http://ebooksmedicine.net • Unisystem Langerhans cell histiocytosis (eosinophilic granuloma) may be unifocal or multifocal. It is characterized by expanding accumulations of Langerhans cells, usually within the medullary cavities of bones or less commonly in the skin, lungs, or stomach. The Langerhans cells are admixed with variable numbers of lymphocytes, plasma cells, neutrophils, and eosinophils, which are usually prominent. Virtually any bone may be involved; the calvaria, ribs, and femur are most commonly affected. Unifocal disease most often involves a single bone. It may be asymptomatic or cause pain, tenderness, and pathologic fracture. It is an indolent disorder that may heal spontaneously or be cured by local excision or irradiation. Multifocal unisystem disease usually affects children and typically manifests with multiple erosive bony masses that sometimes extend into soft tissues. In about 50% of cases, involvement of the posterior pituitary stalk of the hypothalamus leads to diabetes insipidus. The combination of calvarial bone defects, diabetes insipidus, and exophthalmos is referred to as the Hand-Schüller-Christian triad. Many patients experience spontaneous regressions; others are treated effectively with chemotherapy.
A clue to the pathogenesis of Langerhans cell tumors lies in the discovery that the different clinical forms are frequently associated with an acquired mutation in the serine/threonine kinase BRAF, that leads to hyperactivity of the kinase. This same mutation is found in a variety of other tumors, including hairy cell leukemia (described earlier), benign nevi, malignant melanoma, papillary thyroid carcinoma, and some colon cancers (Chapter 6). BRAF is a component of the RAS signaling pathway that drives cellular proliferation and survival, effects that likely contribute to the growth of neoplastic Langerhans cells.
Bleeding disorders are characterized clinically by abnormal bleeding, which can appear spontaneously or follow some inciting event (e.g., trauma or surgery). As described in Chapter 4, normal clotting involves the vessel wall, the platelets, and the clotting factors. It follows that abnormalities in any of these components can lead to clinically significant bleeding. A review of the laboratory tests used in the evaluation of patients with a suspected bleeding disorder, along with the principles involved, is presented next, followed by consideration of specific disorders of coagulation. We finish with a discussion of a few clinically important complications of blood product transfusion.
The most important tests for investigation of suspected coagulopathies include the following:
Prothrombin time (PT). This test assesses the extrinsic and common coagulation pathways. It measures the time (in seconds) needed for plasma to clot after addition of tissue thromboplastin (e.g., brain extract) and Ca2+ ions. A prolonged PT can result from a deficiency of factor V, VII, or X; prothrombin; or fibrinogen or the presence of an acquired inhibitor (typically an antibody) that interferes with the extrinsic pathway.
Partial thromboplastin time (PTT). This test assesses the intrinsic and common coagulation pathways. It measures the time (in seconds) needed for the plasma to clot after the addition of kaolin, cephalin, and Ca2+ . Kaolin activates the contact-dependent factor XII and cephalin substitutes for platelet phospholipids. Prolongation of PTT can be caused by a deficiency of factor V, VIII, IX, X, XI, or XII; prothrombin; or fibrinogen or the presence of an acquired inhibitor that interferes with the intrinsic pathway.
Platelet count. This is obtained on anti-coagulated blood using an electronic particle counter. The reference range is 150,000 to 450,000/µL. Counts outside this range must be confirmed by a visual inspection of a peripheral blood smear.