Historically, once it was recognized that blood clotting factors were components of plasma, the notion of treatment with plasma to correct deficiency states followed quickly. The decay of clotting factor activity in plasma that was stored led to the development of freshly frozen plasma. The problems encountered with fresh frozen plasma—fluid overload and the inability to achieve high clotting factor levels because of the fluid overload—led to efforts to concentrate the clotting factors. The terrible transmission of blood-borne viral illnesses by the concentrates, especially AIDS and hepatitis C, led to efforts to purify factors and develop recombinant products (FIGURE 75.1). Knowledge of the genes for clotting factors, generated by the efforts to develop recombinant products, now drives efforts aimed at gene therapy and proteins with improved function (Chapter 79). Along the way, additional treatments evolved. The discovery and characterization of fibrinolytic enzymes led to development of inhibitors of fibrinolysis, which are used as adjuncts for treatment of bleeding disorders, and profibrinolytics, which are used in the treatment of thrombosis. An analog of vasopressin, DDAVP (1-desamino-8-d-arginine vasopressin), used in diabetes insipidus, was discovered to induce secretion of von Willebrand factor and thereby increase von Willebrand factor and factor VIII levels in patients with milder forms of von Willebrand disease and hemophilia. As a result, the treatment of bleeding disorders has come a very long way from these initial treatments, and today’s clinician caring for patients with inherited bleeding disorders now has a highly sophisticated panel of products that are biologically stable, effective, and safe. This section reviews the various products used in the treatment of hemorrhagic disorders and the approaches in specific situations. The treatment of specific inherited coagulation factor deficiencies, such as hemophilia and von Willebrand disease, is discussed in the chapters dealing with those inherited disorders.

Acute hemorrhage is often a medical emergency and the clinician must have an approach and treatment strategy in mind when called. Knowledge of the agents available, their action, and their toxicities are important in this decision. The clinician must be able to quickly assess the source and the cause of the bleeding. It is important to determine if there is a structural lesion, an acquired bleeding defect, and/or an underlying inherited disorder. Often the input of multiple specialists—surgeons, radiologists, gastroenterologists, and hematologists—is required. The formulation of a treatment plan may require both blood replacement and hemostatic agents. These issues are discussed along with specific approaches for particular situations in Chapter 76. For acute hemorrhage in hemophilia and in acquired inhibitors, the reader is also referred to Chapters 51 and 57. Additional approaches in bleeding disorders associated with disseminated intravascular coagulation and liver disease are referred to Chapters 98 and 126. Treatment of acquired and inherited platelet and vascular disorders is described in Sections III-B and III-C.

Chapter 77 describes the use of antifibrinolytic agents. These have become important adjunct therapies for either the treatment of acute or chronic hemorrhage or for the prevention of hemorrhage. Antifibrinolytics are especially useful in the treatment of chronic hemorrhage from tissues that contain high levels of fibrinolysis activators such as the gastrointestinal tract.^1,2,3 Antifibrinolytics have been used in combination with clotting factor concentrates to reduce factor administration in hemophilia and in combination with bypassing agents for dental work and other treatments in hemophilic individuals with inhibitors.^4,5,6