Please select the eligibility criteria that correspond to the clinical trial below.
Title: RETIC Trial: Reversal of Trauma Induced Coagulopathy Using Coagulation Factor Concentrates or Fresh Frozen Plasma
Brief Summary: Severe traumatized patients (ISS \> 15) admitted to emergency department (ED) University Hospital Innsbruck with obvious bleeding and/or who are at risk for significant hemorrhage will be screened by rotational thrombelastometry (ROTEM) assays during ED treatment and subsequent surgical/radiological interventions for having coagulopathy (T0). If a patient meets the inclusion criteria (T1) and is recruited for the study, a first study related blood sample (40mL) will be drawn, and data collected. Subsequently, 100 patients will be randomized to receive Fibrinogen concentrate and/or Prothrombin complex concentrate and/or FXIII concentrate for reversal of coagulopathy, while the other 100 patients will receive fresh frozen plasma (FFP),respectively.

Treatment failure will be registered if bleeding persists and ROTEM parameters do not improve after two times dosages of study drug. In these cases haemostatic rescue therapy will be administered. CFC (fibrinogen concentrate and/or PCC, and/or FXIII concentrate) will be administered to patients randomized to receive FFP and FFP will be administered to patients of the CFC group.

In cases unresponsive to comprehensive treatment or normal ROTEM combined with diffuse bleeding, other haemostatic medications can be administered (e.g rFVIIa, DDAVP, VWF/FVIII concentrate) as judged by the anesthetist in charge. The need and type of any rescue therapy will be documented and a ROTEM will be performed thereafter.

At admission to ICU (T0 ICU), 24h (T24 ICU) and 48h(T48 ICU) thereafter further study related blood samples are drawn (40mL each).

The indications for transfusion of red blood cells or platelets, administration of antifibrinolytics, treatment of acidosis, hypothermia, hypocalcemia and volume replacement are similar for both groups and treatment is performed according to clinical routine.

Besides coagulation management during ED treatment until 24h on ICU, patient's care is not influenced by the study and follows clinical routine.


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:

At Screening:

* Undergoing elective open surgical procedures on any part of the aorta requiring cardiopulmonary bypass (CPB), with or without other cardiac surgical procedures (e.g. valve replacement or repair, coronary artery bypass grafting, etc.).
* 18 years of age or older.
* Written informed consent for study participation obtained before undergoing any study specific procedures.

Intraoperative (at the 1st 5-minute bleeding mass):

* A 5-minute bleeding mass of 60 to 250 g following discontinuation of CPB, administration of protamine, and establishment of surgical hemostasis.
* Minimum core body temperature 35°C, measured according to local practice.
* Activated clotting time ± 25% of baseline levels.
* Blood pH \> 7.3.

Exclusion Criteria:

At Screening and/or baseline:

* Undergoing emergency aortic repair surgery.
* Reoperative aortic surgery at the same anatomic site as the original procedure such as replacement of a previously placed aortic graft. Resternotomy and rethoracotomy are permitted.
* Any operation for infection.
* Proof or suspicion of a congenital or acquired coagulation disorder (e.g. Von Willebrand's disease, hemophilia or severe liver disease) or a prothrombotic disorder (e.g. protein C or S deficiency).
* Myocardial infarction (MI), acute coronary syndrome or stroke in the 2 months preceding study surgery.
* Low molecular weight or unfractionated heparin in the 24 hours preceding study surgery.
* Clopidogrel administration within 5 days preceding study surgery or prasugrel administration within 7 days preceding study surgery or ticagrelor administration in the 48 hours preceding study surgery.
* Factor Xa inhibitors within 2 days preceding study surgery.
* IIb/IIIa antagonist administration in the 24 hours preceding study surgery.
* Use of direct thrombin inhibitors: within 3 days preceding study surgery for dabigatran and within 24 hours preceding study surgery for all others.
* An international normalized ratio \> 1.3 immediately preceding the start of surgery.

Intraoperative (at the 1st 5-minute bleeding mass):

* Use of any systemic hemostatic therapy (such as FFP, platelets, prothrombin complex concentrates) from the beginning of surgery until IMP administration.
C: 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.
D: 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.

Answer: A