Platelet-derived Microparticles In Patients Research Articles

Increased Platelet-derived Microparticles Counts is Correlated with Elevated Blood LDL Cholesterol in Acute Myocardial Infarction

BACKGROUND: Platelet-derived microparticles (PDMPs) and low-density lipoprotein (LDL) cholesterol are contributing factors to acute myocardial infarction (AMI). However, the association between LDL cholesterol and PDMPs in AMI has not fully discovered. This study assessed the correlation between these two parameters in patients diagnosed with AMI.METHODS: This was an observational cross-sectional study involving 95 subjects with AMI. The blood measurement of PDMPs counts and LDL cholesterol levels were conducted concomitantly within 24 hours of admission. PDMPs count was analyzed by flow-cytometry method, meanwhile the LDL cholesterol was measured with enzymatic and colorimetric methods. For further analysis, subjects were further divided into LDL cholesterol level ≥130 mg/dL and <130 mg/dL. A statistical test was conducted for a correlative and comparative analyses.RESULTS: A correlative analysis to assess the association between PDMPs counts and LDL cholesterol level depicted a low but significant positive correlation (r=0.231, p=0.024). Furthermore, mean PDMPs counts was significantly higher in subjects with LDL cholesterol level ≥130 mg/dL compared to LDL cholesterol level <130 mg/dL (12,499.59 (95% CI: 8,507.44-16,491.74) counts/μL vs. 9,267.23 (95% CI: 4,445.45-14,089.01) counts/μL; p=0.039).CONCLUSION: There was a significant correlation between PDMPs counts and LDL cholesterol levels in AMI. A significantly increased PDMPs counts were found in subjects with LDL cholesterol level ≥130 mg/dL. Therefore, it is recommended to measure PDMPs in patients with high LDL cholesterol levels as both might be significant AMI biomarkers.KEYWORDS: acute myocardial infarction, LDL-cholesterol, platelet microparticles, platelet activation

Platelets Derived Microparticles in COVID-19

BACKGROUND: Evidences indicate that COVID-19 infection causes hypercoagulable state with micro and macrovascular thrombosis. Platelet-derived microparticles (PDMPs) have inflammatory and diverse coagulant roles. AIM: The aim of the study was to assess PDMPs in patients with active and convalescent post COVID-19 infection and correlate PDMPs with clinical, radiological and laboratory findings used in follow up. PATIENTS AND METHODS: The study enrolled 25 patients during active COVID-19 (Group A), of them five patients had thromboembolic events (TEE); and Group B including 32 patients during post COVID-19 stages. Clinical and radiological assessment, routine biomarkers, and detection of PDMPs levels, using enzyme-linked immunosorbent assay method, were done for all patients. RESULTS: In addition to significant differences detected regarding hemoglobin level, total leukocyte count, absolute neutrophil count, absolute lymphocyte count, C-reactive protein level, D-dimer, and serum ferritin, and high significant differences in PDMPs levels were elicited between groups A and B (mean ± standard deviation: 38.7 ± 10.6 IU/mL, and 18.9 ± 15.3 IU/mL) respectively, with discriminative level at 20.5 IU/mL. PDMPs showed nonsignificant difference between patients with and without TEE and no correlation was detected between PDMPs and clinical or radiological severity in post-COVID-19 patients. CONCLUSION: In COVID-19 infection, PDMPs are related to viral activity, and their major role is inflammatory associated.

Effect of intracoronary tirofiban bolus administration on platelet-derived microparticles and short-term clinical benefit in patients with acute ST-segment elevation myocardial infarction

Objective To investigate the effect of intracoronary tirofiban bolus administration on platelet-derived microparticles (PMPs) and its correlation with the short-term clinical benefit in patients with acute ST-segment elevation myocardial infarction (ASTEMI) undergoing emergency percutaneous coronary intervention (PCI). Methods A total of 90 patients with ASTEMI undergoing emergency PCI were selected and randomized into the intracoronary group (intracoronary tirofiban 10.00 μg/kg bolus within 1-3 min followed by intravenous continuous infusion at 0.15 μg·kg-1·min-1 for 36 h, n=30), intravenous group (intravenous tirofiban 10.00 μg/kg bolus within 1-3 min followed by intravenous continuous infusion at 0.15 μg·kg-1·min-1 for 36 h, n=30) and control group (without tirofiban administration, n=30). The 3 ml blood samples from coronary artery were obtained before and 10 min after tirofiban infusion. The 3 ml blood samples from radial artery were collected 24 hours after tirofiban infusion and 12 hours after drug withdrawal. The counts of PMPs were analyzed by flow cytometry. The thrombolysis in myocardial infarction (TIMI) flow grade classification and TIMI Myocardial Perfusion Grade in the culprit blood vessel after PCI, and the incidences of bleeding and major adverse cardiac events (MACE) within 30 days after surgery were recorded. Results There was no significant difference in baseline of PMPs among intracoronary group, intravenous group and control group (all P>0.05). The level of PMPs was decreased in the intracoronary and intravenous group as compared with the control group 〔(3.6±2.3)%, (5.1±2.7)% vs. (6.7±3.2)%, P 0.05), and PMPs levels were lower in intracoronary and intravenous group than in control group (both P 0.05). Immediately after PCI, the TIMI flow grade and TIMI myocardial perfusion grade in the culprit blood vessel in intracoronary group were superior to those in the intravenous group and control group (P 0.05). Conclusions The intracoronary versus intravenous tirofiban administration can effectively and immediately reduce the number of PMPs in patients with acute ST-segment elevation myocardial infarction undergoing emergency interventional treatment, quickly inhibit the activated platelets, and decrease the total major adverse cardiovascular events without increasing the risk of bleeding. Key words: Myocardial infarction; Blood platelets; Angioplasty, intervention, percutaneous coronary

Elevated level of circulating platelet-derived microparticles in patients with oral squamous cell carcinoma: a possible association with increased procoagulant activity

Background: The association between circulating microparticles (MPs) and oral squamous cell carcinoma (OSCC) remains largely unknown.

Platelet-derived microparticles in patients with high cardiovascular risk and subclinical atherosclerosis.

Platelet-derived microparticles in patients with high cardiovascular risk and subclinical atherosclerosis -

Cause or Effect of Arteriogenesis: Compositional Alterations of Microparticles from CAD Patients Undergoing External Counterpulsation Therapy

Recently, a clinical study on patients with stable coronary artery disease (CAD) showed that external counterpulsation therapy (ECP) at high (300 mmHg) but not at low inflation pressure (80 mmHg) promoted coronary collateral growth, most likely due to shear stress-induced arteriogenesis. The exact molecular mechanisms behind shear stress-induced arteriogenesis are still obscure. We therefore characterized plasma levels of circulating microparticles (MPs) from these CAD patients because of their ambivalent nature as a known cardiovascular risk factor and as a promoter of neovascularization in the case of platelet-derived MPs. MPs positive for Annexin V and CD31CD41 were increased, albeit statistically significant (P<0.05, vs. baseline) only in patients receiving high inflation pressure ECP as determined by flow cytometry. MPs positive for CD62E, CD146, and CD14 were unaffected. In high, but not in low, inflation pressure treatment, change of CD31CD41 was inversely correlated to the change in collateral flow index (CFI), a measure for collateral growth. MPs from the high inflation pressure group had a more sustained pro-angiogenic effect than the ones from the low inflation pressure group, with the exception of one patient showing also an increased CFI after treatment. A total of 1005 proteins were identified by a label-free proteomics approach from MPs of three patients of each group applying stringent acceptance criteria. Based on semi-quantitative protein abundance measurements, MPs after ECP therapy contained more cellular proteins and increased CD31, corroborating the increase in MPs. Furthermore, we show that MP-associated factors of the innate immune system were decreased, many membrane-associated signaling proteins, and the known arteriogenesis stimulating protein transforming growth factor beta-1 were increased after ECP therapy. In conclusion, our data show that ECP therapy increases platelet-derived MPs in patients with CAD and that the change in protein cargo of MPs is likely in favor of a pro angiogenic/arteriogenic property.Trial RegistrationClinicalTrials.gov NCT00414297

Platelet-Derived Microparticles in Patients with Colorectal Cancer

Microparticles (MPs) are membrane vesicles released by platelets during activation or apoptosis. PMPs stimulate coagulation and cell adhesion to the vascular endothelium, both of which being important in the development of cancer progression. We investigated the correlation between microparticles and cancer advancement. The percentage of PMPs was measured by flow cytometry in 22 colorectal cancer patients and in 20 healthy subjects. The patients were divided into two groups according to the presence or lack of lymph node metastases. The percentage of PMPs was significantly higher in patients than in healthy subjects (p < 0.001). We observed a positive correlation between PMPs and the presence of lymph node metastases (r = 0.63, p < 0.003). This high correlation may suggest that PMPs are associated with lymph node involvement and cancer progression.

Plasma Levels of Platelet-Derived Microparticles in Patients with Obstructive Sleep Apnea Syndrome

Obstructive sleep apnea syndrome (OSAS) has been associated with high cardiovascular morbidity and mortality, and patients suffer from repeated episodes of hypoxia. Platelet-derived microparticles (PDMPs) are released via platelet activation by various agonists, including inflammatory cytokines or high shear stress. Plasminogen activator inhibitor -1 (PAI-1) is a fibrinolytic marker and soluble fibrin (SF) is a coagulation activation marker. We examined plasma levels of PDMPs, PAI-1 and SF in patients with OSAS. We also examined the effects of continuous positive airway pressure (CPAP) on plasma levels of PDMPs. Full polysomnography (PSG) monitoring was performed on 27 patients. The apneahypopnea index (AHI) of 5 events/h or less than 30 events/h indicated mild to moderate OSAS, and an AHI of 30 events/h or more indicated severe OSAS. Plasma levels of PDMPs were measured using an ELISA kit, and PAI and SF were determined by a latex immunoassay. In addition, the effects of CPAP treatment were studied in 7 patients. The plasma level of PDMPs was significantly higher in patients with severe OSAS (15.8±10.4 U/mL) than normal controls (10.8±7.1 U/mL, p < 0.05) and patients with mild to moderate OSAS (9.2±3.5 U/mL, p < 0.05). The plasma levels of PDMPs correlated with the AHI (r = 0.39, p < 0.05). In addition, CPAP treatment decreased the plasma level of PDMPs (11.9±5.6 U/mL to 6.7±3.2 U/mL, p < 0.05). Patients with OSAS might be at increased cardiovascular risk due to elevated PDMPs. Moreover a decrease in the plasma level of PDMPs by treatment with CPAP might reduce cardiovascular risk.

Acetylsalicylate reduces endothelial and platelet-derived microparticles in patients with coronary artery disease

Previous studies suggest that endothelial progenitor cells (EPCs) contribute to vascular repair processes. In contrast, circulating microparticles (MPs) are reported to be part of a process that is damaging to vascular cells. Numerous studies suggest that the "balance" between EPCs and MPs is important for the integrity of vascular cells and preservation of endothelial function. In the present study, we assess the impact of acetylsalicylate (ASA) - which is, beside statins and physical exercise, a third basic column in the preventive therapy of coronary artery disease (CAD) - on EPCs and MPs in patients with CAD. We investigated the effect of treatment (8weeks) with ASA (100mg/d) on endothelial function (flow-mediated vasodilation, FMD), number of circulating EPCs, and endothelial- and platelet-derived microparticles (eMP, pMP) in 15 male patients (age 59.5± 12.3years) with CAD but nonsignificant stenosis. The number of pMPs and eMPs decreased by 62.7% (p< 0.05) and 28.4% (p< 0.05), respectively. The number of circulating EPCs (VEGFR2(+)CD34(+)), expressed as ‰ of circulating polymorphonuclear leukocytes, remained unchanged. Despite the reduced number of pMPs and eMPs in response to the ASA therapy, the FMD responses and the maximal dilator effects of nitroglycerin were unaffected. In a control experiment, patients (n = 6) treated with the selective COX-2 inhibitor etoricoxib (90mg/day) for 8weeks showed no changes in the number of pMPs, eMPs, and EPCs and in FMD. We report on a novel effect of ASA treatment on the number of circulating endothelial- and platelet-derived microparticles in patients with cardiovascular disease. The mechanism remains elusive, and appears not to be associated with the COX-2 pathway.

Plasma Platelet-derived Microparticles in Patients with Connective Tissue Diseases

To clarify the role of platelet-derived microparticles (PDMP), which are small vesicles with thrombotic and immunological properties, in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis/polymyositis (PM/DM), and mixed connective tissue disease (MCTD). Plasma levels of PDMP were measured by ELISA, and compared among patients with one of the 4 diseases. Association of PDMP levels with clinical characteristics and medication of the patients was also examined. PDMP levels were higher in patients with MCTD and SSc than in controls. Multiple linear regression analysis revealed that patients with Raynaud's phenomenon (RP) showed higher PDMP levels than those without. PDMP levels in individual patients did not fluctuate significantly over several months. PDMP level is associated with MCTD, SSc, and RP, and could be a novel marker for RP.

Atorvastatin reduces thrombin generation and expression of tissue factor, P-selectin and GPIIIa on platelet-derived microparticles in patients with peripheral arterial occlusive disease

We investigated the effects of statin treatment on platelet-derived microparticles (PMPs) and thrombin generation in atherothrombotic disease. Nineteen patients with peripheral arterial occlusive disease were randomised to eight weeks of treatment with atorvastatin or placebo in a cross-over fashion. Expression of GPIIIa (CD61), P-selectin (CD62P), tissue factor (TF, CD142) and phosphatidylserine (PS; annexin-V or lactadherin binding) was assessed on PMPs. Thrombin generation in vivo was assessed by measurement of prothrombin fragment 1+2 in plasma (F1+2) and ex vivo by using the calibrated automated thrombogram (CAT). During atorvastatin treatment, expression of TF, P-selectin and GPIIIa was significantly reduced vs. placebo (p<0.001 for all). No effect on annexin-V or lactadherin binding was seen. Thrombin generation was significantly reduced during atorvastatin as assessed by both the CAT assay (p<0.001) and by measurements of F1+2 (p<0.01). Subsequent in vitro experiments showed that when TF on microparticles (MPs) was blocked by antibodies, the initiation of thrombin generation was slightly but significantly delayed. Blocking PS on MPs using annexin-V or lactadherin resulted in almost complete inhibition of thrombin generation. In conclusion, atorvastatin reduces thrombin generation and expression of TF, GPIIIa and P-selectin on PMPs in patients with peripheral vascular disease. Microparticle-bound TF slightly enhances initiation of thrombin generation whereas negatively charged surfaces provided by MPs or lipoproteins could reinforce thrombin generation. Statins may inhibit initiation of thrombin generation partly through a microparticle dependent mechanism but the main effect is probably through reduction of lipoprotein levels.

Atorvastatin has antithrombotic effects in patients with type 1 diabetes and dyslipidemia

Introduction Diabetes is a prothrombotic state involving a more thrombogenic fibrin network. In the present study we investigated the effects of lipid-lowering therapy with atorvastatin on fibrin network structure and platelet-derived microparticles in patients with type 1 diabetes and dyslipidemia. Materials and Methods Twenty patients were treated with atorvastatin (80 mg daily) or placebo during 2 months in a randomized, double-blind, cross-over study. Fibrin network permeability, expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles, plasma endogenous thrombin potential, plasminogen activator inhibitor-1 and tissue plasminogen activator antigen levels were assessed. Additionally, levels of plasma fibrinogen, high-sensitivity C-reactive protein and glycated haemoglobin were measured. Results During treatment with atorvastatin, fibrin network permeability increased (p = 0.01), while endogenous thrombin potential and expression of glycoprotein IIIa, P-selectin and tissue factor decreased (p < 0.01). In vitro experiments indicated that platelet-derived microparticles influence the fibrin network formation as fibrin network permeability decreased significantly when platelet-derived microparticles were added to normal plasma. Baseline levels of plasminogen activator inhibitor-1 and tissue plasminogen activator antigen as well as plasma fibrinogen and high-sensitivity C-reactive protein were within reference values and not significantly changed during atorvastatin treatment, while glycated haemoglobin increased 0.3% (p < 0.001). Conclusions Novel treatment effects were found in patients with type 1 diabetes and dyslipidemia during atorvastatin therapy, i.e. a more porous fibrin network, to which reduced expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles may contribute. The observed impairment of glycemic control during long-term statin treatment deserves attention.

Effects of blood pressure and the renin-angiotensin system on platelet activation in type 2 diabetes.

Aims/Introduction: Platelet-derived microparticles (PDMP) are released from the platelets either after activation or in response to physical stimulation in vivo. The present study examined the association between blood pressure and PDMP, and the effects of high-dose angiotensin receptor blockers (ARB) on PDMP in patients with type 2 diabetes. The study subjects consisted of 28 type 2 diabetes patients with blood pressure ≥130/80 mmHg who were treated with valsartan (80 mg daily). The patients were randomly assigned to take either 80 mg of telmisartan (Tel group) or 160 mg of valsartan (Val group) and then were followed up for 24 weeks. Thereafter, the patients were switched to combination therapy (5 mg of amlodipine with 40 mg of telmisartan [Tel group] or 80 mg of valsartan [Val group]) for 12 weeks. Although the ambulatory blood pressure did not change, the PDMP levels were significantly decreased from baseline to week 24 (high dose ARB). In contrast, combination therapy reduced both blood pressure and PDMP levels compared with the baseline. Although the PDMP level was significantly correlated with the morning BP elevation at baseline and week 36 (combination therapy), this same relationship was not found at week 24. There were no significant differences in the blood pressure and PDMP levels between the two groups. Patients with morning hypertension might be at risk for cardiovascular diseases. High-dose renin-angiotensin system inhibition and blood pressure control are both considered to reduce cardiovascular events in patients with type 2 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00048.x, 2010).

The Influence of Hyperlipidemia on Platelet Activity Markers in Patients after Ischemic Stroke

Background: To investigate the relationship between hyperlipidemia and platelet activation markers – platelet and soluble P-selectin (sP-selectin), and platelet-derived microparticles (PDMPs) – in patients after ischemic stroke. Methods: 41 patients after ischemic stroke (>3 months) confirmed by CT were divided into 2 groups: with hyperlipidemia (HL, n = 21) and normolipidemia (NL, n = 20). Twenty healthy subjects served as controls. CD62P-positive platelets and PDMPs in whole blood were analyzed by the use of a flow cytometer and anti-CD61 and anti-CD62P monoclonal antibodies. Platelets were activated by thrombin (0.08 units). The level of sP-selectin in serum was measured by ELISA. Results: We observed a significantly higher CD62P expression and percentage of CD62P-positive resting and thrombin-activated platelets in the HL as compared to the NL group. The sP-selectin concentration was also significantly higher in HL than NL subjects (p < 0.05). Moreover, we observed a significantly higher percentage of PDMPs in patients after stroke (NL: p < 0.05; HL: p = 0.005) in comparison with the control group. Conclusions: Patients after stroke present symptoms of platelet hyperreactivity. HL in the patients may be a risk factor for vascular events due to the increase in platelet activation.

Increased Levels of Platelet-Derived Microparticles in Patients with DIC.

Circulating microparticles of various cell types are present in healthy individuals and individuals in various disease states. In these microparticles, platelet-dreived microparticles (PMPs) may be implicated in thrombosis and haemostasis. However, little is known about the role of PMPs in patients with DIC. To investigate the role of PMPs, we measured plasma levels of PMPs in patients with sepsis-associated DIC (n=20) and acute promyelocytic leukemia (APL)-induced DIC (n=5). Plasma samples from those patients groups were assayed for PMPs levels by enzyme-linked immunosorbent assay (ELISA, Japan Immunoresearch Laboratory, Japan). Also, sP-selectin levels were determined by ELISA.The thrombin antithrombin complexes (TAT) levels were higher in both types of DIC patients as reported by others. In the septic patients with DIC, we found significant elevation in PMPs levels as compared with normal controls. However, we did not find any difference in plasma levels of PMPs in the APL patients with DIC. The sP-selectin levels were elevated in the septic patients with DIC. In early phase of septic patients with DIC, plasma levels of PMPs tend to be higher than that in late phase of septic patients with DIC.These results suggest that plasma levels of PMPs may be candidates for a marker of septic DIC. It appears that PMPs may contribute to the processes of septic DIC.Sepsis associated DICAPL with DICControls (n=20)PMPs34.1 ± 50.1*9.6 ± 3.66.5 ± 0.9 U/mlTAT25.4 ± 15.5*22.5 ± 15.3*<;3 μ g/ml*(P<0.05) significantly different controls

Elevated Circulating Platelet-Derived Microparticles in Patients with Active Inflammatory Bowel Disease

Platelet-derived microparticles (PDMPs) are active molecules involved in the hemostatic and inflammatory responses. To evaluate the changes in the platelet function in patients with inflammatory bowel disease (IBD), we measured circulating PDMP levels. Twenty-five healthy controls, 44 patients with ulcerative colitis (UC), and 43 patients with Crohn's Disease (CD) were studied. The PDMP and soluble P-selectin (sP-selectin) levels were measured by enzyme-linked immunosorbent assay (ELISA). In the healthy controls, the PDMP levels were 17.2 +/- 6.2 U/mL. Significant differences were not observed between the healthy controls and inactive UC patients (20.8 +/- 9.5 U/mL, n = 25) or between the healthy controls and inactive CD patients (17.6 +/- 7.8 U/mL, n = 24). In contrast, the PDMP levels were significantly higher in both active UC (49.2 +/- 33.6 U/mL, n = 19) and active CD (48.6 +/- 42.8 U/mL, n = 19) patients than in the healthy controls. A significant correlation was found between the PDMP levels and the clinical activity indexes (CAI) of UC patients (r = 0.65, p < 0.01, n = 44), and between the PDMP levels and Crohn's disease activity indexes (CDAI) (r = 0.72, p < 0.01, n = 43). Elevated PDMP levels in active patients were significantly reduced after remission. A significant correlation was observed between the PDMP levels and the sP-selectin levels (r = 0.60, p < 0.01, n = 122). Elevated circulating PDMPs in active IBD patients suggest a role for platelets in the pathogenesis of IBD.

Increased levels of platelet-derived microparticles in patients with diabetic retinopathy

Diabetic retinopathy is caused by capillary occlusions. Platelet-derived microparticles (PMPs) stimulate the coagulation cascade and increase leukocyte and endothelial cell adhesions, both of which are key events in the development of diabetic retinopathy. However, the correlation between the levels of PMPs and diabetic retinopathy has not been precisely determined. The PMPs levels and the expression of platelet CD62P and CD63 were measured in 92 diabetic patients. The level of PMPs was significantly correlated with the expression of CD62P ( r = 0.76, P < 0.0001) and CD63 ( r = 0.71, P < 0.0001). The mean level of PMPs in diabetics (507 ± 15/10 4 platelets (plt), mean ± S.E.) was significantly higher than that in normal. The PMPs levels increased with the progression of the diabetic retinopathy; 480 ± 28/10 4 plt in diabetic patients without retinopathy ( n = 25), 504 ± 40/10 4 plt with mild or moderate non-proliferative diabetic retinopathy ( n = 13), 512 ± 29/10 4 plt with severe non-proliferative diabetic retinopathy ( n = 25), and 528 ± 25/10 4 plt with proliferative diabetic retinopathy ( n = 29). The PMPs level in patients with non-perfused retinal areas (582 ± 27/10 4 plt, n = 24) was significantly higher than patients without non-perfused areas (469 ± 23/10 4 plt, n = 30; P = 0.0096) and without diabetic retinopathy ( P = 0.024). These high correlations indicate that increased levels of PMPs may accelerate diabetic retinopathy.

Generation of platelet-derived microparticles in patients undergoing cardiac surgery is not affected by complement activation

Objective The mechanisms causing the presence of platelet-derived microparticles in the circulation are unknown. In vitro platelets release platelet-derived microparticles in response to complement activation. This study evaluates the relationship between complement activation and levels of circulating platelet-derived microparticles in patients undergoing cardiac surgery. Methods Prospectively, 71 patients were included who underwent elective coronary artery bypass grafting with cardiopulmonary bypass. The patients were randomly allocated to one of the 3 groups: uncoated oxygenator, UnModified Surface (n = 25) or oxygenator coated with either BioPassive Surface (n = 25) or BioActive Surface (n = 21). Platelet-derived microparticles and terminal complement complexes were determined before bypass and after induction of anesthesia, 15 minutes after the start of cardiopulmonary bypass, at the end of cardiopulmonary bypass, and 30 minutes after administration of protamine sulfate. Results Demographic and cardiopulmonary bypass data were similar for the 3 groups. At the end of cardiopulmonary bypass, platelet-derived microparticle numbers were decreased in all 3 groups. No significant differences were observed among the groups at any sampling point. At the end of cardiopulmonary bypass, terminal complement complex concentrations were increased in all groups ( P < .001), and significant differences among the groups were present ( P = .002). Conclusions Despite significant complement activation, no increase in numbers of circulating platelet-derived microparticles was found in the systemic blood of patients undergoing cardiac surgery with cardiopulmonary bypass. Thus complement activation in vivo does not necessarily affect generation of platelet-derived microparticles.

Platelet-Derived Microparticles in Patients with Arteriosclerosis Obliterans: Enhancement of High Shear-Induced Microparticle Generation by Cytokines

We evaluated the plasma concentrations of cytokines and platelet-derived microparticles in patients with arteriosclerosis obliterans and studied the effect of cytokines on platelet-derived microparticle generation under high shear stress. Interleukin-6 levels peaked at 48 hours after vascular surgery, while thrombopoietin started to increase at 24 to 48 hours postoperatively and peaked on the seventh day. Platelet activation markers were increased in the arteriosclerosis obliterans patients preoperatively. Levels of P-selectin and CD63 both increased further, peaking at 6 to 24 hours postoperatively. Platelet-derived microparticle levels were also increased preoperatively. At 6 hours postoperatively, the plasma level of platelet-derived microparticles was significantly increased. Plasma platelet-derived microparticle level was lower at 12 hours but only returned to the preoperative value at 7 days after grafting. There was a difference in the platelet-derived microparticle level at 7 days between patients with or without antiplatelet therapy (cilostazol). The effect of cytokines on platelet activation under high shear stress was also studied. Interleukin-6 and thrombopoietin enhanced both P-selectin expression and platelet-derived microparticle generation under high shear stress. These results suggest that platelet-derived microparticles are released by platelet activation after vascular grafting when certain cytokines increase under high shear stress and that antiplatelet therapy may reduce platelet-derived microparticle levels postoperatively.

Effect of Ticlopidine on Platelet-Derived Microparticles in Patients with Connective Tissue Diseases

We evaluated the plasma concentrations of platelet activation markers and platelet-derived microparticles (PMP) in patients with connective tissue diseases complaining of peripheral circulation disorders (n = 16) and studied the effect of ticlopidine hydrochloride (ticlopidine) on PMP generation. There were significant differences in the levels of PMP and a platelet activation marker between before and after treatment with ticlopidine (PMP: 695 ± 393 vs. 354 ± 206/10⁴ platelets, p < 0.01; platelet CD63: 9.13 ± 5.64 vs. 5.22 ± 2.74%, p < 0.05). On the other hand, markers of vascular endothelium, such as vascular endothelium-derived small vesicles and serum thrombomodulin levels, were not affected by the administration of ticlopidine. Levels of cytokines and soluble adhesion molecules remained unchanged by ticlopidine administration. These findings suggest that ticlopidine may be useful for the inhibition of PMP-dependent vascular damage in patients with connective tissue diseases complaining of peripheral circulation disorders.