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Platelet Deposition (platelet + deposition)
Selected AbstractsAnticoagulation Options for Pediatric HemodialysisHEMODIALYSIS INTERNATIONAL, Issue 2 2003Andrew Davenport Blood coagulation in the extracorporeal hemodialysis circuit is one of the manifestations of bio-incompatibility that is related to the activation of monocytes, platelets, and the coagulation cascades. Compared to adults, in pediatric patients, the surface area of the extracorporeal circuit is increased relative to blood volume. This is due to the patient's smaller blood volume and the combination of the higher relative surface area of the dialyzer, smaller lumen lines, and small-bore vascular catheters, potentially increasing contact activation of coagulation proteins, platelets, and inflammatory cells. Although unfractionated heparin remains the most commonly used anticoagulant, low molecular weight heparin offers the advantages of a single bolus, less fibrin and platelet deposition in the dialyzer, and perhaps more importantly, less osteoporosis, hyperkalemia, and abnormal lipoprotein profile. Although regional anticoagulants are available, these are often prohibitively expensive or require increased complexity of the dialysis procedure (e.g., citrate), but have the advantage of reducing the risk of bleeding when compared to heparin. Thrombin inhibitors are now available, and with the advent of argatroban, which is metabolized in the liver, have become the anticoagulants of choice for the few patients who develop heparin-induced thrombocytopenia type II. [source] Staphylococcal superantigen-like 5 activates platelets and supports platelet adhesion under flow conditions, which involves glycoprotein Ib, and ,IIb,3JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2009C. J. C. DE HAAS Summary.,Objectives: Staphylococcal superantigen-like 5 (SSL5) is an exoprotein secreted by Staphylococcus aureus that has been shown to inhibit neutrophil rolling over activated endothelial cells via a direct interaction with P-selectin glycoprotein ligand 1 (PSGL-1). Methods and Results: When purified recombinant SSL5 was added to washed platelets in an aggregometry set-up, complete and irreversible aggregation was observed. Proteolysis of the extracellular part of GPIb, or the addition of dRGDW abrogated platelet aggregation. When a mixture of isolated platelets and red cells was perfused over immobilized SSL5 at a shear rate of 300 s,1, stable platelet aggregates were observed, and platelet deposition was substantially reduced after proteolysis of GPIb or after addition of dRGDW. SSL5 was shown to interact with glycocalicin, a soluble GPIb, fragment, and binding of SSL5 to platelets resulted in GPIb-mediated signal transduction as evidenced by translocation of 14-3-3,. In addition, SSL5 was shown to interact with endothelial cell matrix (ECM) and this interaction enhanced aggregation of platelets from whole blood to this ECM. Conclusions: SSL5 activates and aggregates platelets in a GPIb,-dependent manner, which could be important in colonization of the vascular bed and evasion of the immune system by S. aureus. [source] Complementary roles of platelets and coagulation in thrombus formation on plaques acutely ruptured by targeted ultrasound treatment: a novel intravital modelJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2009M. J. E. KUIJPERS Summary.,Background:,Atherothrombosis is a major cause of cardiovascular events. However, animal models to study this process are scarce. Objectives:,We describe the first murine model of acute thrombus formation upon plaque rupture to study atherothrombosis by intravital fluorescence microscopy. Methods:,Localized rupture of an atherosclerotic plaque in a carotid artery from Apoe,/, mice was induced in vivo using ultrasound. Rupture of the plaque and formation of localized thrombi were verified by two-photon laser scanning microscopy (TPLSM) in isolated arteries, and by immunohistochemistry. The thrombotic reaction was quantified by intravital fluorescence microscopy. Results:,Inspection of the ultrasound-treated plaques by histochemistry and TPLSM demonstrated local damage, collagen exposure, luminal thrombus formation as well as intra-plaque intrusion of erythrocytes and fibrin. Ultrasound treatment of healthy carotid arteries resulted in endothelial damage and limited platelet adhesion. Real-time intravital fluorescence microscopy demonstrated rapid platelet deposition on plaques and formation of a single thrombus that remained subocclusive. The thrombotic process was antagonized by thrombin inhibition, or by blocking of collagen or adenosine diphosphate receptor pathways. Multiple thrombi were formed in 70% of mice lacking CD40L. Conclusions:,Targeted rupture of murine plaques results in collagen exposure and non-occlusive thrombus formation. The thrombotic process relies on platelet activation as well as on thrombin generation and coagulation, and is sensitive to established and novel antithrombotic medication. This model provides new possibilities to study atherothrombosis in vivo. [source] Inhibition and reversal of platelet-rich arterial thrombus in vivo: direct vs. indirect factor Xa inhibitionJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2004K. KARNICKI Summary.,Background/objective: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. Methods: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 µg kg,1 bolus +,1.5 µg kg,1 min,1 infusion, n = 6); ZK-807834-Dose 2 (20 µg kg,1 bolus +,0.75 µg kg,1 min,1 infusion; n = 6); enoxaparin (1 mg kg,1 bolus; n = 6); or saline (n = 6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. Results: The prothrombin time ratio was 2.2 ± 0.1; 1.4 ± 0.3; 1.2 ± 0.9 and 1.1 ± 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 ± 226 × 106 cm,2; P = 0.008), whereas ZK-807834-Dose 2 (2325 ± 768) and enoxaparin (1236 ± 383) were not different from saline (2776 ± 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 ± 185). Neither ZK-807834-Dose 2 (1588 ± 480) nor enoxaparin (1618 ± 686) was different from saline control (2222 ± 598). Conclusions: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective. [source] Differential response of platelets to chemokines: RANTES non-competitively inhibits stimulatory effect of SDF-1,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2004B. Shenkman Summary.,Background:,Among the chemokines related to CXC and CC receptor groups and released from platelets, leukocytes and endothelial cells, SDF-1, TARC and MDC have been found to be platelet agonists. Platelets do not contain SDF-1,. In contrast, RANTES is constitutively present in platelet ,-granules and released upon platelet activation. Objectives:,To study a possible role of RANTES as a modulator of SDF-1, effect on platelets, in relation to CXCR4 and various CC receptors. Methods:,CXCR-4 (CXCL12) receptor expression and platelet activation were evaluated by flow cytometry, platelet deposition was studied by cone and plate(let) analyzer, and platelet aggregation by turbidometric aggregometry. Results:,Flow cytometry studies revealed similar expression of CXCR-4, the specific receptor of SDF-1, on intact, inactivated, and activated platelets. Preincubation of platelets with RANTES affected neither CXCR-4 expression, nor SDF-1, binding to the platelet membrane. In the presence of fibrinogen, SDF-1, activated gel-filtered platelets. RANTES did not activate platelets, but substantially (by 70%) inhibited SDF-1,-induced fibrinogen binding. Similarly, RANTES abrogated the promoting effect of SDF-1, on whole blood platelet adhesion to endothelial cell monolayer under venous flow conditions. In platelet-rich plasma, RANTES moderately inhibited SDF-1,-induced platelet aggregation, while it did not affect aggregation induced by thrombin-receptor activation peptide, adenosine diphosphate, or phorbol 12-myristate 13-acetate. A synergistic inhibitory effect of RANTES and prostaglandin E1 used at subthreshold concentrations, on SDF-1,-induced aggregation and SDF-1,-induced fibrinogen binding to platelets was observed, which may suggest involvement of RANTES in a cAMP-dependent signal transduction pathway. Conclusions:,RANTES non-competitively inhibits activation of platelets by SDF-1,, and thus may play a regulatory role in platelet response to inflammation. [source] A novel flow cytometric analysis for platelet activation on immobilized von Willebrand factor or fibrillar collagenJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2003S. Kao Summary., Under flow conditions, platelets adhere singly or in small aggregates on von Willebrand factor (VWF)-coated surfaces, but form large aggregates on immobilized fibrillar collagen. We developed a novel flow cytometric analysis to study the mechanisms underlying these distinct platelet deposition patterns. Flow cytometry was used to measure platelet activation after platelet adherence onto microspheres coated with either VWF or collagen fibrils. Two representative indices were calculated to quantify activated GpIIb,IIIa and P-selectin expression on adherent platelets. The signaling pathways responsible for platelet activation after interacting with fibrillar collagen were elucidated using various inhibitors. An in vitro endothelial cell wound model was also used to study the roles of VWF and fibrillar collagen in platelet deposition onto subendothelial matrixes. The adherent platelets on fibrillar collagen express more activated GpIIb,IIIa and P-selectin than those on VWF. Activation of GpIIb,IIIa and expression of P-selectin after platelet interaction with collagen occur via different intracellular signaling pathways; however, Ca2+ released from intracellular pools is common to both phenomena. Platelets were deposited singly or formed small aggregates on the endothelial cell wounded area, and this deposition pattern was dependent on VWF molecules secreted by endothelial cells and the absence of subendothelial collagen fibrils. As less activated GpIIb,IIIa and P-selectin are expressed after platelets interact with immobilized VWF alone, subsequent flowing platelet recruitment is minimal. Collagen fibrils, however, can activate adherent platelets sufficiently to promote the formation of large platelet aggregates. [source] Development of a Severe von Willebrand Factor/ADAMTS13 Dysbalance During Orthotopic Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009I. T. A. Pereboom Patients with liver disease show profound changes in their hemostatic system, which may further change during liver transplantation. We previously demonstrated that highly elevated levels of the platelet adhesive protein von Willebrand factor (VWF) in patients with cirrhosis lead to an increased VWF-dependent platelet deposition under flow as compared to healthy controls. In this study we examined VWF parameters during the course of liver transplantation. We collected serial plasma samples from 20 patients undergoing liver transplantation in which we determined plasma levels of VWF and the VWF-cleaving protease ADAMTS13. Furthermore, we performed functional tests of VWF-dependent platelet adhesion. We found persistently elevated levels of VWF during and after liver transplantation. The capacity of VWF to interact with platelets normalized during the course of transplantation, and flow-mediated VWF-dependent platelet adhesion remained at levels far exceeding those observed in healthy individuals during and after transplantation. Plasma levels of ADAMTS13 dropped during transplantation, and in four patients levels below 10% of normal were observed after reperfusion. We observed the development of a hyperreactive primary hemostatic system, as evidenced by high levels of fully functional VWF and a temporary ADAMTS13 deficiency, during liver transplantation, and speculate that these changes contribute to postoperative thrombotic complications. [source] Hemocompatibility Assessment of Carbonic Anhydrase Modified Hollow Fiber Membranes for Artificial LungsARTIFICIAL ORGANS, Issue 5 2010Heung-Il Oh Abstract Hollow fiber membrane (HFM)-based artificial lungs can require a large blood-contacting membrane surface area to provide adequate gas exchange. However, such a large surface area presents significant challenges to hemocompatibility. One method to improve carbon dioxide (CO2) transfer efficiency might be to immobilize carbonic anhydrase (CA) onto the surface of conventional HFMs. By catalyzing the dehydration of bicarbonate in blood, CA has been shown to facilitate diffusion of CO2 toward the fiber membranes. This study evaluated the impact of surface modifying a commercially available microporous HFM-based artificial lung on fiber blood biocompatibility. A commercial poly(propylene) Celgard HFM surface was coated with a siloxane, grafted with amine groups, and then attached with CA which has been shown to facilitate diffusion of CO2 toward the fiber membranes. Results following acute ovine blood contact indicated no significant reduction in platelet deposition or activation with the siloxane coating or the siloxane coating with grafted amines relative to base HFMs. However, HFMs with attached CA showed a significant reduction in both platelet deposition and activation compared with all other fiber types. These findings, along with the improved CO2 transfer observed in CA modified fibers, suggest that its incorporation into HFM design may potentiate the design of a smaller, more biocompatible HFM-based artificial lung. [source] Diagnosis of thrombotic thrombocytopenic purpura based on modulation by patient plasma of normal platelet adhesion under flow conditionBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2003Boris Shenkman Summary. We have designed a simple test for the early diagnosis and treatment monitoring of thrombotic thrombocytopenic purpura (TTP). We examined plasma from 24 TTP patients and normal plasma using a cone and plate(let) analyser (CPA). Test plasma was mixed with citrated normal whole blood (group O) and subjected to flow at a shear rate of 1800/s. Mixing normal plasma (12·5, 25, 50 or 75 µl) with heterologous normal whole blood (final volume of 200 µl) resulted in a decrease of surface coverage (SC, maximally by 63%) and, to a lesser extent, of average size (AS, maximally by 37%) due to dilution of the blood sample. In contrast, mixing the same quantities of acute TTP plasma with normal blood yielded an increase in both SC (up to 125%) and AS (up to 130%). Increased SC and/or AS were detected in all 15 patients in acute phase and in three out of 14 patients in remission. Following repeated plasmapheresis, the enhanced platelet deposition in five patients with acute TTP returned to almost normal patterns. Mixing plasma from patients with other thrombocytopenic conditions in this way resulted in a decrease in both SC and AS, and did not differ from control subjects. In conclusion, the CPA is a simple and specific laboratory test that can be used for the diagnosis and monitoring of plasma exchange therapy in TTP. [source] | ||||||||||