Cryoprecipitate

Aka. Cryo

DESCRIPTION

• Fractionated plasma product consisting of Fibrinogen (Factor I), von Willebrand Factor, Factor VIII, and small amounts of Factor XIII and Fibronectin

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:
  • 1 unit per 5-10 kg of body weight should increase fibrinogen level by 0.5-1.0 g/L
  • Typical adult dose is 10 units, approximately equivalent to 3-4 g of fibrinogen
• Children (from RCH guidelines):
  • 5 – 10 mL/kg
  • Administer at 10 – 20 mL/kg/h
• Administration:
  • Mix thoroughly by inversion prior to use and transfuse through a blood administration set incorporating a standard 170-200 µm filter (most pump sets include a 200 µm filter)
  • Administer units as fast as you need to (except in paediatrics)
  • Units must be used within four hours after removal from storage
  • Do not administer amongst other blood products, flush with 0.9% sodium chloride
• The half-life of fibrinogen is 3-5 days

PREPARATION

• Cryoprecipitate is prepared by thawing whole blood-derived Fresh Frozen Plasma (FFP) used for cryoprecipitate production and recovering the precipitate
• The cold-insoluble precipitate is then re-suspended in a small amount of residual plasma (15-20mL) and then re-frozen

PHARMACEUTICS

• Presentation:
  • Whole Blood: Volume 30-40 mL
  • Apheresis: Volume 54-55 mL
• Contents:
  • Whole blood Cryo:
    • Fibrinogen (Factor I) 357 (+/- 110) mg/unit
    • Factor VIIIc 151 (+/- 30) IU/unit
    • vWF 294 (+/- 69) IU/unit
  • Apheresis Cryo:
    • Fibrinogen (Factor I) 1185 (+/- 318) mg/unit
    • Factor VIIIc 418 (+/- 94) IU/unit
    • vWF 670 (+/- 138) IU/unit
• Storage:
  • -25^oC or belowThawed cryoprecipitate should be maintained at 20-24^oC until transfused12-month shelf-life
  • Once thawed it should be used within 6 hours if it is a closed single unit, or four hours if it is an open unit or it has been pooled

GROUP / CROSSMATCH

• Compatibility tests are not necessary, however, preferably ABO compatible with the recipients red cells
• ABO-incompatible cryoprecipitate can be used with caution – particularly in large volumes
• If large volumes of ABO-incompatible cryoprecipitate are used, the recipient may develop a positive direct antiglobulin test and, very rarely, develop haemolysis.
• Plasma components that have low titre anti-A or anti-B pose a lower risk of haemolysis.
• Matching with RhD is not necessary

ADVERSE EFFECTS

• Please see transfusion risks / reactions
• Early
  • Fever
  • Allergy: Mild –> Anaphylaxis
  • Air embolism
  • Hypothermia
  • Acute haemolytic reaction
  • TRALI (Transfusion-related acute lung injury)
  • Volume Overload
  • Citrate Toxicity
• Late
  • Viral infection
  • Bacterial infection
  • Parasitic infection:
  • Prion infection:
  • GVHD (Graft versus Host Disease)
  • Immune sensitisation (Rh D antigen)
  • TRIM (Transfusion-related immunomodulation)

LOCATION OF ACTION

See also, Cell-Based Model of Coagulation:

MECHANISM OF ACTION

• vWF mediates platelet adhesion to damaged vascular subendothelium and thus platelet aggregation (N.B. learn about the Cell-Based Model of Coagulation above)
• 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

• Should not be used to treat haemophilia, von Willebrand’s disease or deficiencies of Factor XIII or fibronectin unless alternative therapies are unavailable

ADVANTAGES AND DISADVANTAGES TO FIBRINOGEN CONCENTRATE

Advantages

• Cheap, roughly half the cost of fibrinogen concentrate (AUD$863.12 per 1g RiaSTAP vs AUD$163.01 per unit of cryo)

Disadvantages

• Needs to be thawed
• Some grouping / cross-match should be undertaken, especially if large volumes are to be used
• Impractical if a large quantity is needed:
  • 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 80 units of O and A each, 70 of B and 30 of AB cryoprecipitate at any one time
• Short shelf-life of 12 months (compared with 60 months)

References and Links

FOAMEd

• Learn about the cell-based model of coagulation

References

• Australian Red Cross Lifeblood. (2020, June). Blood Component Information: An Extension of Blood Component Labels. Retrieved January 27, 2023, from https://www.lifeblood.com.au/sites/default/files/resource-library/2021-12/78.-Blood_Component_Information_1.pdf
• D, J. (2007, April 22). File:coagulation full.svg. Retrieved January 17, 2023, from https://commons.wikimedia.org/wiki/File:Coagulation_full.svg
• Holland, C. (2021, August 04). The cell-based model of coagulation – learnhaem: Haematology Made Simple. Retrieved January 27, 2023, from https://www.learnhaem.com/courses/coagulation/lessons/normal-haemostasis/topic/the-cell-based-model-of-coagulation/
• Peyvandi, F., Garagiola, I., & Baronciani, L. (2011). Role of von Willebrand factor in the haemostasis. Blood transfusion = Trasfusione del sangue, 9 Suppl 2(Suppl 2), s3–s8. https://doi.org/10.2450/2011.002S PMID: 21839029; PMCID: PMC3159913. [Free Full Text]
• 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
• The Royal Children’s Hospital Melbourne. (n.d.). Ordering Blood Products. Retrieved January 27, 2023, from https://www.rch.org.au/bloodtrans/blood_provision/Ordering_Blood_Products/

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