Research Studies

Von Willebrand disease (VWD) is the most common inherited bleeding disorder known in humans, but there are numerous barriers to accurate and timely diagnosis. In January 2021, new evidence-based guidelines were released by the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH) (James et al., 2021). The guidelines were designed to support patients, clinicians, and other health care professionals in promptly, accurately, and efficiently diagnosing VWD. Key recommendations in the guidelines include the use of bleeding-assessment tools when unusual bleeding is present and/or VWD is suspected; diagnostic assays; and the role of genetic vs. phenotypic testing for some types of VWD. Nurse practitioners can aid in identifying potential symptoms of VWD to help shorten the time from onset of symptoms to diagnosis.
 

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Objective:

To clinically validate previously reported stability experience and describe the utilization of continuous infusion (CI) factor VIII (FVIII) replacement therapy with turoctocog alfa for the management of an acute bleeding episode in a patient with hemophilia A.

Methods:

A 46-year-old woman who belongs to a kindred of women who display a unique dominant inheritance pattern of hemophilia A, with baseline FVIII 4% presented with a right thigh posterior compartment hematoma.  After initial bolus administration, on hospital day 2 the hematology consult service initiated a continuous infusion of turoctocog alfa at an initial rate of 4 units/ kilogram/ hour (u/kg/hr), to maintain 100% factor VIII replacement.  The syringe containing the recombinant FVIII (rFVIII) concentrate was changed approximately every 8 hours with a maximum 10-hour stability according to published data.  When FVIII activity levels were suboptimal, intermittent standard bolus infusions were administered and the rate of the continuous infusion was increased incrementally.  The FVIII activity level was measured using the one stage aPTT based clotting assay with STA PTT-Automate reagent on a STAGO model STAR Max.

Summary:

On hospital days 2 though 6, FVIII activity ranged 55% to 131%.  By hospital day 8 the Factor VIII level climbed suddenly to above 200%, and the patient demonstrated marked clinical improvement of the hematoma.  Also, on hospital day 8, her course was complicated by development of an upper extremity superficial venous thrombosis with associated cellulitis at an IV access site, which were treated by IV removal and antibiotics.  The decision was made to complete the remainder of a planned fourteen-day course of rFVIII as an outpatient. The CI was stopped to allow the FVIII activity level to drop below 80%, and subsequently restarted at a lower rate to maintain a level of at least 50% until patient discharge on Day 11. The turoctocog alfa was not restarted during the remainder of the hospitalization as FVIII level remained above 50%.  She had continued clinical resolution of the hematoma and returned to usual activities including moderate exercise after several weeks.

Conclusion:

The safety and efficacy of turoctocog alfa via bolus injection is supported by the guardianTM trials. This report describes the successful use of CI turoctocog alfa for management of an acute severe bleed and confirms prior stability data.  Our patient’s massive hematoma was effectively managed with CI FVIII replacement with turoctocog alfa during her hospitalization. This case highlights the need for close monitoring of FVIII activity and adjustment of CI dosing and illustrates the challenges and potential complications of an unexpected rise in FVIII activity. Reporting of case experiences are crucial to guide future use. Use of CI factor replacement ensures efficient use of expensive resources and effective treatment of acute and surgical bleeds.

Objectives:

The longer-term clinical outcomes of patients using emicizumab in real world settings are not well documented. This study examined hemophilia patient clinical outcomes, specifically bleed rate, emergency room visits/hospitalizations, nurse resource use, adherence and emicizumab wastage in the 6 months before and after initiating emicizumab.

Methods:

This is a retrospective cohort study of patients in the United States who received an emicizumab prescription between July 1, 2018 and July 1, 2019 from a single specialty pharmacy. Patients with moderate (1% to 5% factor activity) to severe (<1% factor activity) hemophilia were included if they took emicizumab for at least 6 months and had 6 months prior use of a prophylactic factor product. Self-reported bleeds, emergency room visits, hospital admissions and nurse visits (a visit by a nurse to provide administration, education and/or infusion of the drug) were obtained from the patient’s electronic medical record. Medication adherence was assessed by calculating proportion of days covered (PDC) (the number of days in period treated divided by number of days in period) using medication dispense date and quantity from the pharmacy dispensing system. Paired Wilcoxon signed-rank and McNemar’s tests were used to assess changes in outcomes. A one-way ANOVA was used to compare emicizumab waste (the amount of drug (mg) not used per month, across the 6 months after initiating emicizumab).

Summary:

The median participant age was 15 years (range 3-53) (N=35); all were male. After initiating emicizumab, patients reported 55% fewer bleeds (m=2.9 vs. 1.3; p=0.001), 83% fewer nurse visits (m=15.5 vs. 2.8; p=0.01) and 15% greater medication adherence (m=0.84 vs. 0.97; p=0.04). When stratifying by age, the reduction in nurse visits was only significant among patients under age 18 (p = 0.01) and the increase in medication adherence was only significant among adults 18+ (p=0.01). There was no difference in emergency room/hospital visits after initiating emicizumab (m=0.40 vs. 0.23; p = 0.4). Most patients (51.4%) reported emicizumab wastage in the first month. After the initial loading dose (month 1), there was a decreasing proportion of emicizumab waste across months 2-6, though comparisons were not statistically significant (13.8%, 13.3%, 12.1%. 12.4% and 10.9%; p>0.6). Although the intent was not to assess cost savings, our study did find a 9.1% savings in drug cost over the course of one year, when comparing factor utilization pre-emicizumab.

Conclusions:

In this study, taking emicizumab was associated with a significant reduction in bleeds and nursing visits which may reduce operational costs and increase medication adherence. No significant change in emergency room/hospital visits were observed. Future prospective studies with larger samples and a control group are needed to assess long-term clinical outcomes, health-related quality of life, and total cost and quality of care among patients using emicizumab.   

• The inherited bleeding disorders (IBD) community has witnessed significant advances in recent years thanks to novel therapeutic advances and technologies and improved diagnostic proficiency.

• Yet important gaps persistent, particularly for those with rare disorders and underserved populations, including women with IBD.

• A new initiative led by the National Hemophilia Foundation (NHF) and shaped by the voices of the patient community is underway to address this gap.

• Our goal: to design and implement a national research blueprint that outlines actionable strategies to address the most important needs within the community and opportunities to accelerate progress through coordinated collaboration.
   

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