RESUMO
Dextran 40 has been used to prevent post-operative thrombosis. However, its antithrombotic and antiplatelet effects in peripheral arterial disease (PAD) are poorly understood. We studied the in vitro effects of Dextran 40 on platelet function in control subjects and PAD patients using whole blood methods. Platelet function was assessed in 20 control subjects and 20 PAD patients. Spontaneous platelet aggregation (SPA) and agonist-induced platelet aggregation in response to increasing concentrations of Dextran 40 in vitro were measured by whole blood aggregometry. Flow cytometric measurements of platelet P-selectin, GpIIb/IIIa, GpIb and PAC-1 binding were also performed. There was no difference in SPA or ADP-induced aggregation in control patients with Dextran 40 in vitro. However, Dextran 40 inhibited collagen-induced aggregation in control patients (P < 0.05, Friedman test). In PAD patients, SPA and ADP (1 microM)-induced aggregation were significantly reduced by Dextran 40 in vitro (P < 0.001, Friedman test). In PAD patients, collagen-induced platelet aggregation (1 and 5 microg/ml) was significantly reduced by Dextran 40 in vitro (P < 0.01, Friedman test). GpIIb/IIIa, PAC-1 and P-selectin expression were significantly reduced in whole blood samples from PAD patients following incubation with Dextran 40 (P < 0.05, Wilcoxon rank test) but not in samples from control patients. Dextran 40 reduces spontaneous and agonist-induced platelet aggregation as well as the surface expression of markers of platelet activation in PAD patients. This antiplatelet effect may be of benefit to patients undergoing vascular surgical procedures where thrombosis is a significant risk.
Assuntos
Dextranos/farmacologia , Doenças Vasculares Periféricas/tratamento farmacológico , Agregação Plaquetária/efeitos dos fármacos , Difosfato de Adenosina/farmacologia , Idoso , Biomarcadores/análise , Estudos de Casos e Controles , Células Cultivadas , Colágeno/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/sangue , Ativação Plaquetária/efeitos dos fármacos , Testes de Função PlaquetáriaRESUMO
OBJECTIVES: patients with peripheral arterial disease (PAD) have a threefold increase in cardiovascular mortality. Standard antiplatelet treatment may not confer uniform benefit in different patient groups. This study aimed to compare platelet function in patients with lower limb PAD, carotid disease and abdominal aortic aneurysm (AAA) with age- and sex-matched healthy controls. METHODS: patients with lower limb PAD (n = 20), carotid disease (n = 40), AAA (n = 13) and age/sex matched healthy controls (n= 20) were studied. Whole blood methods to detect spontaneous platelet aggregation (SPA), and adenosine diphosphate (ADP) and collagen-induced aggregation were used. The detection of platelet P-selectin and the PAC-1 antigen by flow cytometry were also used as markers of platelet activation and aggregation. RESULTS: patients with lower limb PAD or AAA had higher baseline SPA compared to normal controls (p < 0.01). There was significantly higher collagen-induced aggregation in IC patients compared to normal controls (p < 0.01). However, there was no difference in ADP-induced aggregation between lower limb PAD and control patients. There was no difference in PAC-1 binding between control patients and the patients with lower limb PAD, carotid disease or AAA. Patients with carotid disease had a higher expression of P-selectin compared to normal controls (p < 0.05). CONCLUSIONS: this study provides further evidence that platelet hyperactivity is present in patients with PAD despite the use of antiplatelet therapy. Further antiplatelet strategies may be indicated to protect these patients.
Assuntos
Selectina-P/sangue , Doenças Vasculares Periféricas/fisiopatologia , Ativação Plaquetária/fisiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Proteínas Tirosina Fosfatases/sangue , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/fisiopatologia , Plaquetas/fisiologia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/fisiopatologia , Fosfatase 2 de Especificidade Dupla , Feminino , Citometria de Fluxo , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/sangue , Agregação Plaquetária/fisiologia , Proteína Fosfatase 2RESUMO
OBJECTIVE: To determine changes in platelet activation during carotid endarterectomy (CEA) and the antiplatelet effect of Dextran 40. METHODS: Prospective study in 40 patients undergoing CEA. Platelet activity was measured by whole blood flow cytometry and platelet aggregometry during CEA. The expression of P-selectin and the PAC-1 antigen were used as markers of platelet activation and aggregation. Patients received aspirin (75-300 mg) preoperatively and 5,000 units unfractionated heparin during surgery. High intensity transient signals (HITS) in the ipsilateral middle cerebral artery were monitored using transcranial Doppler (TCD) perioperatively. RESULTS: P-selectin expression increased after carotid clamping (P < 0.01) and clamp release (P < 0.05). There was higher expression of PAC-1 after carotid clamping (p < 0.05). Spontaneous and ADP-induced platelet aggregation increased after carotid clamping (P< 0.01) and release (P < 0.01). TCD monitoring showed an increased HITS count from preoperative levels, after clamp release (P < 0.01) and during recovery (P < 0.01). After the operation, patients with more than 50 HITS per 30 min were started on an infusion of dextran 40 (n = 6). P-selectin expression decreased 24 h after dextran 40 (P < 0.01). CONCLUSION: Significant platelet activation and aggregation occurs during CEA despite the current use of antiplatelet treatment. Dextran 40 had an antiplatelet effect after CEA providing further evidence that it may contribute to reducing thromboembolic complications.
Assuntos
Anticoagulantes/farmacologia , Dextranos/farmacologia , Endarterectomia das Carótidas/efeitos adversos , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Idoso , Anticoagulantes/administração & dosagem , Dextranos/administração & dosagem , Avaliação de Medicamentos , Feminino , Citometria de Fluxo , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/etiologia , Embolia Intracraniana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Inibidores da Agregação Plaquetária/administração & dosagem , Testes de Função Plaquetária , Estudos Prospectivos , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Ultrassonografia Doppler TranscranianaRESUMO
BACKGROUND: Dextran 40 has been shown to reduce cerebral embolization following carotid endarterectomy (CEA). This study aimed to determine changes in platelet function during CEA and the antiplatelet effect of dextran 40. METHODS: Platelet function was measured by whole-blood flow cytometry in the peripheral arterial blood of patients during CEA and 24 h later. The binding index of P-selectin and PAC-1 expression were measured as markers of activation and aggregation. Patients were kept on aspirin 75-150 mg until the day of surgery and received an intravenous bolus of 5000 units unfractionated heparin before carotid artery clamping. High-intensity transient signals (HITS) in the ipsilateral middle cerebral artery were measured with transcranial Doppler (TCD) ultrasonography before, during and after operation. Results are presented as median (interquartile range) and statistical significance was determined using the Mann-Whitney U test. RESULTS: Thirty-eight patients undergoing CEA were studied. The P-selectin binding index rose significantly from incision (0.9 (0.2-2.7)) after carotid clamping (1.5 (0.6-3.6); P < 0.01), clamp release (1.7 (0. 3-3.0); P < 0.01), 1 h after operation (1.5 (0.3-2.6); P < 0.05) and 24 h after operation (1.3 (0.6-2.5); P < 0.05). PAC-1 binding index increased from incision (0.4 (0.1-0.8)) after carotid clamping (2.0 (0.4-4.2); P < 0.01) and clamp release (1.8 (0.3-2.9); P < 0.05). TCD monitoring showed an increase in preoperative HITS per 30 min (2 (0-3)) during dissection (8 (1-15); P < 0.05), after clamp release (16 (2-27); P < 0.01) and during recovery (10 (2-29); P < 0.01). After operation, patients with more than 50 HITS per 30 min were started on an infusion of dextran 40. Six patients had a dextran 40 infusion. The P-selectin binding index decreased from 1.6 (0.7-1.9) to 0.6 (0.3-1.5) 1 h after dextran (P < 0.05) and 0.1 (0.1-0.2) 24 h after dextran (P < 0.05). PAC-1 expression decreased from 0.4 (0.3-0. 5) to 0.1 (0.1-0.1) 24 h after dextran (P < 0.05). CONCLUSION: Significant platelet activation and aggregation occurs during CEA despite the use of antiplatelet treatment. A simultaneous increase in HITS was demonstrated with TCD. Dextran 40 was shown to have an antiplatelet effect after CEA; this is further evidence that it may have a role in reducing thromboembolic complications.