Targeting TFPI With Concizumab to Improve Haemostasis in Glanzmann Thrombasthenia Patients: an in Vitro Study

"TTAS (single measurements)~Clot formation in whole blood under flow (2000 s-1) in a microfluidic flow chamber coated with tissue factor and collagen (T-TAS with AR chip)~1. 500 µL of whole blood for each point;~2. 7 points for each condition;~3. Around 4 mL of whole blood will be needed for each patient or healthy subject;~4. Values for Area Under the Curve (Aritrary Unit), Occlusion Starting Time (min), Occlusion Time (min.) will be reported."

"ROTEM (single measurements)~1. ROTEM cups will be added~ * 20 µL calcium reagent (STARTEM)~ * 20 µL of 2,940-fold prediluted r-ExTEM reagent (50,000 fold dilution relative to 340 µL in the cup) added~ * 300 µL spiked PRP at 250 G/L (2.5 mL of PRP/patient)~2. Values for clot time (CT sec, clot formation time (CFT) sec, maximum clot formation (mm) will be reported."

"TGA (single measurements)~1. The following will be added to well:~ * 20 uL of PRP-Reagent~ * 80 uL of spiked PRP (600 µL/patient at 100 G/L)~ * 20 uL FluCa~2. Values for thrombin activity versus time and the derived parameters incl. lag-time (min), time to peak (min), time to peak (min), ETP (Arbitrary Unit) will be reported."

Global fibrinolytic capacity (Lysis Timer) in 100 µL of PRP (250 G/L) using reagents for in vitro triggering of the clot (thrombin and calcium) and its lysis (tissue-plasminogenactivator (t-PA). Around 1 mL of PRP in total Lysis time in min

Thrombin generation assay (TGA), microchip flow-chamber assay (T-TAS, rotational thromboelastometry and global fibrinolytic capacity to investigate and compare the effects of mixing concizumab (200, 1000 and 4000 ng/mL) with the main bleed treatment options for persons with GT