Heparin Cofactor II (HCII) Levels and the Risk of Ischemic Stroke. No Deleterious Role of HCII Deficiency but Potential Protective Role of High Plasma Level

Background: Heparin cofactor II (HCII) is a thrombin inhibitor which activity is dramatically enhanced by heparin and more specifically by dermatan sulfate, another glycosaminoglycan. Its pathophysiological role remains unknown even if cases of HCII deficiency were reported in patients with a history of venous or arterial thrombosis. Recently, it was suggested that high plasma HCII level could play a protective role against atherosclerosis in elderly individuals and protect from restenosis after femoro-popliteal or coronary artery stenting. The aim of this case-control study was to investigate the significance of plasma HCII level in the development of ischemic stroke.

Methods: 81 cases (44 M and 37 F, mean age of 43 years, range: 22–63) and 80 age-and sex-matched healthy controls of the same ethnic origin. HCII activity was evaluated as antithrombin dermatan sulfate cofactor activity using a chromogenic assay. Test results were expressed in arbitrary unit per mL: 1 U/mL is the activity found in 1 mL of pooled normal human plasma.

Results: Plasma HCII activity was not significantly different in cases and in controls (1.04±0.17 vs. 1.00±0.23). The same applied after stratification in males and in females. The normal range for HCII, previously defined in a large cohort of healthy individuals, was between 0.60 and 1.40 U/mL. The frequency of HCII deficiency was not significantly different in cases and in controls [n=3/81 (3.7%) vs. n=2/80, (2.5%); p=1.00] and the same applied to the frequency of HCII level above 1.40 U/mL [n=0/81 (0%) vs. n=2/80 (2.5%); p=0.25]. Interestingly, HCII activity was found above 1.30 U/mL in 7 controls and in only 1 case (p<0.05), none presenting with any of pathophysiological state usually associated with increased HCII levels such as pregnancy, oral contraceptive, inflammation, infection, or acute phase of illness.

Conclusions: These results suggest that HCII deficiency is not in itself a risk factor for the development of ischemic stroke. Even if the frequency of HCII level above the normal range was not statistically different in cases and in controls, the significance of a higher proportion of controls than cases presenting with a HCII level in the high end of the normal range deserves to be further evaluated in connection with a potential protective role against ischemic stroke.