In a nutshell: Explaining joint and muscle bleeding in individuals with haemophilia A and B.

(A) Formation of the platelet-fibrin haemostatic plug. Vascular injury exposes von Willebrand factor (VWF) and tissue factor (TF) to flowing blood. VWF mediates platelet adhesion, leading to platelet activation and aggregation, while TF triggers the coagulation cascade, generating thrombin that converts fibrinogen to fibrin. Thrombin also amplifies platelet activation, integrating the two arms so that platelet aggregates and a fibrin mesh combine to form a stable platelet-fibrin haemostatic plug. (B) Anatomical correlation between bleeding phenotype and tissue factor expression. Typical bleeding sites in haemophilia A and B (intra-articular and intramuscular) are shown relative to the tissue-specific pattern of high tissue factor (TF) expression. Vital organs such as the brain, heart and lungs exhibit high TF expression, proposed to provide additional haemostatic protection, whereas the low TF expression in joints and skeletal muscle leaves these sites more reliant on FVIII- and FIX-dependent amplification and therefore vulnerable to bleeding when these factors are deficient. Figure created with BioRender.com.