PMID- 37766492
OWN - NLM
STAT- MEDLINE
DCOM- 20231114
LR  - 20231114
IS  - 1365-2516 (Electronic)
IS  - 1351-8216 (Linking)
VI  - 29
IP  - 6
DP  - 2023 Nov
TI  - The in vitro effect of anticoagulant agents on coagulation and fibrinolysis in 
      the presence of emicizumab in the plasmas from patients with haemophilia A.
PG  - 1529-1538
LID - 10.1111/hae.14877 [doi]
AB  - INTRODUCTION: Emicizumab is used as hemostatic prophylaxis for patients with 
      hemophilia A (PwHA), irrespective of the presence of inhibitors. Although 
      bacterial infection can lead to a procoagulant state, there is limited 
      information on coagulation and fibrinolysis potentials in emicizumab-treated PwHA 
      and on the use of anticoagulants in such cases. AIM: We examined whether 
      anticoagulants affect the coagulation and fibrinolysis potentials in plasma from 
      PwHA spiked with emicizumab. METHODS: Plasma from PwHA was in vitro supplemented 
      with emicizumab (50 mug/mL; emi-plasma) and anticoagulants (recombinant 
      thrombomodulin (rTM), nafamostat mesylate (NM), unfractionated heparin (UFH), or 
      low-molecular-weight heparin (LMH)). PwHA plasma spiked with rFVIII (1 IU/mL) was 
      used as a reference (ref-plasma). The coagulation and fibrinolysis potentials in 
      plasma was measured by thrombin and plasmin generation assay (T/P-GA) and 
      clot-fibrinolysis waveform analysis (CFWA). RESULTS: In T/P-GA and CFWA, 
      coagulation potentials (maximum coagulation velocity; |min1|, and peak thrombin; 
      Th-Peak) in plasma rose with increasing concentrations of emicizumab and rFVIII, 
      but fibrinolytic potentials (peak plasmin; Plm-Peak, and maximum fibrinolytic 
      velocity; |FL-min1|) remained unchanged. Adding rTM, NM, and UFH to emi-plasma 
      suppressed coagulation and fibrinolysis potentials, similar to ref-plasma. 
      Regarding the heparin, UFH and LMH inhibited the improved coagulation in 
      emi-plasma. UFH inhibited fibrinolysis as well, but LMH did not. CONCLUSIONS: 
      Anticoagulants could exhibit the inhibitory effects on the coagulation and 
      fibrinolysis potentials in plasma from PwHA spiked with emicizumab, similar to 
      those in normal plasma.
CI  - (c) 2023 John Wiley & Sons Ltd.
FAU - Onishi, Tomoko
AU  - Onishi T
AUID- ORCID: 0000-0002-0199-7645
AD  - Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
FAU - Harada, Suguru
AU  - Harada S
AD  - Chugai Pharmaceutical Co., Ltd., Yokohama, Kanagawa, Japan.
FAU - Shimo, Hanako
AU  - Shimo H
AD  - Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
FAU - Tashiro, Yoshihito
AU  - Tashiro Y
AD  - Chugai Pharmaceutical Co., Ltd., Yokohama, Kanagawa, Japan.
FAU - Soeda, Tetsuhiro
AU  - Soeda T
AD  - Chugai Pharmaceutical Co., Ltd., Yokohama, Kanagawa, Japan.
FAU - Nogami, Keiji
AU  - Nogami K
AUID- ORCID: 0000-0002-2415-2194
AD  - Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
LA  - eng
GR  - Chugai Pharmaceutical Co., Ltd./
GR  - 22K16330/Grant-in-Aid for Scientific Research/
PT  - Journal Article
DEP - 20230927
PL  - England
TA  - Haemophilia
JT  - Haemophilia : the official journal of the World Federation of Hemophilia
JID - 9442916
RN  - 0 (Anticoagulants)
RN  - 7NL2E3F6K3 (emicizumab)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
RN  - EC 3.4.21.7 (Fibrinolysin)
RN  - 0 (Antibodies, Bispecific)
RN  - 9001-27-8 (Factor VIII)
SB  - IM
MH  - Humans
MH  - *Hemophilia A/drug therapy
MH  - Fibrinolysis
MH  - Anticoagulants/pharmacology/therapeutic use
MH  - Heparin/pharmacology/therapeutic use
MH  - Thrombin
MH  - Fibrinolysin
MH  - *Antibodies, Bispecific/pharmacology/therapeutic use
MH  - Factor VIII/therapeutic use
MH  - *Thrombosis/drug therapy
OTO - NOTNLM
OT  - anticoagulants
OT  - bispecific antibody
OT  - coagulation
OT  - fibrinolysis
OT  - hemophilia A
OT  - infection
EDAT- 2023/09/28 06:43
MHDA- 2023/11/14 06:42
CRDT- 2023/09/28 02:29
PHST- 2023/09/11 00:00 [revised]
PHST- 2023/07/05 00:00 [received]
PHST- 2023/09/19 00:00 [accepted]
PHST- 2023/11/14 06:42 [medline]
PHST- 2023/09/28 06:43 [pubmed]
PHST- 2023/09/28 02:29 [entrez]
AID - 10.1111/hae.14877 [doi]
PST - ppublish
SO  - Haemophilia. 2023 Nov;29(6):1529-1538. doi: 10.1111/hae.14877. Epub 2023 Sep 27.