Platelet Glycoprotein IIb Research Articles

PB0411 Platelet Glycoprotein IIb- and IIIa Levels are Altered in Persistently Lupus Anticoagulant Positive Patients with a History of Thrombosis

PB0411 Platelet Glycoprotein IIb- and IIIa Levels are Altered in Persistently Lupus Anticoagulant Positive Patients with a History of Thrombosis

The role of platelet glycoprotein IIb / IIIa inhibitors in current treatment of acute coronary syndrome.

Current management of patients with acute coronary syndrome (ACS) includes a dual antiplatelet therapy with acetylsalicylic acid and a platelet P2Y12 receptor inhibitor. For patients without a high risk of bleeding, prasugrel and ticagrelor are preferred, since their effect is more pronounced, less dependent on metabolism of a specific patient, and occurs faster that the effect of clopidogrel. The prescription rate of platelet glycoprotein IIb/IIIa (GP IIb / IIIa) receptor inhibitors has considerably decreased. However, these drugs remain relevant in percutaneous coronary interventions in patients with a high risk of coronary thrombosis or a massive coronary thrombus, in thrombotic complications of the procedure, and in the "no-reflow" phenomenon. The intravenous route of GP IIb / IIIa inhibitor administration provides their effectiveness in patients with difficulties of drug intake or with impaired absorption of oral medications. This review presents clinical and pharmacological characteristics of various GP IIb / IIIa inhibitors and data of randomized clinical studies and registries of recent years that evaluated results of their use in patients with ACS.

Селекция аптамеров к тромбоцитам с применением цифровой эмульсионной ПЦР

The aim of the research. To obtain aptamers-inhibitors of platelet glycoprotein IIb / IIIa receptors, blocking platelet aggregation. Material and methods. Th e selection of aptamers for IIb / IIIa receptors of platelets was carried out according to the SELEX method (Systematic Evolution of Ligands by Exponential Enrichment), modifi ed to select aptamers for a specifi c epitope. Th e method allows selection and in vitro evolution of aptamers with selectivity to a specifi c target from a large library of oligonucleotides. Th e affi nity of aptamers for platelet IIb / IIIa receptors was determined using fl ow cytometry. Results. Pools of aptamers of aptamers with high affi nity for IIb / IIIa platelet receptors were obtained. Th e study of the antiaggregation properties of the pools with the best binding showed that platelet aggregation was minimal when using the aptamers from the pool of the 5th round of selection. Th us, the aptamers of this pool have the greatest potential to be used as an analogue of a synthetic peptide that blocks thromboaggregation. Aptamers from this pool were taken for sequencing in order to obtain sequences of aptamers with the best antiaggregatory properties. Conclusion. Pools of aptamers with high affi nity for IIb / IIIa receptors of platelets and anticoagulant activity were obtained.

GG Polymorphism of Platelet ITGA2B Gene Increases the Magnitude of Interleukin-6 Release after Cardiopulmonary Bypass

Objective: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response which is thought to be a significant cause of postoperative organ dysfunction and mortality. In this study we aimed to investigate the effect of ITGA2B (integrin alpha 2b, platelet glycoprotein IIb of IIb/IIIa complex) gene polymorphism on the magnitude of inflammatory response after CPB

Dealing with prognostic signature instability: a strategy illustrated for cardiovascular events in patients with end-stage renal disease.

BackgroundIdentification of prognostic gene expression markers from clinical cohorts might help to better understand disease etiology. A set of potentially important markers can be automatically selected when linking gene expression covariates to a clinical endpoint by multivariable regression models and regularized parameter estimation. However, this is hampered by instability due to selection from many measurements. Stability can be assessed by resampling techniques, which might guide modeling decisions, such as choice of the model class or the specific endpoint definition.MethodsWe specifically propose a strategy for judging the impact of different endpoint definitions, endpoint updates, different approaches for marker selection, and exclusion of outliers. This strategy is illustrated for a study with end-stage renal disease patients, who experience a yearly mortality of more than 20 %, with almost 50 % sudden cardiac death or myocardial infarction. The underlying etiology is poorly understood, and we specifically point out how our strategy can help to identify novel prognostic markers and targets for therapeutic interventions.ResultsFor markers such as the potentially prognostic platelet glycoprotein IIb, the endpoint definition, in combination with the signature building approach is seen to have the largest impact. Removal of outliers, as identified by the proposed strategy, is also seen to considerably improve stability.ConclusionsAs the proposed strategy allowed us to precisely quantify the impact of modeling choices on the stability of marker identification, we suggest routine use also in other applications to prevent analysis-specific results, which are unstable, i.e. not reproducible.

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome.

Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations. Prospective study at Emergency Unit, Heart Institute (InCor), University of São Paulo. Intrahospital evolution and platelet aggregation in response to tirofiban were analyzed in relation to four glycoprotein mutations in 50 patients indicated for percutaneous coronary intervention: 17 (34%) with unstable angina and 33 (66%) with non-ST-segment elevation myocardial infarction. Platelet aggregation was analyzed using the Born method. Blood samples were obtained before and one hour after tirofiban infusion. Glycoproteins Ia (807C/T ), Ib (Thr/Met) , IIb (Ile/Ser ) and IIIa (PIA ) were the mutations selected. Hypertension, dyslipidemia, diabetes, smoking, previous coronary artery disease and stroke were similar between the groups. Mutant glycoprotein IIIa genotypes had lower platelet aggregation before tirofiban administration than that of the wild genotype (41.0% ± 22.1% versus 55.9% ± 20.8%; P = 0.035). Mutant glycoprotein IIIa genotypes correlated moderately with lower platelet inhibition (r = -0.31; P = 0.030). After tirofiban administration, platelet glycoprotein Ia, Ib, IIb and IIIa mutations did not influence the degree of inhibition of platelet aggregation or intrahospital mortality. Mutations of glycoproteins Ia, Ib, IIb and IIIa did not influence platelet aggregation in response to tirofiban in patients with unstable angina and non-ST-segment elevation myocardial infarction.

Abstract 19565: The Safety and Efficacy of Platelet Glycoprotein Iib Iiia Antagonist by Intracoronary Administration versus Intravenous Administration in Patients With St Segment Elevation Myocardial Infarction: A Meta-analysis

Objective: Evaluate the administration (IC) and intravenous(IV) administration of platelet glycoprotein IIb / IIIa antagonist in STEMI patients. Methods: We searched PubMed, EMBASE, Web of Science, the Chinese Biomedical Medical Literature database, and the Cochrane Library, the retrieval time is May 2015. The papers which compared the safety and efficacy of IC and IV STEMI patients with platelet glycoprotein IIb / IIIa antagonist were included.Two researchers evaluated the trails and collected data according to 5.0.2 Cochrane Handbook. The data were merged by RevMan 5.0 software. Results: Finally we included 17 RCTs(n=8279, including 4260 IC administration patients, and 4019 IV administration patients). The GP IIb / IIIa antagonist was injected in the coronary after stent releasing during PCI in the IC group. Meta analysis showed: In the STEMI trials, intracoronary group had better clinical outcomes than intravenous group in the following index: short time MACE (one month after PCI) [OR=0.47,95%CI:0.23-0.97], congestive heart failure [OR=0.59,95%CI:0.41-0.84], left ventricular ejection fraction [MD=1.11, 95%CI: 0.48-1.74], infarct size [MD=-1.00, 95%CI: -1.65~ -0.35], myocardial blush grade 3 [OR=1.60, 95%CI: 1.12-2.27], drug occupational rate [OR=4.16, 95%CI: 1.45-11.92], wall motion score index[MD=-0.27,95%CI: -0.51~ -0.03]. And the IC and IV group were similar in the death, long time MACE(1 year after PCI), stent thrombosis, sever bleeding, ST-segment resolution -1 month after PCI, target vessel revascularization, myocardial infarction recurrence, TIMI grade 3 after PCI, left ventricular end systolic volume, left ventricular end diastolic volume, intervention success rate, life threatening arrhythmia, stroke after PCI, CK-MB, operation time, E/ A, cardiac death, minor bleeding, with no significant difference (P> 0.05). Conclusions: This updated meta-analysis shows, compared to the IV, IC administration of platelet glycoprotein IIb / IIIa antagonist could reduce the risk of short time MACE (one month after PCI), congestive heart failure, and improve left ventricular ejection fraction, so IC administration of platelet glycoprotein IIb / IIIa antagonist could be a considerable way to be used in STEMI patients.

Platelets are associated with xenograft tumor growth and the clinical malignancy of ovarian cancer through an angiogenesis-dependent mechanism.

Platelets are known to facilitate tumor metastasis and thrombocytosis has been associated with an adverse prognosis in ovarian cancer. However, the role of platelets in primary tumour growth remains to be elucidated. The present study demonstrated that the expression levels of various markers in platelets, endothelial adherence and angiogenesis, including, platelet glycoprotein IIb (CD41), platelet endothelial cell adhesion molecule 1 (CD31), vascular endothelial growth factor (VEGF), lysyl oxidase, focal adhesion kinase and breast cancer anti-estrogen resistance 1, were expressed at higher levels in patients with malignant carcinoma, compared with those with borderline cystadenoma and cystadenoma. In addition, the endothelial markers CD31 and VEGF were found to colocalize with the platelet marker CD41 in the malignant samples. Since mice transplanted with human ovarian cancer cells (SKOV3) demonstrated elevated tumor size and decreased survival rate when treated with thrombin or thrombopoietin (TPO), the platelets appeared to promote primary tumor growth. Depleting platelets using antibodies or by pretreating the cancer cells with hirudin significantly attenuated the transplanted tumor growth. The platelets contributed to late, but not early stages of tumor proliferation, as mice treated with platelet-depleting antibody 1 day prior to and 11 days after tumor transplantation had the same tumor volumes. By contrast, tumor size in the early TPO-injected group was increased significantly compared with the late TPO-injected group. These findings suggested that the interplay between platelets and angiogenesis may contribute to ovarian cancer growth. Therefore, platelets and their associated signaling and adhesive molecules may represent potential therapeutic targets for ovarian cancer.

The Zinc Finger Transcription Factor (Growth Factor Independence 1b) Gfi1b Regulates Megakaryocyte Proliferation and Their Ability To Produce and Release Platelets

Under normal conditions, humans maintain a blood content of 150-400 x 109 platelets per liter, whereas mice can reach 1000 x 109 platelets per liter. Thrombocytopenia occurs when the level of platelets becomes too low, a situation that increases the risk of spontaneous bleeding and hemorrhage. Although the number of platelets is continuously very high, they are produced by a rare cell population the megakaryocytes (MKs), which in turn are produced by megakaryocyte-erythrocyte precursors (MEPs) in the bone marrow. The first report of a potential role for the zinc finger transcription factor Gfi1b in megakarypoiesis and thrombopoiesis showed that the full knock-out of this gene in mice leads to a severe impairment of both erythropoiesis and megakaryopoiesis, translating into a severe thrombocytopenia and a lethality by day e15.5 (Saleque et al Genes Dev 2002). Because of this developmental arrest at mid-gestation, the function of Gfi1b in adult differentiated hematopoietic cells could not be analyzed. We have thus generated conditionally deficient mice carrying floxed Gfi1b alleles, to study the role of Gfi1b in adult hematopoiesis. To ablate Gfi1b expression, we crossed Gfi1b flox/flox mice with animals carrying two different Cre transgenes: a ROSA-Cre-ERT2 transgene that quickly deactivates Gfi1b in all cells upon treatment with tamoxifen, allowing to almost instantly measure effects on already differentiated MKs and ii) a PF4-Cre transgene that constitutively expresses the Cre specifically in MKs, excluding any adverse effects due to other cell types.With these mice, we could show that Gfi1b ablation leads to a strong proliferation and expansion of both MEPs, MK precursors and MKs, which was surprisingly associated with an almost complete loss of platelets (∼99.9% reduction compared to controls in PF4-Cre, Gfi1bflox/flox mice). Most striking was the strong increase in the number of MKs, even from an early stage of differentiation, when Gfi1b was deleted. It was not clear, however, if this expansion of MKs was caused directly by the loss of Gfi1b in early progenitors, or if it was a consequence of the severe thrombocytopenia that could stimulate megakaryopoiesis through a feedback loop. An in vivo kinetic study of platelet loss and MK proliferation in the ROSA-Cre-ERT2, Gfi1bflox/flox mice revealed that the expansion of MKs started as early as 3 days after administration of tamoxifen (over 4-fold increase compared to age matched controls). On the other hand, platelet counts started only to decrease noticeably 4 days after tamoxifen administration (about 400 x 109/L vs 1200 x109/L), although reticulated platelets started to decrease as early as day 2 after tamoxifen injection and almost completely disappeared by day 4 after tamoxifen treatment. This suggests an arrest in platelet release in the absence of Gfi1b. After 4 days of tamoxifen treatment, platelet counts decreased quickly to reach a minimum around day 7-8 (60 x 109/L vs 1350 x 109/L in controls). By this time, the number of MKs literally exploded to reach levels up to 15 fold higher than in wild type controls. These results indicate that the number of MKs increases prior to the decrease in circulating platelet when Gfi1b is deleted. However, the results may also suggest that a feedback loop could contribute to this phenomenon by boosting MK expansion upon platelet loss. A platelet lifespan analysis on the rare remaining platelets in PF4-Cre, Gfi1bflox/flox mice revealed that the low platelet level was not due to accelerated platelet clearance, confirming that the platelet loss was the result of an arrest in platelet release. Gfi1b deficient MKs are still polyploidy, but are significantly smaller and have a different nuclear cytoplasmic ratio than their wt counterparts. In addition, in contrast to normal wt MKs, Gfi1b deficient MKs were unable to properly spread or migrate on fibronectin or fibrinogen surfaces, showed lower F-actin content and an increased expression of the platelet glycoprotein IIb of IIb/IIIa complex (CD41/CD61) on their surface. These data suggest that Gfi1b controls the signaling of the platelet specific integrins to restrict MK proliferation, control MK size and their ability to produce platelets. Disclosures:No relevant conflicts of interest to declare.

C0166 The relationship between platelet glycoprotein IIb RS5911 polymorphism and inflammation in COPD patients

C0166 The relationship between platelet glycoprotein IIb RS5911 polymorphism and inflammation in COPD patients

C0406 The relationship platelet glycoprotein IIb rs 5911 polymorphism and prognostic parameters in female Turkish patients with breast cancer

Breast cancer is one of the most common malign tumours all over the world, and it accounts for about 30% of all cancer in women. Platelet adhesive receptors play a key role in adhesive interactions necessary for tumoral invasion and metastasis. Several polymorphisms affect these molecules. There is no study on the relationship between ITGA2B rs 5911 polymorphism and breast cancer prognostic parameters in Turkish patients with breast cancer. The aim of the study is to determine if there is polymorphism rs5911 ITGA2B gene in Turkish patients with breast cancer and to investigate the correlation between conventional clinicopathological features and gene polymorphism.

Platelet Glycoprotein IIb HPA-3 a/b Polymorphism Is Associated with Native Arteriovenous Fistula Thrombosis in Chronic Hemodialysis Patients

Objective: The aim of this study was to investigate the association of Glycoprotein IIb (GPIIb) human platelet antigen-3 (HPA-3) a/b polymorphism with end-stage renal disease (ESRD) on hemodialysis (HD) and native Arteriovenous fistula (AVF) thrombosis. Methods: The polymorphism in the GPIIb subunit of the receptor HPA-3 (a and b alleles) was identified by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 145 HD patients and 120 healthy controls from a Chinese Han population. The HD patients were classified into two groups: G1 and G2. G1 included 65 HD patients presented at least one AVF thrombosis episode and G2 included 80 HD patients without any episode of AVF thrombosis. Results: There were no significant differences in either HPA-3 a/b genotypes (aa, ab, and bb) frequency distribution (p = 0.396) or allele (a and b) frequency distribution (p = 0.146) between HD patients and control groups. However, there were significant differences in both HPA-3 a/b genotypes (aa, ab, and bb) distribution (χ2 = 6.127, p = 0.047) and allele (a and b) frequency distribution (χ2 = 5.954, p = 0.015) between G1 and G2. The relative risk of native AVF dysfunction in ab + bb patients compared with that of aa patients was 2.31 (95% confidence interval: 1.18–4.52). Conclusions: These findings suggest an association between AVF thrombosis and the HPA-3b allele, and it is likely that HPA-3 a/b polymorphisms could be useful markers for potential risk of native AVF thrombosis in HD patients.

Platelet proteome in healthy volunteers who smoke

Smoking accelerates atherosclerosis and is a well-known risk factor for acute cardiovascular complications; however, the mechanisms of these effects have not been completely clarified. Recently developed proteomic approaches may offer new clues when combined with well-established functional tests. Platelet proteome of healthy smokers and non-smokers was resolved by two-dimensional difference gel electrophoresis, compared by Decyder software and identified by mass spectrometry analysis (nano-LC-MS/MS). In smokers, three proteins (Factor XIII-A subunit, platelet glycoprotein IIb and beta-actin) were significantly up-regulated, whereas WDR1 protein and chaperonine HSP60 were down-regulated. Furthermore, the highest scored network derived by Ingenuity Pathway Analysis using the modulated proteins as input showed the involvement of several proteins to be related to inflammation and apoptosis. Platelet function tests and the levels of markers of platelet and leukocyte activation were not different in smokers vs. non-smoker subjects. The platelet proteomic approach confirms that cigarette smoking triggers several inflammatory reactions and may help clarify some of the molecular mechanisms of smoke effect on cellular systems relevant for vascular integrity and human health.

The ARIC Carotid MRI Study of Blood Cellular Markers: An Inverse Association of Monocyte Myeloperoxidase Content With Peripheral Arterial Disease

We evaluated the association of blood monocyte and platelet activation markers with the risk of peripheral artery disease (PAD) in a multicenter study of atherosclerosis among African American and Caucasian patients. Flow cytometric analysis of blood cells was performed in 1791 participants (209 cases with PAD and 1582 noncases) from the cross-sectional Atherosclerosis Risk in Communities Carotid Magnetic Resonance Imaging ([MRI] ARIC Carotid MRI) Study to assess platelet glycoproteins IIb and IIIa, P-selectin, CD40 ligand, platelet-leukocyte aggregates, monocyte lipopolysaccharide receptor, toll-like receptors (TLRs) 2 and 4, P-selectin glycoprotein ligand 1, cyclooxygenase 2, and myeloperoxidase. Multivariate regression analyses evaluated the association of cellular markers with the risk of PAD. After adjusting for age, race, and gender, platelet CD40L, and monocyte myeloperoxidase (mMPO) levels were significantly lower (P < .001), and monocyte TLR-4 levels were higher (P = .03) in patients with PAD. With additional adjustments for conventional risk factors, mMPO remained inversely and independently associated with the risk of PAD (odds ratio [OR]: 0.35, P = .01).

Safety and feasibility of intraarterial eptifibatide as a revascularization tool in acute ischemic stroke

Experience with the use of platelet glycoprotein (GP) IIb-IIIa inhibitor eptifibatide in patients with ischemic stroke is limited. The authors report the off-label use of intraarterial eptifibatide during endovascular ischemic stroke revascularization procedures for reocclusion after documented recanalization or formed fresh thrombi in distal vessels that were inaccessible to endovascular devices. Patients who received intraarterial eptifibatide were identified from a prospectively collected database of patients in whom endovascular revascularization for acute ischemic stroke was attempted between 2005 and 2008. Data were analyzed retrospectively. The intraarterial eptifibatide dose was a single-bolus dose of 180 μg/kg body weight. Primary outcome measures were angiographic recanalization (Thrombolysis in Myocardial Infarction Grade 2 or 3), symptomatic intracranial hemorrhage rate, overall mortality rate, and favorable 3-month modified Rankin Scale score (≤ 2). The study included 35 patients (mean age 62 years, range 18-85 years). The median presenting National Institutes of Health Stroke Scale score was 13. Two patients received intravenous tissue plasminogen activator before endovascular therapy. The median time from symptom onset to therapy initiation was 230 minutes (range 90-1370 minutes). Twelve patients (34%) received intraarterial tissue plasminogen activator without mechanical measures. Mechanical revascularization measures used were Merci retriever in 19 (54%), Penumbra device in 1 (3%), balloon angioplasty in 15 (43%), and stent placement in 22 (63%) patients. The mean dose of intraarterial eptifibatide was 11.6 mg (range 5-16.6 mg). Partial-to-complete recanalization (Thrombolysis in Myocardial Infarction Grade 2 or 3) was achieved in 27 patients (77%). Postprocedure intracranial hemorrhage occurred in 13 patients (37%), causing symptoms in 5 (14%). In the 5 symptomatic intracranial hemorrhage cases, all patients but one presented more than 8 hours after symptom onset and all received intraarterial recombinant tissue plasminogen activator. The median discharge National Institutes of Health Stroke Scale score was 7 (range 0-17). At 3 months postprocedure, 21 patients (60%) had a modified Rankin Scale score ≤ 2, and 8 patients (23%) had died. Adjunctive intraarterial eptifibatide is a feasible option for salvage of reocclusion and thrombolysis of distal inaccessible thrombi during endovascular stroke revascularization. Its safety and efficacy need to be studied further in larger, multicenter, controlled studies.

Associations between dietary patterns and flow cytometry-measured biomarkers of inflammation and cellular activation in the Atherosclerosis Risk in Communities (ARIC) Carotid Artery MRI Study

BackgroundSpecific foods and overall dietary patterns are associated with soluble biomarkers of systemic inflammation and endothelial activation. However, no large epidemiological studies have evaluated relationships between such dietary factors and cell-specific markers of activation and inflammation as measured by flow cytometry. MethodsCell aggregates and multiple platelet and leukocyte markers were quantified by flow cytometry in fresh whole blood from 1101 white adults participating in the Carotid Artery MRI Study, a subset of the larger Atherosclerosis Risk in Communities (ARIC) Study. Two dietary patterns (“Healthy” and “Western”) were empirically derived via principal components analysis using data collected by food frequency questionnaire. Cross-sectional associations between dietary patterns and flow cytometry-measured biomarkers were evaluated, adjusting for demographics and lifestyle factors, including medications use. ResultsAfter multivariable adjustment, monocyte lipopolysaccharide receptor (CD14), monocyte toll-like receptor-2, and platelet glycoprotein IIb (CD41) showed inverse associations with the Healthy dietary pattern (p=0.01, 0.04, and 0.01, respectively). In contrast, the Western dietary pattern was positively associated with CD41 and platelet–granulocyte aggregates (p=0.01 and 0.04, respectively). Independent of other dietary factors, alcohol consumption was inversely associated with levels of pan-leukocyte marker (CD45), P-selectin (CD62P) on PLA1 and on PLA2 platelets, and platelet–monocyte, platelet–granulocyte, and platelet–lymphocyte aggregates. ConclusionDietary patterns and alcohol intake were each cross-sectionally associated with select markers of cellular activation and inflammation measured by flow cytometry. These data are consistent with the hypothesis that holistic measures of dietary intake are associated with inflammation.

Functional genomics in zebrafish permits rapid characterization of novel platelet membrane proteins

AbstractIn this study, we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for functional screening of novel platelet genes in vivo by reverse genetics. Comparative transcript analysis of platelets and their precursor cell, the megakaryocyte, together with nucleated blood cell elements, endothelial cells, and erythroblasts, identified novel platelet membrane proteins with hitherto unknown roles in thrombus formation. We determined the phenotype induced by antisense morpholino oligonucleotide (MO)–based knockdown of 5 of these genes in a laser-induced arterial thrombosis model. To validate the model, the genes for platelet glycoprotein (GP) IIb and the coagulation protein factor VIII were targeted. MO-injected fish showed normal thrombus initiation but severely impaired thrombus growth, consistent with the mouse knockout phenotypes, and concomitant knockdown of both resulted in spontaneous bleeding. Knockdown of 4 of the 5 novel platelet proteins altered arterial thrombosis, as demonstrated by modified kinetics of thrombus initiation and/or development. We identified a putative role for BAMBI and LRRC32 in promotion and DCBLD2 and ESAM in inhibition of thrombus formation. We conclude that phenotypic analysis of MO-injected zebrafish is a fast and powerful method for initial screening of novel platelet proteins for function in thrombosis.

Functional Genomics in Zebrafish Permits Rapid Characterization of Novel Platelet Membrane Proteins

In this study we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for functional screening of novel platelet genes in vivo by reverse genetics. Comparative transcript analysis of platelets and their precursor cell the megakaryocyte, together with nucleated blood cell elements, endothelial cells and erythroblasts, identified novel platelet membrane proteins with hitherto unknown role in thrombus formation. We determined the phenotype induced by antisense morpholino oligonucleotide (MO)-based knockdown of five of these genes in a laser-induced arterial thrombosis model. To validate the model, the genes for platelet Glycoprotein (GP) IIb and the coagulation protein Factor VIII were targeted. MO-injected fish showed normal thrombus initiation but severely impaired thrombus growth, consistent with the mouse knockout phenotypes, and concomitant knockdown of both resulted in spontaneous bleeding. Knockdown of four of the five novel platelet proteins altered arterial thrombosis, as demonstrated by modified kinetics of thrombus initiation and/or development. We identified a putative role for BAMBI and LRRC32 in promotion and DCBLD2 and ESAM in inhibition of thrombus formation. We conclude that phenotypic analysis of MO-injected zebrafish is a fast and powerful method for initial screening of novel platelet proteins for function in thrombosis.

Indirect evidence for a Fc gamma receptor on guinea pig platelets: Guinea pig represents a promising species for the investigation of human disorders with immune platelet activation

0049-3848/$ see front matter © 2008 Elsevier Ltd. All rights reserv doi:10.1016/j.thromres.2008.06.005 guinea pig represents a suitable species for in vivo or ex vivo investigation [1–3]. The aggregation patterns observed with guinea pigs in responsiveness to ADP, platelet activating factor and collagen were comparable with those observed with human platelets [4]. Platelets from guinea pigs appeared to resemblemore closely those from humans as compared with those of rabbits, dogs or pigs [5,6]. Moreover, guinea pig platelets have functional receptors for vonWillebrand factor and fibrinogen that are structurally homologous to human platelet glycoproteins Ib, IIb and IIIa [7,8]. So, guinea pigs have been extensively used to study the effect of drugs ex vivo (see for instance [1,2,9– 12]). However, the presence of Fc receptors on guinea pig platelets has not yet been investigated, whereas human platelets express a FcγIIa receptor with low affinity for monomeric IgG but with the capacity to bind IgG aggregates and immune complexes [13,14]. This receptor is likely involved in heparin-induced thrombocytopenia for instance.

A 10‐Base‐Pair Deletion in the Gene Encoding Platelet Glycoprotein IIb Associated with Glanzmann Thrombasthenia in a Horse

Journal of Veterinary Internal MedicineVolume 21, Issue 1 p. 196-198 Open Access A 10-Base-Pair Deletion in the Gene Encoding Platelet Glycoprotein IIb Associated with Glanzmann Thrombasthenia in a Horse Peter W. Christopherson, Peter W. Christopherson Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL.Search for more papers by this authorVicky L. van Santen, Vicky L. van Santen Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL.Search for more papers by this authorLeanda Livesey, Leanda Livesey Large Animal Hospital, Department of Clinical Sciences, Vaughan Teaching Hospital, Auburn University, Auburn, AL.Search for more papers by this authorMary K. Boudreaux, Corresponding Author Mary K. Boudreaux Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL. Department of Pathobiology, 166 Greene Hall, College of Veterinary Medicine, Auburn University, Auburn, AL 36849–5519; e-mail: boudrmk@vetmed.auburn.edu.Search for more papers by this author Peter W. Christopherson, Peter W. Christopherson Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL.Search for more papers by this authorVicky L. van Santen, Vicky L. van Santen Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL.Search for more papers by this authorLeanda Livesey, Leanda Livesey Large Animal Hospital, Department of Clinical Sciences, Vaughan Teaching Hospital, Auburn University, Auburn, AL.Search for more papers by this authorMary K. Boudreaux, Corresponding Author Mary K. Boudreaux Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL. Department of Pathobiology, 166 Greene Hall, College of Veterinary Medicine, Auburn University, Auburn, AL 36849–5519; e-mail: boudrmk@vetmed.auburn.edu.Search for more papers by this author First published: 05 February 2008 https://doi.org/10.1111/j.1939-1676.2007.tb02947.xCitations: 15AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume21, Issue1January 2007Pages 196-198 ReferencesRelatedInformation