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DOI: 10.1055/s-0037-1614080
The Effect of DDAVP Infusion on Thrombin Generation in Platelet-rich Plasma of von Willebrand Type 1 and in Mild Haemophilia A Patients
The authors thank the technical staff of Haematology, Haemostasis unit (academic hospital Maastricht, The Netherlands) for determination of vWF:RCoF, vWF:Ag and FVIII:c in plasmas. This study was supported by a Program Grant 900-26-192 from the Dutch Organization for Scientific Research (N.W.O.).
Publication History
Received
22 February 2000
Accepted after resubmission
17 May 2000
Publication Date:
11 December 2017 (online)
Summary
In von Willebrand disease (vWD) type 1 and mild haemophilia A patients we studied the effect of an infusion of DDAVP (0.3 µg/kg body weight) on thrombin generation in platelet-rich plasma (PRP) and platelet-poor plasma (PPP). Baseline thrombin generation in PRP was diminished both in the haemophilia A and vWD patients. It was normal in vWD plasma when sufficient procoagulant phospholipids were present, either via adding phospholipid vesicles to PPP or via scrambling of the platelet membrane with ionomycin in PRP. In haemophilia A plasma, thrombin generation did not normalize by providing procoagulant phospholipids. Treatment with DDAVP temporarily restored thrombin generation in PRP to normal in both diseases.
To investigate the individual roles of von Willebrand factor (vWF) and factor VIII, we also studied the effect of factor VIII infusion on thrombin generation in a severe haemophilia patient. It appears that at a fixed normal vWF concentration, <25% factor VIII is sufficient for normal thrombin generation in PRP. At a sufficient factor VIII concentration, however, thrombin generation is still lower than normal in vWD patients; ∼40% of vWF is required for half-normal thrombin generation in PRP.
It thus appears that vWF is also a clotting factor, in the sense that it is required for normal thrombin generation. This underlines the importance of the interaction between coagulation and the platelets in normal haemostasis. Thrombin generation in PRP appears to be a suitable test to reflect the combined function.
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References
- 1 Ruggeri ZM, Ware J. von Willebrand factor. Faseb J 1993; 07 (02) 308-16.
- 2 Sadler JE. von Willebrand factor. J Biol Chem 1991; 266 (34) 22777-80.
- 3 Meyer D, Girma JP. von Willebrand factor: structure and function. Thromb Haemost 1993; 70 (01) 99-104.
- 4 Sixma JJ, Bolhuis PA, Sakariassen KS. Thrombogenesis: interaction of blood components with the vessel wall. Recent Results Cancer Res 1979; 69: 111-8.
- 5 Béguin S, Kumar R, Keularts I, Seligsohn U, Coller BS, Hemker HC. Fibrin-dependent platelet procoagulant activity requires GPIb receptors and von Willebrand factor. Blood 1999; 93 (02) 564-70.
- 6 Lethagen S. Desmopressin – a haemostatic drug: state-of-the-art review. Eur J Anaesthesiol Suppl 1997; 14: 1-9.
- 7 Federici AB, Mannucci PM. Optimizing therapy with factor VIII/von Willebrand factor concentrates in von Willebrand disease. Haemophilia 1998; 04 (Suppl. 03) 7-10.
- 8 Hendrix H, Lindhout T, Mertens K, Engels W, Hemker HC. Activation of human prothrombin by stoichiometric levels of staphylocoagulase. J Biol Chem 1983; 258 (06) 3637-44.
- 9 Rosing J, Tans G, Govers-Riemslag JW, Zwaal RF, Hemker HC. The role of phospholipids and factor Va in the prothrombinase complex. J Biol Chem 1980; 255 (01) 274-83.
- 10 Boedeker BG. The manufacturing of the recombinant factor VIII, Kogenate. Transfus Med Rev 1992; 06 (04) 256-60.
- 11 Newman DJ, Henneberry H, Price CP. Particle enhanced light scattering immunoassay. Ann Clin Biochem 1992; 29 (Pt 1): 22-42.
- 12 Allain JP, Cooper HA, Wagner RH, Brinkhous KM. Platelets fixed with paraformaldehyde: a new reagent for assay of von Willebrand factor and platelet aggregating factor. J Lab Clin Med 1975; 85 (02) 318-28.
- 13 Hemker HC, Willems GM, Béguin S. A computer assisted method to obtain the prothrombin activation velocity in whole plasma independent of thrombin decay processes. Thromb Haemost 1986; 56 (01) 9-17.
- 14 Hemker HC, Béguin S. Thrombin generation in plasma: its assessment via the endogenous thrombin potential. Thromb Haemost 1995; 74 (01) 134-8.
- 15 Kawabata S, Morita T, Iwanaga S, Igarashi H. Staphylocoagulase-binding region in human prothrombin. J Biochem (Tokyo) 1985; 97 (01) 325-31.
- 16 Béguin S, Kumar R. Thrombin, fibrin and platelets: a resonance loop in which von Willebrand factor is a necessary link. Thromb Haemost 1997; 78 (01) 590-4.
- 17 Bevers EM, Comfurius P, Zwaal RF. The nature of the binding for prothrombinase at the platelet surface as revealed by lipolytic enzymes. Eur J Bioch 1982; 122 (01) 81-5.
- 18 Aledort LM. Some aspects on the management of hemophilia. Thromb Haemost 1995; 74 (01) 440-3.
- 19 Roberts HR, Graham JB, Webster WP, Penick GD. Plasma transfusion therapy in hemophilia. In: The hemophilias. Brinkhous KM, Hemker HC. Chapel Hill: University of North Carolina Press; 1964: 323-7.
- 20 Loeliger EA. Therapeutic target values in oral anticoagulation-justification of Dutch policy and a warning against the so-called moderate-intensity regimens. Ann Hematol 1992; 64 (02) 60-5.
- 21 Azar AJ, Cannegieter SC, Deckers JW, Briet E, van Bergen PF, Jonker JJ. et al. Optimal intensity of oral anticoagulant therapy after myocardial infarction. J Am Coll Cardiol 1996; 27 (06) 1349-55.
- 22 Biggs R, Macfarlane RG. Haemophilia and related conditions: a survey of 187 cases. Br J Haematol 1958; 04: 1-27.
- 23 Mannucci PM. Haemophilia treatment protocols around the world: towards a consensus. Haemophilia 1998; 04 (04) 421.
- 24 Catto AJ, Carter AM, Barrett JH, Bamford J, Rice PJ, Grant PJ. von Willebrand factor and factor VIII: C in acute cerebrovascular disease. Relationship to stroke subtype and mortality. Thromb Haemost 1997; 77 (06) 1104-8.
- 25 Sadler JE, Matsushita T, Dong Z, Tuley EA, Westfield LA. Molecular mechanism and classification of von Willebrand disease. Thromb Haemost 1995; 74 (01) 161-6.
- 26 Sadler JE. A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 1994; 71 (04) 520-5.