Boy’s rare case shows complexity of bleeding disorder diagnosis

A 3-year-old boy in Texas was the first known person with two bleeding disorders — type 1 von Willebrand disease (VWD) and hemophilia A — who responded well to preventive treatment with Altuviiio (efanesoctocog alfa), according to a case report.

The coexistence of VWD and hemophilia A “complicates diagnostic assessment and is likely underrecognized due to limitations in testing and overlapping phenotypes [presentations],” the scientists wrote.

Because of this complexity, “individualized evaluation and management” are essential, the researchers said. While “prophylaxis is typically reserved for moderate to severe [hemophilia A] and type 3 VWD,” in the boy’s case it was “deemed necessary to preserve joint health,” they wrote.

The report, “Efanesoctocog Alfa Prophylaxis in a Patient With Combined Mild Hemophilia A and Type 1 von Willebrand Disease,” was published as a letter to the editor of Pediatric Blood & Cancer.

Both VWD and hemophilia A can be inherited and interfere with the body’s ability to form blood clots. While they can share symptoms, such as easy bruising and abnormal bleeding, they stem from different problems in the clotting process.

Fall prompts visit to emergency department

In hemophilia A, mutations in the F8 gene impair the activity of factor VIII (FVIII), a protein crucial for blood clotting. Patients often experience bleeding into muscles and joints in the disorder, which primarily affects males. Type 1 VWD, the most common form of the disease, is caused by reduced levels of von Willebrand factor (VWF) — a protein that helps blood platelets stick together to form clots and stabilizes FVIII. When the two conditions occur together, bleeding may be more severe and harder to control.

The 3-year-old boy was brought to the University of Texas Southwestern Medical Center emergency department three weeks after a fall caused knee swelling and difficulty walking. Imaging ruled out a fracture, but an ultrasound revealed fluid in a joint.

Two weeks after hospital discharge, the fluid accumulation was worse, prompting aspiration and an arthroscopy — a minimally invasive procedure to look inside a joint — which revealed bleeding (hemarthrosis).

The boy returned five days later with pain, swelling, and bleeding at the incision site. Lab tests showed low hemoglobin (the protein that carries oxygen in red blood cells) and low FVIII activity, consistent with mild hemophilia A. He began treatment with lab-made FVIII (rFVIII) infusions to provide a working protein.

When further testing revealed that his VWF levels were also low, doctors initially suspected type 2N VWD, a rare form in which VWF cannot properly bind to FVIII. However, follow-up tests showed normal FVIII-VWF binding, ruling out this diagnosis.

Dosing frequency was progressively spaced. The boy had better range of motion and could walk without pain by the time he was discharged from the hospital.

He continued on rFVIII prophylaxis and outpatient physical therapy, but another injury to his left knee sent him to the hospital for joint bleeding treatment. Testing confirmed type 1 VWD. Prophylaxis therapy was extended, during which time the boy’s joint mobility was fully restored.

But a spontaneous joint bleed in his left knee made the clinicians decide to start the boy on weekly Altuviiio (efanesoctocog alfa) — a long-lasting FVIII replacement therapy used to decrease the frequency of bleeding episodes or control and manage active bleeds in people with hemophilia A.

After the switch, his FVIII trough levels (the lowest concentration in the bloodstream before the next dose is administered) rose from 3% to 15% in four weeks. He had remained bleed-free for six months by the time this study was concluded, with no development of FVIII inhibitors (neutralizing antibodies that reduce the effectiveness of replacement therapies). A genetic test later confirmed a mutation in the F8 gene, supporting the hemophilia A diagnosis.

“This represents the first reported case of a patient with combined [hemophilia A] and type 1 VWD receiving efanesoctocog alfa [Altuviiio] prophylaxis,” the researchers wrote.