Hematology is the subspecialty of internal medicine concerned with disorders of the blood and blood-forming organs. Oncology is a subspecialty of internal medicine that focuses on medical treatment of cancer. Because cancers of blood-forming cells were the first for which reasonably effective chemotherapy was developed, hematology and oncology have often been linked, although now many oncologists are not hematologists. Radiation oncology is a subspecialty of radiology that focuses on providing radiation therapy to cancer patients. Also, certain surgeons specialize in the treatment of cancer. Regardless of the branch of medicine to which they belong, cancer specialists work together to ensure a comprehensive approach to treatment for each patient.
Hematology and Oncology
Hematology and Oncology Chapters (A-Z)
Anemias Caused by Deficient Erythropoiesis
Anemia (a decrease in the number of RBCs, Hb content, or Hct) can result from decreased RBC production (erythropoiesis), increased RBC destruction, or blood loss. Anemias due to decreased erythropoiesis are recognized by reticulocytopenia, which is usually evident on the peripheral smear (see Testing). The RBC indices, mainly the MCV, narrow the differential diagnosis of deficient erythropoiesis and determine what further testing is necessary.
Anemias Caused by Hemolysis
At the end of their normal life span (about 120 days), RBCs are removed from the circulation. Hemolysis involves premature destruction and hence a shortened RBC life span (< 120 days). Anemia results when bone marrow production can no longer compensate for the shortened RBC survival; this condition is termed hemolytic anemia. If the marrow can compensate, the condition is termed compensated hemolytic anemia.
Approach to the Patient With Anemia
Red blood cell (RBC) production (erythropoiesis) takes place in the bone marrow under the control of the hormone erythropoietin (EPO). Juxtaglomerular cells in the kidney produce EPO in response to decreased O 2 delivery (as in anemia and hypoxia) and increased levels of androgens. In addition to EPO, RBC production requires adequate supplies of substrates, mainly iron, vitamin B 12 , and folate. Vitamin B 12 and folate are discussed in Vitamin Deficiency, Dependency, and Toxicity; iron is discussed in Iron Deficiency and Toxicity and discussed in Iron Deficiency Anemia. Heme synthesis is discussed in see Overview of Porphyrias
Bleeding Due to Abnormal Blood Vessels
Bleeding may result from abnormalities in platelets, coagulation factors, or blood vessels. Vascular bleeding disorders result from defects in blood vessels, typically causing petechiae, purpura, and bruising but, except for hereditary hemorrhagic telangiectasia, seldom leading to serious blood loss. Bleeding may result from deficiencies of vascular and perivascular collagen in Ehlers-Danlos syndrome and in other rare hereditary connective tissue disorders (eg, pseudoxanthoma elasticum, osteogenesis imperfecta, Marfan syndrome—see Marfan Syndrome). Hemorrhage may be a prominent feature of scurvy (see Vitamin C Deficiency) or of Henoch-Schönlein purpura, a hypersensitivity vasculitis common during childhood (see Immunoglobulin A–Associated Vasculitis (IgAV)). In vascular bleeding disorders, tests of hemostasis are usually normal. For most disorders, diagnosis is clinical; specific tests are available for some.
Abnormal bleeding can result from disorders of the coagulation system (see Overview of Hemostasis), of platelets, or of blood vessels. Disorders of coagulation can be acquired or hereditary. The major causes of acquired coagulation disorders are vitamin K deficiency (see Vitamin K Deficiency), liver disease, disseminated intravascular coagulation, and development of circulating anticoagulants. Severe liver disease (eg, cirrhosis, fulminant hepatitis, acute fatty liver of pregnancy) may disturb hemostasis by impairing clotting factor synthesis. Because all coagulation factors are made in the liver, both the PT and PTT are elevated in severe liver disorders. (PT results are typically reported as INR.) Occasionally, decompensated liver disease also causes excessive fibrinolysis and bleeding due to decreased hepatic synthesis of α 2 -antiplasmin.
Eosinophils are granulocytes derived from the same progenitor cells as monocytes-macrophages, neutrophils, and basophils. They are a component of the innate immune system (see Innate immunity). Eosinophils have a variety of functions but are especially important in defense against parasitic infections. However, although eosinophilia commonly accompanies helminthic infections and eosinophils are toxic to helminths in vitro, there is no direct evidence that they kill parasites in vivo. Although they are phagocytic, eosinophils are less efficient than neutrophils in killing intracellular bacteria. Eosinophils may modulate immediate hypersensitivity reactions by degrading or inactivating mediators released by mast cells, such as histamine, leukotrienes (which may cause vasoconstriction and bronchoconstriction), lysophospholipids, and heparin . Prolonged eosinophilia may result in tissue damage by mechanisms that are not fully understood.
The histiocytic syndromes are clinically heterogeneous disorders that result from an abnormal proliferation of histiocytes—either monocyte-macrophages (antigen-processing cells) or dendritic cells (antigen-presenting cells). Classifying these disorders is difficult (see Some Histiocytic Syndromes) and has changed over time as an understanding of the biology of these cells has evolved. There are other rare histiocytic disorders such as Erdheim-Chester disease, juvenile xanthogranuloma, and others.
Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems. The major types are Hodgkin lymphoma and non-Hodgkin lymphoma (NHL— Comparison of Hodgkin Lymphoma and Non-Hodgkin Lymphoma).
Overview of Cancer
Cancer is an unregulated proliferation of cells. Its prominent properties are a lack of differentiation of cells, local invasion of adjoining tissue, and, often, metastasis (spread to distant sites through the bloodstream or the lymphatic system). The immune system likely plays a significant role in eliminating early cancers or premalignant cells because immunodeficiency states are associated with an increased incidence of various kinds of cancer, particularly those associated with viral infection, and tumors arising in the lymphatic system and the skin.
Plasma Cell Disorders
Principles of Cancer Therapy
Thrombocytopenia and Platelet Dysfunction
Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes, which in turn shed platelets from their cytoplasm. Thrombopoietin is produced in the liver at a constant rate and its circulating level is determined by the extent to which circulating platelets are cleared, and possibly by bone marrow megakaryocytes. Platelets circulate for 7 to 10 days. About one third are always transiently sequestered in the spleen. The platelet count is normally 140,000 to 440,000/μL. However, the count can vary slightly according to menstrual cycle phase, decrease during near-term pregnancy (gestational thrombocytopenia), and increase in response to inflammatory cytokines (secondary, or reactive, thrombocytosis). Platelets are eventually destroyed by apoptosis, a process independent of the spleen.
In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces (see Overview of Hemostasis). Numerous genetic, acquired, and environmental factors can tip the balance in favor of coagulation, leading to the pathologic formation of thrombi in veins (eg, deep venous thrombosis [DVT]), arteries (eg, MI, ischemic stroke), or cardiac chambers. Thrombi can obstruct blood flow at the site of formation or detach and embolize to block a distant blood vessel (eg, pulmonary embolism, embolic stroke).
Tumor recognition is a complex, challenging problem for the immune system, which must distinguish proper cellular growth and organization from neoplastic transformation. This process involves recognition of tumor antigens by effector cells and induction of immunity. The development of tumors despite the presence of antigens, the significance of immune recognition in the pathogenesis of tumors, and the potential for therapeutic augmentation of immune responses remain the subject of intense investigation.