcome in patients with COVID-19. However, therapeutic options are actually limited to unspecific supportive therapy. Whether viscoelastic testing can provide additional value in predicting clinical course, need for hospital resources and patient's outcome or in guiding anticoagulation in COVID-19-associated coagulopathy is still incompletely understood and currently under investigation (eg, in the rotational thromboelastometry analysis and standard coagulation tests in hospitalized patients with COVID-19 [ROHOCO] study). This article summarizes what we know already about COVID-19-associated coagulopathy and-perhaps even more importantly-characterizes important knowledge gaps.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/terapia , Inflamação/terapia , Pneumonia Viral/terapia , Embolia Pulmonar/terapia , Tromboembolia Venosa/terapia , Trombose Venosa/terapia , Anti-Inflamatórios/efeitos adversos , Anticoagulantes/efeitos adversos , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Medicina Baseada em Evidências , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Mortalidade Hospitalar , Interações Hospedeiro-Patógeno , Humanos , Inflamação/sangue , Inflamação/mortalidade , Inflamação/virologia , Mediadores da Inflamação/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Prognóstico , Embolia Pulmonar/sangue , Embolia Pulmonar/mortalidade , Embolia Pulmonar/virologia , Fatores de Risco , Tromboembolia Venosa/sangue , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/virologia , Trombose Venosa/sangue , Trombose Venosa/mortalidade , Trombose Venosa/virologia
5.
Clin Appl Thromb Hemost ; 26: 1076029620960797, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33079569

RESUMO

The incidence of venous thromboembolism (VTE) events in patients with COVID-19 treated with a standard thromboprophylaxis dose of anticoagulants remains high. We conducted a systematic review in order to explore the association between therapeutic-dose anticoagulation and its effect on mortality in patients with COVID-19. A systematic search was carried out using the electronic databases of PubMed, EuropePMC, and the Cochrane Central Database, using specific keywords. All articles that fulfilled the inclusion criteria were included in the qualitative analysis. There were 8 observational studies included in the final qualitative analysis. Quality assessment using the Newcastle-Ottawa Scale (NOS) showed a mean score of 7.5 ± 1.06, indicating moderate to high quality of the studies. Three retrospective cohort studies reported a reduction in the mortality rate, while 6 other studies showed no mortality benefits among patients with COVID-19 treated with therapeutic-dose anticoagulation. There was a slight tendency toward a reduction in the mortality rate among mechanically-ventilated patients with COVID-19 receiving therapeutic-dose anticoagulation. Bleeding events and thrombotic complications among patients receiving therapeutic-dose anticoagulation were reported in 3 studies. Although it is too soon to draw any conclusions, this systematic review draws attention to current evidence regarding the association between therapeutic-dose anticoagulation and its effect on mortality in patients with COVID-19.


Assuntos
Anticoagulantes/administração & dosagem , Betacoronavirus , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Tromboembolia/prevenção & controle , Infecções por Coronavirus/epidemiologia , Saúde Global , Humanos , Incidência , Pneumonia Viral/epidemiologia , Taxa de Sobrevida/tendências , Tromboembolia/epidemiologia , Tromboembolia/etiologia
6.
Clin Appl Thromb Hemost ; 26: 1076029620954913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33030036

RESUMO

INTRODUCTION: Sulodexide represents a mixture of fast-moving heparin (FMH) and dermatan sulfate (DS) and has been used for the management of venous diseases such as DVT and related disorders. The purpose of this study is to compare sulodexide and its components with unfractionated heparin (UFH) to determine its suitability for the indications in which UFH is used. MATERIALS AND METHOD: Active pharmaceutical ingredients (API) versions of sulodexide, FMH and DS were obtained from Alfasigma. API versions of UFH were obtained from Medefil Inc. Normal human citrated plasma was obtained from blood bank of the Loyola University Medical Center. Each of the individual agents were supplemented in plasma at a graded concentration of 0.0-10 µg/mL. Clotting assays (PiCT, aPTT, PT and TT), anti-Xa and anti-IIa and thrombin generation studies were carried out. Results were compiled as mean ± SD of 3 individual determination. RESULT: In the clot based (PiCT, aPTT and TT), anti-Xa and IIa assays, both the UFH and FMH produced stronger activities in these assays followed by sulodexide. DS did not show any anticoagulant activity. In the thrombin generation assay, FMH and UFH produced comparable inhibition of thrombin generation as measured by various parameters. Sulodexide was slightly weaker in this assay, whereas DS produced relatively weaker effects. CONCLUSION: In comparison to sulodexide, both UFH and FMH exhibit comparable anticoagulant activity despite differences in their molecular weight. These results suggest that sulodexide can be developed as a parenteral anticoagulant for indications in which UFH is used.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Glicosaminoglicanos/farmacologia , Trombina/farmacologia , Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Antitrombinas/farmacologia , Glicosaminoglicanos/administração & dosagem , Heparina/administração & dosagem , Heparina/farmacologia , Humanos , Itália , Sensibilidade e Especificidade , Trombina/administração & dosagem
7.
Trials ; 21(1): 770, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907635

RESUMO

OBJECTIVES: The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. TRIAL DESIGN: The OVID study is conducted as a multicentre open-label superiority randomised controlled trial. PARTICIPANTS: Inclusion Criteria 1. Signed patient informed consent after being fully informed about the study's background. 2. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment. 3. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5° C. 4. Ability of the patient to travel to the study centre by private transportation, performed either by an accompanying person from the same household or by the patient themselves 5. Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant. 6. Ability to walk from car to study centre or reach it by wheelchair transport with the help of an accompanying person from the same household also complying with standard hygiene requirements. 7. Ability to self-administer prefilled enoxaparin injections after instructions received at the study centre or availability of a person living with the patient to administer enoxaparin. Exclusion Criteria 1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior venous thromboembolism (VTE), acute confirmed symptomatic VTE, acute coronary syndrome. 2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis: a. Any of the following events occurring in the prior 30 days: fracture of lower limb, hospitalization for heart failure, hip/knee replacement, major trauma, spinal cord injury, stroke, b. previous VTE, c. histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable. 3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 30 days prior to randomization or sign of acute bleeding. 4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial haemorrhage. 5. Haemoglobin <8 g/dL and platelet count <50 x 109 cells/L confirmed by recent laboratory test (<90 days). 6. Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy. 7. Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days). 8. Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity. 9. Current use of dual antiplatelet therapy. 10. Participation in other interventional studies over the past 30 days. 11. Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment. 12. Cognitive impairment and/or inability to understand information provided in the study information. Patient enrolment will take place at seven Swiss centres, including five university hospitals and two large cantonal hospitals. INTERVENTION AND COMPARATOR: Patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4,000 IU anti-Xa activity (40 mg/0.4 ml) once daily for 14 days. Patients randomized to the comparator group will receive no anticoagulation. MAIN OUTCOMES: Primary outcome: a composite of any hospitalization or all-cause death occurring within 30 days of randomization. SECONDARY OUTCOMES: (i) a composite of cardiovascular events, including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke within 14 days, 30 days, and 90 days of randomization; (ii) each component of the primary efficacy outcome, within 14 days, 30 days, and 90 days of randomization; (iii) net clinical benefit (accounting for the primary efficacy outcome, composite cardiovascular events, and major bleeding), within 14 days, 30 days, and 90 days of enrolment; (iv) primary efficacy outcome, within 14 days, and 90 days of enrolment; (v) disseminated intravascular coagulation (ISTH criteria, in-hospital diagnosis) within 14 days, 30 days, and 90 days of enrolment. RANDOMISATION: Patients will undergo block stratified randomization (by age: 50-70 vs. >70 years; and by study centre) with a randomization ratio of 1:1 with block sizes varying between 4 and 8. Randomization will be performed after the signature of the informed consent for participation and the verification of the eligibility criteria using the electronic data capture software (REDCAP, Vanderbilt University, v9.1.24). BLINDING (MASKING): In this open-label study, no blinding procedures will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation is based on the parameters α = 0.05 (2-sided), power: 1-ß = 0.8, event rate in experimental group, pexp = 0.09 and event rate in control group, pcon = 0.15. The resulting total sample size is 920. To account for potential dropouts, the total sample size was fixed to 1000 with 500 patients in the intervention group and 500 in the control group. TRIAL STATUS: Protocol version 1.0, 14 April 2020. Protocol version 3.0, 18 May 2020 Recruiting start date: June 2020. Last Patient Last Visit: March 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04400799 First Posted: May 26, 2020 Last Update Posted: July 16, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Anticoagulantes/administração & dosagem , Betacoronavirus/patogenicidade , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Enoxaparina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Enoxaparina/efeitos adversos , Estudos de Equivalência como Asunto , Interações Hospedeiro-Patógeno , Humanos , Estudos Multicêntricos como Assunto , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Trombose/sangue , Trombose/diagnóstico , Trombose/virologia , Fatores de Tempo , Resultado do Tratamento
9.
J Thromb Haemost ; 18(9): 2138-2144, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32881336

RESUMO

Hypercoagulability is an increasingly recognized complication of SARS-CoV-2 infection. As such, anticoagulation has become part and parcel of comprehensive COVID-19 management. However, several uncertainties exist in this area, including the appropriate type and dose of heparin. In addition, special patient populations, including those with high body mass index and renal impairment, require special consideration. Although the current evidence is still insufficient, we provide a pragmatic approach to anticoagulation in COVID-19, but stress the need for further trials in this area.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus/patogenicidade , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/mortalidade , Transtornos da Coagulação Sanguínea/virologia , Tomada de Decisão Clínica , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Seleção de Pacientes , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Fatores de Risco , Resultado do Tratamento
12.
Toxicon ; 187: 223-231, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32971099

RESUMO

Snake venom metalloproteinases (SVMPs) are an important component in viperid and crotalid venoms, and these SVMPs play important and versatile roles in the pathogenesis of snakebite envenoming. The SVMPs from elapid venoms are not well elucidated compared with those from viperid and crotalid venoms. Atrase B is a nonhemorrhagic P-III SVMP purified from the Naja atra venom, which possesses a weak fibrinogenolytic activity. In this paper, the activity and mechanism of atrase B against platelet aggregation and blood coagulation were investigated. The in vitro assay showed that atrase B remarkably inhibited ristocetin- and thrombin-induced platelet aggregation by cleavage of the platelet membrane glycoprotein Ib, and the coagulation of normal human plasma, which may be caused by inhibiting coagulation factor VIII predominantly. When atrase B was intravenously injected into rats at doses of 0.05 and 0.30 mg/kg, the activated partial thromboplastin and the thrombin times were significantly prolonged in a dose-dependent manner. Similarly, the fibrinogen level decreased, but only a high dose of atrase B showed remarkable activity against platelet aggregation. Results suggested that anticoagulation was a more important function of atrase B compared with its activity against platelet aggregation. These results indicated that atrase B may play an important role in the anticoagulant properties of Naja atra venom. In addition, atrase B may be a potent anticoagulant agent because its effectiveness in vivo against platelet aggregation and blood coagulation.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Venenos Elapídicos/toxicidade , Metaloproteases/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Animais , Humanos , Ratos
14.
Nat Commun ; 11(1): 3890, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753636

RESUMO

Inhibiting thrombosis without generating bleeding risks is a major challenge in medicine. A promising solution may be the inhibition of coagulation factor XII (FXII), because its knock-out or inhibition in animals reduced thrombosis without causing abnormal bleeding. Herein, we have engineered a macrocyclic peptide inhibitor of activated FXII (FXIIa) with sub-nanomolar activity (Ki = 370 ± 40 pM) and a high stability (t1/2 > 5 days in plasma), allowing for the preclinical evaluation of a first synthetic FXIIa inhibitor. This 1899 Da molecule, termed FXII900, efficiently blocks FXIIa in mice, rabbits, and pigs. We found that it reduces ferric-chloride-induced experimental thrombosis in mice and suppresses blood coagulation in an extracorporeal membrane oxygenation (ECMO) setting in rabbits, all without increasing the bleeding risk. This shows that FXIIa activity is controllable in vivo with a synthetic inhibitor, and that the inhibitor FXII900 is a promising candidate for safe thromboprotection in acute medical conditions.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Fator XIIa/antagonistas & inibidores , Peptídeos Cíclicos/efeitos dos fármacos , Trombose/prevenção & controle , Animais , Cloretos/efeitos adversos , Clonagem Molecular , Modelos Animais de Doenças , Descoberta de Drogas , Oxigenação por Membrana Extracorpórea/métodos , Fator XII/antagonistas & inibidores , Feminino , Compostos Férricos/efeitos adversos , Humanos , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Coelhos , Proteínas Recombinantes/farmacologia , Suínos
15.
Chem Biol Interact ; 329: 109223, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32781033

RESUMO

Thromboembolism is a major cause of morbidity and mortality worldwide. Most therapeutic drugs for treating thrombosis can cause hemorrhage and have short half-lives within human blood circulation resulting in a need to discover and develop novel anticoagulants/antithrombotics. EuRP-61 has been isolated from a plant latex (Euphorbia resinifera) and characterized as a serine protease. In this study, EuRP-61 was able to hydrolyze all chains of human fibrin clots. The enzyme may have long term stability in blood circulation as its fibrinogenolytic activity was not affected by human blood circulating inhibitors such as α2-macroglobulin and antithrombin III. The enzyme may affect the extrinsic, intrinsic or common pathways of the human blood coagulation cascade as evidenced by its prolonged of both prothrombin (PT) and activated partial thromboplastin (APTT) time. Moreover, the enzyme inhibited platelet aggregation via the ADP-receptor pathway. EuRP-61 was not toxic to human red blood cells in the 4 common blood groups (A, B, O and AB) (all Rh+) or human peripheral blood mononuclear cells (hPBMCs). The enzyme may protect human peripheral blood cells from aggregation without destroying them. This study provides evidence that EuRP-61 may have potential as an agent for the treatment of thrombosis.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Euphorbia/enzimologia , Fibrinolíticos/farmacologia , Peptídeo Hidrolases/farmacologia , Proteínas de Plantas/farmacologia , Anticoagulantes/isolamento & purificação , Antitrombina III/antagonistas & inibidores , Antitrombina III/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Fibrinolíticos/isolamento & purificação , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Peptídeo Hidrolases/isolamento & purificação , Proteínas de Plantas/isolamento & purificação , Agregação Plaquetária/efeitos dos fármacos , alfa 2-Macroglobulinas Associadas à Gravidez/antagonistas & inibidores , alfa 2-Macroglobulinas Associadas à Gravidez/metabolismo
16.
J Thromb Thrombolysis ; 50(4): 814-821, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32748122

RESUMO

Many aspects of care such as management of hypercoagulable state in COVID-19 patients, especially those admitted to intensive care units is challenging in the rapidly evolving pandemic of novel coronavirus disease 2019 (COVID-19). We seek to systematically review the available evidence regarding the anticoagulation approach to prevent venous thromboembolism (VTE) among COVID-19 patients admitted to intensive care units. Electronic databases were searched for studies reporting venous thromboembolic events in patients admitted to the intensive care unit receiving any type of anticoagulation (prophylactic or therapeutic). The pooled prevalence (and 95% confidence interval [CI]) of VTE among patients receiving anticoagulant were calculated using the random-effects model. Subgroup pooled analyses were performed with studies reported prophylactic anticoagulation alone and with studies reported mixed prophylactic and therapeutic anticoagulation. We included twelve studies (8 Europe; 2 UK; 1 each from the US and China) in our systematic review and meta-analysis. All studies utilized LMWH or unfractionated heparin as their pharmacologic thromboprophylaxis, either prophylactic doses or therapeutic doses. Seven studies reported on the proportion of patients with the previous history of VTE (range 0-10%). The pooled prevalence of VTE among ICU patients receiving prophylactic or therapeutic anticoagulation across all studies was 31% (95% CI 20-43%). Subgroup pooled analysis limited to studies reported prophylactic anticoagulation alone and mixed (therapeutic and prophylactic anticoagulation) reported pooled prevalences of VTE of 38% (95% CI 10-70%) and 27% (95% CI 17-40%) respectively. With a high prevalence of thromboprophylaxis failure among COVID-19 patients admitted to intensive care units, individualised rather than protocolised VTE thromboprophylaxis would appear prudent at interim.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Estado Terminal , Feminino , Fibrinolíticos/efeitos adversos , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/virologia
18.
Toxicol Lett ; 333: 211-221, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32841740

RESUMO

Bothrops (lance-head pit vipers) venoms are rich in weaponised metalloprotease enzymes (SVMP). These toxic enzymes are structurally diverse and functionally versatile. Potent coagulotoxicity is particularly important for prey capture (via stroke-induction) and relevant to human clinical cases (due to consumption of clotting factors including the critical depletion of fibrinogen). In this study, three distinct isoforms of P-III class SVMPs (IC, IIB and IIC), isolated from Bothrops neuwiedi venom, were evaluated for their differential capacities to affect hemostasis of prey and human plasma. Furthermore, we tested the relative antivenom neutralisation of effects upon human plasma. The toxic enzymes displayed differential procoagulant potency between plasma types, and clinically relevant antivenom efficacy variations were observed. Of particular importance was the confirmation the antivenom performed better against prothrombin activating toxins than Factor X activating toxins, which is likely due to the greater prevalence of the former in the immunising venoms used for antivenom production. This is clinically relevant as the enzymes displayed differential potency in this regard, with one (IC) in particular being extremely potent in activating Factor X and thus was correspondingly poorly neutralised. This study broadens the current understanding about the adaptive role of the SVMPs, as well as highlights how the functional diversity of SVMP isoforms can influence clinical outcomes. Key Contribution: Our findings shed light upon the hemorrhagic and coagulotoxic effects of three SVMPs of the P-III class, as well as the coagulotoxic effects of SVMPs on human, avian and amphibian plasmas. Antivenom neutralised prothrombin-activating isoforms better than Factor X activating isoforms.


Assuntos
Antivenenos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Hemorragia/prevenção & controle , Metaloproteases/toxicidade , Venenos de Serpentes/enzimologia , Animais , Bothrops , Feminino , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hemorragia/fisiopatologia , Humanos , Microscopia Intravital , Masculino , Metaloproteases/química , Camundongos , Microcirculação/efeitos dos fármacos , Microvasos/diagnóstico por imagem , Microvasos/efeitos dos fármacos , Microvasos/patologia , Isoformas de Proteínas
19.
Vascul Pharmacol ; 133-134: 106783, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32835836

RESUMO

BACKGROUND: Low-molecular-weight heparins (LMWHs) influence the fibrin network structure in in vitro models. There have been no reports on LMWH-induced modifications of fibrin clot characteristics and their determinants in acute pulmonary embolism (PE). AIM: We investigated how enoxaparin alters fibrin clot properties in acute PE patients. METHODS: Clots were generated from plasma of 46 acute PE patients, aged 47-77 years treated with enoxaparin 1 mg/kg bid. Fibrin clot permeability (Ks) and clot lysis time (CLT), along with coagulation and fibrinolysis proteins were determined. Plasma fibrin clot nanostructure was assessed using scanning electron microscopy (SEM). RESULTS: Both Ks and CLT were associated with anti-factor (F)Xa activity (r = 0.75, p < 0.0001 and r = -0.37, p = 0.011). Anti-FXa was positively associated with fibrin fiber diameter and the pore area, and inversely with fibrin fiber density on SEM images. Multiple regression analysis adjusted for age, body-mass index, and fibrinogen levels showed that anti-FXa activity, antithrombin activity, and FVIII activity determined Ks, while anti-FXa activity, plasminogen activator inhibitor-1 level, and presence of right ventricular dysfunction determined CLT. CONCLUSIONS: We identified new laboratory and clinical factors contributing to prothrombotic plasma fibrin clot characteristics during enoxaparin treatment, which might help elucidate mechanisms underlying therapy failure in patients with acute PE.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Enoxaparina/uso terapêutico , Fibrina/metabolismo , Fibrinolíticos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Adulto , Idoso , Feminino , Fibrina/ultraestrutura , Tempo de Lise do Coágulo de Fibrina , Humanos , Masculino , Pessoa de Meia-Idade , Permeabilidade , Porosidade , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Falha de Tratamento
20.
Am J Pathol ; 190(10): 2146-2154, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32745462

RESUMO

Patients with thalassemia exhibit an increased risk of thrombotic events that is augmented after splenectomy. Heparanase protein enhances cancer progression, angiogenesis, and inflammation; it also activates the coagulation system through direct interaction with tissue factor (TF). Additionally, erythropoietin, which is elevated in anemic patients, up-regulates heparanase expression via the Janus kinase 2 (JAK-2) pathway. This study aimed was to explore the heparanase profile in thalassemia. Coagulation factors were analyzed via immunostaining, enzyme-linked immunosorbent assay, and heparanase procoagulant activity assay. In spleen specimens of thalassemia major patients, a higher level of heparanase staining was observed compared with control spleens resected after trauma (P < 0.001). Higher heparanase levels, heparanase and TF procoagulant activity, and erythropoietin levels were found in the plasma of 67 thalassemia major patients compared with 29 control subjects. No difference was found in pediatric patients (23 of 67) compared with adults or splenectomized versus nonsplenectomized patients. Higher levels of heparanase, TF, TF pathway inhibitor, and TF pathway inhibitor-2 were observed in liver, spleen, heart, and kidney tissues of thalassemia intermedia mice (Hbbth3/+). These protein levels significantly reduced when mice were treated with the JAK-2 inhibitor ruxolitinib (P < 0.0001). In summary, heparanase levels are elevated in thalassemia, which may contribute to thrombotic phenomena in these patients. Inhibition of heparanase or the JAK-2 pathway may reduce thrombotic risk in thalassemia.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Glucuronidase/metabolismo , Janus Quinase 2/antagonistas & inibidores , Lipoproteínas/farmacologia , Trombose/tratamento farmacológico , Adulto , Animais , Humanos , Masculino , Camundongos Endogâmicos C57BL , Talassemia/tratamento farmacológico , Talassemia/metabolismo , Tromboplastina/metabolismo , Trombose/metabolismo , Adulto Jovem
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