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Objective Drug-induced immune thrombocytopenia (DITP) is a major adverse drug effect mediated by drugdependent antibodies.It can be actuated by a wide range of medications,including Rifampicin.Methods Rifampicin-dependent antibody (rd-Ab) from a rifampicin-treated tuberculosis patient with thrombocytopenia (RITP) was characterized by in vitro and in vivo assays,which includes flow cytometry,monoclonal antibody immobilization of platelet antigens (MAIPA) assay,platelet aggregation assay and RITP mouse model.Results The rd-Ab could bind glycoprotein (GP) Ⅱ b/Ⅲ a,as shown by the MAIPA assay.The binding of rd-Ab could be blocked by AP2,a monoclonal antibody that binds a calcium dependent site on GP Ⅱ b/Ⅲ a complex and inhibits ADP-induced platelet aggregation.These results suggested that rd-Ab binds the same site or proximal sites on the GP Ⅱ b/Ⅲ a complex as AP2.Furthermore,the rd-Ab inhibited platelet aggregation in vitro.In an established NOD/SCID mouse model of RITP,the rd-Ab caused a rapid clearance of human platelets (MPL=1.1 ± 0.2h).The in vivo platelet loss could be partially prevented by treatments with intravenous immunoglobulin (IVIG) or corticosteroids (MPL=4.7 ± 0.7h and 4.2 ± 1.1h,P＜0.05).Slowing of platelet clearance was observed immediately upon IVIG treatment,while upon corticosteroid treatment at 24h,and reaching its peak at 72h.Combination of IVIG and corticosteroid treatments was more efficacious (MPL=6.2 ± 1.5h,P＜0.05).Conclusions 1.The rd-Ab binds to calcium-dependent-epitopes on the calcium dependent site of GP Ⅱ b/Ⅲ a complex,which causes platelet damage and inhibits platelet aggregation.2.Either IVIG or corticosteroid alone can partially block platelet clearance by rd-Ab.Slowing of platelet clearance is observed immediately upon IVIG treatment,or upon corticosteroid treatment several days later,indicating that IVIG may be more suitable for acutely raising the platelet count than corticosteroid treatment for RITP.3.Combination of IVIG and corticosteroid treatment is more efficacious than IVIG or corticosteroids alone.
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Objective To systematically evaluate the efficacy and safety of intracoronary abciximab administration as compared to intravenous in percutaneous coronary intervention (PCI) .Methods A search was conducted in PubMed ,EMBASE ,OVID ,CBM , CNKI and VIP for the randomized controlled trials (RCTs)of intracoronary abciximab administration versus intravenous in PCI , from the date of their establishment to September 30 ,2013 ,and the domestic relevant papers published in recent 1 year were also searched manually ,the bibliographies of the included studies were searched too .According to the criteria of the cochrane Hand-book ,two reviewers evaluated the quality of the included RCTs and extracted data independently ,and then the extracted data were analyzed by using RevMan 5 .1 software .Results 8 RCTs involving 10 articles with 4 150 patients who treated with PCI were in-cluded .The results of meta-analysis showed that :(1) Compared intravenous administration and intracoronary abciximab administra-tion ,there were no significant differences in the two groups for the major adverse cardiovascular event (MACE) and the mortality (OR=0 .78 ,95% CI 0 .54-1 .14 ,P=0 .20) ,(OR=0 .56 ,95% CI 0 .24-1 .30 ,P=0 .18) .(2)Compared with intravenous adminis-tration ,intracoronary abciximab administration were not associated with any excess of major bleeding complications :(OR=1 .26 , 95% CI 0 .78-2 .02 ,P=0 .35) .Conclusion Compared with standard abciximab regimen of intravenous bolus ,intracoronary admin-istration had equivalent effects in clinical outcomes in patients undergoing PCI ,and did not increase the incidence of bleeding events .
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Objective To unravel the relationship between Toll-like receptor 4 (TLR4) expression in platelets and the activation of platelet in thrombocytopenia (TCP) in case of sepsis. Method A total of 64 patients with sepsis were prospectively studied with control. Platelet count (PC), mean platelet volume (MPV),platelet distribution width (PDW),platelet TLR4 expression, platelet PAC-1 expression, sCD40L and TNF-α concentrations were compared between healthy control group (15 cases) and sepsis group on admission and 3 d,Sd,and 9 days after admission. The changes of MPV and PDW in TCP and non-TCP subgroups of sepsis before and after treatment were recorded. Prognostic index was analyzed. Results The PC was lower in sepsis group (P=0.006), and MPV and PDW were higher in sepsis group than those in healthy control group (P = 0.046, P =0.001). Platelet TLR4 and PAC-1 expressions, and sCD40L and TNF-α levels also increased more significantly in sepsis group (P ＜ 0.001). PAC-1 expression and TNF- level were higher in TCP group than those in non-TCP group before and after treatment (P = 0.023, P = 0.011). The sCD40L concentration and platelet TLR4 expression were significantly higher in treated TCP groups than in non-TCP group (P = 0.047, P = 0.001). Compared with non-TCP,the rate of bleeding was higher (P = 0.024) and the length of ICU stay was longer (P = 0.013).The APACHE Ⅱ score and the 28-day mortality were higher in TCP group (P ＜ 0.01, P = 0.048). Conclusions The elevation of platelet TLR4 expression in sepsis along with platelet activation is closely related to the incidence of thrombocytopenia. The occurrence of TCP is a poor prognosis sign of sepsis.
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Platelet glycoprotein ⅡbⅢa receptor antagonists is a class of novel antiplatelet agents. This article explores the application and prospect of platelet glycoprotein ⅡbⅢa receptor antagonists in ischemic stroke from the aspects of its combination with thrombolytic agents, the application of carotid artery angioplasty and stenting (CAS), and be used alone.
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Objective:To evaluate the efficacy and safety of tirofiban,a platelet glycoproteinⅡb/Ⅲa Inhibitor,in percutaneous coronary intervention(PCI)of patients with acute non-ST segment elevation myocardial infarct(NSTEMI).Methods:A total of 114 patients with acute NSTEMI were enrolled in the trial from Sep.2005 to Jan.2007;they were randomly divided into 2 groups:tirofiban group(n=57)and placebo group(n=57).Patients in tirofiban group were given tirofiban for 24 h after PCI.All patients were routinely given heparin,aspirin and clopidogrel before CPI.The composite occurrence of death,myocardial infarction(MI),need for target vessel revascularization(TVR)after PCI,and the adverse effects(hemorrhage and thrombocypenia)were compared between the 2 groups.Results:One(1.8%)patient had angina pectoris and the other(1.8%)developed subacute thrombus in control group within 24 h after PCl;there was no such event in the tirofiban group.Two(3.6%)patients developed angina pectoris and 2(3.6%) developed subacute thrombus within 30 days after PCI in control group;one patient(1.8%)in birofiban group developed angina pectoris and one patient in birofiban group developed subacute thrombus.Each group had one case(1.8%)of upper digestive tract bleeding during hospitalization.No intracranial hemorrhage,skin/ mucosa hemorrhage,thrombocytopenia,or-death occurred in the 2 groups.Intravenous tirofiban treatment reduced the composite occurrence of death of NSTEMI patients after PCI(P