Global coagulation function assessed by rotational thromboelastometry predicts coagulation-steady state in individual hemophilia A patients receiving emicizumab prophylaxis

Int J Hematol. 2019 Oct;110(4):419-430. doi: 10.1007/s12185-019-02698-8. Epub 2019 Jun 28.

Abstract

Emicizumab is a bispecific antibody to factor (F) IX/IXa and FX/FXa, which mimics FVIIIa cofactor function. Emicizumab prophylaxis significantly decreases bleeding events for patients with hemophilia A (PwHA). However, global hemostatic monitoring in emicizumab-treated PwHA remains poorly investigated. Using rotational thromboelastometry (ROTEM), we evaluated coagulation potentials of whole blood samples from seven emicizumab-treated PwHA who participated in ACE001JP/ACE002JP studies. Dose-dependent coagulation-enhancing effects of emicizumab to whole blood from PwHA mixed with an anti-FVIII C2 antibody in vitro were evident by non-activated ROTEM analysis (NATEM). The relationship between FVIII levels and NATEM parameters in PwHA not participating in the clinical trials demonstrated that CT + CFT inversely correlated with FVIII levels. These parameters were defined as NATEM-based grading of coagulation potential; 'T1' (FVIII < 1 IU/dL), 'T2' (1 ≤ , < 12 IU/dL) and 'T3' (12 ≤ , < 60 IU/dL). Coagulation function in emicizumab-treated PwHA was determined to be 'T2' or 'T3,' and was dependent on plasma emicizumab concentration. Improvement of NATEM-based grades corresponded with significant reduction of bleeding episodes, except for target joints, and differences were due to the time to reach the coagulation-steady state in individual patients. The NATEM analysis may be useful for intra- and inter-individual evaluation of coagulation function in emicizumab-treated PwHA.

Keywords: Annual bleeding rate; Emicizumab; Global coagulation function; Hemophilia A; ROTEM.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bispecific / administration & dosage*
  • Antibodies, Bispecific / pharmacology
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Anticoagulants
  • Blood Coagulation*
  • Child
  • Dose-Response Relationship, Drug
  • Female
  • Hemophilia A / blood*
  • Hemophilia A / complications
  • Hemophilia A / drug therapy*
  • Hemorrhage / etiology
  • Hemorrhage / prevention & control*
  • Humans
  • Male
  • Middle Aged
  • Thrombelastography / methods*
  • Young Adult

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • Anticoagulants
  • emicizumab