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levels is hyperfibrinolysis . Hyperfibrinolysis is reported in a significant percentage of severely injured patients , and is accompanied by a high mortality rate (> 70 %). Aggressive treatment of hyperfibrinolysis with tranexamic acid is the standard of care for severe trauma patients ; replenishment of fibrinogen is also considered within the existing treatment algorithms when low values of fibrinogen are diagnosed ( FibTEM < 7mm ).
Pregnant women have fibrinogen values higher than normal before delivery . In presence of a post-partum haemorrhage ( PPH ), low fibrinogen levels have a negative prognostic value . Values below 2.0g / l or FibTEM < 10mm are predictive of PPH progression and need for massive transfusions . In liver surgery , and namely in liver transplant , the fibrinolytic system is activated during the anhepatic and the reperfusion phases . Additionally , the fibrinogen levels in cirrhotic patients are reduced . Hypofibrinogenemia in these patients is a determinant of severe bleeding . Values below 1.5 – 2.0g / l or FibTEM < 6mm ) should trigger fibrinogen supplementation .
Cardiac surgery is a common clinical scenario for acquired hypofibrinogenemia . Dilution and consumption during cardiopulmonary bypass are the main determinants , but other mechanisms may be involved . Extensive use of cell-saver , with washing of the saved blood , results in a loss of coagulation factors and fibrinogen . Patients undergoing ascending aorta surgery due to acute aortic dissection may form clots inside the false chamber , leading to fibrinogen consumption . Finally , postoperative bleeding from any source ( platelet dysfunction , hyperfibrinolysis , residual heparin , surgical sources and others ) invariably lead to a fibrinogen loss . A study highlighted that postoperative bleeding becomes dependent when fibrinogen levels are below 2.0g / dl , with a 50 % positive predictive value for severe bleeding when the fibrinogen levels fall below 1.15 g / l . 11
Hyperfibrinogenemia High levels of fibrinogen may depend on genetic factors ( G-455A polymorphism ) but is more commonly the result of concomitant inflammatory diseases and lifestyle ( smoking ). Elderly subjects and females have higher fibrinogen values ; 12
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seasonal variations have been reported . 13
The most important consequence of increased fibrinogen levels is the concomitant increase in cardiovascular risk . Many studies demonstrated an association between elevated plasma fibrinogen levels and cardiovascular risk . 14 – 16 Venous thromboembolism can be associated with high fibrinogen levels . It is also true that therapies that reduce the cardiovascular risk ( ACE inhibitors ) simultaneously reduce fibrinogen levels . However , it is not fully established that the link between high fibrinogen levels and cardiovascular events is causative rather than associative . There are several pathways by which fibrinogen triggers acute cardiovascular events . The most intuitive is that fibrinogen is strongly involved in local thrombus formation in the presence of a ruptured atherosclerotic plaque . There are animal models of induced arterial and venous thrombosis demonstrating that higher fibrinogen levels shorten the time to vessel occlusion , and generate a more stable and lysis-resistant clot .
Even chronic atherosclerotic plaque formation can involve fibrinogen . Atherosclerotic plaques contain fibrin ( ogen ) deposits . Fibrin is incorporated in the plaque and contributes to plaque growth and instability . 5
An important link between fibrin ( ogen ) and thrombosis is represented by the contribution of fibrin to the clot physical properties . Different degrees of contribution may result in different clot visco-elastic properties , firmness , and resistance to lysis . Clots characterised by an increased fibrin fibre density ( usually produced by LMW fibrinogen ) are more likely to be associated with cardiovascular events . This was demonstrated in young subjects suffering an acute coronary syndrome . 5
As already mentioned , fibrinogen levels are elevated in a number of conditions characterised by a systemic inflammatory reaction syndrome . It is still unclear if this kind of hyperfibrinogenemia increases the risk of thrombotic events . Of note is that no reports of an increased thrombogenic risk exist in case of exogenous fibrinogen supplementation .
Conclusions Fibrinogen is certainly involved in a number of inflammatory , haemorrhagic , and thrombotic processes . Its peculiar position at the crossroad between
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inflammation and coagulation results in dynamic changes in fibrinogen concentration and structural changes of the fibrin network . Many of the conditions where fibrinogen levels are of clinical interest are acute and emergency situations , and fibrinogen levels are often indirectly measured with point-of-care tests in the emergency room , operating room and intensive care unit . The number of studies addressing the role of fibrinogen in both haemorrhagic and thrombotic syndromes is increasing : in the last three years more than 270 articles per year have been published on fibrinogen in bleeding syndromes , and about 300 per year on fibrinogen and thrombosis . Despite this , some results are still conflicting , and there is certainly room available for further studies .
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