Phenotypic APC resistance as a marker of hypercoagulability in primitive cerebral lymphoma.
Thrombosis is the most frequent complication and the second cause of death in patients with malignant disease. Primary central nervous system non-Hodgkin's lymphoma represents a rare pathology. Resistance to APC is usually linked to a factor V (FV) gene mutation changing an Arg 506 to a Gln in the APC cleavage site.


OBJECTIVE
In our study, we aimed at investigating the presence of activated protein C resistance (APC-r) and other markers of hypercoagulability in 25 selected patients with a diagnosis of primitive cerebral lymphoma who had suffered from an ischemic episode of TIA and/or stroke.


METHODS
25 selected patients with a diagnosis of primitive cerebral lymphoma and 50 healthy subjects acted as control group, were tested. We measured APC-r, natural clotting inhibitors, F1 + 2, aPTT and PAI-1 according to international guidelines. Genomic DNA was extracted from peripheral white blood cells and in order to detect FV Leiden gene polymorphism.


RESULTS
Our results showed that 11 out of 25 patients had a poor response to APC (< or = 0.70, which represents the cut-off point in our general population) without deficiencies in natural clotting inhibitors. All patients had high plasma levels of F1+2 and PAI-1 compared to those found in healthy subjects (2.65 +/- 0.75 nM/L vs 0.40 +/- 0.35 nM/L; 67.5 +/- 18.5 ng/mL vs 17 +/- 11.5 ng/mL, respectively). In 9 patients resistance to APC was not associated to a FV gene defect demonstrating that such phenomenon may occur also as an acquired condition. However, the patients with resistance to APC showed the highest plasma values in F1 + 2 and PAI-1.


CONCLUSIONS
In cerebral lymphoma with hypercoagulability the resistance to APC is not caused by the FV Arg 506-->Gln mutation (82%). APC resistance not caused by this FV gene defect may be an additional risk factor for thrombophilia in this selected population.
De Lucia
Domenico
D
Institute of General Pathology and Oncology, II University of Naples, Naples, Italy. domenico.delucia@unina2.it
De Francesco
Francesco
F
Marotta
Rosa
R
Maisto
Giovanna
G
Meo
Daniela
D
Sessa
Marcella
M
Misso
Margherita
M
Galante
Maria
M
Russo
Teresa
T
Pignalosa
Orlando
O
Napolitano
Mariasanta
M
Papa
Maria Luisa
ML
Niglio
Alferio
A
Di Micco
Pierpaolo
P
D020016:Activated Protein C Resistance; D015415:Biomarkers; D001777:Blood Coagulation; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy*; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics*; D006801:Humans; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000188:drug therapy*; D009154:Mutation; D010446:Peptide Fragments / Q000097:blood; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011516:Prothrombin; D020521:Stroke / Q000209:etiology
D015415:Biomarkers; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; C095381:factor V Leiden; C045879:prothrombin fragment 1.2; D005165:Factor V; D011516:Prothrombin