Cryoprecipitate is the cold-precipitated concentration of factor VIII, the antihemophilic factor (AHF).

It is prepared from FFP thawed slowly between 1_ and 6_C. The product is prepared from a single whole blood unit collected into CPDA1 or CPD and suspended in less than 15 mL of plasma. The product contains most of the factor VIII and part of the fibrinogen from the original plasma. It contains at least 80 units of AHF activity and at least 150 mg of fibrinogen.90 Other significant factors found in cryoprecipitate are factor XIII and von Willebrands factor. Cryoprecipitate has a shelflife of 12 months in the frozen state and must be transfused within 6 hours of thawing or within 4 hours of pooling. Like FFP and PF24, cryoprecipitate should be thawed quickly at 37_C. Once thawed, FDA recommends storing at room temperature (22_ to 24_C) until transfused. Cryoprecipitate is indicated in the treatment of classic hemophilia (hemophilia A), von Willebrands disease, and factor XIII deficiency and as a source of fibrinogen for hypofibrinogenemia. In recent years, cryoprecipitate has also been used to make fibrin glue, a substance composed of cryoprecipitate (fibrinogen) and topical thrombin. Briefly, one to two units of cryoprecipitate are thawed and drawn into a syringe. Topical thrombin with or without calcium is drawn into a second syringe. The contents of the two syringes are simultaneously applied to the bleeding surface, where fibrinogen is converted to fibrin.91 These commercial products are viralinactivated and licensed to control bleeding in cardiovascular surgeries. The whole blood donor requirements and preparation requirements for cryoprecipitate are the same as those for platelets and FFP. A procedure for production of cryoprecipitate follows: 1. The venipuncture must be nontraumatic. 2. The whole blood can be cooled before and during production because platelets are not usually prepared from the units. The volume of plasma required to remain on the RBCs and the platelet concentrate will reduce the amount of plasma available for cryoprecipitate production, enough to reduce the final AHF activity significantly in the precipitate. At least 200 mL of plasma (205 g) should be used to ensure that the final product will contain at least 80 AHF units. 3. The plasma must be frozen within 8 hours of collection and within 1 hour from the time freezing was initiated. 4. The second stage of cryoprecipitate preparation begins by allowing the frozen plasma to thaw slowly in the refrigerator at 1_ to 6_C. This takes 14 to 16 hours when plasma is thawed in a standard blood bank refrigerator. If a circulating cryoprecipitate thaw bath (4_C water bath) is used, the thawing time is reduced to about 4 hours. The endpoint is when the plasma becomes slushy. 5. Centrifuge the plasma at 4_C for a hard spin. 6. Express the supernatant plasma into the attached satellite bag. The cryoprecipitate will be a small white mass in the original plasma bag. Leave only 10 to 15 mL of plasma on the precipitate. 7. Separate and refreeze the cryoprecipitate immediately. Time elapsed should be no more than 1 hour from the time the plasma reaches the slushy stage until the

cryoprecipitate is refrozen. A delay in refreezing or exposure of the unit to elevated temperatures during processing will significantly decrease the factor VIII activity level in the final product. The centrifuge temperature must be at 4_C, and it is better if the centrifuge cups are well chilled. 8. The final product should be placed in a protective container because of the brittle nature of the plastic bag at freezer temperatures. Store at 18_C or colder up to 12 months from the date of whole blood collection. 9. If the supernatant plasma is refrozen at 18_C, it must be labeled as plasma cryoprecipitate reduced. The quality control requirements mandate that the volume and AHF activity of the final product must be tested on at least 4 units monthly. The volume should not exceed 25 mL, and 75 percent of all units tested must show a minimum of 80 IU of AHF activity. Records must be maintained of all quality assurance testing performed.

NovoSeven
Recombinant activated factor VII (NovoSeven, Denmark) induces hemostasis in life- and limb-threatening bleeds and in major surgery of hemophilia A and B patients in the presence of inhibitors. More than 6500 patients have been treated, and NovoSeven has been administered in more than 180,000 standard doses.9295 One theory for the mechanism of NovoSeven states that factor VIIa binds to activated platelets and activates small amounts of FX independent of tissue factor and that the platelet surface FXa can restore platelet surface thrombin generation in hemophilia. Studies have shown that full thrombin generation occurred after the addition of up to 150 nm of recombinant FVIIa.96 NovoSeven is useful in hemophilia patients who have developed inhibitors to factor VIII. In one case of hemophilia A,97 the patient had not received factor VIII concentrates since 1997 and had a history of recurrent spontaneous joint dislocations with bleeding. Although porcine factor VIII was an option for hemophiliacs with inhibitors, it was illadvised because of allergic reactions to the product in the past. Instead, NovoSeven was administered during shoulder surgery; not only was a dry surgical field maintained during surgery but hemostasis was achieved long after