Plasma resistance to activated protein C: an important link between venous thromboembolism and combined oral contraceptives - a short review

Author(s):  
J. Jespersen
1987 ◽  
Author(s):  
S J Machin ◽  
I J Mackie ◽  
K Walshe ◽  
M D Gillmer

The haemostatic system was investigated in 26 women taking cyclically administered triphasic combined oral contraceptives for the first time during their first six cycles. Fourteen women received Logynon (mean dose 32.4μg ethinyloestradiol, 92pg progestagen) and 12 received SHD 415G (Schering) which contains a mean dosage of 32.4μg ethinyloestradiol and 78pg gestodene, a recently developed progesterone. The Logynon group showed a significant increase (p<0.005) in fibrinogen (pre-mean 284.4 g/1; after 1 cycle 347.3 g/1, after 6 cycles 318.6 g/1) , factor VII (65.8 u/1 to 73.9 u/1 to 83.2 u/1), factor XII (1.74 u/1 to 2.41 u/1, to 2.25 u/1), plasminogen (100.9 u/1 to 135.1 u/1 to 126.3 u/1); decrease in ATIII (115.9 u/1 to 103.1 u/1 to 93.4 u/1) but no significant change in factor X (98.4 u/1 to 108.9 u/1 to 102.4) or protein C (0.85 u/1 to 0.88 u/1 to 0.94 u/1) activity. The SHD 415G group showed similar changes with an increase in fibrinogen (247.9 g/1 to 330.8 g/1 to 373 .1 g/1), factor VII (63.1 u/1 to 73.1 u/1 to 90.3 u/1, factor X (98.3 u/1 to 112.0 u/1 to 124.4 u/1), factor XII (1.46 u/1, to 1.93 u/1, to 2.03 u/1), plasminogen (110.8 u/1 to 125.4 u/1 to 136.7 u/1); decrease in ATIII (113.1 u/1 to 96.3 u/1 to 89.7 u/1), but no change in protein C (0.84 u/1 to - 0.78 u/1 to 0.85 u/1) activity. These changes were apparent after the first cycle of therapy and the differences were maintained over the six cycle period. There was no increase in protein C activity despite changes in the other vitamin K dependent proteins factors VII and X. Both low oestrogen dose triphasic pills caused similar prothrombotic changes which were not modified by the new progesterone, gestodene.


1996 ◽  
Vol 10 ◽  
pp. 153-154
Author(s):  
O.D. Pedersen ◽  
J. Sidelmann ◽  
J. Gram ◽  
J. Jespersen

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1552-1557 ◽  
Author(s):  
F. Bernardi ◽  
E.M. Faioni ◽  
E. Castoldi ◽  
B. Lunghi ◽  
G. Castaman ◽  
...  

AbstractFactor V gene polymorphisms were investigated to detect components that may contribute to the activated protein C (APC) resistance phenotype in patients with venous thromboembolism. A specific factor V gene haplotype (HR2) was defined by six polymorphisms and its frequency was found to be similar in normal subjects coming from Italy (0.08), India (0.1), and Somalia (0.08), indicating that it was originated by ancestral mutational events. The relationship between the distribution of normalized APC ratios obtained with the functional assay and haplotype frequency was analyzed in patients heterozygous for factor V R506Q (factor V Leiden). The HR2 haplotype was significantly more frequent in patients with ratios below the 15th percentile than in those with higher ratios or in normal controls. Moreover, the study of 10 patients with APC resistance in the absence of the factor V R506Q mutation showed a 50-fold higher frequency of HR2 homozygotes. The HR2 haplotype was associated with significantly lower APC ratios both in patients with venous thromboembolism and in age- and sex-matched controls. However, the two groups showed similar HR2 haplotype frequencies. Plasma mixing experiments showed that an artificially created double heterozygote for the factor V R506Q mutation and the HR2 haplotype had an APC ratio lower than that expected for a simple R506Q heterozygote. Time-course experiments evaluating the decay of factor V in plasma showed the normal stability of the molecule encoded by the factor V gene marked by the HR2 haplotype, which ruled out the presence of a pseudo-homozygous APC resistance mechanism. Our results provide new insights into the presence of factor V genetic components other than the factor V R506Q that are able to contribute to the APC resistance phenotype in patients with venous thromboembolism.


The Lancet ◽  
1994 ◽  
Vol 343 (8902) ◽  
pp. 917 ◽  
Author(s):  
B. Lindblad ◽  
Pj Svensson ◽  
B. Darhlbäck

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