Plasma coagulation markers in patients with solid tumors and venous thromboembolic disease receiving oral anticoagulation therapy.
OBJECTIVE
To correlate the concentration of plasma coagulation markers at baseline and during follow-up in patients with solid tumors and venous thromboembolic disease with the risk of recurrence and death.


METHODS
Patients (N = 223) with first episode of venous thromboembolic disease received oral anticoagulation with warfarin for a target international normalized ratio of 2 to 3. Plasma coagulation markers were measured before instituting warfarin and at 3 monthly intervals, thereafter.


RESULTS
The median duration of oral anticoagulation was 6.7 months (range 2 weeks to 11 months). Major bleeding episodes occurred in 18 patients (8%), and minor hemorrhagic events occurred in 15 (6.7%) patients. Patients with advanced malignancy (P = 0.032), history of surgery (P = 0.057), and those with poor performance status (P = 0.001) were more likely to encounter major bleeding episodes. Recurrence of venous thromboembolic disease was diagnosed in 31 patients (14%). At univariate analysis, advanced stage of cancer (P = 0.03), performance status > 1 (P = 0.001), treatment with chemotherapy (P = 0.01), the presence of metastatic liver disease (P = 0.03), higher d-dimer (P = 0.001), and thrombin antithrombin complex levels (P = 0.01) were features predictive of recurrent venous thromboembolic disease. At multivariate analysis, poor performance status (P = 0.01) and d-dimer levels (P = 0.001) were predictors of recurrent venous thromboembolic disease. Persistent activation of coagulation as indicated by an upward trend in d-dimer (P = 0.001) and antithrombin (P = 0.001) was observed in patients who developed recurrent thrombosis. Similar upward trends in d-dimer (P = 0.001), antithrombin (P = 0.001), and prothrombin fragment F1 + 2 (P = 0.001) was observed in the 76 patients who died during the study period and in the patients who received chemotherapy.


CONCLUSIONS
Successful oral anticoagulation with warfarin in patients with cancer and venous thromboembolic disease is more likely to be achieved in patients with early stage tumors and good performance status. The persistence of activation of hemostasis as shown by plasma coagulation markers is a strong predictor of recurrence and poor outcome.
Sallah
Sabah
S
Thrombosis and Hemostasis Program and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71103, USA. asll@novonordisk.com
Husain
Aisha
A
Sigounas
Vaia
V
Wan
Jim
J
Turturro
Francesco
F
Sigounas
George
G
Nguyen
Nam P
NP
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000096:biosynthesis; D006801:Humans; D019934:International Normalized Ratio; D008107:Liver Diseases / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000097:blood*; D012008:Recurrence; D013923:Thromboembolism / Q000188:drug therapy / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000494:pharmacology
D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D014859:Warfarin