Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 149
Filtrar
2.
Artigo em Inglês | MEDLINE | ID: mdl-35393385

RESUMO

BACKGROUND: Growing evidence supports improved survival with prehospital blood products. Recent trials show a benefit of prehospital tranexamic acid (TXA) administration in select subgroups. Our objective was to determine if receiving prehospital packed red blood cells (pRBC) in addition to TXA improved survival in injured patients at risk of hemorrhage. METHODS: We performed a secondary analysis of all scene patients from the STAAMP trial. Patients were randomized to prehospital TXA or placebo. Some participating EMS services utilized pRBC. Four resuscitation groups resulted: TXA, pRBC, pRBC+TXA, and neither. Our primary outcome was 30-day mortality and secondary outcome was 24-hour mortality. Cox regression tested the association between resuscitation group and mortality while adjusting for confounders. RESULTS: A total of 763 patients were included. Patients receiving prehospital blood had higher injury severity scores in the pRBC (22 [10, 34]) and pRBC+TXA (22 [17, 36]) groups than the TXA (12 [5, 21]) and neither (10 [4, 20]) groups (p < 0.01). Mortality at 30 days was greatest in the pRBC+TXA and pRBC groups at 18.2% and 28.6% compared to the TXA only and neither groups at 6.6% and 7.4% respectively. Resuscitation with pRBC+TXA was associated with a 35% reduction in relative hazards of 30-day mortality compared to neither (HR 0.65; 95%CI 0.45-0.94, p = 0.02). No survival benefit was observed in 24-hour mortality for pRBC+TXA, but pRBC alone was associated with a 61% reduction in relative hazards of 24 h mortality compared to neither (HR 0.39; 95%CI 0.17-0.88, p = 0.02). CONCLUSIONS: For injured patients at risk of hemorrhage, prehospital pRBC+TXA is associated with reduced 30-day mortality. Use of pRBC transfusion alone was associated with a reduction in early mortality. Potential synergy appeared only in longer term mortality and further work to investigate mechanisms of this therapeutic benefit is needed to optimize the prehospital resuscitation of trauma patients. LEVEL OF EVIDENCE: Therapeutic, Level III.

3.
BMJ Open ; 12(4): e053590, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365520

RESUMO

OBJECTIVES: To develop and validate tests to assess the risk of any cancer for patients referred to the NHS Urgent Suspected Cancer (2-week wait, 2WW) clinical pathways. SETTING: Primary and secondary care, one participating regional centre. PARTICIPANTS: Retrospective analysis of data from 371 799 consecutive 2WW referrals in the Leeds region from 2011 to 2019. The development cohort was composed of 224 669 consecutive patients with an urgent suspected cancer referral in Leeds between January 2011 and December 2016. The diagnostic algorithms developed were then externally validated on a similar consecutive sample of 147 130 patients (between January 2017 and December 2019). All such patients over the age of 18 with a minimum set of blood counts and biochemistry measurements available were included in the cohort. PRIMARY AND SECONDARY OUTCOME MEASURES: sensitivity, specificity, negative predictive value, positive predictive value, Receiver Operating Characteristic (ROC) curve Area Under Curve (AUC), calibration curves RESULTS: We present results for two clinical use-cases. In use-case 1, the algorithms identify 20% of patients who do not have cancer and may not need an urgent 2WW referral. In use-case 2, they identify 90% of cancer cases with a high probability of cancer that could be prioritised for review. CONCLUSIONS: Combining a panel of widely available blood markers produces effective blood tests for cancer for NHS 2WW patients. The tests are affordable, and can be deployed rapidly to any NHS pathology laboratory with no additional hardware requirements.


Assuntos
Aprendizado de Máquina , Neoplasias , Adulto , Algoritmos , Humanos , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Atenção Primária à Saúde , Encaminhamento e Consulta , Estudos Retrospectivos
4.
Artigo em Inglês | MEDLINE | ID: mdl-35444156

RESUMO

INTRODUCTION: Posttraumatic venous thromboembolism (VTE) remains prevalent in severely injured patients despite chemoprophylaxis. Importantly, although platelets are central to thrombosis, they are not routinely targeted in prevention of posttraumatic VTE. Further, platelets from injured patients show ex-vivo evidence of increased activation yet impaired aggregation, consistent with functional exhaustion. However, the relationship of this platelet functional phenotype with development of posttraumatic VTE is unknown. We hypothesized that following injury impaired ex-vivo platelet aggregation (PA) is associated with the development of posttraumatic VTE. METHODS: We performed a secondary analysis of 133 severely injured patients from a prospective observational study investigating coagulation and inflammation (2011-2019). PA in response to stimulation with adenosine diphosphate (ADP), collagen, and thrombin was measured at presentation (pre-resuscitation) and 24 h (post-resuscitation). Viscoelastic clot strength and lysis were measured in parallel by thromboelastography. Multivariable regression examined relationships between PA at presentation, 24 h, and the delta between presentation and 24 h with development of VTE. RESULTS: The 133 patients were severely injured (median injury severity score 25) and 14% developed VTE (all >48 hours after admission). At presentation, platelet count and PA were not significantly different between those with and without incident VTE. However, at 24 h, those who subsequently developed VTE had significantly lower platelet counts (126 x109/L vs 164 x109/L, p = 0.01), and lower PA in response to ADP (p < 0.05), collagen (p < 0.05), and thrombin (p = 0.06). Importantly, the magnitude of decrease in PA (Delta) from presentation to 24 h was independently associated with development of VTE (adjusted odds ratios per 10 aggregation unit decrease: Delta-ADP 1.31, p = 0.03; Delta-collagen 1.36, p = 0.01, Delta-thrombin 1.41, p < 0.01). CONCLUSION: Severely injured patients with decreasing ex-vivo measures of platelet aggregation despite resuscitation have an increased risk of developing VTE. This may have implications for predicting development of VTE and for studying platelet targeted chemoprophylaxis regimens. LEVEL OF EVIDENCE: level III, prognostic.

5.
JAMA ; 327(13): 1247-1259, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35315874

RESUMO

Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Interventions: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Results: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). Conclusions and Relevance: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.


Assuntos
COVID-19 , Estado Terminal , Inibidores da Agregação Plaquetária , Tromboembolia Venosa , Adulto , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Teorema de Bayes , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/mortalidade , COVID-19/terapia , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Respiração Artificial , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia
6.
J Clin Invest ; 132(10)2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35358095

RESUMO

Ischemic stroke prompts a strong inflammatory response, which is associated with exacerbated outcomes. In this study, we investigated mechanistic regulators of neutrophil extracellular trap (NET) formation in stroke and whether they contribute to stroke outcomes. NET-forming neutrophils were found throughout brain tissue of ischemic stroke patients, and elevated plasma NET biomarkers correlated with worse stroke outcomes. Additionally, we observed increased plasma and platelet surface-expressed high-mobility group box 1 (HMGB1) in stroke patients. Mechanistically, platelets were identified as the critical source of HMGB1 that caused NETs in the acute phase of stroke. Depletion of platelets or platelet-specific knockout of HMGB1 significantly reduced plasma HMGB1 and NET levels after stroke, and greatly improved stroke outcomes. We subsequently investigated the therapeutic potential of neonatal NET-inhibitory factor (nNIF) in stroke. Mice treated with nNIF had smaller brain infarcts, improved long-term neurological and motor function, and enhanced survival after stroke. nNIF specifically blocked NET formation without affecting neutrophil recruitment after stroke. Importantly, nNIF also improved stroke outcomes in diabetic and aged mice and was still effective when given 1 hour after stroke onset. These results support a pathological role for NETs in ischemic stroke and warrant further investigation of nNIF for stroke therapy.

7.
J Am Coll Surg ; 234(1): 86-94, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35213466

RESUMO

BACKGROUND: Severely injured patients are at particularly high risk for venous thromboembolism (VTE). Although thromboprophylaxis (PPX) is employed during the inpatient period, patients may continue to be at high risk after discharge. Comparative evidence from surgical subspecialities (eg oncology) reveals benefits of postdischarge (ie extended) PPX. We hypothesized that an extended, postinjury oral thromboprophylaxis regimen would be cost-effective. STUDY DESIGN: A cost-utility model compared no PPX with a 30-day course of apixaban, dabigatran, enoxaparin, fondaparinux, or rivaroxaban in trauma patients. Immediate events including deep venous thrombosis, pulmonary embolus, or bleeding within 30 days of injury were modeled in a decision tree with patients entering a Markov process to account for sequelae of VTE, including postthrombotic syndrome and chronic thromboembolic pulmonary hypertension. Effectiveness was measured in quality-adjusted life years. One-way and probabilistic sensitivity analyses were performed to identify conditions under which the preferred PPX strategy changed. RESULTS: Rivaroxaban was the dominant strategy (ie less costly and more effective) compared with no PPX or alternative regimens, delivering 30.21 quality-adjusted life years for $404,546.38. One-way sensitivity analyses demonstrated robust preference for rivaroxaban. When examining only patients with moderate-high or high VTE Risk Assessment Profile scores, rivaroxaban remained the preferred strategy. Probabilistic sensitivity analysis demonstrated a preference for rivaroxaban in 100% of cases at a standard willingness-to-pay threshold of $100,000/quality-adjusted life year. CONCLUSIONS: A 30-day course of rivaroxaban is a cost-effective extended thromboprophylaxis strategy in trauma patients in this theoretical study. Prospective studies of postdischarge thromboprophylaxis to prevent postinjury VTE are warranted.


Assuntos
Tromboembolia Venosa , Assistência ao Convalescente , Anticoagulantes/uso terapêutico , Análise Custo-Benefício , Humanos , Alta do Paciente , Estudos Prospectivos , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
8.
J Clin Med ; 11(3)2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35160311

RESUMO

Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy.

10.
J Trauma Acute Care Surg ; 92(5): 839-847, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35081595

RESUMO

INTRODUCTION: Low titer group O whole blood (LTOWB) resuscitation is increasingly common in both military and civilian settings. Data regarding the safety and efficacy of prehospital LTOWB remain limited. METHODS: We performed a single-center, prospective, cluster randomized, prehospital through in-hospital whole blood pilot trial for injured air medical patients. We compared standard prehospital air medical care including red cell transfusion and crystalloids followed by in-hospital component transfusion to prehospital and in-hospital LTOWB resuscitation. Prehospital vital signs were used as inclusion criteria (systolic blood pressure ≤90 mm Hg and heart rate ≥108 beats per minute or systolic blood pressure ≤70 mm Hg for patients at risk of hemorrhage). Primary outcome was feasibility. Secondary outcomes included 28-day and 24-hour mortality, multiple organ failure, nosocomial infection, 24-hour transfusion requirements, and arrival coagulation parameters. RESULTS: Between November 2018 and October 2020, 86 injured patients were cluster randomized by helicopter base. The trial has halted early at 77% enrollment. Overall, 28-day mortality for the cohort was 26%. Injured patients randomized to prehospital LTOWB (n = 40) relative to standard care (n = 46) were similar in demographics and injury characteristics. Intent-to-treat Kaplan-Meier survival analysis demonstrated no statistical mortality benefit at 28 days (25.0% vs. 26.1%, p = 0.85). Patients randomized to prehospital LTOWB relative to standard care had lower red cell transfusion requirements at 24 hours (p < 0.01) and a lower incidence of abnormal thromboelastographic measurements. No transfusion reactions during the prehospital or in-hospital phase of care were documented. CONCLUSION: Prehospital through in-hospital LTOWB resuscitation is safe and may be associated with hemostatic benefits. A large-scale clinical trial is feasible with protocol adjustment and would allow the effects of prehospital LTOWB on survival and other pertinent clinical outcomes to be appropriately characterized. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level II.


Assuntos
Serviços Médicos de Emergência , Ressuscitação , Sistema ABO de Grupos Sanguíneos , Transfusão de Sangue , Humanos , Projetos Piloto , Estudos Prospectivos , Ressuscitação/métodos
11.
Sci Transl Med ; 14(629): eabb8975, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-35080915

RESUMO

Treatment of bleeding disorders using transfusion of donor-derived platelets faces logistical challenges due to their limited availability, high risk of contamination, and short (5 to 7 days) shelf life. These challenges could be potentially addressed by designing platelet mimetics that emulate the adhesion, aggregation, and procoagulant functions of platelets. To this end, we created liposome-based platelet-mimicking procoagulant nanoparticles (PPNs) that can expose the phospholipid phosphatidylserine on their surface in response to plasmin. First, we tested PPNs in vitro using human plasma and demonstrated plasmin-triggered exposure of phosphatidylserine and the resultant assembly of coagulation factors on the PPN surface. We also showed that this phosphatidylserine exposed on the PPN surface could restore and enhance thrombin generation and fibrin formation in human plasma depleted of platelets. In human plasma and whole blood in vitro, PPNs improved fibrin stability and clot robustness in a fibrinolytic environment. We then tested PPNs in vivo in a mouse model of thrombocytopenia where treatment with PPNs reduced blood loss in a manner comparable to treatment with syngeneic platelets. Furthermore, in rat and mouse models of traumatic hemorrhage, treatment with PPNs substantially reduced bleeding and improved survival. No sign of systemic or off-target thrombotic risks was observed in the animal studies. These findings demonstrate the potential of PPNs as a platelet surrogate that should be further investigated for the management of bleeding.


Assuntos
Plaquetas , Nanopartículas , Animais , Hemorragia , Hemostasia/fisiologia , Camundongos , Modelos Animais , Ratos
12.
JAMA ; 327(3): 227-236, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040887

RESUMO

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/tratamento farmacológico , Heparina/administração & dosagem , Pacientes Internados , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , COVID-19/sangue , COVID-19/mortalidade , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Comorbidade , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Mortalidade Hospitalar , Humanos , Masculino , Futilidade Médica , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Oxigenoterapia/estatística & dados numéricos , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Receptores Purinérgicos P2Y12 , Respiração Artificial/estatística & dados numéricos , Trombose/epidemiologia , Ticagrelor/administração & dosagem , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
13.
J Clin Med ; 11(2)2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35054050

RESUMO

Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy-especially in austere or challenging environments-is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.

14.
J Trauma Acute Care Surg ; 92(1): 167-176, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34629458

RESUMO

BACKGROUND: Rapid platelet function testing is frequently used to determine platelet function in patients with traumatic intracranial hemorrhage (tICH). Accuracy and clinical significance of decreased platelet response detected by these tests is not well understood. We sought to determine whether VerifyNow and whole blood aggregometry (WBA) can detect poor platelet response and to elucidate its clinical significance for tICH patients. METHODS: We prospectively enrolled patients with isolated tICH between 2018 and 2020. Demographics, medical history, injury characteristics, and patient outcomes were recorded. Platelet function was determined by VerifyNow and WBA testing at the time of arrival to the trauma bay and 6 hours later. RESULTS: A total of 221 patients were enrolled, including 111 patients on no antiplatelet medication, 78 on aspirin, 6 on clopidogrel, and 26 on aspirin and clopidogrel. In the trauma bay, 29.7% and 67.7% of patients on no antiplatelet medication had poor platelet response on VerifyNow and WBA, respectively. Among patients on aspirin, 72.2% and 82.2% had platelet dysfunction on VerifyNow and WBA. Among patients on clopidogrel, 67.9% and 88.9% had platelet dysfunction on VerifyNow and WBA. Patients with nonresponsive platelets had similar in-hospital mortality (3 [3.0%] vs. 6 [6.3%], p = 0.324), tICH progression (26 [27.1%] vs. 24 [26.1%], p = 0.877), intensive care unit admission rates (34 [34.3%] vs. 38 [40.0%), p = 0.415), and length of stay (3 [interquartile range, 2-8] vs. 3.2 [interquartile range, 2-7], p = 0.818) to those with responsive platelets. Platelet transfusion did not improve platelet response or patient outcomes. CONCLUSION: Rapid platelet function testing detects a highly prevalent poor platelet response among patients with tICH, irrespective of antiplatelet medication use. VerifyNow correlated fairly with whole blood aggregometry among patients with tICH and platelet responsiveness detectable by these tests did not correlate with clinical outcomes. In addition, our results suggest that platelet transfusion may not improve clinical outcomes in patients with tICH. LEVEL OF EVIDENCE: Diagnostic tests, level II.


Assuntos
Transtornos Plaquetários , Lesões Encefálicas Traumáticas , Hemorragia Intracraniana Traumática , Inibidores da Agregação Plaquetária , Testes de Função Plaquetária/métodos , Transfusão de Plaquetas , Idoso , Transtornos Plaquetários/diagnóstico , Transtornos Plaquetários/etiologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Hemorragia Intracraniana Traumática/sangue , Hemorragia Intracraniana Traumática/complicações , Hemorragia Intracraniana Traumática/mortalidade , Hemorragia Intracraniana Traumática/terapia , Tempo de Internação , Masculino , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/classificação , Inibidores da Agregação Plaquetária/uso terapêutico , Transfusão de Plaquetas/métodos , Transfusão de Plaquetas/estatística & dados numéricos , Centros de Traumatologia/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos/epidemiologia
15.
Blood Coagul Fibrinolysis ; 33(1): 14-24, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34889809

RESUMO

Acute kidney injury (AKI) is common after trauma, but contributory factors are incompletely understood. Increases in plasma von Willebrand Factor (vWF) with concurrent decreases in ADAMTS13 are associated with renal microvascular thrombosis in other disease states, but similar findings have not been shown in trauma. We hypothesized that molecular changes in circulating vWF and ADAMTS13 promote AKI following traumatic injury. VWF antigen, vWF multimer composition and ADAMTS13 levels were compared in plasma samples from 16 trauma patients with and without trauma-induced AKI, obtained from the Prehospital Air Medical Plasma (PAMPer) biorepository. Renal histopathology and function, vWF and ADAMTS13 levels were assessed in parallel in a murine model of polytrauma and haemorrhage. VWF antigen was higher in trauma patients when compared with healthy controls [314% (253-349) vs. 100% (87-117)] [median (IQR)], while ADAMTS13 activity was lower [36.0% (30.1-44.7) vs. 100.0% (83.1-121.0)]. Patients who developed AKI showed significantly higher levels of high molecular weight multimeric vWF at 72-h when compared with non-AKI counterparts [32.9% (30.4-35.3) vs. 27.8% (24.6-30.8)]. Murine plasma cystatin C and vWF were elevated postpolytrauma model in mice, with associated decreases in ADAMTS13, and immunohistologic analysis demonstrated renal injury with small vessel plugs positive for fibrinogen and vWF. Following traumatic injury, the vWF-ADAMTS13 axis shifted towards a prothrombotic state in both trauma patients and a murine model. We further demonstrated that vWF-containing, microangiopathic deposits were concurrently produced as the prothrombotic changes were sustained during the days following trauma, potentially contributing to AKI development.


Assuntos
Injúria Renal Aguda , Fator de von Willebrand , Proteína ADAMTS13 , Animais , Humanos , Rim , Camundongos , Peso Molecular , Plasma
16.
Platelets ; 33(1): 35-47, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34455908

RESUMO

Platelets are anucleate blood cells produced from megakaryocytes predominantly in the bone marrow and released into blood circulation at a healthy count of 150,000-400,00 per µL and circulation lifespan of 7-9 days. Platelets are the first responders at the site of vascular injury and bleeding, and participate in clot formation via injury site-specific primary mechanisms of adhesion, activation and aggregation to form a platelet plug, as well as secondary mechanisms of augmenting coagulation via thrombin amplification and fibrin generation. Platelets also secrete various granule contents that enhance these mechanisms for clot growth and stability. The resultant clot seals the injury site to stanch bleeding, a process termed as hemostasis. Due to this critical role, a reduction in platelet count or dysregulation in platelet function is associated with bleeding risks and hemorrhagic complications. These scenarios are often treated by prophylactic or emergency transfusion of platelets. However, platelet transfusions face significant challenges due to limited donor availability, difficult portability and storage, high bacterial contamination risks, and very short shelf life (~5-7 days). These are currently being addressed by a robust volume of research involving reduced temperature storage and pathogen reduction processes on donor platelets to improve shelf-life and reduce contamination, as well as bioreactor-based approaches to generate donor-independent platelets from stem cells in vitro. In parallel, a complementary research field has emerged that involves the design of artificial platelets utilizing biosynthetic particle constructs that functionally emulate various hemostatic mechanisms of platelets. Here, we provide a comprehensive review of the history and the current state-of-the-art artificial platelet approaches, along with discussing the translational opportunities and challenges.


Assuntos
Plaquetas/metabolismo , Transfusão de Plaquetas/métodos , Humanos
17.
Ann Am Thorac Soc ; 19(4): 625-632, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34644242

RESUMO

Rationale: Extremity threat and amputation after sepsis is a well-publicized and devastating event. However, there is a paucity of data about the epidemiology of extremity threat after sepsis onset. Objectives: To estimate the incidence of extremity threat with or without surgical amputation in community sepsis. Methods: Retrospective cohort study of adults with Sepsis-3 hospitalized at 14 academic and community sites from 2013 to 2017. Vasopressor-dependent sepsis was identified by administration of epinephrine, norepinephrine, phenylephrine, vasopressin, or dopamine for more than 1 hour during the 48 hours before to 24 hours after sepsis onset. Outcomes included the incidence of extremity threat, defined as acute onset ischemia, with or without amputation, in the 90 days after sepsis onset. The association between extremity threat, demographics, comorbid conditions, and time-varying sepsis treatments was evaluated using a Cox proportional hazards model. Results: Among 24,365 adults with sepsis, 12,060 (54%) were vasopressor dependent (mean ± standard deviation age, 64 ± 16 years; male, 6,548 [54%]; sequential organ failure assessment [SOFA], 10 ± 4). Of these, 231 (2%) patients had a threatened extremity with 26 undergoing 37 amputations, a risk of 2.2 (95% confidence interval [CI], 1.4-3.2) per 1,000, and 205 not undergoing amputation, a risk of 17.0 (95% CI, 14.8-19.5) per 1,000. Most amputations occurred in lower extremities (95%), a median (interquartile range) of 16 (6-40) days after sepsis onset. Compared with patients with no extremity threat, patients with threat had a higher SOFA score (11 ± 4 vs. 10 ± 4; P < 0.001), serum lactate (4.6 mmol/L [2.4-8.7] vs. 3.1 [1.7-6.0]; P < 0.001), and more bacteremia (n = 37 [37%] vs. n = 2,087 [26%]; P < 0.001) at sepsis onset. Peripheral vascular disease, congestive heart failure, SOFA score, and norepinephrine equivalents were significantly associated with extremity threat. Conclusions: The evaluation of a threatened extremity resulting in surgical amputation occurred in 2 per 1,000 patients with vasopressor-dependent sepsis.


Assuntos
Amputação , Sepse , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sepse/epidemiologia , Resultado do Tratamento
18.
Platelets ; 33(4): 520-530, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34369848

RESUMO

We carried out a literature search in MEDLINE (PubMed) and EMBASE literature databases to provide a concise review of the role of viscoelastic testing in assessing peri-interventional platelet function and coagulation. The search identified 130 articles that were relevant for the review, covering the basic science of VHA and VHA in clinical settings including cardiac surgery, cardiology, neurology, trauma, non-cardiac surgery, obstetrics, liver disease, and COVID-19. Evidence from these articles is used to describe the important role of VHAs and platelet function testing in various peri-interventional setups. VHAs can help us to comprehensively assess the contribution of platelets and coagulation dynamics to clotting at the site-of-care much faster than standard laboratory measures. In addition to standard coagulation tests, VHAs are beneficial in reducing allogeneic transfusion requirements and bleeding, in predicting ischemic events, and improving outcomes in several peri-interventional care settings. Further focused studies are needed to confirm their utility in the peri-interventional case.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Hemostasia , Humanos , Tromboelastografia
19.
J Leukoc Biol ; 111(1): 93-111, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34533241

RESUMO

Traumatic injury is a major cause of morbidity and mortality worldwide, despite significant advances in treatments. Most deaths occur either very early, through massive head trauma/CNS injury or exsanguination (despite advances in transfusion medicine), or later after injury often through multiple organ failure and secondary infection. Extracellular vesicles (EVs) are known to increase in the circulation after trauma and have been used to limited extent as diagnostic and prognostic markers. More intriguingly, EVs are now being investigated as both causes of pathologies post trauma, such as trauma-induced coagulopathy, and as potential treatments. In this review, we highlight what is currently known about the role and effects of EVs in various aspects of trauma, as well as exploring current literature from investigators who have begun to use EVs therapeutically to alter the physiology and pathology of traumatic insults. The potential effectiveness of using EVs therapeutically in trauma is supported by a large number of experimental studies, but there is still some way to go before we understand the complex effects of EVs in what is already a complex disease process.


Assuntos
Vesículas Extracelulares , Ferimentos e Lesões , Animais , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Vesículas Extracelulares/transplante , Hemostasia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/terapia , Trombose/metabolismo , Trombose/patologia , Trombose/terapia , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/patologia , Ferimentos e Lesões/terapia
20.
Curr Pathobiol Rep ; : 1-11, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34900401

RESUMO

PURPOSE OF REVIEW: COVID-19 has rapidly evolved into a global pandemic infecting over two hundred and forty-four million individuals to date. In addition to the respiratory sequelae and systemic infection that ensues, an alarming number of micro and macrovascular thrombotic complications have been observed. This review examines the current understanding of COVID-19-associated thrombotic complications, potential mechanisms, and pathobiological basis for thromboses development. RECENT FINDINGS: The endothelium plays a major role in the process due to direct and indirect injury. The immune system also contributes to a pro-thrombotic environment with immune cell dysregulation leading to excessive formation of cytokines, also called cytokine storm, and an eventual promotion of a hypercoagulable environment, known as immunothrombosis. Additionally, neutrophils play an important role by forming neutrophil extracellular traps, which are shown to be pro-thrombotic and further enhanced in COVID-19 patients. A disruption of the fibrinolysis system has also been observed. SUMMARY: Multiple pathways likely contribute synergistically to form a pro-thrombotic milieu. A better understanding of these factors and the complex interplay between them will lead to the improvement of diagnostic and therapeutic interventions.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...