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随着人口老龄化，长期接受抗血小板治疗的患者在神经外科手术治疗人群中的比例不断增加。抗血小板药物导致的潜在血小板功能低下会影响术中止血效果，并增加术中大出血和术后出血并发症风险。因此，如何在术前快速准确地评估血小板功能，对于全面评估患者止血功能具有重要意义。本文通过总结相关文献，结合血小板功能检测在神经外科的使用现状，分析目前常用血小板功能检测方法的优缺点，介绍改善血小板功能的相关疗法，以期提高神经外科医师对血小板功能的认识。 Abstract: With the aging of the population, the proportion of patients receiving long-term antiplatelet therapy among those undergoing surgical treatment is increasing. Potential platelet hypofunction caused by antiplatelet drugs can affect intraoperative hemostasis and increase the risks of massive intraoperative hemorrhage and postoperative bleeding complications. Therefore, a quick and accurate assessment of platelet function before surgery is of great significance in comprehensively evaluating a patient’s hemostatic function. Based on the summary of relevant literature and the current status of the application of platelet function tests in neurosurgery, this paper analyzed the advantages and disadvantages of the currently commonly used platelet function tests, and introduced relevant therapies to improve platelet function, with the aim of improving the understanding of platelet function among neurosurgeons.

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The crucial role of platelets in hemostasis and their broad implications under various physiological conditions underscore the importance of accurate platelet-function testing. Platelets are key to clotting blood and healing wounds. Therefore, accurate diagnosis and management of platelet disorders are vital for patient care. This review outlines the significant advancements in platelet-function testing technologies, focusing on their working principles and the shift from traditional diagnostic methods to more innovative approaches. These improvements have deepened our understanding of platelet-related disorders and ushered in personalized treatment options. Despite challenges such as interpretation of complex data and the costs of new technologies, the potential for artificial-intelligence integration and the creation of wearable monitoring devices offers exciting future possibilities. This review underscores how these technological advances have enhanced the landscape of precision medicine and provided better diagnostic and treatment options for platelet-function disorders. [ABSTRACT FROM AUTHOR]

Blood platelets are crucial to prevent excessive bleeding following injury to blood vessels. Platelets are crucial for the formation of clots and for clot strength. Platelet activation involves aggregation, attachment to fibrin and clot retraction. Most assays that address platelet function measure platelet aggregation, not clot retraction. Here, we describe a 96-well-based clot retraction assay that requires a relatively short runtime and small sample volume. The assay involves continuous optical density monitoring of platelet-rich plasma that is activated with thrombin. The data can be analyzed using time-series analytical tools to generate quantitative information about different phases of clot formation and clot retraction. The assay demonstrated good repeatability and reproducibility and was robust to different calcium concentrations. Impairment of platelet bioenergetics, actin polymerization, fibrin interaction, and signaling significantly affected clot retraction and was detected and showed good agreement with light transmission aggregometry, suggesting that clot retraction is predictive of platelet function. Using this microplate clot retraction assay, we showed a significant difference in platelets stored in autologous plasma compared with platelet additive solution after 7 days of room temperature storage. [ABSTRACT FROM AUTHOR]

The crucial role of platelets in hemostasis and their broad implications under various physiological conditions underscore the importance of accurate platelet-function testing. Platelets are key to clotting blood and healing wounds. Therefore, accurate diagnosis and management of platelet disorders are vital for patient care. This review outlines the significant advancements in platelet-function testing technologies, focusing on their working principles and the shift from traditional diagnostic methods to more innovative approaches. These improvements have deepened our understanding of platelet-related disorders and ushered in personalized treatment options. Despite challenges such as interpretation of complex data and the costs of new technologies, the potential for artificial-intelligence integration and the creation of wearable monitoring devices offers exciting future possibilities. This review underscores how these technological advances have enhanced the landscape of precision medicine and provided better diagnostic and treatment options for platelet-function disorders.

Blood platelets are crucial to prevent excessive bleeding following injury to blood vessels. Platelets are crucial for the formation of clots and for clot strength. Platelet activation involves aggregation, attachment to fibrin and clot retraction. Most assays that address platelet function measure platelet aggregation, not clot retraction. Here, we describe a 96-well-based clot retraction assay that requires a relatively short runtime and small sample volume. The assay involves continuous optical density monitoring of platelet-rich plasma that is activated with thrombin. The data can be analyzed using time-series analytical tools to generate quantitative information about different phases of clot formation and clot retraction. The assay demonstrated good repeatability and reproducibility and was robust to different calcium concentrations. Impairment of platelet bioenergetics, actin polymerization, fibrin interaction, and signaling significantly affected clot retraction and was detected and showed good agreement with light transmission aggregometry, suggesting that clot retraction is predictive of platelet function. Using this microplate clot retraction assay, we showed a significant difference in platelets stored in autologous plasma compared with platelet additive solution after 7 days of room temperature storage.

Regular exercise training is essential in prevention and treatment of cardiovascular disease (CVD), yet the beneficial effects of exercise remain only partly explained. Platelets play a key role in CVD and may be affected by regular exercise training. We aimed to systematically summarise studies investigating the effect of regular exercise training on platelet function in patients with CVD and in healthy individuals. Studies were identified by PubMed, Embase and Web of Science May 16, 2022. We selected studies investigating markers of platelet function in relation to regular exercise training in patients with CVD and in healthy individuals. Regular exercise was defined as exercise training for four weeks or more. Of the included studies, 11 investigated patients with CVD and 29 were on healthy individuals. Studies were heterogeneous regarding design, study population and methodology, and the results were ambiguous. In total, 52 different markers of platelet function were investigated with platelet aggregation, soluble P-selectin, and thromboxane B 2 (TXB 2) as the most frequently examined. When evaluating between-group changes after regular exercise, two studies found a reduced platelet aggregation in the exercise group whilst three studies did not find a difference between groups. With respect to TXB 2 , three studies reported a reduction and two studies an increase in the exercise group. There were no between-group differences in the seven studies examining soluble P-selectin. Regular exercise training has no clear impact on platelet function in patients with CVD or healthy individuals. CRD42022350539. [ABSTRACT FROM AUTHOR]

Background: The bleeding risk of patients with mild platelet function disorders is difficult to assess and their phenotype remains ill-explored. Aim: This study was designed to establish a comprehensive biological phenotype of patients with mild platelet function disorders. Methods: Twenty patients were included with persistent abnormal light transmission aggregometry (LTA). The ISTH bleeding assessment tool (ISTH-BAT) was assessed to identify laboratory analyses associated with an abnormal hemorrhagic score. Results: The majority of patients had defects that might affect Gai protein signaling pathways or minor abnormalities. No LTA nor flow cytometry parameters were associated with an above-normal hemorrhagic score. However, prothrombin consumption, which corresponds to the ratio of serum residual factor II to plasma residual factor II, was significantly higher (p = .006) in the abnormal ISTH-BAT group (mean = 14%, SD = 6) compared with the normal ISTH-BAT group (mean = 8%, SD 4). Prothrombin consumption was significantly associated with ISTH-BAT score (r = .5287, IC 95% 0.0986-0.7924, p = .0165). Conclusion: In this group of patients, there was an association between a pathological bleeding score and increased prothrombin consumption. This test could be used as an additional indicator of platelet function abnormality liable to be related to bleeding risk. [ABSTRACT FROM AUTHOR]

The key role played by platelets in the atherosclerosis physiopathology, especially in the acute setting, is ascertained: they are the main actors during thrombus formation and, thus, one of the major investigated elements related to atherothrombotic process involving coronary arteries. Platelets have been studied from different points of view, according with the technology advances and the improvement in the hemostasis knowledge achieved in the last years. Morphology and reactivity constitute the first aspects investigated related to platelets with a significant body of evidence published linking a number of their values and markers to coronary artery disease and cardiovascular events. Recently, the impact of genetics on platelet activation has been explored with promising findings as additional instrument for patient risk stratification; however, this deserves further confirmations. Moreover, the interplay between immune system and platelets has been partially elucidated in the last years, providing intriguing elements that will be basic components for future research to better understand platelet regulation and improve cardiovascular outcome of patients. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke is a leading cause of death and major disability worldwide. Approximately 50% of ischemic strokes are caused by atherothrombotic occlusion of the cerebral arteries, and antiplatelets are the mainstay of secondary stroke preventative treatment. Aspirin is beneficial if given early, and short‐term treatment using aspirin and clopidogrel is increasingly used for patients with intracranial atherosclerotic disease, minor stroke, and or transient ischemic attack. However, up to 50% of patients continue to have recurrent stroke and major vascular events, which may be partly attributable to resistance to aspirin and or clopidogrel. Although the precise mechanisms are unknown, clinical and genetic factors associated with bioavailability and binding to target receptors are implicated. This narrative review begins with the concept of aspirin and clopidogrel resistance in ischemic stroke and transient ischemic attack, potential mechanisms including genetic polymorphisms, and an overview of platelet function measures and limitations. We conclude by highlighting practical issues in the management of patients with aspirin andclopidogrel resistance including the emerging interest in ticagrelor, prasugrel, and cilostazol as well as directions for future trials in transient ischemic attack and acute ischemic stroke.

The value of platelet function test in timing of cardiac surgery remains uncertain. Researches on correlation between Platelet Function Analyzer 200 (PFA-200) and bleeding after elective cardiac surgery are still inadequate. The objective of this study was to investigate the predictive value of PFA-200 in blood transfusion after cardiac surgery. A total of 71 patients on aspirin and P2Y12 receptor inhibitors undergoing cardiac surgery in Fuwai Hospital were enrolled. Platelet function after discontinuing of antiplatelet drugs was assessed by PFA-200 using closure time (CT). PFA-200 results before surgery were included in the statistics. The primary endpoint was postoperative blood transfusion. Seventeen patients (21.9%) received blood transfusion after cardiac surgery. The preoperative PFA-200 CT value in the transfused group was significantly higher than that in the non-transfused group (147.24± 85.54 s vs 98.06±61.59 s, P=.011). Using 106 seconds as the dividing point, the incidence of blood transfusion in the elevated PFA- 200 (CT > 106 s) group was significantly higher than those in normal PFA-200 (CT≤106 s) group (10/24 patients, 41.9% vs 7/47 patients, 14.7%, P=.012). Multivariate logistic regression analysis showed that PFA-200 CT value > 106 s was an independent predictor of postoperative blood transfusion (OR: 4.05, 95%CI: 1.19-13.86, P=.026). The platelet function test PFA-200 had a predictive value for postoperative blood transfusion in elective cardiac surgery and had a promising prospect in the timing of cardiac surgery. [ABSTRACT FROM AUTHOR]

Pathogenic variants of the X‐linked FLNA gene encoding filamin A protein have been associated with a wide spectrum of symptoms, including the recently described pulmonary phenotype with childhood‐onset panlobular emphysema. We describe three female patients from two families with novel heterozygous FLNA variants c.5837_2del and c.508C > T. Analysis of immunofluorescence of peripheral blood smears and platelet function was performed for all patients. FLNA‐negative platelets were observed, suggesting that these variants result in the loss of a functional protein product. All three patients also had periventricular nodular heterotopia and panlobular emphysema. However, they had considerably milder symptoms and later age of onset than in the previously reported cases. Therefore, patients with pathogenic FLNA variants should be studied actively for lung involvement even in the absence of pronounced respiratory symptoms. Conversely, any patient with unexplained panlobular emphysema should be analyzed for pathogenic FLNA variants. We also suggest that immunofluorescence analysis is a useful tool for investigating the pathogenicity of novel FLNA variants. [ABSTRACT FROM AUTHOR]

BackgroundPlatelet function testing to monitor antiplatelet therapy is important for reducing thromboembolic complications, yet variability across testing methods remains challenging. Here we evaluated the agreement of four different testing platforms used to monitor antiplatelet effects of aspirin (ASA) or P2Y12 inhibitors (P2Y12-I).MethodsBlood and urine specimens from 20 patients receiving dual antiplatelet therapy were analyzed by light transmission aggregometry (LTA), whole blood aggregometry (WBA), VerifyNow PRUTest and AspirinWorks. Result interpretation based on pre-defined cutoff values was used to calculate raw agreement indices, and Pearson's correlation coefficient determined using individual units of measure.ResultsAgreement between LTA and WBA for P2Y12-I-response was 60% (r = 0.65, high-dose ADP; r = 0.75, low-dose ADP). VerifyNow agreed with LTA in 75% (r = 0.86, high-dose ADP; r = 0.75, low-dose ADP) and WBA in 55% (r = 0.57) of cases. Agreement between LTA and WBA for ASA-response was 45% (r = 0.09, high-dose collagen WBA; r = 0.19, low-dose collagen WBA). AspirinWorks agreed with LTA in 60% (r = 0.32) and WBA in 35% (r = 0.02, high-dose collagen WBA; r = 0.08, low-dose collagen WBA) of cases.ConclusionsOverall agreement varied from 35 to 75%. LTA and VerifyNow demonstrated the highest agreement for P2Y12-I-response, followed by moderate agreement between LTA and WBA. LTA and AspirinWorks showed moderate agreement for aspirin response, while WBA showed the weakest agreement with both LTA and AspirinWorks. The results from this study support the continued use of LTA for monitoring dual antiplatelet therapy, with VerifyNow as an appropriate alternative for P2Y12-I-response. Integration of results obtained from these varied testing platforms with patient outcomes remains paramount for future studies.

Abstract Background Platelet‐fibrin clot contraction is critical for wound closure and maintenance of vessel patency, yet a molecular understanding of the process has lagged because of a lack of flexible quantitative assay systems capable of assaying multiple samples simultaneously. Objectives We devised a sensitive and inexpensive method to assess clot contraction kinetics under multiple conditions. Methods Clot contraction was measured using time‐lapse digital photography, automated image processing with customized software, and detailed kinetic analysis using available commercial programs. Results Our system was responsive to alterations in platelet counts and calcium, fibrinogen, and thrombin concentrations, and our analysis detected and defined three phases of platelet‐fibrin clot formation: initiation, contraction, and stabilization. Lag time, average contraction velocity, contraction extent, and area under the curve were readily calculated from the data. Using pharmacological agents (blebbistatin and eptifibatide), we confirmed the importance of myosin IIA and the interactions of integrin αIIbβ3‐fibrinogen/fibrin in clot contraction. As further proof of our system's utility, we showed how 2‐deoxyglucose affects contraction, demonstrating the importance of platelet bioenergetics, specifically glycolysis. Conclusions Our system is an adaptable platform for assessing the effects of multiple conditions and interventions on clot contraction kinetics in a regular laboratory setting, using readily available materials. The automated image processing software we developed will be made freely available for noncommercial uses. This assay system can be used to directly compare and define the effects of different treatments or genetic manipulations on platelet function and should provide a robust tool for future hemostasis/thrombosis research and therapeutic development.

Mortality after aneurysmal subarachnoid hemorrhage (aSAH) is augmented by rebleeding and delayed cerebral ischemia (DCI). A range of assays evaluating the dynamic process of blood coagulation, from activation of clotting factors to fibrinolysis, has emerged and a comprehensive review of hemostasis and fibrinolysis following aSAH may reveal targets of treatment. We conducted a systematic review of existing literature assessing coagulation and fibrinolysis following aSAH, but prior to treatment. PubMed, Embase, and Web of Science were searched on November 18, 2020, without time boundaries. In total, 45 original studies were eventually incorporated into this systematic review, divided into studies presenting data only from conventional or quantitative assays ( n  = 22) and studies employing dynamic assays ( n  = 23). Data from conventional or quantitative assays indicated increased platelet activation, whereas dynamic assays detected platelet dysfunction possibly related to an increased risk of rebleeding. Secondary hemostasis was activated in conventional, quantitative, and dynamic assays and this was related to poor neurological outcome and mortality. Studies systematically investigating fibrinolysis were sparse. Measurements from conventional or quantitative assays, as well as dynamic fibrinolysis assays, revealed conflicting results with normal or increased lysis and changes were not associated with outcome. In conclusion, dynamic assays were able to detect reduced platelet function, not revealed by conventional or quantitative assays. Activation of secondary hemostasis was found in both dynamic and nondynamic assays, while changes in fibrinolysis were not convincingly demonstrable in either dynamic or conventional or quantitative assays. Hence, from a mechanistic point of view, desmopressin to prevent rebleeding and heparin to prevent DCI may hold potential as therapeutic options. As changes in fibrinolysis were not convincingly demonstrated and not related to outcome, the use of tranexamic acid prior to aneurysm closure is not supported by this review. [ABSTRACT FROM AUTHOR]

Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel are known to be less effective at reducing platelet function for some patients because of a phenomenon called high on-treatment platelet reactivity (HTPR). However, the clinical effect of this for patients undergoing endovascular intervention for peripheral arterial disease is unclear. The aim of this study was to assess the impact of ADP receptor inhibitor HTPR on clinical outcomes following lower limb arterial endovascular intervention for peripheral arterial disease. A systematic review and meta-analysis was performed. Primary outcomes included all cause mortality and major bleeding. Secondary outcomes were major adverse cardiovascular events, major adverse limb events, restenosis, and target lesion revascularisation. Outcome quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. There were 10 eligible studies including 1 444 patients included in the meta-analysis. The most commonly tested ADP receptor inhibitor was clopidogrel (seven studies). The pooled rate of ADP receptor inhibitor HTPR was 29% (95% CI 27 – 32). The meta-analysis showed that ADP receptor inhibitor HTPR was associated with a greater risk of major adverse limb events (OR 6.25, 95% CI 2.09 – 18.68, p =.001) and a trend towards a higher all cause mortality (OR 1.71, 95% CI 0.99 – 2.94, p =.050) and more major adverse cardiovascular events (OR 4.23, 95% CI 0.46 – 38.92, p =.20) after endovascular intervention. Overall strength of evidence was very low for all outcomes. ADP receptor inhibitor HTPR was associated with worse clinical outcomes after lower limb endovascular intervention for peripheral arterial disease. Prospective studies are required to determine the impact of modifying the antithrombotic regimen on clinical outcomes. [ABSTRACT FROM AUTHOR]

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder caused by defects in 10 human HPS genes, characterized by oculocutaneous albinism (OCA) and bleeding diathesis associated to platelet δ-storage pool defect (SPD). We report a case of 4-year-old boy from non-consanguineous parents with OCA and negative personal and familiar hemorrhagic history, referred to us for severe bleeding after mild trauma. His platelet function, studied by lumi-aggregometry, showed normal first wave of aggregation in response to exogenous agonists and impaired second wave with defective ATP release. This, in combination with impaired platelet δ-granules content (serotonin, ATP, ADP) and the OCA phenotype suggested the HPS diagnosis. HPS3 sequencing revealed a novel pathogenic homozygous variant (NM_032383.4:c.7>T, p.Gln3*) resulting in a premature stop codon at the amino acid 3. Moreover, our report highlights the importance of evaluating platelet function in children with OCA without bleeding diathesis to identify HPS early and prevent bleeding complications.

Background. Studies of platelet aggregation (PA) in essential thrombocythemia (ET) reported contrasting results, likely due to differences in analytical conditions. Objective. We investigated platelet aggregation using different techniques and analytical conditions. Patients and Methods. PA was studied by light-transmission aggregometry (LTA) in platelet-rich plasma (PRP) and impedance aggregometry in PRP and whole blood (WB). ADP, collagen, thrombin receptor activating peptide (TRAP-14) and adrenaline were used as agonists. Since ET patients (n = 41) were on treatment with aspirin (100 mg/d), healthy controls (n = 29) were given aspirin (100 mg/d) for 5 days before testing: therefore, thromboxane A2-independent PA was tested in all subjects. Blood samples were collected in citrate (C) [low Ca2+] or lepirudin (L) [physiological Ca2+]; platelet count was adjusted to 250 x 109/L in a set of C-PRP (adjusted C-PRP) and left unmodified in the other samples. Results. Results of PA in 17 ET patients who were poor responders to aspirin (high serum thromboxane B2 levels) were not included in the analysis. With LTA, PA in ET was lower than in controls in adjusted C-PRP and normal in native C-PRP and L-PRP. With impedance aggregometry, PA in L-PRP and L-WB tended to be higher in ET than in controls. Platelet serotonin and ADP contents were reduced in ET. The percentages of circulating platelets expressing P-selectin and platelet-leukocyte hetero-aggregates were higher in ET. Conclusions. Analytical conditions dramatically affect in vitro PA of ET patients, which appears defective under the least physiological conditions and normal/supranormal under conditions that are closer to the physiological.

Background: Light transmission aggregometry with lumiaggregometry are methods commonly recommended as a first-line test in platelet dysfunction diagnostic work-up. They are poorly standardized and usually performed in specialized laboratories. For proper interpretation, each laboratory should establish its own diagnostic approach in order to recognize abnormal aggregation patterns. The aim of this study was to measure plasma lumiaggregometry with basic agonists to establish the analyzer-reagent reference intervals (RI) for adults and to test the method response to aspirin. Methods: The Chrono-Log Model 700 lumiaggregometer using Chrono-Par and Chrono-lume reagents (Chrono-Log Corp., Havertown, PA, USA) was used to measure the maximal aggregation and adenosine triphosphate release using adenosine diphosphate (2 mmol/L), collagen (2 mg/mL), arachidonic acid (1 mmol/L), epinephrine (5.5 mmol/L) and ristocetin (1.25 mg/mL), and thrombin (1 U/mL). The effect of aspirin on platelet aggregation and granule release was inspected. Results: RIs derived from 40 healthy adults were calculated using the non-parametric approach. Wider intervals and low lower limits were determined for weak agonist as well as absence or impaired aggregation in up to one of 7 healthy controls. The response of platelets to aspirin shows response comparable to previously reported study. Conclusions: Locally established RI in our study enable us to investigate platelet function in patients with a high probability of bleeding disorders. Values are agonist and equipment specific. The variability of the method can be reduced by considering standardized preanalytical and analytical variables. Pathological results must be interpreted in the context of other hemostasis test results and clinical findings.

ObjectiveTo explore the influence of CYP2C19 gene combined with platelet function test on clinical prognosis of patients with complex coronary artery disease receiving antiplatelet therapy after PCI.MethodsA total of 200 patients undergoing PCI in our hospital due to complex coronary artery disease from February 2019 to February 2021 were selected and divided into the control group and the observation group according to whether CYP2C19 gene detection was performed. The control group was treated with dual antiplatelet therapy of classical aspirin combined with clopidogrel, and the observation group was treated with individual antiplatelet therapy. The patients in the two groups were followed up for 1 year after PCI, and their quality of life was assessed using the Seattle Angina Questionnaire (SAQ score). The occurrence of major adverse cardiovascular events (MACE) during the follow-up period was also recorded.ResultsThe incidence of total MACE events in the observation group was slightly less than that in the control group, and the difference was statistically significant (P = 0.040). In particular, the observation group was superior to the control group in reducing the readmission rate of recurrent unstable angina pectoris, and the difference was statistically significant (P = 0.023). The location of coronary culprit lesions with recurrent ischemic events was commonly seen in non-interventional target lesions (interventional/non-interventional target sites: 12.9%: 77.1%). The SAQ score in the observation group was larger than that in the control group, and the difference was statistically significant (P = 0.012). There was no statistical difference in the incidence of major bleeding between the two groups (P = 0.352).ConclusionUsing CYP2C19 genotype combined with platelet function test to guide individualized antiplatelet therapy after complex coronary artery PCI is beneficial to reducing ischemic events in a short period (1 year), mainly due to reducing the risk of readmission for recurrent unstable angina pectoris, and improving the quality of daily life of patients without increasing the risk of massive hemorrhage, which can improve clinical prognosis.

Background Patients with essential thrombocythemia (ET) and coronary artery disease (CAD) have increased risk of thromboembolic complications. In addition, a reduced antiplatelet effect of aspirin has been demonstrated in both patient groups. As ET is a platelet disorder, platelets may be more important for the thromboembolic risk in ET than in CAD. We aimed to investigate the antiplatelet effect of aspirin and platelet turnover in ET versus CAD patients. Methods We included 48 ET patients and an age-matched group of 48 CAD patients. The effect of aspirin was evaluated by thromboxane B2 (TXB2) levels and platelet aggregation. Platelet turnover was assessed by immature platelet count (IPC) and immature platelet fraction (IPF). Results ET patients had reduced effect of aspirin compared with CAD patients, demonstrated by significantly higher TXB2 levels (median of differences = 22.3 ng/mL, p

Context: The Platelet Function Analyzer (PFA-100™) assesses primary hemostasis in vitro under high shear stress to simulate the conditions to which platelets are exposed at the site of an injured blood vessel wall. Aims: We investigated preanalytical variables in healthy Algerian adults, and we also assess the performance of the test. Subjects and Methods: Closure time (CT) was measured in 302 well-characterized healthy Algerian adults with the collagen/epinephrine (CEPI) and the collagen/adenosine diphosphate (CADP) cartridges. Results: Age and sex did not affect CT values. Blood group O was associated significantly with longer CEPI CT and CADP CT than non-O groups (P 0.0001 for both). CTs were shorter in samples collected in the morning vs the afternoon (P < 0.0001 for both). We found a strong positive correlation between CT CEPI and CT CADP with r = 0.72 and P < 0.001 and an inverse mean correlation between von Willebrand factor level and CT with r = −0.56, r = −0.45 for CT CEPI and CT CADP, respectively P < 0.001. Duplicate analysis of PFA-100™ CT revealed a mean difference of 3.6% ±19.1% for the CEPI cartridge and 1.5% ±10% for the CADP cartridge. The mean coefficient of variation was 7.4% for the CADP CT and 7.6% for the CEPI CT. No marked difference between test positions. Conclusions: The PFA-100™ showed good reproducibility. The variables influencing the test in healthy Algerian adults are similar to Western and Asian populations. Standardization of preanalytical and analytical conditions is essential for obtaining reliable PFA-100™ results. [ABSTRACT FROM AUTHOR]

Studies using whole blood platelet aggregometry as a laboratory research tool, provided important insights into the mechanism and modulators of platelet aggregation. Subsequently, a number of point-of-care (POC) platelet function tests (PFTs) were developed for clinical use, based on the concept that an individual's thrombotic profile could be assessed in vitro by assessing the response to stimulation of platelet aggregation by specific, usually solo agonists such as adenosine diphosphate (ADP), collagen and thrombin. However, adjusting antiplatelet medication in order to improve the results of such POC PFTs has not translated into a meaningful reduction in cardiovascular events, which may be attributable to important differences between the POC PFT techniques and in vivo conditions, including patient-to-patient variability. Important limitations of most tests include the use of citrate-anticoagulated blood. Citrate directly and irreversibly diminishes platelet function and even after recalcification, it may result in altered platelet aggregation in response to ADP, epinephrine or collagen, and interfere with thrombin generation from activated platelets. Furthermore, most tests do not employ flowing blood and therefore do not assess the effect of high shear forces on platelets that initiate, propagate and stabilize arterial thrombi. Finally, the effect of endogenous thrombolysis, due to fibrinolysis and dislodgement, which ultimately determines the outcome of a thrombotic stimulus, is mostly not assessed. In order to accurately reflect an individual's predisposition to arterial thrombosis, future tests of thrombotic status which overcome these limitations should be used, to improve cardiovascular risk prediction and to guide pharmacotherapy. [ABSTRACT FROM AUTHOR]

Objective: Concern about thromboembolic events after flow diversion (FD) warrants dual antiplatelet therapy for 3 to 6 months. Platelet function tests are routinely performed prior to the procedure to detect clopidogrel responsiveness, as resistance is associated with CYP2C19 gene polymorphisms. This study aimed to identify optimal cutoff values in light transmission aggregometry (LTA) for clopidogrel and aspirin as predictive indicators of thromboembolic complications., Methods: The authors conducted a retrospective analysis of aneurysms treated with FD between 2013 and 2023 at a single academic institution. Patients with LTA data for adenosine diphosphate (ADP) and arachidonic acid (ARA) were included, excluding those with aborted procedures. Receiver operating characteristic curves were plotted for ADP and ARA assays to determine optimal cutoff values., Results: A total of 442 patients harboring 552 aneurysms treated in 485 procedures were selected for this analysis. Complete and near-complete aneurysm occlusion on the last radiological follow-up was achieved in 81.8% of aneurysms in a median last imaging follow-up of 13.9 months. A good functional outcome (modified Rankin Scale score ≤ 2) was achieved in 96.3% of patients on the last follow-up. Thromboembolic complications occurred in 4.9% of procedures, and intracranial hemorrhagic complications in 1.9%. For the ADP assay, a value ≥ 40% reached a sensitivity of 82.1% and a specificity of 42.9% with a positive likelihood ratio (LR) of 1.50. For the ARA assay, a value ≥ 13.5% reached a sensitivity of 82.1% and a specificity of 45.6% with a positive LR of 1.51., Conclusions: This study analyzed the largest FD-treated cohort in which optimal LTA platelet function thresholds for clopidogrel were evaluated and is the first to assess LTA values for aspirin. The authors found that values ≥ 40% for clopidogrel and ≥ 13.5% for aspirin were optimal for predicting thromboembolic complications after FD in treating aneurysms.

Introduction: The platelet function disorders remain largely undiagnosed or incompletely diagnosed in developing nations due to lack of availability of tests like lumiaggregometry, granule release assay or molecular testing. We performed a retrospective analysis of all the platelet function test (PFT) carried out in past 5 years by Light transmission aggregometery (LTA) using a panel of agonist. The indications and the test results were analyzed by two hematopathologist with the aim to look into the present diagnostic facilities or lack of it for correct diagnosis. This is essential for better management and genetic counselling. Materials and Methods: The PFT was performed both on patients and healthy unrelated age specific controls by light transmission aggregometry on Chronolog platelet aggregometer using platelet rich plasma. The panel of agonists included ADP (10μm/l and 2.0 μm/l), epinephrine (10.0 μm/l), collagen (2μg/ml), arachidonic acid (0.75 mM) and ristocetin (1.25 mg/ml & 0.25 mg/l). Results: The 5 years records of 110 cases were audited, 101 of these were tested for clinical bleeding , 35 adults and 66 children. The adults included 29 women and 6 men, 17 to 82 years of age. The children were 16 years to 3 months of age, 30 girls and 36 boys. Platelet function test abnormality was found in 31.6% (32/101) cases ,a majority remained undiagnosed of these about 21% had clinically significant bleeding.The cases diagnosed included Glanzmann Thromboasthenia-11 , von Willebrand Disease-6, Bernard Soulier'syndrome-1, storage pool disorder-6, mild defect of Epinephrine-3, isolated defect with collagen in1. Conclusion: An epidemiologically large proportion of platelet function disorders amongst people living in developing nations remain undiagnosed. This lacunae needs to be highlighted and addressed on larger scale. The options available are to increase the available armamentarium of tests or international collaboration with a specialized laboratory to aid in complete diagnosis.

Introduction: Platelet aggregation test using light transmission aggregometry (LTA) is considered as the gold standard for evaluation of platelet function. Variations of platelet aggregation had been reported in apparently healthy individuals whereby a normal cut-off value established locally is highly recommended. This study aims to determine the platelet aggregation pattern and the preliminary findings on reference values for multiple agonists-induced platelet aggregation among Malaysian healthy individuals in a single centre. Method: A total number of 63 informed consented healthy individuals consisted of Malay, Chinese and Indian were recruited among staff and blood donors at National Blood Centre, Kuala Lumpur. Platelet aggregation was measured using LTA against adenosine diphosphate 10 μM (ADP10), collagen 0.19 mg/mL (COL), ristocetin 1.5 mg/mL (RIS), arachidonic acid 1 mM (AA) and epinephrine 10 μM (EPI). Results were expressed as percent final aggregation (%FA). Reference values were calculated from mean±2SD. Results: Age, gender and ethnic groups had no significant effect on platelet aggregation. A variability of platelet aggregation response to EPI was observed among the healthy individuals. Ten of 33 respondents (30%) had impaired aggregation with <20% FA in response to EPI. The local population showed a slightly higher aggregation pattern in response to COL, RIS, AA and EPI (excluding non-responders) compared to manufacturer's reference values. Conclusion: This study has provided a glimpse of the aggregation pattern of the local nationality showing considerable differences in the reference values from manufacturer's; thus highlighting the need of establishing local reference values. [ABSTRACT FROM AUTHOR]

Background: Light transmission aggregometry with lumiag-gregometry are methods commonly recommended as a first-line test in platelet dysfunction diagnostic work-up. They are poorly standardized and usually performed in specialized laboratories. For proper interpretation, each laboratory should establish its own diagnostic approach in order to recognize abnormal aggregation patterns. The aim of this study was to measure plasma lumiaggregometry with basic agonists to establish the analyzer-reagent reference intervals (Rd) for adults and to test the method response to aspirin. Methods: The Chrono-Log Model 700 lumiaggregometer using Chrono-Par and Chrono-lume reagents (Chrono-Log Corp., Havertown, PA, USA) was used to measure the maximal aggregation and adenosine triphosphate release using adenosine diphosphate (2 pmol/L), collagen (2 pg/mL), arachidonic acid (1 pmol/L), epinephrine (5.5 pmol/L) and ristocetin (1.25 mg/mL), and thrombin (1 U/mL). The effect of aspirin on platelet aggregation and granule release was inspected. Results: RIs derived from 40 healthy adults were calculated using the non-parametric approach. Wider intervals and low lower limits were determined for weak agonist as well as absence or impaired aggregation in up to one of 7 healthy controls. The response of platelets to aspirin shows response comparable to previously reported study. Conclusions: Locally established Rl in our study enable us to investigate platelet function in patients with a high probability of bleeding disorders. Values are agonist and equipment specific. The variability of the method can be reduced by considering standardized preanalytical and analytical variables. Pathological results must be interpreted in the context of other hemostasis test results and clinical findings. [ABSTRACT FROM AUTHOR]

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder caused by defects in 10 human HPS genes, characterized by oculocutaneous albinism (OCA) and bleeding diathesis associated to platelet δ-storage pool defect (SPD). We report a case of 4-year-old boy from non-consanguineous parents with OCA and negative personal and familiar hemorrhagic history, referred to us for severe bleeding after mild trauma. His platelet function, studied by lumi-aggregometry, showed normal first wave of aggregation in response to exogenous agonists and impaired second wave with defective ATP release. This, in combination with impaired platelet δ-granules content (serotonin, ATP, ADP) and the OCA phenotype suggested the HPS diagnosis. sequencing revealed a novel pathogenic homozygous variant (NM_032383.4:c.7>T, p.Gln3*) resulting in a premature stop codon at the amino acid 3. Moreover, our report highlights the importance of evaluating platelet function in children with OCA without bleeding diathesis to identify HPS early and prevent bleeding complications. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine whether half-dose loading (30 mg) of prasugrel is sufficient to achieve adequate platelet inhibition, and whether such a loading dose of prasugrel together with aspirin followed by a 10 mg/day prasugrel maintenance, could serve as a first-line antiplatelet strategy for patients undergoing flow-diverting stent (FDS) implantation. Methods: Data from a group of consecutive patients treated for intracranial aneurysm with FDS were retrospectively collected. Platelet P2Y12 receptor responsiveness was assessed by a rapid platelet function test just prior to the procedure. All ischemic and hemorrhagic complications as well as morbidity and mortality rates were documented. Results: A total of 138 patients with 153 aneurysms (32 were symptomatic and 121 were incidental) underwent FDS treatment in a total of 147 loading sessions. Adequate platelet inhibition was obtained in 136/138 (98.5%) patients and 145/147 (98.6%) loading sessions. Overall, there was one case of (hemorrhagic) mortality (0.7%), one of (ischemic) morbidity (0.7%), one of symptomatic (hemorrhagic) clinical complications without permanent deficits (0.7%), and six transient ischemic attacks (4.1%). The 6‑month control angiography, available for all patients, revealed a 95.4% aneurysm occlusion rate. Conclusion: Half-dose (30 mg) prasugrel loading results in effective platelet P2Y12 receptor inhibition in more than 98% of patients. Dual antiaggregant loading with half dose prasugrel followed by prasugrel maintenance as a first-line therapy appears to be feasible in patients treated with FDS implantation for intracranial aneurysm. [ABSTRACT FROM AUTHOR]

VerifyNow-directed personalized antiplatelet therapy for aneurysm embolization with a Pipeline Embolization Device (PED) remains controversial. Evaluate thrombotic complications between patients who received VerifyNow-directed personalized antiplatelet therapy versus those who did not after PED flow diversion of complex cerebral aneurysms. This was a retrospective cohort of consecutive patients undergoing flow diversion with PED at the Medical University of South Carolina between January 2012 and May 2018. Patients who received VerifyNow-directed personalized antiplatelet therapy were compared with those who received antiplatelet therapy without platelet function testing. Patients with a P2Y12 reaction unit (PRU) ≥194 were deemed to be clopidogrel hyporesponsive. The primary outcome is the rate of thrombotic complications, and the secondary outcomes are the rate of hemorrhagic and thrombotic complications stratified by PRU and high-risk clinical and procedure-related candidate predictors. Thrombotic complications were not different between patients managed with (n = 159) versus without (n = 110) VerifyNow (6.9% vs. 7.3%; P = 0.911). Hemorrhagic complications were also no different (3.1% vs. 4.5%; P = 0.550). PRU stratification revealed no difference in thrombotic or hemorrhagic complications (P = 0.488 and P = 0.136, respectively). The only significant predictors for thrombotic complications were the presence of diabetes (OR 2.9; P = 0.034), obesity (OR 5.1; P ≤ 0.001), fusiform aneurysm (OR 3.3; P = 0.023), posterior circulation implantation (OR 3.4; P = 0.016), and >1 PED implanted (OR 2.4; P = 0.046). The role of VerifyNow and personalized antiplatelet therapy in patients undergoing flow diversion with PED to treat complex aneurysms did not demonstrate a benefit in reducing thrombotic complications. [ABSTRACT FROM AUTHOR]

Background. Studies of platelet aggregation (PA) in essential thrombocythemia (ET) reported contrasting results, likely due to differences in analytical conditions. Objective. We investigated platelet aggregation using different techniques and analytical conditions. Patients and Methods. PA was studied by light-transmission aggregometry (LTA) in platelet-rich plasma (PRP) and impedance aggregometry in PRP and whole blood (WB). ADP, collagen, thrombin receptor activating peptide (TRAP-14) and adrenaline were used as agonists. Since ET patients (n = 41) were on treatment with aspirin (100 mg/d), healthy controls (n = 29) were given aspirin (100 mg/d) for 5 days before testing: therefore, thromboxane A2-independent PA was tested in all subjects. Blood samples were collected in citrate (C) [low Ca2+] or lepirudin (L) [physiological Ca2+]; platelet count was adjusted to 250 x 109/L in a set of C-PRP (adjusted C-PRP) and left unmodified in the other samples. Results. Results of PA in 17 ET patients who were poor responders to aspirin (high serum thromboxane B2 levels) were not included in the analysis. With LTA, PA in ET was lower than in controls in adjusted C-PRP and normal in native C-PRP and L-PRP. With impedance aggregometry, PA in L-PRP and L-WB tended to be higher in ET than in controls. Platelet serotonin and ADP contents were reduced in ET. The percentages of circulating platelets expressing P-selectin and platelet-leukocyte hetero-aggregates were higher in ET. Conclusions. Analytical conditions dramatically affect in vitro PA of ET patients, which appears defective under the least physiological conditions and normal/supranormal under conditions that are closer to the physiological. [ABSTRACT FROM AUTHOR]

Objectives: Protamine reduces platelet aggregation after cardiopulmonary bypass (CPB). We studied the inhibitory effect of a reduced protamine dose, the duration of impaired platelet function and the possible correlation to postoperative bleeding. Design: Platelet function was assessed by impedance aggregometry in 30 patients undergoing cardiac surgery with CPB at baseline, before protamine administration, after 70% and 100% of the calculated protamine dose, after 20 minutes and at arrival to the intensive care unit. Adenosine diphosphate (ADP), thrombin receptor activating peptide-6 (TRAP), arachidonic acid (AA) and collagen (COL) were used as activators. Blood loss was measured during operation and three hours after surgery. Results are presented as median (25th-75th percentile). Results: Platelet aggregation decreased markedly after the initial dose of protamine (70%) with all activators; ADP 89 (71-110) to 54 (35-78), TRAP 143 (116-167) to 109 (77-136), both p < .01; AA 25 (16-49) to 17 (12-24) and COL 92 (47-103) to 60 (38-81) U, both p < .05. No further decrease was seen after 100% protamine. The effect was transient and after twenty minutes platelet aggregation had started to recover; ADP 76 (54-106), TRAP 138 (95-158), AA 20 (10-35), COL 70 (51-93) U. Blood loss during operation correlated to aggregometry measured at baseline and after protaminization. Conclusions: Protamine after CPB induces a marked decrease in platelet aggregation already at a protamine-heparin ratio of 0.7:1. The impairment seems to be transient and recovery had started after 20 minutes. [ABSTRACT FROM AUTHOR]

• We performed the first study of biological variation for platelet function tests (PFT). • Three of four PFT should be interpreted only relative to a patient's previous values. • VerifyNow is superior to Multiplate in detecting small changes in PFT over weeks. In order to manage risks of bleeding and thrombosis after some surgical procedures, platelet function is often measured repeatedly over days or weeks using laboratory tests of platelet function. To interpret test results in the perioperative period, it is necessary to understand analytical, biological and between-person variation. We collected three separate blood specimens from 16 healthy volunteers on the first study day, and one additional specimen from each volunteer 1, 2, and 3 months later. Arachidonic acid-induced and adenosine diphosphate (ADP)-induced platelet function were measured in duplicate by whole blood impedance aggregometry using Multiplate (ASPI/ADP tests) and VerifyNow (Aspirin Reaction Units [ARU] and P2Y12 Reaction Units [PRU]). The analytical variation (CV A), within-subject variation (CV I), between-subject variation (CV G), index of individuality (II), and reference change values (RCV) were calculated. VerifyNow ARU demonstrated the smallest short-term and long-term variability (CV A , CV I , and CV G ~1%), resulting in short- and long-term RCV values <5%. II was also higher (1.92) for VerifyNow ARU than other platelet function tests. Multiplate ASPI and ADP tests had the highest RCV both short-(19.0% and 25.2%, respectively) and long-term (32.1% and 39.6%, respectively) due to increased CV A (>5%) and CV I (3.9–13.1%). VerifyNow PRU had a lower RCV than Multiplate ADP; but was the only test with II <0.6. VerifyNow ARU results can be interpreted relative to a fixed cut-off or population-based reference interval; or relative to small changes in an individual's previous values. VerifyNow PRU and Multiplate ASPI and ADP tests should only be interpreted based upon relative change; and can only distinguish relatively large (>23%) changes over several weeks. [ABSTRACT FROM AUTHOR]

Patients on P2Y12 inhibitors may still develop thrombosis or bleeding complications. Tailored antiplatelet therapy, based on platelet reactivity testing, might reduce these complications. Several tests have been used, but failed to show a benefit of tailored antiplatelet therapy. This could be due to the narrowness of current platelet reactivity tests, which are limited to analysis of platelet aggregation after stimulation of the adenosine diphosphate (ADP)-pathway. However, the response to ADP does not necessarily reflect the effect of P2Y12 inhibition on platelet function in vivo. Therefore, we investigated whether measuring platelet reactivity toward other physiologically relevant agonists could provide more insight in the efficacy of P2Y12 inhibitors. The effect of in vitro and in vivo P2Y12 inhibition on αIIbβ3-activation, P-selectin and CD63-expression, aggregate formation, release of alpha, and dense granules content was assessed after stimulation of different platelet activation pathways. Platelet reactivity measured with flow cytometry in 72 patients on P2Y12 inhibitors was compared to VerifyNow results. P2Y12 inhibitors caused strongly attenuated platelet fibrinogen binding after stimulation with peptide agonists for protease activated receptor (PAR)-1 and -4, or glycoprotein VI ligand crosslinked collagen-related peptide (CRP-xl), while aggregation was normal at high agonist concentration. P2Y12 inhibitors decreased PAR-agonist and CRP-induced dense granule secretion, but not alpha granule secretion. A proportion of P2Y12-inhibitor responsive patients according to VerifyNow, displayed normal fibrinogen binding assessed with flow cytometry after stimulation with PAR-agonists or CRP despite full inhibition of the response to ADP, indicating suboptimal platelet inhibition. Concluding, measurement of platelet fibrinogen binding with flow cytometry after stimulation of thrombin- or collagen receptors in addition to ADP response identifies different patients as nonresponders to P2Y12 inhibitors, compared to only ADP-induced aggregation-based assays. Future studies should investigate the value of both assays for monitoring on-treatment platelet reactivity.

Epidemiological studies have suggested an increased risk of cardiovascular events (CVE) during acute stressful and/or frightful moments. A possible explanation for this could be an effect of acute stress on hemostasis. A recent study demonstrated an increase in factor VIII after watching a horror movie. Primary hemostasis, however, is thought to play a more prominent role in the etiology of CVE. The objective of this study was therefore to assess the influence of viewing a 'bloodcurdling' horror movie on platelet reactivity in healthy volunteers. We performed a randomized cross-over study in healthy adults. Subjects were allocated to two movies in random sequence: a horror and a control movie. Blood was drawn at baseline and after 24 min of viewing time. The primary endpoint was the change in Platelet Function Analyzer® Closure Time (Δ PFA-CT) after watching the movie. In total, 20 participants, aged 18–30 years, completed the study protocol. The delta PFA-CT was statistically significantly shorter with a mean in the delta difference of −9.7 s (SEM 4.0, 95% C.I. −18.0 to −1.3) during the horror movie versus the control movie. The Light Transmission Aggregometry endpoints were in line with the PFA-CT, albeit only the highest level of Arachidonic Acid agonist demonstrated a statistically significant mean difference in the delta of aggregation of 13.15% (SEM 7.0, 95% C.I. 1.6–27.9). A 'blood curdling' horror movie increases platelet reactivity. These data are supportive of a role of platelet reactivity in acute stress induced cardiovascular event risk. • There is an increase of cardiovascular events during acute stressful moments. • Primary hemostasis plays a prominent role in the etiology of CVE. • A horror movie was used to simulate psychological stress in a research setting. • A horror movie increases platelet reactivity. • These results help elucidate the profound physiological effects of stress. [ABSTRACT FROM AUTHOR]

Early assessment of thrombogenicity and antithrombotic drug effects may be important for therapeutic decision making in patients presenting with acute stroke. In this prospective, single center, pilot study, a bedside thrombelastography assay (TEG6s) was used to measure thrombogenicity and antithrombotic drug response in serial patients presenting emergently with symptoms of acute stroke (n = 90). TEG6s measures were compared against diagnosis obtained by NIH Stroke Scale/Score and imaging. Acute ischemic stroke (AIS) was diagnosed in 30 patients, intracerebral hemorrhage (ICH) in 19, transient ischemic attack (TIA) in 10 and stroke mimic (SM) in 31. Patients with AIS had a higher prevalence of A-Fib (33.3% vs. 11.6%, p = 0.01), and ACE inhibitor use (56.3% vs. 21.6%, p < 0.001) compared to combined non-AIS group. Time to initial clot formation (R) was shorter in AIS vs. TIA, ICH, and SM (p < 0.05). Comparing patients with AIS and combined non-AIS group the AUC for R was 0.83 (cut point of ≤ 4.8, sensitivity = 67%; specificity = 84%, p < 0.001). In AIS patients, 46% had suboptimal response (< 30% MAAA inhibition) to aspirin and 80% of patients on P2Y12 therapy had high platelet reactivity (> 50% ADP-induced platelet aggregation). Patients receiving tissue plasminogen activator had significant reduction in clot strength and near complete lysis at 30 min which normalized within 2 h after treatment (p < 0.001 for both). The rapid bedside measurement of thrombogenicity and antithrombotic drug effects is feasible in patients presenting with symptoms of acute stroke. Our preliminary data suggest that AIS is associated with faster ex-vivo clot formation, and poor antiplatelet response. Future study of the TEG6s to "blueprint" hemostasis is warranted in the stroke population. [ABSTRACT FROM AUTHOR]

Objectives:Deep surgical site infection (DSSI) is one of the most serious complications after open induction internal fixation (ORIF) for traumatic limb fractures. In this study, we aimed to investigate the diagnostic role of platelet indices (platelet count [PLT], mean platelet volume [MPV], and platelet distribution width [PDW]) in DSSI.Patients and methods:Data obtained between January 2011 and December 2017 in The Affiliated Drum Tower Hospital of Nanjing University Medical School from cases (n=29) with DSSI and fracture control subjects (n=29) matched for age, gender, and fracture type were analyzed. The white blood cell (WBC) count, neutrophil count, neutrophil percentage, and platelet indices from blood samples were compared between case and control groups. In addition, the cutoff value, sensitivity, and specificity were calculated by receiver-operating characteristic (ROC) curves.Results: No significant differences were detected in demographic features, the WBC count, neutrophil count, neutrophil percentage, and MPV values between two groups (P>0.05). The PLT values were significantly higher in the case group than in the control group (303.00±139.27 vs 196.10±59.61 [109/μL], P=0.001). The PDW values of the case and control groups were 11.77±2.71 and 13.19±2.39%, respectively, and were significantly lower in the case group (P=0.001). ROC curve analysis suggested a cutoff point for PLT as 215.50 (109/μL, larger values indicate pathology) for the diagnosis of DSSI with the sensitivity and specificity of 79.3 and 72.4%, respectively. For PDW, the cutoff point was 10.35% (smaller values indicate patients) for the diagnosis of DSSI with the sensitivity and specificity of 37.9 and 96.6%, respectively.Conclusion: Our results suggest that PDW combined with PLT can be used as an important additional test for the diagnosis of DSSI after ORIF for traumatic limb fractures, thus reducing the cost and loss of time. [ABSTRACT FROM AUTHOR]

Background: Clopidogrel low response (CLR) is an independent risk factor of adverse outcomes in patients undergoing percutaneous coronary intervention (PCI), and intensified antiplatelet treatments (IAT) guided by platelet function assays might overcome laboratory CLR. However, whether IAT improves clinical outcomes is controversial. Methods: Relevant trials were identified in PubMed, the Cochrane Library, and the Chinese Medical Journal Network databases from their establishment to September 9, 2014. Trials were screened using predefined inclusion criteria. Conventional meta-analysis and cumulative meta-analysis were performed using the Review Manager 5.0 and STATA 12.0 software programs. Results: Thirteen randomized controlled trials involving 5111 patients with CLR were recruited. During a follow-up period of 1–12 months, the incidences of cardiovascular (CV) death, nonfatal myocardial infarction (MI), and stent thrombosis were significantly lower in the IAT arm than in the conventional antiplatelet treatment arm (relative risk [RR] = 0.45, 95% confidence interval [CI]: 0.36–0.57, P < 0.000,01), whereas bleeding was similar between the two arms (RR = 1.05, 95% CI: 0.86–1.27, P = 0.65). Conclusions: IAT guided by platelet function assays reduces the risk of CV death, nonfatal MI, and stent thrombosis (ST) without an increased risk of bleeding in patients undergoing PCI and with CLR.

This review provides a comprehensive and up-to-date overview of point-of-care (POC) devices most commonly used for coagulation analyses in the acute settings. Fast and reliable assessment of hemostasis is essential for the management of trauma and other bleeding patients. Routine coagulation assays are not designed to visualize the process of clot formation, and their results are obtained only after 30–90 m due to the requirements of sample preparation and the analytical process. POC devices such as viscoelastic coagulation tests, platelet function tests, blood gas analysis and other coagulometers provide new options for the assessment of hemostasis, and are important tools for an individualized, goal-directed, and factor-based substitution therapy. We give a detailed overview of the related tests, their characteristics and clinical implications. This review emphasizes the evident advantages of the speed and predictive power of POC clot measurement in the context of a goal-directed and algorithm-based therapy to improve the patient’s outcome. Interpretation of viscoelastic tests is facilitated by a new visualization technology.

The effect of omega-3 fatty acids on platelet aggregation and coagulation is highly unclear. Studies both support and refute the impacts of omega-3 fatty acids on prolonged bleeding time and platelet inhibition as well as its purported positive effects on cardiovascular disease. In a previous pilot study we suggested an inhibition of platelet aggregation measured with multiple electrode aggregometry. Following on that, the aim of the present study was to investigate the effects of supplementary high doses of omega-3 fatty acids on platelet aggregation and coagulation in a sample-size calculated number of healthy volunteers using Sonoclot, multiple electrode aggregometry, and flow-based Cellix instruments after 10 days of omega-3 fatty acid intake. Twelve healthy human volunteers ingested 2520 mg of supplementary omega-3 fatty acids per day for 10 days. Venous blood was sampled and platelet aggregation and coagulation were measured before and after the treatment period. The viscoelastic test instrument Sonoclot, multiple electrode aggregometry, and flow-based Cellix instruments with collagen-coated channels were used to evaluate platelet aggregation and coagulation. There were no differences in any of the measured variables after the treatment period as compared to before. In this well-powered study on healthy volunteers, no effects of high doses of omega-3 fatty acids after 10 days of intake could be demonstrated, either on coagulation or platelet function. Further studies are needed to clarify whether omega-3 fatty acids have a role in the regulation of the putative complex processes in vivo. [ABSTRACT FROM AUTHOR]

Highlights • Not all aspirin-users respond to platelet transfusion or respond equally at 1 h. • A fixed-dose transfusion results in heterogeneous platelet activities up to 48 h. • A fixed-dose transfusion is unnecessary or ineffective in close to 70% of patients. • Platelet transfusion should be guided by point-of-care platelet function assay. Abstract Background An increasing number of patients with intracranial haemorrhages are aspirin-users. Neurosurgeons commonly attempt to minimize the risk of re-bleeding by withholding the medication and giving platelet transfusion. However, recent studies raised safety concerns and showed poorer outcome with platelet transfusion when the latter was not guided by changes in platelet function. Aim of study To study the temporal pattern and degree of changes in platelet activities following a fixed dose of platelet transfusion in aspirin-users with intracranial haemorrhages. Methods Aspirin-users with intracranial haemorrhages underwent baseline aspirin response units (ARU) using the VerifyNow® assay. Those who showed abnormal platelet activity received a single dose of 4 units of platelet concentrate. ARU were then repeated at 4 h, 24 h and 48 h post-transfusion. Patients were classified according to their responses to transfusion. Results Twenty patients were recruited. At 4 h after transfusion, 11 (55%) patients had normalised platelet activities while the rest may show delayed or absent of normalization. Overall, eight (40%) patients were 'early and persistent transfusion responders', five 'delayed transfusion responders', and five (25%) had persistently abnormal platelet function. Two (10%) patients who initially responded to transfusion failed to maintain normalized platelet activity. Conclusion Platelet activities in aspirin-users showed considerable heterogeneity up to 48 h following a blanket approach of platelet transfusion. The need for repeated transfusion or alternative therapy strongly argues for a guided practice for transfusion based on point-of-care platelet function assay. Future research should also adopt this approach to re-examine the safety and effectiveness of platelet transfusion in these patients. [ABSTRACT FROM AUTHOR]

Summary: Introduction: There is potential value in testing individual response to P2Y12 inhibitors to predict ischemic and bleeding risk in patients undergoing percutaneous coronary intervention. The aims of this study were: (1) to validate the ability of a novel point of care (POC) assay, thrombelastography (TEG) 6s, to detect changes in adenosine diphosphate (ADP)‐induced whole blood clotting in volunteers and patients given clopidogrel using TEG 5000 as a reference and (2) to compare a novel, rapid parameter, area under the curve at 15 minutes (AUC15), with the traditional maximum clot amplitude (MA) in TEG 6s. Methods: A total of 25 participants were included in whom ADP‐induced clotting was measured at 4 time points: (1) 12 healthy volunteers given 600 mg of clopidogrel; (2) 12 patients with ACS given 600 mg of clopidogrel; (3) 1 healthy volunteer given 600 mg of clopidogrel on 5 separate occasions. All samples were tested using conventional TEG 5000 and the new POC TEG 6S, and a new parameter called AUC15 was compared with MA in TEG 6s. Results: (1) TEG 5000 and TEG 6s both detected changes in ADP‐induced platelet activation. Bland‐Altman analysis demonstrated a good level of agreement between them. (2) For TEG 6S, correlation between MA and the novel AUC15 was strong for both thrombin and ADP channels (R2 = 0.867, R = .936, P < .001), and the AUC15 result was available on average 13.3 minutes earlier. Conclusions: Thrombelastography 6s is a rapid, easy to use and accurate test of ADP‐induced clotting using TEG 5000 as a reference. A novel parameter, AUC15, is a viable, time‐saving option for this test and has potential value in personalized P2Y12 inhibitor therapy. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing percutaneous coronary intervention react differently to antiplatelet drugs. Those with low responsiveness to clopidogrel have a higher risk of cardiac ischemic events. The goal of this study is to conduct a head-to-head comparison of the safety and effectiveness of intensified antiplatelet therapies (either double-dose clopidogrel [DOUBLE] or adjunctive cilostazol [TRIPLE]) and conventional strategy (STANDARD) in patients after percutaneous coronary intervention.Methods: In this single-center, randomized, controlled trial, we used thromboelastography, a platelet function test, to select 1078 patients undergoing percutaneous coronary intervention at high thrombotic risk and compared the intensified antiplatelet therapies with standard antiplatelet therapy. The primary outcome was the incidence of major adverse cardiac and cerebrovascular events at 18 months after percutaneous coronary intervention, defined as a composite of all-cause death, myocardial infarction, target vessel revascularization, or stroke. Bleeding Academic Research Consortium defined bleeding complications (types 1, 2, 3, or 5) were the safety end points.Results: The primary end point occurred in 52 patients (14.4%) in the STANDARD group, 38 patients (10.6%) in the DOUBLE group, and 30 patients (8.5%) in the TRIPLE group (hazard ratio, 0.720; 95% confidence interval, 0.474-1.094, DOUBLE versus STANDARD; hazard ratio, 0.550; 95% confidence interval, 0.349-0.866, TRIPLE versus STANDARD). No significant difference in the rates of major bleeding (Bleeding Academic Research Consortium grade≥3) was found in the DOUBLE group (3.34% versus 1.93% in STANDARD, P=0.133) and the TRIPLE group (2.53% versus 1.93% in STANDARD, P=0.240). The rate of Bleeding Academic Research Consortium-defined minor bleeding increased in the DOUBLE group (27.4% versus 20.3% in STANDARD, P=0.031), but not in the TRIPLE group (23.6% versus 20.3% in STANDARD, P=0.146).Conclusions: In patients with low responsiveness to clopidogrel, as measured by thromboelastography, the intensified antiplatelet strategies with adjunctive use of cilostazol significantly improved the clinical outcomes without increasing the risk of major bleeding. Decreased trend of negative outcomes could be observed in patients with double dosage of clopidogrel, but the difference was not significant.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01779401. [ABSTRACT FROM AUTHOR]

We investigated the impact of suboptimal platelet reactivity on clinical outcomes after percutaneous coronary intervention (PCI). We enrolled 500 patients with stable coronary artery disease undergoing elective PCI. Platelet reactivity was measured before PCI using the VerifyNow P2Y12 assay. Primary endpoint was the incidence of ischemic or bleeding events at 1 month and 5 years. Patients with high platelet reactivity (HPR) showed significantly higher rates of ischemic events both during the 1st month after PCI (HR 2.06, 95% CI 1.02-4.06), and beyond 1 month compared with patients without HPR (HR 1.73, 95% CI 1.02-2.95). Conversely, compared with patients without low platelet reactivity (LPR), patients with LPR presented significantly higher rates of bleeding only during the 1st month (HR 3.67, 95% CI 1.68-8.02). In conclusion, pre-procedural HPR is associated with ischemic events even beyond the 1st month after PCI. The association of LPR with bleeding events seems to be confined to the periprocedural period. [ABSTRACT FROM AUTHOR]