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1.
Sci Rep ; 12(1): 13155, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35915103

RESUMO

There has been growing attention toward the predictive value of the coagulation parameters abnormalities in COVID-19. The aim of the study was to investigate the role of coagulation parameters namely Prothrombin concentration (PC), activated Partial thromboplastin Time (aPTT), D-Dimer (DD), Anti Thrombin III (ATIII) and fibrinogen (Fg) together with hematological, and biochemical parameters in predicting the severity of COVID-19 patients and estimating their relation to clinical outcomes in hospitalized and severe COVID-19 Patients. In a prospective study, a total of 267 newly diagnosed COVID-19 patients were enrolled. They were divided into two groups; hospitalized group which included 144 patients and non-hospitalized group that included 123 patients. According to severity, the patients were divided into severe group which included 71 patients and non-severe group that included 196 patients who were admitted to ward or not hospitalized. Clinical evaluation, measurement of coagulation parameters, biochemical indices, outcome and survival data were recorded. Hospitalized and severe patients were older and commonly presented with dyspnea (P ≤ 0.001). Differences in coagulation parameters were highly significant in hospitalized and severe groups in almost all parameters, same for inflammatory markers. D-dimer, AT-III and LDH showed excellent independently prediction of severity risk. With a cut-off of > 2.0 ng/L, the sensitivity and specificity of D dimer in predicting severity were 76% and 93%, respectively. Patients with coagulation abnormalities showed worse survival than those without (p = 0.002). Early assessment and dynamic monitoring of coagulation parameters may be a benchmark in the prediction of COVID-19 severity and death.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , Coagulação Sanguínea , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Tempo de Tromboplastina Parcial , Estudos Prospectivos
2.
Rinsho Ketsueki ; 63(7): 733-739, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35922940

RESUMO

Acquired factor V deficiency is a rare disease that presents with various bleeding symptoms because of the acquired production of factor V inhibitors and decrease in factor V activity. We have experienced five cases of acquired factor V deficiency diagnosed on the basis of abnormalities in coagulation tests in the last 10 years. All five patients were older men, of whom one had no bleeding symptoms, and three had a history of renal failure and malignant tumors. In the cross-mixing test, two of three cases demonstrated an inhibitor pattern, but one case showed a deficient pattern. In all cases, steroid treatment improved factor V activity as well as prothrombin time and activated partial thromboplastin time. However, patients with intracranial hemorrhage had a poor prognosis. Although this disease is rare, careful management is necessary, especially in the absence of bleeding symptoms and where cross-mixing test does not show an inhibitor pattern.


Assuntos
Deficiência do Fator V , Idoso , Testes de Coagulação Sanguínea/efeitos adversos , Fator V/genética , Deficiência do Fator V/complicações , Deficiência do Fator V/diagnóstico , Hemorragia/etiologia , Humanos , Masculino , Tempo de Tromboplastina Parcial , Tempo de Protrombina
3.
Perm J ; 26(2): 153-157, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35933672

RESUMO

Introduction Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against clotting factor VIII. It occurs most commonly in the elderly population. AHA is associated with malignancy, autoimmune diseases, pregnancy, and drugs. However, up to 50% of reported cases remain idiopathic. AHA is very rarely associated with multiple sclerosis. Case Presentation A 56-year-old patient with a history of MS presented with thigh and arm swelling and associated pain. Imaging revealed diffuse iliopsoas hematoma. Laboratory studies showed that prothombin time was not elevated and there was prolongation of activated partial thromboplastin time that was not corrected by mixing studies. Clotting factor VIII activity level was reduced, and the inhibitor level was elevated. He was treated with factor eight inhibitor bypassing agents, rituximab, and steroids. Conclusion AHA should be suspected in any patient with new-onset bleeding in the presence of a prolonged activated partial thromboplastin time. Prompt diagnosis and treatment are important as AHA carries a high mortality rate.


Assuntos
Hemofilia A , Esclerose Múltipla , Idoso , Fator VIII/uso terapêutico , Feminino , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Hemorragia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Tempo de Tromboplastina Parcial , Gravidez
4.
Int J Mol Sci ; 23(13)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35806285

RESUMO

In recent decades, the use of adult multipotent stem cells has paved the way for the identification of new therapeutic approaches for the treatment of monogenic diseases such as Haemophilia A. Being already studied for regenerative purposes, adipose-derived mesenchymal stem cells (Ad-MSCs) are still poorly considered for Haemophilia A cell therapy and their capacity to produce coagulation factor VIII (FVIII) after proper stimulation and without resorting to gene transfection. In this work, Ad-MSCs were in vitro conditioned towards the endothelial lineage, considered to be responsible for coagulation factor production. The cells were cultured in an inductive medium enriched with endothelial growth factors for up to 21 days. In addition to significantly responding to the chemotactic endothelial stimuli, the cell populations started to form capillary-like structures and up-regulated the expression of specific endothelial markers (CD34, PDGFRα, VEGFR2, VE-cadherin, CD31, and vWF). A dot blot protein study detected the presence of FVIII in culture media collected from both unstimulated and stimulated Ad-MSCs. Remarkably, the activated partial thromboplastin time test demonstrated that the clot formation was accelerated, and FVIII activity was enhanced when FVIII deficient plasma was mixed with culture media from the untreated/stimulated Ad-MSCs. Overall, the collected evidence supported a possible Ad-MSC contribution to HA correction via specific stimulation by the endothelial microenvironment and without any need for gene transfection.


Assuntos
Hemofilia A , Células-Tronco Mesenquimais , Adulto , Testes de Coagulação Sanguínea , Diferenciação Celular , Células Cultivadas , Meios de Cultura/metabolismo , Hemofilia A/genética , Hemofilia A/metabolismo , Hemofilia A/terapia , Humanos , Células-Tronco Mesenquimais/metabolismo , Tempo de Tromboplastina Parcial
5.
Hematology ; 27(1): 802-808, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35866546

RESUMO

OBJECTIVES: To identify the clinical phenotypic and molecular pathogeneses of four cases of coagulation factor XII deficiency and to deepen the cognition of this disease. METHODS: Coagulation tests were performed through one stage of coagulation on a STAGO coagulation analyser. Coagulation factor XII antigen was detected using enzyme-linked immunosorbent assay. The species conservatism and structural change of mutant proteins were analysed using MegAlign and PYMOL. Meanwhile, missense variants and a novel splice site variant were identified using PolyPhen2 and NetGene2. RESULTS: The four cases had an observably prolonged activated partial thromboplastin time but without obvious bleeding tendency. Their coagulation factor XII activity (FⅫ:C) and antigen (FXII:Ag) were greatly reduced. Six mutations were detected: NM_000505.4:c.398-1G>A, NP_000496.2:p.(Pro182Leu), NP_000496.2:p.(Ser479Ter), NP_000496.2:p.(Cys559Arg), NC_000005.10:g.7217_7221delinsGTCTA and NM_000505.4:c.1681-1G>A. The first five are newly discovered mutations. The two missense mutation sites were highly conservative, and their protein secondary structure changes may occur not only on the mutation sites but also on other domains. In silico analysis revealed that NP_000496.2:p.(Pro182Leu) may be BENIGN, NP_000496.2:p.(Cys559Arg) may be damaging, and that NM_000505.4:c.398-1G>A and NM_000505.4:c.1681-1G>A are crucial for splicing. CONCLUSION: We found six types of mutations, of which five were novel. The two missense mutation sites might be closely related to the function of coagulation factor XII. The mutations were the primary culprits of factor XII deficiency.


Assuntos
Deficiência do Fator XII , Fator XII/genética , Deficiência do Fator XII/genética , Humanos , Mutação , Mutação de Sentido Incorreto , Tempo de Tromboplastina Parcial
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(7): 817-820, 2022 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-35894199

RESUMO

A boy, aged 2 years and 5 months, had recurrent epistaxis, and the coagulation function examination showed that activated partial thromboplastin time (APTT) was significantly prolonged. Further laboratory examinations showed that the prolonged APTT was not immediately corrected in the APTT correction test, with positive lupus anticoagulant and low prothrombin activity. The boy was diagnosed with hypoprothrombinemia-lupus anticoagulant syndrome. The condition was improved after treatment with glucocorticoid, immunoglobulin, and vitamin K1. The boy has been followed up for 6 months, and no epistaxis was observed. Prothrombin activity returned to normal, and lupus anticoagulant remained positive. This is a relatively rare disease, and for patients with bleeding symptoms and coagulation disorders, it is recommended to perform the tests such as APTT correction test, lupus anticoagulant testing, and coagulation factor dilution test, which can improve the detection rate of this disease, so as to achieve early diagnosis, provide rational treatment in the early stage, and improve the prognosis.


Assuntos
Síndrome Antifosfolipídica , Transtornos da Coagulação Sanguínea , Hipoprotrombinemias , Síndrome Antifosfolipídica/diagnóstico , Pré-Escolar , Epistaxe/etiologia , Humanos , Hipoprotrombinemias/diagnóstico , Inibidor de Coagulação do Lúpus , Masculino , Tempo de Tromboplastina Parcial , Protrombina
7.
Am J Vet Res ; 83(10)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35895758

RESUMO

OBJECTIVE: To assess the safety and efficacy of the platelet-like nanoparticle (PLN), and to assess its safety in repeated administration. ANIMALS: 6 purpose-bred dogs. PROCEDURES: The PLN was administered IV at 3 different doses using a randomized crossover design. Each dog received a full dose of 8 X 1010 particles/10 kg, half dose, and 10 times the dose, with a 14-day washout period between doses. Biochemical, prothrombin time, partial thromboplastin time, and fibrinogen analyses were performed at baseline and 96 hours postinfusion. A CBC, kaolin-activated thromboelastography, platelet function assay closure time, and buccal mucosal bleeding time were performed at baseline and 1, 6, 24, 48, 72, and 96 hours postinfusion. RESULTS: No significant changes were observed over time in the thromboelastography parameters, closure time, and buccal mucosal bleeding time. After the administration of the half dose, hematocrit levels decreased significantly at 1, 6, 24, 48, and 96 hours, with all values within the reference range. The platelet count was decreased significantly at hours 1, 6, 24, 48, and 72 after administration of the half dose, with values less than the reference range at all hours but hour 72. No significant changes in serum biochemistry, coagulation panel, and fibrinogen were observed for all doses. No adverse events were noted during the first infusion. Three dogs experienced transient sedation and nausea after repeat infusion. CLINICAL RELEVANCE: The PLN resulted in a dilution of hematocrit and platelets, and did not significantly alter hemostasis negatively. The safety of repeated doses should be investigated further in dogs.


Assuntos
Hemostasia , Nanopartículas , Animais , Cães , Fibrinogênio , Nanopartículas/efeitos adversos , Tempo de Tromboplastina Parcial/veterinária , Tempo de Protrombina/veterinária , Tromboelastografia/veterinária
8.
Clin Lab ; 68(6)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35704730

RESUMO

BACKGROUND: The purpose of this study is to evaluate the prognostic roles of hemostatic tests including prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, and antithrombin III in the progression of disease, monitorization of severe, mild and moderate cases, and also to show their relationship with inflammatory markers including C-reactive protein (CRP), procalcitonin, and interleukin-6 (IL-6). METHODS: The study comprised 604 patients (360 men and 244 women) with confirmed SARS-CoV-2 infection admitted to Emergency Department of Istanbul Faculty of Medicine between March 15 and April 15, 2020. The variations in the concentration of coagulation tests and inflammatory markers were observed from the admission to hospital to the 10th day with three-day periods. RESULTS: PT level and PT activity of severe cases were significantly different compared to mild cases (p = 0.012, p = 0.010, respectively). Similarly, aPTT and D-dimer levels in severe cases were significantly higher compared to the mild cases. However, fibrinogen levels of mild cases were significantly lower compared to either moderate or severe cases (p < 0.001, for both). The PT, PT activity, aPTT, and D-Dimer levels in severe cases were significantly different compared with the mild cases. However, fibrinogen level was the highest in severe cases, and higher than either mild or moderate cases. CONCLUSIONS: Our findings reveal the vital importance of measuring coagulation parameters at the time of admission and monitoring them at regular intervals in clinical monitoring of COVID-19 patients, in determining the severity of the disease in terms of the patient's prognosis, and in choosing and applying the appropriate treatment at the right time.


Assuntos
COVID-19 , Biomarcadores , COVID-19/diagnóstico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Fibrinogênio/análise , Humanos , Masculino , Tempo de Tromboplastina Parcial , Prognóstico , Tempo de Protrombina , SARS-CoV-2
9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(5): 509-513, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35728853

RESUMO

OBJECTIVE: To explore the diagnosis process and treatment experience of severe coronavirus disease 2019 (COVID-19) patients with heparin resistance (HR). METHODS: The medical team of the First People's Hospital of Lianyungang admitted 2 severe COVID-19 patients with HR in intensive care unit (ICU) during their support to the designated hospital for the treatment of COVID-19 patients in Lianyungang City in November 2021. The clinical features, laboratory examinations, imaging features, treatment and prognosis of the two patients were analyzed. RESULTS: Both severe COVID-19 patients received mechanical ventilation, 1 patient was treated with extracorporeal membrane oxygenation (ECMO) support. Both patients were complicated with lower extremity deep venous thrombosis and HR phenomenon under routine dose anticoagulant therapy. The maximum daily dose of unfractionated heparin exceeded 35 000 U (up to 43 200 U), the 2 patients failed to meet the standard of anticoagulation treatment, and the course of disease was prolonged. After that, argatroban was given 0.4 µg×kg-1×min-1 combined with anticoagulant therapy, the activated partial thromboplastin time (APTT) of patients undergoing ECMO could be maintained at 55-60 seconds and the activated coagulation time (ACT) of them could be maintained at 180-200 seconds. After ECMO support or later sequential mechanical ventilation, both patients recovered and were discharged, and deep venous thrombosis was also effectively controlled. CONCLUSIONS: HR phenomenon often occurs during the treatment of severe COVID-19 patients, the anticoagulation regimen should be adjusted in time, and the anticoagulation effect combined with argatroban is clear.


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Anticoagulantes/uso terapêutico , Oxigenação por Membrana Extracorpórea/métodos , Heparina/uso terapêutico , Humanos , Tempo de Tromboplastina Parcial
10.
Lakartidningen ; 1192022 06 17.
Artigo em Sueco | MEDLINE | ID: mdl-35713306

RESUMO

Activated partial thromboplastin time (APTT) is widely practiced in preoperative screening. The value of using this test to predict the risk of perioperative bleeding is not well documented in Sweden. In this article, a literature review is performed to determine whether unselected APTT testing can predict abnormal perioperative bleeding. The current literature does not support coagulation screening with APTT in routine perioperative bleeding assessment, as preoperative screening with APTT has a low sensitivity for detection of clinically significant bleeding disorder. While a comprehensive bleeding history is crucial, the APTT test should only be performed on patients with a history of increased bleeding tendency. The conclusion of this literature review is that patients with a negative bleeding history do not require routine screening with APTT prior to surgery, which, if implemented, would lead to a more cost-effective perioperative routine.


Assuntos
Hemorragia , Programas de Rastreamento , Testes de Coagulação Sanguínea , Humanos , Tempo de Tromboplastina Parcial , Suécia
11.
Br J Haematol ; 198(3): 587-594, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35655415

RESUMO

We examined the associations between haematological and inflammatory variables with future venous thromboembolism (VTE), in 3494 men aged 60-79 years, with no previous history of VTE or myocardial infarction, who were not receiving oral anticoagulants. After a mean follow-up period of 18 years, there were 149 confirmed cases of fatal or non-fatal VTE (deep vein thrombosis and/or pulmonary embolism). Among classical cardiovascular risk factors, only obesity and cigarette smoking were associated with VTE risk. After adjustment for age, obesity and smoking, VTE risk was associated with coagulation factor VIII, factor IX, von Willebrand factor (VWF), activated partial thromboplastin time (APTT), and fibrin D-dimer. Hazard ratios (95% CI) for top to bottom quarters (bottom to top for APTT), were respectively 2.17 (1.37, 3.44), 2.15 (1.30, 3.53), 2.02 (1.27, 3.22), 2.43 (1.47, 4.02) and 3.62 (2.18, 6.08). The 11% of men with both the shortest APTT and highest D-dimer combined had a 5.02 (2.37, 10.62) higher risk of VTE. VTE risk was not associated with fibrinogen, factor VII or activated protein C resistance; full blood count variables or with inflammatory markers, plasma viscosity, C-reactive protein or interleukin-6. The combination of D-dimer and APTT merits evaluation as an adjunct to VTE risk prediction scores.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio , Tromboembolia Venosa , Biomarcadores , Produtos de Degradação da Fibrina e do Fibrinogênio/química , Humanos , Masculino , Obesidade , Tempo de Tromboplastina Parcial , Fatores de Risco , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
12.
Scanning ; 2022: 2312972, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601870

RESUMO

In order to explore the clinical characteristics of hemodialysis in curing poisoning from snakebites, a two-classification model of nuclear logistic neural network based on restricted Boltzmann machine is proposed. The model combines kernel logistic regression with artificial neural networks, enabling the model to both learn autonomously and handle linearly inseparable problems. The network first performs feature learning through unsupervised training of restricted Boltzmann machines and obtains the initial values of the parameters to be identified, which reduces the influence of the randomness of the initial parameters. The variable universe learning rate with scaling factor is used to learn the parameters to be identified, and the model convergence speed is improved by dynamic adjustment of the learning rate. Experimental results show the following: Compared with before treatment, patient's activated partial thromboplastin time (APTT) after treatment and the prothrombin time (PT) level decrease, fibrinogen (FIB) levels are elevated, aspartate transferase (AST) and creatine kinase isoenzyme (CK-MB) level decreased, and the differences were statistically significant (p < 0.05). It is proved that continuous hemodiafiltration combined with plasma exchange treatment can effectively improve the blood coagulation index and myocardial index of severe snakebite poisoning patients.


Assuntos
Mordeduras de Serpentes , Humanos , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Diálise Renal , Mordeduras de Serpentes/terapia
13.
Molecules ; 27(9)2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35566376

RESUMO

Laminaria japonica is widely consumed as a key food and medicine. Polysaccharides are one of the most plentiful constituents of this marine plant. In this study, several polysaccharide fractions with different charge numbers were obtained. Their physicochemical properties and anticoagulant activities were determined by chemical and instrumental methods. The chemical analysis showed that Laminaria japonica polysaccharides (LJPs) and the purified fractions LJP0, LJP04, LJP06, and LJP08 mainly consisted of mannose, glucuronic acid, galactose, and fucose in different mole ratios. LJP04 and LJP06 also contained minor amounts of xylose. The polysaccharide fractions eluted by higher concentration of NaCl solutions showed higher contents of uronic acid and sulfate group. Biological activity assays showed that LJPs LJP06 and LJP08 could obviously prolong the activated partial thromboplastin time (APTT), indicating that they had strong anticoagulant activity. Furthermore, we found that LJP06 exerted this activity by inhibiting intrinsic factor Xase with higher selectivity than other fractions, which may have negligible bleeding risk. The sulfate group may play an important role in the anticoagulant activity. In addition, the carboxyl group and surface morphology of these fractions may affect their anticoagulant activities. The results provide information for applications of L. japonica polysaccharides, especially LJP06 as anticoagulants in functional foods and therapeutic agents.


Assuntos
Laminaria , Anticoagulantes/química , Anticoagulantes/farmacologia , Laminaria/química , Tempo de Tromboplastina Parcial , Polissacarídeos/química , Polissacarídeos/farmacologia , Sulfatos
15.
Int J Clin Pharmacol Ther ; 60(8): 364-366, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35603684

RESUMO

The direct-acting oral anticoagulant dabigatran etexilate (DE prevent systemic thromboembolism and cerebral apoplexy in patients with nonvalvular atrial fibrillation. On September 22, 2021, an 86-year-old female patient in Peking University People's Hospital presented with a severely reduced fibrinogen level and significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). She had a history of hypertension, hyperlipidemia, arrhythmia, and a 1-year history of taking DE (110 mg, p.o., b.i.d.). She had no apparent bleeding tendency but had abnormalities in coagulation markers. She denied taking a DE overdose. Before deciding whether to transfuse plasma for replacement therapy, the attending physician wanted to ascertain if the abnormal results resulted from the drug or the abnormal coagulation mechanism of the patient. Tentatively, we used activated charcoal to treat plasma and then retested her coagulation markers: all coagulation tests nearly returned to normal levels. Hence, the cause was a DE overdose. Re-investigation revealed that she had lived alone in the previous week and possibly mistook the number of doses taken due to confusion. DE was withdrawn, and diuretics (Furosemide injection, 40 mg, QD2) were administered simultaneously to accelerate drug excretion. Five days after drug withdrawal, the coagulation tests returned to normal levels. This case report shows that activated charcoal could be used to show that the coagulation disorder was caused by a DE overdose, thereby providing support for the clinical diagnosis and treatment.


Assuntos
Carvão Vegetal , Dabigatrana , Idoso de 80 Anos ou mais , Coagulação Sanguínea , Testes de Coagulação Sanguínea/métodos , Carvão Vegetal/uso terapêutico , Feminino , Humanos , Tempo de Tromboplastina Parcial
16.
Med J Malaysia ; 77(3): 388-392, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35638497

RESUMO

Acquired Haemophilia A (AHA) is a rare potentially lifethreatening bleeding disorder caused by the presence of autoantibodies against coagulation factors. It is usually characterised by severe spontaneous haemorrhage, which can lead to high morbidity and mortality. The diagnosis is often challenging. Treatment requires vigilant and accurate laboratory investigations, control of bleeding episodes, and eradication of inhibitors using bypassing agents and/or immunosuppressive agents. Hereby, we present a case report of unusual bleeding episodes with isolated raised activated partial thromboplastin time (APTT).


Assuntos
Hemofilia A , Autoanticorpos , Hemofilia A/complicações , Hemofilia A/diagnóstico , Hemorragia/diagnóstico , Hemorragia/etiologia , Humanos , Tempo de Tromboplastina Parcial
17.
J Thromb Haemost ; 20(7): 1684-1695, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35490404

RESUMO

BACKGROUND: Bleeding is a clinically significant issue with all current anticoagulants. Safer antithrombotic strategies are required. OBJECTIVES: To investigate the safety, pharmacodynamics, and pharmacokinetics of BAY 1831865, a humanized, factor XI (FXI)-directed monoclonal antibody, after single intravenous (i.v.) or subcutaneous (s.c.) doses in healthy volunteers. PATIENTS/METHODS: In a first-in-human, phase I study, 70 volunteers were randomly assigned (4:1) to receive single-dose BAY 1831865 (3.5, 7, 17, 35, 75, or 150 mg i.v. or 150 mg s.c.) or placebo. Adverse events, pharmacodynamics, and pharmacokinetics were evaluated. RESULTS: In this study, no hemorrhage, or hypersensitivity or infusion-/injection-related reactions were reported. Drug-related adverse events occurred in 3 (5.4%) of 56 volunteers; all were mild and self-limited. Dose-dependent prolongation of activated partial thromboplastin time (aPTT) and inhibition of FXI clotting activity was observed with BAY 1831865 i.v. (geometric mean maximum ratio-to-baseline: aPTT, range, 1.09-3.11 vs. 1.05 with placebo; FXI, range, 0.70-0.04 vs. 0.91 with placebo). Onset of effect was rapid after i.v. administration, with duration of effect (up to 55 days) determined by dose. BAY 1831865 s.c. had similar pharmacodynamic effects but a slower onset of action. Terminal half-life increased continuously with increasing i.v. dose (range, 28-208 h), leading to strong and continuous increases in systemic exposure to BAY 1831865. Absolute bioavailability of BAY 1831865 s.c. was 47.2% (95% confidence interval, 30.2-73.7). CONCLUSIONS: BAY 1831865 i.v. or s.c. was well tolerated, with no evidence of bleeding in healthy volunteers. BAY 1831865 exhibited pronounced, sustained dose-dependent prolongation of aPTT and duration of FXI inhibition.


Assuntos
Anticoagulantes , Fator XIa , Anticorpos Monoclonais Humanizados/farmacologia , Anticoagulantes/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos , Masculino , Tempo de Tromboplastina Parcial
18.
Clin Lab ; 68(4)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35443600

RESUMO

BACKGROUND: In this study, we investigated the predictive value of routine coagulation parameters including D-dimer, Prothrombin Time (PT), International Normalized Ratio (INR), activated Partial Thromboplastin Time (aPTT) and Complete Blood Count (CBC) test parameters in children with COVID-19 infection. METHODS: Retrospective and observational study carried out in Abuzar Hospital, Ahvaz Jundishapur University of Medical Sciences (Ahvaz, Iran) included COVID-19 patients. RESULTS: Deceased patients (n = 5) compared to alive patients (n = 76) showed higher RDW (p = 0.005), PT (p = 0.005), INR (p = 0.004), PTT (p = 0.009), platelet count (p < 0.001), PLR (p < 0.001), and hospitalization time (p < 0.001). The area under the curve (AUC) of RDW was 0.85 (95% CI 0.75 - 0.96) which indicates its high power for mortality prediction in hospitalized children with COVID-19. We did not find significant differences in parameters in comparison between different severities. CONCLUSIONS: To our knowledge, our study is one of the few studies to evaluate routine coagulation tests and the CBC test parameters predictive value in children with COVID-19. RDW has the most power to predict the mortality of children with COVID-19, followed by PT, INR, aPTT, platelet count, PLR, and hospitalization time have a high power to predict the risk of death in patients.


Assuntos
COVID-19 , Biomarcadores , Criança , Humanos , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Estudos Retrospectivos
19.
Ann Card Anaesth ; 25(2): 229-232, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35417978

RESUMO

Factor XII (FXII) deficiency is a congenital disorder inherited as an autosomal recessive condition. In his heterozygous form, it is relatively common in the general population. However, a total absence of FXII as seen in homozygous patients, is rare, with an incidence of approximately 1/1,000,000 individuals. Surprisingly, FXII deficiency is rather associated with thromboembolic complications. Patients do not experience a higher risk of surgical bleeding despite a markedly prolonged activated partial thromboplastin time. Given its low incidence in the general population, the finding of an unknown FXII deficiency is rare during cardiac surgery. This unique case describes a patient with an unanticipated prolonged baseline activated clotting time (ACT) during cardiac surgery in which his bleeding history and rotational thromboelastometry tracings lead us to the diagnosis of a FXII deficiency. The finding of a hypocoagulable INTEM tracing and a concurrent normal EXTEM tracing in a sample of a patient with prolonged ACT and adverse anamnestic bleeding history should prompt clinicians to consider a FXII deficiency. It may help clinicians in further perioperative management where there is not enough time to wait for the results of individual coagulation factor testing.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Deficiência do Fator XII , Fator XII , Deficiência do Fator XII/complicações , Deficiência do Fator XII/diagnóstico , Humanos , Tempo de Tromboplastina Parcial
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