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1.
J Trauma Acute Care Surg ; 91(5): 803-808, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34695058

RESUMO

BACKGROUND: Preinjury antiplatelet agent (APA) use in trauma patients can increase traumatic hemorrhage and worsen outcomes. Thromboelastography with platelet mapping (TEGPM) has characterized platelet function via arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition in nontrauma settings, but limited data exist in the acute trauma population. METHODS: A prospective observational study of adult trauma patients with suspected preinjury APA use who received TEGPM testing from 2017 to 2020 was performed. Patients on anticoagulants were excluded. Patients were grouped according to preinjury APA regimen: 81 mg or 325 mg of aspirin daily, 81 mg of aspirin and 75 mg of clopidrogrel daily, 75 mg of clopidrogrel daily, or no antiplatelet. Ability of TEGPM to detect APA use was assessed using predictive statistics and area under receiver operating characteristic curves (AUROCs). RESULTS: A total of 824 patients were included with most patients taking 81 mg of aspirin (n = 558). Patients on no antiplatelet were younger and had higher baseline platelet counts, while patients on 75 mg of clopidrogrel were more likely to be admitted after ground level fall. All other baseline characteristics were balanced. Admission TEG values were similar between groups. Median AA inhibition was higher in patients on aspirin containing regimens (p < 0.0001). Median ADP inhibition was higher in patients on clopidogrel containing regimens and those taking 325 mg of aspirin (p < 0.0001). Arachidonic acid inhibition accurately detected preinjury APA use and aspirin use (AUROC, 0.89 and 0.84, respectively); however, ADP inhibition performed poorly (AUROC, 0.58). Neither AA nor ADP inhibition was able to discern specific APA regimens or rule out APA use entirely. CONCLUSION: High AA inhibition accurately detects preinjury APA use in trauma patients. High ADP inhibition after trauma is common, limiting its utility to accurately identify preinjury APA use. Further study is needed to identify assays that can reliably detect and further characterize preinjury APA use in trauma populations. LEVEL OF EVIDENCE: Diagnostic test, level II.


Assuntos
Hemorragia/prevenção & controle , Reconciliação de Medicamentos/métodos , Inibidores da Agregação Plaquetária/efeitos adversos , Tromboelastografia/estatística & dados numéricos , Ferimentos e Lesões/complicações , Idoso , Idoso de 80 Anos ou mais , Ácido Araquidônico/análise , Ácido Araquidônico/antagonistas & inibidores , Ácido Araquidônico/metabolismo , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Domperidona/administração & dosagem , Domperidona/efeitos adversos , Domperidona/análogos & derivados , Feminino , Hemorragia/sangue , Hemorragia/etiologia , Humanos , Masculino , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Ferimentos e Lesões/sangue , Ferimentos e Lesões/terapia
2.
Nat Commun ; 12(1): 5922, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635666

RESUMO

Death from acute hemorrhage is a major problem in military conflicts, traffic accidents, and surgical procedures, et al. Achieving rapid effective hemostasis for pre-hospital care is essential to save lives in massive bleeding. An ideal hemostasis material should have those features such as safe, efficient, convenient, economical, which remains challenging and most of them cannot be achieved at the same time. In this work, we report a rapid effective nanoclay-based hemostatic membranes with nanoclay particles incorporate into polyvinylpyrrolidone (PVP) electrospun fibers. The nanoclay electrospun membrane (NEM) with 60 wt% kaolinite (KEM1.5) shows better and faster hemostatic performance in vitro and in vivo with good biocompatibility compared with most other NEMs and clay-based hemostats, benefiting from its enriched hemostatic functional sites, robust fluffy framework, and hydrophilic surface. The robust hemostatic bandages based on nanoclay electrospun membrane is an effective candidate hemostat in practical application.


Assuntos
Bandagens , Hemorragia/tratamento farmacológico , Hemostáticos/farmacologia , Caulim/farmacologia , Nanoestruturas/química , Ferida Cirúrgica/tratamento farmacológico , Animais , Argila/química , Modelos Animais de Doenças , Hemorragia/sangue , Hemorragia/patologia , Hemostasia/efeitos dos fármacos , Hemostáticos/química , Humanos , Caulim/química , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/lesões , Masculino , Nanoestruturas/administração & dosagem , Nanoestruturas/ultraestrutura , Povidona/química , Povidona/farmacologia , Ratos , Ratos Sprague-Dawley , Baço/irrigação sanguínea , Baço/efeitos dos fármacos , Baço/lesões , Ferida Cirúrgica/sangue , Ferida Cirúrgica/patologia
3.
Blood Coagul Fibrinolysis ; 32(7): 480-490, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34475331

RESUMO

Inherited thrombocytopenia is a heterogeneous group of hereditary disorders with varying bleeding tendencies, not simply related to platelet count. Platelets transform into different subpopulations upon stimulation, including procoagulant platelets and platelet microparticles (PMPs), which are considered critical for haemostasis. We aimed to investigate whether abnormalities in PMP and procoagulant platelet function were associated with the bleeding phenotype of inherited thrombocytopenia patients. We enrolled 53 inherited thrombocytopenia patients. High-throughput sequencing of 36 inherited thrombocytopenia related genes was performed in all patients and enabled a molecular diagnosis in 57%. Bleeding phenotype was evaluated using the ISTH bleeding assessment tool, dividing patients into bleeding (n = 27) vs. nonbleeding (n = 26). Unstimulated and ADP, TRAP or collagen-stimulated PMP and procoagulant platelet functions were analysed by flow cytometry using antibodies against granulophysin (CD63), P-selectin (CD62P), activated GPIIb/IIIa (PAC-1) and a marker for phosphatidylserine expression (lactadherin). Procoagulant platelets were measured in response to collagen stimulation. An in-house healthy reference level was available. Overall, higher levels of activated platelets, PMPs and procoagulant platelets were found in nonbleeding patients compared with the reference level. Nonbleeding patients had higher proportions of phosphatidylserine and PMPs compared with bleeding patients and the reference level, in response to different stimulations. Interestingly, this finding of high proportions of phosphatidylserine and PMPs was limited to PMPs, and not present in procoagulant platelets or platelets. Our findings indicate that nonbleeding inherited thrombocytopenia patients have compensatory mechanisms for improved platelet subpopulation activation and function, and that generation of phosphatidylserine expressing PMPs could be a factor determining bleeding phenotype in inherited thrombocytopenia.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Hemorragia/metabolismo , Fosfatidilserinas/metabolismo , Trombocitopenia/metabolismo , Adulto , Idoso , Coagulação Sanguínea , Plaquetas/citologia , Plaquetas/metabolismo , Feminino , Hemorragia/sangue , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilserinas/sangue , Ativação Plaquetária , Trombocitopenia/sangue , Trombocitopenia/complicações , Adulto Jovem
4.
Hematology ; 26(1): 769-774, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34565307

RESUMO

OBJECTIVE: To explore the relationship between platelet count and bleeding score in immune thrombocytopenia purpura (ITP) and compare the clinical practicability of two bleeding grading systems with adult patients with ITP. METHODS: A total of 204 patients were retrospectively analyzed with the ITP bleeding scale (IBLS) and the ITP bleeding assessment tool (version 2016) (ITP-2016). The correlation between the two bleeding score systems and the relations among the platelet counts were respectively analyzed. RESULTS: (1) There is a linear relationship between platelet count and bleeding score, no matter which scoring system it is based on (rs = -0.429, p < 0.001; rs = -0.331, p < 0.001, the analysis of the number of sites of Grade 1/2 bleeding were done; and rs = -0.466, p < 0.05, the analysis between platelet count and bleeding score by ITP-2016 respectively). (2) Platelet count and bleeding scores are negatively correlated in those with extremely low platelet counts ( < 10*109/L). The number of sites of Grade 2 bleeding and the ITP-2016 scores are negatively correlated with platelet counts (rs = -0.15 and rs = -0.244, p < 0.05, respectively). Significantly, there is no correlation between the platelet count and bleeding scores when the platelet count is more than 10*109/L. (3) It takes less time to score with ITP-2016 than IBLS (z = -3.825, P < 0.001). CONCLUSIONS: There is good responsiveness, strong assessment consistency, close correlation between ITP-2016 and IBLS. ITP-2016 takes less time-consuming in clinical application. It can be used as an effective tool of condition judgement, risk assessment and efficacy evaluation of patients with ITP.


Assuntos
Hemorragia/complicações , Hemorragia/diagnóstico , Púrpura Trombocitopênica Idiopática/complicações , Feminino , Hemorragia/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Estudos Retrospectivos , Medição de Risco
5.
PLoS One ; 16(8): e0251216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34343182

RESUMO

BACKGROUND: Coagulation disorders are common in patients with hemophagocytic lymphohistiocytosis (HLH), associated with an increased risk of bleeding and death. We aim to investigate coagulation disorders and their outcome implications in critically ill patients with HLH. METHODS: We prospectively evaluated 47 critically ill patients with HLH (median age of 54 years [42-67]) between April 2015 and December 2018. Coagulation assessments were performed at day 1. Abnormal standard coagulation was defined as prothrombin time (PT) <50% and/or fibrinogen <2g/L. HLH aetiology was mostly ascribed to haematological malignancies (74% of patients). RESULTS: Coagulation disorders and severe bleeding events were frequent, occurring in 30 (64%) and 11 (23%) patients respectively. At day 1, median fibrinogen level was 2∙65g/L [1.61-5.66]. Fibrinolytic activity was high as suggested by increased median levels of D-dimers, fibrin monomers, PAI-1 (plasminogen activator inhibitor) and tPA (tissue plasminogen activator). Forty-one (91%) patients had a decreased ADAMTS13 activity (A Disintegrin-like And Metalloproteinase with ThromboSpondin type 1 repeats, member 13). By multivariable analysis, the occurrence of a severe bleeding (OR 3.215 [1.194-8.653], p = 0∙021) and SOFA score (Sepsis-Related Organ Failure Assessment) at day 1 (OR 1.305 per point [1.146-1.485], p<0∙001) were independently associated with hospital mortality. No early biological marker was associated with severe bleeding. CONCLUSIONS: Hyperfibrinolysis may be the primary mechanism responsible for hypofibrinogenemia and may also participate in ADAMTS13 degradation. Targeting the plasmin system appears as a promising approach in severe HLH-related coagulation disorders.


Assuntos
Transtornos da Coagulação Sanguínea , Hemorragia , Mortalidade Hospitalar , Linfo-Histiocitose Hemofagocítica , Proteína ADAMTS13/sangue , Adulto , Idoso , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/mortalidade , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , França/epidemiologia , Hemorragia/sangue , Hemorragia/etiologia , Hemorragia/mortalidade , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Estudos Prospectivos , Índice de Gravidade de Doença , Ativador de Plasminogênio Tecidual/sangue
6.
J Trauma Acute Care Surg ; 91(2): 344-351, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397955

RESUMO

BACKGROUND: Hemorrhage with trauma-induced coagulopathy (TIC) and hyperfibrinolysis (HF) increases the mortality risk after severe trauma. While TIC at hospital admission is well studied, little is known about coagulopathy at the incident site. The aim of the study was to investigate coagulation disorders already present on scene. METHODS: In a prospective single-center observational study, blood samples of trauma patients obtained before and at hospital admission were analyzed. Data on rotational thromboelastometry, blood gas analysis, prehospital treatment, injury severity, in-hospital blood transfusions, and mortality were investigated according to the presence of coagulation disorders at the incident site. The patients were divided into three groups according to the presence of coagulation disorders (no coagulopathy, TIC, TIC with HF). In a subgroup analysis, patients with a Trauma-Induced Coagulopathy Clinical Score (TICCS) of ≥10 were investigated. RESULTS: Between August 2015 and February 2018, 148 patients were enrolled in the study. The mean Injury Severity Score was 22.1, and overall mortality was 7.4%. Trauma-induced coagulopathy and HF were already detectable at the incident site in 18.2% and 6.1%, respectively. Patients with HF had significantly altered circulation parameters with significant changes in pH, hemoglobin, lactate, and base excess at the incident site. In patients with TICCS of ≥10 (14.2%), TIC was detected in 47.6% of the cases and HF in 28.6%. Furthermore, in these patients, blood gas parameters significantly changed and the need for blood transfusion and mortality. CONCLUSION: Trauma-induced coagulopathy and HF can be detected in severely injured patients even before medical treatment is started. Furthermore, in patients with HF and TICCS of ≥10, blood gas parameters were significantly changed at the incident site. LEVEL OF EVIDENCE: Prognostic study, level III.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Serviços Médicos de Emergência/métodos , Hemorragia/diagnóstico , Traumatismo Múltiplo/diagnóstico , Adulto , Idoso , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/terapia , Gasometria , Feminino , Hemorragia/sangue , Hemorragia/terapia , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/sangue , Traumatismo Múltiplo/terapia , Estudos Prospectivos , Tromboelastografia , Adulto Jovem
7.
Curr Opin Hematol ; 28(5): 315-322, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397591

RESUMO

PURPOSE OF REVIEW: To summarize the recent literature related to female hemophilia A carriers with respect to prevalence in the population, the impact of baseline factor VIII levels and other influences on bleeding phenotype, and clinical management needs. RECENT FINDINGS: Many female hemophilia A carriers are at risk for abnormal bleeding, yet they are underrecognized by healthcare providers and their bleeding symptoms are underreported. Low FVIII levels are consistently associated with clinically significant bleeding and correlate well with skewed X chromosome inactivation (XCI). Most interestingly, bleeding tendency is also observed in some hemophilia A carriers with normal factor VIII levels and requires further investigation. Well controlled studies investigating peripartum and periprocedural FVIII levels and adequate hemostatic treatment are necessary to inform management guidelines. SUMMARY: Prevalence and bleeding tendency of hemophilia A carriers remain underreported, despite a significant proportion having low FVIII levels. Skewed XCI may explain low FVIII but does not explain the bleeding risk encountered in a larger proportion of hemophilia A carriers with random XCI and borderline/normal FVIII.


Assuntos
Cromossomos Humanos X/genética , Fator VIII , Hemofilia A , Hemorragia , Heterozigoto , Fenótipo , Fator VIII/genética , Fator VIII/metabolismo , Feminino , Hemofilia A/sangue , Hemofilia A/genética , Hemorragia/sangue , Hemorragia/genética , Humanos
8.
Transfusion ; 61 Suppl 1: S243-S251, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269443

RESUMO

BACKGROUND: In traumatic bleeding, transfusion practice has shifted toward higher doses of platelets and plasma transfusion. The aim of this systematic review was to investigate whether a higher platelet-to-red blood cell (RBC) transfusion ratio improves mortality without worsening organ failure when compared with a lower ratio of platelet-to-RBC. METHODS: Pubmed, Medline, and Embase were screened for randomized controlled trials (RCTs) in bleeding trauma patients (age ≥16 years) receiving platelet transfusion between 1946 until October 2020. High platelet:RBC ratio was defined as being the highest ratio within an included study. Primary outcome was 24 hour mortality. Secondary outcomes were 30-day mortality, thromboembolic events, organ failure, and correction of coagulopathy. RESULTS: In total five RCTs (n = 1757 patients) were included. A high platelet:RBC compared with a low platelet:RBC ratio significantly improved 24 hour mortality (odds ratio [OR] 0.69 [0.53-0.89]) and 30- day mortality (OR 0.78 [0.63-0.98]). There was no difference between platelet:RBC ratio groups in thromboembolic events and organ failure. Correction of coagulopathy was reported in five studies, in which platelet dose had no impact on trauma-induced coagulopathy. CONCLUSIONS: In traumatic bleeding, a high platelet:RBC improves mortality as compared to low platelet:RBC ratio. The high platelet:RBC ratio does not influence thromboembolic or organ failure event rates.


Assuntos
Contagem de Eritrócitos , Hemorragia/sangue , Contagem de Plaquetas , Ferimentos e Lesões/sangue , Plaquetas/citologia , Eritrócitos/citologia , Hemorragia/mortalidade , Humanos , Ferimentos e Lesões/mortalidade
9.
Transfusion ; 61 Suppl 1: S252-S263, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269434

RESUMO

BACKGROUND: Multiple thresholds are defined to identify patients at risk of death from hemorrhage, including massive transfusion (MT), critical administration threshold (CAT), and resuscitation intensity (RI). All fail to account for the use of whole blood (WB). We hypothesized that a definition including WB transfusion would better predict early mortality following trauma. METHODS: This is a retrospective review of all trauma patients with activation of the MT protocol from December 2018 to February 2020. Combinations of WB, RBCs, and fresh frozen plasma (FFP) units transfused during the initial hour of resuscitation were compared using receiver operating characteristic and area under the receiver curve (AUC) for 3- and 6-h mortality. WB massive transfusion (WB MT) score was defined as the sum of each unit RBC plus three times each unit of WB transfused within the first hour of resuscitation. RESULTS: There were 235 patients eligible for analysis with 60 resuscitated using ≥1 unit of WB. Overall, 27 and 29 patients died in the first 3 and 6 h, respectively. WB MT ≥7 had the greatest 3-h and 6-h mortality AUC values (0.78 and 0.79, respectively) when compared to MT, CAT, RI4+, and other attempted definitions using units of WB, RBC, and FFP. Compared to WB MT-, WB MT+ patients died at significantly higher rates at 3 h (28.9% vs. 3.1%, p < .001), 24 h (35.5% vs. 5.7%, p < .001), and 28 days (42.1% vs. 11.9%, p < .001). CONCLUSION: WB MT is the first measure of massive resuscitation to incorporate WB and better identifies early mortality than other definitions.


Assuntos
Transfusão de Sangue/métodos , Hemorragia/terapia , Ressuscitação/métodos , Ferimentos e Lesões/terapia , Adulto , Feminino , Hemorragia/sangue , Hemorragia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ferimentos e Lesões/sangue , Ferimentos e Lesões/mortalidade
10.
Transfusion ; 61 Suppl 1: S167-S173, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269439

RESUMO

INTRODUCTION: We conducted a prospective observational study on 205 trauma patients at a level I trauma facility to test the hypothesis that a compensatory reserve measurement (CRM) would identify higher risk for progression to shock and/or need a life-saving interventions (LSIs) earlier than systolic blood pressure (SBP) and blood lactate (LAC). METHODS: A composite outcome metric included blood transfusion, procedural LSI, and mortality. Discrete measures assessed as abnormal (ab) were SBP <90 mmHg, CRM <60%, and LAC >2.0. A graded categorization of shock was defined as: no shock (normal [n] SBP [n-SBP], n-CRM, n-LAC); sub-clinical shock (ab-CRM, n-SBP, n-LAC); occult shock (n-SBP, ab-CRM, ab-LAC); or overt shock (ab-SBP, ab-CRM, ab-LAC). RESULTS: Three patients displayed overt shock, 53 displayed sub-clinical shock, and 149 displayed no shock. After incorporating lactate into the analysis, 86 patients demonstrated no shock, 25 were classified as sub-clinical shock, 91 were classified as occult shock, and 3 were characterized as overt shock. Each shock subcategory revealed a graded increase requiring LSI and transfusion. Initial CRM was associated with progression to shock (odds ratio = 0.97; p < .001) at an earlier time than SBP or LAC. CONCLUSIONS: Initial CRM uncovers a clinically relevant subset of patients who are not detected by SBP and LAC. Our results suggest CRM could be used to more expeditiously identify injured patients likely to deteriorate to shock, with requirements for blood transfusion or procedural LSI.


Assuntos
Transfusão de Sangue , Hemorragia/terapia , Choque Hemorrágico/terapia , Ferimentos e Lesões/terapia , Pressão Sanguínea , Feminino , Hemorragia/sangue , Hemorragia/diagnóstico , Hemorragia/fisiopatologia , Humanos , Lactatos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Choque Hemorrágico/sangue , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/fisiopatologia , Triagem , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/fisiopatologia
11.
Transfusion ; 61 Suppl 1: S294-S300, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269448

RESUMO

Massive bleeding remains a major source of morbidity and mortality worldwide. Recent studies have shed light on the pathophysiology of traumatic-induced coagulopathy and the central role of endotheliopathy. Transfusion therapy has changed dramatically in the last decade with use of red cells and plasma in a 1:1 ratio. The use of early transfusion increases the likelihood of a favorable outcome. Early intervention-preferably less than 60 min of injury-is a major factor in improved survival. Experience with dried plasma products-lyophilized or freeze-dried-in Europe and South Africa has demonstrated both safety and efficacy. Dry plasma products are not available in the United States but several products are in development. Spray-dried plasma contains clinically meaningful levels of coagulation activity and in vitro data suggest robust ability to generate thrombus. The decentralized, blood-center based manufacturing model of spray-dried plasma offers advantages for availability to meet routine and extraordinary demands.


Assuntos
Transfusão de Componentes Sanguíneos/métodos , Preservação de Sangue , Hemorragia/terapia , Plasma , Ferimentos e Lesões/terapia , Preservação de Sangue/métodos , Hemorragia/sangue , Humanos , Plasma/química , Ressuscitação/métodos , Secagem por Atomização , Ferimentos e Lesões/sangue
12.
Transfusion ; 61 Suppl 1: S43-S48, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269453

RESUMO

BACKGROUND: Low-titer group O whole-blood (LTOWB) is being used for children with life-threatening traumatic bleeding. A survey was conducted to determine current LTOWB utilization and interest in participation in a randomized control trial (RCT) of LTOWB versus standard blood component transfusion in this population. STUDY DESIGN AND METHODS: Transfusion medicine (TM) directors and pediatric trauma directors at 36 US children's hospitals were surveyed by e-mail in June 2020. Hospitals were selected by participation in the Massive Transfusion Epidemiology and Outcomes in Children Study or being among the largest 30 children's hospitals by bed capacity per the Becker Hospital Review. RESULTS: The response rate was 83.3% (30/36) from TM directors and 88.9% (32/36) from trauma directors. The median of massive transfusion protocol activations for traumatic bleeding was reported as 12 (IQR 5.8-20) per year by TM directors. LTOWB was used by 18.8% (6/32) of trauma directors. Survey responses indicate that 86.7% (26/30) of TM directors and 90.6% (29/32) of trauma directors either moderately or strongly agree that a LTOWB RCT is important to perform. About 83.3% (25/30) of TM directors and 93.8% (30/32) of trauma directors were willing to participate in the proposed trial. About 80% (24/30) of TM directors and 71.9% (23/32) of trauma directors would transfuse RhD+ LTOWB to male children, but fewer would transfuse Rh + LTOWB to females [20% (6/30) TM directors and 37.5% (12/32) of trauma directors]. CONCLUSIONS: A majority of respondents supported an RCT comparing LTOWB to component therapy in children with severe traumatic bleeding.


Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Transfusão de Componentes Sanguíneos , Hemorragia/terapia , Ferimentos e Lesões/terapia , Transfusão de Componentes Sanguíneos/métodos , Criança , Pré-Escolar , Feminino , Hemorragia/sangue , Humanos , Lactente , Masculino , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Ressuscitação/métodos , Inquéritos e Questionários , Ferimentos e Lesões/sangue
13.
Transfusion ; 61 Suppl 1: S2-S7, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269463

RESUMO

BACKGROUND: Whole blood therapy-which contains the ideal balance of components, and particularly fresh whole blood-has been shown to be beneficial in adult trauma. It remains unclear whether there is potential benefit in the pediatric population. STUDY DESIGN AND METHODS: This is a secondary analysis of previously published data analyzing pediatric casualties undergoing massive transfusion in the Department of Defense Trauma Registry. Pediatric patients with traumatic injury who were transfused at least one blood product were included in the analysis. We compared children who received component therapy exclusively to those who received any amount of warm fresh whole blood. RESULTS: Of the 3439 pediatric casualties within our dataset, 1244 were transfused at least one blood product within the first 24 h. There were 848 patients without severe head injury. Within this cohort, 23 children received warm fresh whole blood overall, 20 of whom did not have severe head injury. In an adjusted analysis, the odds ratio (95% confidence interval [CI]) for survival for warm fresh whole blood recipients was 2.86 (0.40-20.45). After removing children with severe brain injury, there was an independent association with improved survival for warm fresh whole blood recipients with an odds ratio (95% CI) of 58.63 (2.70-1272.67). DISCUSSION: Our data suggest that warm fresh whole blood may be associated with improved survival in children without severe head injury. Larger prospective studies are needed to assess the efficacy and safety of whole blood in children with severe traumatic bleeding.


Assuntos
Transfusão de Sangue , Ferimentos e Lesões/terapia , Adolescente , Afeganistão/epidemiologia , Criança , Pré-Escolar , Feminino , Hemorragia/sangue , Hemorragia/epidemiologia , Hemorragia/terapia , Humanos , Lactente , Iraque/epidemiologia , Masculino , Análise de Sobrevida , Resultado do Tratamento , Ferimentos e Lesões/sangue , Ferimentos e Lesões/epidemiologia
14.
Curr Opin Hematol ; 28(5): 331-338, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34267078

RESUMO

PURPOSE OF REVIEW: Management of isolated distal deep vein thrombosis (IDDVT) remains controversial. We summarize recent studies regarding the natural history of IDDVT as well as pertinent therapeutic trials. We also provide our management approach. RECENT FINDINGS: IDDVT is more commonly associated with transient risk factors and less often associated with permanent, unmodifiable risk factors than proximal DVT. IDDVT has a significantly lower risk of proximal extension and recurrence than proximal DVT. Cancer-associated IDDVT has a similar natural history to cancer-associated proximal DVT, with substantially less favourable outcomes than noncancer-associated IDDVT. Anticoagulant treatment reduces the risk of proximal extension and recurrence in IDDVT at the cost of increased bleeding risk. Intermediate dosing of anticoagulation may be effective for treating noncancer-associated IDDVT in patients without prior DVT. SUMMARY: IDDVT with a transient risk factor can be treated for 6 weeks in patients without a prior DVT. Unprovoked IDDVT in patients without malignancy can be treated for 3 months. Outpatients without malignancy or a prior DVT can be left untreated and undergo surveillance compression ultrasound in one week to detect proximal extension, but few patients opt for this in practice. Cancer-associated IDDVT should be treated analogously to cancer-associated proximal DVT.


Assuntos
Anticoagulantes/uso terapêutico , Neoplasias/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Anticoagulantes/efeitos adversos , Hemorragia/sangue , Hemorragia/induzido quimicamente , Humanos , Neoplasias/complicações , Fatores de Risco , Trombose Venosa/sangue , Trombose Venosa/etiologia
15.
Am J Hematol ; 96(10): 1331-1337, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197664

RESUMO

Viscoelastic hemostatic assays (VHA) are point of care tests that allow for a global assessment of coagulation using whole blood. The technology to allow this assessment has evolved from the original thromboelastography (TEG, Haemonetic, Boston, MA) to now include thromboelastometry (ROTEM, Instrumentation Laboratory, Bedford, MA), and, most recently, the Quantra Hemostasis Analyzer (Hemosonics, Charlottesville, VA). Diagnosis and treatment algorithms incorporating viscoelastic hemostatic tests for bleeding patients in a variety of clinical situations have now been developed. The original ROTEM and TEG technologies have been updated with emphasis placed on a cartridge-based technologies. Results from the new devices show good correlation with those from the previous versions of the devices, while cartridge-based technology has increased device stability and enhanced portability to the bedside. In this article, we will review recent advances in TEG and ROTEM technology and introduce the Quantra Hemostasis Analyzer device.


Assuntos
Hemostasia , Tromboelastografia/métodos , Animais , Coagulação Sanguínea , Desenho de Equipamento , Hemorragia/sangue , Humanos , Tromboelastografia/instrumentação
16.
J Trauma Acute Care Surg ; 91(4): 655-662, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34225348

RESUMO

BACKGROUND: This pilot assessed transfusion requirements during resuscitation with whole blood followed by standard component therapy (CT) versus CT alone, during a change in practice at a large urban Level I trauma center. METHODS: This was a single-center prospective cohort pilot study. Male trauma patients received up to 4 units of cold-stored low anti-A, anti-B group O whole blood (LTOWB) as initial resuscitation followed by CT as needed (LTOWB + CT). A control group consisting of women and men who presented when LTOWB was unavailable, received CT only (CT group). Exclusion criteria included antiplatelet or anticoagulant medication and death within 24 hours. The primary outcome was total transfusion volume at 24 hours. Secondary outcomes were mortality, morbidity, and intensive care unit- and hospital-free days. RESULTS: Thirty-eight patients received LTOWB, with a median of 2.0 (interquartile range [IQR] 1.0-3.0) units of LTOWB transfused. Thirty-two patients received CT only. At 24 hours after presentation, the LTOWB +CT group had received a median of 2,138 mL (IQR, 1,275-3,325 mL) of all blood products. The median for the CT group was 4,225 mL (IQR, 1,900-5,425 mL; p = 0.06) in unadjusted analysis. When adjusted for Injury Severity Score, sex, and positive Focused Assessment with Sonography for Trauma, LTOWB +CT group patients received 3307 mL of blood products, and CT group patients received 3,260 mL in the first 24 hours (p = 0.95). The adjusted median ratio of plasma to red cells transfused was higher in the LTOWB + CT group (0.85 vs. 0.63 at 24 hours after admission; p = 0.043. Adjusted mortality was 4.4% in the LTOWB + CT group, and 11.7% in the CT group (p = 0.19), with similar complications, intensive care unit-, and hospital-free days in both groups. CONCLUSION: Beginning resuscitation with LTOWB results in equivalent outcomes compared with resuscitation with CT only. LEVEL OF EVIDENCE: Therapeutic (Prospective study with 1 negative criterion, limited control of confounding factors), level III.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Transfusão de Sangue/métodos , Hemorragia/terapia , Ressuscitação/métodos , Ferimentos e Lesões/terapia , Adulto , Feminino , Hemorragia/sangue , Hemorragia/etiologia , Hemorragia/mortalidade , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Ressuscitação/efeitos adversos , Reação Transfusional/sangue , Reação Transfusional/epidemiologia , Reação Transfusional/prevenção & controle , Centros de Traumatologia/estatística & dados numéricos , Resultado do Tratamento , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações , Ferimentos e Lesões/mortalidade , Adulto Jovem
17.
PLoS One ; 16(7): e0255413, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34329360

RESUMO

BACKGROUND: During hematopoietic stem cell transplantation (HSCT) the patients perform activities of low and moderate intensity because have reduced hematological lineages, leaving them susceptible to hemorrhagic events. The objective of this study was to describe the frequency of bleeding events, severity, and possible association with physical exercise in thrombocytopenic patients. METHODS: A retrospective study with seventy-seven HSCT patients hospitalised, that had a platelet count ≤ 50,000 /µL and received physical exercise during physiotherapy intervention. RESULTS: Regarding bleeding events, only six were related to physical exercise, and bleeding events occurred more frequently at platelet levels ≤ 10,000 /µL. The most frequent bleeding event was epistaxis, considered of low severity, and with the moderate possibility of being related to physical exercise; followed by extremity hematoma, considered of medium severity and highly related to physical exercise. In this study, there was no occurrence of bleeding events considered of high severity. CONCLUSION: Bleeding frequency in supervised physical exercise during physiotherapy in adults with thrombocytopenia undergoing HSCT is minor and relatively rare but occurs more frequently in patients with platelet count ≤10,000 /µL. These results encourage the maintenance of physical activity in this population who is at high risk of developing immobility-related complications.


Assuntos
Terapia por Exercício , Transplante de Células-Tronco Hematopoéticas , Hemorragia , Adulto , Idoso , Aloenxertos , Feminino , Hemorragia/sangue , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Trombocitopenia/sangue , Trombocitopenia/terapia
18.
J Am Coll Cardiol ; 77(24): 2987-3001, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34140101

RESUMO

BACKGROUND: Direct oral anticoagulants (DOACs) have shown a positive benefit-risk balance in both clinical trials and real-world data, but approximately 2% to 3.5% of patients experience major bleeding annually. Many of these patients require hospitalization, and the administration of reversal agents may be required to control bleeding. OBJECTIVES: The aim of this study was to investigate clinical outcomes associated with the use of 4-factor prothrombin complex concentrates, idarucizumab, or andexanet for reversal of severe DOAC-associated bleeding. METHODS: The investigators systematically searched for studies of reversal agents for the treatment of severe bleeding associated with DOAC. Mortality rates, thromboembolic events, and hemostatic efficacy were meta-analyzed using a random effects model. RESULTS: The investigators evaluated 60 studies in 4,735 patients with severe DOAC-related bleeding who were treated with 4-factor prothrombin complex concentrates (n = 2,688), idarucizumab (n = 1,111), or andexanet (n = 936). The mortality rate was 17.7% (95% confidence interval [CI]: 15.1% to 20.4%), and it was higher in patients with intracranial bleedings (20.2%) than in patients with extracranial hemorrhages (15.4%). The thromboembolism rate was 4.6% (95% CI: 3.3% to 6.0%), being particularly high with andexanet (10.7%; 95% CI: 6.5% to 15.7%). The effective hemostasis rate was 78.5% (95% CI: 75.1% to 81.8%) and was similar regardless of the reversal agent considered. The rebleeding rate was 13.2% (95% CI: 5.5% to 23.1%) and 78% of rebleeds occurred after resumption of anticoagulation. The risk of death was markedly and significantly associated with failure to achieve effective hemostasis (relative risk: 3.63; 95% CI: 2.56 to 5.16). The results were robust regardless of the type of study or the hemostatic scale used. CONCLUSIONS: The risk of death after severe DOAC-related bleeding remains significant despite a high rate of effective hemostasis with reversal agents. Failure to achieve effective hemostasis strongly correlated with a fatal outcome. Thromboembolism rates are particularly high with andexanet. Comparative clinical trials are needed.


Assuntos
Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Hemostasia/efeitos dos fármacos , Administração Oral , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/administração & dosagem , Coagulação Sanguínea/fisiologia , Fatores de Coagulação Sanguínea/farmacologia , Fatores de Coagulação Sanguínea/uso terapêutico , Fator Xa/farmacologia , Fator Xa/uso terapêutico , Hemorragia/sangue , Hemostasia/fisiologia , Humanos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos
19.
Int J Hematol ; 114(3): 325-333, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34117991

RESUMO

INTRODUCTION: We identified a patient with a novel heterozygous variant fibrinogen, γp.C352R (Niigata II; N-II), who had a bleeding episode and failed infertility treatment and was suspected to have hypodysfibrinogenemia based on low and discordant fibrinogen levels (functional assay 0.33 g/L, immunological assay 0.91 g/L). We analyzed the mechanism of this rare phenotype of a congenital fibrinogen disorder. MATERIALS AND METHODS: Patient plasma fibrinogen was purified and protein characterization and thrombin-catalyzed fibrin polymerization performed. Recombinant fibrinogen-producing Chinese hamster ovary (CHO) cells were established and the assembly and secretion of variant fibrinogen analyzed by ELISA and western blotting. RESULTS: Purified N-II plasma fibrinogen had a small lower molecular weight band below the normal γ-chain and slightly reduced fibrin polymerization. A limited proportion of p.C352R fibrinogen was secreted into the culture medium of established CHO cell lines, but the γ-chain of p.C352R was synthesized and variant fibrinogen was assembled inside the cells. CONCLUSION: We demonstrated that fibrinogen N-II, γp.C352R was associated with markedly reduced secretion of variant fibrinogen from CHO cells, that fibrin polymerization of purified plasma fibrinogen was only slightly affected, and that fibrinogen N-II produces hypodysfibrinogenemia in plasma.


Assuntos
Afibrinogenemia/genética , Alelos , Fibrinogênio/genética , Hemorragia/sangue , Hemorragia/etiologia , Infertilidade/etiologia , Mutação , Afibrinogenemia/sangue , Afibrinogenemia/complicações , Substituição de Aminoácidos , Animais , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Células CHO , Catálise , Cricetulus , Fibrina/metabolismo , Hemorragia/diagnóstico , Humanos , Infertilidade/diagnóstico , Infertilidade/terapia , Polimerização , Trombina/metabolismo
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