This is a link to the full academic paper entitled: Patients with paroxysmal nocturnal hemoglobinuria demonstrate a prothrombotic clotting phenotype which is improved by complement inhibition with eculizumab
Plain language (lay) summary:
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare disorder, characterized by the breakdown of red blood cells and the formation of blood clots within vessels. The formation of blood clots within blood vessels can result in many complications including heart attacks, strokes and liver failure. The reason for the increased incidence of blood clot formation in PNH is still poorly understood. However, it is thought to be driven by the loss of a protein found on blood cell surfaces which normally protects them from the immune system. Without this protein the immune system starts to break down blood cells in the blood releasing harmful material that may trigger clot formation. Treatment with a drug called eculizumab, which dampens the immune response, has been shown to significantly reduce blood clot formation in PNH patients. In many cardiovascular diseases such has diabetes and heart attacks, patients have been found to have changes in how their blood clots form possibly giving them a predisposition to disease. Based on this our aim in this study was to investigate changes in clot formation and structure as a possible mechanism for increased blood clot formation in patients with PNH. We explored the formation, structure and breakdown of blood clots in plasma samples from 82 patients from the National PNH Service in Leeds, UK. PNH patients who were not on any form of treatment were found to have increased levels of two clotting proteins, called fibrinogen and thrombin, in their blood. Increases in these proteins also led to clots forming faster with a subsequent clot structure that was harder to break down. PNH patients on eculizumab treatment were found to have decreased levels of fibrinogen and thrombin in their blood. This resulted in slower forming clots with an improved clot structure. As the length of time on eculizumab treatment increased the positive effects on clotting increased. Our study suggests that PNH patients have a predisposition to increased blood clot formation due to increased fibrinogen and thrombin levels leading to faster clot formation. Treatment with eculizumab helps to reduce clot formation by reducing fibrinogen and thrombin levels and this has positive downstream effects on clotting.