Cryoprecipitate

Cryoprecipitate, also called "Cryoprecipitated Antihemophilic Factor", "Cryoprecipitated AHF", and most commonly just "cryo", is a frozen blood product prepared from plasma.

It is often transfused as a four to six unit pool instead of as a single product. Many uses of the product have been replaced by factor concentrates, but it is still routinely stocked by many hospital blood banks.

Like fresh frozen plasma, compatibility testing is not indicated, but it is given as ABO compatible. Compatibility is reversed for plasma products: AB type is the universal plasma donor and O type is the universal plasma recipient.

Composition

Each 15 mL unit typically contains 100 IU of factor VIII, and 250 mg of fibrinogen. It also contains von Willebrand factor (vWF) and factor XIII.

US standards require manufacturers to test at least four units each month, and the products must have an average of 150 mg or more of fibrinogen and 80 IU of factor VIII.^[1] Individual products may actually have less than these amounts as long as the average remains above these minimums. Typical values for a unit are substantially higher, and aside from infants it is rare to transfuse just one unit.

Indications

Indications for giving cryoprecipitate include:^[2]

• Haemophilia - Used for emergency back up when factor concentrates are not available.
• von Willebrands's disease - Not currently recommended unless last reserve. dDAVP is first line, followed by factor concentrates.
• Hypofibrinogenaemia (low fibrinogen levels), as can occur with massive transfusions
• Bleeding from excessive anticoagulation - FFP contains most of the coagulation factors, and is a much better choice when anticoagulation has to be quickly reversed.
• Massive haemorrhage - RBCs and volume expanders are preferred therapies.
• Disseminated intravascular coagulation

Manufacture

The product is manufactured by slowly thawing a unit of FFP at temperatures just above freezing (1-6 °C), typically in a water bath or a refrigerator. The product is then centrifuged to remove the majority of the plasma, and the precipitate is resuspended in the remaining plasma or in sterile saline. The product may be pooled and frozen or frozen as individual units.

History

The first publication of the method of concentrating clotting factors from plasma was by Judith Graham Pool at Stanford University in 1964, writing in Nature.^[3]

Cryoprecipitate was originally known as "Cryoprecipitate AHF", where AHF stands for "Anti-hemophiliac factor." AHF is now known as Factor VIII.

According to Dr. Charles Abildgaard, who was a Stanford medical resident at the time:

They obtained frozen plasma in very large containers that they got from Japan. They would thaw that and send her [Pool] samples of the liquid parts to assay. She wasn't really finding very much Factor VIII activity, and then someone mentioned to her that when they thawed this large amount of plasma, there was always some mucky stuff at the bottom of it, and she said, "Well, send me some of that, too." She found that at least half of the Factor VIII activity was in the residue. What was happening that, because of the large volume, as the mass thawed, it stayed cold. So this was cryoprecipitate.^[4]

Others had been close to discovering cryoprecipitate but failed to make the connection between the lack of plasma clotting activity after thawing and the precipitate. According to Dr. Frederick Rickles:

I made a mistake in an experiment, and instead of putting frozen plasma back in the freezer at the end of the day's experiment, I instead stuck it in the refrigerator. When I came in the next morning, there was all this junk in the bottom of the tube which I spun out, and I used the plasma for my experiment. My experiment didn't work because there was no Factor VIII in it. And I went back and fished the junk out of the trash and assayed the junk and got these outrageously high values for Factor VIII in the junk, and neither Charlie nor I believed it, and so it was one of those things. And sure enough, about a year later Judith Graham Pool discovered cryoprecipitate.^[4]

References