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Can canine fresh frozen plasma be thawed in a microwave? | VETgirl Veterinary Continuing Education Podcasts

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In this VETgirl online veterinary continuing education podcast, we review whether or not you can thaw your unit of Fresh Frozen Plasma (FFP) in the microwave versus in the more traditional warm-water bath.

Plasma – or what we criticalists call “liquid gold” – is used to help replace essential clotting factors in patients that have either consumed their clotting factors (e.g., DIC), have an inherent clotting factor deficiency (e.g., von Willebrands), have suffered a drug toxicity (e.g., anticoagulant rodenticides), or are experiencing organ damage preventing them from supplying an adequate amount of clotting factors (e.g., hepatotoxicants like sago palm, xylitol, etc.). Plasma can also be used to replace the ever-so-essential protein, albumin, but it must be given in quite high volumes (45 ml/kg to raise albumin by 0.5-1.0 g/dL, compared to only 10 ml/kg to treat a coagulopathy). Plasma can be purchased from canine and feline blood banks in the form of fresh frozen plasma, which contains clotting factors and albumin, or as frozen plasma (FP). With FFP, these factors and albumin remain stable for up to one year if stored properly at -30°C. If the plasma is thawed and re-frozen, or if the plasma is over a year old (stored at -30°C the whole time), then this plasma is called “frozen” plasma and is deficient in factors V and VIII. Frozen plasma still retains the other clotting factors as well as albumin and is good for another 5 years. BTW, frozen plasma is ideal for anticoagulant rodenticide toxicity patients!

When clinicians require FFP for replacing a patient’s coagulation factors, these situations can be time-sensitive emergencies such as in the case of hemorrhage. Unfortunately, the plasma thawing process delays the administration of this potentially life-saving transfusion to the patient. In veterinary medicine, we typically use traditional warm water baths to thaw the plasma. The downside to the warm water bath method of thawing are 1) time to thaw 2) contact between the plasma bag and the water which could potentially lead to contamination of the plasma (Hence why VETgirl always recommends double bagging it in plastic Ziploc bags). In the human sector, they have microwave devices to permit faster thawing of the plasma with special devices used inside the microwave to limit superheating of the plasma and/or “cold spots” within the plasma.

So, Pashmakova out of Texas A&M University’s College of Veterinary Medicine wanted to evaluate this in a study called Stability of hemostatic proteins in canine fresh frozen plasma thawed with a modified commercial microwave warmer or warm water bath. Their study aimed to determine if thawing via a warm water bath or thawing via a modified microwave device created any degradation to the plasma product when using FFP. In this study, plasma was collected from 8 dogs that were donors at a blood bank and aliquoted into two 60 mL bags each and two 3 mL aliquots to be used for controls. These samples were kept frozen at the standard -20°C after collection up until the time of study. One bag from each dogs’ plasma samples was thawed via a modified commercial microwave (MCM) warmer until the surface of the bag reached 19°C. If the plasma was still partially frozen, the bag was agitated and returned to the microwave warmer until it again reached a surface temperature of 19°C. This process was repeated (typically 1 to 3 times) until all the plasma within the bag was thawed. The other bag of plasma from each donor was thawed by submersion in a warm water bath at 37°C until all plasma within the bag was completely thawed. The two 3mL plasma aliquots were thawed at room temperature (22°C), and served as controls for hemostatic protein testing, albumin, AT, fibrinogen concentrations, and PT/aPTT measurements.

So, what’d they find in this study? Analysis of the thawed plasma samples revealed significant decreases in concentrations of various hemostatic proteins when a MCM warmer was used compared to a warm water bath. Specifically, factors II, IX, X, XI, fibrinogen, vWF:Ag, vWF:CBA, AT, and protein C, as well as albumin, all had significant drops in concentration from the MCM warmer as compared to the warm water bath. These decreases in clotting factors translated to prolongation in both PT and aPTT times for plasma thawed via the MCM warmers. Factors VII, VIII, and XII were also significantly decreased in the MCM warmed plasma comparable to the decreases seen in the warm water bath-thawed plasma (likely a Type II error in the study).

Interestingly, plasma thawed by any method – including room-temperature thawing – produced elevated concentrations of D-dimers. The observers did not have a definitive explanation for the increase in D-dimers seen in all thawing techniques, and the clinical implications of this finding are not yet known. We know that D-dimers are produced as a degradation product of the breakdown of cross-linked fibrin (found in blood clots); as such, elevated concentrations of D-dimers indicates that clotting is happening in the bloodstream. D-dimers have been used as an indicator of thromboembolic diseases and are one of the criteria for diagnosing disseminated intravascular coagulation. So this discovery leaves the question unanswered: Could D-dimers found in the thawed plasma cause a significant elevation in our patient’s measured D-dimers after the patient has been administered a transfusion of thawed plasma? (That’s another study waiting to be done!).

It isn’t shocking that this study found that the MCM warmers produced the quickest thaw times of the plasma at a median of 184 seconds for a 60 mL bag. The warm water bath produced plasma-thawing times of a median of 348 seconds for a 60 mL bag. This paper did not list the average or median thaw time for its controls (e.g., room-temperature thawing), but since such small aliquots (3 mL samples) were used as controls, this time measurement wouldn’t be relevant in comparison to thawing a 60 mL bag of plasma.

Despite the microwave thawing method being much quicker than using the traditional warm water bath thawing method, plasma quality was deteriorated by this method. The observers found the MCM-thawed plasma samples to be grossly more turbid in appearance after thawing, which suggests that coagulation was activated in the bag during thawing. Fibrinogen is known to precipitate at 56°C and observers noted that the corners of the plasma bags where the plasma would be at its thinnest and subject to super heating is where the majority of white fibrin strands were seen. The presence of these white fibrin strands and overall plasma turbidity suggest that coagulation was occurring in the plasma bag during thawing and likely resulted in the consumption of clotting factors by this method.

So, what do we take from this VETgirl podcast? The findings in this study are in conflict to prior studies, which suggested that there was no significant difference in hemostatic factors as result of warm water bath and MCM thawing of fresh frozen plasma. However, these older studies only evaluated a handful of plasma hemostatic factors, whereas this study included a more thorough investigation into the hemostatic factors. In conclusion, based on the findings of this study, plasma should continue to be warmed at room temperature if time permits or in a controlled warm water bath to preserve the hemostatic factors. No microwaves, yo.

Abbreviations:
MCM = modified commercial microwave
vFW:Ag = von Willebrands factor antigen
vFW:CBA = von Willeband factor collagen-binding activity
AT = antithrombin
PT = prothrombin time
aPTT = activated partial thromboplastin time

References:
Pashmakova MB, Barr JW, Bishop MA. Stability of hemostatic proteins in canine fresh-frozen plasma thawed with a modified commercial microwave warmer or warm water bath. Am J Vet Res 2015;76(5):420-425.

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