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Should you use FFP in your critically ill veterinary patients? | VETgirl Veterinary Continuing Education Podcasts

In today’s VETgirl online veterinary continuing education podcast, we review whether or not you should use fresh frozen plasma (FFP) in your critically ill veterinary patients. Do you use FFP in your practice? What clinical situations prompt you to consider its use? Bleeding patients? Patients with prolonged clotting times? Patients with hypoalbuminemia or pancreatitis? Before we discuss our use of FFP and the evidence (or lack thereof!) behind it, let’s make sure we’re all on the same page about what FFP is. It’s plasma that has been separated from whole blood and frozen within 8 hours, and it contains not only our coagulation factors, but also anticoagulation factors, fibrinogen, albumin and alpha-macroglobulins. Once it’s frozen, it can be stored for up to one year. [After which, it becomes expired plasma or frozen plasma (FP), which still has it’s uses!]

In general, human and veterinary patients are administered FFP for two major reasons: either to stop active bleeding, or to prevent it. Interestingly, the use of FPP in human medicine continues to grow, and a large proportion of patients receive it for prolonged clotting times alone, even though they don’t have evidence of clinical bleeding or a perceived risk of clinical bleeding.1,2 These critically ill patients are of particular interest in both human and veterinary medicine, since little evidence exists to support giving them FFP, yet many of us continue to do it. Not only is FFP transfusion costly, it is also associated with risks, including reactions that can range from mild to life-threatening, transfusion-associated cardiac overload (TACO), and transfusion-related acute lung injury (TRALI). Because of these reasons, it is important to understand when we should – and when we shouldn’t – administer FFP to our patients.

So Beer et al3 out of University of Pennsylvania School of Veterinary Medicine discussed the physiology of the normal coagulation system, what happens in disease, associations between coagulopathy and risk of bleeding, and evidence in human and veterinary medicine to support or refute the use of FFP in critically ill patients. While the classic model of coagulation, which involves two separate parts of primary and secondary hemostasis, is helpful for understanding coagulation testing, a newer model of coagulation is more accurate in terms of what actually happens in the body. This model is called the cell-based model, and it involves three overlapping phases (e.g., initiation, amplification and propagation) and two cell types: tissue factor-bearing cells and platelets.4 The cell-based model provides a more global picture of how coagulation occurs – in a number of overlapping steps involving primary and secondary hemostasis at the same time.

The classic tests of coagulation used to look for hypocoagulable states are the prothrombin time (PT) and activated partial thromboplastin time (aPTT). These tests were originally developed to look for factor deficiencies in human patients with bleeding tendencies like hemophiliacs and to monitor warfarin therapy. Other tests include the international normalized ratio (INR) in human patients, which is a standardization of the PT test, and thromboelastography (TEG), which provides a more global assessment of coagulation. Currently, PT and aPTT are still the most commonly used tests in veterinary medicine for evaluation of hypocoagulability.

In human medicine, prolonged clotting times are fairly common in critically ill patients (14-28%) and are a strong predictor of mortality.5 While the incidence is unknown in veterinary medicine, coagulopathy of critical illness likely occurs for the same reasons. Widespread inflammation in the body triggers activation of mononuclear and endothelial cells, exposes tissue factor and activates coagulation. At the same time, anticoagulant mechanisms become impaired. A tip in the balance of coagulation and anticoagulation ensues, with initial hypercoagulability followed by hypocoagulability and critically low levels of platelets and hemostatic factors. So even though this happens, the bigger question is: are these patients at risk of bleeding when they become hypocoagulable? Should we give them FFP to try to prevent it?

Evidence in human medicine suggests that the presence of coagulopathy, defined by prolonged PT, aPTT or both, is not suggestive of a risk of bleeding.6 No evidence exists yet in our veterinary patients examining this association. Interestingly, human medicine evidence also suggests that the administration of FFP to patients with coagulopathy does not have any benefit if the patient is not actively bleeding. In veterinary medicine, very little evidence exists to support or refute the use of FFP, especially in critically ill patients. While hypoalbuminemia is an often-cited reason for giving FFP, one veterinary study showed no difference in pre- and post-FFP albumin concentrations, and since FFP contains a fairly small concentration of albumin, it is not a very effective means of increased serum albumin.7 While the use of FFP for disseminated intravascular coagulation is often discussed in veterinary medicine, there is no current evidence to support its use. And a study of FFP in canine patients with pancreatitis (to replenish antiproteases) revealed a higher mortality in dogs that received FFP, although illness severity scoring was not performed.8

So, what can we take away from this VETgirl podcast? In human medicine, the guidelines for use of FFP suggest it should be reserved for patients with active bleeding, or for patients with a risk of bleeding AND a planned procedure that might cause that bleeding. While no guidelines exist in veterinary medicine and further studies are needed, there are associated costs and risks to FFP administration. Because of this, the potential risks and benefits should be considered very carefully before deciding to transfuse a patient with FFP. This clinical practice review suggests that in critically ill patients with a coagulopathy, it may not be appropriate to administer FFP unless the patient is bleeding or at risk of bleeding, based on human guidelines and evidence. However, more evidence is needed in veterinary patients to examine these questions.

References:
1. Walsh TS, Stanworth S, Prescott RJ et al. Writing committee of the Intensive Care Study of Coagulopathy (ISOC) investigators. Prevalence, management and outcomes of critically ill patients with prothrombin time prolongation in United Kingdom intensive care units. Crit Care Med 2010;38:1939-1946.
2. Stanworth SJ, Walsh TS, Prescott RJ et al. The Intensive Care Study of Coagulopathy (ISOC) investigators. A national study of plasma use in critical care: clinical indications, dose and effect on prothrombin time. Crit Care 2011;15:R108.
3. Beer KS, Silverstein DC. Controversies in the use of fresh frozen plasma in critically ill small animal patients. J Vet Emerg Crit Care 2015;25(1):101-106.
4. Smith SA. The cell-based model of coagulation. J Vet Emerg Crit Care 2009;19(1):3-10.
5. Levi M, Opal SM. Coagulation abnormalities in critically ill patients. Crit Care 2006;10(4):222-231.
6. Segal JB, Dzik WH. Paucity of studies to support that abnormal coagulation tests predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion 2005;45:1413-1425.
7. Snow SJ, Jutkowitz LA, Brown AJ. Trends in plasma transfusion at a veterinary teaching hospital: 308 patients (1996-1998 and 2006-2008). J Vet Emerg Crit Care 2010;20(4):441-445.
8. Weatherton LK, Streeter Em. Evaluation of fresh frozen plasma administration in dogs with pancreatitis: 77 cases (1995-2005). J Vet Emerg Crit Care 2009;19(6):617-622.

Abbreviations:
aPTT: activated partial thromboplastin time
FFP: fresh frozen plasma
INR: international normalized ratio
PT: prothrombin time
TEG: thromboelastography

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