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61.
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Milani Junior R; Jorge MT; de Campos FP; Martins FP; Bousso A; Cardoso JL; Ribeiro LA; Fan HW; Franca FO; Sano-Martins IS; Cardoso D; Ide Fernandez C; Fernandes JC; Aldred VL; Sandoval MP; Puorto G; Theakston RD; Warrell DA 《QJM : monthly journal of the Association of Physicians》1997,90(5):323-334
The jararacucu, one of the most dreaded snakes of Brazil, southern Bolivia,
Paraguay and northeastern Argentina, is a heavily-built pit viper which may
grow to a length of 2.2 m. Up to 1000 mg (dry weight) of highly-lethal
venom may be milked from its venom glands on a single occasion. It has
accounted for 0.8% to 10% of series of snake bites in Sao Paulo State,
Brazil. We examined 29 cases of proven jararacucu bites recruited over a
20-year period in two Sao Paulo hospitals. Severe signs of local and
systemic envenoming, (local necrosis, shock, spontaneous systemic bleeding,
renal failure) were seen only in patients bitten by snakes longer than 50
cm; bites by shorter specimens were more likely to cause incoagulable
blood. Fourteen patients developed coagulopathy, six local necrosis
(requiring amputation in one) and five local abscesses. Two became shocked
and four developed renal failure. Three patients, aged 3, 11 and 65 years,
died 18.75, 27.75 and 83 h after being bitten, with respiratory and
circulatory failure despite large doses of specific antivenom and
intensive-care- unit management. In two patients, autopsies revealed acute
renal tubular necrosis, cerebral oedema, haemorrhagic rhabdomyolysis at the
site of the bite and disseminated intravascular coagulation. In one
survivor with chronic renal failure, renal biopsy showed bilateral cortical
necrosis; the patient remains dependent on haemodialysis. Effects of
polyspecific Bothrops antivenom were not impressive, and it has been
suggested that anti-Bothrops and anti-Crotalus antivenoms should be given
in combination.
相似文献
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Relation of soluble and platelet P-selectin to early outcome in patients with acute myocardial infarction after thrombolytic therapy 总被引:2,自引:0,他引:2
Gurbel PA O'Connor CM Dalesandro MR Serebruany VL 《The American journal of cardiology》2001,87(6):774-7, A7
Pre- and post-treatment platelet and soluble P-selectin were measured in a group of patients enrolled in the GUSTO-III study and were correlated with clinical outcomes. A peak in soluble P-selectin levels at 3 hours after thrombolytic therapy and lower baseline platelet P-selectin were associated with successful thrombolysis. 相似文献
65.
Serebruany VL Malinin AI O'connor CM Gurbel PA;Roxifiban Oral Compound Kinetics Evaluation Trial-I Platelet Substudy 《American heart journal》2003,146(1):91-98
Background
It has been expected that therapy with oral glycoprotein (GP) IIb/IIIa blockers including roxifiban will reduce mortality and vascular complications in a long-term. However, platelet-related properties of roxifiban in the clinical setting are not well known. We measured platelet characteristics during chronic treatment in patients with coronary artery disease enrolled in the Roxifiban Oral Compound Kinetics Evaluation Trial (ROCKET-I).Methods
ROCKET-I was designed as a randomized, double blind, multicenter, dose-ranging study of roxifiban, administered either as monotherapy or concomitantly with aspirin, compared with aspirin alone. Thirty-one patients were assigned for 24 weeks of therapy with aspirin (n = 7), roxifiban (n = 9), or roxifiban plus aspirin (n = 15). Platelets were assessed 5 times in each patient at baseline, and at weeks 2, 4, 12, 18, and 24 thereafter with aggregometry and flow cytometry.Results
Baseline platelet characteristics were similar in all 3 groups. There was a consistent significant decrease of adenosine diphosphate- (P = .0001) and collagen-induced (P = .002) platelet aggregation in the patients treated with roxifiban when compared with patients treated with aspirin alone. Flow cytometry revealed paradoxical late activation of GP IIb/IIIa expression (P = .007) when roxifiban was used without aspirin, which was significant compared with the aspirin and aspirin-roxifiban groups. There were no differences among groups in GP Ib expression, although its rise was more profound in the patients treated with roxifiban. There were substantial differences in the P-selectin expression. Although aspirin time dependently decreased the percent of P-selectin positive platelets (P = .02), treatment with roxifiban resulted in the phasic changes with the early inhibition (P = .01) and then 2-fold activation (P = .0001) starting at week 12 of the therapy. There was an early transient activation of platelet endothelial cell adhesion molecule-1 expression (P = .008) at week 2, followed by the later inhibition of this receptor (P = .003) in patients treated with roxifiban.Conclusion
Despite achieving sustained inhibition of platelet aggregation, therapy with roxifiban has been associated with over expression or phasic changes of major platelet receptors. These data may explain clinical concerns about the use of oral GP IIb/IIIa inhibitors linking higher mortality rates and incidence of thrombotic episodes with paradoxical switching to alternative passways of platelet activation. 相似文献66.
Gurbel PA Cummings CC Bell CR Alford AB Meister AF Serebruany VL;Plavix Reduction Of New Thrombus Occurrence 《American heart journal》2003,145(2):239-247
Background Despite the common practice of clopidogrel loading for coronary stenting, the time dependence and degree of platelet inhibition after this therapy are not well defined. We sought to establish an optimal clopidogrel dosing regimen for sustained platelet inhibition in stented patients. Methods and Results Platelets were assessed by conventional aggregation with 5 μmol/L adenosine diphosphate (ADP), 1 μg/mL collagen (COLL), and 750 μmol/L arachidonic acid; whole blood aggregation by 1 μg/mL collagen (WBA); shear-induced closure time (CT); contractile force (CF); and expression of 9 surface receptors by flow cytometry in 100 patients undergoing elective stent placement without glycoprotein (GP) IIb/IIIa receptor antagonists. Blood was obtained at baseline and serially over 5 days poststenting after different clopidogrel loading regimens: 300 mg 24 hours before (Group A), 12 hours before (Group B), 3 to 6 hours before (Group C), and 75 mg at the time of intervention (Group D). Before stenting, ADP, COLL, CT, and WBA were reduced by clopidogrel loading (P < .05). CF was not affected by clopidogrel. Before stenting, GP IIb/IIIa expression increased in groups A through C (P < .05), whereas PECAM-1 and CD107a were reduced (P < .05). At 2 hours and 2 days poststenting, platelets, in general, exhibited an increase in activity that was most inhibited by clopidogrel loading. Clopidogrel inhibited GP Ib, platelet/endothelial cell adhesion molecule-1, CD 107a, CD 151, and GP IIb/IIIa expression at day 5 poststenting. Conclusion A 300 mg clopidogrel load given 3 to 24 hours before stenting inhibits platelets at the time of the procedure and reduces poststent activity more than a 75 mg dose given at the time of the procedure. The inhibition of adhesive molecule expression may also contribute an antithrombotic effect. Poststent activation of platelets may warrant higher periprocedural dosing. (Am Heart J 2003;145:239-47.) 相似文献
67.
Platelets are heterogeneous in the content of membrane glycoprotein (GP)IIb/IIIa complex. To determine whether this heterogeneity is related to changes associated with platelet aging in the circulation, newly released platelets, obtained during recovery from nonimmune- mediated acute experimental thrombocytopenia in baboons, were studied. Monoclonal antibody (MoAb) binding to epitopes expressed on GPIIb/IIIa complex (LJ-CP8), GMP-140 (S12), and GPIa/IIa (12F1) was measured on control platelets (comprising platelets with a normal age distribution; mean age 60 to 72 hours) and newly formed platelets (mean age 12 hours), both in the resting state and after thrombin stimulation. Whereas LJ-CP8 binding to resting control platelets increased by 34% upon stimulation by gamma-thrombin from 30,885 +/- 1,171 to 41,458 +/- 1,311 molecules/platelet at saturating concentrations of antibody, LJ- CP8 binding to resting young platelets did not increase significantly upon thrombin stimulation (31,878 +/- 3,330 and 33,791 +/- 3,486 molecules/platelet, respectively). Similarly, binding of antibody S12 in response to maximal thrombin stimulation was reduced by 42% from 10,246 +/- 834 molecules/platelet at saturating concentrations of S12 for control platelets to 5,971 +/- 665 molecules/platelet for young platelets (P = .001). S12 binding to unstimulated platelets was less than 10% of the binding observed after thrombin stimulation at all concentrations of S12 for both control and young platelets. However, maximal binding of antibody 12F1 to resting control platelets did not differ significantly from that observed with resting young platelets (2,926 +/- 167 and 2,857 +/- 208 molecules/platelet, respectively), and 12F1 binding was unchanged after thrombin stimulation for both control and young platelets. We conclude that the thrombin-induced increase in the expression of epitopes on platelet membrane GPIIb/IIIa complex and GMP-140 is a function of platelet age. 相似文献
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69.
Serebruany VL Malinin AI Ferguson JJ Vahabi J Atar D Hennekens CH 《Fundamental & clinical pharmacology》2008,22(3):315-321
A number of antiplatelet drugs, principally aspirin alone or in combination, have been evaluated in randomized trials of survivors of prior occlusive vascular disease events or of individuals at high risk because of multiple cardiovascular risk factors. In this meta-analysis we compare single and dual antiplatelet regimens to quantitate the risks of bleeding. Data from randomized trials published in English in 1988-2006 were retrieved from MEDLINE, OVID, and CARDIOSOURCE. Inclusion criteria were clinical follow-up for at least 1 month and the presence of data on bleeding complications. Information was compiled on sample size, antiplatelet agents tested, patient characteristics as well as major, minor, fatal and intracranial bleeding. Using these criteria, we identified 18 randomized trials, which included 129,314 patients. For each endpoint, relative risk (RR) and 95% confidence intervals (CI) were calculated. Dual antiplatelet therapy is associated with a significantly increased risk of major (RR 1.47, CI = 1.36-1.60) and minor bleeding events (RR 1.56, CI = 1.47-1.66) compared to single agent therapy. Although based on small numbers, there were no significant differences in fatal (RR 1.10, CI = 0.87-1.40) or intracranial (RR 1.07, CI = 0.85-1.35) bleedings although the CIs are wide to make definite assessments. Patients treated with dual antiplatelet therapy have an approximately 40-50% increase in risks of major and minor bleeding compared to those receiving single agent therapy during the duration of the scrutinized trials. The magnitude of this excess risk is not so remote from the approximately 60% increase observed in trials comparing single antiplatelet agents to placebo. This excess risk should be considered when choosing the optimal antiplatelet strategy for long-term treatment of patients with prior occlusive vascular events or those at high risk of developing occlusive vascular disease. 相似文献
70.