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The Use of Chromogenic Factor VIII Assay Changes Treatment Approach - 2019 - BL
The Use of Chromogenic Factor VIII Assay Changes Treatment Approach - 2019 - BL
http://doi.org/10.1182/blood-2019-123799
Introduction
The objectives of this retrospective study were to determine the proportion of patients with OSA/CSA
discrepancies defined by OSA to CSA ratio of >1.5 or <0.5, to identify previously reported and new F8
gene mutations and to classify the impact of assay discrepancy on clinical treatment approach. Also,
the study aimed to re-evaluate published discrepant OSA/CSA ratios to identify a ratio with the highest
sensitivity to indicate that a change of treatment approach or intensity may be required.
Methods
We reviewed the charts of adult (>18 years old) patients with mild or moderate hemophilia A followed at
the Adult British Columbia Hemophilia clinic with concomitant OSA and CSA results between January
2013 and March 2019. Data collected included patient age, disease severity classification, baseline OSA
FVIII:C, and F8 gene mutation. Bleeding phenotype and impact of discrepancy on treatment approach
was evaluated and determined independently by two individuals and was correlated with concomitant
OSA and CSA. Gene mutation data was collected to determine whether OSA/CSA discrepancy has
been previously reported in the international hemophilia A mutation database (www.factorviii-db.org).
Descriptive data was reported as medians and ranges. Statistical analyses using Spearman's correlation,
logistic regression and receiver operating characteristics (ROC) curve were performed using IBM SPSS v.
22.0.
Results
98 patients were included in the study with median age of 53 years (18-88). 75 patients were classified
by OSA at baseline as mild and 23 patients as moderate severity. Median FVIII:C by OSA was 15%
(6%-40%) in the mild group and 3% (1%-5%) in the moderate severity group. Median FVIII:C using CSA
was 13% (2%-66%) in the mild group and 4% (1%-7%) in the moderate group. Based on ratio alone,
OSA/CSA discrepancy was detected in 51 (52%) patients out of which 3 (3%) were reverse discrepancies
(CSA higher than OSA).
Treatment approach was changed as a result of CSA introduction in 14 (27%) patients with OSA/CSA
discrepancy (14% of the entire study population). OSA had overall good correlation with CSA (r = 0.84)
and as expected, there was no correlation between age and OSA to CSA ratio (r = 0.03). In the patients
with OSA/CSA discrepancies, neither age nor OSA/CSA predicted a change of treatment approach (OR
1.02 for age; 95% CI 0.99-1.06; p value 0.213 and OR 1.48 for OSA/CSA; 95% CI 0.96-2.28; p value
0.08).
The OSA to CSA ratio of 1.8 to 3.5 demonstrated the highest area under the ROC curve and sensitivity
for identification of requirement for treatment change in patients with OSA/CSA discrepancy (AUC 0.75;
sensitivity 71%, negative predictive value 75%).
Six F8 gene mutations with OSA/CSA discrepancies previously not reported in the database were
identified.
Conclusions
OSA/CSA discrepancies were detected in 52% of the patients with mild or moderate hemophilia
A and resulted in change of treatment approach in 27% of discrepant patients. Use of an adjusted
OSA/CSA ratio between 1.8 to 3.5 was more likely to detect cases with a requirement for change of
treatment approach and use of this ratio to indicate discrepancy may be more clinically meaningful. Six
gene mutations associated with OSA/CSA discrepancies previously not described in the international
hemophilia A mutation database were identified in the study population, highlighting the need for
genotyping discrepant cases.
Disclosures
No relevant conflicts of interest to declare.
Author notes
*Asterisk with author names denotes non-ASH members.