Acquired fibrinogen deficiency

Acquired hypofibrinogenaemia is much more common than congenital fibrinogen deficiency and is defined by a fibrinogen level of less than 1.5 g/L (Figure 6).

Fibrinogen levels in acquired fibrinogen deficiencies

Figure 6: Fibrinogen levels in acquired fibrinogen deficiencies (Reviewed in Besser et al., 2016; Kozek-Langemecker et al., 2017).

Common causes of acquired fibrinogen deficiency include excessive blood loss (for example during major trauma, surgery and postpartum haemorrhage), haemodilution (during massive transfusion), consumptive coagulopathies (disseminated intravascular coagulation and hyperfibrinolysis) and end stage liver disease (Fries & Martini, 2010; Besser & MacDonald, 2016) (Figure 7).

Acquired hypofibrinogenaemia

Figure 7. Acquired hypofibrinogenaemia (Reviewed in Franchini & Lippi, 2012; Besser et al., 2016).

Acquired fibrinogen deficiency is a lot more complex than congenital fibrinogen deficiency. Congenital fibrinogen deficiency is associated directly with defects in fibrinogen protein synthesis, secretion or quality whilst other coagulation factors function normally. In acquired fibrinogen deficiency, fibrinogen is often associated with multiple factor deficiencies as well as pathophysiologic conditions such as shock, fibrinolysis, hypothermia and acidosis (Maegele et al., 2017). Indeed, traumatic coagulopathy (TC) together with acidosis and hypothermia is often referred to as the ‘lethal triad’ of death which is further aggravated by further accumulation of coagulation factor deficits, termed trauma induced coagulopathy (TIC) (Maegele et al., 2017). Diagnosis and treatment of acquired fibrinogen deficiency is subsequently more complex and difficult.

Consumptive coagulopathy

Consumptive coagulopathy, sometimes referred to as disseminated intravascular coagulation (DIC), is usually associated with an unusually high level of activation in the coagulation system and involves dysregulation of both procoagulants and anticoagulants. The outcome is the depletion of factors required for coagulation completion, one of which is fibrinogen. The measurable outcome of DIC varies according to the trigger factor, which can include sepsis, cancer, trauma and hepatic or obstetric disorders. It is important to note that in some scenarios, fibrinogen levels may remain in the normal range; however, it is unable to play its role in coagulation as a result of other consumptive complications related to DIC (Venugopal, 2014). It is therefore important to measure not only fibrinogen levels, but also other markers of clot formation in the diagnosis of DIC. 

Hyperfibrinolysis

Fibrinolysis is the normal process for clearing blood clots once they are no longer needed. In the case of hyperfibrinolysis, blood clots are cleared too efficiently, thus preventing adequate platelet aggregation and clot establishment. It is often caused by high plasmin levels, a key factor responsible for the degradation of fibrin. Hyperfibrinolysis leads to increased bleeding and has been observed in patients of liver disease, trauma and surgical procedures (Teufelsbauer et al., 1992; Palmer et al., 1995; Ferro et al., 2009; Theusinger et al., 2011).

Dilutional coagulopathy

Extensive fluid replacement with red blood cells and intravenous fluids that do not have platelets or coagulant factors can lead to the dilution of both pro- and anticoagulants. This leads to a loss of coagulation regulation and is frequently observed with massive transfusions. The outcome is the onset of thrombocytopenia (low blood platelet count) and fibrinogen levels below 1.5 g/L after a 1–1.5 blood volume replacement (JPAC Transfusion Handbook, 2014).

Blood loss

A major haemorrhage can be defined by speed of bleeding (150 mL/minute) and volume of blood lost; either one blood volume (approximately 70 mL/kg in an adult) within 24 hours or 50% total volume in less than 3 hours. It is characterised by a systolic blood pressure of less than 90 mm Hg or a heart rate of more than 110 beats/minute (JPAC Transfusion Handbook, 2014). Notably, the amount and cause of bleeding is influenced by various patient-specific factors and diagnosis must be interpreted in the context of the individual clinical scenario (JPAC Transfusion Handbook, 2014). The importance of fibrinogen levels in major blood loss has been extensively studied, particularly in cardiac surgery and postpartum haemorrhaging.