Aspirin responsiveness safely lowers perioperative cardiovascular risk

IntroductionVascular surgeries are related to high cardiac morbidity and mortality, and the maintenance of aspirin in the perioperative period has a protective effect. The purpose of this study was to evaluate the association between preoperative platelet aggregability and perioperative cardiovascular (CV) events.MethodsA preoperative platelet aggregation test was performed on an impedance aggregometer in response to collagen and to arachidonic acid (AA) for 191 vascular surgery patients under chronic use of aspirin. We analyzed the following CV events: acute myocardial infarction, unstable angina, isolated troponin elevation, acute ischemic stroke, reoperation, and cardiac death. Hemorrhagic events were also evaluated and classified according to the Thrombolysis In Myocardial Infarction criteria.ResultsThe incidence of CV events was 22% (n = 42). Higher platelet response to AA was associated with CV events, so that patients in the fourth quartile (higher than 11Ω) had almost twice the incidence of CV events when compared with the three lower quartiles: 35% vs 19%; P = .025. The independent predictors of CV events were hemodynamic instability during anesthesia (odds ratio [OR], 4.12; 95% confidence interval [CI], 1.87-9.06; P < .001), dyslipidemia (OR, 3.9; 95% CI, 1.32-11.51; P = .014), preoperative anemia (OR, 2.64; 95% CI, 1.19-5.85; P = .017), and AA platelet aggregability in the upper quartile (OR, 2.48; 95% CI, 1.07-5.76; P = .034). Platelet aggregability was not associated with hemorrhagic events, even when we compared the lowest quartile of AA platelet aggregability (0-1.00 Ω) with the three upper quartiles (>1.00 Ω; OR, 0.77; 95% CI, 0.43-1.37; P = .377).ConclusionsThe degree of aspirin effect on platelet aggregability maybe important in the management of perioperative CV morbidity, without increment in the bleeding toll

Antiplatelet activity of Croton celditifolius

Croton celtidifolius Baill é uma árvore encontrada na Mata Atlântica, no sul do Brasil, principalmente no estado de Santa Catarina. A infusão da casca e folhas dessa planta medicinal é utilizada na medicina popular para o tratamento de doenças inflamatórias. A atividade antiagregante do extrato bruto de C. celtidifolius (CE) e de seus flavonóides isolados por coluna cromatográfica (CC), catequina e galocatequina, foi avaliada em plaquetas humanas. O plasma rico em plaquetas (PRP) foi incubado com diferentes concentrações dos flavonóides testados (50 - 200 µg/mL) e posteriormente a agregação foi induzida pelos agonistas adenosina 5'difosfato (ADP) e colágeno. Na concentração de 200 µg/mL o CE, a catequina e a galocatequina inibiram a agregação plaquetária induzida pelos agonistas. A produção de ATP foi utilizada como um índice de capacidade de secreção plaquetária e observamos uma diminuição na produção de ATP nas plaquetas tratadas com os flavonóides e estimuladas com o colágeno. Por outro lado, os flavonóides não promoveram um efeito inibitório no tempo de protrombina (PT), tempo de tromboplastina parcial ativada (APTT) e tempo de trombina (TT). Essas observações sugerem que o C. celtidifolius exerce, in vitro, uma ação inibitória nas plaquetas através da inibição da secreção e agregação plaquetária.Croton celtidifolius Baill is a tree found in the Atlantic Forest South of Brazil, mainly in Santa Catarina. The bark and leaf infusions of this medicinal plant have been popularly used for the treatment of inflammatory diseases. The anti-aggregant activity of C. celtidifolius crude extract (CE) and the column chromatography (CC) isolated compounds flavonoids, catechin and gallocatechin were evaluated in human blood platelets. The platelet-rich plasma (PRP) was incubated with different concentrations of flavonóides (50 - 200 µg/mL) to be tested before platelet aggregation was induced by the agonists adenosine 5'diphosphate (ADP) and collagen. At 200 µg/mL the CE, catechin and gallocatechin markedly inhibited platelet aggregation with the aggregant agents. Using ATP production as an index of platelet secretory capacity, we observed a decreased production of ATP in platelets treated with flavonoids when stimulated by collagen. On the other hand, the flavonoids did not promote inhibitory effect on prothrombin time (PT), thromboplastin time (APTT) and thrombin time (TT). In conclusion, these observations suggest that C. celtidifolius is likely to exert an inhibitory action on platelets in vitro by suppressing secretion and platelet aggregation

A Prospective Study of Conventional and Expanded Coagulation Indices in Predicting Ulcer Bleeding After Variceal Band Ligation

BACKGROUND & AIMS: There is controversy over whether coagulation status predicts bleeding caused by ulceration after esophageal varices band ligation (EVL). METHODS: EVL was performed for primary (n = 45) or secondary (n = 105) prophylaxis in 150 patients with cirrhosis (Child A, n = 74, 49%; Child B, n = 42, 28%; Child C, n = 34, 23%). International normalized ratio (INR) and platelet counts were assessed in all. In 92 patients, levels of factor V, fibrinogen, D-dimer, protein C and protein S, von Willebrand factor, and thromboelastography (TEG) were assessed. Platelet count < 50 x 10(3)/mm(3) and INR > 1.5 were considered high-risk cutoff for bleeding. Conversely, platelet count >= 50 x 10(3)/mm(3) with INR <= 1.5 were safe cutoffs. RESULTS: Overall, 11 patients (7.3%) had post-EVL ulcer bleeding. Bleeding occurred in S patients with Child A/B (4.3%) and 6 patients with Child C (17%) (P = .0174 for Child A/B versus Child C). Eight patients with bleeding were among the 110 below the cutoff for INR and platelet count, whereas only 3 of the patients with bleeding were among the 40 patients with purported high-risk values (P = 1.0). Among the 92 patients with expanded coagulation tests, bleeding occurred in S. There was no difference in any of the coagulation parameters, including overall TEG patterns, between patients who did and did nor bleed. CONCLUSIONS: Post-EVL ulcer bleeding was associated with Child C status but not with conventional or expanded coagulation indices in cirrhotic patients without renal failure or infection undergoing elective EVL. These results call into question the common use of prophylactic procoagulants in the elective setting

Study of pro-thrombotic and pro-inflammatory factors in chagas cardiomyopathy

FUNDAMENTO: A relação entre atividade inflamatória e pró-trombótica na cardiomiopatia chagásica e em outras etiologias é obscura. OBJETIVO: Estudar o perfil de marcadores pró-trombóticos e pró-inflamatórios em pacientes com insuficiência cardíaca chagásica e compará-los com os de etiologia não chagásica. MÉTODOS: Coorte transversal. Critérios de inclusão: fração de ejeção do VE (FEVE) < 45% e tempo de início de sintomas &gt; um mês. Os pacientes foram divididos em dois grupos: grupo 1 (G1) - sorologias positivas para Chagas - e grupo 2 (G2) - sorologias negativas para Chagas. Fator pró-inflamatório: PCR ultrassensível. Fatores pró-trombóticos: fator trombina-antitrombina, fibrinogênio, antígeno do fator de von Willebrand, P-selectina plasmática e tromboelastograma. Amostra calculada para poder de 80%, assumindo-se diferença de 1/3 de desvio-padrão; p significativo se < 0,05. Análise estatística: teste exato de Fischer para variáveis categóricas; teste t de Student não pareado para variáveis contínuas paramétricas e teste de Mann-Whitney para variáveis contínuas não paramétricas. RESULTADOS: Entre janeiro e junho de 2008, foram incluídos 150 pacientes, 80 no G1 e 70 no G2. Ambos os grupos mantinham médias de PCR ultrassensível acima dos valores de referência, porém, sem diferença significativa (p=0,328). Os níveis de fibrinogênio foram maiores no G2 do que no G1 (p=0,015). Entre as variáveis do tromboelastograma, os parâmetros MA (p=0,0013), G (p=0,0012) e TG (p=0,0005) foram maiores no G2 em comparação ao G1. CONCLUSÃO: Não há indícios de maior status pró-trombótico entre chagásicos. A dosagem de fibrinogênio e dos parâmetros MA, G e TG do tromboelastograma apontam para status pró-trombótico entre não chagásicos. Ambos os grupos tinham atividade inflamatória exacerbada.BACKGROUND: The relationship between inflammatory and prothrombotic activity in chagas cardiomyopathy and in other etiologies is unclear. OBJECTIVE: To study the profile of pro-thrombotic and pro-inflammatory markers in patients with Chagas' heart failure and compare them with patients of non-chagas etiology. METHODS: Cross-sectional cohort. Inclusion criteria: left ventricle ejection fraction (LVEF) < 45% and onset time to symptoms &gt; one month. The patients were divided into two groups: group 1 (G1) - seropositive for Chagas - and group 2 (G2) - seronegative for Chagas. Pro-inflammatory factor: Ultra-sensitive CRP. Pro-thrombotic factors: thrombin-antithrombin factor, fibrinogen, von Willebrand factor antigen, plasma P-selectin and thromboelastography. Sample calculated for 80% power, assuming a standard deviation difference of 1/3; significant p if it is < 0.05. Statistical analysis: Fisher's exact test for categorical variables; unpaired Student's t-test for parametric continuous variables and Mann-Whitney test for nonparametric continuous variables. RESULTS: Between January and June 2008, 150 patients were included, 80 in G1 and 70 in G2. Both groups maintained the averages of high sensitivity CRP above baseline values, however, there was no significant difference (p = 0.328). The fibrinogen levels were higher in G2 than in G1 (p = 0.015). Among the thromboelastography variables, the parameters MA (p=0.0013), G (p=0.0012) and TG (p =0.0005) were greater in G2 than in G1. CONCLUSION: There is no evidence of greater pro-thrombotic status among patients with Chagas disease. The levels of fibrinogen and the MA, G and TG parameters of the thromboelastography point to pro-thrombotic status among non-chagas patients. Both groups had increased inflammatory activity

Endoscopic activity, tissue factor and Crohn’s disease: findings in clinical remission patients

Background: As Crohn’s disease (CD) is associated with a high risk of thromboembolic events (TE), including patients with subclinical inflammation, we aim to evaluate the correlation between the impact of endoscopic activity (EA) in the coagulation profiling of CD patients while in clinical remission. Methods: From 164 consecutive CD patients included in clinical remission [Crohn’s disease activity index (CDAI) < 150], 75 were in the EA group [Simplified Endoscopic Score for CD (SES-CD) ⩾ 7], 89 were in the endoscopic remission (ER) group (SES-CD ⩽ 2), and 50 were included as healthy controls in the study. Blood samples were analyzed for tissue factor (TF), factor VIII (FVIII), thrombomodulin (TM), ADAMTS-13, von Willebrand factor (VWF), and endogenous thrombin potential (ETP), as well as collecting data regarding risk factors for TE and CD profile. Results: Mean plasma TF activity showed significantly higher levels in the EA group when compared with the ER and control groups (127 pM versus 103 pM versus 84 pM; p  = 0.001), although the VWF:Ag (160% versus 168% versus 110%; p  = 0.001), VWF/ADAMTS-13 (191 versus 219 versus 138; p  = 0.003), FVIII (150% versus 144% versus 90%; p  = 0.001) and TM (5.13 ng/ml versus 4.91 ng/mL versus 3.81 ng/ml; p  < 0.001) were only increased in CD regardless of EA status when compared with controls. Lastly, ETP with and without TM remained the same in all three groups. Conclusions: CD patients in clinical remission with EA present endothelial lesion inducing TF exposure and subsequent coagulation cascade activation. Recommended thromboprophylaxis for EA outpatient subgroups will require additional investigation in order to be validated