A recent study led by MedUni Vienna provides new insights into the mechanisms of coagulation in persons with haemophilia A, the most common form of haemophilia. The research team was able to show that saliva contains special vesicles that trigger rapid coagulation of the blood of haemophilic patients. The results, which were recently published in the renowned scientific journal “Blood”, contribute significantly to a better understanding of the disease.
Haemophilia is a hereditary blood disorder characterised by a deficiency of certain coagulation factors, which can lead to life-threatening bleeding if left untreated. Why haemophilia A (with factor VIII deficiency) often leads to joint bleeding, but rarely to mucosal bleeding, was previously unclear. In search of an explanation, the scientific team led by Johannes Thaler and Cihan Ay (Clinical Division of Hematology and Hemostaseology, Department of Medicine I, MedUni Vienna) and Rienk Nieuwland (Amsterdam University Medical Centers) studied research into the importance of the body’s own fluids for blood coagulation, which had been forgotten for decades.
The researchers discovered that the saliva of haemophilia A patients contains extrinsic tenase complexes, which are located on vesicles. Extrinsic tenase complexes are protein complexes that consist of two coagulation factors (tissue factor TF and factor VIIa) and initiate the activation of the coagulation cascade when they come into contact with blood. Analyses by the study authors confirm that mucosal bleeding in the mouth of these patients is indeed rare and stops quickly. Patients without this protein complex in their saliva lack this protective mechanism. “They therefore often suffer from oral mucosal bleeding,” reports Johannes Thaler.
Body fluids as activators of blood coagulation
The importance of body fluids for coagulation was first described in the 1930s. At that time, the average life expectancy of haemophilia patients was just eight years. The Viennese paediatrician Alphons Solé discovered that maternal milk is a strong activator of coagulation. In a clinical study, he showed that tamponades soaked in maternal milk quickly brought acute, previously unstoppable bleeding to a halt in haemophilia patients. However, Solé’s findings, which were confirmed by independent researchers, were forgotten. It was only a few years ago that the team led by Johannes Thaler, Cihan Ay and Rienk Nieuwland revived this historical research. The scientists were able to prove that the coagulation-promoting properties of maternal milk, amniotic fluid, urine – and now also saliva – are due to the presence of extracellular vesicles with extrinsic tenase complexes.
The results provide important insights into the mechanisms of coagulation and contribute to a better understanding of haemophilia A. “At the same time, they show that it can be very rewarding to re-evaluate historical scientific work in order to develop innovative approaches for research and potentially also for the targeted treatment of patients,” says Johannes Thaler about the significance of the findings.
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