Complement-Coagulation Cross-talk: Factor H-mediated regulation of the Complement Classical Pathway activation by fibrin clots.

The classical pathway of the complement system is activated by the binding of C1q in the C1 complex to the target activator, including immune complexes. Factor H is regarded as the key downregulatory protein of the complement alternative pathway. However, both C1q and factor H bind to target surfaces via charge distribution patterns. For a few targets, C1q and factor H compete for binding to common or overlapping sites. Factor H, therefore, can effectively regulate the classical pathway activation through such targets, in addition to its previously characterized role in the alternative pathway. Both C1q and factor H are known to recognize foreign or altered-self materials, e.g., bacteria, viruses, and apoptotic/necrotic cells. Clots, formed by the coagulation system, are an example of altered self. Factor H is present abundantly in platelets and is a well-known substrate for FXIIIa. Here, we investigated whether clots activate the complement classical pathway and whether this is regulated by factor H. We show here that both C1q and factor H bind to the fibrin formed in microtiter plates and the fibrin clots formed under in vitro physiological conditions. Both C1q and factor H become covalently bound to fibrin clots, and this is mediated via FXIIIa. We also show that fibrin clots activate the classical pathway of complement, as demonstrated by C4 consumption and membrane attack complex detection assays. Thus, factor H downregulates the activation of the classical pathway induced by fibrin clots. These results elucidate the intricate molecular mechanisms through which the complement and coagulation pathways intersect and have regulatory consequences.

Camel-related major vascular injuries: A 20-years' experience.

BACKGROUND: Majority of human animal-related injuries in the United Arab Emirates are caused by camels. These may involve major vessels and can be life-threatening. We aimed to study the biomechanism, injured regions, management, and outcome of major camel-related human vascular injuries. METHODS: We retrospectively studied all patients who were admitted to Al-Ain Hospital with camel-related major vascular injury during January 2001 to January 2020. Studied variables included demography, mechanism of injury, injured structures, clinical presentation, vital signs on arrival, associated injuries, surgical management, ICU stay, length of hospital stay, complications, and outcome. RESULTS: Seven patients were studied; all were males having a median age of 26 years. Five out of six bite injuries (83%) occured during the camel rutting season. The injuries were severe and life-threatening. A camel bite causes four small elliptical wounds of the canine teeth which resembles two stab wounds of 8 cm long, penetrating deeply and injuring major vessels. Four involved the carotid artery, one the femoral artery and vein, one the external iliac vein and one the aorta which was due to a fall from a camel. Although the standard of surgical care was high, the outcome was poor. Six patients were admitted to the ICU for a median of 5 days. One patient died, one became vegetative, and one had arm paralysis. CONCLUSIONS: Major camel-related vascular injuries have a poor clinical outcome. This is related to the biomechanism of injury which combines penetrating, crushing and blunt trauma. Neck wounds of camel bites can be closed primarily after debridement.