Hematologic genetic testing in high-risk patients before knee arthroplasty: a pilot study

Clin Orthop Relat Res. 2011 Jan;469(1):131-7. doi: 10.1007/s11999-010-1514-2.


Background: Patients with a personal or familial history of thromboembolism are considered at higher risk for thromboembolic disease after knee arthroplasty. While it remains unclear why some patients develop deep vein thrombosis (DVT) or pulmonary embolism (PE) despite similar operative procedures and the same prophylactic regimen, we presume one explanation would be genetic predisposition.

Questions/purposes: We determined the frequency of 12 factors including antithrombin III activity, prothrombin gene mutations, and the presence of phospholipid antibodies in a high-risk patient cohort and compared those findings with the known prevalence in the population at large.

Patients and methods: Patients identified preoperatively as having a personal or familial history of DVT and/or PE were referred for hemostatic serum and genetic tests, including % antithrombin III activity (ATIII), protein C and protein S activities, APC resistance, Factor V gene (Leiden) mutations, prothrombin gene mutations, lupus anticoagulant antibody presence, cardiolipin antibody presence, phosphatidyl antibody presence, β2-glycoprotein antibody presence, and serum homocysteine and lipoprotein(a) levels The frequencies of varying abnormalities were identified and compared to the prevalence reported in the literature.

Results: Forty-three of 1944 patients undergoing knee arthroplasty had a history of DVT or PE. Sixteen of 43 (37%) patients had an abnormality and eight of these (19%) had two or more abnormalities. The frequency of nine of the 12 tests appeared to be greater in this cohort than in the population at large.

Conclusions: Patients with a personal or familial history of DVT or PE appear to have a high frequency of hereditary prothrombotic abnormalities. Preoperative evaluation by a hematologist may be warranted in patients with a personal or familial history of DVT or PE as the postoperative anticoagulation protocols may be altered and identification of these abnormalities may affect a patient's risk for other disease states.

Level of evidence: Level IV, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use
  • Arthroplasty, Replacement, Knee / adverse effects*
  • Biomarkers / blood*
  • Blood Coagulation / drug effects
  • Blood Coagulation / genetics*
  • Chi-Square Distribution
  • Chicago
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Humans
  • Male
  • Middle Aged
  • Patient Selection
  • Pedigree
  • Phenotype
  • Pilot Projects
  • Preoperative Care
  • Pulmonary Embolism / blood
  • Pulmonary Embolism / diagnosis*
  • Pulmonary Embolism / etiology
  • Pulmonary Embolism / genetics
  • Pulmonary Embolism / prevention & control
  • Risk Assessment
  • Risk Factors
  • Surveys and Questionnaires
  • Venous Thrombosis / blood
  • Venous Thrombosis / diagnosis*
  • Venous Thrombosis / etiology
  • Venous Thrombosis / genetics
  • Venous Thrombosis / prevention & control


  • Anticoagulants
  • Biomarkers