Fibrinogen is critical for clotting¹

The role of fibrinogen in haemostasis

Fibrinogen is crucial for maintaining and restoring haemostasis.¹ Thus, its absence and/or reduced effectiveness can have a significant impact on bleeding and/or thrombosis.² There are two types of fibrinogen deficiencies: CFD (congenital fibrinogen deficiency) and AFD (acquired fibrinogen deficiency).² The following diagram outlines its role in the clotting cascade, followed by a review of each type of fibrinogen deficiency.

Figures adapted from: Cleveland Clinic. 20245

Congenital fibrinogen deficiency

What are the causes?

Congenital fibrinogen deficiencies are a group of rare, inherited abnormalities of blood coagulation that occur due to mutations in FGA, FGB or FGG genes.⁷ These disorders can be diagnosed using the Clauss assay (measuring fibrinogen function) and an antigenic fibrinogen level and categorised as follows:⁷

• Quantitative disorders include afibrinogenaemia (complete absence of fibrinogen) and hypofibrinogenemia (proportional decrease of functional and antigenic fibrinogen levels)

• Qualitative disorders

How are they managed?

The United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO) guidelines recommend the therapeutic goal of maintaining fibrinogen levels at >1.0 g/L for severe bleeding or major surgery in afibrinogenaemia, hypofibrinogenaemia.⁸ A prophylaxis target of >0.5 g/l should be considered with a history of severe bleeding or with fibrinogen activity <0.1 g/l.⁸

Why are fibrinogen concentrates used as standard of care over cryoprecipitate to prevent and manage bleeding in indicated CFD patients?

• They undergo multistep validated viral safety procedures to ensure pathogen safety⁹, namely solvent/detergent treatment and nanofiltration for fibryga®¹⁰

• They provide a defined fibrinogen content enabling accurate dosing⁹

• They have a faster preparation time and lower volume per dose⁹

Other factors behind the preference to use fibrinogen concentrate over cryoprecipitate in indicated CFD patients include:

• The potential for reduced exposure to allogeneic blood products with fibrinogen concentrate^11,12

• Cryoprecipitate results in the infusion of large amounts of other plasma proteins not required for the replacement of fibrinogen¹³

• It must be thawed before use¹³

Acquired fibrinogen deficiency

What are the causes?

Acquired hypofibrinogenaemia is more common than congenital fibrinogen disorders¹⁴ and is defined by fibrinogen level of < 1.5 g/L (<2.0 g/L for postpartum haemorrhage). Common causes include:¹⁵

• Excessive blood loss (e.g. during major trauma, surgery and postpartum haemorrhage)

• Haemodilution (during massive transfusion)

• Consumptive coagulopathies (disseminated intravascular coagulation and hyperfibrinolysis)

Causes of fibrinogen deficiency

Major haemorrhage is a leading cause of morbidity and mortality worldwide.¹⁶ The causes of haemorrhage vary geographically.¹⁶ In a study of three English regions reviewing the patterns and indications of cryoprecipitate usage in adults, the main clinical scenarios where cryoprecipitate was used in major haemorrhage were:¹⁷

How are they managed?

During major haemorrhage, fibrinogen is the first coagulation factor to drop to critically low levels (<1.0 g/L).¹⁸ The aggressive replacement of fibrinogen is one of the core principles of modern management of major haemorrhage.¹⁹

FFP contains insufficient fibrinogen to achieve the rapid rise in levels required to support haemostasis; replacement therapy is recommended with fibrinogen concentrate or cryoprecipitate.⁸

How does fibrinogen concentrate compare to cryoprecipitate?

The following table summarises the main comparators between fibryga®, and cryoprecipitate in the form of pooled bags of 5 single units – the cryoprecipitate presentation found in most major haemorrhage protocols.²⁰

Effective management of major haemorrhage

As major haemorrhage is often accompanied by volume loss, haemodilution, acidaemia, hypothermia and coagulopathy (factor consumption and fibrinolysis), guidelines recommend a multifaceted approach for effective management, including¹⁶

• Early recognition (e.g. via point-of-care testing [PoCT])

• Planned responses (e.g. following a defined protocol)

• Readily available resources (e.g. timely use of appropriate blood products to address hypofibrinogenaemia)

• Advanced critical care support (e.g. to avoid the lethal triad of hypothermia, acidaemia and coagulopathy)

• Rapid access to surgery or interventional radiology (for surgical or radiological control of bleeding)

For more than 10 years, UK clinical practice has adopted the principles of Patient Blood Management (PBM) as standard of care to ensure appropriate use of blood components and improve patient outcomes.²⁴ This multimodal multidisciplinary patient-centred strategy²⁵ consists of the following three pillars:²⁴

1. Detecting and managing pre-operative anaemia

2. Minimising blood loss and treating coagulopathy

3. Harnessing and optimising the patient’s physiological reserve in the setting of anaemia

The effective management of major haemorrhage in the context of fibrinogen replacement forms part of an overall PBM strategy. This should take an individualised approach, with consideration of the clinical setting and patient preference (where possible).²⁴

2024 Association of Anaesthetists (AoA) Guidelines on the use of blood components and their alternatives advocate for regular reviews of Trust protocols to ensure they align with the latest evidence that may suggest change in practice.16 Many UK centres are protocolising the move towards fibrinogen concentrate in acquired fibrinogen deficiency due to its logistical benefits in reducing transfusion delays, and lower volume.²⁶

What is Point of Care testing (PoCT) and why is it important in managing major haemorrhage?

PoCT is defined as any diagnostic test undertaken by staff other than laboratory healthcare scientists, usually carried out near the patient.²⁷ Viscoelastic haemostatic assays (VHA) are recommended as a tool to facilitate goal-directed therapy in active bleeding, given their rapid turnaround time and ability to provide information on all phases of coagulopathy.²⁴

The use of PoCT to guide haemostatic therapy is associated with a reduction in transfusion utilisation, improved morbidity and better outcomes in patients with active bleeding.²⁸

PoCT:

• Enables clotting parameters in whole blood to be monitored in almost real time at, or very near to, the patient’s bedside¹⁸

• Allows clinicians like you to differentiate between coagulopathy or surgical reasons for bleeding²⁸

• Allows individualised patient management, with specific, targeted, and rapid replacement of depleted coagulation factors, e.g. fibrinogen¹⁸

• Is recommended by the British Society for Haematology (BSH) in the following specialties:²⁹

Managing major haemorrhage

Common options for PoCT devices

The two commonly used viscoelastic point-of-care testing devices in the UK are thromboelastography (TEG®*) or rotational thromboelastometry (ROTEM®^†) (see table below).³⁰ Please review your local guideline and protocol for further information on the system available to you. Octapharma Ltd is not affiliated with any of the companies offering PoCT equipment.

Typical TEG and ROTEM tracings

R/CT measure clot rate/clotting time; this determines the deficiency of clotting factors and indicates whether replacement therapy with plasma is required.^34,35

K/CFT measure clot formation time, which is mostly fibrinogen dependent. A reduced alpha angle or K/CFT measure indicates a deficiency in fibrinogen.³⁴

MA/MCF measure the maximum amplitude/clot firmness; an early indication of this is provided by A10 – amplitude/clot firmness 10 minutes post clot rate/clotting time. A decreased reading can be attributed to a fibrinogen or platelet deficiency.^34,35 For ROTEM, an abnormal FIBTEM reading should be followed by the replacement of fibrinogen. If FIBTEM is normal, platelet deficiency should be addressed.34

For TEG, a low amplitude indicates low fibrinogen levels. If this is accompanied with a normal MA, this indicates a platelet deficiency.35

LI/LY measure clot lysis; an increased reading gives an indication of the level of fibrinolysis.^34,35

R, reaction time/CT, clotting time: time from the beginning of the test to the first detectable clot formation at an amplitude of 2mm; K, kinetics/CFT, clot formation time: time from the beginning of the clot to an amplitude of 20 mm; α angle, formed between the horizontal axis at clot formation to and a tangent that intercept the tracing curve; MA, maximum amplitude/MCF, maximum clot formation; A30, amplitude at 30 minutes post-MA/MCF; LI30, lysis index at 30 minutes: percentage of clot firmness remaining 30 minutes after CT; LY30, lysis at 30 minutes: percentage decrease in amplitude 30 minutes after MA.33

UK-FIB-2500020 | May 2026

Abbreviations
AFD, acquired fibrinogen deficiency; AoA, Association of Anaesthetists; BHS, British Society for Haematolog; CFD, congenital fibrinogen deficiency; FGA, gene encoding alpha chain of fibrinogen; FGB, gene encoding beta chain of fibrinogen; FGG, gene encoding gamma chain of fibrinogen; UKHCDO, United Kingdom Haemophilia Centre Doctors’ Organisation; GI, gastrointestinal; FFP, fresh frozen plasma; FXIII, coagulation factor XIII; IU, international units; POCT, point-of-care testing; PBM, patient blood management; ROTEM, rotational thromboelastometry; TEG, thromboelastography; VHA, viscoelastic haemostatic assays; WFI, water for injection.

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