Editor’s note: This article extends the discussion of plasma-based transfusion therapy that appeared in the last issue of rvetILLINOIS. Read more on preparations for transfusion in the February issue of rvetILLINOIS.
Plasma is the liquid, non-cellular portion of blood constituting approximately 55% of whole blood in health. Over 90% of plasma is water, but the remainder contains vital proteins, hormones, electrolytes, and other nutrients.
Hypoalbuminemia—Cause and Consequence
By weight (and possibly by duty), albumin is the most substantial constituent of plasma. Albumin is the major oncotic protein in plasma and also serves as a carrier protein for lipophilic compounds. It plays a role in acid-base homeostasis via its action as a buffer molecule and also has antioxidant and anti-inflammatory properties.
Hypoalbuminemia is both a cause and a consequence of critical illness. Albumin synthesis may be impaired in hepatic dysfunction/failure for any cause (toxin, infiltrative disease, shunt, etc.). In addition, inflammatory conditions may lead to preferential hepatic synthesis of acute phase proteins, resulting in low plasma albumin concentrations simply due to a shift in priorities for hepatic machinery. This impaired albumin synthesis may be coupled with increased loss via inflammation-induced permeability of postcapillary venules. These factors combined may yield a clinically important hypoalbuminemia in inflammatory states. Albumin can be lost through the GI tract and the glomerulus when diseased, as well as through exudative wounds or proteinaceous cavitary effusions. Hemorrhage from any source will result in global loss of proteins alongside cellular blood constituents. This loss is most apparent after resuscitation with products devoid of protein (crystalloid fluids, synthetic colloid, and/or pRBC). Hypoadrenocorticism is also often associated with hypoalbuminemia, likely for multiple reasons including impaired synthesis and GI loss.
Hypoalbuminemia, a result of various types of illness and injury, creates a multitude of problems in its own right. These include poor wound healing and risk of intestinal dehiscence, cavitary effusions, tissue and organ edema, altered drug metabolism, increased risk of AKI and mortality in sick people. Even veterinary studies evaluating the impact of albumin therapy in sick dogs have documented an association between survival and higher serum albumin concentration.
Albumin Replacement Therapy
Though hypoalbuminemia appears to be a risk factor for death and morbidity in people, there is some controversy over whether or not replenishment of albumin via transfusion mitigates this risk. A 1998 Cochrane systematic review indicated increased mortality associated with albumin administration in critically ill patients (NNH 1 in 17). Since this time, the SAFE and ALBIOS trials suggested the opposite effect: that albumin-treated patients with severe sepsis or septic shock have improved survival over those treated with crystalloid. Similar information is not available for dogs and cats treated with albumin, be it allogenic or canine-specific. However, albumin transfusion does appear to be effective in raising plasma COP, blood pressure, and albumin concentrations early after administration in septic dogs. In animals, a survival advantage for albumin recipients over nonrecipients has not been discerned, but studies consistently indicate survival advantages in patients with higher serum albumin concentration regardless of treatment group.
Unfortunately, we have repeatedly learned that administration of human serum albumin (HSA) has the potential to elicit acute and delayed hypersensitivity reactions in dogs and cats. These reactions have been reliably documented in healthy dogs receiving HSA, but oddly critically ill dogs and cats appear less vulnerable. Multiple datasets indicate that sick animals receiving HSA are less prone to hypersensitivity reactions and early development of anti-human albumin antibodies. Despite this discrepancy, HSA is indeed capable of producing hypersensitivity reactions ranging in severity from mild to deadly even in sick pets. Importantly, repeat administration of HSA in dogs reliably causes immediate reactions during the second transfusion. Interestingly, some never-transfused, healthy animals possess anti-human albumin antibodies, which helps explain the type I hypersensitivity reactions noted in some of the human albumin recipients. Some have proposed that exposure to homologous bovine albumin in food or vaccine products can account for the development of these seemingly “natural” antibodies in some dogs.
Lyophilized canine-specific albumin is available in the U.S. and Canada and is generally safe upon initial as well as repeated administration in healthy dogs. Hypoalbuminemic, septic dogs have been treated with the product resulting in higher albumin, plasma COP and blood pressure two hours after administration when compared to similarly treated non-recipients. The albumin effect persists at 24 hours.
Practical Application of Albumin Therapy
Canine-specific albumin is label-indicated for treatment of hypovolemic shock or hypoalbuminemia regardless of etiology. Depending on the manufacturer, the product can be rehydrated to different concentrations ranging from 5% to 25% with various iso-osmotic diluents or sterile water.
According to one manufacturer, approximately 450 mg/kg is required to raise serum albumin by 0.5 g/dL with a suggested maximum dose of 2 g/kg. Enders et al. found that administration of 1 g/kg resulted in a mean increase in serum albumin of 0.48 g/dL at 2 hours. Speed of administration varies depending on the clinical situation. Lyophilized canine albumin is particularly useful in that it requires no cold-chain storage (except for up to 24 hours following rehydration). It is shelf stable for 3 years. The product is shipped at room temperature but one manufacturer recommends cold storage until use if possible.
Albumin transfusion should be considered in cases where hypoalbuminemia is leading to clinical consequences (e.g., enteropathy resulting in moderate to severe cavitary effusion). In this circumstance, the goal is truly to raise serum albumin to a degree that signs improve or, at a minimum, do not progress. Beyond this indication, canine-specific albumin can be used as an adjunct or alternative to crystalloid therapy in patients that are vulnerable to hypoalbuminemia and in those with multiple risk factors for tissue or organ edema (for example, dogs with acute inflammatory conditions such as sepsis or severe pancreatitis). Albumin transfusion can also be considered in post-surgical settings when the risk of dehiscence or poor wound healing is high. Because albumin is the sole constituent of this transfusion product, there is no worry about additional coagulation factors or inflammatory mediators creating a procoagulant state, which may be a particularly wise choice in highly inflammatory conditions wherein thrombosis is a concern.
A complete list of references related to this article may be found at https://vetmed.illinois.edu/2024/12/05/plasma-based-transfusion-therapy/
By Erin Long, DVM, DACVECC
