scholarly journals Antibody-mediated procoagulant platelets in SARS-CoV-2- vaccination associated immune thrombotic thrombocytopenia

Haematologica ◽  
2021 ◽  
Author(s):  
Karina Althaus ◽  
Peter Möller ◽  
Günalp Uzun ◽  
Anurag Singh ◽  
Annika Beck ◽  
...  
Keyword(s):  
High Titer ◽  
Fatal Outcome ◽  
Severe Infection ◽  
Aggregation Assay ◽  
Platelet Factor ◽  
Platelet Aggregation Assay ◽  
Thrombotic Complications ◽  
Vaccination Campaigns ◽  
Immune Assays ◽  
Glomerular Capillaries

The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide. To prevent severe infection, mass COVID-19 vaccination campaigns with several vaccine types are currently underway. We report pathological and immunological findings in 8 patients who developed vaccine-induced immune thrombotic thrombocytopenia (VITT) after administration of SARS-CoV-2 vaccine ChAdOx1 nCoV-19. We analyzed patient material using enzyme immune assays, flow cytometry and heparin-induced platelet aggregation assay and performed autopsies on two fatal cases. Eight patients (5 female, 3 male) with a median age of 41.5 years (range, 24 to 53) were referred to us with suspected thrombotic complications 6 to 20 days after ChAdOx1 nCoV-19 vaccination. All patients had thrombocytopenia at admission. Patients had a median platelet count of 46.5 x109/L (range, 8 to 92). Three had a fatal outcome and 5 were successfully treated. Autopsies showed arterial and venous thromboses in various organs and the occlusion of glomerular capillaries by hyaline thrombi. Sera from VITT patients contain high titer antibodies against platelet factor 4 (PF4) (OD 2.59±0.64). PF4 antibodies in VITT patients induced significant increase in procoagulant markers (P-selectin and phosphatidylserine externalization) compared to healthy volunteers and healthy vaccinated volunteers. The generation of procoagulant platelets was PF4 and heparin dependent. We demonstrate the contribution of antibody-mediated platelet activation in the pathogenesis of VITT.

Excluding HIT Diagnosis by a Particle Gel Immunoassay.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3405-3405
Author(s):  
Katharina Schallmoser ◽  
Camilla Drexler ◽  
Eva Rohde ◽  
Dirk Strunk ◽  
Andrea Groselj-Strele ◽  
...  
Keyword(s):  
High Titer ◽  
Rapid Test ◽  
Roc Curves ◽  
Serotonin Release ◽  
Aggregation Assay ◽  
Platelet Factor ◽  
Predictive Values ◽  
Specificity And Sensitivity ◽  
Platelet Aggregation Assay ◽  
Alternative Anticoagulation

Abstract Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition, characterized by a platelet drop of >50% and/or thrombosis with a temporal relationship of 1–2 weeks after initiation of heparin treatment. These surrogate markers are useful for the clinical assessment but are hardly applicable in multi-morbid patients with clinical conditions mimicking HIT. Platelet activation assays (heparin-induced platelet aggregation assay, HIPA; serotonin release assay, SRA) and platelet factor-4/polyanion enzyme immunoassays (PF4-ELISA) confirm HIT. HIPA and SRA are highly specific but laborious requiring selected donor platelets and extended experience. High titer IgG antibodies correlate with clinical HIT, but ELISA is also time-consuming. The alternative H/PF4-antigen particle gel immunoassay (ID-PaGIA H/PF4®) is easy, provides results within one hour and detects mainly IgG, but also IgA/M antibodies. We evaluated specificity and sensitivity of the PaGIA in comparison to HIPA and ELISA (PF4-ENHANCED®) in 285 patients (median 71yrs, range 1–97, 45% cardiovascular surgery; f/m 56/73, and 55% medical, f/m 78/78) with undetermined likelihood for HIT and 89 healthy controls (median 42yrs, range 26–64, f/m 49/40) to validate it as a rapid assay to exclude HIT. HIPA was positive in 12% of patients. Based on ROC curves (ELISAs vs HIPA), OD-cutoff values for the IgG/A/M- and IgG-ELISA were 0.761 and 0.564, respectively. In controls the OD of IgG-ELISA was 0.066 (0.028–0.500) and lower than from patients’ samples negative by PaGIA and IgG/A/MELISA (n=158; 0.074; 0.009–0.339; p=0.017). PaGIA was positive in 70 patients (25%). In both patient groups both ELISA ODs were higher if PaGIA and IgG/A/MELISA were positive compared to negative PaGIA but positive IgG/A/MELISA (p<0.001; data are shown as median; range). Analyzed by ROC curves (ELISAs vs HIPA), IgG/A/MELISA (OD-cutoff 0.761) and IgG-ELISA (OD-cutoff 0.564) had sensitivities of 81% and 86%, and specificities of 75% and 81%. Positive and negative predictive values were 31% and 97% (IgG/A/MELISA) and 39% and 98% (IgG-ELISA), respectively. PaGIA, IgG/A/M- and IgG-ELISA were significant predictors for the results of HIPA (p<0.001) and the IgG-ELISA had the highest explained variance (41%). Based on our results the PaGIA may serve as a rapid test to exclude HIT since a negative PaGIA is rarely associated with high titer IgG PF4-antibodies or a positive HIPA. In cases of positive PaGIA results and in patients highly suspicious for HIT but with negative PaGIA, alternative anticoagulation should be considered until results from functional testing are available.

Effect of fondaparinux on platelet activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 139-144 ◽  
Author(s):  
Pierre Savi ◽  
Beng H. Chong ◽  
Andreas Greinacher ◽  
Yves Gruel ◽  
John G. Kelton ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Factor Xa ◽  
Annexin V ◽  
Heparin Therapy ◽  
Cross Reactivity ◽  
Serotonin Release ◽  
Aggregation Assay ◽  
Platelet Factor ◽  
Platelet Aggregation Assay ◽  
History Of

Abstract Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy caused by antibodies against a complex of platelet factor 4 and heparin. Fondaparinux (Arixtra) is a new synthetic selective factor Xa inhibitor. We performed a serologic study to determine the cross-reactivity of HIT sera with fondaparinux. Using a prospective, blinded study design, 39 clinically and serologically confirmed sera from patients with HIT and 15 control sera were sent to 3 different laboratories, each of which specialized in a particular HIT assay. These include the serotonin release assay, heparin-induced platelet agglutination assay, and platelet aggregation assay. Two of 82 assays (2.4%) performed in the presence of control sera were positive, both with unfractionated heparin. In the presence of HIT sera, 75 of 94 (79.8%) evaluable assays were positive with unfractionated heparin; fondaparinux was significantly (P &lt; .001) less reactive than unfractionated heparin, only 3 of 91 evaluable assays (3.3%) being positive. Using flow cytometry, unlike unfractionated heparin, fondaparinux did not induce the binding of PAC1 and anti-CD62 monoclonal antibodies or of annexin V to platelets with HIT sera. Together, these results suggest that fondaparinux is nonreactive to HIT sera and raise the possibility that the drug may be used for prophylaxis and treatment of thrombosis in patients with a history of HIT.

scholarly journals Cerebral Venous Thrombosis Developing after COVID-19 Vaccination: VITT, VATT, TTS, and More

2021 ◽  
Author(s):  
Giuseppe Lippi ◽  
Emmanuel J. Favaloro
Keyword(s):  
Sinus Thrombosis ◽  
Severe Disease ◽  
Fatal Outcome ◽  
Cerebral Venous Sinus Thrombosis ◽  
Young Female ◽  
Enzyme Linked Immunosorbent Assay ◽  
Platelet Factor ◽  
Viral Spread ◽  
Thrombotic Complications ◽  
Respiratory Coronavirus

AbstractDespite the huge efforts globally underway for preventing or limiting the spread of severe acute respiratory coronavirus disease 2 (SARS-CoV-2), the coronavirus disease 2019 (COVID-19) pandemic outbreak appears still virtually unstoppable. As for many other infectious diseases, COVID-19 vaccination has now become crucial for limiting viral spread, especially for averting hospitalizations, need for intensive care, and fatal outcome. Nonetheless, as for other vaccines, COVID-19 vaccination is not completely free from side effects. Among the adverse events that have been reported after receiving COVID-19 vaccination, special emphasis has been given to an unexpected number of thrombocytopenic episodes with or without thrombotic complications, especially in recipients of adenovirus-based COVID-19 vaccines. Along with a specific clinical presentation, encompassing “atypical” thrombosis (especially cerebral venous [sinus] thrombosis, CVT) more prevalent in young female subjects, this new syndrome called vaccine-induced thrombocytopenia and thrombosis (VITT) is characterized by, and thereby diagnosed for, the presence of three paradigmatic laboratory abnormalities, i.e., low platelet count (<150 × 109/L), elevated plasma D-dimer levels (>0.5 mg/L), accompanied by a positive test for anti-PF4 (platelet factor 4) antibodies assayed with ELISA (enzyme-linked immunosorbent assay) techniques. Timely identification of these important abnormalities by both clinicians and laboratory professional is essential for early diagnosis and management of VITT, since the outcome of this condition may be fatal in half or even more of effected patients with severe disease. Therefore, this narrative review aims to review here the epidemiology, pathogenesis, clinical, and laboratory characteristics of VITT and other COVID-19 vaccine-associated thrombocytopenias.

scholarly journals ROLE OF NITRIC OXIDE (NO) IN CAPSAICIN MEDIATED ANTI-PLATELET ACTIVITY IN IN VITRO, IN VIVO, EX-VIVO MODEL OF PLATELET AGGREGATION ASSAY AND ARTERIAL THROMBOSIS IN RAT: POTENTIAL THERAPEUTIC TARGET?

2018 ◽  
Vol 10 (4) ◽  
pp. 44
Author(s):  
Mihir K Patel ◽  
Kiranj K. Chaudagar ◽  
Anita A. Mehta
Keyword(s):  
Platelet Aggregation ◽  
Arterial Thrombosis ◽  
Ex Vivo ◽  
Platelet Activity ◽  
Aggregation Assay ◽  
Thrombosis Model ◽  
Platelet Aggregation Assay

Objective: Although recent advances in the treatment of congestive heart disease, mortality among patients’ remains a questionable remark. Therefore, we evaluated the role of capsaicin on in vitro and ex vivo platelet aggregation induced by Adenosine Di-Phosphate (ADP) as well as in in vivo thrombosis models and role of NO, KATP was also identified in the capsaicin-induced anti-platelet animal model as well as in vivo model of arterial thrombosis.Methods: According to body weight wistar rats were divided into five groups. Group I and Group II was treated with saline and capsaicin (3 mg/kg, i. v), while animals from Group III were treated with N(ω)-nitro-L-arginine methyl ester (L-NAME) (30 mg/kg, i. v) 30 min before administration of capsaicin (3 mg/kg, i. v). Group IV animals were treated with glibenclamide (10 mg/kg,i. v) 30 min before administration of capsaicin (3 mg/kg, i. v). Group V was considered as a positive control and administered clopidogrel (30 mg/kg, p. o). Animals were subjected for in vitro, ex-vivo platelet aggregation assay. ADP (30µM) was utilized as an aggregating agent in these experiments. After these assays; animals of each group were subjected for subaqueous tail bleeding time in a rat model and FeCl3-induced arterial thrombosis model in rats.Results: In ADP-induced in vitro platelet aggregation, a significant reduction in % platelet aggregation was observed at 50µM (64.35±4.641) and 100µM (52.72±4.192) concentration of capsaicin as compared to vehicle control (85.82±3.716). Capsaicin (3 mg/kg, i. v) also showed a significant reduction (49.53±4.075) in ex-vivo ADP-induced platelet aggregation as compared to vehicle control (89.38±2.057). In FeCl3 induced arterial thrombosis model, Capsaicin (3 mg/kg, i. v) exhibited an increase in time to occlusion in this rodent model and presence of the L-NAME and glibenclamide had inhibited the activity of capsaicin.Conclusion: In our study, capsaicin (50 µM, 100µM) exhibited potent anti-platelet activity in ADP-induced platelet aggregation, similarly capsaicin exhibited significant anti-platelet action in the ex-vivo study. Moreover, the presence of L-NAME and glibenclamide inhibited the anti-thrombotic and anti-platelet action of capsaicin. Therefore, it was concluded that NO and KATP may be involved in the anti-thrombotic action of capsaicin.

scholarly journals Prediction of Heparin Induced Thrombocytopenia (HIT) Using a Combination of 4Ts Score and Screening Immune Assays

2020 ◽  
Vol 26 ◽  
pp. 107602962096285
Author(s):  
Rajat Thawani ◽  
Srikant Nannapaneni ◽  
Vivek Kumar ◽  
Phone Oo ◽  
Michael Simon ◽  
...  
Keyword(s):  
High Risk ◽  
Community Hospital ◽  
Antibody Test ◽  
Elisa Test ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
T Score ◽  
Risk Patients ◽  
Immune Assays ◽  
Antibody Tests

Clinical assessment (4Ts) followed by testing for Heparin/platelet factor 4 (HPF4) antibody in intermediate and high risk patients is the standard algorithm of pretest for Heparin induced thrombocytopenia (HIT), and the diagnosis is confirmed by serotonin releasing assay (SRA) in those who have positive antibodies. We conducted a retrospective analysis in a cohort of patients treated in a community hospital who had HIT antibody test by either ELISA or a rapid Particle Immunofiltration Assay (PIFA), regardless of their 4Ts scores. Among 224 patients, 17 had HIT. The PPV for those with a 4 T score ≥4 was 10.4%, which misdianosed 3 patients with HIT who tested positive for antibodies. Combining 4 T score ≥4 AND positive HIT antibody showed a PPV of 20.3% and a sensitivity of 70.6%, misdiagnosing 5 HIT patients. Using 4Ts ≥4 OR positive HIT antibody showed 100% sensitivity and 100% negative predictive value (NPV). The ELISA test had 100% sensitivity and 100% NPV, while the PIFA test missed 2 HIT patients, with sensitivity of 60% and NPV of 96.7%. Our results suggest that SRA testing should be conducted if a patient presents with a 4 T score ≥4 OR a positive HIT antibody, and antibody tests should be conducted for every patient suspected of HIT.

Is Heparin-Induced Thrombocytopenia (HIT) Overdiagnosed by the Conventional EIA Detecting IgG/M/A Antibodies Against Heparin-Platelet Factor 4-Complex? First Experience with the New EIA Detecting Only IgG-Class Antibodies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3208-3208 ◽  
Author(s):  
Frauke Bergmann ◽  
Bruns Christiane ◽  
Groening Arndt
Keyword(s):  
Platelet Aggregation ◽  
Sensitivity And Specificity ◽  
Platelet Activation ◽  
Functional Test ◽  
Thrombosis Prophylaxis ◽  
Functional Assay ◽  
Antigen Test ◽  
Aggregation Assay ◽  
Platelet Factor ◽  
Small Series

Abstract Introduction: If HIT is considered, it should be confirmed or ruled out immediately to guarantee optimal (and low cost) anticoagulation or thrombosis prophylaxis for the patient. When diagnosis is not made, it may cause fatal thromboembolic disease in the patient due to enhanced platelet activation. The pathomechanism is well established: Antibody (ab) binding to heparin/PF4-complex (antigen) forms an immunocomplex. The complex binds to the Fc-Receptor of the platelet membrane resulting in platelet activation and further thrombin generation. Persistent exposure to heparinleads to continuous complex formation. To increase sensitivity and specificity, combination of an antigen test with a functional test is recommended: the antigen-test (EIA) detects ab binding (IgG, IgA und IgM) to heparin/PF4-complex or polyvinylsulfat-complex. Functional tests (HIPA-Test, Serotonin-release test or platelet aggregation studies) detect HIT- ab against different antigens - however, only IgG class. Therefore, the positive predictive value of a functional test is higher than for an antigen test to diagnose HIT. Ab of the IgA and IgM class have no platelet activating capacity and therefore, they are thought to be of minor clinical relevance. Aim of the study: With HIT-IgG-EIA tests approaching the market, the question is, which EIA-test should be performed and will the result change our diagnosis made before by the conventional EIA together with the functional assay and complete clinical data. Material and Methods: We compared the results of 28 out of 85 samples send over a one month period to our lab for HIT-testing. For this study positive or borderline positive samples were selected and only 5 of the negative’s. All samples we run the same day with the conventional EIA (GTI) and later with the ID-PaGIA gel-particle-card (IgG/IgM/IgA) (DIAMED Comp., Suisse) and two different EIA (only IgG) by GTI Diagnostics (Waukesha, WI) and Haemochrom Diagnostica (Essen, Germany). Results: Out of the 28 samples, initially 5 were tested negative, 21 were tested positive (OD 0.5– 3.1, mean OD 1.41; positive if OD >0.4) and 2 being at the cut off. All 5 samples were tested negative in all assays, the 2 borderline samples were tested negative in the other assays. Of the 21 positive. samples 5 were negative by the ID-PaGIA gel-particle-card. Of the 21 positive. samples 13 were positive in the GTI-EIA (IgG only) and 7 in the Haemochrom EIA (IgG only) and 4 out of those had positive functional studies (platelet aggregation assay) - confirming the presence of IgG ab. However, the ID-PaGIA gel-particle-card missed 3 positive samples, when compared to the IgG-only EIAs. Conclusion: As expected there were fewer positive samples in the EIA detecting only IgG class ab, however the comparability of those two EIAs was pure, surprisingly. Further investigation will be done to confirm this observation. Sensitivity and specificity of the ID-PaGIA gel-particle-card is lower then of the EIA. In our small series we could not find an OD-cut-off-point for positive EIA-results (IgG/M/A) in comparison with a positive or negative result for the IgG-EIA. In the future we might add an IgG-only EIA to the established GTI-EIA (IgG/M/A) to our work up and use the clinical scoring system (4T’s) vigorously before the diagnosis HIT will be made, to avoid overdiagnosing patients having positive results in the GTI-EIA (IgG/M/A) due to other underlying clinical conditions.

scholarly journals Assessment of HIT Antibody Complex in Hip Fracture Patients Receiving Enoxaparin or Unfractionated Heparin

2011 ◽  
Vol 17 (6) ◽  
pp. 567-571
Author(s):  
Justin W. Griffin ◽  
William J. Hopkinson ◽  
Michael R. Lassen ◽  
Indermohan Thethi ◽  
Evangelos Litinas ◽  
...  
Keyword(s):  
Hip Fracture ◽  
Elderly Patients ◽  
Unfractionated Heparin ◽  
Standard Of Care ◽  
The Elderly ◽  
Enzyme Linked Immunosorbent Assay ◽  
Platelet Factor ◽  
Surgical Fixation ◽  
Thrombotic Complications ◽  
Antibody Complex

Thromboembolic disease is a common complication of hip fracture in the elderly. Anticoagulants represent a standard of care in preventing postoperative thrombotic complications following surgical fixation. We asked whether levels of antibody to heparin–platelet factor 4 (PF4) complex were differentially present in unfractionated heparin (UFH) versus Enoxaparin, following hip fracture and whether one particular subtype of antibodies was more prevalent. Plasma samples from elderly patients sustaining a hip fracture treated with either enoxaparin or UFH were collected pre- and postoperatively and analyzed using enzyme-linked immunosorbent assay (ELISA) sandwich method for the prevalence of antiheparin-PF4 antibodies and later subtyped. The prevalence of antiheparin-PF4 antibodies was higher in the UFH group especially on postoperative day 7. Patients treated with UFH showed a greater prevalence of antiheparin-PF4 antibodies and a greater prevalence of immunoglobulin G (IgG) subtype. Heparin and enoxaparin are capable of generating heparin-induced thrombocytopenia (HIT) antibodies in elderly patients undergoing orthopedic surgery but perhaps not to the same extent. When comparing low-molecular-weight heparin (LMWH) with UFH, the incidence of new antiheparin-PF4 antibody production is higher in patients treated with UFH.

scholarly journals Proteinase-activated Receptors, Targets for Kallikrein Signaling

2006 ◽  
Vol 281 (43) ◽  
pp. 32095-32112 ◽  
Author(s):  
Katerina Oikonomopoulou ◽  
Kristina K. Hansen ◽  
Mahmoud Saifeddine ◽  
Illa Tea ◽  
Michael Blaber ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Vascular Ring ◽  
Receptor Activation ◽  
Human Platelets ◽  
Aggregation Assay ◽  
Peptide Cleavage ◽  
Mass Spectral ◽  
Proteinase Activated Receptors ◽  
Platelet Aggregation Assay ◽  
Endogenous Regulators

Serine proteinases like thrombin can signal to cells by the cleavage/activation of proteinase-activated receptors (PARs). Although thrombin is a recognized physiological activator of PAR1 and PAR4, the endogenous enzymes responsible for activating PAR2 in settings other than the gastrointestinal system, where trypsin can activate PAR2, are unknown. We tested the hypothesis that the human tissue kallikrein (hK) family of proteinases regulates PAR signaling by using the following: 1) a high pressure liquid chromatography (HPLC)-mass spectral analysis of the cleavage products yielded upon incubation of hK5, -6, and -14 with synthetic PAR N-terminal peptide sequences representing the cleavage/activation motifs of PAR1, PAR2, and PAR4; 2) PAR-dependent calcium signaling responses in cells expressing PAR1, PAR2, and PAR4 and in human platelets; 3) a vascular ring vasorelaxation assay; and 4) a PAR4-dependent rat and human platelet aggregation assay. We found that hK5, -6, and -14 all yielded PAR peptide cleavage sequences consistent with either receptor activation or inactivation/disarming. Furthermore, hK14 was able to activate PAR1, PAR2, and PAR4 and to disarm/inhibit PAR1. Although hK5 and -6 were also able to activate PAR2, they failed to cause PAR4-dependent aggregation of rat and human platelets, although hK14 did. Furthermore, the relative potencies and maximum effects of hK14 and -6 to activate PAR2-mediated calcium signaling differed. Our data indicate that in physiological settings, hKs may represent important endogenous regulators of the PARs and that different hKs can have differential actions on PAR1, PAR2, and PAR4.

scholarly journals Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Liu ◽  
Qiongling Zhang ◽  
Shunli Xiao ◽  
Zhengxiao Sun ◽  
Shilan Ding ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Panax Notoginseng ◽  
Underlying Mechanism ◽  
Cerebrovascular Diseases ◽  
Signal Pathway ◽  
Therapeutic Action ◽  
Aggregation Assay ◽  
Platelet Aggregation Assay ◽  
Calpain 2

XueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of Panax notoginseng roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombosis formation but the underlying mechanism remained unclear. This study aimed to investigate the hypothesis that XST inhibited shear-induced platelet aggregation via targeting the mechanosensitive Ca2+-permeable Piezo1 channel by performing platelet aggregation assay, Ca2+ imaging and Western blotting analysis. Exposure to shear at physiologically (1,000–2000 s−1) and pathologically related rates (4,000–6,000 s−1) induced platelet aggregation that was inhibited by treatment with GsMTx-4. Exposure to shear evoked robust Ca2+ responses in platelets that were inhibited by treatment with GsMTx-4 and conversely enhanced by treatment with Yoda1. Treatment with XST at a clinically relevant concentration (0.15 g L−1) potently inhibited shear-induced Ca2+ responses and platelet aggregation, without altering vWF-mediated platelet adhesion and rolling. Exposure to shear, while resulting in no effect on the calpain-2 expression in platelets, induced calpain-2-mediated cleavage of talin1 protein, which is known to be critical for platelet activation. Shear-induced activation of calpain-2 and cleavage of talin1 were attenuated by treatment with XST. Taken together, our results suggest that XST inhibits shear-induced platelet aggregation via targeting the Piezo1 channel to prevent Piezo1-mediated Ca2+ signaling and downstream calpain-2 and talin1 signal pathway, thus providing novel insights into the mechanism of the therapeutic action of XST on platelet aggregation and thrombosis formation.

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