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After studying this chapter you should:

  • Understand the pathogenesis and treatment of vitamin K deficiency.

  • Understand the pathogenesis, diagnosis, and treatment of disseminated intravascular coagulation.

One of the most challenging aspects of clinical medicine is the diagnosis and treatment of acquired bleeding disorders. These problems commonly arise in hospitalized patients on medical, surgical, and obstetrical services. The immediate question of whether the bleeding is due to recent trauma or surgery is sometimes difficult to answer with certainty. A careful history may reveal an inherited bleeding disorder or exposure to drugs or toxins that might adversely affect platelet or coagulation functions. A thorough physical examination will usually reveal whether the bleeding is local and restricted to the area of trauma or surgery, rather than widespread. In any case, a patient with unexplained hemorrhage, local or systemic, should be initially evaluated and then closely monitored with baseline screening tests that include a platelet count, prothrombin time, and partial thromboplastin time. Occasionally, additional coagulation tests are needed to delineate the cause of the bleeding and to guide appropriate therapy. Skillful management of these patients, who often have complex illnesses, must be based on a solid understanding of the pathophysiology of hemostasis, as presented in Chapter 13 and amplified in this chapter.

In contrast to inherited conditions such as hemophilia (Chapter 15), acquired bleeding disorders usually involve deficiencies of multiple clotting factors. This chapter will focus primarily on three problems commonly encountered on medical and surgical floors: vitamin K deficiency, severe liver disease, and disseminated intravascular coagulation (DIC).


Vitamin K is a fat-soluble organic compound found primarily in leafy green vegetables but also in meat and dairy products. It is composed of a bicyclical naphthoquinone backbone and an aliphatic side chain. As shown in Figure 16-1, vitamin K is converted to the hydroquinone by a vitamin K reductase. The hydroquinone is an essential cofactor utilized by the vitamin K–dependent carboxylase to catalyze the oxidative fixation of carbon dioxide onto specific glutamic acid residues to form γ-carboxyglutamic acid. During this reaction vitamin K is converted to an epoxide, which is then converted back to the quinone by a vitamin K epoxide reductase. This vitamin K–dependent post-translational modification takes place in the Golgi apparatus of many cell types and is restricted to specific domains on a small number of proteins—those known as vitamin K–dependent proteins. In hepatocytes, γ-carboxylation is necessary for the biologic activity of the vitamin K– dependent coagulation factors: the zymogens prothrombin, factors VII, IX, and X (Fig. 16-2), as well as protein C and protein S. In bone, γ-carboxylation is necessary for the synthesis of osteocalcin and matrix Gla protein. In all cases, this structural modification enables binding of divalent calcium. The function of vitamin K– dependent clotting factors requires calcium binding in order to form procoagulant complexes on membrane ...

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