Porth's Essentials of Pathophysiology, 4e

275

Disorders of Hemostasis

C h a p t e r 1 2

are more directly related to the bleeding problems that occur. The bleeding may be present as petechiae, pur- pura, oozing from puncture sites, or severe hemorrhage. Uncontrolled postpartum bleeding may indicate DIC. Microemboli may obstruct blood vessels and cause tis- sue hypoxia and necrotic damage to organ structures, such as the kidneys, heart, lungs, and brain. As a result, common clinical signs may be due to renal, circulatory, or respiratory failure; acute bleeding ulcers; or con- vulsions and coma. A form of hemolytic anemia may develop as red cells are damaged passing through vessels partially blocked by thrombus. The treatment of DIC is directed toward managing the primary disease, replacing clotting components, and preventing further activation of clotting mechanisms. Transfusions of fresh-frozen plasma, platelets, or fibrin- ogen-containing cryoprecipitate may correct the clot- ting factor deficiency. Heparin may be given to decrease blood coagulation, thereby interrupting the clotting process. Heparin therapy is controversial, however, and the risk of hemorrhage may limit its use to severe cases. It typically is given as a continuous intravenous infusion that can be interrupted promptly if bleeding is accen- tuated. Tissue factor pathway inhibitors, antithrombin, protein C concentrates, and anti-inflammatory cyto- kines such as interleukin-10 are being evaluated in clini- cal trials as potential therapies. ■■ Bleeding disorders or impairment of blood coagulation can result from defects in any of the factors that contribute to hemostasis: platelets, coagulation factors, or vascular integrity. ■■ Disorders of platelet plug formation include a decrease in platelet numbers due to inadequate platelet production (bone marrow dysfunction), excess pooling of platelets in the spleen, excess platelet destruction (thrombocytopenia), abnormal platelet function (thrombocytopathia), or defects in vonWillebrand factor. ■■ Impairment of blood coagulation can result from deficiencies of one or more of the known clotting factors. Deficiencies can arise because of acquired disorders (i.e., liver disease or vitamin K deficiency) or inherited disorders (i.e., hemophilia A or vonWillebrand disease). ■■ Bleeding may also occur from structurally weak vessels that result from impaired synthesis of vessel wall components (i.e., vitamin C deficiency, excessive cortisol levels as in Cushing disease, or the aging process) or from damage by genetic mechanisms (i.e., hemorrhagic telangiectasia) or the presence of microthrombi. SUMMARY CONCEPTS

■■ Disseminated intravascular coagulation (DIC) is characterized by widespread coagulation and bleeding in the vascular compartment. It begins with massive activation of the coagulation cascade and generation of microthrombi that cause vessel occlusion and tissue ischemia. Clot formation consumes all available coagulation proteins and platelets, and severe hemorrhage may occur.

R E V I EW E X E R C I S E S 1. A 55-year-old man has begun taking one 81-mg aspirin tablet daily on the recommendation of his physician. The physician had told him that this would help to prevent heart attack and stroke. A. What is the action of aspirin in terms of heart attack and stroke prevention? B. The drug clopidogrel (Plavix) is often prescribed along with aspirin to prevent thrombosis in persons with severe atherosclerotic disease who are at risk for myocardial infarction or stroke. Explain the rationale for using the two drugs. 2. The drug desmopressin acetate (DDAVP), which is a synthetic analog of arginine vasopressin, increases the half-life of factor VIII and is sometimes used to treat bleeding in males with mild hemophilia. A. Explain. 3. A 29-year-old new mother, who delivered her infant three days ago, is admitted to the hospital with chest pain and is diagnosed as having venous thrombosis with pulmonary emboli. A. What factors would contribute to this woman’s risk of developing thromboemboli? 4. The new mother is admitted to the intensive care unit and started on low–molecular-weight heparin and warfarin. She is told that she will be discharged in a day or two and will remain on the heparin for 5 days and the warfarin for at least 3 months. A. Use Figure 12-3 to explain the action of heparin and warfarin. Why is heparin administered for 5 days during the initiation of warfarin treatment? B. Anticoagulation with heparin and warfarin is not a definitive treatment for clot removal in pulmonary embolism, but a form of secondary prevention. Explain.