Please select the eligibility criteria that correspond to the clinical trial below.
Title: Fibrinogen Concentrate as Initial Treatment for Postpartum Haemorrhage - A Randomised Clinically Controlled Trial
Brief Summary: Severe maternal bleeding is a serious complication of birth and causes 125.000 deaths worldwide each year. The investigators aim to investigate if early treatment with fibrinogen concentrate versus saline can reduce the incidence of blood transfusion in women with postpartum haemorrhage.

A low level of fibrinogen has been associated with increased blood loss and transfusion requirements in different clinical settings including obstetrical bleeding. Early up-front treatment with fibrinogen may reduce incidence of transfusion by securing optimal haemostatic capacity in women with postpartum haemorrhage.

The investigators plan to enrol 245 patients on four hospitals in the Capital Region of Denmark during a two year period.

As safety measure the investigators plan to use TEG®/Functional Fibrinogen/Rapid-TEG as haemostatic monitoring of all participants during the trial: Baseline test is taken at inclusion before administration of fibrinogen concentrate/placebo. Further tests are taken immediately after intervention, 4 hours and 24 hours after. Baseline test is blinded to the providers of treatment - the rest is clinically available.


Options:
A: 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.
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:

1. Informed consent from participant.
2. Women who develop PPH defined as bleeding from uterus and/or the birth canal within 24 hours postpartum.
3. Age ≥ 18 years.
4. If vaginal birth: indication of one of the following procedures at the operation theatre with anaesthetic assistance: a) Estimated blood loss ≥ 500 ml and indication of manual removal of placenta or b) Indication of manual exploration of the uterus due to continuous bleeding after the birth of placenta.
5. If birth by Caesarean section: A perioperative blood loss ≥ 1000 ml.

Exclusion Criteria:

1. Patients with known inherited deficiencies of coagulation.
2. Patients in anti-thrombotic treatment prepartum due to increased risk of thrombosis.
3. Patients with a pre-pregnancy weight \<45 kg.
4. Patients who refuse to receive blood transfusion.
D: Inclusion Criteria:

* Males and Females
* Age 6 months to 17 years
* Scheduled for elective scoliosis surgery or major craniofacial surgery
* Written informed consent has been obtained
* Intraoperative hypofibrinogenemia according to definition of treatment groups

Exclusion Criteria:

* Preexisting congenital or acquired coagulation disorder
* Medical history of estimated increased bleeding tendency
* Ongoing coagulation therapy
* Clinical signs or diagnosis of acute thromboembolism
* Intolerance of study drug
* Participation at another clinical trial
* Pregnant or lactating women

Answer: C