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Indexed/Abstracted in: e-psyche, EMBASE, PubMed/MEDLINE, Neuroscience Citation Index, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,651
Online ISSN 1827-1855
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.