Please select the eligibility criteria that correspond to the clinical trial below.
Title: Fibrinogen Concentrate vs Cryoprecipitate in Traumatic Haemorrhage: A Pilot Randomised Controlled Trial
Brief Summary: * Haemorrhage in severe trauma is a significant cause of mortality and is potentially the most preventable cause of death in trauma patients
* Trauma Induced Coagulopathy (TIC) is a complex coagulopathy associated with severe trauma
* Hypo/dysfibrinogenaemia plays an important role in TIC
* Early replacement of fibrinogen may improve outcomes
* Fibrinogen replacement is potentially inadequate in standard fixed ratio Major Haemorrhage Protocols (MHP) utilising Plasma and/or Cryoprecipitate
* The majority of centres utilise cryoprecipitate for additional fibrinogen supplementation as part of a MHP
* Cryoprecipitate administration is often delayed (between 60 - 120 minutes) in a fixed ratio MHP
* It is clear early intervention in severe traumatic haemorrhage is associated with improved outcomes - CRASH 2 and PROPPR studies
* Increasing interest in the use of Fibrinogen Concentrate (FC) in severe bleeding but not supported by high level evidence
* Benefits of FC - viral inactivation, known dose, easily reconstituted, can be administered quickly in high dose and stored at room temperature in the trauma resuscitation bay
* No previous studies comparing FC and Cryoprecipitate in bleeding trauma patients
* Fibrinogen supplementation will be guided by an accepted ROTEM targeted treatment algorithm
* It will be a pilot, multi-centre randomised controlled trial comparing FC to Cryoprecipitate (current standard practise in fibrinogen supplementation)
* Hypothesis: Fibrinogen replacement in severe traumatic haemorrhage can be achieved quicker with a more predictable dose response using Fibrinogen Concentrate compared to Cryoprecipitate
* It is imperative that robust and clinically relevant trials are performed to investigate fibrinogen supplementation in trauma before widespread adoption makes performing such studies unfeasible


Options:
A: Inclusion Criteria:

1. Male and female subjects =/\> 18 years and =/\< 80 years
2. Major trauma (ISS \> 15)
3. Clinical signs of ongoing bleeding or patients who are at risk for significant haemorrhage assessed and judged by the ED team in charge of patient
4. Presence of coagulopathy defined by ROTEM assays as follows,

   * Patients with concomitant decreased fibrinogen polymerisation (ROTEM® FibTEM A10 of \< 7 mm after 10 min)
   * Patients with concomitant decreased coagulation factor levels (ROTEM® ExTEM CT of \> 90 sec)

Exclusion Criteria:

1. Lethal injury
2. CPR on the scene,
3. Isolated brain injury, burn injury
4. Avalanche injury
5. Administration of FFP or coagulation factor concentrates before ED admission
6. Delayed (\> 6hours after trauma) admittance to ED
7. Known use of oral anticoagulants, or platelet aggregation inhibitors within 5 days before injury
8. Known history of severe allergic reaction to plasma products
9. Known history of congenital hemostasis disturbance, IgA or Protein C deficiency
10. Patients with a history of thromboembolic events or heparin induced thrombocytopenia (HIT) type 2 within the last year
11. Patients with a body weight \< 45kg and \> 150kg
12. Patients that are known to be pregnant
13. Jehova's Witness
14. Known participation in another clinical trial
15. Patient with known refusal of a participation in this clinical trial
B: Inclusion Criteria:

* The patients will be screened according to a modified TRUST1 Transfusion Score. This score attributes 1 point to each of the following conditions:

  * Hb level \< 13.5 g/dL
  * Weight \< 77 kg
  * Female sex
  * Age \> 65 years
  * Non elective surgery
  * Serum creatinine \> 1.36 mg/dL
  * Redo operation
  * Non isolated surgery
  * Factors are hemodilution-related factors, and will not be included. Non isolated surgery is mandatory for inclusion. Patients will be included in presence of at least 1 within the remaining 4 risk factors:
  * Age \> 65 years
  * Non elective surgery
  * Serum creatinine \> 1.36 mg/dL '8Redo operation INCLUSION CRITERIA (patients randomized)

    1. Combined cardiac operation with expected CPB duration \> 90 minutes
    2. At least one additional risk factor within the following: Age \> 65 years; Non elective surgery; Serum creatinine \> 1.36 mg/dL; Redo operation

Exclusion Criteria:

1. Age \< 18 years
2. Patients under thienopyridines
3. Known coagulopathy
4. Known autoimmune disorders
5. Participation in another RCT
6. Pregnancy
7. Emergency operation
8. Baseline HCT \< 35%
9. Baseline Antithrombin \< 80%
10. BSA \< 1.7 m2

WITHDRAWAL CRITERION:

1. Lowest HCT on CPB \< 23%
2. Transfusions during CPB

   * Patients randomized and not withdrawn will be DOSED with the investigational drugs.
C: All legally adult women with postpartum haemorrhage following vaginal or caesarean section delivery who have a clinical diagnosis of postpartum haemorrhage. The clinical diagnosis of PPH may be based on any of the following:

* Blood loss after vaginal delivery \> 500 mL OR
* \> 1,000 mL after caesarean section OR blood loss sufficient to compromise the haemodynamic status of the woman The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular woman with postpartum haemorrhage.
* Women for whom the responsible doctor considers there is a clear indication for antifibrinolytic therapy should not be randomised.
* Women for whom there is considered to be a clear contraindication to antifibrinolytic therapy should not be randomised.

Where the responsible clinician is substantially uncertain as to whether or not to use an antifibrinolytic, all these women are eligible for randomisation and should be considered for the trial.

There are no other pre-specified exclusion criteria.
D: Inclusion Criteria:

1. Adult affected by Trauma (\>18yrs) and
2. Judged to have significant haemorrhage or
3. Predicted to require significant transfusion with ABC Score ≥ 2 or by treating clinician judgement

Exclusion Criteria:

1. Injury judged incompatible with survival
2. Pregnancy
3. Known objection to blood products
4. Previous Fibrinogen replacement this admission
5. Pre-Trauma Centre fibrinogen replacement
6. Participation in competing study

Answer: D