. 2021 Jan 5;48(2):763–774. doi: 10.1007/s00068-020-01563-2

Table 1.

Summary of European guidelines for the treatment of trauma-induced coagulopathy

Guidelines	First-line treatment	Other recommendations	FCH indicated for acquired hypofibrinogenemia
Europe: The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition [10]	Initial management of expected massive haemorrhage: FFP (or pathogen-inactivated FFP) (1C) or FCH (1C), with RBC FCH or cryoprecipitate for major bleeding with viscoelastic signs of fibrinogen deficit or a plasma fibrinogen level ≤ 1.5 g/L (1C) Initial FCH dose of 3–4 g is suggested; repeat doses guided by viscoelastic monitoring and fibrinogen laboratory tests (2C) Avoid FFP for hypofibrinogenaemia (1C)	PCC is recommended if fibrinogen levels are normal and viscoelastic monitoring indicates delayed coagulation initiation (2C) rFVIIa should be considered if major bleeding and coagulopathy continue despite all other attempts to control bleeding and best-practice use of conventional haemostatic measures (2C)	Yes
Czech and Slovak Republic: Diagnosis and treatment of life-threatening bleeding in adult patients in intense and perioperative care (Czech-Slovak interdisciplinary recommended procedure) [31]	Initial treatment with FFP and ETP (1:2, 1B) or FCH and ETP (1C) at appropriate values/levels Initial dose of at least 50 mg/kg FCH (1C) FCH when fibrinogen level < 1.5–2 g/L or by equivalent by viscoelastic testing (1C)	To maintain fibrinogen level at 2 g/L PCC (25–50 U/kg) is recommended when coagulation factor deficit is assumed (2C); risk/benefit should be assessed rFVIIa (90–100 µg/kg) to be considered if all standard measures fail and there is still life-threatening bleeding	Yes
Sweden: Hemostasis and severe bleeding: Care program prepared by The Swedish Society for Thrombosis and Hemostasis working group [32]	Early transfusion with plasma and erythrocytes (1:1) with platelet unit for every four units plasma/erythrocytes, if bleeding > 1–1.5 blood volume FCH (2–4 g) for > 1 blood volume	Subsequent fibrinogen supplementation based on viscoelastic testing; aim for fibrinogen level > 2 g/L and INR < 1.5	Yes
Germany: Level 3 guideline on the treatment of patients with severe/multiple injuries (Polytrauma Guideline Update Group) [26]	FFP is recommended for massive transfusion (4:4:1 FFP:pRBC:PLT ratio) FCH is recommended should a patient present with a fibrinogen level < 1.5 g/L (target fibrinogen level ≥ 1.5 g/L) PCC is recommended as a treatment option outside of VKA reversal if needed FXIII is also recommended if needed	N/A	Yes
Spain: Spanish Consensus Statement on alternatives to allogeneic blood transfusion: the 2013 update of the "Seville Document" [27]	Early PCC administration is recommended in non-VKA-treated patients presenting with coagulopathy FCH should be given if plasma fibrinogen < 2 g/L rFVIIa is recommended for severe refractory haemorrhge	N/A	Yes
Spain: Multidisciplinary consensus document on the management of massive haemorrhage (HEMOMAS document) [28]	FFP should be administered early for massive haemorrhage FCH should be given if plasma fibrinogen < 2 g/L rFVIIa is not recommended as a first-level option for massive haemorrhage	PCC is only recommended in non-VKA-treated patients if there is a risk of TACO or TRALI, or depending on the urgency of treatment and availability of FFP	Yes
UK: A practical guideline for the haematological management of major haemorrhage (British Society of Haematology) [30]	Present or expected massive haemorrhage: 1:1 ratio of FFP:RBC (1B) Further FFP* should be guided by laboratory tests with a transfusion trigger of PT and/or aPTT > 1.5 times normal (2C) If laboratory results are unavailable and bleeding continues: FFP and RBC in at least 1:2 ratio, before switching to blood product use guided by laboratory results (2C) Use of FFP should not delay fibrinogen supplementation if it is required (2C) Fibrinogen levels < 1.5 g/L: cryoprecipitate (2 pools) (1C)	PCC and rFVIIa are not recommended for major haemorrhage unless as part of a clinical trial (1D)	No
UK: Blood transfusion and the anaesthetist: management of massive haemorrhage (Association of Anaesthetists of Great Britain and Ireland Membership) [29]	Early infusion of FFP (15 mL/kg) Established coagulopathy (widespread microvascular oozing or inadequate haemostasis) indicated by fibrinogen < 1 g/L or PT/aPTT > 1.5 × normal): FFP at doses likely to correct coagulation factor deficiencies (≥ 30 mL/kg) Hypofibrinogenaemia unresponsive to FFP: cryoprecipitate is often recommended, but FCH (30–60 mg/kg) can achieve fibrinogen replacement more rapidly and predictably PCC and intravenous vitamin K (5–10 mg) for warfarin reversal	Some centres use PCC in certain clinical situations, such as liver disease and post-CPB; local protocols must be agreed in advance rFVIIa has been used for massive haemorrhage unresponsive to conventional therapy, but there may be a risk of arterial thrombotic complications; local protocols must be agreed in advance	No

Guidelines

First-line treatment

Other recommendations

FCH indicated for acquired hypofibrinogenemia

Europe:

The European guideline on management of

major bleeding and coagulopathy

following trauma: fifth edition [10]

Initial management of expected massive haemorrhage: FFP (or pathogen-inactivated FFP) (1C) or FCH (1C), with RBC

FCH or cryoprecipitate for major bleeding with viscoelastic signs of fibrinogen deficit or a plasma fibrinogen level ≤ 1.5 g/L (1C)

Initial FCH dose of 3–4 g is suggested; repeat doses guided by viscoelastic monitoring and fibrinogen laboratory tests (2C)

Avoid FFP for hypofibrinogenaemia (1C)

PCC is recommended if fibrinogen levels are normal and viscoelastic monitoring indicates delayed coagulation initiation (2C)

rFVIIa should be considered if major bleeding and coagulopathy continue despite all other attempts to control bleeding and best-practice use of conventional haemostatic measures (2C)

Yes

Czech and Slovak Republic:

Diagnosis and treatment of life-threatening bleeding in adult patients in intense and perioperative care (Czech-Slovak interdisciplinary recommended procedure) [31]

Initial treatment with FFP and ETP (1:2, 1B) or FCH and ETP (1C) at appropriate values/levels

Initial dose of at least 50 mg/kg FCH (1C)

FCH when fibrinogen level < 1.5–2 g/L or by equivalent by viscoelastic testing (1C)

To maintain fibrinogen level at 2 g/L

PCC (25–50 U/kg) is recommended when coagulation factor deficit is assumed (2C); risk/benefit should be assessed

rFVIIa (90–100 µg/kg) to be considered if all standard measures fail and there is still life-threatening bleeding

Yes

Sweden:

Hemostasis and

severe bleeding:

Care program prepared by

The Swedish Society for

Thrombosis and Hemostasis working group [32]

Early transfusion with plasma and erythrocytes (1:1) with platelet unit for every four units plasma/erythrocytes, if bleeding > 1–1.5 blood volume

FCH (2–4 g) for > 1 blood volume

Subsequent fibrinogen supplementation based on viscoelastic testing; aim for fibrinogen level > 2 g/L and INR < 1.5

Yes

Germany:

Level 3 guideline on the treatment of patients with severe/multiple

injuries (Polytrauma Guideline Update Group) [26]

FFP is recommended for massive transfusion (4:4:1 FFP:pRBC:PLT ratio)

FCH is recommended should a patient present with a fibrinogen level < 1.5 g/L (target fibrinogen level ≥ 1.5 g/L)

PCC is recommended as a treatment option outside of VKA reversal if needed

FXIII is also recommended if needed

N/A

Yes

Spain:

Spanish Consensus Statement on alternatives to allogeneic blood transfusion: the 2013 update of the "Seville Document" [27]

Early PCC administration is recommended in non-VKA-treated patients presenting with coagulopathy

FCH should be given if plasma

fibrinogen < 2 g/L

rFVIIa is recommended for severe refractory haemorrhge

N/A

Yes

Spain:

Multidisciplinary consensus document on the management of massive haemorrhage (HEMOMAS document) [28]

FFP should be administered early for massive haemorrhage

FCH should be given if plasma

fibrinogen < 2 g/L

rFVIIa is not recommended as a first-level option for massive haemorrhage

PCC is only recommended in non-VKA-treated patients if there is a risk of TACO or TRALI, or depending on the urgency of treatment and availability of FFP

Yes

UK:

A practical guideline for the haematological management of major haemorrhage (British Society of Haematology) [30]

Present or expected massive haemorrhage: 1:1 ratio of FFP:RBC (1B*)

Further FFP should be guided by laboratory tests with a transfusion trigger of PT and/or aPTT > 1.5 times normal (2C)

If laboratory results are unavailable and bleeding continues: FFP and RBC in at least 1:2 ratio, before switching to blood product use guided by laboratory results (2C)

Use of FFP should not delay fibrinogen supplementation if it is required (2C)

Fibrinogen levels < 1.5 g/L: cryoprecipitate (2 pools) (1C)

PCC and rFVIIa are not recommended for major haemorrhage unless as part of a clinical trial (1D)

UK:

Blood transfusion and the anaesthetist: management of

massive haemorrhage (Association of Anaesthetists of Great Britain and Ireland

Membership) [29]

Early infusion of FFP (15 mL/kg)

Established coagulopathy (widespread microvascular oozing or inadequate haemostasis) indicated by fibrinogen < 1 g/L or PT/aPTT > 1.5 × normal): FFP at doses likely to correct coagulation factor deficiencies (≥ 30 mL/kg)

Hypofibrinogenaemia unresponsive to FFP: cryoprecipitate is often recommended, but FCH (30–60 mg/kg) can achieve fibrinogen replacement more rapidly and predictably

PCC and intravenous vitamin K (5–10 mg) for warfarin reversal

Some centres use PCC in certain clinical situations, such as liver disease and post-CPB; local protocols must be agreed in advance

rFVIIa has been used for massive haemorrhage unresponsive to conventional therapy, but there may be a risk of arterial thrombotic complications; local protocols must be agreed in advance

aPTT, activated partial thromboplastin time; CBP, cardiopulmonary bypass; ETP, erythrocyte transfusion unit preparations; FCH, fibrinogen concentrate; FFP, fresh frozen plasma; Hb, haemoglobin; IV, intravenous; INR, international normalized ratio; MCF, maximum clot firmness; PCC, prothrombin complex concentrate; PLT, platelet; PT, prothrombin time; pRBC, packed red blood cells; RBC, red blood cells; rFVIIa, activated recombinant factor VII; TACO, transfusion-associated circulatory overload; TRALI, transfusion-related acute lung injury; VKA, vitamin K antagonist