Larger Mean Platelet Volume Research Articles

Mean platelet volume modifies the contribution of homocysteine to cardiovascular disease: A real-world study

Background and aimsThe effect of reductions in homocysteine (Hcy) on cardiovascular disease (CVD) was suggested to be modified by platelet activation, but the interaction between Hcy and platelet activation on CVD events is not well studied. Here, we aimed to examine the interaction between Hcy and platelet activation on CVD in a large, real-world population. Methods and resultsA total of 27,234 patients with hypertension (mean 63 years, 48% male) who were registered in Taicang city and free of CVD were prospectively followed up for new CVD events from 2017 to 2020. Hcy and platelet indices including mean platelet volume (MPV) were assayed at baseline. A total of 1063 CVD events were recorded during follow-up. Hcy at baseline was significantly associated with a higher risk of CVD (HR = 1.85, P < 0.001 for log-transformed Hcy). MPV showed a significant interaction effect with Hcy on CVD (HR = 1.20, P = 0.030 for the interaction term). The association between Hcy and CVD was significantly stronger in participants with a large (vs. small) MPV (HR = 2.71 vs. 1.32, P = 0.029 for log-transformed Hcy). For participants with both elevated Hcy and a large MPV, the attributable proportion of CVD events due to their interaction was 0.26 (95% CI: 0.06–0.45). ConclusionsThe association between Hcy and CVD was significantly stronger in patients with hypertension with a larger MPV. MPV may modify the contribution of Hcy to CVD events through synergistic interactions with Hcy. These findings suggest that MPV could be monitored and controlled in the prevention of CVD.

Retrospective Evaluation of COVID-19 Therapeutics

Background: The pandemic outbreak of COVID-19 created panic all over the world. As therapeutics that can effectively wipe out the virus and terminate transmission is not available, supportive therapeutics is the main clinical treatments for COVID-19. Repurposing available therapeutics from other viral infections is the primary surrogate in ameliorating and treating COVID-19. The therapeutics should be tailored individually by analyzing the severity of COVID-19, age, gender, and the underlying conditions. Here, we retrospectively revisit the clinical data collected in China and systematically analyze the efficacy and target patients of different therapeutics and find that Arbidol and Traditional Chinese Medicine (TCM) increase the survival rate significantly, whereas antibacterial treatment is ineffective for viral and bacterial co infection. Multicenter collaboration and large cohort of patients will be required to evaluate therapeutics combinations in the future. Methods: This study is a single-center retrospective observational study of COVID-19 clinical data in China. We screen 2844 COVID-19 patients from the patients admitted to Tongji Hospital (Wuhan) between January 18, 2020, and April 25, 2020 and exclude cases with missing information or false positive diagnosis. Then the patients’ information with different severity will be study to evaluate the efficacy of treatment, including treatment modalities, past medical records, individual disease history, and clinical outcomes were analyzed. As the severity of illness is correlated with laboratory or clinical data, the information can be used to evaluate disease severity. We divide the patients into three groups with moderate, severe, and critical illness. Kaplan-Meier method, univariate and multivariate Cox regression are used to explore different treatment methods on clinical outcomes. Results: After screening, 2844 patients are selected for the study. The mean age of all the patients was 58.74 years (Standard Deviation, SD =15.28), and 49.0% is male. It shows that treatment with TCM (Hazard Ratio (HR) 0.191 [95% Confidence Interval (CI), 0.14 – 0.25]; p &lt; 0.0001), antiviral therapy (HR 0.331 [95% CI 0.19 – 0.58]; p =0.000128), or Arbidol (HR 0.454 [95% CI 0.34 – 0.60]; p &lt; 0.0001) is associated with good prognostic of patients. Multivariate Cox regression showed TCM treatment decreased the mortality hazard ratio by 69.4% (p &lt; 0.0001). Larger Mean Platelet Volume (MPV), international standardized ratio of prothrombin (PT-INR), and K+ are associated with poorer survival. In contrast, larger Eosinophil Count (Eos#), Basophil Count (Baso#), Percentage of Basophils (Baso%), Total Calcium (Ca), Albumin/Globulin Ratio (ALB/GLO), Lymphocyte Count (Lymph#), and Percentage of Eosinophils (Eos%) are associated with better survival.

Thrombocytopenia in patients with 22q11.2 deletion syndrome and its association with glycoprotein Ib-β

Purpose: To elucidate whether thrombocytopenia in 22q11.2 deletion syndrome patients is associated with the hemizygosity of glycoprotein Ib-β and to clarify the correlation of phenotype and genotype of this gene in 22q11.2 deletion syndrome patients with thrombocytopenia.Methods: Platelet number, mean platelet volume, platelet agglutination, and the protein level of glycoprotein Ib-β were measured in 22q11.2 deletion syndrome patients and controls. Phenotypes other than that of thrombocytopenia were also analyzed in these patients.Results: The 22q11.2 deletion syndrome patients with thrombocytopenia had a larger mean platelet volume, lower agglutination to ristocetin, and lower protein level of glycoprotein Ib-β than control patients. The 22q11.2 deletion syndrome patients with thrombocytopenia showed an increased risk of developing schizophrenia.Conclusions: Thrombocytopenia in 22q11.2 deletion syndrome patients is associated with decreased expression of glycoprotein Ib-β because of the hemizygosity. 22q11.2 deletion syndrome patients with thrombocytopenia require total management, especially for schizophrenia.

Hyperacute postprocedural high platelet reactivity: a novel predictor for in-hospital adverse events in acute coronary syndrome with prasugrel loading

Abstract Introduction Postprocedural High platelet reactivity (HPR) seems to associate long term adverse cardiovascular events, mainly intrastent thrombosis. However, the relationship between hyper-acute postprocedural HPR with prasugrel loading and clinical outcomes in acute coronary syndrome (ACS) is still unclear. Moreover, factors contributing HPR in ACS with prasugrel loading are also unknown. Purpose This study aimed to assess the impact of hyper-acute postprocedural HPR with prasugrel loading on clinical outcomes in ACS during hospitalization, as well as to define appropriate cut-off values and identify contributing factors of HPR. Methods We performed a single-centre, retrospective observational study that enrolled 207 patients who underwent emergent PCI for ACS with prasugrel loading. The P2Y12reaction unit (PRU) value was measured immediately after PCI with the VerifyNow System. The primary endpoint was major adverse cardiac events (MACE, defined as the composite of death, myocardial infarction, stroke, heart failure, ventricular arrhythmia needing defibrillation). Results Mean patient age (standard deviation) was 70.5 (±13.0) years, 78.7% were male, and average time from prasugrel intake to PRU calculation was 98.3 (±49.1) min. During a mean hospital stay of 15.9 (±9.3) days, there were 34 in-hospital MACE (16.4%) and 10 deaths (4.8%). Thrombosis events, didn't stand out and mechanical complications, such as cardiac rupture and cardiac tamponade occupies most of cardiovascular death which occurred before 10 days on admission. PRU was significantly higher in MACE group than Non-MACE group (279±65 vs 227±72, p&amp;lt;0.001 respectively). The ROC curve analysis of PRU for discriminating significant in-hospital MACE showed the cut off value of 293 (sensitivity:52.9%, specificity:83.2% [AUC=0.709, p&amp;lt;0.0001]). 47patients (29.4%) were thus categorized as HPR (PRU&amp;gt;293) immediately after emergent PCI. Kaplan-Meyer curve showed MACE events occurred in HPR group than non-HPR group (38.2% vs 10.0%, p&amp;lt;0.001). Multiple cox analysis demonstrated that HPR was independent predictors of MACE in patients with ACS underwent PCI (OR 5.416, 95% CI 2.157–13.598, p&amp;lt;0.0001). Multiple logistic regression model showed female sex, low haemoglobin value, and large mean platelet volume were independent predictors of HPR. Conclusion PRU was significantly higher in MACE group, and appropriate cut-off value of HPR in this study was 293. HPR was independent predictor of MACE during hospitalization, however thrombosis event was not significant. Evidence of clinical impact with postprocedural HPR within 120 minutes after prasugrel loading is scarce. This study shows post-procedural HPR, even without sufficient time after prasugrel intake, can be a useful predictive marker of adverse events during hospitalization. Funding Acknowledgement Type of funding sources: None. PRU between Non-MACE and MACE groupKaplan-Meyer curve

Association between mean platelet volume and major adverse cardiac events in percutaneous coronary interventions: a systematic review and meta-analysis.

Platelets with high hemostatic activity play a key role during percutaneous coronary interventions (PCI), and in recent years, mean platelet volume (MPV) has been looked upon as a crucial indicator of platelet reactivity. Thus, MPV may emerge as a potential gauge for the measurement of major adverse cardiac event (MACE) risks in PCI patients. This study aimed to conduct a meta-analysis illustrating the association between MPV and long-term MACE in PCI. The Cochrane Library, Pubmed, EMBASE, Ovid MEDLINE, and BIOSIS databases were used to search for relevant studies from their inception to 30 June 2019. All studies reporting incidences of MACE and MPV in PCI patients were retained. Data extraction was performed by three independent reviewers. A total of 33 studies were included in this meta-analysis. The results indicated that patients with MACE had a significantly larger MPV than those without, with an unstandardized mean difference (USMD) of 0.29 fL (95% CI, 0.04-0.54). The USMD of MPV in deceased patients was 0.39 fL (95% CI, 0.09-0.68). The results also indicated that patients with larger MPV were at greater risks of having MACE and higher incidence of mortality than those with smaller MPV, with a pooled risk ratio of 1.81 (95% CI, 1.29-2.55) and 2.34 (95% CI, 1.52-3.60), respectively. These findings indicate a significant association between larger MPV and MACE in PCI patients. Consequently, MPV, an easily accessible indicator, might be helpful in PCI patients' risk assessment and stratification.

Association of Platelet Count and Mean Platelet Volume with Overall Survival in Patients with Cirrhosis and Unresectable Hepatocellular Carcinoma

Background: Platelets have been reported to influence tumor biology and may promote metastasis. Traditionally, thrombocytopenia, a hallmark of cirrhosis, was associated with hepatocellular carcinoma (HCC) development. However, the impact of platelet count on outcome in patients with established HCC is not well studied. Methods: Outcomes of patients with cirrhosis diagnosed with HCC between 1995 and 2013 (derivation cohort) and 2000–2016 (validation cohort) who were not eligible for surgical treatment and did not receive antiplatelet therapy were retrospectively studied. Thrombocytopenia was defined as platelet count < 150 g/L. High mean platelet volume (MPV) was defined as ≥median value of the respective cohort (derivation cohort: ≥11 fL; validation cohort: ≥10.6 fL). Results: Among 626 patients with unresectable HCC, thrombocytopenia was present in 378 (60.4%) and was associated with favorable baseline tumor characteristics: lower diameter of the largest nodule (5.6 ± 3.2 vs. 7.6 ± 4.2 cm), less extrahepatic spread (9.5 vs. 20.2%, both p < 0.001), less macrovascular invasion (21.2 vs. 31.0%, p = 0.005), and lower BCLC stages (63.0 vs. 73.4% BCLC C/D; p = 0.007) as compared to patients with normal platelet count. On univariate analysis, thrombocytopenia and larger MPV were associated with longer overall survival (OS) (thrombocytopenia: median OS [95% CI], 11.5 [9.3–13.8] vs. 5.5 [3.8–7.1] months; p = 0.001; MPV ≥11 fL: 11.7 [9.1–14.2] vs. 6.0 [4.4–7.6] months; p < 0.001). In multivariate analysis, the combined variable of thrombocytopenia and larger MPV was independently associated with longer OS (HR [95% CI], 0.80 [0.65–0.98]; p = 0.029). These results were confirmed in an independent external validation cohort of 525 patients with cirrhosis and HCC. Again, patients with thrombocytopenia and high MPV had significantly longer OS (15.3 [11.7–18.9] vs. 9.3 [7.4–11.2] months; p < 0.001). Conclusions: Thrombocytopenia and higher MPV are associated with better outcome in patients with advanced HCC. These findings may prompt further clinical research on additive antiplatelet therapy in the prevention and management of HCC.

Mean platelet volume, platelet distribution width and platelet count in erectile dysfunction: A systematic review and meta-analysis

The aim of this study was to investigate the relationship between mean platelet volume (MPV), platelet distribution width (PDW), platelet count (PC) and erectile dysfunction (ED). We searched for observational studies from PubMed, EMBASE, Web of Science and CNKI up to 31 March 2016. Two reviewers independently selected the studies and extracted the data. MPV, PDW, and PC and mean differences in these platelet indices between healthy subjects and ED patients were explored using the Comprehensive Meta-Analysis software package. Seven studies including 795 patients and 524 healthy subjects met the inclusion criteria. The MPV was significantly larger in patients with ED than controls with the standardised mean difference of 0.596 fL (95% CI: 0.378, 0.815, p<0.001). In ED patients, the pooled mean difference in MPV between vasculogenic ED patients and nonvasculogenic ED patients was 0.706 fL in case-control studies (95% CI: 0.410, 1.002, p<0.001). There was no significant difference in PDW and PC between healthy subjects and ED patients. The available data suggest that larger MPV was associated with ED. Patients with vasculogenic ED tend to have higher MPV than nonvasculogenic ED patients. Further studies are needed to assess whether increased MPV in ED patients is associated with increased cardiovascular disease.

Mean platelet volume is associated with lower risk of overall and non-vascular mortality in a general population. Results from the Moli-sani study.

Larger mean platelet volume (MPV) has been associated with adverse health outcomes in high-risk populations or patients with cardiovascular disease (CVD). We tested the association of MPV with mortality in a prospective cohort study including 17,402 subjects randomly recruited from an adult general population within the Moli-sani study (2005-2010). Two distinct subgroups (with or without CVD at baseline) were subsequently analysed. Hazard ratios (HR) were calculated using multivariable Cox-proportional hazard models. Over a median follow up of eight years (137,547 person-years), 925 all-cause deaths occurred (330 vascular, 351 cancer and 244 other deaths). In a multivariable model, the highest MPV quintile (mean MPV=10.0 fL), as compared to the lowest one, was associated with reduced risk of overall mortality (HR=0.79; 95 % confidence interval 0.64-0.98), cancer death (HR=0.70; 0.49-1.00) and death from other non- vascular/non cancer causes (HR=0.55; 0.36-0.84) but not with vascular mortality. The inverse association with overall death appeared even stronger in the subgroup without CVD at baseline (HR=0.64; 0.50-0.81). In contrast, within 920 subjects reporting a previous CVD event, larger MPV was associated with higher risk of total mortality (HR=1.69; 1.05-2.72; p for interaction=0.048) and with a trend of risk for other cause-specific deaths. In conclusion, larger MPV is associated with lower risk of overall and non-vascular death in subjects apparently free from CVD, but appears to be a predictive marker of death in patients with CVD history. The latter is a likely effect modifier of the association between MPV and death.

Impact of age on mean platelet volume and its relationship with coronary artery disease: A single-centre cohort study

Elderly patients represent a high risk category among subjects with atherosclerosis, due to the presence of comorbidities and suboptimal response to antiplatelet drugs. Mean platelet volume (MPV) has been indicated as a marker of platelet reactivity, with contrasting data on its role on coronary artery disease. Aim of the present study was to evaluate the impact of age on the MPV and its role on the extent of coronary artery disease (CAD). MethodsOur population is represented by a cohort of 3750 patients undergoing coronary angiography. Elderly were defined according to age≥75years. MPV was measured at admission. Significant coronary artery disease was defined as a stenosis >50% in at least 1 coronary vessel, while severe CAD was defined as left main and/or three-vessel disease. ResultsA total of 1170 out of 3750 (31.2%) patients were ≥75years old. Advanced age was associated with female gender (p<0.001), hypertension (p<0.001), renal failure (p<0.001), previous myocardial infarction (p=0.03) coronary artery bypass grafting (p<0.001) indication to angiography (p<0.001), therapy with angiotension-receptor blockers, (p=0.003), nitrates, diuretics and calcium-antagonists (p<0.001), serum creatinine (p<0.001), fibrinogen (p<0.001) and C reactive protein (p=0.02), but inversely to percutaneous coronary interventions (p=0.02), dyslipidemia, family history of CAD and smoking (p<0.001, respectively), use of statins (p=0.02) and beta blockers (p=0.003), haemoglobin, total cholesterol and triglycerides (p<0.001, respectively), white blood cells (p=0.009) and platelet count (p=0.006).Elderly patients displayed a significantly larger platelet volume (p<0.001), with a direct linear relationship between age and the MPV (r=0.08, p<0.001), with age being confirmed as an independent predictor of larger MPV (≥10.85fl) at multivariate analysis (adjusted OR [95% CI]=1.18 [1.01–1.40], p=0.04).Among the elderly, MPV value above the median (≥10.85fl) was not associated with a higher prevalence of coronary artery disease (77.3 vs. 79.4%, p=0.39, adjusted OR [95% CI]=0.94 [0.66–1.33], p=0.71), or higher prevalence of severe CAD (35.2 vs. 32.4%, p=0.28, adjusted OR [95% CI]=1.34 [0.99–1.82], p=0.06). ConclusionAdvanced age was directly associated with larger mean platelet volume that, however, did not contribute to explain the higher prevalence and extent of coronary artery disease observed in elderly patients.

Mean platelet volume and coronary artery disease: a systematic review and meta-analysis

BackgroundPlatelets with high hemostatic activity play an important role in the pathophysiology of coronary artery disease(CAD) and mean platelet volume(MPV) has been proposed as an indicator of platelet reactivity. Thus, MPV may emerge as a potential marker of CAD risk. The aim of this study was to conduct a systematic review and meta-analysis comparing mean difference in MPV between patients with CAD and controls and pooling the odds ratio of CAD in those with high versus low MPV. MethodsMedline and Scopus databases were searched up to 12 March 2013. All observational studies that considered MPV as a study's factor and measured CAD as an outcome were included. Two reviewers independently selected the studies and extracted the data. ResultsForty studies were included in this meta-analysis. The MPV was significantly larger in patients with CAD than controls with the unstandardized mean difference of 0.70fL (95% CI: 0.55, 0.85). The unstandardized mean difference of MPV in patients with acute coronary event and in patients with chronic stable angina was 0.84fL (95% CI: 0.63, 1.04) and 0.46fL (95% CI: 0.11, 0.81) respectively. Patients with larger MPV (≥7.3fL) also had a greater odds of having CAD than patients with smaller MPV with a pooled odds ratio of 2.28 (95% CI: 1.46, 3.58). ConclusionLarger MPV was associated with CAD. Thus, it might be helpful in risk stratification, or improvement of risk prediction if combining it with other risk factors in risk prediction models.

Effects of lead exposure on the status of platelet indices in workers involved in a lead-acid battery manufacturing plant.

This study was carried out to determine the effect of Pb exposure on the status of platelet indices in workers exposed to Pb during lead-acid battery plant process. Platelet indices and blood lead levels (BLLs) were determined in 429 male workers. BLLs were determined by using an atomic absorption spectrophotometer. Platelet indices in the samples were quantified by using the Sysmex KX-21 hematology analyzer. The levels of platelet count (PLT), plateletcrit (PCT) and mean platelet mass (MPM) were significantly decreased and platelet distribution width (PDW), platelet large cell ratio (P-LCR) and mean platelet volume were increased with an increase in BLLs. The results of linear multiple regression analysis showed that the platelet count (β -0.143, P=0.005), PCT (β -0.115, P=0.023) and MPM (β -0.110, P=0.030) were negatively associated with BLLs and P-LCR (β 0.122, P=0.016) was positively associated with BLLs. The variable of body mass index showed a positive association with PCT (β 0.105, P=0.032) and MPM (β 0.101, P=0.039). The results of the study may indicate that lead exposure may impair coagulation function through endothelial tissue injury and reduction of nitric oxide.

Diabetes, glucose control and mean platelet volume: a single-centre cohort study

Diabetes is a major determinant of cardiovascular risk, mainly due to higher prothrombotic status and enhanced platelet reactivity. Mean platelet volume (MPV) has been suggested as indicator of platelet reactivity and moreover, diabetics have been shown to have larger MPV. The aim of our study was to evaluate the impact of diabetes and glycemic control on MPV in a large cohort of patients. MethodsOur population is represented by 3414 patients undergoing coronary angiography at Azienda Ospedaliera-Universitaria, “Maggiore della Carità”, Novara, Italy. We obtained a fasting blood sample for glycemic assessment and for MPV evaluation. History of diabetes and pharmacological treatment, together with main cardiovascular risk factors were recorded. New diagnosis of diabetes was defined as nonfasting glucose >200mg/dL, fasting glucose ≥126mg/dL, or HbA1c >48mmol/L. ResultsDiabetes was observed in 1272 patients (37.2%). Diabetes was related to older age, waist circumference, arterial hypertension, smoking, hypercholesterolemia, renal failure, previous MI and PCI, therapy with ACE-inhibitors, ARBs, beta-blockers, diuretics, statins (respectively p<0.001) and ASA (p=0.004). Diabetics had lower haemoglobin (p<0.001), higher fibrinogen (p=0.001) and worst lipid profile (p<0.001). MPV was related with diabetes mellitus (p<0.001) and glycemic control (p=0.05; at linear regression r=0.07; p<0.001 for fasting glycaemia; r=0.09; p<0.001 for HbA1c, respectively).However, this relationship was not confirmed at multivariate analysis (OR[95%CI]=1.2[0.97–1.5], p=0.09 for diabetes, OR[95%CI]=1.05[0.96–1.15], p=0.25 for HbA1c). Independent predictors of MPV above median value (10.8fL) resulted to be age (OR[95%CI]=1.02[1.01–1.03], p=0.002), treatment with ARBs (OR[95%CI]=1.4[1.1–1.8], p=0.007) and haemoglobin levels (OR[95%CI]=1.2[1.15–1.23], p<0.001), while inverse relationship was found with total cholesterol (OR[95%CI]=0.99[0.99–1], p=0.002). ConclusionLarger MPV is associated with ageing, treatment with ARBs, cholesterol and haemoglobin levels. Diabetes mellitus and glycemic control are not independently associated with larger platelet size.

Association between the rs342293 polymorphism and adverse cardiac events in patients undergoing percutaneous coronary intervention

The single nucleotide polymorphism (SNP) rs342293 has been shown to influence platelet number and mean platelet volume (MPV). We investigated the association between the rs342293 polymorphism and cardiovascular outcome in a prospective cohort study. The rs342293 polymorphism was analysed in 404 patients with coronary artery disease undergoing percutaneous coronary intervention. The rates of cardiac adverse events were recorded during two years of follow-up. The polymorphism was associated with MPV (median 10.1 fL, interquartile range [IQR]: 9.6 to 10.6 in patients with the CC-allele vs 10.4 fL, IQR: 9.9 to 11.1 in G>C SNP carriers; p<0.001), but not with platelet count. Survival analysis indicated that carriers of the rs342293 G variant had a substantially higher risk to develop cardiac adverse events compared with wild type carriers during two years of follow-up (33% vs 22%; adjusted hazard ratio = 1.63, 95% confidence interval = 1.06-2.52, p=0.027). The rs342293 SNP could explain 2.9% of the variability in MPV (p=0.01). In conclusion, patients undergoing coronary stenting who carry the G-variant of the rs342293 SNP which is associated with larger MPV are at higher risk for adverse cardiovascular outcome.

Mean platelet volume is not associated with platelet reactivity and the extent of coronary artery disease in diabetic patients

Platelets play a central role in the pathogenesis of coronary artery disease (CAD). Mean platelet volume (MPV) is an indicator of platelet activation, and has been demonstrated to be correlated with platelet reactivity. Diabetic patients have been shown to have larger MPV, that may contribute to higher platelet reactivity and atherothrombotic complications observed in these patients. Therefore, the aim of the current study was to investigate whether MPV is associated with platelet reactivity and the extent of CAD among diabetic patients. We performed a cohort study including 1016 consecutive diabetic patients undergoing coronary angiography at the University Hospital 'Maggiore della Carita', Novara, Italy. CAD is defined as stenosis above 50% in at least one coronary vessel at coronary angiography. Platelet reactivity was evaluated in 50 diabetic patients without history of CAD and who were free (in the past month) from medications which may affect platelet aggregation. Platelet aggregation was evaluated by light transmission aggregometry after stimulation with 1 μg/ml collagen type I. We additionally evaluated platelet surface expression of P-selectin after stimulation with U46619 (a stable synthetic analogue of the prostaglandin PGH2) and plasma concentration of thromboxane B2 (TxB2). Patients were grouped according to tertile values of MPV (<10.6 fl, group 1; 10.6-11.3 fl, group 2; >11.4 fl, group 3). MPV was associated with age (P=0.011), baseline fasting glucose (P=0.044), glycosylated haemoglobin (P=0.005), creatinine (P=0.052) and haemoglobin (P=0.003), but inversely related to platelet count (P<0.001) and triglycerides (P=0.031). Larger MPV was associated with therapy with statins (P=0.012) and diuretics (P=0.021). CAD was observed in 826 patients (81.3%). MPV was not associated with the prevalence of CAD [odds ratio (OR), 0.85 (0.7-1.03), P=0.11]. The results were confirmed in terms of severe CAD [OR, 1.03 (0.88-1.21), P=0.7]. The absence of any significant relationship between MPV and CAD was confirmed after correction for baseline confounding factors [OR, 0.9 (0.75-1.08), P=0.19]. Finally, MPV was not related to platelet reactivity. This is the first study showing that in diabetic patients MPV is not related to platelet reactivity and the prevalence and extent of CAD. Therefore, MPV may not be considered a risk factor for CAD among diabetic patients.

Short-term effects of aspirin and clopidogrel on mean platelet volume among patients with acute coronary syndromes. A single-center prospective study

Mean platelet volume (MPV) has been correlated with platelet reactivity, thus its changes might be used to monitor the effects of antiplatelet therapy. However, no data have been reported on platelet remodelling after antiplatelet therapy. The aim of the current study was to investigate the short-term effects of oral antiplatelet therapy on MPV. Our population is represented by 62 consecutive patients with acute coronary syndrome (ACS), who did not receive GpIIb-IIIa inhibitors. We measured MPV before starting dual antiplatelet therapy, at day 1, day 2, and day 3-5 from starting adjunctive antiplatelet therapy. We additionally analyzed the relationship between platelet aggregation and MPV at admission by Multiplate in patients who were on chronic aspirin therapy. We observed a significant paradoxical increase in MPV, with a reduction in platelet count. We observed at all time intervals a significant inverse relationship between MPV and platelet count (T0: r = -0.44, P < 0.0001; T1: r = -0.36, P = 0.006; T2: r = -0.3, P = 0.026; T3-5: r = -0.29, P = 0.046). No relationship was observed between MPV and the extent of platelet aggregation inhibition by aspirin. This study showed a paradoxical increase in MPV after starting antiplatelet therapy. In addition, we did not observe any relationship between baseline MPV and the extent of platelet aggregation inhibition by aspirin. Thus, larger MPV does not imply higher platelet reactivity and may not be considered to monitor platelet reactivity and the efficacy of antiplatelet therapies.

Serum anion gap, bicarbonate and biomarkers of inflammation in healthy individuals in a national survey.

In vitro data suggest that lower extracellular pH activates the immune system. We conducted a population-based study of the relation between serum acid-base status and inflammation. We examined the serum anion gap and serum levels of bicarbonate and inflammatory biomarkers in 4525 healthy adults who participated in the National Health and Nutrition Examination Survey during 1999-2006. We excluded participants who had chronic disease, recent infection and an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2. The mean values of serum anion gap, bicarbonate level, leukocyte count and C-reactive protein level were all within normal limits. After adjustment for age, sex, ethnic background, body mass index, serum albumin level and other factors, we found that a higher anion gap and lower bicarbonate level were associated with a higher leukocyte count and higher C-reactive protein level. Compared with participants in the lowest quartile of anion gap, those in the highest quartile had a leukocyte count that was 1.0x10(9)/L higher and a C-reactive protein level that was 10.9 nmol/L higher (p<0.01). Compared with participants in the highest quartile of bicarbonate level, those in the lowest quartile had a leukocyte count that was 0.7x10(9)/L higher and a C-reactive protein level that was 4.0 nmol/L higher (p<or=0.02). A higher anion gap and lower bicarbonate level were also associated with a higher platelet count, a larger mean platelet volume and a higher ferritin level. A higher serum anion gap and lower bicarbonate level were associated with higher levels of inflammatory biomarkers in a healthy sample of the general population. Further studies are needed to elucidate the relation between acid-base status and inflammation.

Thrombocytopenia in patients with 22q11.2 deletion syndrome and its association with glycoprotein Ib-β

To elucidate whether thrombocytopenia in 22q11.2 deletion syndrome patients is associated with the hemizygosity of glycoprotein Ib-beta and to clarify the correlation of phenotype and genotype of this gene in 22q11.2 deletion syndrome patients with thrombocytopenia. Platelet number, mean platelet volume, platelet agglutination, and the protein level of glycoprotein Ib-beta were measured in 22q11.2 deletion syndrome patients and controls. Phenotypes other than that of thrombocytopenia were also analyzed in these patients. The 22q11.2 deletion syndrome patients with thrombocytopenia had a larger mean platelet volume, lower agglutination to ristocetin, and lower protein level of glycoprotein Ib-beta than control patients. The 22q11.2 deletion syndrome patients with thrombocytopenia showed an increased risk of developing schizophrenia. Thrombocytopenia in 22q11.2 deletion syndrome patients is associated with decreased expression of glycoprotein Ib-beta because of the hemizygosity. 22q11.2 deletion syndrome patients with thrombocytopenia require total management, especially for schizophrenia.

The Prognostic Value of Mean Platelet Volume in Acute Myocardial Infarction

Background and Objectives:An increased platelet volume is associated with increased platelet reactivity, and may influence the outcome following a myocardial infarction. Subjects and Methods:One hundred patients with acute myocardial infarction, who visited Kyungpook National University Hospital between 2001 January and 2001 December, were included in this study. To determine the mean platelet volume (MPV), blood samples, taken at the time of arrival, were analyzed in an automated haematology analysis system (CELL-DYN3000, ABBOTT, USA). EDTA in the blood bottles was used as an anticoagulant. All samples were processed within 30 minutes of venipuncture, to avoid bias due to platelet swelling. The patients were followed for one year for readmission due to acute coronary syndrome, congestive heart failure or death. To stratify the prognostic value of the MPV, the patients were divided into 4 equal groups according to the percentiles of the platelet volume. Results:Eight patients died, and 20 were readmitted due to acute coronary syndrome or congestive heart failure. The MPV is not a significant predictor of death. However, in the prediction of MACE, death and readmission, the MPV and age were significant factors (p 8.8fL) had a 7 times greater risk of MACE than the lowest quartile group (MPV<7.4 fL). Conclusion:The MPV measured in the emergency room is a significant predictor of MACE with an acute myocardial infarction. Therefore, patients with a large MPV might require more intensive, closely controlled treatment strategies for secondary prevention. (Korean Circulation J 2003;33 (10):878-883)

Decreased serglycin proteoglycan size is associated with the platelet alpha granule storage defect in Wistar Furth hereditary macrothrombocytopenic rats. Serglycin binding affinity to type I collagen is unaltered.

The Wistar Furth (WF) rat has a hereditary defect in platelet formation that resembles gray platelet syndrome of man with a large mean platelet volume and platelet alpha granule deficiency. The alpha granule abnormality is suggestive of a defect in granule packaging and/or stability. Proteoglycans are hypothesized to play a role in granule packaging. Therefore, we have analyzed the structure of the platelet proteoglycan, serglycin, in platelets of WF and normal Wistar rats. Normal and Wistar Furth rats were injected with 35S-sulfate to label platelet proteoglycans via synthesis by the megakaryocytes, and platelets were isolated 3 days later. We found that WF rat platelets have only one-third of the normal proteoglycan mass per unit platelet volume, and the proteoglycans are smaller in hydrodynamic size with shorter glycosaminoglycan chains than those of Wistar rats. However, WF rat platelet proteoglycans showed no defect in binding to collagen on affinity coelectrophoresis gels. We conclude that the structure of WF rat platelet proteoglycans is abnormal, and speculate that this abnormality may contribute to abnormal packaging of the alpha granule contents. Leakage of alpha granule contents into the marrow by platelets and megakaryocytes could perturb the marrow matrix, and promote the development of myelofibrosis noted in gray platelet syndrome.

The Effect of Cigarette-Smoking on Cardiovascular Risk Factors: a Study of Monozygotic Twins Discordant for Smoking

The association of cigarette smoking with the development of occlusive vascular disease is firmly established. Unfavourable changes in a series of variables held independent risk factors for the development of vascular lesions (HDL-cholesterol, haematocrit, white blood cell count, fibrinogen and plasminogen activator inhibitor-1 (PAI-1)) are thought to be directly influenced by cigarette smoking. However, the role played by the genotype in the effect of smoking on the above parameters has not been investigated. To control the genotype, we studied the relationship between cigarette smoking and a series of cardiovascular risk factors in 27 monozygotic twin pairs (7 male and 20 female pairs, mean age +/- SD: 47.4 +/- 12.9 yrs) with a life-long discordance for smoking. Smoking twins had a life-long dose of smoking (Brickman index) of 287.3 +/- 241.5. Body mass index, blood pressure, haematocrit, haemoglobin and red blood cell counts, total cholesterol levels and the acute phase reactants alpha 1-acid glycoprotein and C-reactive protein were similar in smokers and non-smokers. Triglyceride was higher by 12.6% (9.5-35%, 95% confidence interval, p = 0.02) and HDL-cholesterol lower by 7.5% (0.2-15%, p = 0.04) in the smoking co-twins, who also had 8.4% (-0.2-17%, p = 0.06) higher white blood cell counts and 4.1% (1.2-7%, p < 0.01) larger mean platelet volume. There was no significant difference in clottable fibrinogen (by two methods) or in the activity of plasminogen activator inhibitor-1 between the two groups, nor was the within-pair difference in these parameters related to the smoking dose. Echo-doppler examination of the carotid arteries of 24 twin pairs showed mostly minor atherosclerotic lesions in 46% and 42% of the smoking and non-smoking co-twins. After adjustment for age, systolic blood pressure and platelet count and volume were the only variables significantly associated to the presence of vascular lesions. Cigarette smoking is associated with an atherogenic lipid profile and with changes in platelets and white cells potentially reflecting endothelial cell damage. When controlling the genotype, fibrinogen and PAI-1 activity levels did not seem directly influenced by cigarette smoking.