Drugs & Blood Products Used to Manage Bleeding Disorders

Armi Pigott, DVM, DACVECC, BluePearl Pet Hospital, Glendale, Wisconsin

ArticleLast Updated July 20225 min readPeer Reviewed
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Normal hemostasis is a complex process that leads to blood clot formation at the site of blood vessel injury and is divided into stages of primary hemostasis (platelet plug formation), secondary hemostasis (coagulation), or fibrinolysis (clot degradation).1 Disorders can occur in all stages of hemostasis, may be inherited or acquired, and can affect a single stage or multiple stages.2 Basic understanding of these stages can help guide treatment of specific bleeding disorders.

Primary Hemostasis

Primary hemostasis is the process that forms the platelet plug at the site of vessel wall injury and involves complex interactions between the vessel wall, von Willebrand factor, and platelets.1 A disorder of primary hemostasis is a functional or absolute deficiency of one of these components. The most common causes of life-threatening hemorrhage due to disorders of primary hemostasis in veterinary medicine are thrombocytopenia and von Willebrand disease.3

Secondary Hemostasis

Secondary hemostasis includes fibrin formation through the coagulation cascade, which has classically been divided into intrinsic, extrinsic, and common pathways.1,2 Although the extrinsic tissue-factor–dependent pathway has been considered the primary mechanism for initiation of coagulation, the cell-based coagulation model may be a more accurate representation of secondary hemostasis in the body.1,2,4 The classical divisions however can help with understanding diagnostic tests used to identify coagulation defects and choosing appropriate treatments for coagulation disorders. 

Inherited clotting factor deficiencies and vitamin K antagonism are the most common causes of failures of secondary hemostasis. Hemophilia A and hemophilia B (inherited factor VIII and factor IX deficiency, respectively) are the most common inherited clotting factor deficiencies.5 Anticoagulant rodenticide ingestion is the most common cause of vitamin K antagonism.6

Fibrinolysis

Fibrinolysis is the normal process of fibrin clot degradation that prevents clots from becoming more extensive than necessary and breaks down clots when no longer needed.1,7 

Disorders that increase the rate of fibrinolysis (ie, hyperfibrinolysis, which is a pathophysiologic state) can result in significant bleeding.1,4,7 Hyperfibrinolysis is associated with several acquired and congenital disorders (eg, cavitary effusion, trauma, liver disease, lungworm [Angiostrongylus vasorum] infection).7 A bleeding disorder in greyhounds that results in delayed hemorrhage after trauma or routine surgery is likely an inherited defect in fibrinolysis but is yet to be characterized.7

Treatment & Management

Patients with clinically significant bleeding or a known or suspected bleeding disorder (including major trauma) scheduled to undergo invasive diagnostic or therapeutic procedures should be treated with drugs or blood products appropriate for the underlying etiology to stop, slow, or prevent bleeding. Identifying the underlying cause helps with selection of the correct blood products and drugs. 

In cases in which it is possible to provide treatment with multiple blood products, consideration should be given to the total amount that should (or may need to) be administered, current available products, and potential adverse effects. It is helpful to understand how different blood products are derived. For example, cryoprecipitate would generally be considered the blood product of choice for pre-emptive treatment of von Willebrand disease before ovariohysterectomy. To make one unit of cryoprecipitate, one unit of fresh whole blood is centrifuged to make one unit of fresh frozen plasma, which is then processed to make one unit of cryoprecipitate. Fresh whole blood, fresh frozen plasma, and cryoprecipitate all contain an equal amount of von Willebrand factor. Each round of processing concentrates the von Willebrand factor into a smaller volume of blood product; therefore, the difference is the total volume of blood product needed to provide that amount of von Willebrand factor, with fresh whole blood being the largest volume and cryoprecipitate being the smallest. In addition, fresh frozen plasma and cryoprecipitate do not contain RBCs, thus there is less antigenic exposure to the recipient, which is important in patients with a bleeding disorder that may need multiple blood transfusions over their lifetime. 

Whole blood doses listed in this article are intended to provide clotting factors or platelets to deficient patients and may differ significantly from the amount of blood needed to treat anemia. Clinically anemic patients may need more, less, or additional RBC-containing products. Transfusions of any blood product should be administered, and patients monitored for adverse transfusion reactions, according to established hospital protocols. The Association of Veterinary Hematology and Transfusion Medicine has published consensus statement guidelines for transfusion monitoring, as well as diagnosing and treating transfusion reactions in small animal patients.8-10 

Ideally, patients receiving RBC products should undergo blood typing and crossmatching prior to transfusion; however, these can be skipped in a life-threatening, time-sensitive crisis in dogs receiving a first-time transfusion, as naturally occurring alloantibodies (and, therefore, life-threatening transfusion reactions) are rare in dogs receiving transfusion for the first time. Cats should always undergo blood typing and crossmatching prior to transfusion because they have naturally occurring alloantibodies to multiple red cell antigens that can result in severe, life-threatening transfusion reactions to incompatible blood. 

More resources and in-depth discussion of blood typing, crossmatching, and transfusion reactions are available. All blood products discussed in this article are species-specific.

Blood Products

Platelet-Containing Products for Transfusion

Transfused platelets have a relatively fast clearance rate, particularly in patients with immune-mediated thrombocytopenia.3,11 Platelet transfusions are typically reserved for actively bleeding patients with thrombocytopenia or are administered prophylactically to patients with severe thrombocytopenia (ie, platelets, <60,000/µL) about to undergo a surgical procedure.3,11 Prophylactic platelet transfusions should be given immediately preoperatively to maximize benefits.

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