Hemophilia: Why Mild or Moderate Doesn’t Always Mean “Mild”—New Research on Classification

What You’ll Learn From This Article

This article summarizes a 2025 study that challenges how we classify hemophilia—especially “mild” and “moderate” forms. You’ll discover why relying solely on blood clotting factor levels (like factor VIII or IX) might not capture the true bleeding risk for some people. We’ll break down what the research means for patients, including how it could change treatment decisions and improve quality of life.

A Quick Look at Hemophilia

Hemophilia is an inherited bleeding disorder where the body lacks enough of a protein (factor VIII for hemophilia A, factor IX for hemophilia B) that helps blood clot. For decades, doctors have classified hemophilia as:

• Severe: Factor levels <1% of normal (spontaneous bleeds, often in joints/muscles).
• Moderate: Factor levels 1–5% (bleeds after minor trauma or surgery).
• Mild: Factor levels 6–40% (bleeds only after major trauma or surgery).

But this study asks a critical question: What if someone with “mild” or “moderate” hemophilia has severe bleeding?

Why This Research Matters

For many patients, the label “mild” or “moderate” suggests a lower risk of serious bleeds. But the study found that over 20% of people with mild/moderate hemophilia experience severe bleeding events—like joint damage (arthropathy), life-threatening intracranial hemorrhages (ICH), or reactions to treatment (inhibitors).

This matters because classification affects:

• Treatment access: New therapies (e.g., emicizumab) are often approved only for “severe” hemophilia.
• Quality of life: Undiagnosed severe bleeds can lead to chronic pain, disability, or even death.
• Care planning: Doctors need accurate information to prevent bleeds and manage risks.

The Core of the Research: Reclassifying Hemophilia

The study analyzed data from 46 papers (including 1,197 patients with mild/moderate hemophilia A/B and 47 with hemophilia B Leyden). Researchers used strict criteria to define “severe” bleeding:

• Joint bleeds: Disproportionate to trauma, requiring hospitalization, or causing long-term damage (arthropathy).
• Non-joint bleeds: Fatal, life-threatening (e.g., ICH), or not controlled by standard treatment.
• Inhibitors: Antibodies that block factor replacement therapy (making treatment harder).

Key Findings:

1. Severe Bleeds Are Common in “Mild/Moderate” Hemophilia

   • 20.8% of mild hemophilia A patients had severe joint bleeds/arthropathy.
   • 79.4% of moderate hemophilia A patients had severe joint issues.
   • Even “mild” patients experienced life-threatening bleeds (e.g., ICH after trauma).

2. Inhibitors Are a Risk

   • 3.1% of mild hemophilia A patients and 9.1% of moderate patients developed inhibitors—complicating treatment.

3. Hemophilia B Leyden Is Unique

   • This rare form causes low factor IX levels in childhood, but levels rise with age. Most severe bleeds occurred before age 15 (when factor levels were lowest).

What This Means for Patients and Families

If you or a loved one has “mild” or “moderate” hemophilia, this research is a call to action:

• Your bleeding history matters more than your factor level. If you’ve had severe bleeds (even once), talk to your doctor about re-evaluating your classification.
• Inhibitors are a real risk. Ask about monitoring for inhibitors, especially if you’re on factor replacement therapy.
• Treatment options may expand. The European Medicines Agency already approves emicizumab for moderate hemophilia with a “severe bleeding phenotype”—this study supports broader access.

For example, if you have mild hemophilia but have had multiple joint bleeds, your doctor might recommend prophylaxis (regular factor infusions) to prevent long-term damage—something traditionally reserved for severe cases.

Gaps in Knowledge & Future Steps

The study has limitations:

• Short follow-up: Most patients were followed for less than 50 years, so long-term risks (e.g., late-onset bleeds) aren’t fully known.
• Missing data: Few papers reported factor levels at the time of bleeds, making it hard to link levels to risk.
• Small sample sizes: Hemophilia B Leyden and mild hemophilia B data were limited.

Future research will focus on:

• Identifying individual risk factors (e.g., genetics, lifestyle) for severe bleeds.
• Long-term studies to track outcomes in mild/moderate patients.
• Standardizing how bleeding phenotypes are measured (e.g., using the ISTH-BAT scale).

Key Points to Remember

• Factor levels don’t tell the whole story. “Mild” hemophilia can cause severe bleeds.
• Bleeding phenotype matters. Your history of bleeds (e.g., joint damage, ICH) should guide treatment.
• Inhibitors are a risk. Ask your doctor about monitoring.
• Advocate for yourself. If you’re not getting the care you need, push for a re-evaluation of your classification.

Talk to Your Doctor

Use this information to start a conversation with your healthcare team:

• “Have my bleeding events ever been classified as ‘severe’ using the ISTH-BAT scale?”
• “Should I be monitored for inhibitors?”
• “Could my classification change based on my bleeding history?”

Remember: You know your body best. Sharing details about your bleeds—even “minor” ones—can help your doctor provide better care.

Hemophilia is a spectrum, and your treatment should reflect your experience—not just a number on a lab report.