EP03: Unmasking Thrombophilia

Werfen is committed to Powering Patient Care and raise global awareness of thrombosis to enhance patient outcomes.
Thrombophilia discoveries reflect the dynamic nature of medical science and its continuous quest for better healthcare solutions.

Unmasking Thrombophilia

Werfen is committed to Powering Patient Care and raise global awareness of thrombosis to enhance patient outcomes. By exploring together the history of thrombosis, we can better appreciate the advancements in our medical knowledge and technology.

Terminology

“Thrombophilia”, from the Greek words “trombo” (blood clot) and “philia” (affinity), indicates an increased tendency to form pathological intravascular thrombosis, which may develop spontaneously or at young age. Screening is typically limited to high-risk individuals rather than the general population.

Initial Breakthrough

In the early 1980s, both Protein C and Protein S deficiencies were identified in the United States. These autosomal dominant conditions increase thrombosis risk 5- to 10-fold in heterozygotes, while homozygosity is often fatal without treatment.

In 1994, Prof. Bertina and his team discovered FV Leiden. This mutation, converting arginine 506 to glutamine, makes FV resistant to inactivation by activated protein C, significantly raising VTE risk and is observed in 1 to 5% of the general population which represents 30 to 50% of all congenital thrombophilia cases.

Advances in Understanding

In the early 1980s, both Protein C and Protein S deficiencies were identified in the United States. These autosomal dominant conditions increase thrombosis risk 5- to 10-fold in heterozygotes, while homozygosity is often fatal without treatment.

In 1994, Prof. Bertina and his team discovered FV Leiden. This mutation, converting arginine 506 to glutamine, makes FV resistant to inactivation by activated protein C, significantly raising VTE risk and is observed in 1 to 5% of the general population which represents 30 to 50% of all congenital thrombophilia cases.

Bridging Discovery and Clinical Practice

Antiphospholipid Syndrome (APS) is a common autoimmune disorder affecting 40-50 per 100,000 people, with higher prevalence in specific stratified population groups.

The identification of antiphospholipid antibodies (aPL) began in the early 20th century and was linked to syphilis testing, sometimes revealing "false positives" in lupus patients. Dr. Hughes formally described APS in the 1980s, linking aPL to thrombotic and obstetric events, with interest in APS growing rapidly due to multidisciplinary physician involvement.

Modern Diagnostic and Therapeutic Approaches

In recent decades, the diagnosis and management of thrombophilia have seen substantial advancements.

Blood and genetic tests specifically identify mutations and deficiencies, assessing thrombosis risk and hereditary thrombophilias. Anticoagulant therapies like heparin and warfarin have long been the mainstay of thrombosis prevention and treatment. Recently, DOACs have been introduced, offering effective prevention with fewer dietary restrictions and monitoring.

From a Thrombophilia Condition to a Hemophilia Treatment

Though less known, a disease called hyperactive Factor IX Padua has recently been characterized. This condition, where an arginine 338 to leucine mutation increases FIX clotting activity eightfold, is also an independent risk factor for VTE, prevalent in 20% of VTE patients and 5% of the general population.

Recent advancements have used this variant to improve Hemophilia B gene therapy, leading to better bleeding control and fewer doses in patients - a great example of translational medicine.

Conclusions and Outlook The history of thrombophilia is a testament to the evolution of medical science. From the early identification of antithrombin deficiency to the more recent treatment therapies, its story highlights the complexity of thrombotic disorders and the need of a more personalized medicine, where treatments are tailored to the individual’s genetic profile and specific risk factors.