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Blood Bank

Cryoprecipitated AHF

Cryoprecipitated Antihemophilic Factor (AHF), often simply called “Cryo.” While it sounds complex, think of it as a highly concentrated “super-glue” kit derived from plasma, packed with specific clotting factors

What is Cryoprecipitated AHF?

  • Definition: Cryoprecipitated AHF is the cold-insoluble protein fraction that precipitates out when a unit of Fresh Frozen Plasma (FFP) is thawed slowly under controlled refrigerated conditions (1°C to 6°C)
  • Composition: It’s a concentrate, not whole plasma. Each small unit (typically 10-20 mL) contains a significant portion of specific coagulation factors derived from the original ~250 mL unit of FFP. The key components concentrated in Cryo are:
    • Fibrinogen (Factor I): Essential for forming the fibrin meshwork of a blood clot. This is the most important component and the primary reason Cryo is used today.
    • Factor VIII (Antihemophilic Factor): A key factor in the intrinsic coagulation cascade. Deficiency causes Hemophilia A
    • von Willebrand Factor (vWF): Important for platelet adhesion to injured vessel walls and acts as a carrier protein for Factor VIII
    • Factor XIII: Stabilizes the fibrin clot by cross-linking fibrin strands
    • Fibronectin: Involved in cell adhesion and wound healing

Preparation Method

The process is quite specific:

  1. Start with a unit of Fresh Frozen Plasma (FFP)
  2. Thaw the FFP slowly in a controlled refrigerator (1°C to 6°C) over several hours
  3. As it thaws, a white, gelatinous precipitate forms (this is the cryoprecipitate)
  4. Once thawing is complete but the precipitate remains, the unit (now containing slushy plasma and the precipitate) is centrifuged heavily (“hard spin”)
  5. The supernatant plasma (now called Cryoprecipitate-Reduced Plasma) is expressed off into another bag, leaving behind the concentrated precipitate in a small volume (10-20 mL) of residual plasma
  6. This remaining concentrate is Cryoprecipitated AHF, which is then refrozen rapidly at ≤ -18°C for storage

Indications for Transfusion

Cryo is used primarily to replace the specific factors it contains, particularly fibrinogen:

  • Primary Indication: Treatment of bleeding associated with low fibrinogen levels (hypofibrinogenemia) or functionally abnormal fibrinogen (dysfibrinogenemia). This is common in situations like:
    • Disseminated Intravascular Coagulation (DIC)
    • Severe liver disease
    • Massive transfusion protocols (where fibrinogen is consumed or diluted)
    • Congenital fibrinogen deficiency
  • Secondary Indications (Less Common Now due to specific factor concentrates)
    • Hemophilia A (Factor VIII deficiency): Only if Factor VIII concentrates are unavailable
    • von Willebrand Disease (vWD): Only if vWF-containing concentrates are unavailable
    • Factor XIII deficiency: (Rare)
  • Other Use: As a source for Fibrin Sealant (often prepared by pharmacy or used commercially) for topical application to control surgical bleeding

Important Note Cryo is NOT indicated for general volume replacement or as a source of coagulation factors other than those listed above (e.g., it’s a poor source of Factor V, Factor II, etc., compared to FFP)

Storage and Expiration

  • Frozen State
    • Storage Temperature: ≤ -18°C
    • Expiration: 1 year from the date of the original whole blood collection
  • Thawed State
    • Thawing: Done rapidly in a 30-37°C water bath or approved thawing device
    • Storage Temperature: 20°C to 24°C (Room Temperature) - Do NOT refrigerate after thawing!
    • Expiration (Critical):
      • Single Units: Expire 6 hours after thawing
      • Pooled Units (Open System): If multiple units are pooled together using needles/syringes (an open system), the pool expires 4 hours after pooling begins

Quality Control / Specifications

Regulatory requirements (e.g., AABB Standards) mandate minimum levels of key factors in QC testing of manufactured units:

  • Fibrinogen: ≥ 150 mg per individual unit
  • Factor VIII: ≥ 80 International Units (IU) per individual unit

Administration

  • Pooling: Because a single unit contains a relatively small amount of factors, multiple units (often 5-10, sometimes more) are typically pooled together into one bag to provide a therapeutic dose for an adult. The number of units pooled depends on the clinical indication and patient size
  • Compatibility: ABO compatibility is preferred but not strictly required due to the small volume of plasma and antibodies. Hospital policies often require ABO-compatible Cryo. Rh type is generally not considered relevant for Cryo transfusion
  • Filtration: Must be administered through a standard blood filter (170-260 microns)
  • Infusion: Usually infused rapidly, as quickly as the patient can tolerate, often over 10-30 minutes. Must be completed before the 4-hour (pooled) or 6-hour (single unit) expiration time
  • Dosage: Calculated based on the patient’s weight, clinical situation, and the desired increase in factor levels (especially fibrinogen)

Potential Risks / Adverse Reactions

Risks are similar to those associated with other plasma components, although the small volume per unit reduces some risks unless large numbers are pooled and transfused:

  • Febrile Non-Hemolytic Reactions
  • Allergic Reactions (Urticaria to Anaphylaxis)
  • Transfusion-Transmitted Infections (TTIs) - very low risk
  • Transfusion-Related Acute Lung Injury (TRALI) - risk associated with plasma
  • Circulatory Overload (less common unless many units given rapidly)

Key Terms

  • Cryoprecipitate (Cryo): The cold-insoluble protein fraction precipitated from thawed FFP
  • Fibrinogen (Factor I): The primary protein in Cryo, essential for clot formation; most common reason for transfusion
  • Factor VIII (AHF): Antihemophilic Factor, concentrated in Cryo; deficiency causes Hemophilia A
  • von Willebrand Factor (vWF): Aids platelet adhesion, carries Factor VIII; concentrated in Cryo
  • Factor XIII: Stabilizes fibrin clots; concentrated in Cryo
  • Pooling: Combining multiple single units of Cryo into one container for transfusion
  • Hypofibrinogenemia: Low level of fibrinogen in the blood
  • Labile Factors: Coagulation factors (like V and VIII) that degrade relatively quickly, especially when not frozen
  • Fibrin Sealant: A topical hemostatic agent made from fibrinogen (often from Cryo) and thrombin