Cryoprecipitate
Encyclopedia
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 Many uses of the product have been replaced by factor concentrates, but it is still routinely stocked by many hospital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 bank
s.
Like fresh frozen plasma
, compatibility testing is not strictly necessary, but cryo is given as ABO compatible
when possible. (Compatibility is reversed for plasma products: AB type is the universal plasma donor and O type is the universal plasma recipient.)
, 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. 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.
at Stanford University
in 1964, writing in Nature
.
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:
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:
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
.
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 Many uses of the product have been replaced by factor concentrates, but it is still routinely stocked by many hospital
Hospital
A hospital is a health care institution providing patient treatment by specialized staff and equipment. Hospitals often, but not always, provide for inpatient care or longer-term patient stays....
blood bank
Blood bank
A blood bank is a cache or bank of blood or blood components, gathered as a result of blood donation, stored and preserved for later use in blood transfusion. The term "blood bank" typically refers to a division of a hospital laboratory where the storage of blood product occurs and where proper...
s.
Like fresh frozen plasma
Fresh frozen plasma
The term fresh frozen plasma refers to the liquid portion of human blood that has been frozen and preserved after a blood donation and will be used for blood transfusion...
, compatibility testing is not strictly necessary, but cryo is given as ABO compatible
ABO blood group system
The ABO blood group system is the most important blood type system in human blood transfusion. The associated anti-A antibodies and anti-B antibodies are usually IgM antibodies, which are usually produced in the first years of life by sensitization to environmental substances such as food,...
when possible. (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 VIIIFactor VIII
Factor VIII is an essential blood clotting factor also known as anti-hemophilic factor . In humans, Factor VIII is encoded by the F8 gene...
, and 250 mg of fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
. It also contains von Willebrand factor
Von Willebrand factor
von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...
(vWF) and factor XIII
Factor XIII
Factor XIII or fibrin stabilizing factor is an enzyme of the blood coagulation system that crosslinks fibrin.- Function :Factor XIII is a transglutaminase that circulates in the plasma as a heterotetramer of two catalytic A subunits and two carrier B subunits...
.
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. 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
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
just one unit.
Indications
Indications for giving cryoprecipitate include:- HaemophiliaHaemophiliaHaemophilia is a group of hereditary genetic disorders that impair the body's ability to control blood clotting or coagulation, which is used to stop bleeding when a blood vessel is broken. Haemophilia A is the most common form of the disorder, present in about 1 in 5,000–10,000 male births...
- Used for emergency back up when factor concentrates are not available. - von Willebrands's disease - Not currently recommended unless last reserve. ddAVPDesmopressinDesmopressin is a synthetic replacement for vasopressin, the hormone that reduces urine production. It may be taken nasally, intravenously, or as a tablet...
is first line, followed by factor concentrates. - Hypofibrinogenaemia (low fibrinogenFibrinogenFibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
levels), as can occur with massive transfusions - Bleeding from excessive anticoagulation - Fresh frozen plasma contains most of the coagulation factors and is a much better choice when anticoagulation has to be reversed quickly.
- Massive haemorrhage - RBCsRed blood cellRed blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
and volume expandersBlood substitutesA blood substitute is a substance used to mimic and fulfill some functions of biological blood, usually in the oxygen-carrying sense...
are preferred therapies. - Disseminated intravascular coagulationDisseminated intravascular coagulationDisseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
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 PoolJudith Graham Pool
Judith Graham Pool was an American scientist. She is best known for the discovery of cryoprecipitation, a process for creating concentrated blood clotting factors which significantly improved the quality of life for hemophiliacs around the world.-References:*...
at Stanford University
Stanford University
The Leland Stanford Junior University, commonly referred to as Stanford University or Stanford, is a private research university on an campus located near Palo Alto, California. It is situated in the northwestern Santa Clara Valley on the San Francisco Peninsula, approximately northwest of San...
in 1964, writing in Nature
Nature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...
.
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.
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.