The in vitro cross-reactivity and blood coagulation potential of recombinant porcine factor VIII in Japanese patients with acquired hemophilia A.

Recombinant porcine factor VIII (rpFVIII) is a hemostatic agent for acquired hemophilia A (AHA). Cross-reaction of auto-antibodies against rpFVIII has been reported, although no data are available in Japanese patients. This study investigated the cross-reactivity and coagulation potential of rpFVIII in plasma samples from Japanese patients with AHA.

Longitudinal dynamic changes in factor VIII inhibitor titers in patients with hemophilia A and inhibitors receiving emicizumab prophylaxis.

Emicizumab prophylaxis dramatically reduces bleeding events in patients with hemophilia A (PwHA) with or without factor VIII (FVIII) inhibitors. However, long-term dynamic changes in FVIII inhibitor titers during emicizumab prophylaxis remain to be investigated. We conducted a retrospective follow-up study of FVIII inhibitor titers after initiation of emicizumab prophylaxis in 25 PwHA carrying current or historical FVIII inhibitors.

Factor VIII A3 domain residues 1793-1795 represent a factor IXa-interactive site in the tenase complex.

Background: Factor (F)VIII functions as a cofactor in the tenase complex responsible for conversion of FX to FXa by FIXa. Earlier studies indicated that one of the FIXa-binding sites is located in residues 1811-1818 (crucially F1816) of the FVIII A3 domain. A putative, three-dimensional structure model of the FVIIIa molecule suggested that residues 1790-1798 form a V-shaped loop, and juxtapose residues 1811-1818 on the extended surface of FVIIIa.

Longitudinal profiling of anti-factor VIII antibodies in Japanese patients with congenital hemophilia A during factor VIII replacement and immune-tolerance induction therapy.

When patients with hemophilia A develop factor VIII (FVIII) inhibitors, FVIII replacement therapy becomes ineffective. Although immune-tolerance induction (ITI) therapy has been used to eradicate inhibitors, treatment is unsuccessful in approximately 30% of cases. However, the mechanism behind treatment failure remains unclarified.

Comprehensive blood coagulation potential in patients with acquired hemophilia A: retrospective analyses of plasma samples obtained from nationwide centers across Japan.

Global coagulation potential was assessed in 59 patients with acquired hemophilia A (PwAHA) by clot waveform analysis (CWA) and/or thrombin and plasmin generation assay. Relationships between factor VIII activity (FVIII:C) and the parameters from CWA and T/P-GA in patients with congenital HA were compared by grading coagulation potential related to FVIII:C: T1 (FVIII:C < 1 IU/dL), T2 (1 ≤ , ≤ 5 IU/dL), T3 (5 < , 12 ≤ IU/dL), and T4 (12 < , ≤ 50 IU/dL). The median FVIII:C and inhibitor titers in PwAHA on admission were 3.

A novel simultaneous clot-fibrinolysis waveform analysis for assessing fibrin formation and clot lysis in haemorrhagic disorders.

Simultaneous evaluation of coagulation and fibrinolysis facilitates an overall understanding of normal and pathological haemostasis. We established an assay for assessing clot formation and fibrinolysis simultaneously using clot waveform analysis by the trigger of a mixture of activated partial thromboplastin time reagent and an optimized concentration of tissue-type plasminogen activator (0·63 μg/ml) to examine the temporal reactions in a short monitoring time (<500 s). The interplay between clot formation and fibrinolysis was confirmed by analysing the effects of argatroban, tranexamic acid and thrombomodulin.

Contribution of Factor VIII A2 Domain Residues 400-409 to a Factor X-Interactive Site in the Factor Xase Complex.

The link between factor (F)VIII and FX is essential for optimum activity of the tenase complex. The interactive site(s) in FVIII for FX remains to be completely clarified, however. We investigated the FVIII A2 domain-FX association that was speculated from inhibitory mechanism(s) by an anti-A2 autoantibody.