APC Resistance | Activated Protein C Resistance | Factor V Leiden



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• February

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.

• July

First commercial test for APC resistance (Coatest® APC Resistance) available.

• December

Lancet 342,1503-1506 (1993).

Leiden Thrombophilia study showing APC resistance as a major risk factor for venous thrombosis.


• February

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.

• May

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.

• July

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.


• October

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.

• December

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.

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