The Influence Of Unfractionated Heparin, Dalteparin And Enoxaparin On Platelet Activation During Coronary Angioagraphy

Objective: Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are anticoagulants that widely used in clinical practice at present. They are used in the prevention and treatment of arterial and venous thromboembolism diseases, such as acute coronary syndromes (ACS), deep venous thrombosis and pulmonary embolism, etc. The researchers pay less attention to the effect of UFH and LMWH on the platelet activation expect for heparin-induced thrombocytopenia. Previous studies showed that UFH could activate the platelet both in vivo and in vitro, simultaneously increase platelet aggregation rate. Platelet activation is the main mechanism of many diseases at least partially. The increased of platelet activity can promote the progress of atherosclerosis; furthermore it is the important reason that causes coronary artery thrombosis and acute myocardial infarction. During percutaneous coronary interventions (PCI) at present, the application of heparin or LMWH is advocated, and the level of platelet activation during the procedure of PCI may have effects on the post-operation complications. In addition, patients with ACS are generally need to give UFH or LMWH intravenously for the purpose of rapidly reaching the requirement of anticoagulation after visiting hospital, but the species of heparin medicine can activate the platelet. Therefore, the selection of heparin species which have different effect on platelet activation and planned countermeasure of this effect may have important significance in coronary interventional treatment and clinical conventional anticoagulation. Plasma von Willebrand factor (vWF), sCD40L and platelet membrane GPⅡb/Ⅲa as well as CD62P were the specific markers of platelet activation. The purpose of the present study was to compare the difference in platelet activation among unfractionated heparin, dalteparin and enoxaparin by measuring plasma CD62P, sCD40L, vWF, and platelet membrane GPⅡb/Ⅲa.Methods: 58 patients who were performed coronary angiography in catheterization room of cardiology department were enrolled between March 2007 and November 2008. There were 40 males and 18 females, with a mean age of 53.08±6.71 years and the average weight was 64.15±10.22 Kg. All patients did not receive any anticoagulation and antiplatelet treatment within 1 week. All patients were randomly assigned to unfractionated heparin group, dalteparin group or enoxaparin group. Before the coronary angiography, measuring the patients'body weight; after arterial puncture, injecting unfractionated heparin or LMWH (dalteparin or enoxaparin) through arterial sheath. The dosages were according to patients' body weight (50U/Kg). All intraoperative use of contrast agents were Ultravist (370). Blood samples were obtained through arterial sheath immediately after arterial puncture, 10 and 20 minutes after drug administration. The platelet membrane GPⅡb/Ⅲa was detected by flow cytometry, and plasma sCD40L, CD62P and vWF were measured by enzyme linked immunoadsorbent assay (ELISA). Continuous variables were expressed as the mean value±standard deviation (SD); categorical variables were summarized as percentages. The comparison of GPⅡb/Ⅲa, sCD40L, CD62P and vWF was evaluated by repeated measures engineered variance analysis. A P value of <0.05 was considered statistically significant.Results: The baseline characteristics such as age, body weight, body height and gender were not significantly different among the three groups (all P>0.05). The expression of platelet membrane GPⅡb/Ⅲa in UFH group, dalteparin group and enoxaparin group at 10 minutes and 20 minutes after corresponding drug administration were obviously higher than pre-administration (P<0.05). The expression of platelet membrane GPⅡb/Ⅲa in dalteparin group and enoxaparin group at 10 minutes of post-administration were lower than UFH group (P<0.05), but there were not statistically significant differences between the two groups (P>0.05). The level of sCD40L in UFH group at 10 minutes and 20 minutes of post-administration were significantly higher than pre-administration (P<0.05); The level of sCD40L in dalteparin group and enoxaparin group at 10 minutes after drug administration were higher than pre-administration, however, there were not significant differences (P>0.05). The level of CD62P in UFH group at 10 minutes after drug administration was significantly higher than pre-administration (P<0.05); The level of CD62P in UFH was significant higher than dalteparin group and enoxaparin group at 10 minutes of post-administration (P<0.05), but there were not significant differences at 20 minutes of post-administration among the three groups (P>0.05). The level of vWF in dalteparin group at 10 minutes of post-administration and enoxaparin group at 20 minutes of post-administration were significantly lower than pre-administration (P<0.05), there were not obviously changing in UFH (P>0.05).Conclusions: The markers of platelet activation, i.e., platelet membrane GPⅡb/Ⅲa was detected by flow cytometry, plasma vWF, CD62P and CD40L were measured by enzyme linked immunoadsorbent assay (ELISA). The results show that intrathecal injection of unfractionated heparin or LMWH (dalteparin or enoxaparin) in coronary angiography all can activate platelet. Compare to UFH, dalteparin and enoxaparin have less effect on platelet activation; however, there were not significant differences between the effect of dalteparin and enoxaparin on platelet activation.