The activation of the contact phase of coagulation by physiologic surfaces in plasma: the effect of large negatively charged liposomal vesicles

Abstract

The endogenous, negatively charged surface that induces activation of the contact coagulation factors was investigated in plasmas taken from women in late pregnancy and control subjects of child-bearing age. The plasmas from the two groups of subjects were incubated at 4 degrees C for 24 hours either in plastic or in glass tubes and the factor VII coagulant activity (VIIc) was assayed in the treated plasmas. The activation of factor VII under these conditions involves the generation of enzymes derived from factor XII (XIIa). The contact surface is rate- limiting for the activation of factor VII in the plasmas in both groups of subjects and can be supplemented by large multilamellar liposomal vesicles carrying the appropriate density of negative charge. The size of these vesicles is within the range of sizes of the large lipoprotein particles (chylomicrons, very low and intermediate-density lipoproteins). The relationship between the density of negative charge on the liposomal vesicles and VIIc was similar in the late pregnancy and the control plasmas incubated in plastic tubes. At a saturating density of negative charge the observed relative VIIc was similar in both sets of plasmas. The incubation of late pregnancy or control plasma in plastic tubes in the presence of sodium stearate caused VIIc to increase with increasing concentration of the added fatty acid. These results suggest that large lipoprotein particles carrying the appropriate free fatty acid at a sufficient density of negative charge could provide the contact surface that induces the generation of factor XIIa and the subsequent activation of factor VII. Moreover, plasmas from women in late pregnancy have a higher concentration of potential surface and a higher density of negative charge than the plasmas from nonpregnant women.

Impact ofn-3 fatty acid supplemented parenteral nutrition on haemostasis patterns after major abdominal surgery

“…2), which is a component of the contact system of blood coagulation which also includes prekallikrein, HMW kininogen and factor XI. Because the main physiological activators of factor XII include fatty acids and the surface of certain types of lipoprotein particles (Mitropoulos et al 1989), analysis of factor XIIa during differential PUFA administration was of special interest. In contrast to the effect on extrinsic factor VIIa, surgical trauma was of minor influence for intrinsic factor XIIa levels.…”

Non-Fasting Factor VII Coagulant Activity (FVII:C) Increased by High-Fat Diet

“…How dietary fat promotes activation of FVII is unclear. It has earlier been proposed that triglyceride-rich lipoproteins [chylomicrons and very low density lipoproteins (VLDL)] are capable of activating FXII to FXIIa, and that FXIIa subsequently may cleave FVII zymogen to the active form, FVIIa (8,15,16). Recent observations by Mitropoulos et al indicate that it is rather products from the lipolytic degradation of triglyceride-rich lipoproteins than the lipoproteins themselves that promote the initial activation of FXII (17).…”

“…Blood samples were drawn at 8.00 h. 16.30 h and 19.30 h after 10 min of standardized resting (5 min in a chair followed by 5 min of supine resting). Blood samples at 8.00 h were drawn after at least 10 h fasting and non-smoking, and 24 h abstention from alcohol.…”

Coagulation Factor VII, Dietary Fat and Blood Lipids: A Review

“…Several in vitro experi ments showed that when stearic acid or vesicles, with a negative charge and size similar to TRLP, were added to plasma, FVIIc increased in a dose-dependent manner. Oleic acid and other unsaturated fatty acids had no effect on FVIIc (39,40). Lipoprotein lipase (LPL) seems to be A 2% lower important in this reaction; when plasma of hypertriglyceridaemic patients with LPL deficiency was treated with LPL factor XII was promptly activated (41).…”