Heparin cofactor II levels are increased by the use of combined oral contraceptives.

Heparin cofactor II (HCII) was assayed by a microtitre amidolytic substrate technique. A linear response was obtained up to 1.5 U/ml and HCII levels were not affected by freezing and thawing the plasma. The assay was validated by comparing HCII and antithrombin III (AT III) levels in AT-III-deficient plasmas and samples from critically ill patients. Higher HCII levels were found in healthy normal women than in healthy normal men (means 1.16 and 0.97 U/ml, respectively, P less than 0.01). A significant increase in HCII levels from 0.86 to 1.10 U/ml (mean values) was seen in healthy normal women starting on combined oral contraceptive (COC) preparations (P less than 0.001). Increased HCII levels were maintained over a 6-month period, but fell towards normal 14 days after stopping COC, although they were still significantly higher than before starting COCs. The discrepancy in HCII level between normal men and women may be due to COC use. In clinical studies, different reference ranges should be used for men and women, and the need for careful questioning about the use of COCs is emphasized.

PIP: Heparin cofactor II, a less well characterized heparin-dependent antithrombin factor than antithrombin III, was determined in 11 women before, during and after a 6 month trial of oral contraceptives, in 16 women aged 18-60, in 16 men aged 22-55, in 5 patients with known antithrombin III deficiency, and in a series of 16 patients in a critical care unit. The oral contraceptives used in the trial were Femodene (Schering, Burgess, Hill, U.K.) in 6 women and Marvelon (Organon, Cambridge, U.K.) in 5. The assay was an amidolytic microtiter method standardized against normal human serum. The assay was linear up to 1.5 U/ml, and HCII was not lost by repeated freezing and thawing. HCII levels were normal in patients with AT III deficiency, but ranged from 0.10-1.11 in intensive care patients. In normal subjects the mean HCII levels were 1.07 U/ml, and were significantly higher for women, 1.16, than for men, 0.97 U/ml. During intake of oral contraceptives, HCII rose significantly from 0.86 u/ml to 1.10 at cycle 1, 1.08 at cycle 3, and 1.19 at cycle 6. 2 weeks after stopping pills, the mean HCII level fell to 1.03. In contrast, AT III declined during pill cycles.

[Prothrombotic and prethrombotic markers in obese diabetic and non-diabetic subjects]. / Indici protrombotici e pretrombotici in soggetti obesi diabetici e non diabetici.

The Authors studied the behaviour of some prothrombotic (fibrinogen, factor VII, antithrombin III and tissue plasminogen activator) and prethrombotic (beta thromboglobulin, D-dimer) markers in a group of obese subjects in relation to various physiopathological parameters. The series consist of 93 obese subjects (29 m, 64 f, mean age 55 +/- 6 yrs, BMI 33 +/- 1), of whom 62 suffering from type 2 diabetes in good metabolic control obtained by oral hypoglycemic (42 cases) or insulin (20 cases) treatment. For each subject the Authors determined the plasmatic levels of glucose, total cholesterol, triglycerides (enzymatic method, Boehringer kits), fibrinogen (coagulometric method, Organon kit), factor VII (chromogenic method, IL kit), antithrombin III (chromogenic method, IL kit), tissue plasminogen, beta thromboglobulin and D-dimer (ELISA method, Boehringer kits). The results were examined in relation to sex, age, overweight degree, waist/thigh ratio, total cholesterol, triglycerides and, for diabetics, to the therapeutical treatment. The fibrinogen plasma levels proved statistically (0.05) increased proportionally to the overweight degree (BMI over 35), cholesterol levels (over 250 mg%) and age (51-65 yrs); factor VII showed a significant increase (0.05) related to the cholesterol levels, the overweight degree and, surprisingly, to female sex; as regards antithrombin III, its sharp reduction was related with ageing and with the "gynoid type" waist/thigh ratio; tissue plasminogen activator showed a statistically significant reduction (0.05) in the group with older age (over 65 yrs); the beta thromboglobulin levels were obviously increased (0.05) in the hypercholesterolemic and hypertriglyceridemic subjects (over 250 mg%), the D-dimer values increased proportionally with age (0.05).(ABSTRACT TRUNCATED AT 250 WORDS)