Blood Transfusion cryoprecipitate: The director of clinical virology and vice-chair practice in the Department of Laboratory Medicine and pathology at Mayo Clinic transfusion of cryoprecipitate is used for patients. who are in need of fibrinogen replacement and occasionally for inherited disorders. In this month’s hot topic my colleagues from the component laboratory. The division of transfusion medicine will discuss a process of improvement that helped to decrease.
The standard cryo precipitate dosage and the positive impact on patients. I hope you enjoyed this month’s hot topic. I want to personally thank you for allowing Mayo Clinic the opportunity to partner in your patients. We are talking to you about the secrets of cryoprecipitate a blood baking process improvement the objectives of this presentation, Are what is crowd precipitate discuss product storage and requirements for manufacturing. What are some indications for use defining the standard dosed and describe the process improvement of Kyra precipitate in detail?
cryoprecipitate: Crowd precipitate often called cryo is a frozen blood product prepared from fresh frozen plasma. It is comprised of cold insoluble proteins that precipitate. when fresh frozen plasma also called FFP. It is thawed it is rich in plasma proteins such as factor 8 fibrinogen factor 13 von Willebrand factor and fibronectin. One of those components factor 8 is also called antihemophilic factor or AHF. Which is why cryo is sometimes called crowd precipitate anti hemophiliac factor or crowd precipitated.
Here is a thawed crowd precipitate pool ready for transfusion, they range in color from pale to dark yellow and can even appear as an even thick whitish liquid on a history note current cryo use. It is far removed from that, which it was originally intended. let’s have a broad overview of how cryoprecipitate is manufactured. Cryo is manufactured from fresh frozen plasma collected. whole blood donation fresh frozen plasma is for plasma frozen within eight hours of collection.
Why is freezing plasma with an eight hour significant for making cryo, research has shown the number of liable factors degrades overtime prior to freezing, FFP of the same ABO is slowly thawed at 1 to 6 degrees. Celsius until a slightly slushy consistency, is achieved this can be done by thawing in a refrigerator for 18 to 24 hours or a few hours in a cooling water bath here we have an F F P pulled from a water bath.circled are there precipitates that are visible prior to centrifugation. There are opaque white and appearance, once the plasma is thawed, the liquid plasma is separated from the Cryer precipitate by centrifugation utilizing a heavy spin.
This is done to concentrate the precipitates to the bottom of the bag, the precipitates will have a thick white to opaque ish consistency. It can be mistaken as a fibrin clot after centrifugation. The supernatant is removed by gravity drain or plasma expresser approximately 10 to 15 mils of supernatant plasma remains with the crab precipitate. It is used to resuspend those precipitates at this point. The cryo may be refrozen immediately or pooled pictured on the left. is a single cryoprecipitate containing approximately 25 to 30 grams of supernatant and the precipitate pellet circled are those factors the supernatant plasma pictured. on the right can be refrozen as a transfusible product, called cryo pour plasma. As a noninjectable product called recovered plasma, both crowd pore plasma and recover plasma are deficient of those cryo factors crowd pore plasma.
It is an injectable product, that is typically used for plasma exchange recovered plasma. It is an unlicensed product that can be shipped to manufacturers of plasma products to create a pool single. Claro is welded onto a pooling harness set the process of welding, Is sterile and allows the product to be a closed system. The single cryo is pulled to provide a single combined therapeutically effective blood product. Crowd precipitation is a 5 unit pool now let’s discuss the storage and shelf-life of cryo cram precipitate are stored at negative. 18 Celsius or colder and has a shelf life of one year for pooled cryo the expiry date.
It is determined to be 12 months from the earliest date of FFP collection, to prepare crowd precipitate for transfusion. It is thought quickly at 30 to 37 degrees Celsius and then stored at room temperature 20 to 24 degrees Celsius thought single cryo and pooled cryo. which are sterile II manufactured have a shelf life of six hours currently thawed cryo cannot be refrozen or refrigerated due to regulatory standards, fun fact refrigeration causes factors to reap recipient making it unsuitable for transfusion? each crowd product has to meet regulatory agency requirements. The Food and Drug Administration requires cryo to the quality control tested.
On at least four representative containers each month each unit must contain, a minimum of 80 international, units of factor 8, and a minimum of a hundred and 50 milligrams of fibrinogen times. The number of units in the pool per AABB standards, for example, Mayo Clinic Rochester manufactures pools of five units. Therefore the QC values we need to pass are greater than, or equal to 400 international units per pool effector,8 and greater than or equal to 750 milligrams per pool of fibrinogen, crowd precipitate was originally prepared.
As a source of factor 8 for hemophilia 8 patients and to treat patients with von. Willebrand’s disease is no longer the preferred product for treatment of hemophilia. A von Willebrand’s disease as coagulation factor concentrates are readily available patients, That benefit from crab precipitate are typically patients needing fibrinogen replacement. When clinical bleeding has occurred and individuals with disseminated intravascular coagulation or di C occasionally.
Cryo is transfused for inherited disorders of fibrinogen and uremic bleeding another indication for Crowl. It is during a massive transfusion and which helps to maintain hemostasis due to postpartum hemorrhage in surgical cases, such as cardiac gastrointestinal transplants, or trauma incidents just like other blood products. It is subject to misuse common misuse of cryo is a reversal of wherein therapy replacement therapy in patients with normal fibrinogen levels and treatment of bleeding, without evidence of fibrinogen deficiency.
It can also be underutilized in massive transfusions with dilution coagulopathy and bleeding. when choosing crowd precipitate for transfusion, Crowl should be selected as ABO compatible. In some instances, large volumes of cryo may cause a positive direct antiglobulin test and mild hemolytic transfusion reactions. This can be caused by the ISIL hemagglutinin anti a and anti B, however, cryo can be administered regardless of our age. This is due to the fact that neither plasma nor cryo precipitate contains red cell compatibility testing.
Is also not required transfusion of cryoprecipitate carries, The same risks as plasma transfusion potential risks and adverse events such as infection viral or bacterial volume overload and transfusion reactions. crowd precipitate has a lower risk of causing hemolytic transfusion reactions. Than plasma because of the smaller volume administered. Cryo is administered utilizing aseptic technique through a filter designed to remove clots. Aggregates transfusion is started before cryo expires and completed within four hours.
The standard adult dose of cryoprecipitate at Mayo Clinic Rochester is 10 units or two pools, with each pool containing on average 277 milligrams per unit. or 1389 milligrams per pool of fibrinogen external suppliers such as American Red Clara’s, provide plug products to others.Mayo campuses these sites are producing cryo pools of five units at dosages greater than 300 milligrams per unit. or greater than 1500 milligrams per pool. This allows for other Mayo campuses to drop their standard dose from 10 units to 5 units.
Mayo Clinic Rochester recognized the need to standardize and improve their concentrations to decrease, the patient does the goal was to drop. The adult dose from 10 units to 5 allowing ordering consistency across all. Mayo sites now that you have some background information of cryoprecipitate requirements and indications.let’s learn about a case study presented by Michelle Thank You.
A middle-aged man underwent a reoperation. A Horta surgery this surgery required a long cardiopulmonary bypass run and cooling of the patient to 18 degrees Celsius for a good duration. The patient started to bleed, A lot and like most, their new graft caused depletion of fibrinogen levels significantly. In the end, the patient was transfused 40 units of cryo, That’s five donors in each pooled Cryo 200 FFP.
We were manufactured into 200 single cryo and were used to create 40 pools, That means this patient was exposed to 200 donors, therefore if we benchmarked a process improvement, then this patient could have had fewer products less donor exposure and less inventory used on. one individual now let’s talk about this process improvement project. That took place in the component laboratory at Mayo Clinic Rochester, we experimented with 12 different process changes including, but not limited to centrifuge settings thaw rates and differing product manipulation.
Our group also toured other product manufacturers, to see their processes we re-evaluated multiple steps in the process, starting with implementing new thawing techniques, fresh frozen plasma varies in volume due to various donor factors.
It is important to thaw them evenly even thawing helps prevent some FFP from being completely thawed, while another FFP could be icy in the batch to slushy or too icy of a product, Is difficult to manipulate to increase. This chance that your products will thaw evenly. The process is now defined to choose FFP that is within 20 grams of each other.
We defined the desired consistency of thought FFP for best recovery, They should be thawed to a slushy or slightly slushy state, therefore impacting factor 8 as, It is a temperature-sensitive product, we also defined thought time. In the water bath as a reminder crowd precipitates are cold insoluble proteins. Therefore it is important to closely monitor, Thaw we implemented this by checking the FFP at approximately 1 hour 30 minutes and adding additional time as needed. when checking the products keep manipulation of the product to a minimum.
We don’t want to resuspend factors prior to senna friction heat is also important to factor. That can be negatively affecting the recovery next step, we investigated was centrifugation factors such as time speed like rpm and brake settings alter the force applied to the precipitates. We also investigated the fact since we have a Childress centrifuge. We should also chill the cup liners to prevent further unnecessary heat transfer here in the component laboratory. We have access to two different centrifuges for manufacturing.
So it is also important to have the settings match each other as a result of testing, We increased rpm time and adjusted brake settings for both centrifuges allowing products to spin faster and longer to get, the most recipients collected to the bottom of. The to bag the next change was looking at the separation of crowd precipitates and byproducts previous manufacturer’s separation of cryo was by inversion and draining. We noticed any free precipitates that did not get compacted into a pellet would drain into the supernatant to counterbalance. This we created a shelf the spun FFP would lie on the shelf and gravity drain horizontally.
This helps prevent the free precipitates from draining instead stay in the precipitate bag, we further emphasize keeping the product cold by laying the precipitate bag, on top of clothes on a raised shelf. while it’s draining we increase single cryo weight to 25 to 30 grams, with an optimum of 28 grams this helps ensure. we are only adding 10 to 15 milliliters of supernatant to resuspend the precipitates, prior to pooling increased weight also aided in removing, all of the precipitates from the product bag. The next process we re-evaluated was pooling. pooling ensures 5 single krauts are sterile II connected without being exposed to air contaminants.
This instrument works by placing tubing from two separate products into a clamp then a wafer is heated this slices the tubing while maintaining sterility and welds them, together with without any contamination. This process is repeated until all five single krauts are connected to the pooling harness set changes to the pooling process include. The use of a scraper no rinsing and reducing heat transfer. The second Article process which implemented the use of a scraper to mix the crowd precipitates, and plasma using a scraper every single unit is scraped and mixed until the precipitates are resuspended. ask then we visually inspect each bag. This is done to ensure there is no precipitate stuck to the proc bag.
If precipitates are found further mixing with the scraper is required the single, cryo is then drained by rolling into the pooling bag. This process is repeated for all five single crowns. ‘It’s the implemented process also advises no rinsing of the products. Unless there are precipitates that need to be further mixed and put into solution, this further reduces manipulation of the product between bags and prevents loss of product,and tubing lines and product bags. The previous manufacturing process required menu manipulation with our hands-free suspending the precipitates was done by massaging the single cryo with our hands.
Therefore the new process of using a scraper for mixing reduced hand heat transfer, the precipitate factors are greatly affected by temperature as exposure to excessive. The heat will significantly decrease the efficacy of the final product as you see in the article. We now roll the bags empty to make sure, all the products are removed from the individual bags into the pooling harness, that bag excess air is expressed from the final bank to prevent bag breakage. When it is frozen and the pooling bag, is then heat sealed off thus creating a five-unit cryo pool. The new manufacturing process was validated to increased average fibrinogen of greater than or equal to 14 50 milligrams per crowd pool and was implemented.
November 5th of 2018 part of the ongoing process improvement, we are continuing to monitor our results since implementation pre-intervention of our factor. H average results were 823 international units per pool post-intervention. a factor 8 average results are 782 international units per pool .we are not just concerned about this decrease because it is still. well above regulatory requirements cryoprecipitate is not typically used for the treatment, 2 factors 8 deficiencies because of factor 8, concentrates are readily available for use. However, these values will continue to be monitored pre-implementation fibrinogen average results. were 1389 milligrams per pool post-implementation fibrinogen average, is now fifteen hundred and seventy-four milligrams per pool in conclusion.
The process improvement will help standardize the cryoprecipitate dosage and benefit, the patient as the needs of the patient come first, the process change led to decreasing the adult standard dose of two pools to one pool per transfusion, furthermore it reduced donor exposure from 10 donors to 5 donors exposure to multiple donors creates. An increased incidence of transfusion reactions and potentially.
A higher risk of disease transfer the process change might also increase inventory, Which is especially helpful when Crowl usage is higher than normal, it could also be potentially cost-saving for patients.when they would only pay for one cryo pool and a shorter transfusion time with continual monitoring and potential improvements. The joseph´s change was recently effective to summarize, what we presented cryoprecipitate is cold insoluble proteins, that precipitated from fresh frozen plasma frozen. Cryo is stored at negative 18 degrees Celsius or colder and has a shelf life of one year thawed.
Cryo is stored at 20 to 24 degrees, cells is a closed system crowd pool has a shelf, life of six hours indications for use are for patients needing fibrinogen replacement and occasionally inherited disorders standard. The dose is now five units of single Kyle or one crowd pool, we hope you enjoyed the presentation here are our references for your perspective process improvement ideas and educational reading. we hope you found this presentation informative.