Plasma Levels of Heparin Cofactor II (HCII) and Thrombin-HCII Complex in Patients with Disseminated Intravascular Coagulation

Abstract

Plasma levels of heparin cofactor II (HCII), thrombin-HCII complex (THC), antithrombin (AT), and thrombin-AT complex (TAT) were evaluated in patients with disseminated intravascular coagulation (DIC) associated with several underlying diseases. Plasma levels of AT were significantly reduced in almost all underlying diseases associated with DIC, but the plasma levels of HCII and HCII/AT ratio were significantly reduced only in patients with infections. While the plasma level of TAT was significantly increased in patients with all underlying diseases associated with DIC, the increase of THC was not significant. Plasma levels of AT were significantly reduced in DIC and pre-DIC associated with almost all underlying diseases, but those of HCII were significantly reduced only in DIC and pre-DIC patients with inflammatory diseases. The plasma levels of TAT were significantly increased in DIC, pre-DIC, and non-DIC patients with all underlying diseases, and those of THC were significantly increased in DIC and pre-DIC patients with inflammatory diseases. The plasma levels of THC were not significantly increased in non-DIC patients of any disease group. The decrease of AT may be caused by thrombin generation or inflammatory reaction that occurs in DIC associated with underlying diseases, while the decrease of HCII might be caused by both thrombin generation and inflammatory reaction. Finally, AT inhibits thrombin more strongly than HCII in several underlying diseases associated with DIC except for inflammatory diseases. In inflammatory diseases, HCII might play an important role in preventing the onset of DIC.

Keywords

Heparin cofactor II Thrombin-heparin cofactor II complex DIC Infection

References

1. Bick RL . Disseminated intravascular coagulation and related syndromes: A clinical review. Semin Thromb Hemost 1998;14:299-299.

2. Muller-Berghaus G. Pathophysiologic and biochemical events in desseminated intravascular coagulation: Dysregulation of procoagulant and anticoagulant pathways. Semin Thromb Hemost 1989;15:58-58.

3. Buller HR , ten Cate JW . Acquired antithrombin III deficiency: Laboratory diagnosis, incidence, clinical implications, and treatment with antithrombin III concentrate. AmJMed 1989;87(Suppl. 3B):44S-44S.

4. Mammen EF , Miyakawa T , Murano G , et al. Human antithrombin concentrates and experimental disseminated intravascular coagulation. Semin Thromb Haemost 1985; 11:373-373.

5. Okugawa Y , Wada H , Noda N , et al. Increased plasma levels of tissue factor pathway inhibitor-activated factor X complexes in patients with disseminated intravascular coagulation. Am J Hematol 2000;65:210-210.

6. Wada H , Gabazza E , Nakasaki T , et al. Diagnosis of disseminated intravascular coagulation by hemostatic molecular markers. Semin Thromb Hemost 2000;26:17-17.

7. Roman K , Rosenthal E , Razavi R. Pulmonary arterial thrombosis in a neonate with homozygous deficiency of antithrombin III: Successful outcome following pulmonary thrombectomy and infusions of antithrombin III concentrate. Cardiol Young 2000;10:275-275.

8. Matsuo T , Kario K , Sakamoto S , et al. Hereditary heparin cofactor II deficiency and coronary artery diseases. Thromb Res 1992;65:495-495.

9. Tollefsen DM , Majerus DW , Blank MK . Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma. J Biol Chem 1982;257:2162-2162.

10.

10. Anderson TR , Sie P , Pelzer H , et al. Elevated levels of thrombi-heparin cofactor II complex in plasma from patients with disseminated intravascular coagulation. Thromb Res 1992;66:591-591.

11.

11. Smith D. Report of the International Meetig on Intensive Care Medicine, Rome, Italy, October 1-4, 2000. Crit Care 2000;4:255-255.

12.

12. Bernard GR , Vincent JL , Laterre PF , et al. Efficacy and safety for recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-699.

13.

13. Kobayashi N , Maegawa K , Takada M , et al. Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the Research Committee on DIC in Japan. Bibl Haematol 1987;49:265-265.

14.

14. Wada H , Minamikawa K , Wakita Y , et al. Hemostatic study before onset of disseminated intravascular coagulation. Am J Hematol 1993;44:85-85.

15.

15. Wada H , Sakuragawa N , Shiku H. Hemostatic molecular markers before onset of disseminated intravascular coagulation in leukemic patients. Semin Thromb Hemost 1998; 24:293-293.

16.

16. Nielsen JD . The effect of antithrombin on the systemic inflammatory response in disseminated intravascular coagulation. Blood Coagul Fibrinol 1998;9(suppl 3):S11-S11.

17.

17. Waydhas C , Nast-Kolb D , Gippner-Steppert C , et al. Highdose antithrombin III treatment of severely injured patients: Results of a prospective study. J Trauma 1998;45: 931-931.

18.

18. Esmon C. Role of coagulation inhibitors in inflammation. Thromb Haemost 2001;86:51-51.

19.

19. Kario K , Matsuo T , Kodama K , et al. Preferential consumption of heparin cofactor II in disseminated intravascular coagulation associated with acute promyclocytic leukemia. Thromb Res 1992;66:435-435.

20.

20. McGuire EA , Tollefsen DM . Activation of heparin cofactor II by fibroblasts and vascular smooth muscle cells. J Biol Chem 1987;262:169-169.