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1.
Biomolecules ; 14(6)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38927117

RESUMEN

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.


Asunto(s)
Trastornos de las Plaquetas Sanguíneas , Plaquetas , Pruebas de Función Plaquetaria , Humanos , Plaquetas/metabolismo , Trastornos de las Plaquetas Sanguíneas/diagnóstico , Trastornos de las Plaquetas Sanguíneas/terapia , Trastornos de las Plaquetas Sanguíneas/sangre , Pruebas de Función Plaquetaria/métodos , Medicina de Precisión/métodos , Hemostasis
2.
J Neurosurg ; : 1-9, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38820610

RESUMEN

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.

3.
J Clin Med ; 12(18)2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37763014

RESUMEN

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.

4.
Platelets ; 34(1): 2254403, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37700390

RESUMEN

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.


Platelets are cell fragments in the blood that are necessary for clot formation. They are crucial to preventing excessive bleeding following trauma. To form clots, platelets clump (aggregate) and attach to fibrin protein and cells inside the blood vessels to form strong web-like structures. Platelets also contract to pull the edges of the wound close. Most measurements of platelet function involve aggregation. This paper focuses on platelet contraction. Here, we describe a new assay to measure platelets contraction that is repeatable and reproducible. The assay uses standard and common laboratory equipment and can be performed by most laboratory personnel and has the potential to detect clinical pathologies of clot formation. The assay could be developed for bedside patient care where platelet function could be assessed rapidly and assist in the diagnosis of coagulation and platelet disorders.


Asunto(s)
Activación Plaquetaria , Plasma Rico en Plaquetas , Humanos , Reproducibilidad de los Resultados , Pruebas de Función Plaquetaria , Fibrina
5.
Clin Appl Thromb Hemost ; 29: 10760296231187627, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37563887

RESUMEN

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.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Inhibidores de Agregación Plaquetaria , Humanos , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Aspirina/uso terapéutico , Aspirina/farmacología , Plaquetas , Pruebas de Función Plaquetaria/métodos , Transfusión Sanguínea
6.
Eur J Haematol ; 111(5): 787-795, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37553915

RESUMEN

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 Gαi 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.

7.
Methods Mol Biol ; 2663: 627-636, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37204741

RESUMEN

Platelet function testing is critical in the diagnosis of bleeding disorders and allows monitoring of antiplatelet therapy. The gold standard assay, light transmission aggregometry (LTA), was developed 60 years ago and remains widely used worldwide. It requires, however, access to expensive equipment and is time-consuming, and the interpretation of results requires evaluation by an experienced investigator. It also suffers from a lack of standardization, resulting in widely variable results between laboratories. 96-well plate-based Optimul aggregometry utilizes the same principles of LTA and aims to standardize agonist concentrations with the development of 96-well plates which are precoated with 7 concentrations of each lyophilized agonist (arachidonic acid, adenosine diphosphate, collagen, epinephrine, TRAP-6 amide, and U46619) and stored at ambient room temperature (20-25 °C) for up to 12 weeks. For platelet function testing, 40 µL of platelet-rich plasma is added to each well, and the plate is placed onto a plate shaker, after which platelet aggregation is determined by changes in light absorbance. This method reduces the blood volume required and allows for in-depth platelet function analysis without specialist training, or the need to purchase expensive, dedicated equipment.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Ensayos Analíticos de Alto Rendimiento , Humanos , Agregación Plaquetaria , Pruebas de Función Plaquetaria/métodos , Inhibidores de Agregación Plaquetaria/farmacología , Plaquetas
8.
Thromb Res ; 231: 223-235, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-36609119

RESUMEN

INTRODUCTION: 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. METHODS: 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. RESULTS: 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 B2 (TXB2) 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 TXB2, 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. CONCLUSION: Regular exercise training has no clear impact on platelet function in patients with CVD or healthy individuals. PROSPERO REGISTRATION: CRD42022350539.


Asunto(s)
Enfermedades Cardiovasculares , Selectina-P , Humanos , Enfermedades Cardiovasculares/terapia , Agregación Plaquetaria , Plaquetas , Ejercicio Físico
9.
World Neurosurg ; 171: 159-166.e13, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36529432

RESUMEN

BACKGROUND: The use of stents with various porosities for treating cerebral aneurysms requires dual antiplatelet therapy (DAPT) without clear guidelines on the utility of platelet function tests (PFTs) and the duration of DAPT. We sought to determine the effects of stent porosity, PFT usage, and DAPT duration on the radiographic and clinical outcomes after stenting of cerebral aneurysms. METHODS: PubMed was searched on March 29, 2021 for studies of cerebral aneurysm stenting that had specified the stent type and DAPT duration. A random effects meta-analysis was used to measure the prevalence of nonprocedural thrombotic and hemorrhagic events, clinical outcomes, aneurysm occlusion, and in-stent stenosis stratified by stent porosity, PFT usage, and DAPT duration. RESULTS: The review yielded 105 studies (89 retrospective and 16 prospective) with 117 stenting cohorts (50 high porosity, 17 intermediate porosity, and 50 low porosity). In the high-, intermediate-, and low-porosity stenting cohorts, PFT usage was 26.0%, 47.1%, and 62.0% and the mean DAPT duration was 3.51 ± 2.33, 3.97 ± 1.92, and 5.18 ± 2.27 months, respectively. The intermediate-porosity stents showed a reduced incidence of hemorrhagic events (π = 0.32%) compared with low-porosity stents (π = 1.36%; P = 0.01) and improved aneurysm occlusion (π = 6.18%) compared with high-porosity stents (π = 14.42%; P = 0.001) and low-porosity stents (π = 11.71%; P = 0.04). The prevalence of in-stent stenosis was lower for the intermediate-porosity (π = 0.57%) and high-porosity (π = 1.51%) stents than for the low-porosity stents (π = 3.30%; P < 0.05). PFT use had resulted in fewer poor clinical outcomes (π = 3.54%) compared with those without PFT use (π = 5.94%; P = 0.04). The DAPT duration had no effect on the outcomes. CONCLUSIONS: In the present meta-analysis, which had selected for studies of cerebral aneurysm stenting that had reported the DAPT duration, intermediate-porosity stents and PFT use had resulted significantly improved outcomes. No effect of DAPT duration could be detected.


Asunto(s)
Aneurisma Intracraneal , Inhibidores de Agregación Plaquetaria , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Aneurisma Intracraneal/tratamiento farmacológico , Porosidad , Estudios Retrospectivos , Estudios Prospectivos , Constricción Patológica/tratamiento farmacológico , Quimioterapia Combinada , Stents , Hemorragia/epidemiología
10.
Neurol Ther ; 11(4): 1749-1766, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36163415

RESUMEN

INTRODUCTION: Clopidogrel resistance causes recurrent stroke. However, outcomes of modified antiplatelet medications to prevent recurrent ischemic stroke are not well known. METHODS: Patients who received clopidogrel with and without modification as initial treatment for stroke were recruited and compared. The primary outcome was ischemic stroke and myocardial infarction at the 1-year follow-up. The secondary outcome was bleeding complications. RESULTS: Overall, 206 patients treated with clopidogrel were enrolled and were divided into the modification (n = 39) and no modification (n = 167) groups. There was a significant difference in the incidence of severe cerebral arterial stenosis between the two groups (modification group, 16/39, 41.03%; no modification group, 36/167, 21.56%, P = 0.012) at baseline. The loss to follow-up rate was 12.14% (25/206). After adjustment for severe cerebral artery stenosis, antiplatelet modification based on the platelet reactivity unit (PRU) value significantly improved in the per protocol set (odds ratio 0.142, 95% confidential interval 0.022-0.898, P = 0.038). The area under the curve of the different PRU cutoff values were 0.630, 0.605, and 0.591 (P = 0.016, 0.051, and 0.092) for PRU 190, 208, and 235, respectively. CONCLUSION: Verifynow P2Y12 PRU-guided modification of clopidogrel for ischemic stroke significantly improved or prevented recurrence at the 1-year follow-up. Our findings suggest that clopidogrel therapy based on the PRU cutoff value of 190 should be considered to improve outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02618265 (December 1, 2015).

11.
Cureus ; 14(5): e25497, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35783880

RESUMEN

Background Platelet transfusions may be indicated to prevent and treat bleeding in patients with quantitative or qualitative platelet defects. Millions of platelet components are transfused worldwide. It is well known that platelet dysfunction predicts blood loss after surgery. Hence, the quality of the platelet donation and the resulting platelet concentrate are critical for the transfusion. The aim of this study is to assess platelet function in well-qualified blood donors. Methodology Blood samples from 275 blood donors were collected in 0.129 M (3.8%) sodium citrate tubes prior to routine blood donation. Platelet function was assessed by measuring the closure time (CT) on the platelet function analyzer (PFA-100™; Siemens Health Diagnostics, Marburg, Germany) using collagen/epinephrine (CEPI) and collagen/ADP (CDP) cartridges. Results Using the PFA-100™, 20.4% of donors had an abnormal platelet function test, of whom 9.4% had prolonged CT with two cartridges, 7% had only prolonged CEPI CTs consistent with aspirin-like defect, and 4% had prolonged CADP CTs only. We found no closure (>300 seconds) in 6.54% of donors, including 1.45% with the CEPI cartridge, 2.9% with the CADP cartridge, and 2.18% with CEPI and CADP cartridges. Level of von Willebrand factor ristocetin cofactor (vWF: RCo) activity was 112% (56-168%). Of the factors examined (age, sex, cigarette smoking, blood donation type, ABO, and Rhesus blood group), only blood group O was significantly linked with impaired platelet function test in qualified blood donors (p = 0.023; odds ratio = 1.981; 95% confidence interval (1.091-3.595)). Conclusions Some qualified blood donors present abnormal platelet function results. More research is required to provide greater insight into the impact of platelet dysfunction in blood donors on the clinical efficacy of their platelet components. This study has confirmed that the influence of ABO blood group on the CT PFA-100™is not wholly dependent on vWF.

12.
Front Cardiovasc Med ; 9: 899594, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35845048

RESUMEN

Background: Platelet 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). Methods: Blood 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. Results: Agreement 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. Conclusions: Overall 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.

13.
Res Pract Thromb Haemost ; 6(5): e12755, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35873218

RESUMEN

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 αIIbß3-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.

14.
Front Surg ; 9: 839157, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35223980

RESUMEN

OBJECTIVE: To 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. METHODS: A 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. RESULTS: The 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). CONCLUSION: Using 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.

15.
Am J Med Genet A ; 188(6): 1716-1722, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35156755

RESUMEN

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.


Asunto(s)
Heterotopia Nodular Periventricular , Enfisema Pulmonar , Niño , Femenino , Filaminas/genética , Humanos , Mutación , Heterotopia Nodular Periventricular/diagnóstico , Heterotopia Nodular Periventricular/genética , Fenotipo
16.
Eur J Vasc Endovasc Surg ; 63(1): 91-101, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34844834

RESUMEN

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Asunto(s)
Clopidogrel/administración & dosificación , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Extremidad Inferior/cirugía , Enfermedad Arterial Periférica/cirugía , Activación Plaquetaria/efectos de los fármacos , Antagonistas del Receptor Purinérgico P2/administración & dosificación , Causas de Muerte , Humanos , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/fisiopatología , Pruebas de Función Plaquetaria , Complicaciones Posoperatorias , Hemorragia Posoperatoria , Resultado del Tratamiento
17.
J Clin Med ; 10(17)2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34501440

RESUMEN

On-treatment platelet reactivity in clopidogrel-treated patients can be measured with several platelet function tests (PFTs). However, the agreement between different PFTs is only slight to moderate. Polymorphisms of the CYP2C19 gene have an impact on the metabolization of clopidogrel and, thereby, have an impact on on-treatment platelet reactivity. The aim of the current study is to evaluate the differential effects of the CYP2C19 genotype on three different PFTs. METHODS: From a prospective cohort study, we included patients treated with clopidogrel following percutaneous coronary intervention (PCI). One month after PCI, we simultaneously performed three different PFTs; light transmission aggregometry (LTA), VerifyNow P2Y12, and Multiplate. In whole EDTA blood, genotyping of the CYP2C19 polymorphisms was performed. RESULTS: We included 308 patients treated with clopidogrel in combination with aspirin (69.5%) and/or anticoagulants (33.8%) and, based on CYP2C19 genotyping, classified them as either extensive (36.4%), rapid (34.7%), intermediate (26.0%), or poor metabolizers (2.9%). On-treatment platelet reactivity as measured by LTA and VerifyNow is significantly affected by CYP2C19 metabolizer status (p < 0.01); as metabolizer status changes from rapid, via extensive and intermediate, to poor, the mean platelet reactivity increases accordingly (p < 0.01). On the contrary, for Multiplate, no such ordering of metabolizer groups was found (p = 0.10). CONCLUSIONS: For VerifyNow and LTA, the on-treatment platelet reactivity in clopidogrel-treated patients correlates well with the underlying CYP2C19 polymorphism. For Multiplate, no major effect of genetic background could be shown, and effects of other (patient-related) variables prevail. Thus, besides differences in test principles and the influence of patient-related factors, the disagreement between PFTs is partly explained by differential effects of the CYP2C19 genotype.

18.
Cureus ; 13(7): e16625, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34458036

RESUMEN

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm associated with thrombosis. A 48-year-old female with PV presented with right eye pain following a low-impact head trauma. She consumed aspirin for analgesia and took preparations of Chinese herbs. CT head revealed right-sided subdural hematoma. She had reduced Von Willebrand activity to 26%. Direct angiographic imaging showed an aneurysm arising from a right middle cerebral atery (MCA) branch. The patient was given 1-deamino-8-D-arginine vasopressin (DDAVP) prior to the craniotomy. Intra-operative examination revealed that the aneurysm-like structure was a small grape-like structure of the fibrinous part of the subdural membrane that had formed from the subdural hematoma. Acquired von Willebrand syndrome (AVWS) is an important risk factor for bleeding in PV. DDAVP may be useful to increase levels of Von Willebrand Factor (VWF) and decrease the risk of bleeding perioperatively. Exogenous substances such as ginseng should be investigated as possible contributors to bleeding tendency and discontinued.

19.
Int J Appl Basic Med Res ; 11(3): 154-159, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34458117

RESUMEN

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.

20.
Anesthesiol Clin ; 39(3): 525-535, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34392883

RESUMEN

The main goal of perioperative coagulation monitoring is to improve safety of patients undergoing surgical procedures. Various conditions can affect the coagulation system during surgery and bleeding. The value of traditional standard coagulation tests is limited in detecting hemostatic dysfunctions and they are particularly ineffective in diagnosing hyperfibrinolysis. This article reports on key issues and pathophysiologic changes that affect the hemostatic system in the perioperative setting. Values of preoperative coagulation tests are discussed and the basic principles for point-of-care coagulation devices, including platelet analyzers and their clinical use, are evaluated.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Coagulación Sanguínea , Trastornos de la Coagulación Sanguínea/diagnóstico , Pruebas de Coagulación Sanguínea , Hemorragia , Humanos , Sistemas de Atención de Punto
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