Pathological process resulting in a rapid drop in packed cell volume (PCV), whole blood loss with rapid circulating volume depletion even before a drop in PCV is noted, or slow decline in PCV over time to below a critical threshold, often result in the need for blood transfusions to replenish lost erythrocytes and restore the oxygen-carrying capacity of the blood ^[1][8]. Horses require whole blood or packed red cell transfusion when the erythrocyte count, and, therefore, the blood oxygen delivery capacity, drops below the threshold at which increased tissue oxygen extraction can compensate for decreased oxygen delivery ^[2][9]. Whole blood loss can rapidly result in the need for transfusion, to replace circulating volume and maintain tissue perfusion.

Traumatic external whole blood loss anemia may be the easiest to quantify, as the clinician may be able to visually estimate the volume of blood lost and estimate the volume depleted. The time of onset and origin of blood loss may be apparent, helping the clinician to accurately estimate lost volume, and hopefully, ongoing losses can be curtailed. In human critical care, hemorrhage is graded I-IV, based on percentage blood loss with treatment criteria and evidence for prognostication associated with each grading ^[3][10]. Hemorrhage resulting in loss of a significant percentage of circulating volume is relatively straightforward to understand, as the same proportions of all blood components are lost at the same rate ^[1][8]. A cause of significant, often fatal hemorrhage in equids specifically, is carotid arterial hemorrhage secondary to mycotic infection of the guttural pouch ^[4][11]. Whole blood loss can occur into body cavities as well as externally, with the abdomen being the most common site, followed by into or around the reproductive tract and/or into the thorax ^[5][6][7][12,13,14]. Broad ligament hemorrhage can be a life-threatening occurrence in periparturient mares requiring emergency treatment, with lesions occurring most commonly in the proximal uterine artery ^[8][9][15,16]. Certain surgeries in vascular regions are associated with acute hemorrhage, specifically surgery of the sinuses, ethmoid turbinates and vascular structures ^[10][11][17,18], which are discussed in greater detail in the surgical hemorrhage section. Whole blood loss can also be due to hemostatic disorders in the face of usually insignificant trauma ^[12][13][14][3,19,20].

Certain surgeries are associated with an increased risk of both intra- and postoperative hemorrhage. As mentioned above, these include surgeries involving the head and paranasal sinuses, reproductive tract and spleen, as well as the foot, and various foreign-body and tumor removal surgeries ^{[15][16][17][18][19][20]}[21,22,23,24,25,26]. Intraoperative hemorrhage is deemed to be a surgical complication if it is unexpected and/or severe enough to warrant blood transfusion ^[21][27]. It can hamper the surgical field of view and result in a number of sequelae, such as anemia, postoperative seroma formation as the free blood within the surgical site coagulates and the clot contracts leading to a seroma, and surgical site infection. Even mortality induced by hemorrhagic shock has been reported ^[16][21][22,27]. Careful preoperative screening prior to elective procedures, as well as proper surgical planning, can help to reduce the risk of complications associated with intra- and postoperative blood loss ^[16][21][22,27]. A thorough history-taking may highlight pertinent features such as recent use of non-steroidal anti inflammatory drugs (NSAIDs) or other drugs known to impair coagulation ^[21][27]. Physical examination may highlight potential issues such as pallor or petechiation, or other findings, which could prompt clinical pathologic assessment. Careful attention should be paid not only to hematologic values, but also to liver enzymes ^[21][27]. If pre-anesthetic screening indicates, further coagulation testing should be performed. In elective cases, the option exists to delay the surgery to facilitate investigation and treatment, or at least, to allow for sufficient preparation.

Where a patient is identified as being at increased risk of intraoperative hemorrhage, attention should be paid to positioning. For example, where paranasal sinus surgeries are performed under general anesthesia, the horse can be positioned in reverse Trendelenberg (elevating the region being operated on relative to the heart, to reduce perfusion and, therefore, reduce hemorrhage) to reduce blood loss ^[21][27]. Depending on the surgical site, tourniquets can be applied if blood loss from the distal limb is anticipated ^[18][24]. Good anatomical knowledge of the intended surgical site is essential to identify and isolate major blood vessels in order to avoid iatrogenic damage to such vital structures which could result in hemorrhage, as well as employing best surgical practice in line with Halsted’s principles, which are the seven pillars of excellent surgical technique, including gentle tissue handling, meticulous hemostasis, obliteration of dead space, asepsis, preservation of blood supply, gentle tissue handling and accurate apposition of tissues ^[22][28]. Surgical preparedness is essential for responding to, and minimizing, hemorrhage where it occurs ^[22][28]. Where intraoperative hemorrhage occurs, efforts should be made to record the volume of blood lost, to monitor on-going losses and facilitate later transfusion calculations if necessary. Where hemorrhage occurs, surgical hemostasis techniques can include mechanical hemostasis, such as the application of pressure and use of ligatures and vascular staples ^[22][28]. Thermal hemostasis using electrosurgery, and chemical hemostasis, such as use of topical epinephrine to achieve vasoconstriction, are commonly used. Various sponge materials are available (e.g., gelatin foams, celluloses and collagen) which can be applied topically to wounds to provide a scaffold for clot formation ^[22][28]. In cases of bleeding from bone, topical bone wax can also be applied ^[22][28]. Where surgical hemostasis techniques fail, medical options are the next logical step. Antifibrinolytic lysine analogues (e.g., aminocaproic acid and tranexamic acid) act by inhibition of clot breakdown, and can contribute to achieving hemostasis in emergency situations ^[22][28]. The decision for blood transfusion should not necessarily be left to the final option. Several factors should be considered before deciding to perform a blood transfusion, as outlined below.

Abnormalities in any aspect of the coagulation cascade can lead to excessive bleeding in response to usually unremarkable levels of trauma ^[23][24][29,30]. Disorders of hemostasis can be genetic or acquired. Genetic/heritable coagulopathies include Won Willebrand’s disease, Hemophilia A, inherited Prekallikrein deficiency, and Glanzmann’s and atypical Thrombasthenia ^[23][29]. These conditions are characterized by a heritable lack of production of specific proteins in the coagulation cascade. Acquired coagulopathies have a broader range of inciting causes. The two most common are disseminated intravascular coagulation (DIC) secondary to endotoxemia, and purpura hemorrhagica (PH). PH is a severe complication of Streptococcus equi var equi infection, vaccination and rarely Corynebacterium pseudotuberculosis infection ^[25][31]. In all these cases, the horse’s ability to clot adequately is decreased, which may result in excessive and hard to control hemorrhage.

Anemia is defined as a decrease in erythrocyte concentration in the circulating blood. Anemia can be acute or chronic, can have a varying degree of clinical significance, and has an extensive list of differentials. Anemia can be initially divided into two categories, decreased red blood cell production, and increased red cell loss ^[13][19]. Post hemorrhage anemia occurs in the 3–28 days following blood loss, when the plasma volume has returned to normal, but the erythrocyte concentration has not yet rebounded ^[3][10].

Anemia attributable to decreased erythrocyte production is either primary, due to immune-mediated or neoplastic destruction of the bone marrow, or secondary, due to a systemic, extra-hematopoietic-system insult. Primary bone marrow destruction may be transient or permanent, due to immune-mediated or neoplastic conditions. Secondary bone marrow suppression is due to chronic disease, absolute iron deficiency, viral infection, plant or medication toxicosis, or heavy metal toxicity ^[12][13][14][3,19,20].

Anemia caused by increased destruction of erythrocytes is classified as either intravascular or extravascular. Intravascular hemolysis occurs when erythrocytes are lysed and destroyed within the vascular space. Extravascular hemolysis leads to anemia when an excessive number of erythrocytes are removed from circulation, by macrophage populations in the spleen, liver and bone marrow. Extravascular hemolytic anemia uses physiological erythrophagocytic mechanisms, with excessive efficiency usually due to changes in the structure, antigenic expression or pliability of the erythrocyte membranes, inducing increased elimination from circulation and breakdown ^[26][32].

The hallmark of intravascular hemolysis is the lysis of erythrocytes within the circulating space, causing discolored serum, hemoglobinemia hemoglobinuria ^[27][33]. Mechanisms inducing intravascular hemolysis are varied but include toxin ingestion, envenomation particularly by rattle snake, metabolic disturbances, intracellular parasitemia, and iatrogenic administration of fluids of improper tonicity ^{[28][29][30][31]}[34,35,36,37], but causes can be varied and individual.

Anemia of chronic disease is one of the most common causes of anemia in horses, with a complex pathophysiology. In horses, as in people, chronic inflammation leads to decreased naturally occurring erythropoietin (EPO) production and simultaneously attenuated bone marrow response to EPO, while chronic inflammatory conditions increase erythrocyte breakdown due to increased hemophagocytosis by macrophages. This leads to sequestration of iron within the phagocytic cell populations and depletion from the erythrocyte precursor cell lineages, while inflammation increases hepcidin concentrations, further sequestering biologically-available iron stores ^[32][33][38,39]. The use of recombinant human erythropoietin (rhEPO) is a controversial topic in equine medicine, as it has been used in some cases in an attempt to increase red cell volume, and, therefore, oxygen carrying capacity in performance horses ^[34][40]. It is, of course, banned in that capacity for competition horses, and has been associated with fatalities, erythroid hypoplasia, and anemia, so it is not advised for use in equines ^[35][41]. rhEPO is now frequently screened for in anti-doping labs, using specific antigens against the recombinant human proteins in equine plasma ^[36][42] and is not recommended for use in clinical cases of anemia, instead, addressing the underlying issues is recommended, and allowing the horse to recover PCV naturally.

There is a subset of cases where whole blood transfusion may be beneficial, even when the PCV is normal. If blood components are not available to the practitioner, administration of a whole blood transfusion may provide lifesaving clotting factors ^[24][30], albumin, and plasma proteins to restore oncotic pressure to the horse. Additionally, in rare circumstances such as carbon monoxide poisoning, transfusion may be required to provide erythrocytes with oxygen carrying capacity even when the absolute erythrocyte count is normal ^[37][43].