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Biomedical subjects

I Ott

Publications and source records attributed to I Ott.

At least 19 recordsLinked to original sources
PubMed2006

[Tissue factor in acute coronary syndromes].

Rupture of an atherosclerotic plaque with subsequent thrombosis and myocardial ischemia is the patho-physiological mechanism in acute coronary syndromes. Tissue factor (TF) as the main initiator of the extrinsic coagulation cascade plays a central role in the pathogenesis of acute coronary syndromes. The extent of the thrombotic process is modulated by local vascular TF of the ruptured plaque as well as by circulating TF. In addition, TF alters signaling pathways and, thereby, contributes to inflammatory reactions and vascular remodeling. This review addresses current concepts of the role of TF in acute coronary syndromes and discusses potential consequences and therapeutic approaches.

Acute Disease↗
PubMed2001

Regulation of monocyte procoagulant activity in acute myocardial infarction: role of tissue factor and tissue factor pathway inhibitor-1.

In acute myocardial infarction (AMI), monocyte procoagulant activity is increased and may contribute to the risk for recurrence and other thrombotic events. This study sought to investigate the role tissue factor (TF) and tissue factor pathway inhibitor-1 (TFPI-1) in the regulation of monocyte procoagulant activity in AMI. Serial venous blood samples were obtained from 40 patients with AMI undergoing revascularization by stent placement. Twenty patients with elective stenting for stable angina served as control subjects. TF proteolytic activity was measured with spectrozyme factor Xa (FXa), TF and TFPI-1 surface expression on monocytes by flow cytometry, RNA expression in whole blood by reverse transcription-polymerase chain reaction, and concentrations of plasma prothrombin fragments F(1 + 2) by immunoassay. Forty-eight hours after AMI, an increase was found in TF RNA, followed by an increase in TF surface expression by 24% +/- 4% and in plasma concentration of F(1 + 2) by 103% +/- 17% (P <.05). These changes could not be attributed to the intervention because they did not occur in the control group. TFPI-1 RNA and binding to the monocyte surface remained unchanged. FXa generation by monocytes of patients with AMI increased 53.6% +/- 9% in the presence of polyclonal antibodies to TFPI-1, indicating that cell-associated TFPI-1 inhibits monocyte TF activity. The increased monocyte procoagulant activity in AMI was caused by an up-regulation of TF that was partially inhibited by surface-bound TFPI-1. Anticoagulant therapy by direct inhibition of TF activity may, thus, be particularly effective in AMI. (Blood. 2001;97:3721-3726)

Adult↗
PubMed2001

Surfactant protein B labelled with [(99m)Tc(CO)3(H20)3](+) retains biological activity in vitro..

UNLABELLED: Labelling of the hydrophobic surfactant protein B (SP-B) under non-reducing conditions was achieved with [(99m)Tc(CO)(3)(H2O)(3)](+) prepared according to Alberto et al. (JACS, 1998). The binding of radioactivity was protein-specific, with an overall radiochemical yield of 50%. Gel electrophoresis and Westernblot analyses showed no structural changes of SP-B. Spreading properties and surface activity of (99m)Tc-labelled SP-B in an air/water interface coincided with those of unlabelled SP-B. (99m)Tc-SP-B seems to be a promising agent to observe surfactant spreading under clinical conditions. BACKGROUND: Therapeutic results for surfactant instillation in clinical trials are conflicting. The (99m)Tc-labelling of surfactant would allow to observe its spreading in the lung under clinical conditions. METHODS: [(99m)Tc(CO)(3)(H2O)(3)](+) was prepared as described by Alberto et al. (JACS, 1998). This carbonyl complex was used for the direct labelling of surfactant protein B (SP-B) under non-reductive conditions by direct incubation with SP-B at elevated temperature followed by extraction into CHCl(3)/MeOH. RESULTS: The hydrophobic protein SP-B was labelled with [(99m)Tc(CO)(3)(H2O)(3)](+). An overall radiochemical yield of about 50% was achieved. HPLC-analysis revealed a single radiolabelled species according to UV elution profile of SP-B, supported by paper and size exclusion chromatography. Gel electrophoresis confirmed that the dimer structure of SP-B was preserved. Spreading properties of (99m)Tc-labelled SP-B in an air/water interface coincided with those of unlabelled SP-B. Spreading of radioactivity observed in a glass trough of 26 cm x 27 cm with a gamma camera was completed during the first 7-9 sec after application of (99m)Tc-labelled SP-B. The corresponding decrease of surface tension to 45 mN/m at the peripheral surface tension sensors took 7 sec +/- 2 sec (MEAN +/- STD; n = 3). CONCLUSIONS: Direct and specific (99m)Tc-labelling of the hydrophobic surfactant protein B was achieved using the [(99m)Tc(CO)(3)(H2O)(3)](+) precursor. This procedure can easily be used to prepare specifically labelled surfactant mixtures with spreading properties that coincide with those of unlabelled surfactant.

Animals↗
PubMed2000

Reversible regulation of tissue factor-induced coagulation by glycosyl phosphatidylinositol-anchored tissue factor pathway inhibitor.

Endothelial and tumor cells synthesize tissue factor pathway inhibitor (TFPI-1), which regulates tissue factor (TF) function by TF. VIIa. Xa. TFPI-1 quaternary complex formation (where VIIa and Xa are coagulation factors) and by translocation of these complexes into glycosphingolipid-rich microdomains of the cell membrane. Recombinant TFPI-1 added exogenously to cells is targeted to a degradation pathway. This study analyzes whether quaternary complex formation with endogenous TFPI-1 results also in internalization and degradation. We demonstrate that endogenous TFPI-1 and recombinant TFPI-1 differ in their distribution on the cell surface. Recombinant TFPI-1 is found in phospholipid- and glycosphingolipid-rich membrane domains, whereas endogenous TFPI-1 preferentially localizes to glycosphingolipid-rich microdomains. On quaternary complex formation, endogenous TFPI-1 remains protease sensitive and accessible for antibodies on intact cells, demonstrating that it is not appreciably internalized. Rather, regulation of TF by TFPI-1 is restored within 12 hours, consistent with dissociation of quaternary complexes on the cell surface. Endogenous TFPI-1 can be released from the cell surface by phospholipase treatment, indicating that TFPI-1 either is a glycosyl phosphatidylinositol (GPI)-anchored protein or binds to a GPI-linked receptor. We demonstrate that expression of a recombinant GPI-anchored form of TFPI-1 targets TF. VIIa complexes to glycosphingolipid-rich membrane fractions. Thus, GPI anchoring of TFPI-1 is sufficient for regulation of TF. VIIa complex function by a pathway of reversible inhibition rather than internalization and degradation.

Animals↗
PubMed2000

Diverse functions of protease receptor tissue factor in inflammation and metastasis.

Accumulating evidence suggests that protease receptors and their cognate protease ligands play important roles in cell-signaling events that regulate cell adhesion and migration in inflammation as well as tumor invasion and metastasis. Tissue factor (TF), the cell surface receptor for the serine protease VIIa and the initiator of the coagulation pathways, supports metastatic implantation by activating extracellular, protease-dependent signaling pathways and by intracellular links to the actin cytoskeleton. The adhesion of TF-expressing tumor cells can be mediated by interactions of the receptor-protease complex with specific matrix-associated inhibitors, suggesting a novel bridging mechanism by which proteases participate in migratory functions of cells.

Humans↗
PubMed1999

Effect of glycoprotein IIb/IIIa receptor blockade on platelet-leukocyte interaction and surface expression of the leukocyte integrin Mac-1 in acute myocardial infarction.

OBJECTIVES: This prospective randomized study investigated platelet-induced upregulation of Mac-1 on monocytes and its inhibition by glycoprotein (GP) IIb/IIIa blockage in patients with acute myocardial infarction (AMI). BACKGROUND: In experimental AMI, Mac-1 on leukocytes is the pivotal adhesion molecule for detrimental inflammatory responses. In vitro, platelet adhesion to monocytes upregulates Mac-1. METHODS: Patients undergoing stenting in AMI within 48 h after onset of symptoms were randomly assigned to receive either standard-dose heparin (n = 50) or abciximab plus low-dose heparin (n = 50). In serial blood samples, we assessed platelet-monocyte interaction and Mac-1 surface expression by triple color immunofluorescence flow cytometry. RESULTS: Compared with platelet-negative monocytes, Mac-1 surface expression on monocytes with attached platelets was upregulated (median fluorescence intensity [interquartile range]: 259 [179 to 367] vs. 135 [78 to 195] arbitrary units, p < 0.001). As an indicator of platelet-monocyte interaction, mean fluorescence of the platelet marker GP Ib alpha in the monocytes population decreased after abciximab, although it remained unaffected by heparin alone. Abciximab achieved this effect by a reduction in platelet mass attached to monocytes (GP Ib alpha fluorescence intensity of heterotypic aggregates at 24 h [arbitrary units]: 187 [143 to 236] after abciximab vs. 228 [156 to 332] after heparin, p = 0.02), whereas it did not affect the percentage of monocytes with adherent platelets. Reduction of platelet-monocyte interaction resulted in decreased Mac-1 surface expression (fluorescence intensity at 24 h [arbitrary units]: 116 [68 to 153] after abciximab vs. 162 [117 to 239] after heparin, p = 0.001). CONCLUSIONS: In patients with AMI, platelet-leukocyte interactions modulate Mac-1 expression on monocytes. Glycoprotein IIb/IIIa blockade is a therapeutic option to interfere with this mechanism.

Abciximab↗
PubMed1998

Procoagulant inflammatory responses of monocytes after direct balloon angioplasty in acute myocardial infarction.

This study sought to investigate monocyte procoagulant activity and Mac-1 expression after successful percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI). An increased leukocyte count is an important risk factor for subsequent adverse cardiac events in AMI. Cellular procoagulant responses may contribute to the risk of thrombotic events after AMI. In 20 patients with AMI serial venous blood samples were obtained before, 4, 8 hours, and daily after direct PTCA. Twenty patients with elective PTCA served as a control group. We measured leukocyte procoagulant activity with a 1-stage clotting assay, Mac-1 expression of monocytes by flow cytometry, concentrations of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-8 using immunoassays. Forty-eight hours after PTCA in patients with AMI, an increase in systemic IL-6 and C-reactive concentrations was found (p = 0.001, p = 0.008) associated with an increase in monocyte Mac-1 expression by 49 +/- 18% (p = 0.04) and followed by an increase in monocyte procoagulant activity by 140 +/- 63% 72 hours after PTCA (p = 0.01). None of these changes were detectable in the control group. No changes in the concentrations of the cytokines IL-1beta, tumor necrosis factor-alpha, or IL-8 were found. The present study demonstrates an increase in procoagulant activity along with an increase in Mac-1 expression on circulating monocytes after successful PTCA in AMI associated with an increase in systemic IL-6. These cellular procoagulant responses may limit the clinical benefit from timely reperfusion.

Aged↗
PubMed1998

A role for tissue factor in cell adhesion and migration mediated by interaction with actin-binding protein 280.

Tissue factor (TF), the protease receptor initiating the coagulation system, functions in vascular development, angiogenesis, and tumor cell metastasis by poorly defined molecular mechanisms. We demonstrate that immobilized ligands for TF specifically support cell adhesion, migration, spreading, and intracellular signaling, which are not inhibited by RGD peptides. Two-hybrid screening identified actin-binding protein 280 (ABP-280) as ligand for the TF cytoplasmic domain. Extracellular ligation of TF is necessary for ABP-280 binding. ABP-280 recruitment to TF adhesion contacts is associated with reorganization of actin filaments, but cytoskeletal adaptor molecules typically found in integrin-mediated focal contacts are not associated with TF. Chimeric molecules of the TF cytoplasmic domain and an unrelated extracellular domain support cell spreading and migration, demonstrating that the extracellular domain of TF is not involved in the recruitment of accessory molecules that influence adhesive functions. Replacement of TF's cytoplasmic Ser residues with Asp to mimic phosphorylation enhances the interaction with ABP-280, whereas Ala mutations abolish coprecipitation of ABP-280 with immobilized TF cytoplasmic domain, and severely reduce cell spreading. The specific interaction of the TF cytoplasmic domain with ABP-280 provides a molecular pathway by which TF supports tumor cell metastasis and vascular remodeling.

Binding Sites↗
PubMed1997

Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets.

BACKGROUND: Activated platelets tether and activate myeloid leukocytes. To investigate the potential relevance of this mechanism in acute myocardial infarction (AMI), we examined cytokine induction by leukocyte-platelet adhesion and the occurrence of leukocyte-platelet conjugates in patients with AMI. METHODS AND RESULTS: We obtained peripheral venous blood samples in 20 patients with AMI before and daily for 5 days after direct percutaneous transluminal coronary angioplasty (PTCA) and in 20 patients undergoing elective PTCA. Throughout the study period, CD41 immunofluorescence of leukocytes (flow cytometry) revealed increased leukocyte-platelet adhesion in patients with AMI compared with control patients (mean +/- SE of fluorescence [channels] before PTCA: 77 +/- 16 versus 35 +/- 9; P = .003). In vitro, thrombin-stimulated fixed platelets bound to neutrophils and monocytes. Within 2 hours, this resulted in increased mRNA for interleukin (IL),1 beta, IL-8, and monocyte chemoattractant protein (MCP)-1 in unfractionated leukocytes. After 4 hours, IL-1 beta and IL-8 concentration of the cell-free supernatant had increased by 268 +/- 36% and 210 +/- 7%, respectively, and cellular MCP-1 content had increased by 170 +/- 8%. Addition of activated platelets to adherent monocytes had a similar effect and was associated with nuclear factor-kappa B activation. Inhibition of binding by anti-P selectin antibodies reduced the effect of activated platelets on cytokine production. CONCLUSIONS: In patients with AMI, leukocyte-platelet adhesion is increased. Binding of activated platelets induces IL-1 beta, IL-8, and MCP-1 in leukocytes. Our findings suggest that leukocyte-platelet adhesion contributes to the regulation of inflammatory responses in AMI.

Adult↗
PubMed1997

Induction of cytokine expression in leukocytes in acute myocardial infarction.

OBJECTIVES: This study sought to investigate whether cytokine expression in leukocytes may be induced by plasma from the reperfused heart of patients with an acute myocardial infarction (MI). BACKGROUND: Reperfusion in acute MI is associated with deleterious local and systemic inflammatory responses that are regulated by cytokines. Induction of cytokine expression in resident leukocytes could contribute to inflammatory responses of the ischemic and reperfused heart. METHODS: Blood samples of 10 patients with an acute MI were obtained simultaneously from the coronary sinus and the aorta before and 5 min after recanalization of the coronary occlusion. Ten patients with elective percutaneous transluminal coronary angioplasty served as a control group. We incubated leukocytes from healthy donors with plasma samples and analyzed mRNA expression of interleukin (IL)-1 beta, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) by Northern blot analysis. RESULTS: In patients with an acute MI, plasma obtained from the coronary sinus after recanalization increased the mRNA expression of IL-1 beta and IL-8 compared with that of plasma before recanalization (median [quartiles] difference before vs. after recanalization: 34.5 [4, 137], p = 0.017, for IL-1 beta; 18.5 [4, 35], p = 0.032, for IL-8) and simultaneously obtained aortic plasma (median [quartiles] coronary sinus-aortic differences after recanalization: 45.5 [-3, 115], p = 0.021, for IL-1 beta; 16 [4, 52], p = 0.005, for IL-8). No induction of IL-6 and TNF-alpha expression could be observed. No changes found in the study patients were detectable in the control group. CONCLUSIONS: Plasma from the ischemic and reperfused heart stimulates the expression of IL-1 beta and IL-8 in leukocytes. Therefore, leukocyte-derived cytokines may contribute to the regulation of cardiac inflammatory responses in patients with an acute MI.

Adult↗
PubMed1997

Reduction of monocyte-platelet interaction and monocyte activation in patients receiving antiplatelet therapy after coronary stent implantation.

BACKGROUND: Monocyte activation induces different procoagulant and proadhesive inflammatory responses and thus may play a role in thrombotic complications after coronary interventions. Monocyte-platelet interaction may trigger these effects inducing monocyte activation. AIMS: To characterize the effect of antiplatelet vs anticoagulation therapy on monocyte-platelet interaction and monocyte function after intracoronary stenting. METHODS AND RESULTS: Immediately before, and during the first 12 days after successful coronary stenting, monocyte-platelet conjugates and monocyte function were assessed by flow cytometric detection of GPIIb/IIIa (CD41) on monocytes and by monocyte surface exposure of Mac-1 (CD11b/CD18) and L-selectin (CD62L). Twenty patients receiving combined antiplatelet therapy (ticlopidine, aspirin) were compared to 20 patients with standard anticoagulation (phenprocoumon, overlapping heparin, aspirin). Before stenting, monocyte-platelet conjugates and Mac-1 surface expression in both groups were significantly increased, while L-selectin was significantly diminished. Anticoagulation did not change these variables significantly during the subsequent 12 days. In contrast, antiplatelet therapy reduced platelet-monocyte conjugates by 46 +/- 9.3% (mean +/- SEM, P = 0.0019) within 4 days, which was associated with a decrease in Mac-1 expression (28 +/- 6.7%, P = 0.0013) and an increase in L-selectin (56 +/- 15.0%, P = 0.0061). CONCLUSION: After intracoronary stenting, combined antiplatelet therapy, but not anticoagulation, causes reduction of monocyte-platelet interaction, which is associated with monocyte deactivation. This may contribute to a decreased risk for thrombotic events.

Adult↗
PubMed1997

Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity.

Interleukin (IL)-6 and IL-8 are important regulators of inflammatory responses in myocardial infarction. Induction of monocyte procoagulant activity (PCA) by these cytokines could present a mechanism that links inflammatory responses to thrombotic events. We therefore investigated the effect of IL-6 and IL-8 on monocyte tissue factor (TF) expression. Recombinant human IL-6 and IL-8 caused a time- and dose-dependent increase in PCA (recalcification time) of monocytic U937 cells and of mononuclear leukocytes. Using blocking anti-TF monoclonal antibodies and factor VII-deficient control plasma, this PCA was shown to be TF dependent. Compared with unstimulated cells, mononuclear cell PCA increased by 4.5-fold to 17 +/- 2 mU/5x10(5) cells after exposure to 100 ng/L IL-6 for 4 hours and by 6.6-fold to 27 +/- 4 mU/5x10(5) cells after exposure to IL-8 under the same conditions. Northern blot analysis showed an increase in TF mRNA after stimulation with IL-6 or IL-8 for 2 hours, and after 4 hours an increase in cellular TF protein content was found by immunoassay. Flow cytometry demonstrated that IL-6 and IL-8 induced an increase in TF surface expression on monocytes. Thus, IL-6 and IL-8 induce monocyte PCA by increasing mRNA, protein content, and surface expression of TF.

Blood Coagulation Factors↗
PubMed1996

Increased neutrophil-platelet adhesion in patients with unstable angina.

BACKGROUND: Neutrophil-platelet adhesion may occur as a consequence of platelet activation. The role of this heterotypic adhesion in ischemic disorders is poorly understood thus far. METHODS AND RESULTS: Systemic venous blood samples were taken from 25 patients with stable angina pectoris and 25 patients with unstable angina pectoris. Neutrophil activation and neutrophil-platelet adhesion were evaluated by two-color flow cytometry. Patients with unstable angina showed a significant increase in neutrophil-platelet adhesion compared with patients with stable angina (mean +/- SEM, 132.1 +/- 20.5 versus 29.8 +/- 4.7 anti-glycoprotein IIb/IIIa mean fluorescence intensity, P = .0001). Systemic neutrophil activation was found in patients with unstable angina compared with those with stable angina assessed by cell surface CD11b expression and shedding of L-selectin (115.6 +/- 10.3 versus 74.0 +/- 6.3 anti-CD11b mean fluorescence intensity, P = .002; 49.8 +/- 6.0 versus 72.1 +/- 4.0 anti-L-selectin mean fluorescence intensity, P = .006). Markers of neutrophil activation were related to the extent of neutrophil-platelet adhesion (CD11b: r = .5, P = .0005; L-selectin: r = .42, P = .012). In vitro studies revealed that binding of purified platelet membranes to control neutrophils caused a dose-dependent increase in CD11b surface expression, a decrease in surface L-selectin, and the release of superoxide anions. CONCLUSIONS: Thus, this study demonstrates that increased neutrophil-platelet adhesion may contribute to neutrophil activation in unstable angina.

Aged↗
PubMed1996

Platelet activation and coronary stent implantation. Effect of antithrombotic therapy.

BACKGROUND: Platelet activation and surface expression of adhesive glycoproteins play a key role in ischemic thrombotic complications after coronary intervention. The purpose of this case-control study was to evaluate the effects of two different antithrombotic regimens on platelet function after coronary Palmaz-Schatz stent implantation. METHODS AND RESULTS: The study group consisted of 46 "low-risk" patients who were treated with ticlopidine (250 mg BID) and aspirin (100 mg BID) after stenting. The control group was derived from a cohort of 151 patients receiving conventional anticoagulation therapy, including phenprocoumon (target international normalized ratio, 3.5), heparin (activated partial thromboplastin time, 80 to 120 seconds), and aspirin (100 mg BID) after stenting. Criteria for matching were indication for stenting, target vessel, balloon size, inflation pressure, and number of inserted stents. Matches were obtained for 38 patients. Platelet function was evaluated before and daily for 12 days after stenting in venous blood samples with immunologic activation markers. Patients receiving anticoagulation therapy showed a significantly increased surface exposure of LIBS1 (activated fibrinogen receptor; P < .05) and CD62P (P-selectin; P < .001) above prestent values, peaking days 3 to 6 after stenting. In contrast, in patients receiving ticlopidine, expression of LIBS1 decreased (P < .01) and expression of CD62P remained basically unchanged after stenting. Platelet count significantly decreased after stenting in patients treated by anticoagulation (day 3; P < .01), whereas no significant changes were found in the ticlopidine group. CONCLUSIONS: Significant platelet activation occurs in patients receiving anticoagulation therapy after stenting, while platelet deactivation is found in patients treated with combined antiplatelet therapy. This may contribute to a lowering of the incidence of subacute stent thrombosis.

Adult↗
PubMed1996

Neutrophil and platelet activation at balloon-injured coronary artery plaque in patients undergoing angioplasty.

OBJECTIVES: This study sought to investigate changes in the expression of activation-dependent adhesion receptors on neutrophils and platelets after exposure to the balloon-injured coronary artery plaque. BACKGROUND: Activation of blood cells at the balloon-injured coronary artery plaque may contribute to abrupt vessel closure and late restenosis after percutaneous transluminal coronary angioplasty. METHODS: In 30 patients undergoing elective coronary angioplasty, blood specimens were obtained through the balloon catheter proximal to the plaque before dilation and distal to the plaque after dilation. Simultaneous blood samples obtained through the guiding catheter served as control samples. Total surface expression of the inducible fibrinogen receptor (CD41) and surface expression of the activated fibrinogen receptor (LIBS1) on platelets as well as Mac-1 (CD11b) and L-selectin (CD62L) surface expression on neutrophils were assessed by flow cytometry. RESULTS: After exposure to the dilated coronary artery plaque, surface expression of LIBS1 on platelets increased by 40.5 +/- 11.0 mean (+/-SE) fluorescence (p=0.001) and that of CD11b on neutrophils increased by 20.1 +/- 4.4 mean fluorescence (p=0.018). Concomitantly, anti-CD62L binding on neutrophils decreased by 6.6 +/- 2.4 mean fluorescence (p=0.022). In contrast, surface expression of the adhesion receptors did not change significantly between the coronary ostium and the prestenotic coronary segment. CONCLUSIONS: The results of this study demonstrate neutrophil and platelet activation at the balloon-injured coronary artery plaque. This cellular activation may serve as a target for pharmacologic interventions to improve the outcome of coronary angioplasty.

Adult↗
PubMed1996

Platelet function in acute myocardial infarction treated with direct angioplasty.

BACKGROUND: In acute myocardial infarction (AMI), platelets play a key role in thrombotic processes that limit the patency of the recanalized, infarct-related coronary artery and contribute to reperfusion injury. Platelet function in the course of AMI treated by direct percutaneous transluminal coronary angioplasty (PTCA) has not been evaluated. METHODS AND RESULTS: In 15 patients with anterior AMI, peripheral venous blood samples were obtained before and 4, 8, 24, and 48 hours after recanalization of the occluded artery by PTCA. Fifteen patients who had stable coronary heart disease and were undergoing elective balloon angioplasty served as control subjects. Fibrinogen receptor function and surface expression of P-selectin on platelets were determined by flow cytometry. In addition, we evaluated generation of platelet-derived microparticles and the effect of systemic plasma from patients with AMI on normal platelet function and on platelet adhesion to human endothelial cells in culture. We found fibrinogen receptor activity and P-selectin expression on circulating platelets 8 hours after direct PTCA are decreased (P < .01). This coincided with a decrease in peripheral platelet count (P < .05) and an increase in generation of microparticles (P < .002). Twenty-four to 48 hours after PTCA, fibrinogen receptor activity and P-selectin expression increased again. Systemic plasma obtained before and after direct PTCA sensitized normal platelets to hyperaggregate in vitro (P < .001) and stimulated platelet adhesion to endothelial cells in culture (P < .01). None of the changes found in AMI were detectable in the control group. CONCLUSIONS: After transient apparent deactivation of circulating platelet, probably caused by sequestration of hyperactive platelets, the level of platelet activation increases in patients with AMI treated by direct PTCA. These findings underscore the need for novel antiplatelet strategies in AMI.

Adult↗
PubMed1996

Prospective evaluation of hemostatic predictors of subacute stent thrombosis after coronary Palmaz-Schatz stenting.

OBJECTIVES: This study sought to investigate hemostatic predictors of subacute occlusive coronary stent thrombosis. BACKGROUND: Better hemostatic monitoring may improve antithrombotic therapy after stenting. METHODS: In 140 consecutive patients undergoing Palmaz-Schatz stent implantation for suboptimal angioplasty results, we obtained serial blood samples immediately before and daily for 12 days after stenting. We prospectively tested the hypothesis that subacute stent thrombosis was more frequent if the surface expression of the inducible fibrinogen receptor on platelets (flow cytometry) or the concentration of plasma fibrinogen or that of the prothrombin fragments F1 + 2 before stent implantation exceeded the 75th percentile of the entire study cohort. RESULTS: All five stent occlusions encountered during the study occurred in patients with platelet fibrinogen receptor expression above the 75th percentile. Thus, the rate of stent occlusion differed significantly between the groups defined by platelet fibrinogen receptor expression (14.3% vs. 0%, p = 0.0008). In both the group with fibrinogen concentration and that with F1 + 2 concentration above the 75th percentile, three stent occlusions occurred. Between the groups defined by these variables, the rate of stent occlusion did not differ significantly (8.6% vs. 1.9%, p = 0.10). Logistic regression analysis, including angiographic and hemostatic variables, confirmed platelet fibrinogen receptor expression as an independent predictor of stent occlusion (p = 0.020). Stent occlusion could not be predicted by the time course of any of the hemostatic variables. CONCLUSIONS: Platelet fibrinogen receptor expression is an independent predictor of subacute stent occlusion. However, fibrinogen and F1 + 2 concentrations do not show a strong relation to the risk of stent occlusion.

Adult↗