Porth's Essentials of Pathophysiology, 4e

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Hematopoietic Function

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junctions. For example, the regulatory control of cap- illary permeability in the skin and mucosal surfaces is far different from that in the brain. Common sites for spontaneous bleeding from platelet disorders are the skin and mucous membranes of the nose, mouth, gas- trointestinal tract, and uterine cavity. Cutaneous bleed- ing is seen as purple areas of bruising (purpura) and pinpoint hemorrhages (petechiae) in dependent areas where the capillary pressure is higher. Petechiae are seen almost exclusively in conditions of platelet deficiency, not platelet dysfunction. They are also seen in condi- tions of poor collagen synthesis and impaired formation of capillary intercellular junctions 15 (Fig. 12-4). Because tight regulation of capillary permeability in the brain is essential to prevent intercellular leakage, nontraumatic intracranial bleeding is relatively rare, even in persons with severe thrombocytopenia. 16 The major causes of thrombocytopenia are decreased platelet production, decreased platelet survival, splenic sequestration, and dilution. 3,4,16 Decreased platelet pro- duction due to loss of bone marrow function may occur because of congenital anemia (e.g., Wiskott-Aldrich syn- drome [see Chapter 16]), acquired anemia (e.g., aplastic anemia [see Chapter 13]), bone marrow infiltration by malignant cells (e.g., leukemia), or bone marrow depres- sion (e.g., radiation therapy, chemotherapy). Infection with human immunodeficiency virus (HIV) or cytomeg- alovirus may suppress the production of megakaryo- cytes, the platelet precursors. Reduced platelet survival is caused by a variety of immune and nonimmune mechanisms. Platelet destruc- tion may be caused by antiplatelet antibodies. These antibodies may be directed against platelet self-antigens or against antigens formed on the platelets from prior blood transfusions or pregnancy. In acute disseminated intravascular clotting or thrombotic thrombocytopenic purpura (TTP), excessive platelet consumption leads to a deficiency.

Production of platelets may be normal, but exces- sive pooling of platelets in the spleen may occur (splenic sequestration). When necessary, hypersplenic thrombo- cytopenia may be treated with splenectomy. Massive blood or plasma transfusions may cause a dilutional thrombocytopenia because blood stored for more than 24 hours has no viable platelets. Immune Thrombocytopenic Purpura. Immune thrombocytopenic purpura (ITP) is an autoimmune disorder that results in platelet antibody formation and excess destruction of platelets. 7,18 The thrombo- cytopenia that occurs in ITP is thought to result from multiple mechanisms, including antiplatelet antibodies against glycoproteins (IIb/IIIa and Ib/IX) in the platelet membrane. The platelets are made more susceptible to phagocytosis because of the antibodies and are subse- quently destroyed in the spleen. The disorder can occur in the absence of any known risk factors (primary or idiopathic ITP) or as a secondary disorder due to an underlying condition; it can also be classified as acute (duration of 6 months or less) or chronic. Secondary forms of ITP may be associated with acquired immunodeficiency syndrome (AIDS), systemic lupus erythematosus, antiphospholipid syndrome, chronic lymphocytic leukemia, lymphoma, hepatitis C, and drugs such as heparin and quinidine. About half of the cases of ITP occur as an acute primary disorder in children, affecting both boys and girls. 18 The disorder occurs in young children (5 years of age), commonly following a viral infection. It is characterized by sudden onset of petechiae and pur- pura and is usually a self-limited disorder requiring no treatment. Most children recover in a few weeks. In contrast, primary ITP is often a chronic disorder in adults with an insidious onset that seldom follows an infection. Peak incidence is between the ages of 18 and 40 years, and is seen three times as often in women as in men. Manifestations of ITP include a history of easy bruising, bleeding from gums, epistaxis, melena, and abnormal menstrual bleeding in those with moderately reduced platelet counts. Because the spleen is the site of platelet destruction, splenic enlargement may occur. The condition may be discovered incidentally or as a result of signs of bleeding, often into the skin (i.e., purpura and petechiae) or oral mucosa. About half of adults with primary ITP present with a platelet count of less than 10,000/ μ L and are at risk for internal hemorrhage. 18 Diagnosis of ITP usually is based on severe thrombo- cytopenia (platelet counts <20,000 to 30,000/ μ L) and exclusion of other causes. Tests for the platelet-bound antibodies are available but lack specificity (e.g., they react with platelet antibodies from other sources). The secondary form of ITP sometimes mimics the idio- pathic form of the disorder; therefore, the diagnosis is made only after excluding other known causes of thrombocytopenia. The decision to treat ITP is based on the platelet count and the degree of bleeding. Many persons with

FIGURE 12-4. Leg of a 9-year-old boy with petechiae due to vitamin C deficiency. (From Duggan CP, Westra SJ, Rosenberg AE. Case 23–2007: A 9-year-old body with bone pain, rash, and gingival hyperplasia. N Engl J Med. 2007;357:395. Copyright © 2007. Massachusetts Medical Society.)