Effect of DDAVP on Platelet Activation and Platelet-Derived Microparticle Generation

Abstract

Background The way by which 1-deamino-8-D-arginine vasopressin (DDAVP) acts on platelets remains unclear. Data from the literature tend to show that there is no definite effect on platelet activation, but recent work has suggested that a subtype of platelets, activated by the combined action of collagen and thrombin, was triggered by DDAVP. Moreover, platelet microparticles (PMPs), which have been shown to be procoagulant, have rarely been studied in this context. The goal of this study was to analyze the effects of DDAVP on PMPs' release through platelet activation.

Methods Fifteen out of 18 consecutive patients undergoing a therapeutic test with DDAVP were included. They were suffering from factor VIII deficiency or from von Willebrand disease. The expression of P-selectin and PAC-1 binding on platelets and the numbers of circulating PMPs were evaluated ex vivo before and after DDAVP infusion. Peripheral blood was collected on CTAD to limit artifactual platelet activation.

Results DDAVP induced a significant decrease of platelet counts and volume. Only small changes of P-selectin expression and PAC-1 binding were observed. Considering PMPs, two populations of patients could be defined, respectively, with (120%, n = 6) or without (21%, n = 7) an increase of PMPs after DDAVP. The decrease in platelet counts and volume remained significant in the group of responders.

Conclusion This study shows that DDAVP induces the generation/release of PMPs in some patients with factor VIII deficiency and von Willebrand disease 1 hour after DDAVP infusion.

Keywords

blood platelets - platelet activation - platelet function - platelet-derived microparticles - deamino D-arginine vasopressin

• References

• 1 Mannucci PM, Ruggeri ZM, Pareti FI, Capitanio A. 1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands' diseases. Lancet 1977; 1 (8017): 869-872
• 2 Cash JD, Gader AM, da Costa J. Proceedings: the release of plasminogen activator and factor VIII to lysine vasopressin, arginine vasopressin, I-desamino-8-d-arginine vasopressin, angiotensin and oxytocin in man. Br J Haematol 1974; 27 (02) 363-364
• 3 Mannucci PM, Aberg M, Nilsson IM, Robertson B. Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 1975; 30 (01) 81-93
• 4 Kaufmann JE, Vischer UM. Cellular mechanisms of the hemostatic effects of desmopressin (DDAVP). J Thromb Haemost 2003; 1 (04) 682-689
• 5 Yang X, Disa J, Rao AK. Effect of 1-desamino-8-D-arginine vasopressin (DDAVP) on human platelets. Thromb Res 1990; 59 (05) 809-818
• 6 Calmer S, Ferkau A, Larmann J. et al. Desmopressin (DDAVP) improves recruitment of activated platelets to collagen but simultaneously increases platelet endothelial interactions in vitro. Platelets 2014; 25 (01) 8-15
• 7 Tsakiris DA, Haefeli WE, Linder L, Steiner B, Marbet GA. Platelet surface activation markers after DDAVP infusion in healthy subjects. Thromb Haemost 1995; 74 (03) 991-992
• 8 Balduini CL, Noris P, Belletti S, Spedini P, Gamba G. In vitro and in vivo effects of desmopressin on platelet function. Haematologica 1999; 84 (10) 891-896
• 9 Wun T, Paglieroni TG, Lachant NA. Desmopressin stimulates the expression of P-selectin on human platelets in vitro. J Lab Clin Med 1995; 126 (04) 401-409
• 10 Sloand EM, Alyono D, Klein HG. et al. 1-Deamino-8-D-arginine vasopressin (DDAVP) increases platelet membrane expression of glycoprotein Ib in patients with disorders of platelet function and after cardiopulmonary bypass. Am J Hematol 1994; 46 (03) 199-207
• 11 Horstman LL, Valle-Riestra BJ, Jy W, Wang F, Mao W, Ahn YS. Desmopressin (DDAVP) acts on platelets to generate platelet microparticles and enhanced procoagulant activity. Thromb Res 1995; 79 (02) 163-174
• 12 Pearson K, Jensen H, Kander T, Schött U. Desmopressin in vitro effects on platelet function, monitored with Multiplate, ROTEM and Sonoclot. Scand J Clin Lab Invest 2016; 76 (04) 282-290
• 13 Swieringa F, Lancé MD, Fuchs B. et al. Desmopressin treatment improves platelet function under flow in patients with postoperative bleeding. J Thromb Haemost 2015; 13 (08) 1503-1513
• 14 Ogiwara K, Nogami K, Hosokawa K, Ohnishi T, Matsumoto T, Shima M. Comprehensive evaluation of haemostatic function in von Willebrand disease patients using a microchip-based flow chamber system. Haemophilia 2015; 21 (01) 71-80
• 15 Sinauridze EI, Kireev DA, Popenko NY. et al. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost 2007; 97 (03) 425-434
• 16 Owens III AP, Mackman N. Microparticles in hemostasis and thrombosis. Circ Res 2011; 108 (10) 1284-1297
• 17 Burnouf T, Goubran HA, Chou ML, Devos D, Radosevic M. Platelet microparticles: detection and assessment of their paradoxical functional roles in disease and regenerative medicine. Blood Rev 2014; 28 (04) 155-166
• 18 Arraud N, Linares R, Tan S. et al. Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration. J Thromb Haemost 2014; 12 (05) 614-627
• 19 Lacroix R, Robert S, Poncelet P, Kasthuri RS, Key NS, Dignat-George F. ISTH SSC Workshop. Standardization of platelet-derived microparticle enumeration by flow cytometry with calibrated beads: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop. J Thromb Haemost 2010; 8 (11) 2571-2574
• 20 Iversen LV, Ostergaard O, Nielsen CT, Jacobsen S, Heegaard NH. A heparin-based method for flow cytometric analysis of microparticles directly from platelet-poor plasma in calcium containing buffer. J Immunol Methods 2013; 388 (1-2): 49-59
• 21 Fouassier M, Babuty A, Debord C, Béné MC. Platelet immunophenotyping in health and inherited bleeding disorders, a review and practical hints. Cytometry B Clin Cytom 2020; 98 (06) 464-475
• 22 Colucci G, Stutz M, Rochat S. et al. The effect of desmopressin on platelet function: a selective enhancement of procoagulant COAT platelets in patients with primary platelet function defects. Blood 2014; 123 (12) 1905-1916
• 23 Dale GL. Coated-platelets: an emerging component of the procoagulant response. J Thromb Haemost 2005; 3 (10) 2185-2192
• 24 Dale GL, Remenyi G, Friese P. Quantitation of microparticles released from coated-platelets. J Thromb Haemost 2005; 3 (09) 2081-2088
• 25 Szasz R, Dale GL. COAT platelets. Curr Opin Hematol 2003; 10 (05) 351-355
• 26 Heemskerk JW, Mattheij NJ, Cosemans JM. Platelet-based coagulation: different populations, different functions. J Thromb Haemost 2013; 11 (01) 2-16
• 27 Tani M, Neely JR. Na+ accumulation increases Ca2+ overload and impairs function in anoxic rat heart. J Mol Cell Cardiol 1990; 22 (01) 57-72
• 28 Palty R, Sekler I. The mitochondrial Na(+)/Ca(2+) exchanger. Cell Calcium 2012; 52 (01) 9-15
• 29 Tomasiak MM, Stelmach H, Bodzenta-Łukaszyk A, Tomasiak M. Involvement of Na+/H+ exchanger in desmopressin-induced platelet procoagulant response. Acta Biochim Pol 2004; 51 (03) 773-788
• 30 Trummer A, Haarmeijer B, Werwitzke S. et al. Increased amounts of von Willebrand factor are bound to microparticles after infusion of desmopressin. Haemophilia 2013; 19 (02) 236-241
• 31 Kaufmann JE, Iezzi M, Vischer UM. Desmopressin (DDAVP) induces NO production in human endothelial cells via V2 receptor- and cAMP-mediated signaling. J Thromb Haemost 2003; 1 (04) 821-828
• 32 Egberg N. Effect of venous occlusion and DDAVP injection on platelet aggregation and platelet cyclic AMP. Thromb Res 1980; 19 (1-2): 263-265
• 33 Smolenski A. Novel roles of cAMP/cGMP-dependent signaling in platelets. J Thromb Haemost 2012; 10 (02) 167-176