5.2 Plasma & Cryoprecipitated AHF
Key Takeaways
- Fresh Frozen Plasma (FFP) must be separated from whole blood and frozen at -18C or colder within 8 hours of collection to preserve labile factors V and VIII near normal levels.
- PF24 is frozen within 24 hours of phlebotomy and carries slightly reduced factor V and VIII activity but is used interchangeably with FFP for most indications, including massive transfusion protocols.
- Cryoprecipitated AHF concentrates factor VIII (at least 80 IU/unit), fibrinogen (at least 150 mg/unit), von Willebrand factor, factor XIII, and fibronectin from a single unit of plasma.
- Cryoprecipitate's primary modern indication is fibrinogen replacement in hypofibrinogenemia/DIC/massive transfusion; factor concentrates and DDAVP have largely replaced it for hemophilia A and von Willebrand disease.
- If FFP or PF24 is not transfused within 24 hours of thawing, it can be relabeled 'Thawed Plasma' and stored at 1-6C for up to 5 days total from the time of thawing.
Why Plasma and Cryoprecipitate Matter on the SBB Exam
Plasma-derived components fill a niche distinct from whole blood or red cells: replacing coagulation factors, correcting dilutional coagulopathy, and, for cryoprecipitate, delivering a concentrated dose of fibrinogen and factor VIII from a small volume. The SBB exam tests the freeze-timing distinctions between plasma products, the content and modern indications for cryoprecipitate, and the practical dating rules blood banks apply once these products are thawed.
Fresh Frozen Plasma (FFP)
Fresh Frozen Plasma (FFP) is the liquid portion of whole blood separated by centrifugation and frozen solid at -18C or colder within 8 hours of phlebotomy. That 8-hour window is deliberate: it preserves the labile coagulation factors V and VIII at levels close to those in fresh circulating plasma, in addition to the more stable factors, fibrinogen, complement, and plasma proteins such as albumin and immunoglobulins. Whole blood-derived FFP volume is typically 200-250 mL; apheresis-collected plasma units are larger, often up to several hundred mL depending on donor eligibility limits. FFP may be stored frozen for up to 12 months at -18C or colder, or up to 7 years at -65C or colder per AABB Standards.
PF24 and PF24RT24
PF24 (Plasma Frozen Within 24 Hours After Phlebotomy) is frozen between 8 and 24 hours after collection rather than within 8 hours. The longer interval allows some decline in the most labile factors, V and VIII, but PF24 remains suitable for the great majority of plasma transfusion indications. PF24RT24 describes plasma - typically apheresis-collected - that is held at room temperature for up to 24 hours during collection and processing, then frozen within 24 hours of phlebotomy; it is used clinically the same way as PF24. Because most plasma transfusions (dilutional coagulopathy correction, warfarin reversal, DIC, liver disease) do not depend on normal factor V/VIII activity, FFP and PF24 are used interchangeably in most transfusion protocols, including massive transfusion protocols (MTPs).
Thawed Plasma and Liquid Plasma
Once FFP or PF24 is thawed (in a 30-37C water bath or an FDA-cleared plasma-thawing device), the FDA-approved label allows it to be stored at 1-6C for only 24 hours before it must be transfused or discarded. AABB Standards and the Circular of Information provide a further pathway: if not transfused within that 24-hour window, the unit can be relabeled "Thawed Plasma" (its original license number removed, since it is now an unlicensed but AABB-recognized product) and stored refrigerated at 1-6C for an additional 4 days, for a total of 5 days from the time of thawing. Factor V and VIII activity continue to decline gradually during this period but remain adequate for most non-hemophilia indications, which is why many blood banks keep a rotating supply of pre-thawed plasma ready for immediate release in trauma and massive transfusion situations. Liquid Plasma is a separate product: it is separated from whole blood and refrigerated at 1-6C without ever being frozen, so it is immediately available with no thaw delay, at the cost of a less certain labile factor level than a product frozen promptly after collection.
| Product | Frozen Within | Storage / Shelf Life | Factor V/VIII Level | Typical Use |
|---|---|---|---|---|
| FFP | 8 hours of phlebotomy | Up to 12 months at -18C or colder | Near-normal | General coagulopathy, all indications |
| PF24 / PF24RT24 | 24 hours of phlebotomy | Up to 12 months at -18C or colder | Slightly reduced | Interchangeable with FFP for most uses |
| Thawed Plasma | N/A (post-thaw relabel) | Up to 5 days total at 1-6C from thaw time | Gradually declining | Immediate-release trauma/MTP inventory |
| Liquid Plasma | Never frozen | Refrigerated, 1-6C | Variable, less certain | Immediate availability, no thaw needed |
Cryoprecipitated AHF
Cryoprecipitated antihemophilic factor (cryoprecipitate) is prepared by thawing a unit of FFP (or, at some FDA-approved centers, PF24) slowly at 1-6C and recovering the cold-insoluble precipitate that forms in about 10-20 mL of residual plasma, which is then refrozen within 1 hour of preparation. AABB and FDA quality control standards require each unit to contain at least 80 IU of factor VIII and 150 mg of fibrinogen (typical units average well above these minimums, often around 325 mg of fibrinogen), and it also concentrates von Willebrand factor, factor XIII, and fibronectin. Frozen cryoprecipitate may be stored for up to 12 months from the original whole blood collection date. After thawing at 30-37C, a single unit must be transfused within 6 hours, while units pooled in an open system must be transfused within 4 hours because entering the closed system introduces contamination risk. Adult doses typically pool 5-6 units to raise fibrinogen meaningfully in a 70 kg adult without ongoing consumption. ABO compatibility is generally not required for cryoprecipitate because the residual plasma volume per unit is small.
Modern Indications
Cryoprecipitate's dominant modern indication is fibrinogen replacement: hypofibrinogenemia or dysfibrinogenemia in DIC, massive transfusion/dilutional coagulopathy, or liver disease, generally when fibrinogen falls below an institutional threshold (commonly 150 mg/dL for active bleeding, or 200 mg/dL for life-threatening hemorrhage). Factor XIII deficiency and use as a component of surgical fibrin sealant are secondary indications. Historically, cryoprecipitate treated hemophilia A and von Willebrand disease, but plasma-derived and recombinant factor concentrates and desmopressin (DDAVP) have largely replaced it for those conditions because concentrates carry dedicated viral inactivation and standardized potency, while cryoprecipitate does not.
Worked Example
A massive transfusion patient's fibrinogen returns at 90 mg/dL, below the trauma protocol's 150 mg/dL active-bleeding threshold. A pool of 10 units of cryoprecipitate is ordered. Because a standard 5-6 unit pool typically raises fibrinogen well above the minimum threshold in an average adult, a 10-unit pool should raise the level substantially further, assuming ongoing consumption or dilution does not outpace the increase; repeat testing after infusion confirms the response.
Common Traps
- Mixing up the 8-hour FFP window with the 24-hour PF24 window.
- Forgetting that cryoprecipitate must be refrozen within 1 hour of preparation to remain valid cryoprecipitate.
- Assuming cryoprecipitate is still first-line therapy for hemophilia A or von Willebrand disease rather than a fibrinogen-replacement product.
- Confusing Thawed Plasma's 5-day total post-thaw dating with the initial 24-hour window for issuing freshly thawed FFP/PF24 under its original label.
Within how many hours of whole blood collection must plasma be frozen at -18C or colder to qualify as Fresh Frozen Plasma (FFP) rather than PF24?
Which coagulation component is NOT concentrated in cryoprecipitated AHF?
A trauma patient's fibrinogen level is 85 mg/dL during a massive transfusion. Which blood product is most specifically indicated to raise the fibrinogen level?
Once FFP is thawed and, after 24 hours, relabeled as 'Thawed Plasma' and stored at 1-6C, how much longer may it be stored before it must be transfused or discarded?