Further Studies on the Modulation of Blood Coagulation by Human Serum Amyloid P Component and Its Acute Phase Homologue C-Reactive Protein

Summary

Serum amyloid P component (SAP), and its acute phase homologue C-reactive protein (CRP), prolonged activated partial thromboplastin times (APTT) in cell free plasma when assayed at physiological concentrations in the presence of heparin. SAP also inhibited clot formation initiated through the extrinsic and terminal phases of coagulation in heparinized cell free plasma, an activity not shared with CRP. When CRP and SAP were similarly evaluated in whole blood using the thromboelastograph (TEG), CRP delayed the onset of coagulation and the initial rate of fibrin formation/polymerization; final clot patency was unaltered. SAP suppressed the anticoagulant activity of heparin in the TEG assay, unlike results obtained in heparinized cell free plasma, by facilitating a more rapid onset of coagulation, increasing the rate of fibrin formation/polymerization, and correcting clot patency. The data provided offer further evidence that these homologues can intercede in blood coagulation.

Keywords

C-reactive protein - Coagulation - Heparin - Serum amyloid P component - Thromboelastograph

• References

• 1 Pepys MB, Dash AC, Markham RE, Thomas HC, William BD, Petrie A. Comparative clinical study of protein SAP (Amyloid P Component) and C-reactive protein in serum. Clin Exp Immunol 1978; 32: 119-124
• 2 Cathcart ES, Comerford FR, Cohen AS. Immunological studies on a protein extracted from human secondary amyloid. N Engl J Med 1965; 273: 143-146
• 3 Pepys MB, Dash AC, Ashley J. Isolation of C-reactive protein by affinity chromatography. Clin Exp Immunol 1977; 30: 32-37
• 4 Pepys MB, Dash AC, Munn A, Feinstein A, Skinner M, Cohen AS, Gewurz H, Osmand AP, Painter RH. Isolation of amyloid P component (protein AP) from normal serum as a calcium-dependent binding protein. Lancet 1977; i: 10229-10231
• 5 Painter RH. Evidence that Clt (amyloid-P component) is not a subcomponent of the first component of complement (C1). J Immunol 1977; 119: 2203-2205
• 6 Boxer GJ, Bang NU, Ferroni JW, Benson MD. Plasma amyloid P component inhibits heparin activity. Blood 1977; (Suppl. 50) (Supplement) 260 (Abstr)
• 7 Hansen B, Hutchcraft C, Gewurz H. Interaction of serum amyloid P component with heparin. Fed Proc 1982; 41: 560
• 8 Thompson AR, Enfield DL. Human plasma P component: isolation and characterization. Biochemistry 1978; 17: 4304-4311
• 9 Pepys MB, Dyck RF, de Beer FC, Skinner M, Cohen AS. Binding of serum amyloid P component (SAP) by amyloid fibrils. Clin Exp Immunol 1979; 38: 284-293
• 10 Hutchcraft C, Hansen B, Harling VO, Gewurz H. Binding reactivities of serum amyloid P component. Ann NY Acad Sci 1982; 389: 449-450
• 11 Hutchcraft C, Gewurz H, Hansen B, Dyck RF, Pepys MB. Agglutination of complement-coated erythrocytes by SAP. J Immunol 1981; 126: 1217-1219
• 12 Baltz ML, de Beer FC, Feinstein A, Pepys MB. Calcium-dependent aggregation of human serum amyloid P component. Biochem Biophys Acta 1982; 701: 229-236
• 13 Baltz ML, Holford S, de Beer FC, Whaley K, Pepys MB. The interaction between human serum amyloid P component (SAP) on fixed complement. Ann NY Acad Sci 1982; 389: 429-430
• 14 de Beer FC, Baltz ML, Holford S, Feinstein A, Pepys MB. Fibronectin and C4-binding protein are selectively bound by aggregated amyloid P component. J Exp Med 1981; 154: 1134-1149
• 15 Dyck RF, Lockwood CM, Kershaw M, McHugh N, Duance V, Baltz M, Pepys MB. Amyloid P component is a constituent of normal human glomerular basement membrane. J Exp Med 1980; 152: 1162-1164
• 16 Breathnach SM, Melrose SM, Tennent B, Black MM, Pepys MB. Amyloid P component is located on elastic fibre: microfibrils in normal human tissue. Nature (London) 1981; 293: 652-654
• 17 Osmand AP, Friedensen B, Gewurz H, Painter RH, Hofman T, Shelton E. Characterization of C-reactive protein and the complement subcomponent Clt as homologous proteins displaying cyclic pen-tameric symmetry (Pentraxins). Proc Natl Acad Sci USA 1977; 74: 739-743
• 18 Gewurz H, Mold C, Siegel J, Fiedel B. C-reactive protein and the acute phase response. In Advances in Internal Medicine Stollerman GH. (ed.) Vol 27, pp 345-372 Year Book Medical Pub; Chicago: 1982
• 19 Ku CS L, Fiedel BA. Modulation of fibrin clot formation by human serum amyloid P component (SAP) and heparin. J Exp Med 1983; 158: 767-780
• 20 Pepys MB, Becker GJ, Dyck RF, McCraw A, Hilgard P, Merten RF, Thomas DP. Studies of human serum amyloid P component (SAP) in relation to coagulation. Clin Chim Acta 1980; 105: 83-91
• 21 Marder RJ, Fiedel BA, Osmand AP, Gewurz H. Inhibition of rabbit platelet aggregation and clot retraction by rabbit and human C-reactive proteins. Proc Soc Exp Biol Med 1977; 155: 44-47
• 22 Lowry O, Rosenbrough NJ, Farr AL, Randall RJ. Protein measurement with folin phenol-reagent. J Biol Chem 1951; 193: 265-275
• 23 Haupt H, Heimbruger N, Bauder S. Humanserum-Protein mit hoher Affinität zu Carboxymethyl-Cellulose. III. Physikalisch-chemische und immunologische Charakterisierung eines metallbindenden 9,5s-α₁Glykoproteins (CM-Protein III). Hoppe-Seyler’s Z Physiol Chem 1972; 353: 1841-1849
• 24 Fiedel BA, Potempa LA, Frenzke ME, Simpson RM, Gewurz H. Platelet inhibitory effects of CRP preparations are due to a co-isolating low molecular weight factor. Immunology 1982; 45: 15-22
• 25 Seegers WH. The quantity of thrombin required to clot heparinplasma mixtures. Proc Soc Exp Biol Med 1942; 51: 172-173
• 26 Starrett D. Applications of a thromboelastography. American Clinical Product Review 1985; 4: 34-43
• 27 Fiedel BA, Ku CS L. Serum amyloid-P-component (SAP) and hemostasis: a continuing evaluation. In Marker Proteins of Inflammation Laurent P, Grimaud JA, Bienvenu J. (eds.) vol 3 Walter de Gruyter and Co; Berlin: 1986. (in press)
• 28 Niewiarowski S, Paul D. Platelet granule proteins with mitogenic and anti-heparin activity. In Platelets in Biology and Pathology Gordon JL. (ed.) vol 2, pp 91-106 Elsevier/North Holland Biomedical Press; Amsterdam: 1981
• 29 Pepys MB, Baltz ML. Acute phase proteins with special reference to C-reactive protein and related proteins (Pentaxins) and serum amyloid A protein. Adv Immunol 1983; 34: 141-212