A longitudinal study of the factor VII rise during pregnancy.

A longitudinal study of 21 pregnant women has been undertaken using a variety of factor VII assays, including factor VIIa, to investigate the increase of factor VIIc. All assays demonstrated significant rises (p <0.001), most marked for factor VIIa (82%) and factor VIIc rabbit (81%). Smaller rises were seen for factor VIIc bovine (50%) and VII antigen (40%). Three indirect measures of activity state, factor VIIc rabbit:antigen, bovine:antigen and bovine:rabbit, provided conflicting data. Factor VIIa:antigen showed a significant increase of 36% (p <0.001). Within individual pregnancies the change in factor VIIc rabbit and antigen correlated with maternal weight gain (p < 0.05). Two activity state measures, bovine:rabbit and bovine:antigen, showed negative correlation with birthweight. The increases in both zymogen and in activity state appear to contribute to the factor VIIc rise. The extent of this rise appears to be influenced by maternal weight gain. Increased factor VII activation is associated with reduced foetal growth.

The effect of hormone replacement therapy of the age-related rise of factor VIIc, and its activity state.

Although hormone replacement therapy (HRT) appears to protect women from ischaemic heart disease (IHD), its use is associated with increased factor clotting activity (VIIc), an independent risk factor for IHD. The nature of this factor VII rise was therefore examined in a cross-sectional study of 279 women aged between 40 and 65 years. Ninety-four were pre-menopausal, 44 were post-menopausal and taking HRT, whilst 141 were post-menopausal non-users. For those women on oestrogen-only HRT, the mean factor VIIc was 144%, compared to 130% for post-menopausal non-users, and 116% for those on combined HRT. These differences were significant (p = 0.01). Oestrogen-only users also had significantly higher mean levels of factor VIIa (3.3 ng/ml) compared to non-users (2.2 ng/ml) and those on oestrogen-progestogen HRT (2.2 ng/ml-p = 0.015). In contrast for factor VII antigen the mean values of the three groups were similar. Analysis of the age-regression slopes showed a significant age-related rise in factor VIIc of 1.2% per annum (p < 0.01) for post-menopausal non-users. There was a similar increase in factor VII antigen (2.1%) but no rise in factor VIIa. For all HRT users there was no change with age for any of the factor VII measures. Thus the age-related rise in factor VIIc appears to be due to an increase in factor VII zymogen alone, and taking HRT seems to abolish such a rise. In contrast, the increased factor VIIc seen with oestrogen-only HRT appears to be secondary to factor VII activation.

The cause of turbidity in lyophilised plasmas and its effects on coagulation tests.

AIMS: To investigate the cause of turbidity in reconstituted lyophilised plasmas and to determine its effect on coagulometers. METHODS: The turbidities of 20 normal plasmas and 16 reconstituted lyophilised plasmas were determined by comparing a 1 in 4 dilution in distilled water with a standard suspension in an Aminco Fluorocolorimeter (American Instrument Co) in nephelometric mode. The turbidities of five other plasmas were determined before and after lyophilisation. The turbid components of fresh and reconstituted lyophilised plasmas were studied using electron microscopy. The effects of turbidity on five types of coagulometer were determined by adding varying concentrations of a turbidity enhancing material. RESULTS: Reconstituted lyophilised plasmas were more turbid than normal plasmas, because of agglomerated liposomes. Serum depleted of chylomicrons and very low density lipoproteins was not rendered more turbid by lyophilisation. Three out of five types of automated coagulometer tested gave activated partial thromboplastin times which were appreciably affected by plasma turbidity. One of the instruments was unable to detect a clot in a moderately turbid plasma. A second instrument gave results which were significantly affected by turbidity. Turbidity of the substrate plasma did not affect specific factor VIII assays in two types of coagulometer. CONCLUSIONS: Lyophilisation of plasma induces turbidity due to the agglomeration of lipids. Such turbidity can affect the results of coagulation tests. Suppliers of lyophilised plasmas should be aware of this problem.

Production of plasma selectively depleted in fibrinogen by affinity chromatography.

An affinity chromatography column was prepared using a polyclonal anti-fibrinogen antibody bound to Sephacryl S 1000. Normal human plasma was depleted of fibrinogen by passage through this column. The fibrinogen free plasma corrected the prolonged clotting times of plasmas deficient in factors V, VII, VIII and IX. Clottable fibrinogen was recovered from the column. An immunodepleted fibrinogen free plasma could fulfil a useful role in internal and external quality control alone, or in combination with other test materials; it could also be used in research.