polymorphisms at activated protein c cleavage sites of factor v: are they important in the absence of factor v leiden?

introduction : activated protein c (apc) inactivates factor v 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 factor v.  factor v leiden (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 factor v for apc, not due to fvl, would have a role in presenting apc resistance and initiation of a cerebral thrombotic event. methods : a group of 22 patients with history of cvt who were not carriers of fvl enrolled in the study. the patients who had conditions associated with acquired apc resistance were excluded from the study. apc resistance test was performed on the remaining 16 patients, which showed apc resistant in 4 plasma samples. dna sequencing was performed on four exons of factor v of apc resistant patients, encoding arg306, arg506, arg679, and lys994. findings : mutations were not found within nucleotides encoding the cleavage sites, neither were found within their close upstream and downstream sequences. conclusion : our results shows that polymorphisms affecting cleavage sites of factor v other than arg506glu it would be less likely to be the basis for apc resistance and its increased thrombosis susceptibility.additionally it emphasizes on the importance of screening for apc resistance in the patients diagnosed with cvt.