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1.
Blood Coagul Fibrinolysis ; 32(1): 44-49, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33417336

RESUMO

There is an increasing evidence supporting the existence of coagulopathy in coronavirus disease 2019 (COVID-19) patients. Most of reports are mainly focused on d-dimer. Our objective is to describe coagulation parameters in these patients that could be involved in a hypercoagulate state and to test platelet function to see if there are short closure times. We analyzed coagulation samples from 80 patients admitted with COVID-19 in our hospital. We also tested platelet function by closure times in a small subgroup of patients. Most of samples had increased d-dimer (96.2%) (median of d-dimer: 1158 ng/ml FEU), increased fibrinogen (75.2%) (median: 5.23 g/l), increased factor VIII (86%) (median: 264.8 U/dl), decreased protein S (22.5% of women, 62.5% of men) (median: 62.8 and 68.5 U/dl, respectively), decreased protein C (7.6%) (median: 100 U/dl), decreased factor XII (25.3%) (median: 90.3 U/dl) and decreased antithrombin activity (21%) (median: 86 U/dl). International normalized ratio was higher than normal in 24 patients (30%) (median: 1.13). The activated partial thromboplastin time ratio was below the normal range in nine patients (11.2%) and above normal in three (3.75%) (median: 0.93). The closure times were short in the 20% and 40% of samples of collagen and ADP and collagen and epinephrine, respectively. Twelve of the 80 patients (15%) had a thrombotic event and all had several abnormal coagulation parameters related with increased thrombotic risk. The results of this study support a hypercoagulability state in COVID-19 patients and it may help to explain the microvascular thrombosis caused by the inflammatory response.


Assuntos
Anticoagulantes/uso terapêutico , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/etiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/efeitos adversos , Testes de Função Plaquetária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias
2.
PLoS One ; 15(12): e0243604, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33320874

RESUMO

BACKGROUND: Coagulation abnormalities in COVID-19 patients have not been addressed in depth. OBJECTIVE: To perform a longitudinal evaluation of coagulation profile of patients admitted to the ICU with COVID-19. METHODS: Conventional coagulation tests, rotational thromboelastometry (ROTEM), platelet function, fibrinolysis, antithrombin, protein C and S were measured at days 0, 1, 3, 7 and 14. Based on median total maximum SOFA score, patients were divided in two groups: SOFA ≤ 10 and SOFA > 10. RESULTS: Thirty patients were studied. Some conventional coagulation tests, as aPTT, PT and INR remained unchanged during the study period, while alterations on others coagulation laboratory tests were detected. Fibrinogen levels were increased in both groups. ROTEM maximum clot firmness increased in both groups from Day 0 to Day 14. Moreover, ROTEM-FIBTEM maximum clot firmness was high in both groups, with a slight decrease from day 0 to day 14 in group SOFA ≤ 10 and a slight increase during the same period in group SOFA > 10. Fibrinolysis was low and decreased over time in all groups, with the most pronounced decrease observed in INTEM maximum lysis in group SOFA > 10. Also, D-dimer plasma levels were higher than normal reference range in both groups and free protein S plasma levels were low in both groups at baseline and increased over time, Finally, patients in group SOFA > 10 had lower plasminogen levels and Protein C ​​than patients with SOFA <10, which may represent less fibrinolysis activity during a state of hypercoagulability. CONCLUSION: COVID-19 patients have a pronounced hypercoagulability state, characterized by impaired endogenous anticoagulation and decreased fibrinolysis. The magnitude of coagulation abnormalities seems to correlate with the severity of organ dysfunction. The hypercoagulability state of COVID-19 patients was not only detected by ROTEM but it much more complex, where changes were observed on the fibrinolytic and endogenous anticoagulation system.


Assuntos
/sangue , Unidades de Terapia Intensiva , /patogenicidade , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/sangue , Testes de Coagulação Sanguínea , /virologia , Feminino , Fibrinólise/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária/métodos , Proteína C/metabolismo , Proteína S/metabolismo , Tromboelastografia/métodos
3.
J Clin Neurosci ; 78: 91-96, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32624366

RESUMO

Predicting the effectiveness of antiplatelet drugs is critical to precision antiplatelet therapy. However, there is a lack of an acceptable method, although there are a variety of methods for detecting platelet function. In this study, we compared three major platelet function tests to assess their performance and found better methods for platelet function evaluation after aspirin or clopidogrel treatment in ischemic stroke patients by comparative study. A total of 249 ischemic stroke patients were enrolled who were treated with aspirin or clopidogrel or both. Three platelet function tests including light transmittance aggregometry (LTA), thromboelastography (TEG), platelet function analyzer (PFA) were performed as well as CYP2C19 genotype determination. Correlation analyses and kappa statistics were used. All three methods were effective in evaluating aspirin function. However, only LTA and TEG had good correlation and consistency (r = -0.37, kappa = 0.634). TEG-ADP was the least sensitive for clopidogrel, as the platelet inhibition ratio did not differ between the clopidogrel-user group and the control (P = 0.074), while LTA and PFA were sensitive (P < 0.001). Correlations between platelet assays were poor for clopidogrel (the absolute value of r range from 0.13 to 0.35) and so was the agreement (Kappa from 0.232 to 0.314). LTA and PFA have a good correlation with CYP2C19 genotyping (P = 0.034 and 0.014). In conclusion, all three tests were able to evaluate aspirin effect, LTA-AA and TEG-AA had a good correlation. TEG perform badly for clopidogrel effect detection. The fair-to-modest agreement among assays indicated further study was indispensable.


Assuntos
Plaquetas/efeitos dos fármacos , Isquemia Encefálica/sangue , Inibidores da Agregação de Plaquetas/administração & dosagem , Acidente Vascular Cerebral/sangue , Tromboelastografia/normas , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Plaquetas/metabolismo , Isquemia Encefálica/tratamento farmacológico , Clopidogrel/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária/métodos , Testes de Função Plaquetária/normas , Acidente Vascular Cerebral/tratamento farmacológico , Tromboelastografia/efeitos dos fármacos , Tromboelastografia/métodos
4.
Clin Hemorheol Microcirc ; 76(1): 33-42, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32538826

RESUMO

BACKGROUND: Analysis of responsiveness to antiplatelet therapy is crucial in the management of patients with cardiovascular diseases. OBJECTIVE: This study aimed to evaluate a new platelet function analysis system (Anysis-200) and to compare it with VerifyNow (Accumetrics, San Diego, CA, USA) in cardiology patients. METHODS: Overall, 125 citrated blood samples were collected from 85 cardiology patients referred for platelet function testing. In Anysis-200, platelet function was measured as blood migration distance (MD) until clogging of flow passage, which is comparable to aspirin resistance units obtained using VerifyNow. The two devices were simultaneously used and compared. RESULTS: The MDs before and after taking aspirin were 175±51 and 247±27 mm, respectively (p < 0.0001). Compared with VerifyNow (reference), the sensitivity and specificity of Anysis-200 was 91.5% and 75.5%, respectively (area under the curve, 0.829). Further, the true positive rate in patients newly taking aspirin was 85% for VerifyNow and 92.5% for Anysis-200, respectively. The Cohen's kappa coefficient between the two devices was 0.682, indicating a relatively high agreement. CONCLUSIONS: Anysis-200, a novel system for assessing platelet aggregation, has accuracy and precision equivalent to that of, and significant agreement with, VerifyNow. Anysis-200 may be useful in screening patients with abnormal platelet reactivity and aspirin nonresponsiveness.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Doenças Cardiovasculares/sangue , Testes de Função Plaquetária/métodos , Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
BMJ Case Rep ; 13(3)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32169992

RESUMO

A patient undergoes intracranial stent insertion for stent-assisted coiling of a basilar tip aneurysm and left middle cerebral artery aneurysm. A flow diverting stent is also placed across an anterior communicating artery aneurysm. Prior to the procedure, the patient takes dual antiplatelet medications, being aspirin and clopidogrel. Because of the concern regarding in-stent thrombus and thromboembolic complications related to intracranial stenting and the high rate of clopidogrel resistance, preoperative platelet function testing (PFT) was undertaken to ensure platelet inhibition. In this case, PFT was performed on a platelet function analyser which demonstrated platelet inhibition. Ten days following the procedure, the patient represented with thromboembolic stroke. Repeat PFT performed with whole blood impedance aggregometry and despite full medication compliance demonstrated clopidogrel resistance. Clopidogrel was then ceased and prasugrel commenced. This case demonstrates the importance of appropriate platelet inhibition in patients with intracranial stents and the controversy surrounding PFT.


Assuntos
Aneurisma Intracraniano/tratamento farmacológico , Stents/efeitos adversos , Acidente Vascular Cerebral/etiologia , Tromboembolia/complicações , Idoso , Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Diagnóstico Diferencial , Resistência a Medicamentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Ataque Isquêmico Transitório/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Masculino , Inibidores da Agregação de Plaquetas/uso terapêutico , Testes de Função Plaquetária/métodos , Cloridrato de Prasugrel/uso terapêutico , Cuidados Pré-Operatórios/normas , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento , Suspensão de Tratamento
6.
Medicine (Baltimore) ; 99(10): e19336, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150071

RESUMO

BACKGROUND: VerifyNow (VN; Accumetrics, San Diego, CA) P2Y12 reaction unit (PRU) has an inverse relation with hemoglobin level (Hb). Chronic kidney disease (CKD) is associated with low response to clopidogrel and low Hb. Our aim is to investigate the relation between PRU and Hb, and to assess whether Hb directly affects PRU or not in patients with CKD undergoing hemodialysis (HD). METHODS: We analyzed the relation between PRU and Hb in 43 HD patients and compared it with a control group of 127 patients with normal renal function. Both groups underwent percutaneous coronary intervention for stable coronary artery disease. We also compared PRU between the 2 groups considering Hb as a confounding factor. RESULTS: In the control group, Hb and PRU showed a significant inverse correlation (correlation coefficient r = -0.340; P < .001), but not in the HD group (correlation coefficient r = -0.099; P = .53). PRU was higher in the HD group than the control group after adjusting for the influence of Hb (299.2 [95% confidence interval: 278.4-316.7] vs 248.7 [95% confidence interval: 227.7-269.0]; P < .001), even after propensity score matching (299.2 [95% confidence interval: 278.4-316.7] vs 241.7 [95% confidence interval: 221.8-262.2]; P < .001). CONCLUSIONS: PRU was higher regardless of lower Hb in CKD on HD patients than normal renal function patients. Therefore, Hb was not crucial factor to decide PRU in CKD on HD patients in this study.


Assuntos
Clopidogrel/farmacologia , Hemoglobinas/análise , Hemoglobinas/fisiologia , Ativação Plaquetária/fisiologia , Idoso , Clopidogrel/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Testes de Função Plaquetária/métodos , Estudos Prospectivos , Diálise Renal/métodos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia
8.
Pathology ; 52(2): 243-255, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31932033

RESUMO

Inherited disorders of platelet function (IPFD) and/or number (IPND) are heterogeneous conditions that result in variable mucocutaneous bleeding symptoms as a result of deranged primary haemostasis caused by platelet dysfunction or thrombocytopenia. Diagnosis is important to guide post-operative bleeding prophylactic strategies, to avoid treatment with inappropriate medications, and inform prognosis. Achieving an accurate diagnosis has traditionally been hampered by the requirement of multiple, often complex, laboratory tests that are not always available at single centres. To improve the diagnosis of these disorders a research collaborative was established, the Sydney Platelet Group, that explored an integrated approach combining traditional and contemporary platelet phenotypic and genetic diagnostic platforms available at four Sydney tertiary hospitals. Herein we report the outcomes of the first 50 patients evaluated using this approach. The cohort included 22 individuals with suspected IPFD and 28 with thrombocytopenia. Bleeding scores were higher in individuals with IPFD (mean 5.75; SD 4.83) than those with IPNDs (mean 2.14; SD 2.45). In cases with suspected IPFD, diagnosis to the level of the defective pathway was achieved in 71% and four individuals were found not to have a definitive platelet function defect. Dense granule secretion disorders were the most common platelet pathway abnormality detected (n=5). Mean bleeding scores in these individuals were not significantly different to individuals with defects in other commonly detected platelet pathways (dense granules, signal transduction and 'undetermined'). A molecular diagnosis was achieved in 52% of individuals with IPNDs and 5% with IPFD. Likely pathogenic and pathogenic variants detected included variants associated with extra-haematological complications (DIAPH1, MYH9) and potential for malignancy (ANKRD26 and RUNX1). The level of platelet investigation undertaken by this initiative is currently not available elsewhere in Australia and initial results confirm the utility of this integrated phenotypic-genetic approach.


Assuntos
Transtornos Plaquetários/diagnóstico , Testes de Função Plaquetária/métodos , Adolescente , Adulto , Idoso , Austrália , Transtornos Plaquetários/genética , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Platelets ; 31(3): 360-364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31161848

RESUMO

Dabigatran, a direct oral thrombin inhibitor, has two therapeutic effects: anticoagulation; and antiplatelet activity. In the clinical field, evaluation of the effect of dabigatran on thrombin-induced platelet aggregation is difficult because of fibrin clot formation and platelet aggregation. The aim of this study was to establish a new platelet aggregation method and to investigate the effects of dabigatran on thrombin-induced platelet aggregation. Platelet aggregation with thrombin was performed with automated light transmission aggregometry (CS2400; Sysmex, Kobe, Japan) in 40 healthy subjects. Thrombin-induced platelet aggregation was performed using thrombin and platelet-rich plasma (PRP), and thrombin-induced fibrin polymerization was inhibited by adding the peptide Gly-Pro-Arg-Pro (GPRP). The effect of dabigatran was then evaluated using the above method. Thrombin at < 0.2 U/mL did not induce platelet aggregation in most normal subjects. Median maximum aggregation percent (MA%) (25th-75th percentile) with 0.5 and 1.0 U/mL of thrombin was 87.0% (79.3-90.8%), and 90.2% (86.5-92.2%), respectively. The anti-platelet effects of dabigatran were then evaluated with these concentrations of thrombin. Dabigatran (final concentration, 2.5-1000 nM) inhibited platelet aggregation by 0.2-1.0 U/mL of thrombin in a concentration-dependent manner in vitro. Dabigatran showed potent inhibitory effects against platelet aggregation induced by 0.5 and 1.0 U/mL thrombin with half maximal inhibitory concentrations of 10.5 and 40.4 nM, respectively. A standard for thrombin-induced platelet aggregation was developed using the CS2400 in healthy subjects, and dabigatran was confirmed to inhibit thrombin-induced platelet aggregation in vitro with PRP.


Assuntos
Antitrombinas/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Dabigatrana/farmacologia , Agregação Plaquetária , Testes de Função Plaquetária , Trombina/metabolismo , Adulto , Biomarcadores , Coagulação Sanguínea/efeitos dos fármacos , Feminino , Humanos , Masculino , Agregação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas , Testes de Função Plaquetária/métodos , Trombina/farmacologia , Adulto Jovem
11.
Heart Lung Circ ; 29(3): 460-468, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31060910

RESUMO

BACKGROUND: Identifying predictors of bleeding in patients before coronary artery bypass grafting surgery is important, given the complications of bleeding and finite supply of blood. Patient response to aspirin is heterogeneous and can be evaluated using point-of-care platelet function tests. We postulated that patients who hyper-respond to aspirin given preoperatively, as identified by VerifyNow® Aspirin assay (Accumetrics, Inc., San Diego, CA, USA), are at increased risk of bleeding and transfusion. METHODS: This prospective pilot study examined response to aspirin in patients undergoing coronary artery bypass grafting surgery (n = 61) from 2009 to 2013. Patients with aspirin reaction unit (ARU) values in the lower 50th percentile as identified by VerifyNow® assays were defined as aspirin hyper-responders. The proportion of patients transfused and the median adjusted indexed drop in haemoglobin were compared between aspirin hyper-responders and non-hyper-responders. Logistic regression was performed to determine factors associated with increased risk of transfusion. RESULTS: Seventy per cent (70%) of aspirin hyper-responders were transfused perioperatively compared with 39% of patients who did not hyper-respond, (OR 3.694, 95% CI 1.275-10.706, p = 0.014). VerifyNow® Aspirin hyper-responders had a greater median adjusted indexed drop in haemoglobin compared to non-hyper-responders (34.1 g/L versus 26.6 g/L respectively, p = 0.032). Multivariate analysis also showed VerifyNow® Aspirin hyper-response to be an independent predictor of transfusion (p = 0.016). Other variables such as age, gender, body mass index, renal insufficiency, and cross clamp and bypass times were not predictors of postoperative bleeding in this pilot cohort. CONCLUSIONS: VerifyNow® Aspirin is able to preoperatively identify aspirin hyper-responders at an increased risk of bleeding and subsequent transfusion in the context of coronary artery bypass graft surgery.


Assuntos
Aspirina/administração & dosagem , Perda Sanguínea Cirúrgica/prevenção & controle , Plaquetas/metabolismo , Transfusão de Sangue , Ponte de Artéria Coronária/efeitos adversos , Sistemas Automatizados de Assistência Junto ao Leito , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Testes de Função Plaquetária/instrumentação , Testes de Função Plaquetária/métodos , Estudos Prospectivos , Fatores de Risco
12.
J Surg Res ; 246: 605-613, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31668435

RESUMO

BACKGROUND: Platelet function tests such as thrombelastography platelet mapping and impedance aggregometry have demonstrated universal platelet dysfunction in trauma patients. In this study, we introduce the measurement of platelet contraction force as a test of platelet function. We hypothesize that force will correlate with established coagulation tests such as thrombelastography, demonstrate significant differences between healthy subjects and trauma patients, and identify critically ill trauma patients. METHODS: Blood samples were prospectively collected from level 1 trauma patients at initial presentation, assayed for force of and time to contraction and compared with thrombelastography. Blood from healthy subjects was assayed to establish a reference range. Results from trauma patients were compared with healthy controls and trauma patients that died. RESULTS: The study includes one hundred trauma patients with mean age 45 y, 74% were male, and median injury severity score of 14 ± 12. Patients that survived (n = 90) demonstrated significantly elevated platelet contraction force compared with healthy controls (n = 12) (6390 ± 2340 versus 4790 ± 470 µN, P = 0.043) and trauma patients that died (n = 10) (6390 ± 2340 versus 2860 ± 1830 µN, P = 0.0001). Elapsed time to start of platelet contraction was faster in trauma patients that survived compared with healthy controls (660 ± 467 versus 1130 ± 140 s, P = 0.0022) and those that died (660 ± 470 versus 1460 ± 1340 s, P < 0.0001). CONCLUSIONS: In contrast with all existing platelet function tests reported in the literature, which report platelet dysfunction in trauma patients, contractile force demonstrates hyperfunction in surviving trauma patients and dysfunction in nonsurvivors. Platelet contraction reflects platelet metabolic reserve and thus may be a potential biomarker for survival after trauma. Contractile force warrants further investigation to predict mortality in severely injured trauma patients.


Assuntos
Transtornos Plaquetários/diagnóstico , Plaquetas/fisiologia , Ferimentos e Lesões/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea/fisiologia , Transtornos Plaquetários/sangue , Transtornos Plaquetários/etiologia , Transtornos Plaquetários/fisiopatologia , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária/métodos , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Tromboelastografia , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/mortalidade , Adulto Jovem
13.
Int J Artif Organs ; 43(3): 208-214, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31674867

RESUMO

Assessing the platelets' functional status during surgery on cardiopulmonary bypass is challenging. This study used multiple electrode impedance aggregometry (Multiplate®) to create a timeline of platelet aggregation changes as induced by cardiopulmonary bypass in antiplatelet-naive patients undergoing elective surgery for mitral valve regurgitation. We performed six consecutive measurements (T1: pre-operatively, T2: after heparinization, T3: 3 min after establishment of cardiopulmonary bypass, T4: immediately after administration of cardioplegia, T5: 5 min after administration of cardioplegia, and T6: 45 min after administration of cardioplegia). Platelet aggregation was determined after stimulation with 3.2-µg/mL collagen, 6.4-µM adenosine diphosphate, and 32-µM thrombin receptor activating peptide. Five patients were included (age: 64 ± 10 years, one female). We observed a decrease in hematocrit levels by -17.1% ± 3.7% (T1 vs T6) with a drop after establishment of cardiopulmonary bypass (T2 vs T3) and slightly decreasing platelet counts by -6.2% ± 7.7% (T1 vs T6). Immediately after establishment of cardiopulmonary bypass (T2 vs T3), we observed reduced platelet aggregation responses for stimulation with adenosine diphosphate (-19.7% ± 12.8%) and thrombin receptor activating peptide (-19.3% ± 6.3%). Interestingly, we found augmented platelet aggregation for all stimuli 45 min after administration of cardioplegia (T5 vs T6) with the strongest increase for collagen (+83.4% ± 42.8%; adenosine diphosphate: +39.0% ± 37.2%; thrombin receptor activating peptide: +34.5% ± 18.5%). Thus, after an initial drop due to hemodilution upon establishment of cardiopulmonary bypass, platelet reactivity increased over time which was not outweighed by decreasing platelet counts due to mechanical platelet destruction and absorption. These findings have implications for rational transfusion, peri-operative antiplatelet therapy, and for the management of patients on other extracorporeal support, such as extracorporeal life support or extracorporeal membrane oxygenation.


Assuntos
Ponte Cardiopulmonar , Cuidados Intraoperatórios , Insuficiência da Valva Mitral/sangue , Agregação Plaquetária , Testes de Função Plaquetária , Idoso , Procedimentos Cirúrgicos Cardíacos/instrumentação , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/instrumentação , Ponte Cardiopulmonar/métodos , Circulação Extracorpórea , Feminino , Humanos , Cuidados Intraoperatórios/instrumentação , Cuidados Intraoperatórios/métodos , Cinética , Masculino , Teste de Materiais , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/cirurgia , Projetos Piloto , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/fisiologia , Testes de Função Plaquetária/instrumentação , Testes de Função Plaquetária/métodos
14.
Int J Hematol ; 111(3): 369-377, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31741138

RESUMO

Type 2N von Willebrand disease (VWD) is characterized by impaired factor VIII (FVIII) binding to von Willebrand factor (VWF). Type 2N VWD patients generally exhibit mild bleeding tendency, but some exhibit a more severe hemorrhagic pattern. An assay for assessing hemostatic potential and predict clinical severity could significantly improve clinical management in these patients. We examined the relationship between bleeding score (BS) and the potential for thrombus formation in whole blood from type 2N VWD patients with various BS using rotational thromboelastometry (ROTEM) and microchip flow-chamber system (T-TAS®). Collagen-coated PL-chips, or thromboplastin- and collagen-coated AR-chips, were utilized in the T-TAS to assess platelet thrombus formation at high shear flow, or fibrin-rich platelet thrombus formation at low shear flow, respectively. Neither ROTEM nor the T-TAS using PL-chips reflected the BS. The AR-chip parameters in the T-TAS, however, were highly sensitive to different BS levels among these patients, despite similar FVIII/VWF-related measurements including FVIII/VWF binding. Additionally, the results with AR-chip assay were restored to normal after infusions of FVIII/VWF concentrates in the most severe patients. The data indicate that T-TAS using AR-chips may be a useful assay for predicting clinical severity and assessing therapeutic efficiency in type 2N VWD patients.


Assuntos
Testes de Função Plaquetária/métodos , Doença de von Willebrand Tipo 2/diagnóstico , Humanos , Índice de Gravidade de Doença , Tromboelastografia/métodos , Doença de von Willebrand Tipo 2/genética
16.
Ann Thorac Surg ; 109(6): 1931-1936, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31887277

RESUMO

PURPOSE: Infants undergoing a cardiac operation are at high risk for postsurgical bleeding. To date, there are no highly predictive models for postsurgical bleeding in this population. This study's objective was to assess the predictive ability of T2 magnetic resonance (T2MR). DESCRIPTION: T2MR uses magnetic resonance to detect clot formation characteristics on a small blood sample and provides hemostatic indicators that can assess bleeding risk. EVALUATION: This prospective, single-institution study enrolled 100 patients younger than 12 months old undergoing a cardiac operation from April 27, 2015, to September 21, 2016. The primary end point was postsurgical bleeding within 24 hours after the procedure. T2MR data were modeled with a binary recursive partitioning algorithm with randomized cross-validation. The tight clot metric produced the highest univariate discrimination of bleeding (receiver operator characteristic curve, 0.64; classification accuracy, 72%), and along with the platelet function metric, demonstrated highest relative importance based on Gini index splitting (Salford Systems, San Diego, CA). Multivariate modeling with cross-validation showed mean receiver operator characteristic curve area of 0.74 and classification accuracy of 82%. CONCLUSIONS: T2MR tight clot and platelet function metrics were associated with bleeding events.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias Congênitas/cirurgia , Imagem Cinética por Ressonância Magnética/métodos , Hemorragia Pós-Operatória/diagnóstico , Feminino , Cardiopatias Congênitas/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Função Plaquetária/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC
17.
Platelets ; 31(2): 179-186, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30892978

RESUMO

Background. Studies of platelet aggregation (PA) in essential thrombocythemia (ET) reported contrasting results, likely due to differences in analytical conditions.Objective. We investigated platelet aggregation using different techniques and analytical conditions.Patients and Methods. PA was studied by light-transmission aggregometry (LTA) in platelet-rich plasma (PRP) and impedance aggregometry in PRP and whole blood (WB). ADP, collagen, thrombin receptor activating peptide (TRAP-14) and adrenaline were used as agonists. Since ET patients (n = 41) were on treatment with aspirin (100 mg/d), healthy controls (n = 29) were given aspirin (100 mg/d) for 5 days before testing: therefore, thromboxane A2-independent PA was tested in all subjects. Blood samples were collected in citrate (C) [low Ca2+] or lepirudin (L) [physiological Ca2+]; platelet count was adjusted to 250 x 109/L in a set of C-PRP (adjusted C-PRP) and left unmodified in the other samples.Results. Results of PA in 17 ET patients who were poor responders to aspirin (high serum thromboxane B2 levels) were not included in the analysis. With LTA, PA in ET was lower than in controls in adjusted C-PRP and normal in native C-PRP and L-PRP. With impedance aggregometry, PA in L-PRP and L-WB tended to be higher in ET than in controls. Platelet serotonin and ADP contents were reduced in ET. The percentages of circulating platelets expressing P-selectin and platelet-leukocyte hetero-aggregates were higher in ET.Conclusions. Analytical conditions dramatically affect in vitro PA of ET patients, which appears defective under the least physiological conditions and normal/supranormal under conditions that are closer to the physiological.


Assuntos
Plaquetas/fisiologia , Testes de Função Plaquetária/métodos , Plasma Rico em Plaquetas , Trombocitemia Essencial/sangue , Nucleotídeos de Adenina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Ácido Cítrico/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/farmacologia , Contagem de Plaquetas , Plasma Rico em Plaquetas/efeitos dos fármacos , Serotonina/sangue , Trombocitemia Essencial/tratamento farmacológico , Trombocitemia Essencial/patologia , Adulto Jovem
18.
Clin Lab ; 65(12)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31850712

RESUMO

BACKGROUND: Light transmission aggregometry (LTA) is the gold standard for platelet function assessment. The automated coagulation analyzer from Sysmex that performs LTA offers the advantage of being a walk-away technology. Recently, a new parameter "ADP-induced platelet aggregation level (APAL)" was developed to support the interpretation of results. APAL is calculated as a score from 0.0 to 10.0 based on platelet aggregation patterns with 1 and 10 µM adenosine diphosphate (ADP). Here, the basic performance of the newly developed APAL system and comparison with the maximum aggregation rate of ADP (ADP-MA) was evaluated. METHODS: The within-run precision was calculated by conducting five replicate analyses of the platelet-rich plasma (PRP) from healthy volunteers and 0.05 µM of cangrelor-spiked PRP. Cangrelor is a P2Y12 inhibitor that does not require liver CYP activation. The reference interval was calculated from the results of 67 healthy volunteers. The effect of the antiplatelet P2Y12 agent was evaluated using several concentrations of cangrelor. A comparative study was performed using 103 PRP samples with different levels of aggregation. Each test was analyzed with both APAL and ADP-MA. RESULTS: The percentage coefficient of variation in within-run precision was within 7% for APAL and 10 µM ADP-MA. Reference interval of APAL and 10 µM ADP-MA was 7.1 - 10.0 and 80.0 - 99.2%, respectively. APAL signifi-cantly decreased with the addition of 0.02 µM cangrelor, while 10 µM ADP-MA was barely affected. A significant correlation was observed between APAL and 10 µM ADP-MA (r = 0.94; p < 0.0001). CONCLUSIONS: The newly developed APAL system exhibited an acceptable performance. APAL score showed a good correlation with ADP-MA and was adequate to detect the weak effect of P2Y12 inhibitors. APAL is a new platelet aggregation scoring system with the potential to monitor the effects of P2Y12 inhibitor over a wide range.


Assuntos
Difosfato de Adenosina/farmacologia , Testes de Coagulação Sanguínea/instrumentação , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária/instrumentação , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Testes de Coagulação Sanguínea/métodos , Humanos , Inibidores da Agregação de Plaquetas/farmacologia , Testes de Função Plaquetária/métodos , Plasma Rico em Plaquetas/efeitos dos fármacos , Reprodutibilidade dos Testes
19.
J Invasive Cardiol ; 31(12): E369-E375, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31786528

RESUMO

BACKGROUND: The impact of platelet reactivity on periprocedural myonecrosis (PMN) in East Asian patients with stable ischemic heart disease or non-ST elevation acute coronary syndrome undergoing percutaneous coronary intervention (PCI) is unclear. METHODS: We enrolled 256 patients with normal high-sensitivity troponin I levels who underwent PCI for stable ischemic heart disease or non-ST elevation acute coronary syndrome. Residual platelet reactivity was assessed by VerifyNow point-of-care P2Y12 assay before PCI and at 18-24 hours following PCI. High platelet reactivity (HPR) was defined using three cut-off scores for platelet reactivity units (PRUs). PMN was defined as a high-sensitivity troponin I elevation of >5x the 99th percentile upper reference limit (URL) in patients with normal baseline values (<99th percentile URL). RESULTS: The rate of PMN was 55.9% (n = 143) and was significantly higher for pre-PCI and post-PCI PRU values in the fourth quartile compared with those in the first quartile (15% vs 37% [P<.001] and 20% vs 36% [P<.001], respectively). The rate of PMN was higher in patients with HPR, regardless of the criteria used (PRU >208, PRU >235, and PRU >272) and time point. Multivariable analysis revealed that pre-PCI HPR (PRU >208) was an independent predictor of increased risk of PMN (odds ratio, 3.39; 95% confidence interval, 1.87-6.17; P<.001). CONCLUSION: Pre-PCI HPR (PRU >208) was associated with an increased risk of PMN in East Asian patients with stable ischemic heart disease or non-ST elevation acute coronary syndrome undergoing PCI. Achievement of optimal platelet reactivity may decrease the risk of PMN.


Assuntos
Doença da Artéria Coronariana/cirurgia , Isquemia Miocárdica , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas , Complicações Pós-Operatórias , Plaquetas/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/prevenção & controle , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/classificação , Testes de Função Plaquetária/métodos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Período Pré-Operatório , República da Coreia/epidemiologia , Troponina I/sangue
20.
Sci Rep ; 9(1): 16514, 2019 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-31712610

RESUMO

Platelet aggregation and adhesion are critically involved in both normal hemostasis and thrombosis during vascular injury. Before any surgery, it is important to identify the number of platelets and their functionality to reduce the risk of bleeding; therefore, platelet function testing is a requirement. We introduce a novel evaluation method of assessing platelet function with laser speckle contrast imaging. The speckle decorrelation time (SDT) of the blood flowing through a microfluidic channel chip provides a quantitative measure of platelet aggregation. We compared SDTs of whole blood and platelet-poor blood, i.e., whole blood stripped of its buffy coat region, and found a marked reduction in decorrelation time for platelet-poor blood. The measured SDT of platelet-poor blood was 1.04 ± 0.21 ms, while that of whole blood was 2.64 ± 0.83 ms. To further characterize the sensitivity of our speckle decorrelation time-based platelet function testing (SDT-PFT), we added various agonists involved in platelet aggregation, including adenosine diphosphate (ADP), epinephrine (EPI), and arachidonic acid (AA). In this study, the results show that whole blood with ADP resulted in the largest SDT, followed by whole blood with AA, whole blood with EPI, whole blood without agonist, and platelet-poor blood with or without agonist. These findings show that SDT-PFT has the potential for rapid screening of bleeding disorders and monitoring of anti-platelet therapies with only a small volume of blood.


Assuntos
Plaquetas/fisiologia , Plaquetas/efeitos da radiação , Lasers , Microfluídica , Testes de Função Plaquetária , Algoritmos , Bioengenharia , Humanos , Luz , Microfluídica/instrumentação , Microfluídica/métodos , Modelos Teóricos , Testes de Função Plaquetária/instrumentação , Testes de Função Plaquetária/métodos
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