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. 2018 Jul 30;9(8):213-226.
doi: 10.1177/2040620718785363. eCollection 2018 Aug.

Clinicopathological parameters influencing inhibitor development in patients with hemophilia A receiving on-demand therapy

Sanya Arshad  1 , Anshima Singh  1 , Namrata Punit Awasthi  2 , Swati Kumari  1 , Nuzhat Husain  1
Affiliations

Clinicopathological parameters influencing inhibitor development in patients with hemophilia A receiving on-demand therapy

Sanya Arshad et al. Ther Adv Hematol. .

Abstract

Background: Development of inhibitors to transfused factor VIII in patients with hemophilia A continues to be a challenge for professionals involved in hemophilia care. The majority of patients in India receive 'on-demand' rather than prophylactic therapy. The present study was done to assess the prevalence of factor VIII inhibitors in patients with hemophilia A (PWHA) receiving 'on-demand' therapy in a North Indian population and to study the clinicopathological parameters influencing the development of inhibitors.

Methods: The study group comprised of 300 PWHA. Detailed clinical parameters, treatment history, bleeding profile including family history were recorded. Diagnosis of hemophilia A was confirmed by relevant coagulation tests. Inhibitors were screened using mixing based studies followed by quantification by Bethesda assay and Nijmegen modified Bethesda assay. Samples were collected from five cities in North India where a free supply of factor VIII was available and effectively used in three of these cities.

Results: In the 300 PWHA, disease phenotype was severe in 219 (73%), moderate in 62 (20.67%) and mild in 19 (6.34%), based on the factor VIII bioassay. Inhibitor prevalence was 9.6% (n = 29) and seen only in the severe phenotype. Inhibitor titers ranged from 0.8 to 108.8 BU/ml. A total of 12 PWHA had low and 17 had high titers. Correlation of various clinicopathological parameters in inhibitor-positive versus negative PWHA showed significant correlation with age at onset of disease, severity of disease, age at first exposure to treatment, annual factor intake (IU/kg/year), intense treatment episodes and bleeding manifestations like central nervous system bleed and hematuria. The total study sample had blood group B in 33.34% PWHA, followed by O (27.34%), A (24.34%) and AB (15%), however, in inhibitor-positive samples, significant inhibitor formation was associated with the ABO subtype A (19/29, 65.51%).

Conclusions: Factor VIII inhibitor prevalence in PWHA receiving 'on-demand' therapy was 9.6%. Clinicopathological correlates of inhibitor development in such PWHA have been analyzed in this novel study.

Keywords: Bethesda assay; factor VIII; hemophilia A; inhibitors; plasma derived factor VIII.

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Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Comparison of inhibitor-positive versus inhibitor-negative patients with reference to: (a) phenotype of patients with hemophilia A (b) blood products and factor administered, and (c) city-level distribution in relation to the annual factor intake.
Figure 2.
Figure 2.
Figure showing distribution of levels of inhibitors in PWHA; six patients show black bars, where the inhibitor was detected by Nijmigen modified bethesda asssay; others were detected by classical Bethesda assay.
Figure 3.
Figure 3.
Comparison of frequency of average number of bleeds per year in inhibitor-positive and inhibitor-negative severe patients.
See this image and copyright information in PMC

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