Clot waveform analysis for perioperative hemostatic monitoring of arthroscopic synovectomy in a pediatric patient with hemophilia A and inhibitor receiving emicizumab prophylaxis

Mizumachi, Kuniyoshi; Tsumura, Yusuke; Nakajima, Yoji; Koh, Katsuyoshi; Nogami, Keiji

doi:10.1007/s12185-021-03095-w

Cited by 12 publications

(12 citation statements)

References 17 publications

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“…The effect of emicizumab on activated partial thromboplastin time (aPTT) is stronger than that of FVIII. 13 As a result, plasmabased global coagulation assays, CWA, [20][21][22] and thrombin generation assay 15,17,[22][23][24] are more useful for the assessment of the hemostatic potential of emicizumab in clinical practice. In this study, we created an in vitro plasma model of neonate-HA by preincubating plasma from non-HA neonates with an anti-FVIII mAb to assess the coagulant effects of emicizumab using global coagulation assays.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous coagulant potential of emicizumab in neonatal factor VIII–deficient plasma

Takeyama

Furukawa

Onishi

et al. 2022

Pediatric Blood & Cancer

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Background: Emicizumab prophylaxis reduces bleeding in hemophilia A (HA) patients.However, there are few data on emicizumab treatment in neonates with HA (neonate-HA), and the procoagulant effects of emicizumab in these patients are unknown. Aim:To investigate the coagulation activity of emicizumab in vitro in a plasma model of neonate-HA.Methods: Plasmas from 84 neonates with non-HA were enrolled. However, due to the limited plasma volumes in some cases, 50 plasmas were assigned to two different assay groups. To prepare the neonate-HA model, plasma was first preincubated with an antifactor (F) VIII A2 monoclonal antibody (mAb). After further incubation with emicizumab, global coagulation activity was measured: adjusted maximum coagulation velocity (Ad|min1|) in clot waveform analysis (CWA) and peak thrombin in thrombin generation assay (TGA).Results: Because the addition of anti-FVIII mAb to 22 of 43 samples showed little decrease in Ad|min1|, the remaining 21 samples were analyzed by CWA. The addition of emicizumab increased Ad|min1| in 18 of the 19 cases (effective group) but not in the remaining 3 cases (noneffective group). Similarly, TGA found that emicizumab (effective group) improved peak thrombin in seven of the nine samples tested, but two cases did not respond (noneffective group). Although the effective group had lower levels of FX, there was no significant difference between the effective and noneffective groups in terms of FIX, protein S, protein C, antithrombin, and fibrinogen.

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Section: Introductionmentioning

confidence: 99%

Heterogeneous coagulant potential of emicizumab in neonatal factor VIII–deficient plasma

Takeyama

Furukawa

Onishi

et al. 2022

Pediatric Blood & Cancer

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“…This led to a black box warning for emicizumab to prevent combination of high doses of aPCC during a longer period (<100 IU/kg per 24 h). Afterwards, several case reports were published that studied the efficacy of emicizumab and BPA dosage, which was determined with TGAs 61–66 67 The authors included 11 HA patients with an inhibitor who were treated weekly with emicizumab for at least 6 weeks.…”

Section: Emicizumabmentioning

confidence: 99%

Thrombin generation for monitoring hemostatic therapy in hemophilia A: A narrative review

Verhagen

Valke

Schols

2022

Journal of Thrombosis and Haemostasis

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Hemophilia A (HA) is characterized by an abnormal low coagulation factor VIII (FVIII) activity level. HA patients with severe (FVIII activity level <1%) disease have an increased risk of trauma-related and spontaneous bleeding, especially in joints and muscles. Prophylactic replacement therapy with FVIII concentrate is recommended for these patients to prevent bleeding and to preserve musculoskeletal health. 1 The prophylactic scheme is now based on patient body weight and individual pharmacokinetic (PK) studies. Remarkably, there is a large inter-individual variability in PK dosing based on this algorithm. 2 Interestingly, however, some patients still experience breakthrough bleeds despite adequate FVIII trough levels, whereas others do not bleed with trough levels below threshold. 3 In addition, large heterogeneity in bleeding phenotype between patients with the same baseline FVIII activity level is observed. [3][4][5]

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“…Surgical experience in patients on emicizumab out of clinical trials is being increasingly reported in form of either case reports 34,37–39,41,43–46,64–65 or case series 33,40,42,47 . Table 2 summarizes the real‐world experience reported so far in form of case reports.…”

Section: Invasive Procedures In the Era Of Non‐factor Replacement The...mentioning

confidence: 99%

“…All procedures were managed with rFVIIa +/tranexamic acid without any thrombotic complication. 32 Surgical experience in patients on emicizumab out of clinical trials is being increasingly reported in form of either case reports 34,[37][38][39]41,[43][44][45][46][64][65] or case series. 33,40,42,47 Table 2 summarizes the real-world experience reported so far in form of case reports.…”

Section: Perioperative Management Of Pwh Treated With Emicizumabmentioning

confidence: 99%

“…To date, limited information on surgical management of PWH on prophylaxis with fitusiran and anti‐TFPI is available from clinical trials 27–29 . On the other hand, more data have been collected and published on the surgical management of patients on emicizumab prophylaxis both during the clinical trial program 30–32 and in the real‐world setting 33–47 …”

Section: Introductionmentioning

confidence: 99%

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Managing invasive procedures in haemophilia patients with limited resources, extended half‐life concentrates or non‐replacement therapies in 2022

2022

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New treatment possibilities and modalities are now available globally for patients with haemophilia requiring surgery or invasive procedures. The first is the appropriate application of low‐dose protocols of clotting factor concentrates (CFC) achieving adequate perioperative haemostasis in resources constraint environments. The increasing availability of CFC through humanitarian aid programs allows more invasive surgeries to be performed for which efficacy and safety data should be more widely collected and reported. Second, extended half‐life CFC that are increasingly available in many countries represent valuable alternatives to standard half‐life products in surgical patients allowing reduced number of infusions and lower consumption, in particular for extended half‐life factor IX. Third, in the era of recently introduced nonfactor prophylaxis, some minor surgical procedures can now be performed without additional haemostatic treatment, others with few low‐dose administrations of CFC or bypassing agents. Additional factor VIII/IX or recombinant activated factor VII has proven to be safe and effective in association with emicizumab for major surgeries and it was effectively given at low doses in association with fitusiran (including activated prothrombin complex concentrate). No thrombotic complications have been reported in the surgical setting so far. A multidisciplinary team/facility remains crucial to manage major surgery in patients on prophylaxis with these new agents.

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Clot waveform analysis for perioperative hemostatic monitoring of arthroscopic synovectomy in a pediatric patient with hemophilia A and inhibitor receiving emicizumab prophylaxis

Cited by 12 publications

References 17 publications

Heterogeneous coagulant potential of emicizumab in neonatal factor VIII–deficient plasma

Heterogeneous coagulant potential of emicizumab in neonatal factor VIII–deficient plasma

Thrombin generation for monitoring hemostatic therapy in hemophilia A: A narrative review

Managing invasive procedures in haemophilia patients with limited resources, extended half‐life concentrates or non‐replacement therapies in 2022

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