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1.
Trials ; 21(1): 920, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176886

RESUMO

OBJECTIVES: The primary objective is to test if heparin added to a standard regional anticoagulation protocol based on citrate is able to reduce dialysis circuit losses by clotting without increasing the risk of thrombocytopenia or bleeding, in patients with COVID-19 with acute kidney injury requiring dialysis. TRIAL DESIGN: Randomized, parallel-group, open-label trial, with two arms (ratio 1:1) comparing different continuous renal replacement therapy anticoagulation strategies. PARTICIPANTS: Eligibility conditions: All ICU patients of University of Sao Paulo General Hospital (Hospital das Clínicas), Brazil will be screened for eligibility conditions. Adults (> 18 years old) with confirmed COVID-19 and acute kidney injury requiring dialysis with agreement between ICU and nephrology teams for the introduction of renal continuous replacement therapy in daily ICU rounds. Continuous renal replacement therapy will be prescribed by consulting nephrologists based on standard clinical guidelines, including acute kidney injury with hemodynamic instability plus hyperkalemia, severe acidosis, volume overload, respiratory distress, multiorgan failure or some combination of these factors. DATA COLLECTION: Patients demographics and associated clinical data and comorbidities will be recorded at ICU entry. Demographic information will include the patient's age, sex, and admission dates. Clinical data comprise comorbidities, APACHE 2, SAPS 3, need for mechanical ventilation, and use of vasopressor drugs. Physiological data collected by the day of CRRT start will be vital signs, the arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) index, and serum creatinine, blood urea nitrogen, bilirubin, hemoglobin, hematocrit, platelets, white blood cell count levels and Peak D-dimer levels. Patients will be analyzed for the first 72h of CRRT, and they will be evaluated regarding clinical variables, filter patency and any adverse events that could be related to the anticoagulation choice, as bleeding (mild or major) or low platelets counts (<100.000 ui/uL) during treatment period. Mild and major bleeding will be defined by hemorrhagic event without clinical impact or hemoglobin (Hb) fall lesser than 1g/dL and hemorrhagic event with clinical impact or Hb fall higher than 1g/dL, respectively. EXCLUSION CRITERIA: Hypersensitivity to any of the substances going to be used in the study (Citric acid dextrosol 2.2% and unfractionated heparin); Previous diagnosis of coagulopathy or thrombophilia; Contraindication to the use of unfractionated heparin; Risk of citrate poisoning - (Lactate> 30 mg/dL, international normalized ratio > 2.5, Total bilirubin> 15 mg/dL); Pregnancy; Patients unlikely to survive for more than 24 hours. The trial is being undertaken at the University of Sao Paulo General Hospital (Hospital das Clinicas), Brazil. INTERVENTION AND COMPARATOR: Group A (control) - Patients on continuous renal replacement therapy (blood flow 150 ml/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L Group B (experiment): Patients on continuous hemodialysis (blood flow 150 mL/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L associated with unfractionated heparin at 10 U/Kg/h. MAIN OUTCOMES: The percentage of clotted dialyzers within 72 hours in each of the studied groups (Primary outcome) Secondary outcomes: Number of dialyzers used in the first 72 hours of dialysis protocol, Mortality in the first 72 h of dialysis protocol, Bleeding events (Major or minor) in the first 72 h of dialysis protocol, Thrombocytopenia (less than 50.000 platelets) proportion in the first 72 h of dialysis protocol, Dialysis efficiency (Urea sieving) - variation in urea sieving between the first, second and third days of dialysis protocol, Continuous renal replacement therapy pressures (Arterial, Venous, dialysate and pre-filter pressure) in the first 72 h of dialysis protocol, in-hospital mortality. RANDOMIZATION: RedCap→ randomization - 2 blocks randomization by D-dimer level (5000ng/dL cut-off) and catheter site (Right Internal Jugular versus other sites) with 1:1 allocation ratio. BLINDING (MASKING): No blinding - Open label format NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Total number of patients 90 (45 per group) TRIAL STATUS: Trial version 2.0 - ongoing recruitment. First recruitment: June 29, 2020 Estimated date for last recruitment: December 31, 2020 TRIAL REGISTRATION: Responsible Party: University of Sao Paulo General Hospital (Hospital das Clinicas) ClinicalTrials.gov Identifier: NCT04487990 , registered July 27, 2020, ReBec www.ensaiosclinicos.gov.br/rg/RBR-45kf9p/ Other Study ID Numbers: U1111-1252-0194 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
Lesão Renal Aguda , Infecções por Coronavirus , Monitoramento de Medicamentos/métodos , Heparina , Pandemias , Pneumonia Viral , Diálise Renal , Trombose/prevenção & controle , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemoglobinas/análise , Hemorragia/etiologia , Hemorragia/prevenção & controle , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Risco Ajustado/métodos , Trombocitopenia/etiologia , Trombocitopenia/prevenção & controle , Trombose/complicações
2.
Int J Mol Sci ; 21(21)2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33153161

RESUMO

Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection. Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients. In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications. These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure. Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19). Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin. These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes. We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy. Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity. We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs. Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.


Assuntos
Plaquetas/patologia , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Eritrócitos/patologia , Ferritinas/sangue , Selectina-P/sangue , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Coagulação Sanguínea/fisiologia , Plaquetas/virologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/virologia , Eritrócitos/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Trombose/patologia , Trombose/virologia
3.
Toxicon ; 188: 142-149, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33130186

RESUMO

Gloydius tsushimaensis is an endemic species inhabiting only Tsushima, a remote Japanese island, and is a distinct species from Gloydius blomhoffii widely distributed throughout mainland Japan and Gloydius brevicaudus and Gloydius ussuriensis which are geographically distributed in South Korea. This is the first multicenter retrospective study of G. tsushimaensis bites in Japan. A study of seventy-two patients who visited the former Izuhara Hospital, the former Naka Tsushima Hospital, Tsushima Hospital, and Kamitsushima Hospital during the fourteen years from January 1, 2005, to December 31, 2018, revealed the typical clinical characteristics of G. tsushimaensis bites. Five out of seventy-two cases (6.9%) showed severe hypofibrinogenemia, in which fibrinogen levels were below 100 mg/dl, which is an unreported clinical finding for G. blomhoffii bites. Generally, when fibrinogen levels are lower than 100 mg/dl, the bleeding risk increases, and it is perilous. Severe hypofibrinogenemia cases did not improve after G. blomhoffii antivenom administration. Additionally, all five cases had disseminated intravascular coagulation, and there were two cases of acute kidney injury and one death. five cases had a median maximum creatine kinase level of 5171 IU/l (Interquartile range: 4992-41,310). Although the mechanism is not precise, coagulation tests showed that the G. tsushimaensis venom contains a thrombin-like enzyme. Based on this research, we created an algorithm for the treatment of G. tsushimaensis bites and unified the treatment methods used on the island.


Assuntos
Afibrinogenemia/terapia , Mordeduras de Serpentes , Viperidae , Adulto , Animais , Antivenenos , Coagulação Sanguínea , Crotalinae , Feminino , Humanos , Ilhas , Japão , Masculino , Estudos Retrospectivos
4.
BMC Nephrol ; 21(1): 486, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198670

RESUMO

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients have a high risk of acute kidney injury (AKI) that requires renal replacement therapy (RRT). A state of hypercoagulability reduces circuit life spans. To maintain circuit patency and therapeutic efficiency, an optimized anticoagulation strategy is needed. This study investigates whether alternative anticoagulation strategies for RRT during COVID-19 are superior to administration of unfractionated heparin (UFH). METHODS: Retrospective cohort study on 71 critically ill COVID-19 patients (≥18 years), admitted to intensive care units at a tertiary health care facility in the southwestern part of Germany between February 26 and May 21, 2020. We collected data on the disease course, AKI, RRT, and thromboembolic events. Four different anticoagulatory regimens were administered. Anticoagulation during continuous veno-venous hemodialysis (CVVHD) was performed with UFH or citrate. Anticoagulation during sustained low-efficiency daily dialysis (SLEDD) was performed with UFH, argatroban, or low molecular weight heparin (LMWH). Primary outcome is the effect of the anticoagulation regimen on mean treatment times of RRT. RESULTS: In patients receiving CVVHD, mean treatment time in the UFH group was 21.3 h (SEM: ±5.6 h), in the citrate group 45.6 h (SEM: ±2.7 h). Citrate anticoagulation significantly prolonged treatment times by 24.4 h (P = .001). In patients receiving SLEDD, mean treatment time with UFH was 8.1 h (SEM: ±1.3 h), with argatroban 8.0 h (SEM: ±0.9 h), and with LMWH 11.8 h (SEM: ±0.5 h). LMWH significantly prolonged treatment times by 3.7 h (P = .008) and 3.8 h (P = .002), respectively. CONCLUSIONS: UFH fails to prevent early clotting events in the dialysis circuit during COVID-19. For patients, who do not require effective systemic anticoagulation, regional citrate dialysis is the most effective strategy. For patients, who require effective systemic anticoagulation, the usage of LMWH results in the longest circuit life spans. The proposed anticoagulatory strategies are safe, can easily be monitored, and allow an individualized treatment.


Assuntos
Lesão Renal Aguda/terapia , Anticoagulantes/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Terapia de Substituição Renal/métodos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/epidemiologia , Adulto , Idoso , Coagulação Sanguínea , Ácido Cítrico/administração & dosagem , Comorbidade , Infecções por Coronavirus/sangue , Cuidados Críticos , Estado Terminal , Falha de Equipamento , Feminino , Alemanha/epidemiologia , Heparina/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Ácidos Pipecólicos/administração & dosagem , Pneumonia Viral/sangue , Terapia de Substituição Renal/instrumentação , Estudos Retrospectivos , Centros de Atenção Terciária
5.
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
6.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(9): 1121-1124, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33081902

RESUMO

OBJECTIVE: To investigate the changes and clinical significance of blood coagulation function and von Willebrand factor antigen (vWF:Ag) in patients with HELLP syndrome (hemolysis, elevated liver function, low platelet count). METHODS: The clotting data of patients with severe preeclampsia and HELLP syndrome (observation group) admitted to the department of critical care medicine of the Fifth Center Hospital in Tianjin from May 2015 to December 2019 were retrospectively analyzed, and normal late pregnancy women with the same period were enrolled as the control group. The coagulation indexes such as prothrombin time (PT), activated partial thrombin time (APTT), antithrombin (AT), fibrinogen (Fib), D-dimer and plasma vWF:Ag level were compared between the two groups, and among patients with HELLP syndrome with different disease degree. RESULTS: (1) Sixty-five patients with HELLP syndrome and 65 normal pregnant women with third trimester were included. Both groups were women of childbearing age, and there were no significant difference in the baseline data. (2) The levels of Fib, D-dimer in both groups increased, but they were significantly higher in the observation group than those in the control group [Fib (g/L): 4.94 (4.76, 5.85) vs. 3.58 (2.97, 4.14), D-dimer (mg/L): 3.34 (2.55, 4.32) vs. 1.72 (1.29, 2.08), both P < 0.05], the AT was obviously reduced [62.00 (49.00, 73.00)% vs. 97.50 (90.75, 107.00)%, P < 0.01], and both PT and APTT were in the normal reference range in the two groups. In addition, the plasma vWF:Ag level in the observation group was significantly higher than that in the control group [516.50 (467.20, 563.00)% vs. 246.45 (189.95, 274.10)%, P < 0.01]. (3) According to thrombocytopenia, among the 65 patients with HELLP syndrome, 26 cases were mild [platelet count (PLT) > 100×109/L], 22 cases were moderate [PLT (50-100)×109/L], and 17 cases were severe (PLT < 50×109/L). With the aggravation of the disease, the D-dimer, Fib, vWF:Ag levels in the mild, moderate, severe patients significantly increased, while the AT level significantly decreased, and there was statistically significant difference between the two groups [D-dimer (mg/L): 2.63 (2.60, 2.73), 3.15 (2.55, 3.73), 3.84 (3.52, 4.23); Fib (g/L): 4.23 (4.06, 4.47), 4.72 (4.34, 5.04), 5.43 (5.14, 5.76); vWF:Ag: 465.20 (437.20, 495.40)%, 500.10 (472.40, 534.50)%, 543.50 (521.30, 563.00)%; AT: 67.50 (61.60, 78.00)%, 63.70 (53.30, 70.40)%, 54.40 (44.00, 61.20)%; all P < 0.05]. CONCLUSIONS: Patients with HELLP syndrome may show hypercoagulability and excessive expression of peripheral blood vWF:Ag level, which can induce platelet aggregation, leading to thrombocytopenia and thrombotic microangiopathy, and the clinicians should pay attention to that.


Assuntos
Síndrome HELLP , Pré-Eclâmpsia , Coagulação Sanguínea , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Fator de von Willebrand
7.
Rev Med Suisse ; 16(711): 1988-1994, 2020 Oct 21.
Artigo em Francês | MEDLINE | ID: mdl-33085255

RESUMO

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the general population and in patients with sepsis hospitalized in intensive care. The indication for long-term anticoagulation is based on expert recommendations that take into account data from the general population and thus recommend therapeutic anticoagulation for AF longer than 48 hours. However, a majority of new onset AF in intensive care seem to last less than 48 hours and additional risk factors such as the type of sepsis, the drugs administered as well as the presence of a central venous catheters, are involved. Moreover, the increased of minor and major hemorrhage renders it difficult to apply the usual recommendations. In this literature review, we will focus on the various risk factors, prognosis, and indication of long-term anticoagulation in the new onset AF in this population.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial , Sepse , Coagulação Sanguínea , Hemorragia , Humanos , Fatores de Risco
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5374-5377, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019196

RESUMO

Unfractionated heparin (UFH) is commonly used in the intensive care unit (ICU) to prevent blood clotting. Recently, many researchers focus on the development of data- driven methods to solve UFH related problems, which usually involves time series analysis. The performance of data-driven methods depends on whether the inter-correlation of attributes (or variables) in the dataset is closely examined and addressed. This study performs attribute selection, optimal time delay and inter-attributes relations on ICU time series data, in order to provide insights of time series data for UFH related problems. Medical records of 3211 patients with 22 attributes extracted from MIMIC (Medical Information Mart for Intensive Care) III database are used for the experiment. Experimental result shows that some of commonly selected attributes in the literature are less sensitive to the variations of UFH injection. Furthermore, some attributes are inter-dependent, which can increase the complexity of data-driven models, implying that the number of attributes could be reduced. There are 9 attributes found highly related and fast responding in 22 commonly used attributes. This study shows strong potential to provide clinicians with information about sensitive attributes that can help determine the UFH injection policy in ICU.


Assuntos
Heparina , Trombose , Coagulação Sanguínea , Heparina/efeitos adversos , Humanos , Injeções , Projetos de Pesquisa
10.
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
11.
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
12.
PLoS One ; 15(10): e0241329, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33119703

RESUMO

OBJECTIVE: To investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity. METHODS: We retrospectively collected 147 clinically diagnosed COVID-19 patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT). RESULT: The levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (p<0.05), and also higher in the patients with thrombotic disease than without thrombotic disease (p<0.05). What's more, the patients with thrombotic disease had a higher case-fatality (p<0.05). TAT, PIC, TM, t-PAIC, PT, INR, APTT, FIB, DD, and PLT were also found correlated with disease severity. Meanwhile, we found that there were significant difference in TAT, TM, t-PAIC, PT, INR, APTT, DD, and PLT in the death and survival group. Further using univariate and multivariate logistic regression analysis also found that t-PAIC and DD were independent risk factors for death in patients and are excellent predicting the mortality risk of COVID-19. CONCLUSION: Most COVID-19 patients with inordinate coagulation systems, dynamic monitoring of coagulation parameters might be a key in the control of COVID-19 death.


Assuntos
Coagulação Sanguínea , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Adulto , Idoso , Betacoronavirus , Transtornos da Coagulação Sanguínea/virologia , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias
13.
Clin Appl Thromb Hemost ; 26: 1076029620962853, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33074732

RESUMO

Thrombotic complications of the novel coronavirus (COVID-19) are a concerning aspect of the disease, due to the high incidence in critically ill patients and poor clinical outcomes. COVID-19 predisposes patients to a hypercoagulable state, however, the pathophysiology behind the thrombotic complications seen in this disease is not well understood. Several mechanisms have been proposed and the pathogenesis likely involves a host immune response contributing to vascular endothelial cell injury, inflammation, activation of the coagulation cascade via tissue factor expression, and shutdown of fibrinolysis. Treatments targeting these pathways may need to be considered to improve clinical outcomes and decrease overall mortality due to thrombotic complications. In this review, we will discuss the proposed pathophysiologic mechanisms for thrombotic complications in COVID-19, as well as treatment strategies for these complications based on the current literature available.


Assuntos
Betacoronavirus , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Trombofilia/etiologia , Infecções por Coronavirus/epidemiologia , Saúde Global , Humanos , Incidência , Pneumonia Viral/epidemiologia , Trombofilia/sangue , Trombofilia/epidemiologia
14.
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
16.
J Stroke Cerebrovasc Dis ; 29(11): 105209, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066926

RESUMO

BACKGROUND AND PURPOSE: Testing for thrombophilic disorders is often performed in patients after cryptogenic ischemic stroke in an attempt to identify a hematologic explanation for the event. However, the role of commonly tested thrombophilias in ischemic stroke is poorly defined. There is limited evidence to quantify how these disorders affect ischemic stroke risk and testing practices are highly variable. METHODS: Retrospective evaluation of thrombophilia testing practices and clinical outcomes was performed in hospitalized patients with acute ischemic stroke (n = 1898) at a large academic hospital over a two-year period. Variables assessed included testing components, timing of testing, number of abnormal results, and frequency of change in clinical management prompted by abnormal results. A provider survey was also performed to assess perceptions of current testing practices and provider understanding of testing indications. RESULTS: Thrombophilia testing was performed in 190 (10%) patients admitted for acute ischemic stroke. Of those tested, 137 (72.1%) had at least one abnormal result, but this decreased to 37.4% when elevated factor VIII activity was excluded. An abnormal result prompted initiation of anticoagulation in only 4 patients (2%). The provider survey indicated that all providers (100%) were selecting thrombophilia tests using a pre-existing order set and were interested in additional education on testing indications and interpretation. Comparison to similar studies at other institutions revealed significant variation in testing practices, and a small proportion of patients in which testing prompted a change in management (1-8%). CONCLUSIONS: Thrombophilia testing is frequently obtained in hospitalized patients with acute ischemic stroke, yet testing only changed management in 2% of patients. Efforts to improve provider education and the stewardship of testing are needed to ensure appropriate evaluation and treatment of patients with acute ischemic stroke.


Assuntos
Testes de Coagulação Sanguínea/tendências , Coagulação Sanguínea , Isquemia Encefálica/etiologia , Hospitalização , Padrões de Prática Médica/tendências , Acidente Vascular Cerebral/etiologia , Trombofilia/diagnóstico , Adulto , Idoso , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Isquemia Encefálica/diagnóstico , Tomada de Decisão Clínica , Feminino , Disparidades em Assistência à Saúde/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Trombofilia/sangue , Trombofilia/complicações , Trombofilia/tratamento farmacológico
17.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33004529

RESUMO

Novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has rapidly spread throughout the world, resulting in a pandemic with high mortality. There are no effective treatments for the management of severe COVID-19 and current therapeutic trials are focused on antiviral therapy and attenuation of hyper-inflammation with anti-cytokine therapy. Severe COVID-19 pneumonia shares some pathological similarities with severe bacterial pneumonia and sepsis. In particular, it disrupts the haemostatic balance, which results in a procoagulant state locally in the lungs and systemically. This culminates in the formation of microthrombi, disseminated intravascular coagulation and multi-organ failure. The deleterious effects of exaggerated inflammatory responses and activation of coagulation have been investigated in bacterial pneumonia and sepsis and there is recognition that although these pathways are important for the host immune response to pathogens, they can lead to bystander tissue injury and are negatively associated with survival. In the past two decades, evidence from preclinical studies has led to the emergence of potential anticoagulant therapeutic strategies for the treatment of patients with pneumonia, sepsis and acute respiratory distress syndrome, and some of these anticoagulant approaches have been trialled in humans. Here, we review the evidence from preclinical studies and clinical trials of anticoagulant treatment strategies in bacterial pneumonia and sepsis, and discuss the importance of these findings in the context of COVID-19.


Assuntos
Anticoagulantes/uso terapêutico , Betacoronavirus , Coagulação Sanguínea/fisiologia , Infecções por Coronavirus/sangue , Pneumonia Bacteriana/sangue , Pneumonia Viral/sangue , Sepse/sangue , Biomarcadores/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia
18.
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
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1787-1790, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067991

RESUMO

The process of thrombus formation in vivo is complex, which is affected by the platelets, clotting system, and vessels, as well as blood flow. The previous research ways, which were either static or shear stress-mimicking ex vivo, could not reflect the condition in vivo completely. In recent years, The high resolution confocal microscope combined with bioluminescence system was developed which can be used to observe the animal thrombus formation in real time in vivo. By using this system, scientists have gotten a novel knowledge about the thrombus formation. In this review, the operating steps of this system, the hierarchical structure of thrombs revealed by this system and the related mechanism are sammrized briefly.


Assuntos
Trombose , Animais , Coagulação Sanguínea , Plaquetas , Microscopia
20.
Semin Thromb Hemost ; 46(7): 807-814, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32882720

RESUMO

The proinflammatory cytokine storm associated with coronavirus disease 2019 (COVID-19) negatively affects the hematological system, leading to coagulation activation and endothelial dysfunction and thereby increasing the risk of venous and arterial thrombosis. Coagulopathy has been reported as associated with mortality in people with COVID-19 and is partially reflected by enhanced D-dimer levels. Poor vascular health, which is associated with the cardiometabolic health conditions frequently reported in people with severer forms of COVID-19, might exacerbate the risk of coagulopathy and mortality. Sedentary lifestyles might also contribute to the development of coagulopathy, and physical activity participation has been inherently lowered due to at-home regulations established to slow the spread of this highly infectious disease. It is possible that COVID-19, coagulation, and reduced physical activity may contribute to generate a "perfect storm," where each fuels the other and potentially increases mortality risk. Several pharmaceutical agents are being explored to treat COVID-19, but potential negative consequences are associated with their use. Exercise is known to mitigate many of the identified side effects from the pharmaceutical agents being trialled but has not yet been considered as part of management for COVID-19. From the limited available evidence in people with cardiometabolic health conditions, low- to moderate-intensity exercise might have the potential to positively influence biochemical markers of coagulopathy, whereas high-intensity exercise is likely to increase thrombotic risk. Therefore, low- to moderate-intensity exercise could be an adjuvant therapy for people with mild-to-moderate COVID-19 and reduce the risk of developing severe symptoms of illness that are associated with enhanced mortality.


Assuntos
Coagulação Sanguínea , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Exercício Físico , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Anticoagulantes/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Infecções por Coronavirus/complicações , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinólise , Hemostasia , Humanos , Inflamação , Pandemias , Pneumonia Viral/complicações , Risco , Trombose/sangue , Trombose/complicações
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