Thromb Haemost 1985; 54(04): 792-798
DOI: 10.1055/s-0038-1660135
Original Article
Schattauer GmbH Stuttgart

Fibrinopeptide A in Urine from Patients with Venous Thromboembolism, Disseminated Intravascular Coagulation and Rheumatoid Arthritis - Evidence for Dephosphorylation and Carboxyterminal Degradation of the Peptide by the Kidney

O C Leeksma
The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands
,
F Meijer-Huizinga
The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands
,
E A Stoepman-van Dalen
The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands
,
W G van Aken
The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands
,
J A van Mourik
The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 18 February 1985

Accepted 06 September 1985

Publication Date:
19 July 2018 (online)

Summary

Urinary fibrinopeptide A immunoreactivity was determined by radioimmunoassay using two anti-fibrinopeptide A sera with a different specificity in patients with venous thromboembolism, disseminated intravascular coagulation and rheumatoid arthritis. Elevated levels were frequently observed with both sera, and intravenous administration of heparin in patients with a thromboembolic disorder resulted in a decline of urinary fibrinopeptide A (FPA) concentrations to normal or nearly normal values. For both sera significant correlations with plasma levels were found although one of the sera reacted significantly better with the material in urine samples from these patients than the other (p <0.0001, n = 73). Analysis of urinary fibrinopeptide A immunoreactivity by high performance liquid chromatography (HPLC) provided evidence that A peptide material present in this body fluid was heterogeneous. In view of the characteristics of the antisera used in this study, data suggest that urinary FPA immunoreactivity consists to a large extent of carboxyterminally degraded FPA. Excretion of circulating FPA immunoreactive material through the kidneys apparently involves dephosphorylation and carboxyterminal breakdown of the A peptide. Since both synthetic and native phosphorylated or unphosphorylated fibrinopeptide A appeared to be stable in urine in vitro, an active role of the kidney in degrading the A peptide is likely.

 
  • References

  • 1 Blombäck B, Blombäck M, Edman P, Hessel B. Human fibrinopep-tides. Isolation, characterization and structure. Biochim Biophys Acta 1966; 115: 371-396
  • 2 Seydewitz HH, Kaiser C, Witt I. The localization of a second phosphorylation site in the human Aα chain. Thromb Res 1984; 33: 487-498
  • 3 Nossel HL, Younger LR, Wilner GD, Procupez T, Canfield RE, Butler VP. Radioimmunoassay of human fibrinopeptide A. Proc Natl Acad Sci USA 1971; 68: 2350-2353
  • 4 Gerrits W BJ, Flier O ThN, Meer Jvan der. Fibrinopeptide A immunoreactivity in human plasma. Thromb Res 1974; 5: 197-212
  • 5 Cronlund M, Hardin J, Burton J, Lee L, Haber E, Block KJ. Fibrinopeptide A in plasma of normal subjects and patients with disseminated intravascular coagulation and systemic lupus erythematosus. J Clin Invest 1976; 58: 142-151
  • 6 Nossel HL, Yudelman I, Canfield RE, Butler Jr VP, Spanondis K, Wilner GD, Qureshi GD. Measurement of fibrinopeptide A in human blood. J Clin Invest 1974; 54: 43-53
  • 7 Yudelman IN, Nossel HL, Kaplan KL, Hirsh J. Plasma fibrinopeptide A levels in symptomatic venous thromboembolism. Blood 1978; 51: 1189-1195
  • 8 Peuscher FW, van Aken WG, Flier OTh, Stoepman-van Dalen EA, Creemer-Gootte ThM, van Mourik JA. Effect of anticoagulant treatment measurement by fibrinopeptide A (fpA) in patients with venous thromboembolism. Thromb Res 1980; 18: 33-43
  • 9 Leeksma OC, Meijer-Huizinga F, van Mourik JA. Fibrinopeptide A and the phosphorylation of fibrinogen. In: Fibrinogen, fibrin formation and fibrinolysis Lane D, Henschen A, Jasani K. (eds) W de Gruyter; New York: 1985. (in press)
  • 10 Lane DA, Sioddlak M, Thompson E, Allen-Mersh TG. Clearance of human desaminotyrosyl fibrinopeptide A from the rat circulation. Role of the kidney and proteolytic enzymes. Thromb Res 1982; 26: 73-82
  • 11 Alkjaersig N, Fletcher AP. Catabolism and excretion of fibrinopeptide A. Blood 1982; 60: 148-156
  • 12 Harenberg J, Stehle S, Waibel St, Hermann HJ, Eisenhut M, Zimmerman R. Disposition of human fibrinopeptide A in normal and nephrectomized rabbits. Thromb Res 1983; 32: 1-13
  • 13 Lane DA, Ireland H, Knight J, Wolff S, Kyle P, Curtis JR. The significance of fibrinogen derivatives in plasma in human renal failure. Br J Haematol 1984; 56: 251-260
  • 14 Blombäck B. Fibrinogen to fibrin transformation. In: Blood Clotting Enzymology Seegers W. (ed) Academic Press; New York: 1967: 143-215
  • 15 Goodriend TL, Levine L, Fasmann GD. Antibodies to bradykinin and angiotensin: a use of carbodiimides in immunology. Science 1964; 144: 1344-1346
  • 16 Koehn JA, Canfield RE. Purification of human fibrinopeptides by high-performance liquid chromatography. Anal Biochem 1981; 116: 349-356
  • 17 Kehl M, Lottspeich F, Henschen A. Analysis of human fibrinopeptides by high-performance liquid chromatography. Hoppe-Sey-ler’s. Z Physiol Chem 1981; 362: 1661-1664
  • 18 Spackman DH, Stein WH, Moore S. Automatic recording apparatus for use in the chromatography of amino acids. Anal Chem 1958; 30: 1190-1206
  • 19 Merskey C, Kleiner GJ, Johnson AJ. Quantitative estimation of split products of fibrinogen in human serum, relation to diagnosis and treatment. Blood 1966; 28: 1-18
  • 20 Godal MC, Abildgaard U. Gelation of soluble fibrin in plasma by ethanol. Scand J Haematol 1966; 3: 342-350
  • 21 Canfield RE, Dean J, Nossel HL, Butler VP, Wilner GD. Reactivity of fibrinogen and fibrinopeptide A containing fibrinogen fragments with antisera to fibrinopeptide A. Biochemistry 1976; 15: 1203-1208
  • 22 Bilezikian SB, Nossel HL. Unique pattern of fibrinogen cleavage by human leucocyte proteases. Blood 1977; 50: 21-28
  • 23 Wilner GD, Nossel HL, Canfield RE, Butler VP. Immunochemical studies of human fibrinopeptide A using synthetic peptide homologues. Biochemistry 1976; 15: 1209-1213
  • 24 Qureshi GD, Nossel HL. Stability studies of human fibrinopeptide A as measured by radioimmunoassay. Proc Soc Exp Biol 1972; 140: 1069-1072