Transfusion support for the bleeding patient (Proceedings)

Transfusion of blood products is an important lifesaving measure performed frequently in veterinary medicine. The decision to transfuse should not be taken lightly: it is costly and can frequently be clouded by complications. Blood transfusion therapy should be limited to the treatment of anemia, hypoproteinemia, coagulation disorders, or hemodynamic instability. The following review will focus on practical considerations of blood product therapy, including component selection, administration rates, monitoring techniques and transfusion complications, and the use of hemoglobin based oxygen-carrying fluids.

There are limited reasons for which to transfuse a patient. Anemia is the most common reason. Careful evaluation of the underlying cause of anemia should be considered. Anemia can be defined as a decrease I n the number of red blood cells. There are two types of anemia: regenerative and non-regenerative. If the anemia is regenerative, the bone marrow is functional and the anemia will resolve, provided the underlying cause of anemia is treated. Non-regenerative anemia is generally associated with a chronic illness in which the bone-marrow production is insufficient. The cause of the anemia needs to be treated indefinitely.

Keep in mind that every anemic patient that is admitted does not necessarily need to be transfused: the type of anemia must be established, and the cause of the anemia must be found. The duration of the anemia must be determined, and the trends of the PCV/TS must be monitored carefully. (This will be discussed in a later section.)

Hypoproteinemia is another reason to transfuse a patient. Severe protein deficiency (regardless of the cause) can result in pulmonary edema, pleural effusion, abdominal distension (ascites), or subcutaneous edema. Conditions severe enough to cause such clinical signs warrant transfusion of blood or blood products.

Lastly, a patient with a severe coagulation disorder may also require a blood transfusion. Note that not every patient with a coagulopathy requires a blood transfusion. If the coagulopathy results in severe anemia, transfusion medicine is applicable. Patients with thrombocytopenia should not be transfused solely on the platelet count. It would take large amounts of fresh, whole blood to raise a patient's platelet count by a mere 10%. Most coagulopathic patients require clotting factors, not necessarily just the platelets, to help correct a coagulopathy or to prevent hemorrhage. Careful consideration to the type of blood product is vital. (This will be discussed in a later section). The severity of the coagulopathy must also be considered in a timely fashion. For example, a patient that has ingested rodenticide and a patient in DIC would not necessarily be treated in the same fashion, although both are coagulopathic. It is not necessary to transfuse all rodenticide toxicities, nor every DIC patient. The severity of the anemia, the severity of the coagulopathy, and the overall systemic stability of the patient should first be evaluated.

Knowing when to transfuse is critical. The PCV/TS is not the only factor in making this decision. Patient history is extremely important, as well as the duration of the illness. For example, if a patient presents with a PCV of 13, transfusing the patient on this number alone is not founded. This patient with a PCV of 13 might have chronic renal failure and have been at 13 for weeks. Again, establish whether the anemia is regenerative or non-regenerative and carefully evaluate the patient systemically (i.e.: respiratory pattern) to establish proper compensatory mechanisms to the anemia. Conversely, if a patient with a low PCV had history of trauma, suspect abdominal or thoracic bleeding. Evaluate each cavity radiographically (or by centesis, ultrasound), and make the decision to transfuse based on hemodynamic stability (blood pressure, pulse quality), and ventilatory patterns.

Monitoring the trends of the PCV/TS is essential. Know the baseline PCV/TS before fluid administration, before transfusions, before diagnostic tests. If possible, do not take the PCV from a catheter, be consistent with how long the hemocrit tube is spun and who reads it, in order to eliminate margin of error. Understand exactly what a PCV determines, and the value of the total protein.

Component Selection

The following list categorizes the type of blood product and what it supplies to the recipient:

     1. Stored whole blood

          a. Supplies RBC's (increases oxygen delivery to tissues)

          b. Supplies plasma proteins (oncotic volume expansion)

          c. Supplies stable coagulation factors (fibrinogen)

Please note that whole blood does not supply platelet or labile coagulation factors V and VII.

     2. Fresh whole blood

          a. Supplies viable platelets and all clotting factors

          b. Supplies RBC's (increases oxygen delivery to tissues)

          c. Supplies plasma proteins (oncotic volume expansion)

Please be sure a fresh, whole blood transfusion is needed over a stored whole blood transfusion. It is an expensive and time-consuming process to the technician, donor, and to the recipient.

     3. Packed RBC's

          a. Supplies red blood cells only

Most RBC's bought commercially contain the saline reconstitutive agent in the packaging. If the packed red blood cells are made by collecting whole blood and spun down, then saline should be added prior to administration, in order for proper flow through both IV catheter and IV pump sets.

     4. Fresh frozen plasma

          a. Supplies all labile coagulation factors, including Factors V and VIII.

          b. Supplies Con Willebrand's Factor

          c. Supplies plasma proteins

          d. Does not supply viable platelets

*Please note that fresh frozen plasma is separated plasma frozen within 6 hours of collection. This differentiates it from regular frozen plasma, which is devoid of coagulation factors and only supplies plasma proteins.

     5. Platelet-rich plasma

          a. Supplies viable platelets

          b. Supplies plasma proteins

          c. Supplies all coagulation components

*Platelet transfusions provide little support for circulating platelet levels, particularly patients with immune-mediated disorders. Platelet life span is only a few hours! This is a very expensive and time-consuming product to make.

     6. Cryoprecipitate

          a. Supplies a higher concentration of Factor VIII, Von Willebrand's, and fibrinogen per ml over fresh frozen plasma

Advantages of cryoprecipitate include a smaller amount needed over larger doses of fresh frozen plasma, of particular importance if a patient is already volume impaired (vascular overloaded).

Clinical indications on the type of blood product are very important. The following table suggests guidelines of component selection based on clinical findings:

Blood typing and cross-matching

Blood typing is a process by which the red blood cells and serum are separated to determine which antigens appear on a patient's red cells and which antibodies against these red cell antigens are present in a patient's serum. The sole reason to blood type is to prevent the risk of a transfusion reaction. Blood typing is now very inexpensive (less than $10.00) and only takes a few minutes to run. It could save your patient's life.

For felines, there is only one blood group system, the AB system. There are only three types, type A, type B, and type AB. Type A is the most common. Unlike dogs, cats have a natural-occurring antibody (called alloantibodies) against other blood types. Life threatening hemolytic transfusion reactions will occur if the alloantibodies are present in a recipient's system. Again, type A is the most common blood type in cats, with greater than 80% DSH being type A. Type B cats are usually found in the purebred cats (i.e.: Abbysinian, Devon Rex). If type B cats are given type A blood, a fatality will most likely occur. IF type A cats are given type B blood, mild reactions may occur. In short, type all cats! It is cheap and only takes a few minutes to run.

In the canine, there are eight blood groups: DEA (dog erythrocyte antigen) 1.1, 1.2, 3, 4, 5, 6, 7, and 8. DEA negative 1.1 is the most common. Note that you can transfuse a DEA positive dog with negative blood, but transfusing a negative dog with positive DEA blood could be fatal. The most severe immune-mediated reactions are seen with DEA 1.2, DEA 1.2, and 7 blood types. Reactions related to other antigens are generally considered clinically insignificant: naturally occurring isoantibodies to these antigens do not occur in the dog. Thus, immune-mediated reactions are unlikely to occur on initial transfusions. If multiple transfusions are expected, or if the patient has had a transfusion within the last 12 hours or ever in its history, cross matching is essential. Note blood donors and blood type on the patient's record.

Transfusion Reactions

Transfusion reactions are categorized as immune-mediated and non-immune mediated, as summarized below:

     1. Immune Mediated Reactions

          a. hemolytic reactions

          b. antibodies to RBC's present

          c. reactions may be acute (previous transfusions = pre-existing isoantibodies) or delayed, occurring 2-21 days post transfusion

     2. Non-Immune Mediated Reactions

          a. Vascular overload (exceed normovolemic rate)

          b. Reaction from citrate anticoagulant (rare)

          c. Pulmonary microembolism (no filter used)

          d. Improper handling of blood products (poor technique or contaminated product)

Clinical signs of a reaction include restlessness, hyper-salivation, fever, vomiting, tachypnea, pruritis, urticaria, and muscle tremors. The treatments of a transfusion reaction include discontinuing the transfusion, administration of corticosteroids (1mg/lb), administration of diphenhydramine (1mg/lb IV), administration of crystalloid fluids, lasix administration (2mg/kg) if suspecting a vascular overload, and calcium gluconate slow IV (1ml of a 10%solution/kg) if suspecting citrate intoxication. In order to prevent transfusion reactions, cross-match and blood type. Pre-medicate the patient with diphenhydramine and/or corticosteroids, and follow proper administration rates and monitoring procedures.

Administration Rates

The following table summarizes suggested administration rates for the critical patient. It is important to note that administration rates may vary, depending on patient status and history.

               Normovolemic rate           3.0-6.0 ml/kg/hr           over a maximum of 6 hours

               Hypovolemic rate             10-20ml/kg/hr               over a maximum of 6 hours

               Cardiac patient rate           2.0-4.0 ml/kg/hr           over a maximum of 6 hours

After calculating the maximum rate to be given, start out by administering one-fourth the desired rate for the first 30 minutes. If there are no signs of reactions, increase the rate to one half the desired maximum rate over the next 30 minutes. The rate of maximum administration should only be given at the end of the first hour of transfusion, provided that the patient exhibits no signs of reaction. A filter must be used for any type of blood product.

Monitoring Techniques

It is recommended to provide a type of transfusion sheet for proper patient monitoring. A baseline TPR, including pulse quality and ventilatory pattern, should be recorded. Auscultation is important to also monitor lung sounds, which may change during a transfusion due to pulmonary or vascular overload. A baseline PCV/TS should also be recorded both before and after a transfusion. Once the transfusion is in progress, obtaining a TPR, pulse quality, ventilatory pattern, and patient mentation every 15 minutes for the first 30 minutes, and then every hour during the transfusion, is important to avoid patient compromise. Feeding the patient during the transfusion is not recommended, as vomiting may occur.

TREATMENT ALTERNATIVES FOR ANEMIA: THE USE OF HEMOGLOBIN BASED OXYGEN CARRYING SOLUTIONS

Providing blood products to patients is often difficult. The availability of blood may be limited because of great demand or expense to house donors. Typing and cross matching are very important but require accessibility to technical help or laboratories that have the capability of performing such tests. Transfusion reactions can compromise patients, prolong hospital stay, and in some cases can cause death. Blood borne disease transmission can occur without proper donor screening, adding additional costs to donor programs. Because of difficulties in obtaining compatible, disease-free blood, oftentimes the administration of a transfusion is delayed with the hope that the animal will recover without the need for blood. Alternative treatments for anemia in veterinary medicine are now available through hemoglobin-based oxygen carrying solutions such as Oxyglobin. Oxyglobin solution can be stored at room temperature, administered though a standard intravenous set without the need for a filter.

Oxyglobin solution contains 13g/dl of purified, polymerized hemoglobin in a modified Lactated Ringers solution. It is a sterile, dark purple solution with a pH of 7.8. The average molecular weight of Oxyglobin is 200kD. This molecular size is comparable to some of the synthetic colloids such as dextran or hetastarch. These solutions contain large molecules that do not freely cross membranes into the interstitial space. They remain in the vasculature longer than crystalloids, drawing water from the interstitium into the vasculature, thereby expanding the intravascular blood volume. Like other colloids, Oxyglobin will expand intravascular volume but will also carry oxygen, unlike synthetic colloids. The hemoglobin in the Oxyglobin has a lower affinity for oxygen than does the hemoglobin of canine blood, therefore, it on-loads and off-loads oxygen more easily than red cell hemoglobin. Oxyglobin has a low viscosity, similar to crystalloid fluids. This property also improves delivery of oxygen to the tissues because the fluid flows more easily in comparison to blood. By virtue of Oxyglobin's low viscosity and low oxygen affinity, oxygen delivery to the tissues is immediate.

Oxyglobin is universally compatible, containing no red blood cell membranes, the inciting cause of transfusion reactions and incompatibility problems. Blood typing or cross matching is unnecessary for its use. In addition, it has a three-year shelf life unlike the three-week expiration of blood products.

Oxyglobin increases the oxygen content of plasma. Normally, the hemoglobin in the red blood cell carries 98% of the oxygen in the blood. Only 2% of the oxygen in the blood is dissolved in the plasma. Because Oxyglobin is in contact with the wall of the blood vessels, continuous delivery of oxygen is provided to the tissues. Oxyglobin also improves the efficiency of oxygen delivery from the existing red blood cells by increasing the solubility of oxygen in the plasma that surrounds the red blood cells. In this way, Oxyglobin improves the diffusion of oxygen from red cells to the tissues.

Arterial oxygen content is determined by the amount of hemoglobin in the blood. In the presence of Oxyglobin, oxygen is also carried by hemoglobin in the plasma. Thus, arterial oxygen content is determined by the hemoglobin content of the red blood cell and by the plasma. Oxygen delivery is based on arterial oxygen content and cardiac output. Cardiac output is a measure of the heart's ability to circulate blood. Heart rate is a rough clinical estimate of cardiac output. With anemia, the cardiac output and heart rate increase. Non-oxygen carrying fluids such as crystalloids increase blood flow and hence cardiac output to increase oxygen delivery. With Oxyglobin, the oxygen content of the blood is increased so that oxygen delivery improves without increasing cardiac work and heart rate. Most often, the heart rate of an animal decreases with Oxyglobin administration

The recommended dosage of Oxyglobin is 30ml/kg administered intravenously at a rate not to exceed 15ml/kg/hr. As with any administration of any type, the patient should be evaluated first and rates calculated on a case-to-case basis. Because Oxyglobin is a colloid, it will expand plasma volume. Patients receiving Oxyglobin should be monitored for vascular overload by CVP monitoring or simple observation of ventilatory patterns and frequent auscultation. Because Oxyglobin is carried in the plasma, the plasma of the recipient will be discolored slightly, as can the patient's sclera and urine. This discoloration may result in artifactual increases or decreases in the results of some serum chemistry tests, depending upon the type of analyzer used. Thus, samples should be collected from the patient prior to use of Oxyglobin. Electrolytes, coagulogram, and BUN are valid on all analyzers. More specific information can be obtained through the phone number listed on all package inserts. Serum discoloration is dose dependant, and should resolve 3-5 days post administration.

The hemoglobin in Oxyglobin is a protein. The protein will foam if the bag is shaken and may cause pump error on administration. Oxyglobin should be used within 24 hours of opening the bag to avoid bacterial contamination and changes in the hemoglobin structure due to exposure to oxygen. The solution should not be transferred to another collection system to avoid bacterial contamination. Oxyglobin can be used concurrently with any blood products and multiple uses do not require patient preparation such as cross matching.