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In contrast to red blood cells, platelets float rather than sediment when a column of blood is placed in the gravitational field. By the analogy of erythrocyte sedimentation (ESR), it can be expressed with the platelet antisedimentation rate (PAR), which quantitates the difference in platelet count between the upper and lower halves of the blood column after 1 h of 1 g sedimentation. Venous blood samples from 21 healthy subjects were analyzed for PAR. After a 1-h sedimentation, the upper and lower fractions of blood samples were analyzed for platelet count, mean platelet volume (MPV), immature platelet fraction (IPF), and highfluorescence IPF (H-IPF). The mechanisms behind platelet flotation were explored by further partitioning of the blood column, time-dependent measurements of platelet count and comparison with ESR. The structure and function of the platelets were assessed by electron microscopy (EM) and atomic force microscopy (AFM), and platelet aggregometry, respectively. Platelet antisedimentation is driven by density differences and facilitated by a sizeexclusion mechanism caused by progressive erythrocyte sedimentation. The area under the curve (AUC) of the whole blood adenosine diphosphate (ADP) aggregation curves showed significant differences between the upper and lower samples (p < .005). AUC in the upper samples of 38% of healthy subjects exceeded the top of the normal range (53--122) suggesting that ascending platelets show an intensified ADP-induced aggregability ex vivo. H-IPF was significantly higher in the upper samples (p < .05). EM and AFM revealed that platelets in the upper samples were larger in volume and contained 1.6 times more alpha granules compared to platelets in the lower samples. Our results indicate that antisedimentation is able to differentiate platelet populations based on their structural and functional properties. Therefore, PAR may be a suitable laboratory parameter in various thromboinflammatory disorders. [ABSTRACT FROM AUTHOR]

Recombinant human TPO (rhTPO) is effective for refractory/relapsed primary immune thrombocytopenia (ITP), but optimal dosing regimen remains elusive. In this multicenter, randomized, controlled trial, a total of 282 adult ITP patients (mean age 47.3 years; 82 men) with a platelet count ≤30 × 109/L or >30 × 109/L with active bleeding randomly received a once daily (QD) subcutaneous injection of 7500 U (n = 64) or 15000 U rhTPO for 14 injections, or 15000 U or 30000 U rhTPO once every other day (QOD) for 7 injections. The primary outcomes included change from baseline in platelet count and total response rate (TRR) on day 14. On day 14, the median increase of platelet count from baseline was the highest in the 15000-U QD group (167.5 × 109/L, interquartile range [IQR] 23.0-295.0 × 109/L), followed by the 30000-U QOD group (57.5 × 109/L, IQR 9.0-190.0 × 109/L) (ANCOVA P < .001; P = .266 with baseline count as a covariate). The TRR on day 14 was also the highest in the 15000-U QD group (63.2%), followed by the 30000-U QOD group (59.7%). The rate of grade 3 and above adverse events did not differ among the four groups. There were no new safety concerns. All 4 regimens are safe and well-tolerated. The 30000-U QOD regimen is practically indistinguishable in efficacy to the 15000-U QD regimen. [ABSTRACT FROM AUTHOR]

Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with high burden of comorbidities known to increase the mean platelet volume (MPV). This parameter has been associated with morbidity and mortality in HF. However, the role of platelets and the prognostic relevance of MPV in HFpEF remain largely unexplored. We aimed to evaluate the clinical usefulness of MPV as a prognostic marker in HFpEF. We prospectively enrolled 228 patients with HFpEF (79 ± 9 years; 66% females) and 38 controls of similar age and gender (78 ± 5 years; 63% females). All subjects underwent two-dimensional echocardiography and MPV measurements. Patients were followed-up for a primary end point of all-cause mortality or first HF hospitalization. The prognostic impact of MPV was determined using Cox proportional hazard models. Mean MPV was significantly higher in HFpEF patients compared with controls (MPV: 10.7 ± 1.1fL vs. 10.1 ± 1.1fL, p = .005). HFpEF patients (n = 56) with MPV >75th percentile (11.3 fL) displayed more commonly a history of ischemic cardiomyopathy. Over a median follow-up of 26 months, 136 HFpEF patients reached the composite endpoint. MPV >75th percentile was a significant predictor of the primary endpoint (HR: 1.70 [1.08; 2.67], p = .023) adjusted for NYHA class, chronic obstructive pulmonary disease, loop diuretics, renal function, and hemoglobin. We demonstrated that MPV was significantly higher in HFpEF patients compared with controls of similar age and gender. Elevated MPV was a strong and independent predictor of poor outcome in HFpEF patients and may be relevant for clinical use. [ABSTRACT FROM AUTHOR]

Many patients with coronary artery disease (CAD) have reduced the effect of aspirin, which may partly be explained by immature platelets. We aimed to investigate whether immature platelet markers can predict cardiovascular events in a large cohort of stable CAD patients. A total of 900 stable CAD patients were included and followed for a median of 3 years. We measured markers of immature platelets (platelet count, immature platelet count, immature platelet fraction, mean platelet volume, platelet distribution width, platelet mass, and thrombopoietin) using automated flow cytometry and studied their relation to cardiovascular events. Our primary endpoint was a composite of acute myocardial infarction (MI), ischemic stroke, and cardiovascular death. A composite of MI, ischemic stroke, stent thrombosis and all-cause mortality was analyzed as a secondary endpoint. We found no difference in immature platelet markers between CAD patients with or without cardiovascular events. Regression analysis using hazards rates showed that markers of immature platelets did not have any predictive value for endpoints (p-values > .05). Markers of immature platelets did not predict future cardiovascular events during a 3-year followup period in CAD patients. This suggests that immature platelets measured in a stable phase does not have a major role in predicting future cardiovascular events. [ABSTRACT FROM AUTHOR]

ANKRD26-related thrombocytopenia (ANKRD26-RT or THC2, MIM 188 000), an autosomal dominant thrombocytopenia, is unresponsive to immunosuppressive therapy and susceptible to hematological malignancies. A large number of pediatric patients are diagnosed with immune thrombocytopenia (ITP) every year; however, thrombocytopenia of genetic origin is often missed. Extensive characterization of ANKRD26-RT will help prevent missed diagnosis and misdiagnosis. Furthermore, identification of ANKRD26-RT will help in the formulation of an accurate diagnosis and a treatment plan. In our study, we report cases of two Chinese pediatric patients with ANKRD26-RT and analyze their clinical characteristics, gene mutations, and treatment modalities. Both patients were 1-year-old and presented with mild bleeding (World Health Organization(WHO) score grade 1), different degrees of platelet reduction, normal mean platelet volume, and megakaryocyte maturation impairment not obvious. Genetic tests revealed that both patients had ANKRD26 gene mutations. Patient 1 had a mutation c.-140C>G of the 5' untranslated region (UTR), and patient 2 had a mutation of c.-127A>T of 5'UTR. Both patients were treated with eltrombopag, and the treatment was no response, with no adverse reactions. [ABSTRACT FROM AUTHOR]

We have evaluated a commercial-fixed porcine platelet preparation (with and without added fixed human red blood cells (RBC)) for the potential standardization of mean platelet volume (MPV) measurements. The standards (Biotechne) were distributed internationally to 19 laboratories including all major hematology instrument manufacturers and academic/pathology laboratories. Overall, the standards demonstrated excellent stability up to 1 month within both MPV values and platelet counts when stored at 4°C. The presence of RBC significantly increased the platelet count and MPV values compared to platelets alone. However, as expected, there were differences in MPV values between different instruments and manufacturers. MPV values were also significantly higher in the whole blood standard compared to the platelet standard in the majority of instruments except with some instruments, where MPV values were significantly higher in the platelet only preparation. To further investigate this phenomenon, two different Platelet MPV preparations (with low and high MPV) in combination with 3 different RBC MCV preparations (with low, normal or high MCVs) were tested to try and further elucidate how RBC populations may impact upon platelet analysis (count, MPV, and PDW) using a single impedance analyzer. Both MPV and MCV values showed good stability over the course of the study for up to 50 days. As expected, the RBC preparation with the lowest MCV had the greatest impact on the MPV. However, this was not observed with an increase in MCV of the RBC or by a larger MPV of the platelet population. To further understand how different gating strategies may also influence results, we investigated the effect of either fixed or floating gate strategies upon MPV raw data from patient samples in a single impedance analyzer. Overall, it was clear that floating and fixed gate strategies also significantly impact upon MPV values. In conclusion, we have demonstrated the potential of an MPV standard with good stability characteristics for calibrating and comparing full blood counters that use different analysis principles, gating and MPV calculations. This may facilitate future instrument calibration and harmonization of results between different technologies.

ANKRD26-related thrombocytopenia (ANKRD26-RT or THC2, MIM 188 000), an autosomal dominant thrombocytopenia, is unresponsive to immunosuppressive therapy and susceptible to hematological malignancies. A large number of pediatric patients are diagnosed with immune thrombocytopenia (ITP) every year; however, thrombocytopenia of genetic origin is often missed. Extensive characterization of ANKRD26-RT will help prevent missed diagnosis and misdiagnosis. Furthermore, identification of ANKRD26-RT will help in the formulation of an accurate diagnosis and a treatment plan. In our study, we report cases of two Chinese pediatric patients with ANKRD26-RT and analyze their clinical characteristics, gene mutations, and treatment modalities. Both patients were 1-year-old and presented with mild bleeding (World Health Organization(WHO) score grade 1), different degrees of platelet reduction, normal mean platelet volume, and megakaryocyte maturation impairment not obvious. Genetic tests revealed that both patients had ANKRD26 gene mutations.Patient 1 had a mutation c.-140C>G of the 5' untranslated region (UTR), and patient 2 had a mutation of c.-127A>T of 5'UTR. Both patients were treated with eltrombopag, and the treatment was no response, with no adverse reactions. What is the background? ANKRD26-RT is an autosomal dominant thrombocytopenia which is unresponsive to immunosuppressive therapy and susceptible to hematological malignancies. It is rare and lacks specific clinical features, making misdiagnosis easy. Some studies report that eltrombopag is safe and effective for short-term treatment of the disease; however, these reports are limited. What we did and summary of findings. We retrospectively studied the clinical manifestations and diagnosis process of ANKRD26-RT and discussed the treatment efficacy of immunosuppressants and eltrombopag for its management. We found two pediatric cases of patients with ANKRD26-RT with varying degrees of thrombocytopenia, mild bleeding, normal mean platelet volume, and megakaryocyte maturation impairment that was not obvious. Immunosuppressant treatment wasunresponsiveor temporarily responsivebut not sustained , and short-term administration of eltrombopag (25 mg/day) was safe, but it did not effectively improve the patients' platelet counts. What is the impact? If patients clinically diagnosed with immune thrombocytopenia do not respond to immunosuppressive agents, genetic testing should be conducted to exclude hereditary thrombocytopenia, and a normal mean platelet volume should not exclude the possibility of the disease. For patients with ANKRD26-RT, eltrombopag is safe for short-term use;however, 25 mg/day treatment is unresponsive. Ourreport complements data on the diagnosis and management of ANKRD26-RT disease in children. [ABSTRACT FROM AUTHOR]

We have evaluated a commercial-fixed porcine platelet preparation (with and without added fixed human red blood cells (RBC)) for the potential standardization of mean platelet volume (MPV) measurements. The standards (Biotechne) were distributed internationally to 19 laboratories including all major hematology instrument manufacturers and academic/pathology laboratories. Overall, the standards demonstrated excellent stability up to 1 month within both MPV values and platelet counts when stored at 4°C. The presence of RBC significantly increased the platelet count and MPV values compared to platelets alone. However, as expected, there were differences in MPV values between different instruments and manufacturers. MPV values were also significantly higher in the whole blood standard compared to the platelet standard in the majority of instruments except with some instruments, where MPV values were significantly higher in the platelet only preparation. To further investigate this phenomenon, two different Platelet MPV preparations (with low and high MPV) in combination with 3 different RBC MCV preparations (with low, normal or high MCVs) were tested to try and further elucidate how RBC populations may impact upon platelet analysis (count, MPV, and PDW) using a single impedance analyzer. Both MPV and MCV values showed good stability over the course of the study for up to 50 days. As expected, the RBC preparation with the lowest MCV had the greatest impact on the MPV. However, this was not observed with an increase in MCV of the RBC or by a larger MPV of the platelet population. To further understand how different gating strategies may also influence results, we investigated the effect of either fixed or floating gate strategies upon MPV raw data from patient samples in a single impedance analyzer. Overall, it was clear that floating and fixed gate strategies also significantly impact upon MPV values. In conclusion, we have demonstrated the potential of an MPV standard with good stability characteristics for calibrating and comparing full blood counters that use different analysis principles, gating and MPV calculations. This may facilitate future instrument calibration and harmonization of results between different technologies. [ABSTRACT FROM AUTHOR]

The use of mean platelet diameter (MPD) to classify inherited thrombocytopenia (IT) has been demonstrated in several studies. Alternatively, the mean platelet volume (MPV) may be used, but in macrothrombocytopenia this may not be available. We hypothesized that platelet forward scatter (FSC) measurements using flow cytometry may be used for the size-based classification of IT. The study aimed to assess the ability of platelet FSC to measure platelet size and whether it could be used as an alternative to the MPD or MPV. Blood samples were obtained from individuals undergoing investigation for inherited platelet function disorders (IPFD, n = 40) or platelet number disorders (IPND, n = 46). A hematology analyzer was used to obtain MPV and platelet counts, flow cytometry to measure platelet FSC and ImageJ software to measure MPD from stained blood smears. The International Society of Thrombosis and Hemostasis (ISTH) Bleeding Assessment Tool (BAT) was used to calculate bleeding scores. Twenty-nine(63%) of IPND patients had an MPV that could not be reported. A significant correlation to platelet FSC was found to the MPD (p <.0001) and MPV (p <.0001) and an inverse correlation with platelet count (p <.0001). No significant correlation was found between FSC and bleeding history. In conclusion, platelet FSC is an alternative to MPV and may be used in macrothrombocytopenia where the MPV is not recorded [ABSTRACT FROM AUTHOR]

Information regarding the profile of reticulated platelets (RP) in ischemic cerebrovascular disease (CVD) patients is limited. Data from two prospective, observational, case-control studies were combined to compare the %RP using whole blood flow cytometry in patients ≤ 4 weeks of TIA/stroke onset (baseline, N = 210), and 14 ±7 days (14d, N = 182) and ≥ 90 days (90d, N = 145) after starting or changing antiplatelet therapy with healthy controls (N = 34). There were no differences in median %RP between the overall CVD patient population at baseline or 14d vs. controls (P ≥ 0.2). However, the median %RP was significantly higher in CVD patients overall at 90d (P = .036), and in the subgroup of patients with “lacunar” TIA/ischemic stroke at baseline (P = .04) and at 90d (P = .01), but not at 14d (P = .06) vs. controls. There were no significant differences in the median %RP between other TIA/stroke subgroups and controls (P ≥ 0.05). Elevated circulating reticulated platelets, as a marker of increased platelet production/turnover, may occur following an ischemic event in a well-phenotyped TIA/ischemic stroke population overall, but may precede symptom onset at least in the subgroup with small vessel occlusion. These data improve our understanding of the profile of reticulated platelets in CVD patients.

Platelets counts increase in various cancer patients, which is associated with poor prognosis. However, the cause of high platelet counts in cancer patients is still not fully understood. Here we demonstrated that compared with healthy controls, there were significant differences in platelet parameters, mean platelet volume (MPV), platelet distribution width (PDW), platelet larger cell ratio (P-LCR), and platelet crit (PCT), reflecting platelet volume in breast cancer patients by clinical retrospective analysis. The mitochondrial transmembrane potential (ΔΨm) depolarization and phosphatidylserine (PS) externalization declined, accompanied by reduced expression of pro-apoptotic factors Bak, Bax and apoptotic executor caspase-3, and elevated of anti-apoptotic factor Bcl-xl in various cancer patients' platelets. Notably, the phosphorylation level of Akt and its downstream target Bad increased in platelets from cancer patients. MK2206, the inhibitor of Akt, reduced the phosphorylation level of Akt and Bad, and induced apoptosis of platelets. When platelets from healthy controls cocultured with the cultural supernatant of cancer cells, the phosphorylation level of Akt and Bad in the platelets was elevated and the cultural supernatant of cancer cells could rescue the apoptosis of platelet induced by MK2206. Therefore, in our study the apoptosis of platelets in cancer patients was declined, which exerted an influence on the rise of platelet counts in breast cancer patients. The cross-talking between tumor and platelets could affect platelet apoptosis by regulating Akt signaling pathway in platelets. [ABSTRACT FROM AUTHOR]

While the role of platelets in cardiovascular diseases among the general population has been widely reported, evidence is inconsistent regarding the association between platelet indices with hypertension in pregnant women. In this study, we explored the associations between platelet parameters before 20 gestational weeks, an understudied period, with hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PEEC) and gestational hypertension (GH). Based on the Born in Guangzhou Cohort Study, 12053 singleton pregnant women with platelet parameters, including platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) measured at 14–19 gestational weeks were included. Conventional multivariable adjustment and propensity score analysis were used to control for confounders. The restricted cubic spline showed that the risk of PEEC increased linearly for PC, and non-linearly for PCT. For GH, the risk increased linearly for PC, MPV, and PCT, and non-linearly for PDW. When these indices were categorized into quintiles, women with higher PC and PCT were associated with increased risk of both PEEC and GH. Women with MPV exceeding the second quintile (≥ 8.8 fL) had a greater risk for GH, but not for PEEC. When HDP was classified into two groups (early- vs late-onset) based on the occurrence time, significant associations persisted for early-onset PEEC, early-onset GH, and late-onset GH. In conclusion, increased PC and PCT before 20 weeks of gestation were both associated with higher risk of PEEC and GH, while elevated MPV was only linked to GH. [ABSTRACT FROM AUTHOR]

Endovascular aortic repair (EVAR) an alternative to open surgical repair of thoracoabdominal aortic aneurysm (TAAA). The effect of EVAR on platelet reactivity is unknown. We prospectively determined the effect of branched EVAR (bEVAR) on platelet reactivity in patients with TAAA, and evaluated the predictive value of preoperative platelet reactivity for post-operative bleeding in 50 consecutive patients undergoing elective bEVAR (mean age 70.9 ± 5.7 years, 66% male). Blood samples were collected within 24 hours before bEVAR, after bEVAR and at hospital discharge. Platelet reactivity was assessed with impedance aggregometry using ASPI, ADP and TRAP tests. Platelet reactivity decreased within 24 hours after bEVAR compared to the measurement before bEVAR in all tests (p ≤ 0.04), with a further decrease in hospital discharge in the ADP test (p =.004). Twenty-three patients experienced post-operative bleeding complications (transfusion ≥2 red blood cell [RBC] units). Preoperative platelet reactivity below the cutoff value of 30 AUC units predicted post-operative bleeding with 78% sensitivity and 59% specificity (p =.045). In the multivariable analysis, platelet reactivity was the only independent predictor of postoperative bleeding (OR 6.507, 95% CI 1.227–34.506, p =.028). We conclude that platelet reactivity decreases following bEVAR of TAAA and is a strong and independent predictor for postoperative bleeding complications. [ABSTRACT FROM AUTHOR]

Reticulated platelets (RP) are young, functionally active platelet forms which are detected by RNA staining. Their content in the circulation reflects the intensity of bone marrow thrombocytopoesis. The aim of this study was to assess in healthy volunteers the relationship between RP percentage and platelet size and activity. RP were quantitated by thiazole orange staining using flow cytometry. Platelet size indexes included mean platelet volume (MPV), platelet large cell ratio (P-LCR) measured in a Coulter type hematological analyzer and forward scattering (FSC) measured in a flow cytometer. Platelet functional activity was evaluated by expression of activated glycoprotein (GP) IIb-IIIa (PAC-1 antibody binding) and P-selectin with the use of flow cytometry. Platelets were activated by thrombin receptor activating peptide (TRAP) (10 and 1 µM) and ADP (20 and 2.5 µM). The percentage of RP in healthy volunteers varied from 2.9% to 23.8% (mean ± SD ‒ 11.7 ± 4.7%, n = 99) and correlated with all platelet size indexes: MPV, P-LCR and FCS (r from 0.452 to 0.529, p <.001, n = 87–99). On average, RP were distributed at a ratio of 9:1 between 50% subpopulations of large and small platelets according to their FSC index. Expression of GP IIb-IIIa activated form correlated with RP percentage and platelet size indexes when platelets were activated by TRAP and ADP at both applied concentrations (r from 0.309 to 0.560, p from 0.014 to < 0.001, n = 50–62). P-selectin expression correlated with RP percentage and platelet size indexes when platelets were activated by 10 µM TRAP inducing maximum expression of this activation marker (r from 0.332 to 0.556, p from 0.008 to < 0.001, n = 65), but not by weaker agonists: 1 µM TRAP, 20 and 2.5 µM ADP (r < 0.3, n = 54–66). Thus, high RP content in healthy volunteers is associated with increased platelet size and activity in the whole platelet population. [ABSTRACT FROM AUTHOR]

The coronavirus disease 19 (COVID-19) is a highly transmittable viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS‐CoV‐2 utilizes metallocarboxyl peptidase angiotensin receptor (ACE) 2 to gain entry into human cells. Activation of several proteases facilitates the interaction of viral spike proteins (S1) and ACE2 receptor. This leads to cleavage of host ACE2 receptors. ACE2 activity counterbalances the angiotensin II effect, its loss may lead to elevated angiotensin II levels with modulation of platelet function, size and activity. COVID-19 disease encompasses a spectrum of systemic involvement far beyond respiratory failure alone. Several features of this disease, including the etiology of acute kidney injury (AKI) and the hypercoagulable state, remain poorly understood. Here, we show that there is a high incidence of AKI (81%) in the critically ill adults with COVID-19 in the setting of elevated D-dimer, elevated ferritin, C reactive protein (CRP) and lactate dehydrogenase (LDH) levels. Strikingly, there were unique features of platelets in these patients, including larger, more granular platelets and a higher mean platelet volume (MPV). There was a significant correlation between measured D-dimer levels and MVP; but a negative correlation between MPV and glomerular filtration rates (GFR) in critically ill cohort. Our data suggest that activated platelets may play a role in renal failure and possibly hypercoagulability status in COVID19 patients.

Information regarding the profile of reticulated platelets (RP) in ischemic cerebrovascular disease (CVD) patients is limited. Data from two prospective, observational, case-control studies were combined to compare the %RP using whole blood flow cytometry in patients ≤ 4 weeks of TIA/stroke onset (baseline, N = 210), and 14 ±7 days (14d, N = 182) and ≥ 90 days (90d, N = 145) after starting or changing antiplatelet therapy with healthy controls (N = 34). There were no differences in median %RP between the overall CVD patient population at baseline or 14d vs. controls (P ≥ 0.2). However, the median %RP was significantly higher in CVD patients overall at 90d (P =.036), and in the subgroup of patients with "lacunar" TIA/ischemic stroke at baseline (P =.04) and at 90d (P =.01), but not at 14d (P =.06) vs. controls. There were no significant differences in the median %RP between other TIA/stroke subgroups and controls (P ≥ 0.05). Elevated circulating reticulated platelets, as a marker of increased platelet production/turnover, may occur following an ischemic event in a well-phenotyped TIA/ischemic stroke population overall, but may precede symptom onset at least in the subgroup with small vessel occlusion. These data improve our understanding of the profile of reticulated platelets in CVD patients. [ABSTRACT FROM AUTHOR]

Correlation between platelet indices and chronic inflammatory arthritis (CIA) remains a moot point today. This meta-analysis aimed to evaluate whether platelet (PLT) count, mean platelet volume (MPV) and platelet distribution width (PDW) associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). A systematic literature search was performed in PubMed, EMBASE, and Web of Science up to August 2019. Pooled standardized mean differences (SMD) and 95% confidence interval (CI) were calculated using a random-effect model. As a result, 34 studies were included, encompassing 17 on RA, 12 on AS, 3 on PsA and 2 on both RA and AS. In these studies, PLT count was significantly higher in RA (SMD = 0.55, 95% CI = 0.36–0.73, P < .001), AS (SMD = 0.53, 95% CI = 0.36–0.70, P < .001) and PsA patients (SMD = 1.29, 95% CI = 0.82–1.77, P < .001) than that in healthy subjects, while MPV and PDW presented nonsignificant differences in these intergroup comparisons (P > .05), and similar results were observed in subgroup analyses. The meta-regression analysis demonstrated that there were strong positive correlations between erythrocyte sedimentation rate and PLT count, and weak correlation trend between the disease activity score and PLT count in both RA and AS subjects without statistically significant difference. The sensitivity analysis indicated that these results were not unduly influenced by any single study. In conclusion, this meta-analysis demonstrated that PLT count was elevated in CIA patients and could be suitable for evaluating the disease activity, whereas MPV and PDW were independent of CIA.

Changes of mean platelet volume (MPV) and platelet count (PC) could be a marker or a predictor of acute stroke (AS). We conducted a systematic review and meta-analysis of the published literature on the reporting of MPV and PC in AS. Studies were included in accordance with Patient Population or Problem, Intervention, Comparison, Outcomes, and Setting framework. The PRISMA strategy was used to report findings. Risk of bias was assessed with the Newcastle-Ottawa Scale. We included 34 eligible articles retrieved from the literature. PC was significantly lower in AS patients [standardized mean difference (SMD) = − 0.30, (95% CI: − 0.49 to − 0.11), N = 2492, P = .002] compared with controls (N = 3615). The MPV was significantly higher [SMD = 0.52 (95% CI: 0.28–0.76), N = 2739, P < .001] compared with controls (N = 3810). Subgroup analyses showed significantly lower PC in both ischemic stroke (Difference SMD = −0.18, 95% CI: −0.35–0.01) and hemorrhagic stroke (−0.94, −1.62 to −0.25), but only samples by citrate anticoagulant showed significantly lower result for patients compared to controls (−0.36, −0.68 to −0.04). Ischemic stroke patients had higher MPV (0.57, 0.31–0.83), and samples by Ethylenediaminetetraacetic acid (EDTA) anticoagulant showed significantly higher result for patients compared to controls (0.86, 0.55–1.17). PC and MPV appeared to be significantly different between patients with AS and control populations. MPV was significantly higher in ischemic stroke and PC was significantly lower in both ischemic and hemorrhagic strokes. These characteristics might be related to AS and associated with it. It is advisable to pay attention to elapsed time between phlebotomy and hematology analysis, anticoagulant and hemocytometer types in AS. Systematic review registration This meta-analysis is registered on the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42017067864 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=67864).

Platelet function in neonates is sparsely investigated. The majority of previous studies investigated platelets in umbilical cord (UC) blood rather than in peripheral blood. We included 20 term neonates and sampled UC blood and peripheral blood within 20 min and 24 h after birth. Platelet count and mean platelet volume (MPV) were measured. Platelet surface glycoproteins (GP) and platelet activation (bound fibrinogen, CD63 and p-selectin) after agonist stimulation were examined by flow cytometry. Platelet aggregation was evaluated by impedance aggregometry. The significance level was set after Bonferroni correction. Platelet count and MPV did not differ between UC and peripheral blood (p-values >0.08). Expression of platelet surface GP was similar in UC and peripheral blood (all p-values >0.02). Platelet activation was lower in UC blood than in peripheral blood for bound fibrinogen (four out of eight p-values <0.001) but did not differ for CD63 (all p-values >0.01) or P-selectin (all p-values >0.01). Platelet aggregation was significantly higher in UC than in peripheral blood (p-values <0.001). In conclusion, platelet count, MPV and expression of platelet surface GP measured in term neonatal UC blood represented that of peripheral blood. Platelet activation and aggregation in UC blood did not reflect that of peripheral blood. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the association between platelet (PLT) count and mean platelet volume (MPV) and venous thromboembolism (VTE). Thus, this study reviewed and performed a quantitative synthesis on data from the literature. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 18 studies were included in this paper. A random-effect meta-analysis was conducted for the assessment of heterogeneity using thrombosis place, type of analyzer, type of anticoagulant and incubation time of samples as covariates. A mixed-effect meta-regression was performed based on the subgroup for the whole samples using thrombosis place and method of measurement as moderators for MPV and PLT, respectively. The cumulative estimates and 95% confidence interval (95%CI) of specificity, sensitivity, area under the receiver operator characteristic curve (AUC) and diagnostic odds ratio (DOR) for MPV were calculated using a random effect model. The quality assessments were evaluated according to the quality assessment and diagnostic accuracy tool-2 (QUADAS-2). The primary outcome was the occurrence of VTE. Secondary outcomes included PLT and MPV. Patient with deep vein thrombosis is likely to have a higher value of MPV than control group (P

The coronavirus disease 19 (COVID-19) is a highly transmittable viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS‐CoV‐2 utilizes metallocarboxyl peptidase angiotensin receptor (ACE) 2 to gain entry into human cells. Activation of several proteases facilitates the interaction of viral spike proteins (S1) and ACE2 receptor. This leads to cleavage of host ACE2 receptors. ACE2 activity counterbalances the angiotensin II effect, its loss may lead to elevated angiotensin II levels with modulation of platelet function, size and activity. COVID-19 disease encompasses a spectrum of systemic involvement far beyond respiratory failure alone. Several features of this disease, including the etiology of acute kidney injury (AKI) and the hypercoagulable state, remain poorly understood. Here, we show that there is a high incidence of AKI (81%) in the critically ill adults with COVID-19 in the setting of elevated D-dimer, elevated ferritin, C reactive protein (CRP) and lactate dehydrogenase (LDH) levels. Strikingly, there were unique features of platelets in these patients, including larger, more granular platelets and a higher mean platelet volume (MPV). There was a significant correlation between measured D-dimer levels and MVP; but a negative correlation between MPV and glomerular filtration rates (GFR) in critically ill cohort. Our data suggest that activated platelets may play a role in renal failure and possibly hypercoagulability status in COVID19 patients. [ABSTRACT FROM AUTHOR]

Correlation between platelet indices and chronic inflammatory arthritis (CIA) remains a moot point today. This meta-analysis aimed to evaluate whether platelet (PLT) count, mean platelet volume (MPV) and platelet distribution width (PDW) associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). A systematic literature search was performed in PubMed, EMBASE, and Web of Science up to August 2019. Pooled standardized mean differences (SMD) and 95% confidence interval (CI) were calculated using a random-effect model. As a result, 34 studies were included, encompassing 17 on RA, 12 on AS, 3 on PsA and 2 on both RA and AS. In these studies, PLT count was significantly higher in RA (SMD = 0.55, 95% CI = 0.36–0.73, P <.001), AS (SMD = 0.53, 95% CI = 0.36–0.70, P <.001) and PsA patients (SMD = 1.29, 95% CI = 0.82–1.77, P <.001) than that in healthy subjects, while MPV and PDW presented nonsignificant differences in these intergroup comparisons (P >.05), and similar results were observed in subgroup analyses. The meta-regression analysis demonstrated that there were strong positive correlations between erythrocyte sedimentation rate and PLT count, and weak correlation trend between the disease activity score and PLT count in both RA and AS subjects without statistically significant difference. The sensitivity analysis indicated that these results were not unduly influenced by any single study. In conclusion, this meta-analysis demonstrated that PLT count was elevated in CIA patients and could be suitable for evaluating the disease activity, whereas MPV and PDW were independent of CIA. [ABSTRACT FROM AUTHOR]

Platelets are critical for hemostasis, and a low platelet count predicts mortality in trauma. The role of platelet dysfunction in severe traumatic hemorrhage and coagulopathy needs to be further defined. The aim of this study was to evaluate the platelet function in a new model of experimental traumatic hemorrhage. New Zealand white rabbits (n = 10) were subjected to tracheostomy and trauma laparotomy, and then bilateral femur fractures with 40% hemorrhage of their estimated blood volume. Arterial blood gases, standard coagulation tests, mean platelet volume, platelet aggregation using impedance aggregometry with agonist collagen, arachidonic acid (ASPI), and adenosine diphosphate (ADP), rotational thromboelastometry, and fibrinogen binding of platelets were analyzed using flow cytometry. After traumatic hemorrhage, there was a significant physiological response with a rise in lactate (P <.001) and a decrease in base excess (P <.001) and temperature (P <.001). Platelet count decreased from a mean of 244x109/L to 94 x109/L (P =.004) and the mean platelet volume increased from 5.1fL to 6.1fL (P =.002). Impedance aggregometry with the agonist collagen, ASPI, and ADP was all significantly decreased after hemorrhage (P =.007). However, there was an increased fibrinogen binding of ADP-activated platelets after traumatic hemorrhage analyzed by flow cytometry (P <.05). This traumatic hemorrhage model presents two parallel pathophysiological responses of platelets; platelet consumption as evidenced by a significant decrease in platelet count and aggregation, and platelet hyperreactivity as shown by a higher mean platelet volume and enhanced platelet fibrinogen binding. Further studies are needed to characterize these different aspects of platelet function in severe traumatic hemorrhage. [ABSTRACT FROM AUTHOR]

Changes of mean platelet volume (MPV) and platelet count (PC) could be a marker or a predictor of acute stroke (AS). We conducted a systematic review and meta-analysis of the published literature on the reporting of MPV and PC in AS. Studies were included in accordance with Patient Population or Problem, Intervention, Comparison, Outcomes, and Setting framework. The PRISMA strategy was used to report findings. Risk of bias was assessed with the Newcastle-Ottawa Scale. We included 34 eligible articles retrieved from the literature. PC was significantly lower in AS patients [standardized mean difference (SMD) = − 0.30, (95% CI: − 0.49 to − 0.11), N = 2492, P =.002] compared with controls (N = 3615). The MPV was significantly higher [SMD = 0.52 (95% CI: 0.28–0.76), N = 2739, P <.001] compared with controls (N = 3810). Subgroup analyses showed significantly lower PC in both ischemic stroke (Difference SMD = −0.18, 95% CI: −0.35–0.01) and hemorrhagic stroke (−0.94, −1.62 to −0.25), but only samples by citrate anticoagulant showed significantly lower result for patients compared to controls (−0.36, −0.68 to −0.04). Ischemic stroke patients had higher MPV (0.57, 0.31–0.83), and samples by Ethylenediaminetetraacetic acid (EDTA) anticoagulant showed significantly higher result for patients compared to controls (0.86, 0.55–1.17). PC and MPV appeared to be significantly different between patients with AS and control populations. MPV was significantly higher in ischemic stroke and PC was significantly lower in both ischemic and hemorrhagic strokes. These characteristics might be related to AS and associated with it. It is advisable to pay attention to elapsed time between phlebotomy and hematology analysis, anticoagulant and hemocytometer types in AS. This meta-analysis is registered on the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42017067864 (). [ABSTRACT FROM AUTHOR]

Coagulation disorders and thrombocytopenia are common in patients with septic shock, but only few studies have focused on platelet variables beyond platelet count. The aim of this study was to evaluate whether platelets reactivity predicts sepsis-induced thrombocytopenia in patients with septic shock. We therefore enrolled consecutive patients with septic shock and platelets count >150*103/μL on the day of the diagnosis. Platelets reactivity tests were performed daily from the diagnosis of septic shock until day five; platelet volume distribution and mean platelet volume were also recorded daily. Sepsis-induced thrombocytopenia was defined as a platelet count <150*103/μL. Thirty patients were included; sepsis-induced thrombocytopenia occurred in 11 (31%) patients. Platelets reactivity and platelet count at day of septic shock diagnosis were not correlated. Patients who experienced thrombocytopenia had lower maximal aggregation at diagnosis than others. Maximal aggregation tests were predictors of thrombocytopenia (AUROC from 0.756 to 0.797, depending on the agonist used). Both platelet volume distribution width and mean platelet volume were predictors of 90-day mortality (AUROC 0.866 and 0.735, respectively). In this pilot study, impaired platelets reactivity was more common in patients who subsequently developed sepsis-induced thrombocytopenia; also, platelet volume distribution width and mean platelet volume were predictors of 90-day mortality. [ABSTRACT FROM AUTHOR]

Essential thrombocythemia (ET) is characterized by persistently elevated platelet counts and an increased risk of thromboembolic events. Dysregulated expression of small noncoding microRNAs (miRNAs) have been shown in ET and may influence platelet maturity and function in ET patients. In this study, we included 22 ET patients and 19 healthy controls to investigate the expression of 12 platelet miRNAs previously reported to be dysregulated in ET. Further, we investigated the correlation between the expression of selected miRNAs and platelet maturity and platelet function. Total RNA was isolated from platelets, and expression analyses were performed using TaqMan quantitative PCR (qPCR). Mean platelet volume (MPV) and immature platelet count and -fraction (IPC and IPF) were measured using the Sysmex XE-5000 automated haematology system. Platelet function was investigated by multiple electrode aggregometry (agonists: arachidonic acid (AA), thrombin-receptor-activating-peptide (TRAP) and adenosine diphosphate (ADP)), while platelet activation was determined by multi-colour flow cytometry (antibodies: bound-fibrinogen, CD63 and P-selectin (CD62p), agonists: AA, TRAP and ADP). We showed that miR-9 and miR-490 were significantly upregulated in ET patients compared with healthy controls (p-values < 0.01), while miR-10a, miR-28, miR-126, miR-155, miR-221, miR-222, miR-223 and miR-431 were significantly downregulated in ET patients (all p-values < 0.001). A significant positive correlation was observed between miR-431 and MPV, IPC and IPF (all p-values < 0.05). The expression of miR-126 was negatively correlated with platelet aggregation induced by AA and TRAP (p < 0.05). In addition, we found the expression of miR-9 and miR-490 to be negatively correlated with the percentage of fibrinogen-, CD63- and P-selectin- positive platelets using TRAP as agonist (p < 0.05). In conclusion, our data indicate that platelet microRNAs may play a role in ET and that specific microRNAs are correlated with platelet maturity and platelet function. [ABSTRACT FROM AUTHOR]

Newborns from mothers with immune thrombocytopenic purpura (ITP) have a risk of thrombocytopenia due to passage of maternal antiplatelet antibodies into fetal/neonatal circulation. We looked for predictors of neonatal thrombocytopenia (nTP) in pregnant women with ITP. One hundred pregnant women with platelet count <100 × 109/l, no non-immune causes of thrombocytopenia and increased platelet associated IgG (PA-IgG) were included in the study. Thirty seven and 63 of them gave birth to babies with and without nTP, respectively (nTP+ and nTP− groups). Platelet count, mean platelet volume, PA-IgG, antiplatelet circulating antibodies (cAB), time of ITP onset (before or during pregnancy), and frequency of corticosteroid treatment were compared in these groups. There were no differences in all test parameters between nTP+ and nTP− groups except cAB. These antibodies were detected in 33 out of 37 in nTP+ group and in 2 out of 63 mothers in nTP− group (p < 0.001). The sensitivity of this test was 89% and its specificity was 97%. A strong reverse correlation (r = −0.749, p < 0.001) was established between maternal cAB titer and neonatal platelet count. Antibodies against glycoproteins IIb–IIIa and/or Ib were identified in antigen specific MAIPA (Monoclonal Antibody Immobilization of Platelet Antigen) assay only in 10 out of 19 (53%) test sera with cAB. Antiplatelet cAB in pregnant women with ITP could serve as reliable predictors of nTP in their babies. [ABSTRACT FROM AUTHOR]

Taken together, there is ample evidence of the association of cardiovascular disease, cerebrovascular, and inflammatory disease with single nucleotide variants (SNV) due to their impact on platelet size, number, and function. With the use of electronic medical record (EMR) or other phenotypic-linked bioinformatics sources, the more important “functional” variants are emerging and provide valuable information on their specific role in promoting early onset of disease or poor response to therapeutic measures. This review will focus upon the recognized common polymorphisms or gene variants with small, but functional effects, as it is becoming clear that these contribute to hyper- or hypo-responsive platelet phenotypes. The impact of these gene variants is distinguishable among normal individuals, and they are suspected contributors to increased risk of adverse outcomes in patients with underlying disease. There are thousands of gene variants and environmental factors that may mitigate risk or amplify the potential for disease within each of us. When combined with the environment and epigenetic influences, it is clear that whole-genome sequencing and bioinformatics alone will not be enough to truly predict “risk” or probability, but awareness of their potential influence may be a starting point in selective screening and generating prevention strategies to promote a healthy lifestyle or fine-tune therapeutic choices in the future.

Preeclampsia is a serious pregnancy-related complication. Platelets are potentially important in the pathogenesis of preeclampsia, and platelet function analyses may prove as sensitive preeclampsia biomarkers. This study aimed to systematically review and summarise the literature on platelet function markers in preeclampsia. This systematic review was conducted according to PRISMA and registered in PROSPERO. Relevant studies were identified through PubMed and Embase on 15/08/17. As platelet function markers platelet activation, platelet aggregation and platelet adhesion markers were included. If possible, relevant data were extracted for each marker to perform a meta-analysis of the mean difference between women with and without preeclampsia. All 69 included articles underwent quality rating. Some platelet activation markers, especially p-selectin and mean platelet volume (MPV), were significantly increased comparing the two groups of women, while others were not. The meta-analysis demonstrated that, overall, women with preeclampsia had significantly higher MPV than in women without preeclampsia. No significant difference was found regarding platelet aggreg'ation comparing the two groups. Platelet adhesion was investigated in noneof the included studies. In conclusion, further studies are warranted to investigate platelet activation markers future role as predictive markers in preeclampsia. MPV is suggested as the most promising biomarker for evaluating platelet function in preeclampsia. [ABSTRACT FROM AUTHOR]

Platelets represent one of the main actors involved in pathogenesis of coronary artery disease (CAD). Mean platelet volume (MPV) has been proposed as marker of platelet reactivity and thrombotic risk. However, still debated is whether higher MPV constitutes an independent determinant of CAD or just the consequence of an association with several cardiovascular risk factors. Therefore, the aim of the present study was to assess the impact of metabolic syndrome (MetS), on MPV and its relationship with angiographically defined CAD. Consecutive patients undergoing coronary angiography were included. Admission samples were collected for MPV and chemistry assessment. MetS was defined according to IDF-criteria. Significant CAD was defined as at least 1 vessel stenosis > 50%, while severe CAD as left main and/or 3-vessel disease, as evaluated by quantitative coronary angiography. We included 4730 patients, among them 2167 (45.8%) had MetS. Patients with MetS were older (p < 0.001), more often females (p < 0.001), and displayed higher BMI, higher prevalence of hypercholesterolemia, renal failure, hypertension, diabetes mellitus, history of myocardial infarction (MI), previous PCI (p < 0.001, respectively), previous CABG (p = 0.002),treatment with ACE inhibitors, ARB, beta-blockers, nitrates, statins, ASA, calcium channel blockers, diuretics (p < 0.001, respectively), higher values of glycemia, HbA1c, fibrinogen (p < 0.001, respectively), creatinine (p = 0.01), uric acid (p = 0.02), and lower values of hemoglobin (p = 0.001),total-cholesterol, LDL-cholesterol, and HDL-cholesterol (p < 0.001, respectively). MetS patients showed a higher prevalence of CAD (p = 0.002) and severe CAD (p = 0.01). MPV values were slightly higher in patients with MetS (10.91 ± 1.01 vs. 10.84 ± 1.03 fL, p = 0.02), although MetS did not emerge as an independent predictor of higher MPV values (above 4th quartile; adjusted OR OR[95%CI] = 1.01[0.84–1.22], p = 0.93). When metabolic syndrome patients were analyzed according to MPV quartiles, higher MPV values did not result as an independent predictor of CAD (adjusted OR[95%CI] = 0.79[0.61–1.03], p = 0.08) and severe CAD (adjusted OR[95%CI] = 0.82 [0.65–1.03], p = 0.084). Results did not change when applying the new harmonized definition of MetS. This study shows that among patients undergoing coronary angiography MetS is not an independent predictor of higher MPV. Moreover, among MetS patients, larger-sized platelets are not associated to the prevalence and extent of CAD. [ABSTRACT FROM AUTHOR]

Body mass index (BMI) and specifically overweight and obesity have been associated with an increased platelet reactivity in different series of patients. This information is derived by different laboratory platelet function tests (PFTs) like mean platelet volume (MPV), platelet microparticles, thromboxane B2 metabolites, and others. Point-of-care PFT, which are often used in cardiac surgery, are rarely addressed. The present study aims to verify platelet reactivity using multiple-electrode aggregometry (MEA) as a function of BMI in cardiac surgery patients. One-hundred ninety-eight cardiac surgery patients free from the effects of drugs acting on the P2Y12 receptor and undergoing cardiac surgery received MEA-PFT immediately before surgery. Platelet reactivity was compared between normal weight and overweight–obese subjects. There were 99 underweight/normal (BMI < 25), 60 overweight (BMI ≥ 25) and 39 obese (BMI ≥ 30) patients. Overweight–obese patients did not show higher platelet counts nor a clear platelet hyper-reactivity, when tested with MPV and MEA ADP test. At TRAPtest, the overweight/obese patients had a significantly (P = 0.011) higher platelet reactivity (median 118, interquartile range 106–136) than controls (median 112, interquartile range 101–123) and a higher rate of platelet hyper-reactivity (odds ratio 2.19, 95% confidence interval 1.15–4.16, P = 0.016) in a multivariable model. A minor association was found between the BMI and platelet reactivity at TRAPtest, with a higher degree of activity for increasing BMI. The BMI determines an increased thrombin-dependent platelet reactivity in cardiac surgery patients. Thrombin is extensively formed during cardiac surgery, and this may explain the lower postoperative bleeding observed in obese patients in previous studies. [ABSTRACT FROM AUTHOR]

Long-term evidence shows an increased risk of cardiovascular events in the morning hours and recent studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Similar pharmacodynamic analyses of adenosine-diphosphate (ADP) receptor inhibitors are scarce. We therefore investigated changes in clopidogrel-dependent platelet function and activation over 24 h and whether enhanced platelet turnover might explain diurnal variability of platelet function and activation. Twenty-one patients after acute coronary syndromes (ACS) on maintenance doses of clopidogrel (75 mg) and aspirin (100 mg) Once per day (OD) were included. Blood was collected at five time points in 24 h. Platelet function and activation was analyzed by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P), Verify Now, multiple electrode aggregometry (MEA), and platelet PAC-1 and P-selectin (P-sel) expression. Additionally, platelet count, mean platelet volume (MPV), and reticulated platelet fraction (RPF) were analyzed. There was significant diurnal variability of clopidogrel effects as documented with VASP-P, Verify Now, and PAC-1 and P-sel (all p < 0.05), whereas MEA did not differ over 24 h. Neither MPV nor RPF varied significantly over 24 h. In patients with high RPF, platelet function and activation was significantly higher in all assays, compared to patients with low RPF (all p < 0.05). However, the changes over time in low versus high RPF groups were similar. ADP-dependent platelet function and activation recovers significantly at the end of the 24-h dosing interval in patients with ACS on a maintenance dose of clopidogrel and aspirin. Although platelet function and activation is increased in patients with higher RPF, platelet turnover might not explain the observed diurnal variability. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the association between platelet (PLT) count and mean platelet volume (MPV) and venous thromboembolism (VTE). Thus, this study reviewed and performed a quantitative synthesis on data from the literature. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 18 studies were included in this paper. A random-effect meta-analysis was conducted for the assessment of heterogeneity using thrombosis place, type of analyzer, type of anticoagulant and incubation time of samples as covariates. A mixed-effect meta-regression was performed based on the subgroup for the whole samples using thrombosis place and method of measurement as moderators for MPV and PLT, respectively. The cumulative estimates and 95% confidence interval (95%CI) of specificity, sensitivity, area under the receiver operator characteristic curve (AUC) and diagnostic odds ratio (DOR) for MPV were calculated using a random effect model. The quality assessments were evaluated according to the quality assessment and diagnostic accuracy tool-2 (QUADAS-2). The primary outcome was the occurrence of VTE. Secondary outcomes included PLT and MPV. Patient with deep vein thrombosis is likely to have a higher value of MPV than control group (P < 0.001). The presence of pulmonary embolism (PE) had no significant effect on the standardized mean difference of MPV between patients and controls. Patients are likely to have less PLT than the control group regarding all studies. However, subgroup analysis demonstrated that this effect was significant for patients with PE (P < 0.05). The summary receiver operating characteristic (SROC) curve indicated that AUC was 0.745 (95% CI: 0.672-0.834). The DOR for MPV was 4.76 (95%CI: 2.3-9.85), with diagnostic accuracy of 0.66. [ABSTRACT FROM AUTHOR]

Taken together, there is ample evidence of the association of cardiovascular disease, cerebrovascular, and inflammatory disease with single nucleotide variants (SNV) due to their impact on platelet size, number, and function. With the use of electronic medical record (EMR) or other phenotypic-linked bioinformatics sources, the more important “functional” variants are emerging and provide valuable information on their specific role in promoting early onset of disease or poor response to therapeutic measures. This review will focus upon the recognized common polymorphisms or gene variants with small, but functional effects, as it is becoming clear that these contribute to hyper- or hypo-responsive platelet phenotypes. The impact of these gene variants is distinguishable among normal individuals, and they are suspected contributors to increased risk of adverse outcomes in patients with underlying disease. There are thousands of gene variants and environmental factors that may mitigate risk or amplify the potential for disease within each of us. When combined with the environment and epigenetic influences, it is clear that whole-genome sequencing and bioinformatics alone will not be enough to truly predict “risk” or probability, but awareness of their potential influence may be a starting point in selective screening and generating prevention strategies to promote a healthy lifestyle or fine-tune therapeutic choices in the future. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate the diagnostic and prognostic roles of the mean platelet volume (MPV) in various malignant tumors through a systematic review and meta-analysis. The current study included 2,053 patients and 1,396 healthy subjects in 18 eligible studies. We performed a meta-analysis of MPV levels and the mean difference between healthy subjects and pre- and post-treatment patients. Subgroup analysis was conducted based on specific organs and platelet counts. In addition, the correlation between MPV and survival was investigated. The pooled MPVs of healthy subjects, pre-treatment, and post-treatment patients were 8.428 fL (95% confidence interval [CI] 8.118–8.738), 8.831 fL (95% CI 8.582–9.087), and 8.521 fL (95% CI 8.162–8.880), respectively. The mean difference in MPV between healthy subjects and pre-treatment patients was 0.502 (95% CI 0.285–0.719,P< 0.001). However, in lung cancer, the mean difference between pre-treatment patients and healthy subjects was −0.352 (95% CI −0.763–0.060,P= 0.094). The pooled MPV of post-treatment patients was significantly decreased compared to pre-treatment patients. There was no correlation between MPV and disease-free survival rate (hazard ratio 1.033, 95% CI 0.369–2.895). Our results showed that the MPV level was significantly higher in malignant tumors than in healthy subjects and was decreased after treatment. Further cumulative studies will be required before MPV levels can be applied for screening malignant tumors and predicting prognosis. [ABSTRACT FROM AUTHOR]

Several hundreds of studies recently investigated mean platelet volume (MPV) as measured by electronic cell counters in a wide variety of acquired diseases, and most of them found that platelet size was significantly increased with respect to healthy subjects. On this basis, it has been suggested that MPV can be used for diagnostic purposes. Moreover, investigation of subjects with arterial thrombosis not only revealed that their platelets were larger than those of controls, but also found that a high MPV predicted poor prognosis. Despite the large amount of available data, the pathogenesis of increased platelet size in these conditions is unclear. In particular, we do not know whether the increased platelet size is the cause or the consequence of thrombosis. Differences in MPV between patients and controls are usually very small and they reach the statistical significance because of the large number of investigated patients and the standardized methodology for MPV measurement. In real life, the wide variability of MPV possibly due to platelet count, sex, age, and ethnicity, as well as the very poor standardization of the methodologies used for MPV measurement, makes it impossible to decide whether an individual patient has normal or instead slightly increased MPV. So, MPV has presently no role in making diagnosis and defining prognosis in any acquired illness. [ABSTRACT FROM PUBLISHER]

The article discusses a medical study which determines the link between CYCS gene variants and thrombocytopenia. According to the study, both G42S and Y49H cytochromes c have complemented a cytochrome c knockout yeast strain. Moreover, both G42S and Y49H cytochromes c have demonstrated an enhanced ability to activate caspases in vitro.

Inherited thrombocytopenia (IT) is a heterogeneous group of rare diseases that are often confused with immune thrombocytopenia (ITP). The objective of this study was to supply clinicobiological elements that allow a distinction to be drawn between IT and chronic ITP. We then compared 23 adult patients with IT and 9 patients with chronic ITP. Our study revealed six discriminating criteria: (i) an age of discovery <34 years: positive predictive value (PPV) = 88.2% [63.6; 98.5], (ii) a family history of thrombocytopenia: PPV = 100.0% [82.4; 100.0], (iii) a personal history of bleeding: PPV = 100% [76.8; 100.0], (iv) a mean platelet volume >11 fL: PPV = 93.3% [68.1; 99.8], (v) an excess of giant platelets on blood smear: 100.0% [76.8; 100.0], and (vi) a percentage >44% of platelets with a surface area >4 µm2 in electron microscopy: PPV = 83.3% [58.6; 96.4]. If at least three of these criteria were combined, it was possible to distinguish IT from chronic ITP with 91.3% [72.0; 98.9] sensitivity and PPV = 100.0% [66.4; 100.0] specificity. The secondary objective of this study was to assess the prevalence of potential IT diagnosis in patients with chronic thrombocytopenia of uncertain origin. Applying our diagnostic approach to a series of 20 cases allowed us to estimate that 40% of them could be suffering from IT. Finally, our diagnostic approach may help to correctly distinguish IT from chronic ITP, particularly in the context of macrothrombocytopenia. [ABSTRACT FROM AUTHOR]

Background: Mean platelet volume (MPV) is a simple and reliable indicator of platelet size that correlates with platelet activation and their ability to aggregate. We studied the predictive value of MPV in patients with non-ST-segment elevation myocardial infarction (NSTEMI) treated with percutaneous coronary intervention (PCI). Methods: We analyzed the consecutive records of 1001 patients who were hospitalized due to NSTEMI at our center. The primary end point was a composite end point that included the rates of all-cause death, non-fatal myocardial infarction, and acute coronary syndrome (ACS) driven revascularization at 12 months. The enrolled patients were stratified according to the quartile of the MPV level at admission. Results: Along with the increasing quartile of MPV, the 12-month composite end point increased significantly (p= 0.010), and this association remained significant after the risk-adjusted analyses (per 1 fL higher MPV; adjusted hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.02–1.27;p= 0.026). In the multivariate analysis, the MPV was also an independent factor of all-cause mortality (per 1 fL increase; adjusted HR 1.34; 95% CI 1.12–1.61;p= 0.0014) and death or non-fatal myocardial infarction (per 1 fL increase; adjusted HR 1.16; 95% CI 1.03–1.31;p= 0.017). Conclusion: In patients with NSTEMI treated with PCI, a high MPV value was associated with a significantly increased incidence of long-term adverse events, particularly for all-cause mortality. [ABSTRACT FROM PUBLISHER]

Background: Imbalance in hemostatic mechanisms can occur during pregnancy with a tendency for hypercoagulability and increased thrombosis risk. Pregnant women with hypertensive disorder, especially preeclampsia, show alterations in platelet indexes. Immature platelet fraction (IPF) has been suggested as a sensitive index for monitoring changes in platelet production and destruction.Objectives: To evaluate the IPF in patients diagnosed with a gestational hypertensive disorder (GHD).Patients and methods: A cross-sectional study was conducted at an University Hospital to estimate maternal blood IPF index in 99 pregnant women, divided into three groups: normotensive pregnancy (NP), preeclampsia syndrome (PES), and non-proteinuric hypertensive pregnancy (nPHP). Following ethical approval and written informed consent, samples were collected from 33 NP, 34 PES, and 32 nPHP women. Platelet indexes were measured by fluorescent flow cytometry.Results: IPF and mean platelet volume (MPV) counts in GHD were significantly higher than in NP (IPF: 3.8, 2.4–5.1%; 8.6, 5.8–10.6%; 7.3, 4.2–10.2%;p< 0.001 and MPV: 10.6 ± 0.9 fL; 12.1 ± 1.0 fL; 11.6 ± 1.0 fL;p< 0.001 for NP, PES, and nPHP, respectively). No difference was detected between PES and nPHP groups. The distribution of patients with an IPF above 6.1%for NP, PES, and nPHP was 9%, 65%, and 43.8%, respectively (p< 0.001). IPF as a test to differentiate GHD from the controls achieved an area under the curve of 0.83 on a receiver operating characteristics curve.Conclusion: A distinct profile in platelet indexes was detected in hypertensive pregnancies. It suggests that these markers could be used in daily routine as an additional tool in the management of pregnant women. [ABSTRACT FROM AUTHOR]

It is now well known that hemostasis is directly involved in the benefits induced by physical activity. It has recently been shown that the baseline mean platelet volume (MPV) may be a predictor of endurance performance. We aimed to explore whether platelet parameters are associated with VO2maxas well as running duration and speed in a short-duration exhaustive exercise test. Thirty healthy male subjects (10 sedentary and 20 trained) performed an incremental running test until exhaustion. MPV, platelet distribution width (PDW), platelet (Plt) count, and plateletcrit (Pct) were determined before exercise, immediately after exercise and after 30′ recovery. Training status did not produce any difference in the baseline levels or in the post-exercise increases found in all the parameters tested. VO2max, test duration, and running speed were not correlated with any baseline parameter. Although MPV was found to be a predictor of endurance performance in long-duration exercise, the results of the present study are consistent with the hypothesis that MPV may not be a significant marker of performance in short-duration exhaustive exercise. Likewise, more research is needed to ascertain whether platelet activation is a reliable performance predictor in other exercise settings. [ABSTRACT FROM AUTHOR]

Sepsis is an important cause of death in very-low-birth-weight (VLBW) neonates. Although conventional diagnostic indicator of sepsis has been done by blood cultures, this took much longer time. The measurement of platelet-associated parameters such as mean platelet volume (MPV) and platelet distribution width (PDW) become more reliable and accurate parameters as a non-specific marker for sepsis. Our objective is to examine the usefulness of those platelet hematological parameters as a supplementary diagnostic tool for sepsis in VLBW infants. This study is a retrospective cohort study of neonates subject to the diagnosis of sepsis from October 2006 to July 2010. This study was conducted at Korea University medical center. We studied total 2,336 infants for 32 days from birth (Day 0) to Day 31. We compared three groups of infants to examine differences of platelet parameters according to their age from birth to Day 31: (i) full-terms versus VLBW without sepsis, (ii) VLBW without sepsis versus VLBW with sepsis and (iii) thrombocytopenic VLBW without sepsis versus those with sepsis. The platelet-associated parameters were significantly distinguishable between septic and non-septic groups at their early age (∼1 week), especially platelet counts (PLT) (p = 0.0091), MPV (p = 0.007) and PDW (p = 0.0372) in thrombocytopenic VLBW infants. The decreased PLT, elevated MPV and PDW were major characteristics of septic group. We suggested maximum cutoff values of the platelet factors by performing receiver operating characteristic curve analysis between septic and non-septic thrombocytopenic VLBW infants, among which MPV was the most promising index (AUCMPV = 0.7044 > AUCPLT = 0.6921 > AUCPDW = 0.6593). Platelet-associated hematological parameters are useful for the early diagnosis of sepsis as a more efficient and supplementary diagnostic method in thrombocytopenic VLBW infants. [ABSTRACT FROM PUBLISHER]

The article discusses a study which is conduct for the identification of the location of infarct-related artery in patient with non-ST-elevation myocardial infarction (NSTEMI). It mentions the relation of mean platelet volume for the prediction of myocardial infarction and prognosis in patients with acute coronary syndrome. It also mentions that the retrospective analysis of patients with NSTEMI who had undergone coronary angiography.

This study aimed to determine the association of the brachial-ankle pulse wave velocity (baPWV) and mean platelet volume (MPV) with the development of adverse outcomes after percutaneous coronary intervention (PCI). The baPWV and MPV were analyzed in 372 patients who underwent PCI, with the primary endpoint as cardiac death. The secondary endpoint was cardiovascular events (CVE): a composite of cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), ischemic stroke, and stent thrombosis (ST). During the follow-up period (mean, 25.8 months), there were 21 cardiac deaths, 10 MIs including four events of ST, seven ischemic strokes, and 29 TVRs. The baPWV cut-off level was set at 1672 cm/s using the receiver operating characteristic curve; the sensitivity and specificity was 85.7 and 60.1%, respectively, to differentiate between the groups with and without cardiac death. The MPV cut-off level was set at 8.20 fL using the receiver operating characteristic curve; the sensitivity and specificity were 81 and 53.3%, respectively, to differentiate between the groups with and without cardiac death. Kaplan–Meier analysis revealed that the higher baPWV group (≥1672 cm/s) had a significantly higher cardiac death and CVE rate than the lower baPWV group (<1672 cm/s) (11.4 vs. 1.4%, log-rank:p < 0.0001; 25.3 vs. 7.5%, log-rank:p < 0.0001; respectively), and the higher MPV group (median, >8.20 fL,) had a significantly higher cardiac death and CVE rate than the lower MPV group (≤8.20 fL) (9.4 vs. 2.1%, log-rank:p = 0.0026; 23.8 vs. 6.8%, log-rank:p < 0.0001; respectively). Furthermore, the high baPWV and MPV groups were significantly associated with an increased risk of cardiac death. These results show that baPWV and MPV are predictive markers after PCI for cardiac death; they are also additively associated with a higher risk of cardiac death. [ABSTRACT FROM PUBLISHER]

Mean platelet volume (MPV) is a risk factor for cardiovascular complications, cerebrovascular disorders, and low-grade inflammatory conditions prone to arterial and venous thromboses. Cesarean delivery is the most important risk factor for pulmonary embolism, stroke, and intracranial venous thrombosis. The hypothesis is that increase in the prevalence of cesarean section and high MPV may be associated with cardiovascular complications such as stroke along with intracranial complications in addition to known systemic and surgical complications. In this study, platelet counts and MPV for postpartum women who delivered by cesarean section and normal vaginal parturition are compared. The subjects were divided in two groups, one was study group consisting of 118 patients giving birth by cesarean section and the other was the control group consisting 94 patients giving birth by normal vaginal parturition. Peripheral venous blood samples in EDTA tubes were collected from all the subjects 1 week before and after the delivery for their prenatal and postpartum periods, respectively. The values were compared between the groups and also before and after the delivery. In the cesarean group, while the MPV level was 8.60 (1.64) fl in the prenatal period, it increased to 9.10 (2.00) fl in the postnatal period (p < 0.001). Group effect, time effect (independent from group effect), and group*time interaction effect were statistically significant for MPV variable (p = 0.032,p < 0.001, andp = 0.012, respectively). This study concluded that MPV, along with several other factors, may be used as a prognostic, independent, and therapeutic marker in patients who are inclined to thrombotic events after cesarean section. [ABSTRACT FROM PUBLISHER]