Thrombelastographic monitoring of recombinant factor VIIa in acquired haemophilia

Abstract

Monitoring of the global haemostatic capacity is desired to optimize the treatment with bypassing agents in inhibitor patients. Thrombelastographic methods have been used in ex vivo studies and were suggested useful to evaluate the individual response to bypassing agents. This study aimed at assessing changes in thrombelastographic profiles and their association to clinical outcome in patients treated with recombinant factor VIIa (rFVIIa). Ten patients with acquired haemophilia were treated with rFVIIa for acute bleeding. Thrombelastography was performed after activation with a small amount of tissue factor in samples obtained before and after in vivo administration of rFVIIa. In patients studied before and after a first dose, correction of the thrombelastographic profile was observed but did not predict cessation of bleeding. During steady-state dosing, the median Alpha angle tended to be higher in patients with a good clinical treatment response as compared with patients with a partial or poor response. Similar trends were observed for clotting time and clot formation time. A good clinical treatment response was more frequent in patients with a fully corrected trough-level thrombelastographic profile as compared with patients with an abnormal profile. However, a poor treatment response was observed also in a surgical patient with a normal thrombelastographic profile during steady-state dosing. In conclusion, thrombelastographic monitoring was sensitive to haemostatic changes in response to treatment with rFVIIa. In the limited number of patients studied here, a better clotting profile during steady-state dosing was associated with a better clinical treatment response.

Factor VIIa analog has marked effects on platelet function and clot kinetics in blood from patients with hemophilia A

“…(or MCF) response to rFVIIa has been observed previously [10,17,22,24,25] and it may be due to a relatively lower contribution of platelets to these parameters. These data may suggest that the hemostatic effects of rFVIIa and NN1731 can be monitored by the PCF and CEM parameters, respectively.…”

“…This is most likely because we are merely testing a one-time ex-vivo concentration, whereas bleeding patients tend to get repeated rFVIIa doses of 90 mg/kg every 2 h until a desired response is obtained. This hypothesis is corroborated by Dehmel et al who showed that in order to completely correct the TEG profile, in vivo rFVIIa doses tended to be greater than 90 mg/kg and administered at least every 2-4 h. Thus patients benefit from the accumulated total dose, and not just the first 90 mg/kg dose[24]. Secondly, how do ex-vivo spiking experiments correspond to in-vivo dosing?…”

Carbon monoxide releasing molecule-2 increases the velocity of thrombus growth and strength in hemophilia A, hemophilia B and factor VII-deficient plasmas

“…Given that carbon monoxide rapidly diffuses through plasma, our data support the concept that carbon monoxide released from CORM-2 modifies fibrinogen to improve coagulation kinetics. It is not likely that thrombin generation per se was increased with CORM-2, as improved thrombin generation is typically associated with a more rapid onset of coagulation (equivalent to TMRTG) when thrombelastography is used to assess coagulation kinetics [11,[13][14][15][16][17][18]. In summary, with only one exception observed in a FIX-deficient individual, CORM-2 improved the velocity of formation and strength in the deficient plasmas tested.…”

A Comparison of Efficacy Between Recombinant Activated Factor VII (Aryoseven) and Novoseven in Patients With Hereditary FVIII Deficiency With Inhibitor

“…The modern treatment regimens in hemophilia with inhibitor help to decrease bleeding episodes, morbidity, and improve quality of life. [55][56][57][58][59][60][61][62][63][64] New therapeutic strategies are relatively expensive, and they are not affordable for underdeveloped and poor countries. 40,[64][65][66][67] Biosimilar products are comparable hemostatic agents to the branded product and provide better care and wider affordability.…”

“…to270 mg/kg, 2 hours apart, and have been used. We chose 90 to 120 mg/kg dosage, which is similar to other studies 21,[58][59][60][61][62][63][64]. Efficacy and reduction in bleeding were similar in both treatment groups.…”