title: Acquired activated protein C resistance is common in cancer patients and is associated with venous thromboembolism.
abstract: OBJECTIVE
  Cancer patients have an increased risk for venous thromboembolism. Because activated protein C resistance is a common risk factor for venous thromboembolism, we prospectively evaluated the activated protein C sensitivity ratio and factor V Leiden mutation in cancer patients with and without venous thromboembolism.
  
  
  METHODS
  We studied 55 consecutive cancer patients with deep vein thrombosis, 58 cancer patients with no history of venous thromboembolism, 54 patients with venous thromboembolism without malignancy, and 56 healthy controls. The presence of factor V Leiden mutation was determined by polymerase chain reaction and allele specific restriction digestion. The activated protein C sensitivity ratio was expressed as the ratio of activated partial thromboplastin times measured in the presence and absence of activated protein C; a ratio <2.0 in patients who did not have factor V Leiden was considered to indicate acquired activated protein C resistance.
  
  
  RESULTS
  The prevalence of factor V Leiden mutation in cancer patients with thromboembolism (1 of 55, 2%) did not differ significantly from those in cancer patients without thromboembolism (4 of 58, 7%) or normal controls (2 of 56, 4%), but was significantly lower than that of patients with thromboembolism without cancer (18 of 54, 33%, P <0.001). The prevalence of acquired activated protein C resistance was significantly greater in cancer patients with thromboembolism (29 of 54, 54%, P = 0.001) compared with the other groups: 9 of 54 (17%) in cancer patients without thromboembolism, 7 of 36 (19%) in patients with thromboembolism without cancer, and none of the normal controls.
  
  
  CONCLUSIONS
  Although factor V Leiden is not a major risk factor for thrombosis in cancer patients, acquired activated protein C resistance is common and may contribute to the thrombotic tendency in these patients.
authors.affiliation: Department of Oncology, Rambam Medical Center and the Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Haim
authors.forename: N
authors.initials: N
authors.lastname: Lanir
authors.forename: R
authors.initials: R
authors.lastname: Hoffman
authors.forename: A
authors.initials: A
authors.lastname: Haim
authors.forename: M
authors.initials: M
authors.lastname: Tsalik
authors.forename: B
authors.initials: B
authors.lastname: Brenner
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood* / Q000209:etiology / Q000235:genetics; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000150:complications* / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011446:Prospective Studies; D013923:Thromboembolism / Q000097:blood* / Q000209:etiology / Q000235:genetics
chemical_list: C095381:factor V Leiden; D005165:Factor V