Evaluation of rFVIIa (NovoSeven) in Glanzmann patients with thromboelastogram

Abstract

Glanzmann thrombasthenia (GT) is a rare platelet function disorder characterized by a defect in fibrinogen binding to platelet membrane glycoprotein (GP) IIb/IIIa. Recombinant FVIIa (rFVIIa) is a haemostatic agent approved for the treatment of haemophilia patients with inhibitors, patients with acquired haemophilia and in EU also for treatment of factor VII (FVII)-deficient patients and GT patients with antibodies to GPIIb-IIIa. The present study was conducted to evaluate the use of the whole blood test system, rotational thrombelastometry (ROTEM), in measuring the overall haemostasis potential of rFVIIa in 28 GT patients treated with rFVIIa. The correlation of administered rFVIIa and time to start fibrin formation and clot dynamic/stability was assessed and correlation to the clinical response was elucidated. Assessments were performed on predose blood samples spiked with four different concentrations of rFVIIa and whole blood samples taken at 10 and 120 min following dosing. ROTEM parameters clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF) were measured. Both ex vivo and in vivo data showed beneficial effects on CT in the presence of rFVIIa, but no effect of added rFVIIa was seen on CFT and MCF. In conclusion, the use of thrombelastography at least in the modified form of ROTEM seems to be of limited use in predicting an adequate dose of rFVIIa in GT patients. A good clinical haemostatic response was recorded in spite of the limited changes in the ROTEM pattern supporting the conclusion that ROTEM should not be the method of choice for monitoring rFVIIa therapy in Glanzmann patients.

Tests of global haemostasis and their applications in bleeding disorders

“…This is of major consequence in the developing world. In the field of platelet disorders, the thromboelastograph has demonstrated laboratory evidence of response to treatment with agents such as rFVIIa [27]. Other coagulation factor deficiencies such as FXIII deficiency are difficult to diagnose and monitor due to lack of universally available laboratory tests, and thromboelastography has been shown to be extremely useful in this situation [28].…”

The international prospective Glanzmann Thrombasthenia Registry: treatment and outcomes in surgical intervention

“…The data reported here represent the largest dataset available in the literature, including those in other databases. 7,18,19 Furthermore, these registry data represent real-life clinical practices and the standards of care at the participating sites. Narrative information, as provided in the GTR, often provides additional useful insights that might differ from the coding of effectiveness at an earlier time point after surgery.…”

Perioperative haemostatic management of Glanzmann thrombasthenia for abdominal surgery

“…Repeated performance of thrombelastometry and PFA-100 (not shown) added no specific benefit [11,14].…”

“…After application of rFVIIa, a decrease in the CT was detected. The CFT and the MCF only showed a slight beneficial effect after rFVIIa and never reached normal values [14]. Thus, thrombelastometry was not able to display the clinical situation of the coagulation system.…”