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. 2021 Apr;43(2):273-280.
doi: 10.1111/ijlh.13347. Epub 2020 Sep 23.

Overall hemostasis potential and aPTT-clot waveform analysis as powerful laboratory diagnostic tools for identification of hemophilia A patients with unexpected bleeding phenotype

Marija Milos  1 , Désirée Coen Herak  1 , Nida Mahmoud Hourani Soutari  2   3 , Josipa Pavic  4 , Silva Zupancic-Salek  5 , Renata Zadro  6 , Jovan P Antovic  2   3
Affiliations

Overall hemostasis potential and aPTT-clot waveform analysis as powerful laboratory diagnostic tools for identification of hemophilia A patients with unexpected bleeding phenotype

Marija Milos et al. Int J Lab Hematol. 2021 Apr.

Abstract

Introduction: Traditionally used laboratory methods do not always accurately reflect bleeding severity in hemophilia A (HA) patients. The ability of three global assays for identifying patients with unexpected bleeding phenotype was investigated.

Methods: Overall hemostasis potential (OHP), aPTT-clot waveform analysis (aPTT-CWA), endogenous thrombin potential (ETP), FVIII activities, and prothrombin fragment 1 + 2 concentrations were measured in 62 HA patients (30 severe and 32 non-severe) and 27 male controls. Bleeding phenotype was determined using our proposed scoring system including age at first joint bleed, number of target joints, and number of joint/muscle bleeds per year. Bleeding score ≤ 4 defined patients with mild bleeding phenotype (N = 27); score ≥ 5 defined severe bleeding phenotype (N = 35).

Results: The receiver operating characteristic analysis performed for distinguishing patients with severe and mild bleeding phenotype yielded following values of area under the curve: 0.910 (FVIII); 0.891 (aPTT-CWA parameter DELTA); 0.769 (OHP); and 0.634 (ETP). Unexpected bleeding phenotype was identified in 11/62 HA patients: 8/32 (25%) non-severe HA patients had severe, while 3/30 (10%) severe HA patients had mild bleeding phenotype, and global assays enabled the identification of all these patients. OHP and DELTA were revealed as the most reliable parameters for bleeding phenotype determination (10/11 and 9/11 unexpected results, respectively).

Conclusion: This study emphasizes OHP and aPTT-CWA as a powerful laboratory diagnostic tool in identifying HA patients with unexpected bleeding presentations, with the best results achieved by combining both assays. Global assays should not completely replace FVIII activity measurement but should be a part of the HA diagnostic algorithm.

Keywords: aPTT-clot waveform analysis; bleeding phenotype; endogenous thrombin potential; hemophilia A; overall hemostasis potential.

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References

REFERENCES

    1. White GC II, Rosendaal F, Aledort LM, Lusher JM, Rothschild C, Ingerslev J. Recommendations of the Scientific Subcommittee on Factor VIII and Factor IX of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 2001;85:560.
    1. Franchini M, Lippi G. Factor V Leiden and hemophilia. Thromb Res. 2010;125:119-123.
    1. Franchini M, Mannucci PM. Modifiers of clinical phenotype in severe congenital hemophilia. Thromb Res. 2017;156:60-64.
    1. Escuriola-Ettingshausen C, Halimeh S, Kurnik K, et al. Symptomatic onset of severe hemophilia A in childhood is dependent on the presence of prothrombotic risk factors. Thromb Haemost. 2001;85:218-220.
    1. Pavlova A, Oldenburg J. Defining severity of hemophilia: more than factor levels. Semin Thromb Hemost. 2013;39:702-710.

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