KEY REPORTS IN THE HISTORY OF APC RESISTANCE
Proc Natl Acad Sci USA 90,1004-1008 (1993).
First report by Dahlbäck et al on the discovery of APC resistance and its association with familial thrombophilia.
First commercial test for APC resistance (Coatest® APC Resistance) available.
Lancet 342,1503-1506 (1993).
Leiden Thrombophilia study showing APC resistance as a major risk factor for venous thrombosis.
N Engl J Med 330, 517-521 (1994).
Second major study reported by Svensson et al showing APC resistance to be the major cause of venous thrombosis.Proc Natl Acad Sci USA 81, 1396-1400 (1994).
Article published by Dahlbäck and Hildebrand suggesting APC resistance to be caused by a genetic defect in the factor V gene.
Nature 369, 64-67 (1994).
Bertina et al demonstrate the association between a single point mutation in the factor V gene and APC resistance. The mutation results in the substitution of Arg506 with Gln, causing impaired APC inactivation of factor Va.
J Biol Chem 269, 18735-18738 (1994).
Article by Shen et al which demonstrates that intact factor V and protein S are synergistic cofactors to APC in the degradation of factor VIIIa.Ann Intern Med 125, 265-269 (1996).
van der Bom et al show that a low APC ratio is associated with increased risk for stroke, independent of the factor V mutation.
J Biol Chem 270, 24, 4053-4057 (1995).
The mechanism by which the FV:Q506 mutation leads to the APC phenotype is explained by Kalafatis et al. It is shown that the replacement of Arg506 by Gln delays the inactivation of factor Va.N Engl J Med 332, 912-917 (1995).
Prospective study by Ridker et al of healthy men showing APC resistance to an important risk factor for venous thrombosis but not for myocardial infarction.Lancet 346, 1133-1134 (1995).
Rees et al report on the distribution of FV:Q506 in 24 populations. The allele frequence was high among Europeans (4.4%), but low or absent among other ethnic groups.
Lancet 344, 1162-1163 (1994).Lancet 344, 1709 (1994)
Jorquera et al and Trossaërt et al suggest a modification of the original APC resistance test involving the dilution of sample plasma in factor V-deficient plasma.
J Clin Inv 94, 2521-2524 (1994).
Zöller et al identify the same FV:Q506 mutation in 47 out of 50 thrombophilic families with APC resistance.