Transfusion medicine is the mainstay of therapy of hemostatic disorders, whether inherited or acquired. However, other compounds can also be used to facilitate hemostasis, including topical materials such as “fibrin glue”, gelfoam and topical thrombin (all of which aid with localized hemostasis), surgical hemostasis (tying off vessels appropriately, the use of electrocautery to cauterize small vessels), and drugs.
Antifibrinolytic agents (such as epsilonaminocaproic acid) have been used successfully to control local hemorrhage during dental surgery in human patients with vWD, but have not been used extensively in animals. These agents will only be useful when procedures are performed on sites with high natural fibrinolytic activity, such as the oral mucosa. Desmopressin, or DDAVP, is a drug that can be used to treat both diabetes insipidus and vWD.
Synthetic oxygen-carrying compounds (hemoglobin substitutes), such as Oxyglobin, have been produced and licensed for use in dogs. These products are a good alternative to blood transfusions for the treatment of hypoxia in acute anemias.
As a general rule, whole blood transfusions should be limited to those animals requiring coagulation factors, platelets, and red cells. Whole blood should not be given to animals with inherited hemostatic disorders, unless they are concurrently anemic and showing signs of hypoxia (weakness, lethargy, panting, etc). Even if red cells are required, component therapy using packed red cells and specific concentrates (e.g. cryoprecipitate) are preferable to whole blood. Remember that red cell transfusions run the risk of sensitizing the animal to foreign red cell antigens and thus expose the animal to the potential of future transfusion reactions. This can be quite significant in animals with inherited hemostatic disorders, as many will require multiple transfusions over their lifetimes, each transfusion increasing the likelihood of a reaction. However, sometimes, whole blood is the only material available for treatment of hemostatic disorders.
Some general points about administering transfusions:
- Any stored whole blood or packed red cell products that are discolored (brown), bubbly or hemolyzed should not be administered under any circumstances. Out-of-date products should not be given.
- Packed red cells should be diluted with sterile isotonic (0.9%) saline as the fluid is very thick and will flow sluggishly. Transfusion products should not be infused through the same line or catheter (unless the latter is flushed first with sterile saline) as Lactated Ringer’s solution, as this product (and others like it) contain sufficient calcium to overcome the citrate in the transfusion bag and cause clotting of the product. Furthermore, hypotonic solutions (5% dextrose in water) can cause hemolysis of red cell-containing products.
- Platelet-rich plasma should be infused optimally within 8 hours of preparation (and should be kept at room temperature and gently rocked until used). Refrigerated products should be warmed before transfusion (not > 37°C). Frozen products (FFP and cryoprecipitate) should be thawed rapidly at 37°C and used within 24 hours of collection (they can be stored refrigerated after thawing).
- Blood or blood components should be infused through a separate intravenous infusion set, using a 150 um filter.
- The transfusion should be administered slowly; running in the fluid as fast as possible is likely to produce transfusion reactions, including circulatory overload and anaphylaxis.
- The transfusion should be completed within 4 hours (of red cell-containing products in particular) in order to prevent bacterial contamination and growth (blood is an excellent culture medium for bacteria).
- The animal should be observed carefully for transfusion reactions, especially in the first 15 minutes of a transfusion (i.e. do not put the animal in a cage, start the transfusion, then walk away).
Strict attention paid to good transfusion techniques as outlined above will minimize transfusion reactions and will enable you to recognize them quickly and treat them appropriately.
Replacement of red blood cells
Red cells are required in animals with decreased oxygen-carrying capacity and clinical evidence of hypoxia. Clinical status, and not hematocrit, is the most important determinant of the need for red cell replacement. Clinical evidence of hypoxia is shown by pallor, tachycardia and tachypnea at rest, weakness, and exercise intolerance. A sudden drop in hematocrit is more likely to produce clinical signs, than slowly developoing anemias, which allow time for animals to adapt physiologically. Some animals with chronic anemia present with hematocrits as low as 10%, but are clinically stable. These animals do not need blood transfusions, unless unduly stressed by diagnostic procedures or hospitalization. Remember to crossmatch those animals in which it is required (e.g. untyped cats on the first transfusion, dogs on subsequent transfusions).
- Red blood cells can be provided as whole blood (fresh or stored) or packed red blood cells. The ultimate goal is to either normalize the hematocrit or alleviate clinical signs of hypoxia. The volume of whole blood to be transfused can be estimated from the following formula:
2.2 mL/kg will increase the recipient Hct by 1%
Transf. vol. = Blood vol. recip. x BW recip. (kg) x Hct desired – Hct recip.
where blood vol. = 70 mL/kg (dog), 50 mL/kg (cat)
Replacement of platelets
Replacement of platelets is indicated in severely thrombocytopenic animals (< 30,000/µL). However, administration of platelets is of minimal benefit in animals with immune-mediated (primary or secondary) thrombocytopenia as the infused platelets are rapidly destroyed (within hours). Platelet infusions are useful to treat thrombocytopenias due to DIC and bone marrow failure, and to treat inherited or acquired thrombopathias (especially if elective surgery is required). Platelets are provided as whole blood, platelet-rich plasma and platelet concentrates.
Replacement of hemostatic proteins
Plasma products can be used to provide hemostatic proteins without the risk of red cell sensitization and are the preferred treatment for animals with acquired or inherited hemostatic disorders. The various plasma products have different uses:
- Fresh or fresh frozen plasma: These products contain all hemostatic factors, inhibitors (antithrombin) and plasma proteins. They can be used to treat any bleeding disorder (those not due specifically to abnormalities in platelet number or function), as well as being used as plasma volume expanders and as temporary therapy for hypoalbuminemic conditions (e.g. parvoviral enteritis in puppies). The disadvantages of plasma are the risk of volume overload due to the high volumes infused (especially in small patients or patients with congestive heart failure) and anaphylactic transfusion reactions.
- Cryoprecipitate: This is a concentrated source of vWf, Factor VIII, fibrinogen and fibronectin. It is the treatment of choice for vWD, Hemophilia A and fibrinogen disorders. Cryoprecipitate is more effective than plasma (or whole blood) in these disorders and is associated with minimal side-effects (small volumes are infused, so there is no risk of volume overload and anaphylactic reactions do not appear to occur with this product, likely due to the small amount of plasma it contains).
- Cryosupernatant: Cryosupernant can be used to treat all inherited and acquired conditons, in which vWf, fibrinogen or Factor VIII are not required. This is the product of choice for anticoagulant rodenticide toxicosis and Hemophilia B (Factor IX deficiency).
- Frozen plasma: Frozen plasma can be used as a source of vitamin K-dependent factors (as these are quite stable with prolonged storage) and plasma proteins.
The table below summarizes the guidelines for transfusions:
|Whole blood||12-20 ml/kg||q. 24 h||Anemia, platelets, factors anemia|
|PRBC||6-10 ml/kg||q. 12-24 h||As above|
|PRP||6-10 ml/kg||q. 8-12 h||thrombopathia, thrombocytopenia|
|Fresh plasma||6-10 ml/kg||q. 8-12 h||All factor (and vitamin K) deficiencies, vWD, DIC, hypoproteinemia|
|FFP||6-10 ml/kg||q. 8-12 h||As above|
|Frozen plasma||6-10 ml/kg||q. 8-12 h||Hypoproteinemia|
|CPP**||1 unit/10 kg||q. 4-12 h||Hemophilia A, vWD, fibrinogen deficiency|
|Cryosuper||6-10 ml/kg||q. 8-12 h||Factor VII, IX, X and XI deficiency, vitamin K deficiency, hypoproteinemia|
|Definitions: PRBC: packed red blood cells; PRP: platelet-rich plasma; FFP: Fresh frozen plasma; vWD: von Willebrand disease; DIC: disseminated intravascular coagulation; CPP: cryoprecipitate; Cryosuper: cryosupernatant.For definitions of the products themselves, refer to blood components.
* Products should be transfused at a rate of 1 to 2 ml/minute for cats, puppies and dogs in cardiac failure, and 3-6 ml/minute for adult dogs.
** One unit of CPP is defined as that produced from one fresh frozen plasma bag (approximately 250 ml).
(Table modified from notes provided by the Comparative Coagulation Laboratory at Cornell University).
Desmopressin is a synthetic analogue of arginine vasopressin (antidiuretic hormone), 1-deamino-8-arginine vasopressin (DDAVP). It is a useful drug for dogs with von Willebrand disease. Desmopressin elevates plasma vWf:Ag by inducing the release of vWf from stores (Weibel-Palade bodies) in endothelial cells. Factor VIII activity may also increase secondarily to the increased vWf. DDAVP will only work in animals with endothelial stores of vWf, ie. dogs with Type I vWD, e.g. Dobermans, and is ineffective in dogs with Type III vWD, e.g. Scottish Terriers, which lack vWf stores. Repeat injections produce a diminishing response, due to depletion of stores, therefore the drug has limited use in the treatment of hemorrhagic episodes of vWD (although it can be used as an adjunct to plasma products). It is also quite expensive, which limits its use.
Desmopressin is recommended as presurgical prophylaxis in Dobermans “at risk” of hemorrhage (i.e. those with vWf:Ag values < 35% or those that have shown previous bleeding tendencies), and in Dobermans of unknown vWD status with a prolonged BMBT. It is available as a liquid intranasal preparation for treatment of diabetes insipidus in human beings. The latter preparation is injected subcutaneously 30 minutes prior to surgery, at a dose of 1 µg/kg diluted to a “workable” volume (eg. 1 mL) with sterile saline. This dose may shorten the BMBT in vWD Dobermans for up to 4 hours. However, response to the drug is unpredictable in dogs with vWD (some dogs may not respond at all) and DDAVP should not be relied upon to achieve surgical hemostasis. Plasma or cyroprecipitate should be available in the event of excessive surgical hemorrhage.
DDAVP is also used by some people to boost values of vWf:Ag in donor dogs for transfusion purposes.
Hemoglobin-based oxygen carriers
Hemoglobin-based oxygen carriers (HBOCs), the prototype of which is Oxyglobin, can be used as a short-term alternative to red cells for alleviation of hypoxia due to anemia. This product has been approved for use in dogs as a single treatment only.
Oxyglobin is composed of polymerized bovine hemoglobin, which carries oxygen free in the plasma (rather than within erythrocytes). Administration of Oxyglobin improves oxygen-carrying capacity for 24 hours, and may acutely alleviate hypoxia due to severe anemia.
Oxyglobin is red and will discolor plasma, mucous membranes and urine (see below). The discoloration of plasma interferes with the results of coagulation, hematology and biochemistry tests and therefore, blood ideally should be collected for clinical pathologic testing before Oxyglobin is given. It will increase central venous pressure and produce up to 10-fold increases in AST. Administration of Oxyglobin does not appear to blunt the subsequent (desired) erythropoietic response to the anemia (as shown by a phlebotomy-induced anemia study in Beagle dogs). Oxyglobin should be eliminated from the body within 5-7 days after administration.
The most accurate way to monitor the benefit of Oxyglobin treatment is measurement of Hgb (measures both patient Hgb and Oxyglobin) as the hematocrit and red blood cell counts are reduced from the hemodilutory effects of the compound.