허혈성 뇌졸중 환자에서 신속혈소판기능 검사를 이용한 클로피도그렐의 혈소판 응집 억제 반응 측정

김재국,김형일,신혜은,이보람,전종은,이수주 대한신경과학회 2008 대한신경과학회지 Vol.26 No.4

Background: Clopidogrel inhibits platelet P2Y12 adenosine diphosphate (ADP) receptors and has been widely used in patients with ischemic stroke. However, a considerable number of patients suffer from cerebrovascular events despite the use of clopidogrel. The rapid platelet function assay (RPFA) has been used for monitoring the antiplatelet effects on the P2Y12 ADP receptor. This study was performed to measure the platelet response to clopidogrel using RPFA in patients with ischemic stroke, and to identify the clinical factor related with clopidogrel resistance. Methods: A total of 86 patients taking clopidogrel (75 mg/day) were enrolled. Demographic data, vascular risk factors, the presence of obesity and metabolic syndrome, drug history, hemoglobin, platelet counts, and stroke subtypes were recorded. RPFA presented the results as P2Y12 Reaction Units (PRU), base PRU (BASE), and Inhibition (%). Inhibition was calculated as (1-PRU/BASE)×100. The patients showing ineffective aggregation- inhibition (percentage of Inhibition < 20) on RPFA were defined as non-responders to clopidogrel. Results: The response of platelet aggregation-inhibition to clopidogrel showed a variable distribution with mean and standard deviation of 32.2±22.3%. Twenty four (27.9%) patients showed the inhibition below 20%. There was no difference between responders and non-responders regarding the clinical factors above. We found no influence of co-medication with the statins on platelet response to clopidogrel. Conclusions: There is a patient variability in response to clopidogrel and a considerable portion of stroke patients have clopidogrel resistance on the platelet function test. The clinical usefulness of routine platelet function test requires further validation. Background: Clopidogrel inhibits platelet P2Y12 adenosine diphosphate (ADP) receptors and has been widely used in patients with ischemic stroke. However, a considerable number of patients suffer from cerebrovascular events despite the use of clopidogrel. The rapid platelet function assay (RPFA) has been used for monitoring the antiplatelet effects on the P2Y12 ADP receptor. This study was performed to measure the platelet response to clopidogrel using RPFA in patients with ischemic stroke, and to identify the clinical factor related with clopidogrel resistance. Methods: A total of 86 patients taking clopidogrel (75 mg/day) were enrolled. Demographic data, vascular risk factors, the presence of obesity and metabolic syndrome, drug history, hemoglobin, platelet counts, and stroke subtypes were recorded. RPFA presented the results as P2Y12 Reaction Units (PRU), base PRU (BASE), and Inhibition (%). Inhibition was calculated as (1-PRU/BASE)×100. The patients showing ineffective aggregation- inhibition (percentage of Inhibition < 20) on RPFA were defined as non-responders to clopidogrel. Results: The response of platelet aggregation-inhibition to clopidogrel showed a variable distribution with mean and standard deviation of 32.2±22.3%. Twenty four (27.9%) patients showed the inhibition below 20%. There was no difference between responders and non-responders regarding the clinical factors above. We found no influence of co-medication with the statins on platelet response to clopidogrel. Conclusions: There is a patient variability in response to clopidogrel and a considerable portion of stroke patients have clopidogrel resistance on the platelet function test. The clinical usefulness of routine platelet function test requires further validation.

Platelet Function Analyzer(PFA®)-100을 이용한 술전 출혈경향 평가 및 임상적 적용

Jihu han,도언록,김태섭,Chen Zhang,박대환 대한미용성형외과학회 2013 Archives of Aesthetic Plastic Surgery Vol.19 No.1

Routine preoperative tests such as BT/CT, PT/PTT and CBC, could not test abnormal hemostasis that take drugs and health functional food. We used platelet function analyzer (PFA®)-100, to evaluate preoperative bleeding tendencies. From November 2008 to February 2010, 306 surgical patients were tested preoperative PFA in our hospital. There are 2 tests in PFA®-100. The Pre Operative EPI (collagen/epinephrine) assay tests extrinsic platelet function, whereas the Pre Operative ADP (collagen/adenosine diphosphate) assay tests intrinsic platelet function. We divided normal and abnormal groups by the PFA®-100 assay tests. If either of results were abnormal in the two tests, the patient was divided to the abnormal group. 306 surgical patients were observed with hemorrhagic complications. All of the patients were divided normal and abnormal groups by the PFA®-100 test result. The normal group was made up of 286 (93.5 %) patients, the abnormal group was made up of 20 (6.5 %) patients. We observed each group hemorrhage complication including sever echymosis and hematoma, and analyzed each group complication rate. There were 9 (3.1 %) cases of complication in the normal group. There were 3 (15.0 %) cases of complication in the abnormal group. To evaluate preoperative bleeding tendency, PFA®-100 can be complementary examination with previous routine blood coagulation tests.

Bleeding time: Remained or Retired or Removed?

김보현 대한진단검사의학회 2023 Laboratory Medicine Online Vol.13 No.1

The bleeding time (BT) test is one of the oldest hemostasis tests. Although it is simple, rapid, and does not require experienced laboratory personnel, the sensitivity, specificity and reproducibility of the BT for detecting platelet function abnormalities are poor. Therefore, BT is not a suitable screening test for platelet function defects and predictive test for surgical bleeding. Although the PFA-100/200 cannot be totally replaceable to the BT, it has been regarded as a practical and readily available platelet function screening test in clinical laboratories. However, similar to BT, PFA100/200 has unsatisfactory diagnostic sensitivity and specificity for identifying platelet function defects, and assessing preoperative bleeding risk. In this article, the characteristics and clinical utility of BT and other platelet function tests that can be utilized for screening of platelet function defects will be briefly reviewed and the efficient way to use these tests will be suggested.

수술 전 혈소판 기능 검사를 위한 PFA^®-100의 임상적 이용

김성만,양승배,이제훈,Kim, Sung-Man,Yang, Seung-Bae,Lee, Jehoon 대한임상검사과학회 2009 대한임상검사과학회지(KJCLS) Vol.41 No.1

The Platelet Function Analyzer (PFA)$^{(R)}$-100 measures the ability of platelets activated in a high-shear environment to occlude an aperture in a membrane treated with collagen and epinephrine (CEPI) or collagen and ADP (CADP). The time taken for the flow across the membrane to stop (closure time, CT) is recorded. The aim of this study was to assess the potential of the PFA$^{(R)}$-100 as a primary clinical screening tool using the wide spectrum of clinical samples assessed for platelet function as well as to perform the optimal algorithm for the use of PFA$^{(R)}$-100. We established the reference interval in 460 hospital inpatients defined as having normal platelet function based on classical laboratory tests. The reference interval by using the range $5^{th}$ and $95^{th}$ percentile was 84~251 seconds for males CEPI-CT and 85~249 seconds for females CEPI-CT. A total of 1,200 inpatients were enrolled to identify impaired hemostasis before surgical interventions. The abnormal group showing prolonged CEPI-CT was 303 cases (18.9%). Only 3 cases had both abnormal CEPI-CT and CADP-CT. Several factors including sample errors, drugs, hematologic abnoralities were contributed to unexpected prolonged CEPI-CT for screening test. The von Willebrand factor (vWF:Ag) assay was performed only in one patient to verify the algorithm for the use of PFA$^{(R)}$-100. The PFA$^{(R)}$-100 was sensitive and rapid method for primary screening test of platelet dysfunction, so we can substitute it for the bleeding time in routine clinical practice.

Review of Genetic Diagnostic Approaches for Glanzmann Thrombasthenia in Korea

Shim, Ye Jee Interdisciplinary Society of GeneticGenomic Medici 2021 Journal of interdisciplinary genomics Vol.3 No.2

Inherited platelet function disorders (IPFDs) are a disease group of heterogeneous bleeding disorders associated with congenital defects of platelet functions. Normal platelets essential role for primary hemostasis by adhesion, activation, secretion of granules, aggregation, and procoagulant activity of platelets. The accurate diagnosis of IPFDs is challenging due to unavailability of important testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. Among several IPFDs, Glanzmann thrombasthenia (GT) is a most representative IPFD and is relatively frequently found compare to the other types of rarer IPFDs. GT is an autosomal recessive disorder caused by mutations of ITGA2B or ITGB3. There are quantitative or qualitative defects of the GPIIb/IIIa complex in platelet, which is the binding receptor for fibrinogen, von Willbrand factor, and fibronectin in GT patients. Therefore, patients with GT have normal platelet count and normal platelet morphology, but they have severely decreased platelet aggregation. Thus, GT patients have a very severe hemorrhagic phenotypes that begins at a very early age and persists throughout life. In this article, the general contents about platelet functions and respective IPFDs, the overall contents of GT, and the current status of genetic diagnosis of GT in Korea will be reviewed.

수술 전 혈소판 기능 검사를 위한 PFA®-100의 임상적 이용

김성만 ( Sung Man Kim ),양승배 ( Seung Bae Yang ),이제훈 ( Je Hoon Lee ) 대한임상검사과학회 2009 대한임상검사과학회지(KJCLS) Vol.41 No.1

The Platelet Function Analyzer (PFA)®-100 measures the ability of platelets activated in a high-shear environment to occlude an aperture in a membrane treated with collagen and epinephrine (CEPI) or collagen and ADP (CADP). The time taken for the flow across the membrane to stop (closure time, CT) is recorded. The aim of this study was to assess the potential of the PFA®-100 as a primary clinical screening tool using the wide spectrum of clinical samples assessed for platelet function as well as to perform the optimal algorithm for the use of PFA®-100. We established the reference interval in 460 hospital inpatients defined as having normal platelet function based on classical laboratory tests. The reference interval by using the range 5th and 95th percentile was 84~251 seconds for males CEPI-CT and 85~249 seconds for females CEPI-CT. A total of 1,200 inpatients were enrolled to identify impaired hemostasis before surgical interventions. The abnormal group showing prolonged CEPI-CT was 303 cases (18.9%). Only 3 cases had both abnormal CEPI-CT and CADP-CT. Several factors including sample errors, drugs, hematologic abnoralities were contributed to unexpected prolonged CEPI-CT for screening test. The von Willebrand factor (vWF:Ag) assay was performed only in one patient to verify the algorithm for the use of PFA®-100. The PFA®-100 was sensitive and rapid method for primary screening test of platelet dysfunction, so we can substitute it for the bleeding time in routine clinical practice.

Is the platelet function test effective in predicting blood loss in patients undergoing hepatic resection?

Jun Gyo Gwon,Sun-Young Ko,Hyokee Kim 대한외과학회 2022 Annals of Surgical Treatment and Research(ASRT) Vol.103 No.4

Purpose: The platelet function analyzer (PFA)-100/200 is widely used to assess platelet function. However, its role in predicting the perioperative risk of bleeding in patients undergoing liver resection remains controversial. Therefore, we aimed to ascertain whether the platelet function test could be useful in predicting bleeding risk in patients undergoing hepatic surgery. Methods: The study participants were patients who underwent hepatectomy for hepatocellular carcinoma at our hospital over a period of 10 years from January 1, 2010 to May 31, 2020. PFA-200 values of these patients were divided into 2 groups; normal (n = 333) and prolonged (n = 39). Results: There were no significant differences regarding the volumes of calculated blood loss during surgery between the normal and prolonged PFA groups (879.55 ± 1,046.50 mL vs. 819.74 ± 912.64 mL, respectively; P = 0.733); intraoperative RBC transfusion (0.52 ± 2.02 units vs. 0.26 ± 1.02 units, P = 0.419) and postoperative RBC transfusion (0.24 ± 1.17 units vs. 0.46 ± 1.97 units, P = 0.306) were similar between the 2 groups, respectively. Multivariate analysis revealed no association between PFA closure time and calculated blood loss (hazard ratio, 1.06; P = 0.881). Moreover, there was no association between PFA closure time and preoperative laboratory results or assessment of tool-related liver function in multivariate analysis. Conclusion: There was no correlation between the amount of blood loss and platelet function in patients who underwent liver resection. In patients undergoing liver resection who are not managed on antiplatelet agents or do not have chronic kidney disease, the use of routine PFA is not recommended.

Aspirin Resistance May Not Be Associated with Clinical Outcome after Acute Ischemic Stroke: Comparison with Three Different Platelet Function Assays

유남태,배효진,김지은,고리영,한진영,김무현,차재관 대한뇌졸중학회 2012 Journal of stroke Vol.14 No.1

Background: Aspirin resistance (AR) in platelet function assays showed substantial variation depending on the methods used to evaluate it. Methods: In this study, we prospectively compared the results of Multiplate impedance platelet aggregometry (IPA) with those of light transmission aggregometry (LTA) and VerifyNow® system in determination of the prevalence of aspirin resistance (AR) and investigated the correlation between its presence and poor outcome (modifi ed Rankin scale >2) in 105patients with aspirin after acute ischemic stroke (AIS). Results: After 5 days of using aspirin, 15 patients (14.3%) were classifi ed as aspirin-resistance with the use of IPA, 24 patients (22.9%) by the LTA, and 14 patients (13.3%) by VerifyNow. Good agreement between the results of IPA and VerifyNow, was found (R=0.674, P <0.01). The concordance rate of AR detection was high between VerifyNow and IPA (k=0.72, P <0.01), albeit quite low between LTA and IPA. Regarding on its infl uence on clinical outcome after AIS, there wasn’t any signifi cant relationship between occurrence of poor outcome and the presence of AR in three platelet function assays. Conclusion: This study reveals that the incidence of AR in AIS might be highly test-specifi c. IPA seems to be similar to VerifyNow as a platelet function test.

Variability of Platelet Reactivity on Antiplatelet Therapy in Neurointervention Procedure

Yi, Ho Jun,Hwang, Gyojun,Lee, Byoung Hun The Korean Neurosurgical Society 2019 Journal of Korean neurosurgical society Vol.62 No.1

As more intracranial aneurysms and other cerebrovascular pathologies are treated with neurointervention procedure, thromboembolic events that frequently lead to serious neurological deficit or fatal outcomes are increasing. In order to prevent the thromboembolic events, antiplatelet therapy is used in most procedures including coil embolization, stenting, and flow diversion. However, because of variable individual pharmacodynamics responses to antiplatelet drugs, especially clopidogrel, it is difficult for clinicians to select the adequate antiplatelet regimen and its optimal dose. This article reviews the neurointervention literature related to antiplatelet therapy and suggests a strategy for tailoring antiplatelet therapy in individual patients undergoing neurointervention based on the results of platelet function testing.

Determination of the Prevalence of Aspirin and Clopidogrel Resistances in Patients with Coronary Artery Disease by using Various Platelet-function Tests

우광숙,김보람,김지은,고리영,Long-Hao Yu,김무현,한진영 대한진단검사의학회 2010 Annals of Laboratory Medicine Vol.30 No.5

Background: Dual therapy with aspirin and clopidogrel has emerged as the gold standard therapy for patients treated with drug-eluting stents (DES). However, there is variability in patients’ responses to this antiplatelet therapy, and some patients continue to show ischemic recurrences after therapy. The purpose of the study was to compare the simultaneously obtained results of various plateletfunction tests for assessing the prevalence of antiplatelet resistance in coronary artery disease patients undergoing DES therapy. Methods: A total of 66 patients were administered a loading dose of aspirin, clopidogrel, and cilostazol at least 12 hr before stenting. The results of VerifyNow (Accumetrics, USA), multiplate analyzer (Dynabyte Medical, Germany), and vasodilator-stimulated phosphoprotein/P2Y12 (Biocytex,France) assays were compared with those of light transmission aggregometry (LTA) analysis. Results: The P2Y12 reaction units and P2Y12% inhibition values obtained using the VerifyNow assay showed strong correlation (r) with the results of the LTA analysis. All tests results showed low concordance in defining the antiplatelet resistance in patients, and the degrees of agreement were as follows: 0 for aspirin reaction units; 0.25, P2Y12% inhibition; 0, aspirin-sensitive patients’ identification test; 0.21, ADPtest; and 0.14, platelet reactivity index, expressed as the k statistics. The prevalence of aspirin and clopidogrel resistances in patients resulted in remarkable variations, from 0%to 22.7% and from 9.1% to 48.5%, respectively. Conclusions: The clinical usefulness of the different assays for the correct classification of patients in terms of antiplatelet resistance remains unclear. Further studies are required to determine the best method for correlating the occurrences of adverse ischemic events. (Korean J Lab Med 2010;30:460-8)