Author + information
- Joanne van Ryn,
- Thomas Giessmann,
- Ghazaleh Gouya,
- Michael Wolzt,
- Johanna Schurer,
- Maximilian Lobmeyer and
- Martina Brueckmann
The most frequent side effect associated with long term anticoagulant and antiplatelet therapy is bleeding. It has been attempted with different methods to assess blood loss in healthy volunteers (HV). The feasibility of two alternative methods for the assessment of bleeding due to anticoagulation with dabigatran etexilate (DE) vs antiplatelet therapy with ticagrelor was performed.
Washed blood and shed blood methods were tested in two groups of 12 HVs. DE (Pradaxa®, 220 mg, n=8) or ticagrelor (Brilinta®180 mg, n=4) was given as a single dose and bleeding methods were done at 0, 2, (3 only washed blood) and 6 hr. Washed blood: a forearm skin incision with junior Surgicutt® was made and the wound area was washed with saline. Wash solution was collected and measured photometrically. AUC was recorded as blood loss, bleeding time as the first well with optical density (OD) < 0.05. Shed blood: two incisions in the forearm using an adult Surgicutt® were made and blood emerging from the wound was collected over 4 min and placed in a protease inhibitor solution. Plasma was assayed by ELISA for ß–thromboglobulin (ß–TG), thrombin–antithrombin (TAT), prothrombin fragment (F1+2), fibrinopeptide A (FPA). Venous blood was taken at the same time points.
Study drugs were well tolerated. Blood loss (AUC) at predose was 70 ± 42 OD*sec and bleeding time was 3.6 ± 0.6 min. DE increased AUC 2–3–fold over baseline at 2, 3, and 6 hrs in washed blood test, but had no effect on bleeding time prolongation vs control. Ticagrelor increased blood loss (AUC) >10–fold and prolonged bleeding time from 5.4 to >20 min. DE reduced ß–TG, FPA and slightly reduced TAT, but had no effect on F1+2 in shed blood. Ticagrelor reduced ß–TG, but had no effect on other parameters in shed blood. Parameters were unchanged in venous blood.
This study shows that quantification of bleeding with DE and ticagrelor is possible using the washed blood technique. Shed blood increases sensitivity of detecting the pharmacological activity of these compounds compared to venous blood. These two methods could serve as experimental models to sensitively assess blood loss and allow for the investigation of reversal agents.
Poster Sessions, Expo North
Sunday, March 10, 2013, 3:45 p.m.–4:30 p.m.
Session Title: Preclinical and Translational Research
Abstract Category: 52. TCT@ACC–i2: Translation and Pre–clinical Research
Presentation Number: 2111–243
- 2013 American College of Cardiology Foundation