ristocetin and Myocardial-Infarction

Impaired platelet function has been reported in acute myocardial infarction (AMI) and stroke. However, prospective data on the changes of platelet status in patients before the occurrence of hemorrhagic stroke after thrombolytic therapy are unavailable.. An 86-year-old male patient was among the 23 AMI patients enrolled in the platelet study for the GUSTO-III trial. He received 325 mg of aspirin daily for at least 6 years, suffered an AMI, and was successfully reperfused with alteplase, but after 44 hours developed a large hemorrhagic stroke resulting in paraplegia. Platelet aggregation and receptor expression were measured by flow cytometry and ELISA before thrombolysis and at 3, 6, 12, and 24 hours thereafter. The percentage of platelet aggregation was lower in the stroke patient at every time point when induced by 5 micromol/L of ADP, by 10 micromol/L of ADP, and by thrombin than in the rest of the AMI group. Ristocetin and collagen-induced aggregability were within the group range. Decreased platelet glycoprotein Ib, IIb, IIIa, and IIb/IIIa and vitronectin receptor expression were observed in the stroke patient. No other differences in p24 (CD9), very late antigen-2, P-selectin, and platelet/endothelial cell adhesion molecule-1 expression were determined.. Profound depression of platelet status preceded the occurrence of hemorrhagic stroke in an elderly long-term aspirin user treated with thrombolytic therapy. Initial "exhausted" platelets may be responsible for the increased risk for hemorrhagic stroke after coronary thrombolysis.

Topics: Adenosine Diphosphate; Aged; Aged, 80 and over; Antigens, CD; Aspirin; Blood Platelets; Cerebral Hemorrhage; Cerebrovascular Disorders; Collagen; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Follow-Up Studies; Humans; Male; Membrane Glycoproteins; Myocardial Infarction; P-Selectin; Paraplegia; Plasminogen Activators; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Endothelial Cell Adhesion Molecule-1; Platelet Membrane Glycoproteins; Prospective Studies; Receptors, Very Late Antigen; Ristocetin; Tetraspanin 29; Thrombin; Thrombolytic Therapy; Tissue Plasminogen Activator; Vitronectin

Platelets play an important role in the natural history of acute myocardial infarction (AMI).. Platelet aggregation and receptor expression were studied in 23 patients with AMI before reperfusion therapy and compared with 10 healthy control subjects. Platelet aggregation was induced with 5 micromol/L adenosine 5'-diphosphate, 10 micromol/L ADP, 1 microg/mL collagen, 1 mg/mL thrombin, and 1.25 mg/mL ristocetin. Receptor expression was measured by flow cytometry with monoclonal antibodies to p24 (CD9), Ib (CD42b), IIb (CD41b), IIIa (CD61), IIb/IIIa (CD41b/CD61), very late antigen-2 (CD49b), P-selectin (CD62p), platelet/endothelial cell adhesion molecule-1 (CD31); and vitronectin (CD51/CD61). The percentage of platelet aggregation was higher in patients with AMI when induced by 5 micromol/L ADP (64.1+/-12.7 vs 52.0+/-6.7; P=.04), by 10 micromol/L ADP (71.7+/-13.0 vs 59.2+/-7.2, P=.003), by thrombin (75.8+/-10.9 vs 60.5+/-6.9, P=.01), and by ristocetin (92.5+/-7.8 vs 71.3+/-7.4, P=.0001). Collagen-induced platelet aggregation did not differ between groups. Expression of P-selectin (log amplification of fluorescence intensity) (31.5+/-5.0 vs 25.1+/-2.6, P=.003) and platelet/endothelial cell adhesion molecule-1 (56.8+/-17.7 vs 44.5+/-3.7, P=.04) were significantly increased in patients with AMI. The expression of IIb (28.4+/-2.5 vs 37.2+/-1.7, P=.0001) and Ib (103.6+/-29.9 vs 133.8+/-8.0, P=.007) were reduced in patients with AMI.. Platelets are not necessarily systemically activated during the prereperfusion phase of AMI. For each agonist used and surface antigen measured, there was a cohort of patients with AMI within the normal or even below normal range of platelet status.

Topics: Adenosine Diphosphate; Aged; Antibodies, Monoclonal; Blood Platelets; Case-Control Studies; Collagen; Female; Flow Cytometry; Hemostatics; Humans; Male; Middle Aged; Myocardial Infarction; P-Selectin; Platelet Aggregation; Platelet Endothelial Cell Adhesion Molecule-1; Receptors, Cell Surface; Receptors, Cytoadhesin; Ristocetin; Thrombin

In 20 patients with acute myocardial infarction (AMI) treated with streptokinase (SK, n = 7), recombinant single-chain tissue plasminogen activator (rt-PA, n = 7) or urokinase (UK, n = 6), the behavior of plasma von Willebrand factor (vWF) was studied before and 1.5, 3, 24, 48, and 72 hours after beginning thrombolytic therapy. vWF antigen (vWF:Ag) was high in plasma, especially after SK. The ristocetin cofactor (RiCof) activity of vWF, high before therapy, tended to decrease soon after therapy. This pattern of vWF changes was paralleled by the early loss of higher molecular weight multimers. By immunoblotting of immunopurified and reduced vWF and monoclonal antibody epitope mapping, we found that vWF was degraded after thrombolysis, especially after SK, as indicated by the higher values of two plasmin-generated fragments of 176 and 145 Kd. There were more plasmin-generated fragments in the five patients who had bleeding complications than in the remaining 15 who did not. In conclusion, quantitative and qualitative changes of vWF compatible with proteolytic degradation of the protein occur during thrombolytic therapy. Such degradation, roughly proportional to the degree of the general lytic state induced by each agent, might be a cofactor of the bleeding complications occurring in treated patients.

Topics: Fibrinolysin; Hemorrhage; Humans; Immunoblotting; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Ristocetin; Streptokinase; Thrombolytic Therapy; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator; von Willebrand Factor

Topics: Adult; Aged; Female; Hematologic Tests; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation; Ristocetin; von Willebrand Factor