Laboratory Monitoring in Emicizumab-Treated Persons with Hemophilia A.

Laboratory Monitoring in Emicizumab-Treated Persons with Hemophilia A. Thromb Haemost. 2019 Jun 16;: Authors: Müller J, Pekrul I, Pötzsch B, Berning B, Oldenburg J, Spannagl M Abstract Hemophilia A (HA) is an X-linked hereditary bleeding disorder caused by deficiency of coagulation factor (F) VIII activity. One of the greatest complications in the treatment of HA is the development of neutralizing alloantibodies, known as FVIII inhibitors. HA patients who develop FVIII inhibitors have limited treatment options available to them and experience greater disease- and treatment-related burdens than HA patients without FVIII inhibitors. Emicizumab, a recently approved bispecific monoclonal antibody, mimics the function of FVIIIa by bridging FIXa and FX to restore effective hemostasis. Although emicizumab and FVIII show some functional similarities, several key differences influence the results of standard laboratory assays when conducted in the presence of emicizumab, and can result in a misleading interpretation of coagulation assays in emicizumab-treated patients. Here, we discuss current laboratory monitoring methods, including activated partial thromboplastin time, FVIII one-stage clotting assays, FVIII chromogenic assays, and global coagulations assays; address why these conventional methods may be inappropriate for monitoring of HA patients receiving emicizumab; and suggest alternative methods applicable to monitoring HA treatment in an evolvin...
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: Thromb Haemost Source Type: research

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Authors: Escobar M, Santagostino E, Mancuso ME, Coppens M, Balasa V, Taylor JA, Iorio A, Negrier C Abstract Introduction: Prophylaxis with factor replacement therapy is the gold standard for the treatment of hemophilia, but this often requires frequent infusions. A number of long-acting factor products have been developed to reduce the burden on patients. Areas covered: This is an overview of information presented at two symposia held at the World Federation of Hemophilia and International Society on Thrombosis and Haemostasis - Scientific and Standardization Committee annual meetings. The pharmacokinetic, safety a...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
The usefulness of the activated partial thromboplastin time (APTT) waveform has been reported in hemophilia, acquired hemophilia and monitoring for anticoagulants.
Source: Thrombosis Journal - Category: Hematology Authors: Tags: Research Source Type: research
Semin Thromb Hemost DOI: 10.1055/s-0039-1688570Circulating cell-derived microparticles (MPs) exhibit procoagulant activity and have been investigated for a possible role in some human pathologies. However, their potential role in hemostasis has been neglected and often denied. This review brings to attention a specific body of direct clinical evidence supporting an important but distinctive role of MPs in hemostasis. Evidence for a role of MPs in hemostasis includes: (1) two congenital bleeding disorders attributed to impaired release of MPs; (2) two recent studies of trauma patients relating naturally elevated endogenous ...
Source: Seminars in Thrombosis and Hemostasis - Category: Hematology Authors: Tags: Review Article Source Type: research
We report a 54-year-old male with severe HA with FVIII activity of 0.8% when he was first diagnosed, who underwent successful mitral valve repair and coronary artery bypass graft with FVIII replacement perioperatively. Diagnoses: Transthoracic echocardiography and coronary angiography confirmed the HA patient with the diagnosis of severe mitral valve regurgitation and left anterior descending artery stenosis. Interventions: Before surgery, a bolus of 1000 IU FVIII was injected, which obtained an FVIII of 80%. After induction, a 3750 IU bolus of FVIII was injected and subsequent FVIII level reached 135%. Mitral valve ...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
CONCLUSIONS: These results indicate that, in comparison to rFIX, the prophylactic use of extended half-life FIX provides superior protection from bleeding-induced joint damage, manifested by improved correction of histologic parameters. This article is protected by copyright. All rights reserved. PMID: 31148392 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research
AbstractAntithrombotic treatment and perioperative management in patients with hemophilia remains a challenge. As life expectancy in these patients is increasing, a concern about cardiovascular diseases is emerging. Herein we present the case of a 68  year-old patient with mild hemophilia B and multivessel coronary disease who underwent coronary artery bypass grafting (CABG) surgery. Off-pump surgery with continuous infusion FIX treatment was performed successfully with stable factor IX levels, and no bleeding or thrombotic complications. There is a paucity of cases reported regarding management of CABG in this popula...
Source: Journal of Thrombosis and Thrombolysis - Category: Hematology Source Type: research
Factor IX (FIX) binds to collagen IV (Col4) in the subendothelial basement membrane. In hemophilia B, this FIX-Col4 interaction reduces the plasma recovery of infused FIX and plays a role in hemostasis. Studies examining the recovery of infused BeneFix (FIXWT) in null (cross-reactive material negative, CRM–) hemophilia B mice suggest the concentration of Col4 readily available for binding FIX is ~405 nM with a 95% confidence interval of 374 to 436 nM. Thus, the vascular cache of FIX bound to Col4 is several-fold the FIX level measured in plasma. In a mouse model of prophylactic therapy (testing hemostasis by saphenou...
Source: Blood - Category: Hematology Authors: Tags: Thrombosis and Hemostasis, Vascular Biology Source Type: research
CONCLUSION: rFVIIa use in the context of emicizumab prophylaxis does not change the rFVIIa safety profile as described in the product information. This article is protected by copyright. All rights reserved. PMID: 31124272 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: J Thromb Haemost Source Type: research
Hemophilia B is an X-linked recessive bleeding disorder caused by coagulation factor IX (FIX) gene (F9) mutations. Several F9 synonymous mutations have been known to cause hemophilia B; however, the deleterious mechanisms underlying the development of hemophilia B have not been completely understood. To elucidate the molecular pathogenesis causing hemophilia B, we investigated the synonymous F9 mutation: c.87A>G, p.(Thr29=).
Source: Thrombosis Research - Category: Hematology Authors: Tags: Full Length Article Source Type: research
This article discusses the pros and cons of molecular testing in VWD considering the experience obtained through the multicenter project “Molecular and Clinical Profile of VWD in Spain (PCM-EVW-ES).” [...] Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: Seminars in Thrombosis and Hemostasis - Category: Hematology Authors: Tags: Review Article Source Type: research
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