Systematic monitoring of hemostatic management in hemophilia A patients with inhibitor in the perioperative period using rotational thromboelastometry

Abstract

To cite this article: Furukawa S, Nogami K, Ogiwara K, Yada K, Minami H, Shima M. Systematic monitoring of hemostatic management in hemophilia A patients with inhibitor in the perioperative period using rotational thromboelastometry. J Thromb Haemost 2015; 13: 1279-84.Summary. Background: The management of hemophilia A (HA) patients with inhibitors on bypassing therapy remains challenging. In particular, the monitoring of treatment is restricted by the limited reliability and lack of standardization of currently available methods to evaluate the physiological effects of various hemostatic agents. Accurate monitoring of these patients is particularly important in surgical situations. The recently developed comprehensive coagulation assays, including rotational thromboelastometry (ROTEM), may be useful in these circumstances. Objective: We have attempted to establish a systematic monitoring protocol using ROTEM (NATEM triggered by CaCl 2 ) to evaluate the choice and effectiveness of different bypassing agents in the perioperative period. Methods and Results: The hemostatic effects of recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrates (aPCC) were determined using a three-step procedure (spike, preoperative and perioperative) in eight patients with HA inhibitor admitted for elective surgery and assessed for individually tailored therapy. The ROTEM parameters demonstrated similar improvement to approximately normal levels at each stage after treatment with rFVIIa. Results in the presence of aPCC showed a marked improvement in the spike data, although this appeared to be different from those in the preoperative and perioperative assessments. The information derived from the spike and preoperative findings provided a useful guide for establishing an effective dose of therapeutic material, and facilitated good hemostatic control during and after surgery in all cases. Conclusion:The findings suggest that this systematic analysis using ROTEM could provide a promising strategy for the use of bypassing therapy in HA patients with inhibitor.

Disordered hemostasis associated with severely depressed fibrinolysis demonstrated using a simultaneous thrombin and plasmin generation assay during L‐asparaginase induction therapy in pediatric acute lymphoblastic leukemia

“…Other studies have shown that Plt counts and P‐selectin levels increase in the later phases of induction, and it may be that restoration of Plt function plays an important role in these overall mechanisms. Further studies are required to examine the interplay between plasma‐derived components and Plt by using whole blood global clotting assays, for example, rotational thromboelastometry (ROTEM ® ) …”

“…The study population included consecutive newly diagnosed patients with ALL enrolled from August 2014 to March 2018 at four core hospitals for pediatric hematology and oncology in Japan. All patients received induction chemotherapy following the guidelines of either the Japan Association of Childhood Leukemia Study (JACLS) ALL-02 protocol, consisting of a total of six doses of Escherichia coli L-Asp (Leunase R , Kyowa Hakko Kirin Co., Ltd, Tokyo, Japan) 6000 U/m 2 (JACLS group, Day 15,17,19,22,24,and 26) or the Berlin-Frankfurt-Münster (BFM) 95 oriented protocol consisting of a total of eight doses of E. coli L-Asp (Leunase R ) 5000 U/m 2 (BFM group, Days 12,15,18,21,24,27,30, and 33) ( Figure 1). 14,15 Thromboprophylaxis including FFP transfusion, usually without cryoprecipitate because of it being an uncommon product in Japan, for low fibrinogen (Fbg) levels (≤50 mg/dL), AT supplementation for low AT levels (≤70% of control), and administration of Dana for anticoagulation was included in these protocols, if required, ultimately based on the decision of each clinician.…”

Global coagulation assays in hemophilia A: A comparison to conventional assays

“…Researchers have explored the use of global assays to measure coagulation potential with these products . Furthermore, evidence suggests that global assays are a useful tool to detect bleeding tendency in people with HA, might facilitate individualized treatment of patients with HA, and help monitor bypassing agents in patients with inhibitors …”

Hemostatic function in hyperfibrinolytic disseminated intravascular coagulation

“…Figure a–c illustrates representative thromboelastograms during the bleeding phase. CT NATEM reflects the initiation phase of coagulation, and was markedly shortened compared with normal (936 s; 95%CI: 762–1,127 s), especially at BL day –1 (324 s) and BL day +1 (615 s). These data confirmed a hypercoagulant state at these times.…”

“…The coagulation process was assessed using the clotting time (CT NATEM ; the time until detection of clot firmness at 2 mm amplitude) and clot formation time (CFT; the time until detection of clot firmness of 20 mm amplitude; Fig. ) . Measurements were obtained up to a maximum of 3,600 s. The impact of TF derived from AML cells on clot formation was measured by the changes in CT NATEM with the ex vivo addition of anti‐TF monoclonal antibody (mAb; f.c., 50 μg/mL) during the bleeding phase.…”