Iranian Journal of Neurology 2017. 16(1):30-33.

Polymorphisms at activated protein C cleavage sites of factor V: Are they important in the absence of factor V Leiden?
Ehsan Kheradmand, Shaghayegh Haghjooy-Javanmard, Leila Dehghani, Mohammad Saadatnia


Background: Activated protein C (APC) inactivates factor V (FV) by cleavage of its heavy chain at Arg306, Arg506, Arg679, and Lys994. Mutational changes, which abolish APC cleavage sites, may predispose thrombosis by altering the inactivation process of FV. FV Leiden (FVL) (Arg506Glu) has been demonstrated as a strong risk factor for thrombosis. In the current study, we have studied whether mutations in the cleavage sites of FV for APC, not due to FVL, would have a role in presenting APC resistance (APCR) and initiation of a cerebral thrombotic event.

Methods: A group of 22 patients with a history of cerebral venous thrombosis (CVT), who were not carriers of FVL enrolled in the study. The patients who had conditions associated with acquired APCR were excluded from the study. APCR test was performed on the remaining 16 patients, which showed APCR in 4 plasma samples. DNA sequencing was performed on four exons of FV of APCR patients, encoding Arg306, Arg506, Arg679, and Lys994.

Results: Mutations were not found within nucleotides encoding the cleavage sites; neither was found within their close upstream and downstream sequences.

Conclusion: Our results show that polymorphisms affecting cleavage sites of FV other than Arg506Glu it would be less likely to be the basis for APCR and its increased thrombosis susceptibility. In addition, it emphasizes on the importance of screening for APCR in the patients diagnosed with CVT.


Cerebral Venous Thrombosis; Factor V; Activated Protein C Resistance; Cleavage Sites

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