Thromb Haemost 1982; 48(02): 156-161
DOI: 10.1055/s-0038-1657246
Original Article
Schattauer GmbH Stuttgart

The Use of Desmopressin Acetate (DDAVP) as a Test of the Fibrinolytic Capacity of Patients – Analysis of Responders and Non-Responders

E J P Brommer
The Gaubius Institute, Health Research Division TNO, Leiden, The Netherlands
,
M M Barrett-Bergshoeff
The Gaubius Institute, Health Research Division TNO, Leiden, The Netherlands
,
R A Allen
The Gaubius Institute, Health Research Division TNO, Leiden, The Netherlands
,
I Schicht
*   The Dept. of Nephrology, Academic Hospital, Leiden, The Netherlands
,
R M Bertina
**   The Dept. of Haematology, Academic Hospital, Leiden, The Netherlands
,
M A D H Schalekamp
***   The Dept. of Internal Medicine I, Erasmus University, Rotterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 15 March 1982

Accepted 02 August 1982

Publication Date:
13 July 2018 (online)

Summary

Intravenous infusion of desmopressin (DDAVP, 0.4 μg/kg b.w. in 12’) causes an increase in the level of extrinsic plasminogen activator, measured in plasma euglobulin fractions with added C1-inactivator on fibrin plates. A poor response or no response at all was elicited in two out of 21 patients with spontaneous thrombosis, 18/38 with hyperlipoproteinaemia and 10/14 with terminal renal insufficiency requiring haemodialysis.

Haemodilution during the first 30’ after starting the DDAVP-infusion occurred both in responders and in non-responders; so did haemodynamic reactions: increase in heart rate, drop in diastolic blood pressure, facial flushing. The rise of fibrinolytic activity was shown not to be associated with decreased hepatic blood flow. Normal factor VIII-rises in “non-responders” indicate the responsiveness of the receptive organs, including the hypothalamus, to DDAVP.

Despite a normal baseline level of fibrinolytic activity in the blood, as occurs for instance in terminal renal insufficiency, the vascular endothelium may be refractory to stimulation. In some patients, especially in type IV hyperlipoproteinaemia, a selective defect of the release of plasminogen activator is postulated. In subjects with low fibrinolytic activity at rest, as observed in spontaneous thromboembolism and in hypertriglyceridaemia, the failure to release plasminogen activator upon stimulation with DDAVP might be a consequence of an impairment of synthesis as well.

 
  • References

  • 1 Rijken DC, Wijngaards G, Welbergen J. Relationship between uterine tissue plasminogen activator and the activators in blood and vascular wall. Thromb Res 1980; 18: 815-830
  • 2 Camiolo SM, Thorsen S, Astrup T. Fibrinogenolysis and fibrinolysis with tissue plasminogen activator, urokinase, streptokinase-activated human globulin and plasmin. Proc Soc Exp Biol Med 1971; 138: 277-280
  • 3 Thorsen S, Glas-Greenwalt P, Astrup T. Differences in the binding to fibrin of urokinase and tissue plasminogen activator. Thrombos Diathes Haemorrh 1972; 28: 65-74
  • 4 Cash J. A new approach to studies of the fibrinolytic enzyme system in man. Am Heart J 1968; 75: 424-427
  • 5 Gader AMA, Da Costa J, Cash JD. A new vasopressin analogue and fibrinolysis. Lancet 1973; 2: 1417-1418
  • 6 Mannucd PM, Åberg M, Nilsson IM, Robertson B. Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 1975; 30: 81-93
  • 7 Åberg M, Nilsson IM, Vilhardt H. The release of fibrinolytic activator and factor VIII after injection of DDAVP. In: Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JF, C≖pelàk V, Samama MM, Desnoyers PC. (Eds) Vol. 4: Churchill Livingstone, Edinburgh; London - New York: 1979: 92-97
  • 8 Johansson L, Hedner U, Nilsson IM. A family with thromboembolic disease associated with deficient fibrinolytic activity in vessel wall. Acta Med Scand 1978; 203: 477-480
  • 9 Ludlam CA, Peake IR, Allen N, Davies BL, Furlong RA, Bloom AL. Factor VIII and fibrinolytic response to deamino-8-D-arginine vasopressin in normal subjects and dissociate response in some patients with haemophilia and von Willebrand’s disease. Br J Haematol 1980; 45: 499-511
  • 10 Nilsson IM, Holmberg L, Åberg M, Vilhardt H. The release of plasminogen activator and factor VIII after injection of DDAVP in healthy volunteers and in patients with von Willebrand’s disease. Scand J Haematol 1980; 24: 351-359
  • 11 Korninger C, Niessner H, Thaler E, Lechner K. Wirkung von DDAVP auf Fibrinolyse und Gerinnungsparameter. In: Minirin, DDAVP Anwendung bei Blutern. Sutor AH. (Ed) 55-64 Schattauer Verlag; Stuttgart - New York: 1980
  • 12 Brommer EJP, Gevers Leuven JA, Barrett-Bergshoeff MM, Schouten JA. Response of fibrinolytic activity and coagulation factor VIII to stimulation with DDAVP in hyperlipoproteinaemia. J Lab Clin Med 1982; 100: 105-114
  • 13 Cash JD, Gader AMA, Mulder JL, Cort JH. Structure-activity relations of the fibrinolytic response to vasopressins in man. Clin Sci Mol Med 1978; 54: 403-409
  • 14 Sheam SAM, Bloom AL, Peake IR, Giddings JC. The production of factor-VIII-related activities by cultured human endothelial cells. XVIIth Congress Int Soc Haematol Paris 1979; 529 (Abstr.)
  • 15 Cort JH, Fischman AJ, Dodds WJ, Rand JH, Schwartz IL. New category of vasopressin receptor in central nervous system. Int J Peptide Protein Res 1981; 17: 14-22
  • 16 Emeis JJ. The vascular wall and fibrinolysis. Haemostasis 1979; 8: 332-339
  • 17 Cash JD. Control mechanism of activator release. In: Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JF, Rowan RM, Samama MM, Desnoyers PC. (Eds) Vol 3: 65-75 Raven Press; New York: 1978
  • 18 Feamley GR, Balmforth G, Feamley E. Evidence of a diurnal fibrinolytic rhythm; with a simple method of measuring natural fibrinolysis. Clin Sci 1957; 16: 645-650
  • 19 Rosing DR, Brakman P, Redwood DR, Goldstein RE, Beiser GD, Astrup T, Epstein SE. Blood fibrinolytic activity in man: diurnal variation and the response to varying intensities of exercise. Circ Res 1970; 27: 171-184
  • 20 Haverkate F, Brakman P. Fibrin plate assay.. In: Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JF, Samama MM, Desnoyers PC. (Eds) Vol. 1: 151-159 Raven Press; New York: 1975
  • 21 Kluft C. Blood fibrinolysis. Thesis Leiden. 1978
  • 22 Kluft C. Studies on the fibrinolytic system in human plasma: quantitative determination of plasminogen activators and proactivators. Thromb Haemostas 1979; 41: 365-383
  • 23 Laurell CB. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 45-52
  • 24 Muller HP, Van Tilburg NH, Bertina RM, Terwiel JP, Veltkamp JJ. Immunoradiometric assay of procoagulant factor VIII antigen (VIII CAG). Clin Chim Acta 1980; 107: 11-19
  • 25 Bertina RM, Orlando M, Tiedemann-Alderkamp GHJ. Preparation of a human factor VII deficient plasma. Thromb Res 1978; 13: 537-541
  • 26 Edson JR, Krivit W, White JG. Kaolin partial thromboplastin time: High levels of procoagulants producing short clotting times or masking deficiencies of other procoagulants or low concentrations of anti-coagulants. J Lab Clin Med 1967; 70: 463-470
  • 27 Eisenberg S. Effect of posture and position of the venous sampling site on the hematocrit and serum protein concentration. J Lab Clin Med 1963; 61: 755-760
  • 28 Kluft C, Jie AFH. Interaction between the extrinsic and intrinsic system of fibrinolysis.. In: Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JF, Cêpelàk V, Samama MM, Desnoyers PC. (Eds) Vol 4: 25-31 Churchill Livingstone, Edinburgh; London - New York: 1979
  • 29 Mannucci PM, Mari D. Plasminogen activator response after DDAVP: a clinico-pharmacological study.. In: Progress in Fibrinolysis. Davidson JF, Nilsson IM, Åstedt B. (Eds) Vol 5: 65-69 Churchill Livingstone; Edinburgh: 1980
  • 30 Sutor AH. Gegenwärtiger Stand der DDAVP-Anwendung bei Blutern.. In: Minirin, DDAVP-Anwendung bei Blutern. Sutor AH. (Ed) 2-9 Schattauer Verlag; Stuttgart - New York: 1980
  • 31 Holemans R. Origin of blood fibrinolytic activity. Lancet 1963; 2: 364-365
  • 32 Rosing DR, Redwood DR, Brakman P, Astrup T, Epstein SE. The fibrinolytic response of man to vasoactive drugs measured in arterial blood. Thromb Res 1978; 13: 419-428
  • 33 Mannucci PM, Åberg M, Nilsson IM, Robertson B. Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 1975; 30: 81-93
  • 34 Shaldon S, Dolle W, Guevara L, Iber FL, Sherlock S. Effect of pitressin on the splanchnic circulation in man. Circulation 1961; 24: 797-807
  • 35 Edmunds R, West JP. A study of the effect of vasopressin on portal and systemic blood pressure. Surg Gyn Obst 1962; 114: 458-462
  • 36 Freedman AR, Kerr JC, Swan KG, Hobson RW. Primate mesenteric blood flow. Effects of vasopressin and its route of delivery. Gastroenterology 1978; 74: 875-878
  • 37 Kluft C. Quantitation and behaviour of extrinsic or vascular plasminogen activator in blood.. In: Progress in Fibrinolysis. Davidson JF, Nilsson IM, Åstedt B. (Eds) Vol 5: 24-30 Churchill Livingstone; Edinburgh: 1981
  • 38 Roodvoets AP, Neerbos BR, Hooghwinkel GJM, Hulsmann HAM, Beukers H. Hyperlipaemia in patients on regular dialysis treatment. Proc Eur Dial Transpl Assoc 1967; 4: 257-263
  • 39 Bagdade JD, Porte DJr, Bierman EL. Hypertriglyceridemia: a metabolic consequence of chronic renal failure. New Engl J Med 1979; 279: 181-185
  • 40 Daubresse JC, Lerson G, Plomteux G, Rorive G, Luyckx AS, Lefebvre PJ. Lipids and lipoproteins in chronic uraemia. A study of the influence of regular haemodialysis. Eur J Clin Invest 1976; 6: 159-166
  • 41 Nilsson B, Nilsson IM, Hedner U. Δ4-Ethylestrenol in recurrent deep venous thrombosis. Acta Med Scand 1981; 209: 45-49
  • 42 Sundqvist SB, Hedner U, Kullenberg HKE, Bergentz SE. Deep venous thrombosis of the arm: a study of coagulation and fibrinolysis. Br Med J 1981; 283: 265-267