Up-regulation of platelet activation in hemophilia A

Bladel, Esther R. van; Roest, Mark; Groot, Philip G. de; Schutgens, Roger E. G.

doi:10.3324/haematol.2011.042663

Cited by 33 publications

(43 citation statements)

References 9 publications

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“…Plasma Ang-1, Ang-2 and VEGF levels were measured by quantitative sandwich enzyme immunoassay technique according to the instructions of the manufacturer (Quantikine, R&D systems, Minneapolis, USA) at the Eijkman Institute. The platelet activation markers P-selectin and CXCL7 (beta-thromboglobulin) were measured in the Department of Clinical Chemistry and Haematology of the University Medical Center Utrecht as described in detail earlier [18].…”

Section: Methodsmentioning

confidence: 99%

Platelet Activation Determines Angiopoietin-1 and VEGF Levels in Malaria: Implications for Their Use as Biomarkers

et al. 2013

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IntroductionThe angiogenic proteins angiopoietin (Ang)-1, Ang-2 and vascular endothelial growth factor (VEGF) are regulators of endothelial inflammation and integrity. Since platelets store large amounts of Ang-1 and VEGF, measurement of circulation levels of these proteins is sensitive to platelet number, in vivo platelet activation and inadvertent platelet activation during blood processing. We studied plasma Ang-1, Ang-2 and VEGF levels in malaria patients, taking the necessary precautions to avoid ex vivo platelet activation, and related plasma levels to platelet count and the soluble platelet activation markers P-selectin and CXCL7.MethodsPlasma levels of Ang-1, Ang-2, VEGF, P-selectin and CXCL7 were measured in CTAD plasma, minimizing ex vivo platelet activation, in 27 patients with febrile Plasmodium falciparum malaria at presentation and day 2 and 5 of treatment and in 25 healthy controls.ResultsLevels of Ang-1, Ang-2 and VEGF were higher at day 0 in malaria patients compared to healthy controls. Ang-2 levels, which is a marker of endothelial activation, decreased after start of antimalarial treatment. In contrast, Ang-1 and VEGF plasma levels increased and this corresponded with the increase in platelet number. Soluble P-selectin and CXCL7 levels followed the same trend as Ang-1 and VEGF levels. Plasma levels of these four proteins correlated strongly in malaria patients, but only moderately in controls.ConclusionIn contrast to previous studies, we found elevated plasma levels of Ang-1 and VEGF in patients with malaria resulting from in vivo platelet activation. Ang-1 release from platelets may be important to dampen the disturbing effects of Ang-2 on the endothelium. Evaluation of plasma levels of these angiogenic proteins requires close adherence to a stringent protocol to minimize ex vivo platelet activation.

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Section: Methodsmentioning

confidence: 99%

Platelet Activation Determines Angiopoietin-1 and VEGF Levels in Malaria: Implications for Their Use as Biomarkers

et al. 2013

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“…[12][13][14] In the second assay, the platelet reactivity assay, the reactivity in 3 major physiological platelet activation pathways was determined in unprocessed whole blood by flow cytometry on the level of individual platelets. 15 Adenosine diphosphate (ADP), convulxin (CVX), and thrombin receptor activator peptide (TRAP) were used to activate platelets via P2Y receptors (P2Y 1 and P2Y 12 ), GPVI receptor, and proteinase-activated receptor 1, respectively. Furthermore, the platelet activation test quantifies both degranulation (P-selectin expression on the platelet surface) and activation of GPIIbIIIa (binding of fibrinogen to platelets).…”

Section: Introductionmentioning

confidence: 99%

Functional platelet defects in children with severe chronic ITP as tested with 2 novel assays applicable for low platelet counts

Bladel

Laarhoven

Heijden

et al. 2014

Blood

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Key Points• Pediatric chronic ITP patients with a severe bleeding phenotype exhibit functional platelet defects.• The platelet microaggregation test and the platelet reactivity assay are able to assess platelet function at extremely low platelet count.Immune thrombocytopenia (ITP) is an autoimmune disease with a complex heterogeneous pathogenesis and a bleeding phenotype that is not necessarily correlated to platelet count. In this study, the platelet function was assessed in a well-defined cohort of 33 pediatric chronic ITP patients. Because regular platelet function test cannot be performed in patients with low platelet counts, 2 new assays were developed to determine platelet function: first, the microaggregation test, measuring in platelets isolated from 10 mL of whole blood the platelet potential to form microaggregates in response to an agonist; second, the platelet reactivity assay, measuring platelet reactivity to adenosine diphosphate (ADP), convulxin (CVX), and thrombin receptor activator peptide in only 150 mL of unprocessed whole blood. Patients with a severe bleeding phenotype demonstrated a decreased aggregation potential upon phorbol myristate acetate stimulation, decreased platelet degranulation following ADP stimulation, and a higher concentration of ADP and CVX needed to activate the glycoprotein IIbIIIa complex compared with patients with a mild bleeding phenotype. In conclusion, here we have established 2 functional tests that allow for evaluation of platelet function in patients with extremely low platelet counts ( <10 9 ). These tests show that platelet function is related to bleeding phenotype in chronic ITP. (Blood. 2014;123(10):1556-1563

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“…Hemophilia A occurs due to a deficiency of factor (F) VIII and hemophilia B occurs due to a deficiency of FIX [1,2]. According to factor activity, hemophilia can be classified as severe (<1% of normal), moderate (1%-5% of normal), or mild (5%-40% of normal) [1,3]. …”

Section: Introductionmentioning

confidence: 99%

The Effectiveness of a New Hemostatic Agent (Ankaferd Blood Stopper) for the Control of Bleeding following Tooth Extraction in Hemophilia: A Controlled Clinical Trial

Kazancioğlu

Çakır

et al. 2013

tjh

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Objective: To assess the hemostatic efficacy of a new local hemostatic agent, Ankaferd Blood Stopper (ABS), for the control of bleeding following tooth extraction in hemophiliacs.Materials and Methods: Simple tooth extractions were performed in 27 hemophilia A patients. In the treatment group (n=17) local hemostasis was achieved via application of ABS to the extraction sockets, whereas in the control group (n=10) local hemostasis was achieved via direct packing with gauze.Results: In all, 57 (21 primary and 36 permanent) teeth extractions were performed in 27 hemophilia A patients. There were no significant differences in age or factor VIII level distribution between the 2 groups (p>0.05). The most significant clinical difference between the groups was associated with the use of ABS; those in the treatment group had significantly shorter duration of bleeding (p=0.002). Conclusion: This is the first study to evaluate the efficacy of ABS for the control of bleeding following tooth extraction in hemophiliacs. ABS can be considered an alternative local hemostatic agent for reducing clotting factor concentrates in hemophilia patients.Conflict of interest:None declared.

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Up-regulation of platelet activation in hemophilia A

Cited by 33 publications

References 9 publications

Platelet Activation Determines Angiopoietin-1 and VEGF Levels in Malaria: Implications for Their Use as Biomarkers

Platelet Activation Determines Angiopoietin-1 and VEGF Levels in Malaria: Implications for Their Use as Biomarkers

Functional platelet defects in children with severe chronic ITP as tested with 2 novel assays applicable for low platelet counts

The Effectiveness of a New Hemostatic Agent (Ankaferd Blood Stopper) for the Control of Bleeding following Tooth Extraction in Hemophilia: A Controlled Clinical Trial

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