Plasma Platelet-activating Factor (PAF) Levels and Desmopressin Response in Children with Hemophilia A and von Willebrand's Disease

Kavaklı, Kaan; Polat, Azız; Hüseyinof, Afig; Nişli, Güngör; Aydınok, Yeşim

doi:10.1055/s-0037-1614548

Cited by 3 publications

(3 citation statements)

References 3 publications

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“…This agrees with recent studies on paediatric patients: PAF levels were significantly higher in haemophiliacs and children with VWD than in healthy children. One hour after DDAVP treatment, levels of PAF were significantly elevated in responders, in contrast to those in the non‐responders ( Kavakli et al , 1999 ).…”

Section: Substance and Haemostatic Effects Of Ddavpmentioning

confidence: 88%

Ddavp Is Not a Panacea for Children With Bleeding Disorders

Sutor

2000

Br J Haematol

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Section: Substance and Haemostatic Effects Of Ddavpmentioning

confidence: 88%

Ddavp Is Not a Panacea for Children With Bleeding Disorders

Sutor

2000

Br J Haematol

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“…PAF is a biologically active and acetylated phospholipid mediator with diverse potent physiological and physiopathological effects, particularly in inflammation and allergy [5,8,9]. PAF is rapidly synthesized and secreted after stimulation from a wide range of human cells including endothelial cells, neutrophils, monocytes and platelets [15].…”

Section: Discussionmentioning

confidence: 99%

“…[5] showed that in vitro DDAVP‐treated monocytes increased their secretion of PAF, and that the increased level of PAF correlated with enhancement of vWF release from endothelial cells. We have also recently determined that endogenous plasma PAF levels are significantly higher than healthy controls and that there is a strong relationship between plasma PAF levels and response to DDAVP in children with HA and vWD [9]. As it is well known that PAF stimulates the endothelial cells by cell‐to‐cell interactions [8,10,11], the assessment of cellular PAF activities can be used to evaluate the relationship between PAF and response to DDAVP.…”

Section: Introductionmentioning

confidence: 99%

Intraleucocyte platelet‐activating factor levels in desmopressin‐treated patients with haemophilia A and von Willebrand disease

et al. 2001

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Despite the intensive clinical use of 1-deamino-8-D-arginine vasopressin (desmopressin; DDAVP) for 20 years, its mechanism of action is still not completely explained. It has been proposed that DDAVP stimulates release of a 'second messenger' which in turn stimulates release of von Willebrand factor (vWF) from endothelial cells. Platelet-activating factor (PAF) and interleukin (IL)-6 were individually proposed to be mediators for haemostatic action. The aim of this study was to investigate cellular-based PAF levels in patients with haemophilia A (HA) and von Willebrand disease (vWD) before and after DDAVP treatment and also to look for any probable relationship between the haemostatic response of DDAVP and cellular PAF activities. In total, 20 patients (11 HA and nine vWD) were enrolled in the study. DDAVP was given subcutaneously as a single dose (0.3 microg kg(-1)). Ten patients responded to DDAVP and were defined as the 'able group' (four mild HA, six type 1 vWD). The remaining 10 patients did not respond to DDAVP and were defined as the 'unable group' (seven severe HA, three type 3 vWD). Released (extracellular) and intracellular (intraleucocyte) PAF levels under the stimulation of specific agents (A23187 and Zymosan) were measured by high-performance liquid chromatography and radioimmunoassay. Extracellular and intracellular PAF activities were not detected without stimulation in healthy children whereas significantly higher PAF levels were found in the patients (extracellular: 37.5 +/- 34.4 ng per 10(7) cells; intracellular: 24.8 +/- 23.5 ng per 10(7) cells; P=0.0001). Intracellular PAF levels obtained from in vitro unstimulated cells were significantly higher in DDAVP-responsive (able) patients in comparison to DDAVP-unresponsive (unable) patients (52.1 +/- 18.5 vs. 28.9 +/- 8.0 ng per 10(7)cells). After in vitro stimulation by A23187, intracellular PAF activities were significantly higher in patients than in controls (209.3 +/- 26.1 vs. 172 +/- 18.1 ng per 10(7) cells). Intracellular PAF levels obtained from in vitro stimulated cells by A23187 were also significantly higher in the 'able' patients in comparison to the 'unable' patients (277 +/- 43.5 vs. 225 +/- 30 ng per 10(7)cells). In conclusion, cellular PAF activities are significantly higher in patients with HA and vWD. We also suggest that PAF, especially intracellular PAF mediates intracellular signalling and may be one of the important mediators for the haemostatic response of DDAVP.

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Desmopressinin vitroeffects on platelet function, monitored with Multiplate, ROTEM and Sonoclot

Jensen

Kander

Schött

2016

Scandinavian Journal of Clinical and Laboratory Investigation

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Background and aims The vasopressin analogue desmopressin has demonstrated efficacy in decreasing bleeding time by increasing the circulating levels of coagulation factor VIII and von Willebrand factor, but also by direct effects on platelets. Previous studies have demonstrated contrasting results regarding the effect of desmopressin on platelets in vitro. The aim of this study was to investigate the dose-response effects of in vitro desmopressin in whole blood. Our hypothesis was that desmopressin could increase platelet function in anticoagulated whole blood being stored up to 4 hours. Methods Desmopressin was administered with up to four different concentrations to venous whole blood, sampled with standard vacutainer tubes from 10 healthy volunteers after consent. Platelet function was analyzed with three different point-of-care techniques: Multiplate platelet aggregometry with adenosine diphosphate, collagen, thrombin receptor activating peptide-6, ristocetin and arachidonic acid agonists, tissue factor-activated thromboelastometry and Sonoclot glass bead viscoelastic coagulation tests at baseline and 4 hours later using different activator reagents. Results Thromboelastometry and Sonoclot did not show any significant change between baseline and 4 h later. A significant decrease in area under curve (AUC) could be seen with the Multiplate between baseline and after 4 h. Desmopressin did not improve any of these tests at baseline or during a 4 h storage and incubation period. Conclusion In vitro administered desmopressin could not increase normal platelet function or coagulation being measured with thromboelastometry and Sonoclot. Multiplate indicated decreased platelet aggregation over time, without any effect of in vitro added desmopressin.

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Plasma Platelet-activating Factor (PAF) Levels and Desmopressin Response in Children with Hemophilia A and von Willebrand's Disease

Cited by 3 publications

References 3 publications

Ddavp Is Not a Panacea for Children With Bleeding Disorders

Ddavp Is Not a Panacea for Children With Bleeding Disorders

Intraleucocyte platelet‐activating factor levels in desmopressin‐treated patients with haemophilia A and von Willebrand disease

Desmopressinin vitroeffects on platelet function, monitored with Multiplate, ROTEM and Sonoclot

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