Tirofiban-induced thrombocytopenia.

Tirofiban is a small non-peptide ligand-mimetic Glycoprotein (GP) IIb/IIIa inhibitor which can reversibly bind to the arginine-glycine-aspartic acid (RGD) recognition site of GP IIb/IIIa to prevent platelet aggregation. It reduces the incidence of thrombotic cardiovascular events in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Although generally considered safe, tirofiban has been reported to be associated with thrombocytopenia in several case reports and clinical trials. The pathogenesis for this adverse reaction is not entirely understood, is thought to be due to immune-mediated reaction. This side effect caused by tirofiban is especially concerning given how frequently it is used in the practice of contemporary cardiovascular care. The present review provides an overview of the pathophysiology, clinical presentation, management, and risk factors associated with tirofiban-induced thrombocytopenia.

Tirofiban-induced thrombocytopenia usually occurred within the first 24 h of treatment, frequently accompanied by bleeding symptoms. The majority of the time, supportive care is used to manage this adverse event, and the platelet count often returns to normal in a few days.Although the exact cause of this adverse response is unknown, it is thought to be due to drug-dependent antibodies that bind to GP IIb/IIIa, presumably after tirofiban-induced conformational change.Age ≥ 65 years, white blood cell ≥ 12 × 10⁹/L, diabetes mellitus, congestive heart failure, and chronic kidney disease were identified as the risk factors for tirofiban-induced thrombocytopenia. Further investigations are needed for this.

Acute profound thrombocytopenia induced by tirofiban in stent assisted embolization of intracranial ruptured aneurysm-a rare case report.

Objectives: Glycoprotein (GP) IIb/IIIa receptor antagonists (Tirofiban) are often used as antiplatelet agents in patients undergoing interventional therapy due to acute coronary syndrome and cerebrovascular diseases. Thrombocytopenia is a common complication of GP IIb/IIIa receptor antagonist, with an incidence of 1%-5%, whereas acute profound thrombocytopenia (platelet count<20 × 109/L) is extremely rare. We reported a case of acute profound thrombocytopenia due to tirofiban treatment to inhibit platelet aggregation during and after surgery in a patient who underwent stent-assisted embolization for ruptured intracranial aneurysm. Case presentation: A 59-year-old female patient, who visited the Emergency Department of our hospital due to sudden headache, vomiting, and unconsciousness for 2 hours. Neurological examination: the patient was unconscious, the pupils on both sides had the same roundness, and the reflection on light was slow. The Hunt-Hess grade was IV. Head CT showed subarachnoid hemorrhage and Fisher's score was 3. We immediately implemented LVIS stent-assisted embolization, intraoperative heparinization, and intraoperative jailing technology to perform dense embolism on aneurysms. The patient was treated with mild hypothermia and Tirofiban 5mL/h intravenous pump. Since then, the patient had developed acute profound thrombocytopenia. Conclusion: We reported a case of acute profound thrombocytopenia due to tirofiban treatment during and after interventional therapy. For patients after unilateral nephrectomy, we should pay more attention to avoid the occurrence of thrombocytopenia caused by abnormal metabolism of tirofiban, although the Laboratory examination showed normal results.

A Double-Blinded Randomized Controlled Trial Comparing Eptifibatide Bolus Only Versus Bolus Plus Infusion In Patients Undergoing Primary Percutaneous Coronary Intervention For ST-Elevation Myocardial Infarction.

BACKGROUNDS: The use of eptifibatide combined with heparin during percutaneous coronary intervention (PCI) in patients presenting with ST-elevation myocardial infarction (STEMI) is recommended to be followed by continuous infusion. Recently, there are some suggestions that using bolus only may be sufficient and cost-effective but randomized trials are lacking. AIMS: The goal of this study was to evaluate these two approaches in a double-blinded randomized control trial. METHODS: The primary PCI patients who received bolus eptifibatide were randomized to 75 mg IV eptifibatide infusion or placebo blindly. The patients were followed up for the primary outcome of vascular or bleeding complications and secondary outcome of ischemic complications. RESULTS: 330 patients (165 from each group) completed the study. The mean age was 57.67 ± 11.53 years and 77.3 % were male. Major bleeding was seen in 1 patient in each group. Hematoma occurred in 8.5 %. The relative risk of hematoma and ecchymosis in bolus plus infusion group to bolus only group were 0.988 (95 % CI: 0.486-2.006) and 1.032 (95 % CI: 0.729-1.459). Multivariate analysis confirmed no significant differences in the bleeding event. Furthermore, there was no significant difference in in-hospital death or any ischemic events. (Cath lab death: 1.4 % in bolus only vs zero % in the control group, p = 0.217, stent thrombosis was seen in one patient in each group). CONCLUSION: There were no differences in the risk of access site ecchymosis, hematoma or major bleeding. Ischemic events and stent thrombosis rates were also similar. Our study suggests that using eptifibatide bolus only during PCI of patients with STEMI is safe and can be cost-saving.

Factors affecting the outcomes of tirofiban after endovascular treatment in acute ischemic stroke: Experience from a single center.

AIMS: To investigate the predicted factors influencing the outcomes in acute ischemic stroke (AIS) patients who received tirofiban after endovascular treatment (EVT) and the optimal administration of tirofiban. METHODS: In this retrospective study, AIS patients who received EVT followed by tirofiban between January 2017 and October 2021 were enrolled. The dose and duration of tirofiban were adjusted by trained clinicians according to the patient's clinical status. A reduction of at least four points on the National Institutes of Health Stroke Scale (NIHSS) after tirofiban compared with that before tirofiban was defined as an effective response. A modified ranking scale (mRS) of 0-2 was defined as a favorable outcome at a 90-day follow-up. RESULTS: A total of 260 consecutive patients were enrolled, and 36.5% of patients achieved a favorable outcome. The modified thrombolysis in cerebral infarction (mTICI) 2b-3 occurred in 93.5% of patients. Symptomatic intracerebral hemorrhage (sICH) occurred in 6.2% of patients, and the mortality at 90-day follow-up was 16.9%. Duration of tirofiban >24 h (adjusted OR: 2.545; 95% CI: 1.008-6.423; p = 0.048) and effective response to tirofiban (adjusted OR: 25.562; 95% CI: 9.794-66.715; p < 0.001) were related to the favorable outcome (mRS 0-2). Higher NIHSS (adjusted OR: 0.855; 95% CI: 0.809-0.904; p < 0.001) and glucose level on admission (adjusted OR: 0.843; 95% CI: 0.731-0.971; p = 0.018) were predictive for the unfavorable outcome (mRS 3-6). CONCLUSIONS: An effective response to tirofiban is an independent factor in predicting the long-term efficacy outcome, and extending the duration of tirofiban is beneficial for neurological improvement.

GP IIb/IIIa Receptor Inhibitors in Mechanically Ventilated Patients with Cardiogenic Shock due to Myocardial Infarction in the Era of Potent P2Y12 Receptor Antagonists.

Objective: To investigate the association between GP IIb/IIIa receptor inhibitors (GPI) and mortality and bleeding in patients with cardiogenic shock (CS) due to myocardial infarction (MI) who were mechanically ventilated on admission. Methods: We retrospectively divided 153 patients into two groups (with or without GPI). Thirty-day and one-year all-cause mortality and bleeding were studied. Results: The observed 30-day and one-year all-cause mortality were similar in both groups [54 (69.2%) with GPI vs. 62 (82.7%) without GPI; p = 0.06, and 60 (76.9%) with GPI vs. 64 (85.3%) without GPI; p = 0.22, respectively]. Patients with GPI suffered fewer unsuccessful PCI (TIMI 0/1 was 10% in the GPI group vs. 57% in the group without GPI), experienced more improvements in TIMI ≥ 1 flow [68 (87.2%) in the GPI group vs. 38 (50.7%) without GPI; p < 0.0001], and they achieved better cerebral performance category (CPC) scores (1.61 ± 0.99 with GPI vs. 2.76 ± 1.64 without GPI; p = 0.005). The bleeding rate was similar in patients with and without GPI [33 (42.3%) vs. 31 (41.3%): p = 1.00], in patients with P2Y12 receptor antagonists (P2Y12) [18 (46.1%) with GPI vs. 21 (46.7%) without GPI; p = 1.00], and in patients with potent P2Y12 [8 (30.8%) with GPI vs. 9 (37.5%) without GPI; p = 0.77]. Conclusions: Due to the study design (limited sample size, retrospective inclusion with high risk of selection bias), our analysis does not allow us to draw conclusions about the effectiveness of GPI in this context. Despite all these limitations, GPI were associated with improved TIMI flow after PCI in our multivariable model without increasing bleeding rates. In addition, better CPC scores were observed, but no association between GPI and outcome was found. Our analysis suggests that selective use of GPI may be beneficial in mechanically ventilated patients with MI in CS without additional bleeding risk, even in the era of potent P2Y12.

Prolonged Use of Tirofiban Infusion Without Percutaneous Coronary Intervention To Achieve Optimal Results in a COVID-19 Positive Patient With Inferior ST Segment Elevated Myocardial Infarction (STEMI) Secondary to Thromboembolism: A Case Report.

Severe acute respiratory syndrome­coronavirus­2 (SARS­CoV­2), responsible for COVID-19, is mainly a respiratory illness, but it can affect other organs also such as heart, kidneys, and liver. Myocardial injury from COVID-19 has been reported in hospitalized patients ranging from pericarditis and myocarditis to acute coronary syndrome (ACS). COVID-19 is highly hypercoagulable state and is associated with both central and peripheral thromboembolism. COVID 19 patients with ACS may not present with classical features of chest pain and electrocardiogram (ECG) is the most important initial investigation in these patients to assess for any ST or T waves changes. COVID-19 patients with cardiac involvement are the most vulnerable group of patients and have increased morbidity and mortality risk. COVID-19 infections can affect the cardiovascular system in patients with or without history of coronary artery disease (CAD), but the risk of type 1 or 2 myocardial infarction (MI), myocardial injury, ST segment elevation, myocarditis, heart failure, cardiogenic shock, and life threatening arrhythmias are more common in the former group. We present a case of 55-year-old patient who presented to our cardiac center with ST elevated myocardial infarction and high blood sugar level. Patient was recently diagnosed with type 2 diabetes mellitus (T2DM) but was not commenced on medications. Echocardiogram showed mildly impaired left ventricular systolic function (LVSF) with inferior wall hypokinesia, and ECG showed inferior leads ST elevation. Coronary angiogram showed severe mid-vessel lesion and occluded posterior left ventricular branch (PLV). Multiple attempts at aspirating the thrombus resulted in thrombolysis in MI grade 2 (TIMI 2) flow in the vessel and patient was commenced on a tirofiban infusion for 72 hours.

Effects of diagnostic ultrasound with cRGD-microbubbles on simultaneous detection and treatment of atherosclerotic plaque in ApoE-/- mice.

Background: Atherosclerotic vulnerable plaque is the leading cause of acute fatal cardiovascular events. Thus, early rapid identification and appropriate treatment of atherosclerotic plaque maybe can prevent fatal cardiovascular events. However, few non-invasive molecular imaging techniques are currently available for the simultaneous detection and targeted treatment of atherosclerotic plaques. We hypothesized that diagnostic ultrasound (DU) combined with cyclic Arg-Gly-Asp-modified microbubbles (MBR) could provide targeted imaging and dissolution of activated platelets to identify advanced atherosclerotic plaques and improve plaque instability. Methods: Three mouse models, apolipoprotein E-deficient mice on a hypercholesterolemic diet (HCD) or normal chow diet and wild-type mice on an HCD were used. The most appropriate ultrasonic mechanical index (MI) was determined based on the expression of GP IIb/IIIa in sham, DU alone and DUMBR-treated groups at MI values of 0.5, 1.5, and 1.9. The video intensity (VI) values, activated platelets and plaque instability were analyzed by ultrasound molecular imaging, scanning electron microscopy and histopathological methods. Results: We found that the VI values of ultrasound molecular imaging of MBR were positively correlated with plaque GP IIb/IIIa expression, vulnerability index and necrotic center / fiber cap ratio. 24 h after treatment at different MIs, compared with those of the other groups, both the VI values and GP IIb/IIIa expression were significantly reduced in MI 1.5 and MI 1.9 DUMBR-treated groups. The plaque vulnerability index and necrotic center / fiber cap ratio were significantly decreased in MI 1.5-treated group, which may be due to targeted dissolution of activated platelets, with a reduction in von Willebrand factor expression. Conclusion: DUMBR targeting GP IIb/IIIa receptors could rapidly detect advanced atherosclerotic plaques and simultaneously give targeted therapy by dissolving activated and aggregated platelets. This technology may represent a novel approach for the simultaneous identification and treatment of atherosclerotic plaques.

Dysregulation in the Expression of Platelet Surface Receptors in Acute Coronary Syndrome Patients-Emphasis on P2Y12.

The pathological conditions caused by blood platelet activation constitute a fundamental core in the pathogenesis of Acute Coronary Syndrome (ACS). The hyperactivity of platelets in ACS is well-documented, but there is still little research into the molecular basis of phenotypic changes in platelet functionality. To expand the knowledge of this phenomenon, we analyzed the disturbances in the expression of several key platelet receptors and the aspect of regulating potential abnormalities. Platelet surface receptors are responsible for maintaining the hemostatic balance, platelet interaction with immune cells, and support of the coagulation cascade leading to occlusion of the vessel lumen. Due to their prominent role, platelet receptors constitute a major target in pharmacological treatment. Our work aimed to identify the molecular alteration of platelet surface receptors, which showed augmented mRNA expression of P2Y12, GP1BB, ITGA2B, and ITGB3 and increased protein concentrations of P2Y12 and GP IIb/IIIa in ACS. The upregulation of the P2Y12 level was also confirmed by confocal and cytometric visualization. Furthermore, we evaluated the expression of two microRNAs: miR-223-3p and miR-126-3p, which were suggested to regulate platelet P2Y12 expression. Results of our study present new insight into the molecular background of ACS.

Pharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens.

Tirofiban is a glycoproteine (GP) IIb/IIIa receptor antagonist, which inhibits platelet-platelet aggregation and is a potential adjunctive antithrombotic treatment in patients with acute coronary syndromes (ACS) or high-risk percutaneous coronary interventions (PCI). It is administered intravenously as a bolus followed by continuous infusion. However, the dosage recommendations in the United States (US) and European Union (EU) differ considerably. Furthermore, in routine clinical practice, deviations from the recommendations may occur. The objective of the present study was to investigate the impact of different alterations on tirofiban plasma concentrations in US and EU administration regimens and to give suggestions for delay management in clinical practice. We therefore mathematically simulated the effects of different bolus-infusion delays and infusion interruptions in different scenarios according to the renal function. Here, we provide a systematic assessment of concentration patterns of tirofiban in the US versus EU dosage regimens. We show that differences between the two regimens have important effects on plasma drug levels. Furthermore, we demonstrate that deviations from the proper administration mode affect the concentration of tirofiban. Additionally, we calculated the optimal dosage of a second bolus to rapidly restore the initial concentration without causing overdosage. In conclusion, differences in tirofiban dosing regimens between the U.S and EU and potential infusion interruptions have important effects on drug levels that may impact on degrees of platelet inhibition and thus antithrombotic effects. Thus, the findings of our modelling studies may help to explain differences in clinical outcomes observed in previous clinical trials on tirofiban.

The effects of estrogen and hormone replacement therapy on platelet activity: a review.

Many studies have shown that an increase in cardiovascular disease in women is related to hormonal changes occurring particularly after menopause with increasing age. While the results of large clinical trials reporting no benefit of hormone replacement therapy (HRT) in cardiovascular disease have been known for some time, there is an increasing body of knowledge regarding the various mechanisms by which estrogen modulates platelet function that could in part explain the higher cardiovascular risk occurring in postmenopausal women and potential benefits of HRT on cardiovascular health. Our review summarizes our current knowledge regarding the effect of endogenous and exogenous estrogen on platelet activity, which can help researchers design future studies. We collected information from 21 peer-reviewed articles published from 1993 to 2021. Studies have indicated that postmenopausal women have higher platelet activity than premenopausal women, which can increase the risk of thrombo-embolic events and cardiovascular disease. Although some studies have reported pro-thrombotic effects of estrogen replacement therapy such as increased platelet activation and adhesion, other studies demonstrated decreased platelet aggregation by inhibiting GP IIb/IIIa receptor expression. This is mediated by estrogen receptors on the platelet membrane in a non-genomic manner and suggests an opportunity for the usage of estrogen replacement therapy with subtle changes in the formulation and route, particularly if started early after menopause. The effect of estrogen on platelet activity is promising as an important factor in reducing the risk of cardiovascular events, warranting further investigation.

GP IIb/IIIa-Mediated Platelet Activation and Its Modulation of the Immune Response of Monocytes Against Candida albicans.

Candida albicans is the most common fungal pathogen in humans, causing invasive disease and even potentially life-threatening systemic infections when tissue homeostasis is disrupted. Previous studies have identified an essential role of platelets in infection and immunity, especially when they are activated. However, it is still unclear whether platelets can be activated by C. albicans, and even less is known about the role of platelets in C. albicans infection. Herein, we showed that C. albicans induced platelet activation in vitro. C. albicans elevated the levels of AKT Ser473 phosphorylation, and inhibition of the PI3K-AKT signaling pathway reversed C. albicans-induced platelet activation. Surprisingly, C. albicans-induced platelet activation occurred in an integrin glycoprotein (GP) IIb/IIIa-dependent manner but was independent of the pattern recognition receptors toll-like receptor (TLR) 2 and TLR4. Interestingly, platelets enhanced the phagocytosis of human monocytes challenged with C. albicans and upregulated the expression of inflammatory cytokines, which were dependent on platelet activation mediated by GP IIb/IIIa. The present work provides new insights into the role of activated platelets in the defense against C. albicans, highlighting the importance of GP IIb/IIIa in the recognition of C. albicans.

Identification of genetic risk factors associated with ischaemic stroke in young Mexican patients.

BACKGROUND: Numerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis. METHODS: We performed a case-control study of consecutive ischaemic stroke survivors aged ≤45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction-restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke. RESULTS: 204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P=.03), tobacco use (P=.02), and the polymorphisms Glu298Asp (genotype: P=.001, allele frequency: P=.001) and C677T (genotype: P=.01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P=.03) and T (P=.01) alleles, hypertension (P=.03), tobacco use (P=.01) and family history of stroke (P=.04) were identified as independent risk factors. CONCLUSION: The polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors.

Effect of GP IIb/IIIa inhibitor duration on the clinical prognosis of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction with no-/slow-reflow phenomenon.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) accompanied by the no-/slow-reflow phenomenon, the maintenance duration of GP IIb/IIIa inhibitor (GPI) is controversial. We compare the efficacy and safety of short- and long-term GPI infusion in STEMI patients with the no-/slow-reflow phenomenon. METHODS: From June 2016 to December 2019, we continuously included patients with on-set STEMI who underwent pPCI, accompanied by the no-/slow-reflow, during interventional procedures at Guangdong Provincial People's Hospital and Zhuhai Golden Bay Hospital. The hemorrhage events, heart function, and major adverse cardiovascular events (MACE) were compared between < 24 h and ≥ 24 h GPI duration groups. The Kaplan-Meier curve was used to estimate the 1-year MACE-free survival at different GPI utility times. RESULTS: In total, 127 patients were divided into two groups based on the duration of tirofiban use (less and more than 24 h). There was no significant difference between two groups in terms of baseline characteristics, plaque condition, and coronary physiological function. The two groups showed similar in-hospital MACE (1 [1.85%] vs. 4 [5.48%], p = 0.394) and 1-year MACE-free survival (log-rank test p = 0.9085). The 1-year MACE remained consistent between the two groups in all subgroups of different risk factors of no-/slow-reflow. There was no significant difference in heart function and in-hospital hemorrhage events (3.7% vs. 1.37%, p = 0.179). CONCLUSION: In the real world, prolonging the duration of GPI may not significantly improve the clinical outcome in patients with STEMI with no-/slow-reflow.

Identificación de factores de riesgo genéticos asociados a la enfermedad vascular cerebral de tipo isquémico en jóvenes mexicanos / Identification of genetic risk factors associated with ischaemic stroke in young Mexican patients

Introducción: Diversos polimorfismos en genes candidatos que codifican proteínas del sistema hemostático se han propuesto como factores de riesgo para el desarrollo de trombosis.MétodosCasos y controles, sobrevivientes de enfermedad vascular cerebral (EVC) isquémica idiopática ≤ 45 años de edad del servicio de neurología incluidos de manera consecutiva de 2006 a 2014. Por PCR-RFLP se identificaron los polimorfismos: Thr325Ile y Ala147Thr del gen de TAFI, 4G/5G del gen de PAI-1, PLA1/A2 del gen de la glucoproteína plaquetaria IIb/IIIa, Glu298Asp del gen de eNOS, y C677T del gen de la 5,10 MTHFR. Se realizó un análisis multivariado de regresión logística para calcular el riesgo independiente de EVC.ResultadosDoscientos cuatro casos y 204 controles pareados por edad y sexo. Se asoció al polimorfismo Glu298Asp (genotipo p = 0,001 y frecuencia alélica p = 0,001), C677T (genotipo p = 0,01), hipertensión (p = 0,03) y tabaquismo (p = 0,02) con la presencia de EVC isquémico, no así para los polimorfismos Ala147Thr, Thr325IIe, 4G/5G y PLA1/A2. Se identificó como factor de riesgo independiente al alelo 298Asp (p = 0,03), T (p = 0,01), hipertensión (p = 0,03), tabaquismo (p = 0,01) y AHFEAT (p = 0,04).ConclusionesLos polimorfismos Glu298Asp y C677T de los genes que codifican a la enzima eNOS y 5,10 MTHFR, tabaquismo, hipertensión y AHFEAT se asociaron a la presencia de EVC isquémico en jóvenes mexicanos, no así el Thr325Ile, Ala147Thr, 4G/5G, PLA1/A2 en genes que codifican proteínas del sistema de fibrinólisis y receptores plaquetarios. (AU)

Introduction: Numerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis.MethodsWe performed a case-control study of consecutive ischaemic stroke survivors aged ≤ 45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction–restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke.Results204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P = .03), tobacco use (P = .02), and the polymorphisms Glu298Asp (genotype: P = .001, allele frequency: P = .001) and C677T (genotype: P = .01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P = .03) and T (P = .01) alleles, hypertension (P = .03), tobacco use (P = .01) and family history of stroke (P = .04) were identified as independent risk factors.ConclusionsThe polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors. (AU)

Immunization against αIIb ß3 and αv ß3 in Glanzmann thrombasthenia patients carrying the French Gypsy mutation.

Essentials The c.1544+1G>A mutation was identified in Gypsy Glanzmann thrombasthenia (GT) patients. Gypsy GT patients express normal αv ß3 carrying HPA-1b epitopes. To demonstrate HPA-1a alloimmunization by modified antigen capture assays. Gypsy GT patients could develop anti-HPA-1a alloantibodies against ß3 and αv ß3 . ABSTRACT: Background Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by the absence or the dysfunction of the platelet αIIb ß3 integrin. A founder mutation in the ITGA2B gene was previously identified in French Gypsy patients. Interestingly, this mutation was strongly linked to the human platelet antigen-1b (HPA-1b). The HPA-1bb Gypsy patients are at risk of isoimmunization against αIIb ß3 , as this complex is not expressed at their platelet surface. Tentatively, they would, however, not have an increased risk of developing anti-HPA-1a alloantibodies by exposure of αIIb ß3 on platelets from random platelet transfusions. However, the ß3 chain can also associate with the αv subunit expressed at the platelet surface. Because Gypsy GT patients express normal αv ß3 carrying HPA-1b epitopes, these patients might develop anti-HPA-1a alloantibodies reacting with αv ß3 and/or ß3 . Objectives/Patients/Methods To demonstrate this hypothesis, sera from HPA-1bb (n = 5) and HPA-1ab (n = 1) Gypsy GT patients were investigated by modified antigen capture assay using platelets or stable transfected cells. Furthermore, stable transfected cells expressing either αIIb ß3 or αv ß3 together with soluble monomeric chimeric ß3 (as absorbent) were used to differentiate anti-ß3 and anti-αv ß3 reactivity. Results Only HPA-1bb patients developed alloantibodies reacting with HPA-1a cells. Further analysis showed that HPA-1bb patients developed anti-HPA-1a alloantibodies reacting with ß3 and/or αv ß3 . Conclusion In this study, we found that HPA-1bb patients who failed to express αIIb ß3 on the platelet surface can develop alloantibodies against HPA-1a reacting with ß3 as well as αv ß3 . This is of particular importance as anti-HPA-1a alloantibodies might cause fetal neonatal alloimmune thrombocytopenia and/or platelet transfusion refractoriness.

Relationship of Platelet Glycoprotein IIb/IIIa and CD62P With Hypercoagulable State After Oncologic Surgery.

The biomarkers for predicting venous thromboembolic events (VTEs) after oncologic surgery are still lacking. The current study aimed to analyze the relationships of CD62P and GP IIb/IIIa with hypercoagulation after oncologic surgery. A total of 76 patients with primary abdominopelvic tumors in our hospital were enrolled. The patients were divided into groups A (malignancy with no VTE group), B (malignancy with VTE group), and C (benign with no VTE group). Twenty healthy volunteers were selected as control. The plasma CD62P (4.69 ± 2.55 vs. 1.76 ± 0.48) and the GP IIb/IIIa (9.28 ± 3.79 vs. 1.76 ± 0.48) levels in group A were significantly higher than those in the control group preoperatively. The CD62P (31.46 ± 17.13 vs. 13.51 ± 7.43, P < 0.05), GP IIb/IIIa (42.33 ± 21.82 vs. 13.51 ± 7.43, P < 0.05), and D-dimer (7.33 ± 2.34 vs. 2.03 ± 0.55, P < 0.05) levels in group B were markedly higher 7 days after operation compared with those in group A. The CD62P and the GP IIb/IIIa exhibited a positive correlation with the hypercoagulable state after oncologic surgery.

Intra-Arterial Glycoprotein IIb/IIIa Inhibitor Treatment for Symptomatic Intracranial Atherosclerotic Stenosis Presenting as Large Vessel Occlusions.

Introduction There is no consensus on the optimal treatment for acute ischemic stroke (AIS) large vessel occlusions (LVOs) or near-occlusions with underlying intracranial atherosclerotic stenosis (ICAS). We report the first American series using intra-arterial (IA) glycoprotein IIb/IIIa inhibitors (GPIs) as a stand-alone revascularization technique for ICAS presenting with large vessel ischemic syndromes. Methods Records at two centers of 140 patients presenting with AIS undergoing stroke intervention from January 2017 to June 2019 were retrospectively reviewed. Patients treated with IA GPIs were identified, and baseline factors, imaging, procedural characteristics, hospital course, and outcomes were collected. Six patients with ICAS underlying their acute symptomatic near occlusion or LVO were treated with IA GPI. Four near-occlusions were treated with IA GPI as the first-line therapy, while two LVOs were treated with IA GPI as an adjunct therapy to thrombectomy. Results The mean age was 61.3 years (range 36-79), presentation National Institute of Health Stroke Scale (NIHSS) was 10 (4-18), time from last seen well to treatment was 434.5 minutes (164-1290), and time from groin puncture to revascularization was 67.3 minutes (26-94). Three patients received intravenous (IV) tissue plasminogen activator (tPA), and all patients received an IA weight-based GPI infusion. Five patients had thrombolysis in cerebral ischemia (TICI) 3, and one patient had TICI 2b. The mean discharge NIHSS was 2.5 (0-8). The mean modified Rankin scale was 1.3 (range 0-4) at discharge and .8 at three months. No patients had a postprocedural symptomatic hemorrhage. Conclusion Our results highlight the utility of IA GPI administration as the first-line therapy for symptomatic ICAS near occlusions or as a rescue technique after failed thrombectomy for LVO patients suspected of underlying ICAS.

An Unusual Case of Drug-Induced Thrombocytopenia.

Drug-induced thrombocytopenia (DIT) is a differential diagnosis for consideration when acute thrombocytopenia is encountered in the outpatient or inpatient setting. The mechanism of thrombocytopenia induced by different antiplatelet therapies varies. DIT may occur due to antibody formation following the exposure to a drug, or naturally occurring preexisting antibodies may produce rapid-onset thrombocytopenia when a drug molecule binds to a platelet receptor inducing a conformational change thus rendering it to be an antigen target for naturally occurring antibodies. A 66-year-old female with history of hypertension presented with non-ST elevation myocardial infarction, had drug eluting stent placed in first obtuse marginal artery of left circumflex coronary artery. Started on antiplatelet medications aspirin 81 mg, ticagrelor 90 mg (which was later transitioned to clopidogrel 75 mg), as well as tirofiban 12.5 mg (for 12 hours only). Tirofiban is a GP IIb/IIIa antagonist, other drugs in this class have been documented to induce thrombocytopenia as well, but rates for tirofiban appear to be the highest, the reason is unclear. These antibodies are thought to be either naturally occurring or induced from conformational changes to GP IIb/IIIa binding site after binding to the GP IIb/IIIa receptor, binding of these drugs to the receptor precipitates an epitope much more specific for platelet surface antigens. Tirofiban and clopidogrel/ticagrelor can cause thrombocytopenia, but onset in this case is unusual: acute antibody reaction would be expected within hours, not delayed 30 hours after starting antiplatelet medication, and nonacute reaction would present 1 to 2 weeks out.

Intravenous Administration of Standard Dose Tirofiban after Mechanical Arterial Recanalization is Safe and Relatively Effective in Acute Ischemic Stroke.

To investigate the safety and efficacy of intravenous administration of a standard dose of glycoprotein-IIb/IIIa inhibitor tirofiban after vessel recanalization by mechanical thrombectomy in acute ischemic stroke. A consecutive series of patients (n=112) undergoing endovascular ischemic stroke intervention therapy were enrolled. 81 patients were eligible for intravenous (IV) tirofiban treatment for 24 hours after mechanical thrombectomy. The incidence of symptomatic intracranial hemorrhage (sICH), death, National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) were assessed. In the 81 patients receiving tirofiban, 52 patients (64.2%) were treated with IV rt-PA before mechanical thrombectomy. sICH was found in 2 (2.5%) patients with no fatal ICH. Four patients died during 3 months after stroke onset. Successful recanalization with thrombolysis in cerebral infarction (TICI) score ≥2b was achieved in 75 of 81 patients (92.6%) after mechanical thrombectomy. The average number of passes with Solitaire stent retriever was 1.3. At 3 months, 55 of 81 patients (67.9%) had favorable outcomes (mRS<=2). The intravenous application of a standard dose of tirofiban post-Solitaire stent retriever thrombectomy and intravenous thrombolysis appears to be safe and relatively effective in acute ischemic stroke.

Safety and efficacy of Tirofiban in STEMI-patients.

BACKGROUND: Tirofiban is recommended as bail out therapy in patients with ST-elevation myocardial infarction (STEMI). However, evidence regarding safety and efficacy of tirofiban is unclear. Tirofiban has been shown to improve ST-resolution, to decrease infarct size (IS) and to reduce incidence of major adverse cardiac and cerebrovascular events (MACCE). However, bleeding is enhanced in tirofiban treated patients. In this study, we aim to investigate efficacy and safety of Tirofiban in STEMI-patients. METHODS: 610 STEMI patients were analyzed. MACCE (death, myocardial infarction [MI], stroke) and TIMI bleeding events were registered during hospital course and 12 month follow-up. RESULTS: Tirofiban patients were slightly younger (tirofiban 63 ±â€¯13 years vs. control 65 ±â€¯14 years; p = 0.04). They had higher peak-high-sensitive troponin T [Hs-TnT] (tirofiban 6561 ±â€¯11,065 vs. control 4594 ±â€¯11,200, p-value = 0.047) and peak-creatine kinase [CK] (tirofiban 2742 ±â€¯5097 vs. control 1416 ±â€¯2160, p-value < 0.0001). Percutaneous coronary intervention (PCI) was more complex in tirofiban treated patients as radiation time (tirofiban 18 ±â€¯15 vs. control 14 ±â€¯13; p-value = 0.02) and use of contrast agent (tirofiban 240 ±â€¯106 vs. control 209 ±â€¯99; p-value = 0.01) was higher in tirofiban patients. However, there were no differences in MACCE (HR 0.877, 95% CI 0.62-1.25, p = 0.47) and bleeding (major: HR 1.494, 95% CI 0.65-3.44, p = 0.34; minor: HR 1.294, 95% CI 0.67-2.52, p = 0.45). CONCLUSION: MACCE and bleeding events were similar. However, PCI was more complex and infarcts larger in tirofiban treated patients.