Fibrinogen Concentrate

Aka. RiaSTAP or Fibrinogen (Factor I) Concentrate

DESCRIPTION

• Concentrated human factor I (fibrinogen)

INDICATIONS

1. Congenital or acquired hypo- or afibrinogenaemia
2. In a bleeding patient, with fibrinogen level less than 1.5 g/L (2.0 g/L in obstetric haemorrhage or cardiothoracic haemorrhage)
3. Because the ROTEM/TEG algorithm told you to give it

ADMINISTRATION / DOSING

• Intravenous (IV)
• Adults:
  • Generally: 2-4 g (2-4 vials) for average-sized adult
  • If fibrinogen level unknown, administer 70 mg/kg
  • Dosing suggested by manufacturer:
    • mg/kg = [(Target fibrinogen level g/L) – (Actual fibrinogen level g/L)] ÷ 0.017
    • E.g. mg/kg = [2.2 g/L – 1.0 g/L) ÷ 0.017 = 70 mg/kg –> x 75 kg = ~5.3 g
• Children:
  • No manufacturer guidelines however;
  • Suggestion of 30-60 mg/kg and consultation with your relevant haematology service
• Administration:
  • Manufacturer recommends 5 mL/min, and other guidelines recommend 20 mL/min (i.e. slow push over 2.5mins)
  • Can be administered peripherally as with all other blood products
  • Not compatible with any other blood products nor other medications
  • Flush with saline
  • Tips on how to reconstitute are below

PREPARATION

• Manufactured from cryoprecipitate into a glycine precipitate, then filtered further with multiple precipitation/adsorption steps
• It is heat treated (+60^oC for 20 hours in aqueous solution)
• 2x subsequent glycine precipitation steps
• Finally, it is lipophilised (aka. freeze-dried, or cryodesiccated)

PHARMACEUTICS

• Presentation:
  • Single-dose glass vial with 1 g of human fibrinogen and a rubber stopper (latex free)
  • One glass vial of 50 mL water for injection
  • One transfer set
  • One dispensing pin
  • One syringe filter
• Contents:
  • 900-1300 mg of human fibrinogen (1 g)
• Excipients:
  • Albumin (400-700 mg)Arginine hydrochloride (375-660 mg)Sodium hydroxide (for pH adjustment)Sodium chloride (200-350 mg, or ~7.1 mmol per vial)
  • Sodium citrate (50-100 mg).
• Storage:
  • Temperatures of 2-8^oC and is stable for up to 60 months
  • Must be used within 8 hours after reconstituted

GROUP / CROSSMATCH

• Not required

ADVERSE EFFECTS

• Thromboembolic episodes including MI, PE, DVT and arterial thrombosis
• Allergic reaction: anaphylaxis, dyspnoea, rash
• Chills, nausea, vomiting
• Risk of infectious disease transmission such as: CJD, HIV, Hep B and C

LOCATION OF ACTION

MECHANISM OF ACTION

• Fibrinogen (factor I) in the presence of thrombin (factor IIa) and factor XIIIa (fibrin-stabilising factor) and calcium ions is converted into a stable and elastic three-dimensional fibrin (factor Ia) haemostatic clot

CONTRAINDICATIONS

• Known hypersensitivity / anaphylaxis reactions to this product or other concentrated fractionated plasma products

ADVANTAGES AND DISADVANTAGES TO CRYOPRECIPITATE

Advantages

• Does not need to be thawed and so can reduce the time it takes to administer fibrinogen replacement
• No grouping / crossmatch required
• Much more convenient to give a large amount of fibrinogen in a relatively small volume
  • (e.g. to give 1 g of fibrinogen in cryoprecipitate it would take ~3 units (= ~100 mL), or for FFP you would require ~2 units for 1 g = ~600 mL volume)
    • At Institution 1 (a quaternary hospital with ~600 beds in Sydney) there are only 80 units of O and A each, 70 of B and 30 of AB cryoprecipitate at any one time
• Useful in pre-hospital or regional settings where blood product storage is limited
• Long shelf-life of 60 months (vs 12 months for cryoprecipitate)

Disadvantages

• Costly, roughly double the cost of cryoprecipitate (AUD$863.12 per 1 g RiaSTAP vs AUD$163.01 per unit of cryo)
• Lack of familiarity

RECONSTITUTION TIPS

It is a bit of a PITA (pain in the ass) to reconstitute, DO NOT shake when the water for injection has been added, otherwise you will end up with a foamy mess (like teicoplanin, you only ever do it once)

• You will need, in addition to the package contents, a 50-60 mL luer-lock syringe, and a sterile alcohol wipe (or equivalent)
• You will also need a decent amount of bench space if you are reconstituting more than 1 g

References and Links

References

• Albert Health Services. (2021, September 01). RIASTAP™ Fibrinogen Concentrate (human). Retrieved January 13, 2023, from https://www.albertahealthservices.ca/assets/wf/lab/if-lab-clin-tm-riastap.pdf
• CSLBehring. (2021, June). Prescribing Information for RiaSTAP. Retrieved January 17, 2023, from http://cslbehring.vo.llnwd.net/o33/u/central/PI/US/RiaSTAP/EN/RiaSTAP-Prescribing-Information.pdf
• CSL Behring. (2021, June 1). Reconstitution of RiaSTAP. Retrieved January 17, 2023, from https://riastap.healthydigital.net/sites/default/files/pdf/RiastapReconGuide_v5_03.pdf
• D, J. (2007, April 22). File:coagulation full.svg. Retrieved January 17, 2023, from https://commons.wikimedia.org/wiki/File:Coagulation_full.svg
• National Blood Authority Australia. (2023, January 01). What blood products are supplied – national product price list. Retrieved January 18, 2023, from https://www.blood.gov.au/national-product-price-list

James Pearlman

ICU Advanced Trainee BMedSci [UoN], BMed [UoN], MMed(CritCare) [USyd] from a broadacre farm who found himself in a quaternary metropolitan ICU. Always trying to make medical education more interesting and appropriately targeted; pre-hospital and retrieval curious; passionate about equitable access to healthcare; looking forward to a future life in regional Australia. Student of LITFL.