Certain Proteins May Predict Joint Bleeding in Patients with Hemophilia


Patients with hemophilia may experience sudden bleeding, joint pain and inflammation, and deep bruising. But according to Hemophilia News, two proteins may be the cause. Researchers found that patients with severe hemophilia A, a subset of hemophilia, may have elevated levels of C-reactive protein (CRP) and vascular endothelial growth factor (VEGF). These proteins cause inflammation. Studying them could help predict when patients with hemophilia A will experience bleeding in their joints. Read the full study published in Clinical and Applied Thrombosis/Hemostasis.

Hemophilia A

Hemophilia is a genetic disorder in which people lack clotting protein in their blood. This means that someone’s blood does not clot, leading to bruising or extended periods of bleeding. In terms of hemophilia A, people lack factor VIII. For this reason, hemophilia A is also called factor VIII deficiency. Hemophilia A is 4x more common than other subsets, like hemophilia B. Symptoms include severe bruising, nose bleeds, bleeding in the joints, and bleeding in the digestive and urinary tract. These can cause damage the joints, urinary tract, and gastrointestinal system. Learn more about hemophilia A here.

The Study

Researchers wanted to understand how to predict and treat bleeding in the joints. In addition to minimizing bodily damage, early detection would allow for more quick and effective treatments. Researchers examined not only blood clotting factors, but the molecules and proteins that help form blood vessels.

The study followed 144 male patients with hemophilia A, as well as 90 healthy individuals, over a period of 3 years. The average age of the patients was 22 years old. 66 out of the 144 patients (45.8%) had joint bleeding. Researchers examined blood samples looking for:

  • Blood clotting proteins, like factor VIII.
  • Inflammatory molecules and proteins.
  • White blood cells, also known as leukocytes.
  • Blood platelet counts.

Hemophilia A Blood Results

Patients with hemophilia A had elevated levels of plasminogen, d-dimer, CRP, VEGF, ferritin, and macrophage migration inhibitor, with those experiencing joint bleeding have the highest levels. What does this mean?

  • Plasminogen – plasminogen is a glycoprotein that converts to plasmin. Plasmin then plays a role in reducing or preventing blood clots. So, people with high levels of plasminogen are less likely to experience clotting.
  • D-dimer – D-dimer is a fibrin degeneration product. Basically, plasmin degrades and destroys blood clots. Fibrin plays a role in coagulation. So when plasmin degrades the blood clots, the protein d-dimer fragments. If someone has high D-dimer levels, it suggests that someone may have a lot of blood clots forming or degenerating.
  • CRP – C-reactive protein is made in the liver. CRP levels rise when inflammation occurs in the body. However, high CRP levels do not indicate where inflammation is occurring.
  • VEGF – Vascular endothelial growth factor is a protein that promotes the creation and development of new blood vessels. However, VEGF can also promote tumor development. An excess of VEGF causes cells to leak, causing inflammation. Therefore, people with hemophilia A can experience joint bleeding and swelling with high levels of VEGF.
  • Ferritin – Ferritin is a blood protein which contains iron. Iron helps to carry oxygen around the body. So while people with low levels of ferritin may have anemia, people with high levels of ferritin can experience damage to the liver, heart, and joints.
  • Macrophage migration inhibitory factor – Macrophage migration inhibitory factor (MIF) is a cytokine that plays a role in your immune response. MIF is released into the blood when someone is stressed or when the body recognizes a foreign invader. As a result, MIF stimulates the immune system and provokes inflammation.

Overall Findings

Researchers ultimately determined that testing levels of CRP and VEGF could help identify and predict the risk of joint bleeding in patients with hemophilia A. Overall, analyzing CRP was 83% accurate at determining patients with hemophilia and 88% accurate when highlighting which had joint bleeding. VEGF was accurate in identifying 83% of patients with joint bleeding.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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