Challenges of biological monitoring in a hemophilia A patient without inhibitors on emicizumab undergoing major orthopedic surgery: a case report.

A man with severe hemophilia A (HA) without factor VIII (FVIII) inhibitors was admitted for total arthroplasty of his elbow. The patient was being treated with emicizumab, with his last administration given 8 days before surgery. Preoperatively, he received a bolus of 4000 international units (IU) of recombinant (r)FVIII. Throughout the operation, a continuous infusion of 4 IU/kg/h was administered and maintained over 24 hours. On the first postoperative day, the FVIII infusion rate was reduced to 225 IU/h for 4 days and stopped on the fifth day. Under this treatment, no bleeding complications occurred. Emicizumab is known to interfere with a wide range of coagulation assays, thereby challenging replacement therapy monitoring before, during, and after surgery. In this case study, we report on the assessment of FVIII levels at different time points using various reagents. We conclude that for both hematologists and non-hematology clinicians, it is crucial to be aware of emicizumab interferences with routine coagulation tests so as to avoid misinterpretation. In addition, laboratory specialists must be familiar with this treatment in order to select appropriate coagulation tests and provide rapid and reliable result interpretations.

Analytical performances and biological variation of PIVKA-II (des-y-carboxy-prothrombin) in European healthy adults.

BACKGROUND: PIVKA-II (DCP) is increasingly used for the diagnosis and the surveillance of hepatocellular carcinoma (HCC) in at-risk populations. However, to date, few data are available concerning the intra- and inter-individual variability of this marker, which makes the interpretation of serial measurements difficult in the context of monitoring. METHODS: 19 European healthy volunteers (HVs) were taken each week during five consecutive weeks. Samples were analyzed in duplicate on the Lumipulse® analyzer (Fujirebio, Gent, Belgium). Analytical variation (CVA), within-subject biological variation (CVI) and between-subject biological variation (CVG) were calculated using nested ANOVA following normality assessment, outlier exclusion, and homogeneity of variance analysis. RESULTS: No significant difference was observed for the mean values (p = 0.23) between men (mean: 30.66 mAU/mL) and women (mean: 33.90 mAU/mL) subgroups. CVA was 2.82% while sex-independent CVI and CVG were 13.35% and 16.05%, respectively. Taking these values, the calculated reference change value (RCV) and index of individuality were 37.70% and 0.85, respectively. CONCLUSION: We reported for the first-time biological variation data for PIVKA-II in a cohort of European HVs. We believe that our results can be used to set analytical specification goals as well as to improve the interpretation of serial measurements of PIVKA-II for monitoring purposes.