Intraleucocyte platelet-activating factor levels in desmopressin-treated patients with haemophilia A and von Willebrand disease.
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.
Kavakli
K
K
Department of Paediatric Hematology, Faculty of Medicine, Ege University, Izmir, Turkey. kkavakli@med.ege.edu.tr
Hüseyinov
A
A
Coker
I
I
Aydinok
Y
Y
Nisli
G
G
D000293:Adolescent; D000328:Adult; D000001:Calcimycin / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006467:Hemophilia A / Q000097:blood* / Q000188:drug therapy; D006490:Hemostatics / Q000008:administration & dosage*; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D010972:Platelet Activating Factor / Q000187:drug effects / Q000378:metabolism*; D016896:Treatment Outcome; D014842:von Willebrand Diseases / Q000097:blood* / Q000188:drug therapy
D006490:Hemostatics; D007476:Ionophores; D010972:Platelet Activating Factor; D000001:Calcimycin; D003894:Deamino Arginine Vasopressin