Experimental Oncology 27, 159-161, 2005 (June) 159 Exp Oncol 2005 27, 2, 159-161 Thrombosis is the most frequent complication and the second cause of death in patients with malignant disease [1]. Cancer per se represents a high thrombotic risk situ- ation and several molecular mechanisms may contribute to a hypercoagulable state in certain tumor patients. There- fore, alterations of haemostasis are common during on- cological disease and thromboembolic complications have been recognized as one of the most common causes of death in those patients. [24]. Patients with malignancy have a prothrombotic state due to the ability of almost all type of cancer cells to activate the coagulation system. However, none of the haemostatic markers of coagula- tion has any predictive value for the occurrence of the thrombotic events in one individual patient [5, 6]. The pathogenesis of the prothrombotic state in cancer is com- plex and, probably, multifactorial. Prothrombotic factors in malignancy include the tumor production of procoagu- lants (i.e., tissue factor (TF) and cancer procoagulant (CP) [7]), inflammatory cytokines and growth colony stimu- lating factors [8, 9], and the interaction between tumor cells and blood (i.e., monocytes/macrophages, platelets and endothelial cells). Other mechanisms of thrombus pro- motion include some general responses of the host to the PHENOTYPIC APC RESISTANCE AS A MARKER OF HYPERCOAGULABILITY IN PRIMITIVE CEREBRAL LYMPHOMA Domenico De Lucia 1, *, Francesco De Francesco 1 , Rosa Marotta 1 , Giovanna Maisto 1 , Daniela Meo 1 , Marcella Sessa 1 , Margherita Misso 1 , Maria Galante 1 , Teresa Russo 1 , Orlando Pignalosa 1 , Mariasanta Napolitano 1 , Maria Luisa Papa 2 , Alferio Niglio 3 , Pierpaolo Di Micco 4 1 Institute of General Pathology and Oncology, II University of Naples, Naples, Italy 2 Laboratory of Haemostasis and Thrombosis, San Giovanni Bosco Hospital, Naples, Italy 3 Internal Medicine IV Division, Department of Geriatrics and Metabolic Diseases, II University of Naples, Naples, Italy 4 Thrombosis Center, Istituto Clinico Humanitas, Milan, Italy 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. Aim: 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. Patients and 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 (£ 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 demon- strating 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. Conclusion: In cerebral lymphoma with hypercoagu- lability 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. Key Words: non-Hodgkins lymphoma, activated protein C resistance (APC-r), hypercoagulability, thrombophilic state. Received: February 24, 2005. *Correspondence: E-mail: domenico.delucia@unina2.it Abbreviations used: CP  cancer procoagulant; TF  tissue factor. tumor (i.e., acute phase, inflammation, angiogenesis), decreased levels of inhibitors of coagulation, and impaired fibrinolysis [10]. In addition, the prothrombotic tendency of cancer patients is enhanced by anticancer therapy, such as surgery, chemotherapy, hormone therapy and radio- therapy, by indwelling central venous catheter, and by haemodinamic compromise (i.e., stasis) [11]. However, not all of the mechanisms allowing the prothrombotic state of cancer are entirely understood. Therefore, it is pres- ently difficult to rank the relative weight of these multiple interactions on the basis of the well-recognised clinical evidences of enhanced thrombotic episodes in patients with cancer [12]. Thrombosis during non-Hodgkins lym- phoma remains exceptional and is usually locally associ- ated to the tumoral process, raising the issue of its tumor- al or cruoric nature. The mechanism of thrombosis may be multifactorial: associated coagulation inhibitor deficien- cy, vascular compression, tumoral process and chemo- therapy. The treatment of this complication is based on anticoagulation concomitantly to chemotherapy [13, 14]. Primary central nervous system non-Hodgkins lym- phoma represents a rare pathology. They are most fre- quently classified as B immunoblastic lymphoma. Recently, a new mechanism of hereditary throm- bophilia characterized by a poor response to activated protein C resistance (APC-r) has been identified. Re-