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A Journal on Neurosurgery

Indexed/Abstracted in: e-psyche, EMBASE, PubMed/MEDLINE, Neuroscience Citation Index, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,651

Frequency: Bi-Monthly

ISSN 0390-5616

Online ISSN 1827-1855


Journal of Neurosurgical Sciences 1999 March;43(1):45-51


Asso­ci­a­tion of ele­vat­ed lev­els of pro­throm­bin frag­ment 1+2 ­and ­Arg506 to ­Gln muta­tion in ­patients ­with a his­to­ry of ischem­ic ­stroke

De Lucia D. 1, Papa M. L. 3, Ammendola F. 1, Pezzella S. 1, Del Giudice V. 1, Marotta R. 1, Renis V. 1, Di Mauro C. 1, Maisto G. 1, Masi S. 1, Nina P. 2, Franco A. 2, Schisano G. 2

1 Insti­tute of Gen­er­al Pathol­o­gy ­and Oncol­o­gy, II Uni­ver­sity of ­Naples, Ita­ly;
2 Neu­ro­sur­gery Divi­sion, Nuo­vo Pel­le­gri­ni Hos­pi­tal, ­Naples, Ita­ly;
3 Throm­bo­sis ­and Hae­mo­phil­ia Cen­ter, Nuo­vo Pel­le­gri­ni Hos­pi­tal, ­Naples, Ita­ly

Back­ground. ­Recent find­ings ­have indi­cat­ed ­the asso­ci­a­tion ­between ­APC-resis­tance ­and cereb­ro­vas­cu­lar dis­ease. ­These ­reports prompt­ed us to inves­ti­gate wheth­er resis­tance to ­APC ­could be ­found in ­patients suf­fer­ing ­from ­stroke.
Meth­ods. There­fore, we stud­ied ­APC-resis­tance in 50 ­young ­adults (≤45 ­yrs) ­with a his­to­ry of ischem­ic ­stroke. ­Eleven ­out of fif­ty cereb­ro­vas­cu­lar sub­jects ­showed ­APC-resis­tance, ­while 2 ­had PC defi­cien­cy ­and 3 PS defi­cen­cy. No defi­cien­cies in ­the anti­co­ag­u­lant pro­tein AT ­III ­and in fibrin­o­lyt­ic pro­teins ­were ­found. ­The fam­i­ly his­to­ry dem­on­strat­ed a dis­tri­bu­tion of ­APC-resis­tance com­pat­ible ­with dom­i­nant auto­so­mal inher­i­tance. ­The plas­ma con­cen­tra­tion of pro­throm­bin frag­ment 1+2 (F1+2), ­which is a mark­er of hyper­coa­gu­lable ­states, ­was ­also meas­ured in pat­ients ­and fam­i­ly mem­bers of resist­ant sub­jects (n=38).
­Results. ­DNA anal­y­sis ­showed fac­tor V R506Q muta­tion (Leid­en muta­tion) in 11 ­patients ­and ­their rala­tives ­with ­poor ­response to acti­vat­ed pro­tein C detect­ed by ­APTT ­tests. Of 11 inves­ti­gat­ed sub­jects ­with ­APC-resis­tance, 9 ­were het­er­o­zy­gotes ­and 2, ­with ­the low­est ­APC-­ratio val­ues, ­were homo­zy­gotes ­for fac­tor V muta­tion. ­Among 38 rel­a­tives, 22 ­showed a ­poor ­response to ­APC ­and accord­ing to ­the ­APC-­ratio val­ues, 18 ­were het­er­o­zy­gotes ­and 4 homo­zy­gotes ­for FV Leid­en muta­tion. ­The muta­tion, in het­er­o­zy­gous ­form, ­was ­also ­found in 2% of ­our nor­mal pop­u­la­tion (n=100). ­The plas­ma con­cen­tra­tion of F1+2 ­was sig­nif­i­cant­ly high­er ­both in 11 indi­vid­u­als car­ry­ing ­the FV:Q506 muta­tion ­and in 39 ­patients with­out ­APC-resis­tance com­pared to ­that ­found in ­the con­trol ­group. How­ev­er, ­the ­patients ­with FV:Q506 mutation ­showed ­the high­est val­ues in F1+2. In ­the stud­ied fam­i­ly mem­bers F1+2 plas­ma lev­els ­were with­in nor­mal val­ues.
Con­clu­sions. ­Our find­ings indi­cate a pos­sible involve­ment of ­APC-resis­tance in ­the path­o­gen­e­sis of cere­bral throm­bo­sis in ­young ­adults ­and ­agree ­with ­the hypoth­e­sis ­that indi­vid­u­als ­with ­APC-resis­tance ­have an imbal­ance ­between ­pro- ­and ­anti-coag­u­lant forc­es lead­ing to ­increased throm­bin gen­er­a­tion ­and a hyper­coa­gu­lable ­state.

language: English


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