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1.
BMC Med Genet ; 21(1): 9, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914974

RESUMO

BACKGROUND: Coagulation factor XIII (FXIII) plays an essential role in maintaining hemostasis by crosslinking fibrin. Deficiency in FXIII affects clot stability and increases the risk of severe bleeding. Congenital FXIII deficiency is a rare disease. Recently, we identified a Chinese family with FXIII deficiency and investigated the pathogenesis of congenital FXIII deficiency, contributing non-coding pathogenic variants. METHODS: We performed common tests, coding sequencing by targeted next-generation sequencing (NGS), whole-genome sequencing and splice-sites prediction algorithms. The pathogenesis was investigated via minigene and nonsense-mediated mRNA decay (NMD) by experiments in vitro. RESULTS: The proband is homozygote for a novel deep intronic c.799-12G > A mutation in the F13A1 gene. Through direct sequencing of the minigenes mRNA, we found 10 bases of intron 6 insert in the mRNA of mutant minigenes mRNA. The relative expression of EGFP-F13A1 was higher by suppression of NMD in vitro. Furthermore, we found the proband with enhanced thrombin generation (TG). CONCLUSION: We reported a novel deep intronic c.799-12G > A mutation of F13A1 which produced a new acceptor site and frame shifting during translation introducing a premature termination codon. Our results support the premature termination codon triggered NMD. We need to pay attention to the position of potential alterable splicing sites while counselling and genetic test. The finding of enhanced TG indicated that we should be aware of the risk of thrombosis in patients with FXIII deficiency during replacement therapy.


Assuntos
Transtornos da Coagulação Sanguínea/genética , Deficiência do Fator XIII/genética , Fator XIII/genética , Adolescente , Adulto , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/patologia , Pré-Escolar , Deficiência do Fator XIII/sangue , Deficiência do Fator XIII/patologia , Feminino , Humanos , Íntrons/genética , Masculino , Mutação , Degradação do RNAm Mediada por Códon sem Sentido/genética , Linhagem , Processamento de RNA , RNA Mensageiro/genética
2.
J Trauma Acute Care Surg ; 88(2): 279-285, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31738314

RESUMO

BACKGROUND: Trauma-induced coagulopathy is a major driver of mortality following severe injury. Viscoelastic goal-directed resuscitation can reduce mortality after injury. The TEG 5000 system is widely used for viscoelastic testing. However, the TEG 6s system incorporates newer technology, with encouraging results in cardiovascular interventions. The purpose of this study was to validate the TEG 6s system for use in trauma patients. METHODS: Multicenter noninvasive observational study for method comparison conducted at 12 US Levels I and II trauma centers. Agreement between the TEG 6s and TEG 5000 systems was examined using citrated kaolin reaction time (CK.R), citrated functional fibrinogen maximum amplitude (CFF.MA), citrated kaolin percent clot lysis at 30 minutes (CK.LY30), citrated RapidTEG maximum amplitude (CRT.MA), and citrated kaolin maximum amplitude (CK.MA) parameters in adults meeting full or limited trauma team criteria. Blood was drawn ≤1 hour after admission. Assays were repeated in duplicate. Reliability (TEG 5000 vs. TEG 6s analyzers) and repeatability (interdevice comparison) was quantified. Linear regression was used to define the relationship between TEG 6s and TEG 5000 devices. RESULTS: A total of 475 patients were enrolled. The cohort was predominantly male (68.6%) with a median age of 49 years. Regression line slope estimates (ß) and linear correlation estimates (p) were as follows: CK.R (ß = 1.05, ρ = 0.9), CFF.MA (ß = 0.99, ρ = 0.95), CK.LY30 (ß = 1.01, ρ = 0.91), CRT.MA (TEG 6s) versus CK.MA (TEG 5000) (ß = 1.06, ρ = 0.86) as well as versus CRT.MA (TEG 5000) (ß = 0.93, ρ = 0.93), indicating strong reliability between the devices. Overall, within-device repeatability was better for TEG 6s versus TEG 5000, particularly for CFF.MA and CK.LY30. CONCLUSION: The TEG 6s device appears to be highly reliable for use in trauma patients, with close correlation to the TEG 5000 device and equivalent/improved within-device reliability. Given the potential advantages of using the TEG 6s device at the site of care, confirmation of agreement between the devices represents an important advance in diagnostic testing. LEVEL OF EVIDENCE: Diagnostic test, level II.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Tromboelastografia/instrumentação , Ferimentos e Lesões/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ferimentos e Lesões/sangue , Adulto Jovem
3.
Surgery ; 166(6): 1122-1127, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31522748

RESUMO

BACKGROUND: Plasma thrombin generation has been used to characterize trauma-induced coagulopathy, but description of whole blood thrombin generation is lacking. This study aimed to evaluate plasma and whole blood thrombin generation in healthy volunteers and trauma patients. We hypothesized that (1) plasma and whole blood thrombin generation are distinct, (2) whole blood thrombin generation is more pronounced in trauma patients than in healthy volunteers, and (3) thrombin generation correlates with clinical coagulation assays. METHODS: Blood was collected from healthy volunteers and trauma patients at a single, level-1 trauma center. Whole blood thrombin generation was assessed with a prototype point-of-care whole blood thrombin generation device, and plasma thrombin generation was measured with a calibrated automated thrombogram analogue. Plasma and whole blood thrombin generation were compared and correlated with international normalized ratio and thrombelastography. RESULTS: Overall, 10 healthy volunteers (average age 30, 50% men) were included and 58 trauma patients (average age 34, 76% men, 55% blunt mechanism, and with a median new injury severity score of 17) were included. Plasma and whole blood thrombin generation differed with more robust thrombin generation in plasma. Trauma patients had a significantly increased whole blood thrombin generation compared with healthy volunteers]. Plasma thrombin generation correlated with international normalized ratio, whereas whole blood thrombin generation did not correlate with thrombelastography. CONCLUSION: Plasma and whole blood thrombin generation are distinct, highlighting the need to perform standardized assays to better understand their correlation and to assess how whole blood thrombin generation confers differential outcomes in trauma.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Plasma/metabolismo , Trombina/metabolismo , Ferimentos e Lesões/complicações , Adulto , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Feminino , Voluntários Saudáveis , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tromboelastografia/métodos , Trombina/análise , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico
5.
Am J Health Syst Pharm ; 76(16): 1248-1253, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369117

RESUMO

PURPOSE: Results of a study to determine the proportion of anticoagulation clinic workload that could be performed by clinical pharmacy technicians (CPTs) and the potential impact on operational efficiency of pharmacist-managed anticoagulation clinics (ACCs) are reported. METHODS: In a quality improvement project involving 11 Veterans Affairs (VA) medical centers, investigators conducted a 3-day time study in pharmacist-managed ACCs followed by scoring of task appropriateness for CPTs via the RAND/UCLA appropriateness method by the VA Anticoagulation Subject Matter Expert (SME) Workgroup. The primary outcome was the percentage of tasks deemed appropriate for a CPT to perform. RESULTS: The Anticoagulation SME Workgroup determined that a wide variety of mainly administrative ACC tasks could be completed by a CPT. At the 11 VA ACCs, an average of 53.4% (range, 39.9-76.1%) of tasks being performed by pharmacists were deemed appropriate for CPTs. The average percentage of total clinic time associated with performing tasks appropriate for a CPT equated to an estimated 1,111 hours per year. Shifting that portion of the annual work hours to a CPT could potentially result in cost avoidance of $55,302. CONCLUSION: At the ACCs evaluated, a significant proportion of tasks (53.4% on average) may be appropriate to assign to CPTs to improve the operational efficiency of these clinics. This finding supports development of business plans for the addition of CPTs in ACCs along with elements to inform crafting of an effective template for ACC structure, including clearly defined CPT roles.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/prevenção & controle , Hemorragia/prevenção & controle , Ambulatório Hospitalar/organização & administração , Técnicos em Farmácia/organização & administração , Transtornos da Coagulação Sanguínea/sangue , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Eficiência Organizacional , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hospitais de Veteranos/organização & administração , Hospitais de Veteranos/estatística & dados numéricos , Humanos , Coeficiente Internacional Normatizado , Ambulatório Hospitalar/estatística & dados numéricos , Serviço de Farmácia Hospitalar/organização & administração , Serviço de Farmácia Hospitalar/estatística & dados numéricos , Técnicos em Farmácia/estatística & dados numéricos , Papel Profissional , Avaliação de Programas e Projetos de Saúde , Varfarina/uso terapêutico , Carga de Trabalho/estatística & dados numéricos
6.
Blood Coagul Fibrinolysis ; 30(6): 300-303, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31318719

RESUMO

: Activated partial thromboplastin time is a test assessing the intrinsic and common pathways of the coagulation cascade. We presented an asymptomatic case with isolated activated partial thromboplastin time prolongation. After excluding coagulation factor deficiency and lupus anticoagulant, the patient was diagnosed with plasma prekallikrein (PPK) deficiency. We reviewed the literature regarding effects of PPK deficiency which could have both antithrombotic and prothrombotic effects. At the moment, research supports that PPK deficiency in healthy adults rarely causes bleeding as it is not a major contributor of hemastasis; whereas in adults with multiple comorbidities or with predominant systemic inflammation, effects of PPK deficiency remain debatable. Further research is needed to clarify impacts of PPK deficiency in clinical settings.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Tempo de Tromboplastina Parcial , Pré-Calicreína/deficiência , Adulto , Transtornos da Coagulação Sanguínea/diagnóstico , Comorbidade , Diagnóstico Diferencial , Hemorragia/etiologia , Humanos
7.
Transfus Apher Sci ; 58(4): 386-391, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31307835

RESUMO

Adequate function of the coagulation system is vital for an uncomplicated outcome of surgery. Clinically relevant perioperative bleeding complications may occur when surgical hemostasis is inadequate, but can also be caused by insufficient activity of the hemostatic system. Optimal surgical hemostasis and a satisfactory function of the coagulation system are complementary. In this article current insights on normal function and dysfunction of the coagulation system are reviewed as well as drugs that may affect a proper hemostatic response. We discuss coagulation disorders resulting in increased perioperative blood loss and conditions that may enhance the threat of postoperative thrombosis.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/terapia , Coagulação Sanguínea , Perda Sanguínea Cirúrgica/prevenção & controle , Hemostasia Cirúrgica/efeitos adversos , Transtornos da Coagulação Sanguínea/sangue , Humanos
8.
Pediatr Blood Cancer ; 66(10): e27896, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31250546

RESUMO

BACKGROUND/OBJECTIVES: Stagnant blood flow present in slow-flow vascular malformations can lead to localized intravascular coagulopathy (LIC), measured by elevated D-dimer levels, low fibrinogen, and/or thrombocytopenia. LIC can lead to localized thrombosis and/or bleeding, resulting in pain, swelling, and functional limitations. Patients with complex vascular malformations treated with sirolimus show clinical improvement in these symptoms. We hypothesized that the clinical benefits of sirolimus may correlate with improvements in coexisting LIC. DESIGN/METHODS: A retrospective chart review was performed, including D-dimer, fibrinogen, and platelet count, in patients with slow-flow vascular malformations treated with sirolimus. Laboratory values were assessed at three time points (presirolimus, 1-3 months postsirolimus, and last clinic visit). Clinical response, as defined by decreased pain and swelling, was extracted from the record. RESULTS: Thirty-five patients at our vascular anomalies center had been prescribed sirolimus between 2014 and 2017. Fifteen patients (12 combined slow-flow vascular malformations and three pure venous malformations) remained after excluding patients that did not have adequate records or a venous component to their vascular malformation. Patients who did not adhere to the treatment were also excluded. All 15 had elevated D-dimer levels prior to treatment and there was a statistically significant decrease in D-dimer levels following treatment with sirolimus. Symptomatic improvement of pain and swelling was reported after 3 months of starting sirolimus in 13/15 patients. CONCLUSION: This study suggests that sirolimus improves coagulopathy in slow-flow vascular malformations, as evidenced by reduced D-dimer levels. Improvement in LIC symptoms also correlates with sirolimus-corrected coagulopathy.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Sirolimo/uso terapêutico , Malformações Vasculares/sangue , Adolescente , Adulto , Transtornos da Coagulação Sanguínea/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Malformações Vasculares/complicações , Adulto Jovem
9.
BMC Anesthesiol ; 19(1): 90, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31153366

RESUMO

BACKGROUND: Hemostasis is the dynamic equilibrium between coagulation and fibrinolysis. During pregnancy, the balance shifts toward a hypercoagulative state; however placental abruption and abnormal placentations may lead to rapidly evolving coagulopathy characterized by the increased activation of procoagulant pathways. These processes can result in hypofibrinogenemia, with fibrinogen levels dropping to 2 g/L or less and an associated increased risk of post-partum hemorrhage. The aim of the present study was to evaluate the concordance between two methods of functional fibrinogen measurement: the Thromboelastography (TEG) method (also known as FLEV) vs. the Clauss method. Three patient groups were considered: healthy volunteers; non-pathological pregnant patients; and pregnant patients who went on to develop postpartum hemorrhage. METHODS: A prospective observational study. Inclusion criteria were: healthy volunteer women of childbearing age, non-pathological pregnant women at term, and pregnant hemorrhagic patients subjected to elective or urgent caesarean section (CS), with blood loss exceeding 1000 mL. Exclusion criteria were age < 18 years, a history of coagulopathy, and treatment with contraceptives, anticoagulants, or antiplatelet agents. RESULTS: Bland-Altman plots showed a significant overestimation with the FLEV method in all three patient groups: bias was - 133.36 mg/dL for healthy volunteers (95% IC: - 257.84; - 8.88. Critical difference: 124.48); - 56.30 mg/dL for healthy pregnant patients (95% IC: - 225.53; 112.93. Critical difference: 169.23); and - 159.05 mg/dL for hemorrhagic pregnant patients (95% IC: - 333.24; 15.148. Critical difference: 174.19). Regression analyses detected a linear correlation between FLEV and Clauss for healthy volunteers, healthy pregnant patients, and hemorrhagic pregnant patients (R2 0.27, p value = 0.002; R2 0.31, p value = 0.001; R2 0.35, p value = 0.001, respectively). ANOVA revealed a statistically significant difference in fibrinogen concentration between all three patients groups when assayed using the Clauss method (p value < 0.001 for all the comparisons), but no statistically significant difference between the two patients groups of pregnant women when using the FLEV method. CONCLUSIONS: The FLEV method does not provide a valid alternative to the Clauss method due to the problem of fibrinogen overestimation, and for this reason it should not be recommended for the evaluation of patients with an increased risk of hypofibrinogenemia.


Assuntos
Coagulação Sanguínea/fisiologia , Fibrinogênio/metabolismo , Trabalho de Parto/sangue , Gravidez/sangue , Tromboelastografia/métodos , Adulto , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Testes de Coagulação Sanguínea/métodos , Cesárea , Feminino , Humanos , Estudos Prospectivos
10.
Int J Mol Sci ; 20(11)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31159152

RESUMO

Coagulation factor XIII (FXIII) is a plasma-circulating heterotetrameric pro-transglutaminase complex that is composed of two catalytic FXIII-A and two protective/regulatory FXIII-B subunits. FXIII acts by forming covalent cross-links within a preformed fibrin clots to prevent its premature fibrinolysis. The FXIII-A subunit is known to have pleiotropic roles outside coagulation, but the FXIII-B subunit is a relatively unexplored entity, both structurally as well as functionally. Its discovered roles so far are limited to that of the carrier/regulatory protein of its partner FXIII-A subunit. In the present study, we have explored the co-presence of protein excipients in commercial FXIII plasma concentrate FibrogamminP by combination of protein purification and mass spectrometry-based verification. Complement factor H was one of the co-excipients observed in this analysis. This was followed by performing pull down assays from plasma in order to detect the putative novel interacting partners for the FXIII-B subunit. Complement system proteins, like complement C3 and complement C1q, were amongst the proteins that were pulled down. The only protein that was observed in both experimental set ups was alpha-2-macroglobulin, which might therefore be a putative interacting partner of the FXIII/FXIII-B subunit. Future functional investigations will be needed to understand the physiological significance of this association.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/metabolismo , Proteínas de Transporte/metabolismo , Fator XIII/metabolismo , Mapeamento de Interação de Proteínas , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/sangue , Fator H do Complemento/metabolismo , Fibrinogênio/metabolismo , Humanos , Espectrometria de Massas , alfa 2-Macroglobulinas Associadas à Gravidez/metabolismo , Ligação Proteica
11.
Semin Thromb Hemost ; 45(4): 354-372, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31108555

RESUMO

The relationship between malignancy and coagulopathy is one that is well documented yet incompletely understood. Clinicians have attempted to quantify the hypercoagulable state produced in various malignancies using common coagulation tests such as prothrombin time, activated partial thromboplastin time, and platelet count; however, due to these tests' focus on individual aspects of coagulation during one specific time point, they have failed to provide clinicians the complete picture of malignancy-associated coagulopathy (MAC). Viscoelastic tests (VETs), such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), are whole blood analyses that have the advantage of providing information related to the cumulative effects of plasma clotting factors, platelets, leukocytes, and red cells during all stages of the coagulation and fibrinolytic processes. VETs have gained popularity in the care of trauma patients to objectively measure trauma-induced coagulopathy (TIC), but the utility of VETs remains yet unrealized in many other medical specialties. The authors discuss the similarities and differences between TIC and MAC, and propose a mechanism for the hypercoagulable state of MAC that revolves around the thrombomodulin-thrombin complex as it switches between activating the protein C anticoagulation pathway or the thrombin activatable fibrinolysis inhibitor coagulation pathway. Additionally, they review the current literature on the use of TEG and ROTEM in patients with various malignancies. Although limited research is currently available, early results demonstrate the utility of both TEG and ROTEM in the prediction of hypercoagulable states and thromboembolic complications in oncologic patients.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Testes de Coagulação Sanguínea/métodos , Neoplasias/complicações , Trombose/diagnóstico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tromboelastografia/métodos , Tromboembolia/sangue , Tromboembolia/diagnóstico , Tromboembolia/etiologia , Trombose/sangue , Trombose/complicações
12.
PLoS One ; 14(5): e0216724, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31120933

RESUMO

BACKGROUND: The shift towards hypercoagulation during in vitro fertilization (IVF) can lead to the impairment of embryo implantation and placental blood circulation, which is believed to be a factor in an unsuccessful IVF cycle. OBJECTIVES: To assess coagulation in women with infertility before the start of an IVF cycle and during treatment to reveal the association between coagulation imbalance and IVF outcome. PATIENTS/METHODS: We conducted a prospective cohort observational study including 125 participants who underwent fresh IVF cycles. Blood samples were collected at five time points: before IVF, one week after the start of controlled ovarian stimulation (COS), on the day of follicular puncture, on the day of embryo transfer (ET) and one week after ET. Coagulation tests (clotting times: activated partial thromboplastin time (APTT) and prothrombin; fibrinogen and D-dimer concentrations; thrombodynamics) were performed. RESULTS: Women with an elevated clot growth velocity (>32.3 µm/min, detected by thrombodynamics) before IVF demonstrated a higher risk of negative IVF outcomes (adjusted RR = 1.38; 95% CI 1.28-1.49; P<0.001). During the procedure, we observed increases in prothrombin, fibrinogen and D-dimer concentrations, a slight shortening of APTT and a hypercoagulation shift in the thrombodynamics parameters. The hemostasis assay values during COS and after ET had no associations with IVF outcomes. CONCLUSIONS: Hypercoagulation in the thrombodynamics before the start of IVF treatment was associated with negative IVF outcomes. After the start of COS, all tests demonstrated a hypercoagulation trend, but the hypercoagulation did not influence IVF outcome. This research is potentially beneficial for the application of thrombodynamics assay for monitoring hemostasis in infertile women prior to an IVF procedure with the goal of selecting a group requiring hemostasis correction to increase the chances of pregnancy.


Assuntos
Coagulação Sanguínea , Fertilização In Vitro , Infertilidade Feminina/sangue , Infertilidade Feminina/terapia , Adulto , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Testes de Coagulação Sanguínea , Estudos de Coortes , Transferência Embrionária , Feminino , Humanos , Infertilidade Feminina/complicações , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Fatores de Risco
13.
J Trauma Acute Care Surg ; 87(3): 582-589, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31136528

RESUMO

BACKGROUND: Conventional coagulation assays (CCAs), prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT), detect clotting factor (CF) deficiencies in hematologic disorders. However, there is controversy about how these CCAs should be used to diagnose, treat, and monitor trauma-induced coagulopathy. Study objectives were to determine whether CCA abnormalities are reflective of deficiencies of coagulation factor activity in the setting of severe injury. METHODS: Patients without previous CF deficiency within a prospective database at an ACS-verified Level I trauma center had CF activity levels, PT/INR, aPTT, and fibrinogen levels measured upon emergency department arrival from 2014 to 2017. Linear regression assessed how CF activity explained the aPTT and PT/INR variation. Prolonged CCA values were set as INR greater than 1.3 and aPTT greater than 34 seconds. CF deficiency was defined as less than 30% activity, except for fibrinogen, defined as less than 150 mg/dL. RESULTS: Sixty patients with a mean age of 35.8 (SD, 13.6) years and median New Injury Severity Score of 32 (interquartile range, 12-43) were included; 53.3% sustained blunt injuries, 23.3% required massive transfusion, and mortality was 11.67%. Overall, 44.6% of the PT/INR variance and 49.5% of the aPTT variance remained unexplained by CF activity. Deficiencies of CFs were: common pathway, 25%; extrinsic pathway, 1.7%; and intrinsic pathway, 6.7%. The positive predictive value for CF deficiencies were: (1) PT/INR greater than 1.3:4.4% for extrinsic pathway, 56.5% for the common pathway; (2) aPTT greater than 34 seconds:16.7% for the intrinsic pathway, 73.7% for the common pathway. CONCLUSION: Almost half of the variances of PT/INR and aPTT were unexplained by CF activity. Prolonged PT/INR and aPTT were poor predictors of deficiencies in the intrinsic or extrinsic pathways; however, they were indicators of common pathway deficiencies. LEVEL OF EVIDENCE: Prognostic, level III.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Ferimentos e Lesões/sangue , Adolescente , Adulto , Transtornos da Coagulação Sanguínea/sangue , Fatores de Coagulação Sanguínea/análise , Estudos de Casos e Controles , Criança , Transtornos de Proteínas de Coagulação/sangue , Transtornos de Proteínas de Coagulação/complicações , Fibrinogênio/análise , Humanos , Coeficiente Internacional Normatizado , Masculino , Tempo de Tromboplastina Parcial , Ferimentos e Lesões/complicações , Adulto Jovem
14.
Vet Comp Orthop Traumatol ; 32(4): 289-296, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31141824

RESUMO

OBJECTIVE: The aim of this study was to describe coagulation abnormalities and incidence of acute traumatic coagulopathy (ATC) in traumatized cats over the first 24 hours after admission. STUDY DESIGN: This was a prospective observational study at the university teaching hospital including 26 cats with acute (<5 hours) trauma. Blood was sampled for rotational thromboelastometry (ROTEM) parameters at presentation and 6 hours/24 hours thereafter. Rotational thromboelastometry tracings were defined as hypo- or hypercoagulable if ≥ 2 of the following parameters were above or below institutional reference intervals: clotting time, clot formation time (CFT), maximum clot firmness, maximum lysis or maximum clot elasticity. Hypocoagulability at presentation was defined as ATC. Injury severity scores, treatment and survival to hospital discharge were retrieved from patient records. RESULTS: The incidence of ATC was 15% and the most common ROTEM abnormalities in cats with ATC were clotting time and CFT prolongation in both extrinsic and intrinsic ROTEM profiles. After 24 hours, compared with presentation, significantly more cats were hypercoagulable (p = 0.047) and none of the cats showed hypocoagulopathy. Cats with ATC received significantly more blood transfusions (p = 0.008). CONCLUSION: The incidence of ATC in cats is higher than previously reported. Clotting time and CFT prolongations seem to be more common than hyperfibrinolysis and 53% of the cats became hypercoagulable within 24 hours. While the clinical relevance of ATC in cats needs to be investigated, cats diagnosed with ATC required significantly more blood transfusions.


Assuntos
Transtornos da Coagulação Sanguínea/veterinária , Doenças do Gato/sangue , Gatos/sangue , Gatos/lesões , Tromboelastografia/veterinária , Animais , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/epidemiologia , Transtornos da Coagulação Sanguínea/etiologia , Doenças do Gato/epidemiologia , Doenças do Gato/etiologia , Feminino , Hemostasia , Incidência , Masculino , Estudos Prospectivos , Ferimentos e Lesões/sangue , Ferimentos e Lesões/veterinária
15.
Int J Lab Hematol ; 41(4): 530-535, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31062936

RESUMO

INTRODUCTION: Acquired coagulation disorders are a common cause of neonatal bleeding. The thromboelastograph (TEG) comprehensively assesses haemostatic processes in the body. Unfortunately, the reference range of TEG parameters in the neonatal period has not yet been evaluated, which limits the use of the TEG in neonates. In this study, we aimed to establish the reference range of TEG parameters for the neonatal period. METHODS: This study included 371 full-term infants (≥37 weeks of gestation), and we divided these infants into three groups according to age as follows: 1, 2-7 and 8-28 days. We measured their peripheral blood using TEG, coagulation routine and platelet count tests. We analysed differences among the groups. RESULTS: The reference ranges for TEG parameters are presented as medians and reference ranges (2.5th and 97.5th percentiles) as follows: R (clot reaction time, seconds) 4.80 (2.80-7.17), Angle (fibrin production rate) 69.90 (44.91-78.89), K (clot kinetics, min) 1.40 (0.80-4.50), MA (maximum amplitude, mm) 63.50(44.34-74.66) and LY30 (lysis at 30 minutes, %) 0.10 (0.10-6.95). There were significant differences in Angle, K, MA and LY30 values between the different neonatal day age groups. CONCLUSION: This study preliminarily establishes a reference range for TEG parameters during the neonatal period. The age of a newborn had a large influence on TEG parameters. Additionally, we demonstrated a correlation between laboratory tests and TEG parameters for this age period. The reference values provided herein are meaningful for future studies.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Hemostasia , Tromboelastografia/normas , Feminino , Humanos , Recém-Nascido , Masculino , Contagem de Plaquetas/normas , Valores de Referência , Estudos Retrospectivos
16.
Int J Lab Hematol ; 41 Suppl 1: 26-32, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31069975

RESUMO

INTRODUCTION: Platelet function disorders (PFD) are an important group of bleeding disorders that require validated and practical laboratory strategies for diagnosis. METHODS: This review summarizes the authors' experiences, current literature, and an international survey to evaluate the practices of diagnostic laboratories that offer tests for PFD. RESULTS: Blood counts, blood film review, and aggregation tests are the most commonly performed investigations for PFD and help determine whether there is thrombocytopenia and/or defective platelet function due to a variety of causes. The performance characteristics of tests for PFD, and the level of evidence that these tests detect bleeding problems, are important issues to determine where tests are useful for diagnostic or correlative purposes, or research only uses. Platelet aggregation assays, and quantitative analysis of platelet dense granule numbers, are tests with good performance characteristics that detect abnormalities associated with increased bleeding in a significant proportion of individuals referred for PFD investigations. Lumiaggregometry estimates of platelet adenosine triphosphate release show greater variability which limits the diagnostic usefulness. Diagnostic laboratories report that fiscal and other constraints, including a lack of high-quality evidence, limit their ability to offer an expanded test menu for PFD. CONCLUSION: PFD are clinically important bleeding disorders that remain challenging for diagnostic laboratories to investigate. While some PFD tests are well validated for diagnostic purposes, gaps in scientific evidence and resource limitations influence diagnostic laboratory decisions on which PFD tests to offer.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos Plaquetários/diagnóstico , Hemorragia/diagnóstico , Transtornos da Coagulação Sanguínea/sangue , Transtornos Plaquetários/sangue , Hemorragia/sangue , Humanos , Testes de Função Plaquetária/métodos
17.
Int J Mol Sci ; 20(8)2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31013569

RESUMO

Congenital FXIII deficiency is a rare bleeding disorder in which mutations are detected in F13A1 and F13B genes that express the two subunits of coagulation FXIII, the catalytic FXIII-A, and protective FXIII-B. Mutations in FXIII-B subunit are considerably rarer compared to FXIII-A. Three mutations in the F13B gene have been reported on its structural disulfide bonds. In the present study, we investigate the structural and functional importance of all 20 structural disulfide bonds in FXIII-B subunit. All disulfide bonds were ablated by individually mutating one of its contributory cysteine's, and these variants were transiently expressed in HEK293t cell lines. The expression products were studied for stability, secretion, the effect on oligomeric state, and on FXIII-A activation. The structural flexibility of these disulfide bonds was studied using classical MD simulation performed on a FXIII-B subunit monomer model. All 20 FXIII-B were found to be important for the secretion and stability of the protein since ablation of any of these led to a secretion deficit. However, the degree of effect that the disruption of disulfide bond had on the protein differed between individual disulfide bonds reflecting a functional hierarchy/diversity within these disulfide bonds.


Assuntos
Coagulação Sanguínea , Dissulfetos/química , Fator XIII/química , Subunidades Proteicas/química , Transtornos da Coagulação Sanguínea/sangue , Retículo Endoplasmático/metabolismo , Fator XIII/metabolismo , Humanos , Modelos Moleculares , Conformação Proteica , Multimerização Proteica , Subunidades Proteicas/metabolismo , Relação Estrutura-Atividade
18.
Transfusion ; 59(S2): 1601-1607, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30980751

RESUMO

BACKGROUND: Hemorrhage is the leading cause of preventable trauma-related mortality and is frequently aggravated by acute traumatic coagulopathy (ATC). Viscoelastic tests such as rotational thromboelastometry (ROTEM) may improve identification and management of ATC. This study aimed to prospectively evaluate changes in ROTEM among combat casualties during the first 24 hours and compare the capabilities of our conventional clotting assay (international normalized ratio [INR], >1.2) to a proposed integrated ROTEM model (INR >1.2 with the addition of tissue factor pathway activation thromboelastometry [EXTEM] A5 ≤35 mm and/or EXTEM LI30 <97% on admission) to identify ATC and predict massive transfusion (MT). STUDY DESIGN AND METHODS: This was a prospective observational study of trauma patients treated in NATO hospitals in Afghanistan between January 2012 and June 2013. ROTEM (EXTEM, functional fibrinogen thromboelastometry, APTEM, EXTEM with the addition of a fibrinolysis inhibitor) was performed on admission and at 6 and 24 hours by a designated research team. Treatment teams did not have access to the ROTEM results. RESULTS: ROTEM values were available for 40 male casualties. The integrated ROTEM model classified 15% more patients with ATC than with INR alone and increased the detection of those that required MT by 22%. The sensitivity of the integrated ROTEM model to predict MT was higher than with INR greater than 1.2 (86% vs. 64%); however, specificity with both definitions for predicting MT was poor (38% vs. 50%, respectively). CONCLUSION: These observations support the importance of early identification of and intervention in ATC. Integrating ROTEM into the definition of ATC would increase detection of those requiring MT arguing for its use as an adjunct to clinical presentation in the ultimate decision to initiate MT.


Assuntos
Transtornos da Coagulação Sanguínea , Tomada de Decisão Clínica , Hemorragia , Coeficiente Internacional Normatizado , Modelos Biológicos , Tromboelastografia , Ferimentos e Lesões , Adolescente , Adulto , Campanha Afegã de 2001- , Afeganistão , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/terapia , Hemorragia/sangue , Hemorragia/terapia , Hospitais Militares , Humanos , Masculino , Militares , Valor Preditivo dos Testes , Estudos Prospectivos , Ferimentos e Lesões/sangue , Ferimentos e Lesões/terapia
19.
Transfusion ; 59(S2): 1522-1528, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30980753

RESUMO

Traumatic brain injury (TBI)-induced coagulopathy has long been recognized as a significant risk for poor outcomes in patients with TBI, but its pathogenesis remains poorly understood. As a result, current treatment options for the condition are limited and ineffective. The lack of information is most significant for the impact of blood transfusions on patients with isolated TBI and in the absence of confounding influences from trauma to the body and limbs and the resultant hemorrhagic shock. Here we discuss recent progress in understanding the pathogenesis of TBI-induced coagulopathy and the current state of blood transfusions for patients with TBI and associated coagulopathy.


Assuntos
Transtornos da Coagulação Sanguínea , Transfusão de Sangue , Lesões Encefálicas Traumáticas , Choque Hemorrágico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/terapia , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/terapia , Humanos , Choque Hemorrágico/sangue , Choque Hemorrágico/complicações , Choque Hemorrágico/terapia
20.
Gastroenterology ; 157(1): 34-43.e1, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30986390

RESUMO

DESCRIPTION: This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The intent is to evaluate the current data on mechanism of altered coagulation in patients with cirrhosis, provide guidance on the use of currently available testing of the coagulation cascade, and help practitioners use anticoagulation and pro-coagulants appropriately in patients with cirrhosis. METHODS: This review is framed around the best practice points, which were derived from the most impactful publications in the area of coagulation in cirrhosis and agreed to by all authors. BEST PRACTICE ADVICE 1: Global tests of clot formation, such as rotational thromboelastometry, thromboelastography, sonorheometry, and thrombin generation, may eventually have a role in the evaluation of clotting in patients with cirrhosis, but currently lack validated target levels. BEST PRACTICE ADVICE 2: In general, clinicians should not routinely correct thrombocytopenia and coagulopathy before low-risk therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation in patients with hepatic synthetic dysfunction-induced coagulation abnormalities. BEST PRACTICE ADVICE 3: Blood products should be used sparingly because they increase portal pressure and carry a risk of transfusion-associated circulatory overload, transfusion-related acute lung injury, infection transmission, alloimmunization, and/or transfusion reactions. BEST PRACTICE ADVICE 4: The following transfusion thresholds for management of active bleeding or high-risk procedures may optimize clot formation in advanced liver disease: hematocrit ≥25%, platelet count >50,000, and fibrinogen >120 mg/dL. Commonly utilized thresholds for international normalized ratio correction are not supported by evidence. BEST PRACTICE ADVICE 5: Thrombopoietin agonists are a good alternative to platelet transfusion, but require time (about 10 days) to elevate platelet levels. BEST PRACTICE ADVICE 6: The large volume of fresh frozen plasma required to reach an arbitrary international normalized ratio target, limitations of the usual target, minimal effect on thrombin generation, and adverse effects on portal pressure limit the utility of this agent significantly. BEST PRACTICE ADVICE 7: The 4-factor prothrombin complex concentrate contains both pro- and anticoagulant factors that offer an attractive low-volume therapeutic to rebalance a disturbed hemostatic system. However, dosage is, in part, based on international normalized ratio, which is problematic in cirrhosis, and published experience in liver disease is limited. BEST PRACTICE ADVICE 8: Anti-fibrinolytic therapy may be considered in patients with persistent bleeding from mucosal oozing or puncture wound bleeding consistent with impaired clot integrity. Both ε-aminocaproic acid and tranexamic acid inhibit clot dissolution. Neither is believed to generate a hypercoagulable state, although both may exacerbate pre-existing thrombi. BEST PRACTICE ADVICE 9: Desmopressin releases von Willebrand factor as its primary hemostatic mechanism. As this factor is usually elevated in cirrhosis, the agent lacks a sound evidence-based foundation, but may be useful in patients with concomitant renal failure. BEST PRACTICE ADVICE 10: Systemic heparin infusion is recommended for symptomatic deep vein thrombosis and portal and mesenteric vein thrombosis, but there are unresolved issues regarding monitoring with both the anti-Xa assay and the partial thromboplastin time due to cirrhosis-related antithrombin deficiency (heparin cofactor). BEST PRACTICE ADVICE 11: Treatment of incidental portal and mesenteric vein thrombosis depends on estimated impact on transplantation surgical complexity vs risks of bleeding and falls. Therapy with low-molecular-weight heparin, vitamin K antagonists, and direct-acting anticoagulants improve portal vein repermeation vs observation alone. BEST PRACTICE ADVICE 12: Direct-acting anticoagulants, such as the factor Xa and thrombin inhibitors, are relatively safe and effective in stable cirrhotic patients, but are in need of further study in patients with more advanced liver disease.


Assuntos
Transtornos da Coagulação Sanguínea/terapia , Transfusão de Sangue/métodos , Cirrose Hepática/sangue , Trombofilia/terapia , Trombose Venosa/terapia , Anticoagulantes/uso terapêutico , Antifibrinolíticos/uso terapêutico , Antitrombinas/uso terapêutico , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Fatores de Coagulação Sanguínea/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Fibrinogênio/metabolismo , Hematócrito , Heparina/uso terapêutico , Humanos , Coeficiente Internacional Normatizado , Cirrose Hepática/complicações , Plasma , Contagem de Plaquetas , Veia Porta , Tromboelastografia , Trombocitopenia , Trombofilia/sangue , Trombofilia/complicações , Trombopoetina/agonistas , Reação Transfusional , Trombose Venosa/sangue , Trombose Venosa/complicações
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