Abstract TP521: Changes in D-Dimer Levels With Heparin Treatment Indicate the Recurrent Stroke Risk in Patients With Cancer Associated Hypercoagulation

Purpose: In stroke patients with cancer associated hypercoagulation, D-dimer levels were used as a marker of hypercoagulation, and heparin was reported to be more effective than warfarin for secondary prevention. After started heparin, D-dimer levels tend to decrease in such patients. However, the usefulness of D-dimer levels as an indicator of recurrent stroke has not been fully investigated. The aim of this study was to assess the usefulness of D-dimer levels in the setting of heparin treatment for stroke patients with cancer associated hypercoagulation. Methods: We retrospectively analyzed stroke patients with active cancer visited to our hospital within 7 days of onset, from 2008 to 2018. Active cancer was defined as a diagnosis of or treatment for any cancer within 6 months before stroke onset. Among the patients, we enrolled subjects who were treated with heparin and had elevated D-dimer levels (>2 μg/ml). Results: A total of 54 subjects (27 men, mean age 69 years) were registered. Most frequent cancer origin was pancreas (26%). Known metastatic disease was found in 67% of patients. The median pre-heparin D-dimer levels were 11.4μg/ml (IQR 5.5-20.7), and median post-heparin D-dimer levels were 8.0μg/ml (IQR 4.1-12.6). Recurrent stroke occurred in 13% patients during treated with heparin. As compared to patients without recurrent stroke, those with recurrent stroke during heparin treatment had higher ratio of post-heparin to pre-heparin D-dimer levels (1.03 vs 0.54 ; p<0.01). In logistic regression analysis, increase in the ratio of D-dimer levels (per 0.1) was significantly greater risk for stroke recurrence after adjusted for age and gender (Odds Ratio 6.5, 95%CI 1.5-43.8). Among patients without recurrent stroke, 30 patients were discontinued or changed heparin to other antithrombotic agents. Within few days of heparin discontinuation, recurrent stroke accompanied with D-dimer re-elevation was occurred in 5 patients despite of treated with other anticoagulants (Warfarin in 1 and direct oral anticoagulants in 4). Conclusions: During heparin treatment, the ratio of post-heparin to pre-heparin D-dimer levels was an indicator of recurrent stroke. After heparin was changed to other drugs, D-dimer re-elevation may be associated with recurrent stroke.