Family 6: Coagulation and Haematological
Family overview. The haemostatic system balances clot formation and dissolution via coagulation cascade, platelet activation, and fibrinolysis. Pathological low-level activation produces microclotting, endothelial damage, and chronic inflammation without overt thrombosis.
Concrete mechanisms and ME/CFS evidence:
Fibrin/amyloid microclot formation. Platelet-poor plasma from ME/CFS patients contains amyloid fibrin(ogen) microclots at ~10Γ greater area than healthy controls; microclots resist fibrinolysis and may obstruct microvascular perfusion, impairing oxygen delivery to tissues (Jaco M. Nunes et al. 2022).
Platelet hyperactivation. Hyperactivated platelets with increased aggregation propensity; driven by chronic innate immune activation and endothelial injury signals.
Hypercoagulable state. Thromboelastography demonstrates hypercoagulability in a substantial proportion of ME/CFS participants.
Red blood cell deformability loss. Stiffer RBCs with ~14% reduced elongation index cannot transit narrow capillaries efficiently, impeding microvascular flow and oxygen delivery (see also Family 3) (Marshall-Gradisnik et al. 2018).
Dysregulated coagulation proteome. Data-independent LC-MS/MS proteomics of ME/CFS plasma reveals dysregulated coagulation system proteins alongside endothelial dysfunction markers (Jean M. Nunes et al. 2024).
Complement-coagulation crosstalk. Complement C5a amplifies platelet and coagulation activation; provides mechanistic bridge between immune dysregulation (Family 4) and haematological pathology.
Full discussion: shared across Cardiovascular Dysfunction and Immune System Dysfunction.
Evidence status: Probable (microclot and hypercoagulability findings consistent but require larger independent replication; proteomics data strong but single cohort).