BLOOD DISEASE

abnormal condition that involves the corpuscular elements of the bloodred cells, white cells, and plateletsand the tissues in which they are formedthe bone marrow, the lymph nodes, the spleen (i.e., the hematopoietic system). This definition, however, needs expansion and modification. In certain types of illness (e.g., pneumonia, appendicitis) the number of leukocytes is increased. This is called leukocytosis and is a physiological response rather than a disease of the blood. In other diseases, as will be mentioned below, a reduction in the number of red cells in the blood (anemia) occurs; such anemia is not usually thought of as representing a blood disease, but it does represent the response of the hematopoietic system to the underlying disease. Strictly speaking, the term blood disease refers only to those types of anemia and those disorders of leukocytes, of platelets, of coagulation, and of the bone marrow, lymph nodes, and spleen in which the blood-forming organs or coagulation systems are the primary sites involved. In the following, all varieties of alteration in the three corpuscular elements of the blood will be discussed. For convenience, disorders chiefly affecting the red cells, the leukocytes, the platelets, and the process of blood coagulation will be considered in turn, but, as will become apparent, alterations in disease do not necessarily occur in only one of these groups of blood cells; in its reactions in disease the hematopoietic system may demonstrate multiple changes. Since the blood circulates throughout the body and carries nutritive substances as well as waste products, examination of it can be important in detecting the presence of disease. Examination of the blood may be considered in two categories; namely, the analysis of the plasma and the study of the corpuscles. Examination of the plasma includes measurement of plasma proteins, blood sugar, salts (which, being in solution and in the ionic state, are referred to as electrolytes), lipids, enzymes, urea, and various hormones. Such measurements are useful in the identification of diseases that are not classified as blood diseasese.g., diabetes, kidney disease, and thyroid disease. Special studies of plasma or its components can be carried out to determine the status of blood clotting. Long before the nature and composition of blood were known, a variety of complaints were attributed to disordered blood. The red cells were not recognized until the 17th century, and it was another 100 years before one of the forms of the white cells, the lymphocyte, and the clotting of blood were described. In the 19th century other forms of leukocytes were discovered, and a number of diseases of the blood and blood-forming organs were distinguished. In the 19th century and also in the first quarter of the 20th century much attention was given to descriptions of the morphological changesthe changes in form and structurethat take place in the blood during disease and to the signs and symptoms of the various blood diseases. In the years that followed, a more physiological approach began to develop, concerned with the mechanisms underlying the development of disease and with the ways in which abnormalities might be corrected. Following World War II, progress was greatly accelerated by the strong financial support that medical science received during a particularly productive age of medical research. The study of a particular instance of disease involves inquiry into the circumstances of its development, the symptoms, and the course of the illness (the history). A thorough physical examination of the affected person and specific laboratory tests are essential. In the case of the blood, certain features of the physical examination are especially important in diagnosis. These include noting the presence or absence of pallor or, the opposite, an excess of colour; jaundice, red tongue, enlargement of the heart or liver; the presence or absence of small purple spots or larger bruises in the skin; enlargement of lymph glands (nodes); enlargement of the spleen; and tenderness of the bones. Laboratory studies particularly valuable in diagnosis include (1) determination of the number and characteristics of red cells in the blood; i.e., the existence of anemia or polycythemia, (2) study of the white cells, their number and their proportions as to type, (3) enumeration of the blood platelets and a study of the blood-clotting process, and (4) in many instances a study of the bone marrow. It is sometimes necessary to remove a lymph node for microscopic examination, and X-ray examinations may be necessary for the detection of organ or lymph node enlargement or bone abnormalities. The more unusual cases may require further examinationse.g., special serological (serum-related) or biochemical procedures or various measurements using radioactive isotopes to outline an organ or quantitate blood volume. Additional reading The following major texts deal with the whole field of hematology, including the clinical, diagnostic, and therapeutic aspects: Vernon B. Mountcastle (ed.), Medical Physiology, 14th ed., 2 vol. (1980); William J. Williams et al. (eds.), Hematology, 3rd ed. (1983); Maxwell M. Wintrobe et al., Clinical Hematology, 8th ed. (1981); D.E. MacIntyre and J.L. Gordon (eds.), Platelets in Biology and Pathology III (1987); and James H. Jandl, Blood: Textbook of Hematology (1987). See also George Stamatoyannopoulos et al. (eds.), The Molecular Basis of Blood Diseases (1987); Sir John Dacie, Haemolytic Anaemias, 3rd ed. (1985), a classic text with detailed bibliography; I. Chanarin, The Megaloblastic Anaemias, 2nd ed. (1979), a comprehensive work with numerous references; and D.J. Weatherall, The Thalassaemia Syndromes, 2nd ed. (1972). For later research, see D.J. Weatherall (ed.), The Thalassemias (1983); H. Lehmann and R.G. Huntsman, Man's Haemoglobins: Including the Haemoglobinopathies and Their Investigation, rev. ed. (1975); William Dameshek and Frederick Gunz's Leukemia, 4th ed., edited by Frederick W. Gunz and Edward S. Henderson (1983); Oscar D. Ratnoff and Charles D. Forbes (ed.), Disorders of Hemostasis (1984); Rosemary Biggs and C.R. Rizza, Human Blood Coagulation, Haemostasis, and Thrombosis, 3rd ed. (1984); and Sheila T. Callender, Blood Disorders: The Facts (1985), a comprehensive basic introduction. Maxwell M. Wintrobe Robert S. Schwartz Diseases related to platelets and coagulation proteins Bleeding disorders In humans hemostatic failure may result from inherited or acquired defects of clotting or platelet function. The usual consequence is persistent bleeding from injuries that would normally cause little trouble. Some persons may bleed more easily than normal, perhaps even spontaneously, as a result of an increased fragility of the blood vessels. This fragility is not itself a hemostatic defect but may be associated with one. Abnormal bleeding Abnormal bleeding follows a pattern defined by the underlying defect. Platelet abnormalities are associated with spontaneous bleeding from the membranes of the nose, mouth, and gastrointestinal and urogenital tracts. Petechiae, purpuras, and ecchymoses are medical terms denoting different sizes of hemorrhage into the skin. In purpura there is an unexplained and abnormal fragility of the capillaries, resulting in pinpoint hemorrhages in the skin and mucous membranes. Diseases related to white cells Variations in the number of white cells in humans occur normally from hour to hour, the highest counts being recorded in the afternoon and the lowest in the early morning. Temporary increases also normally occur during muscular exercise, menstruation, pregnancy, and childbirth, as well as in certain emotional states. Abnormal changes in the count, appearance, or proportion of the various white cells are indicative of pathological conditions in the body. Leukocytosis The condition in which white cells are present in greater numbers than normal is termed leukocytosis. It is usually caused by an increase in the number of granulocytes (especially neutrophils), some of which may be immature (myelocytes). Most often leukocytosis is the result of the presence of an infection, usually caused by pyogenic (pus-producing) organisms such as streptococcus, staphylococcus, gonococcus, pneumococcus, or meningococcus. Leukocyte counts of 12,000 to 20,000 per cubic millimetre during infections are not unusual. As the number of cells increases, the proportion of immature cells usually rises, perhaps because the demands on the leukocyte-producing tissues in the bone marrow have increased to the point at which there is an insufficient number of mature cells for delivery into the circulation. This picture of immaturity is referred to as a shift to the left. As the infection subsides, the number of younger forms and the total white cell count decrease and ultimately return to normal. During the period of repair following an inflammatory reaction, the monocytes may increase in number, and subsequently the lymphocytes will become more numerous. Certain types of infection are characterized from the beginning by an increase in the number of small lymphocytes unaccompanied by increases in monocytes or granulocytes. Such lymphocytosis is usually of viral origin. Moderate degrees of lymphocytosis are encountered in certain chronic infections such as tuberculosis and brucellosis. Infectious mononucleosis, caused by the EpsteinBarr virus, is associated with the appearance of unusually large lymphocytes (atypical lymphocytes). Those cells represent part of the complex defense mechanism against the virus, and they disappear from the blood when the attack of infectious mononucleosis subsides. Infectious mononucleosis occurs predominantly in persons from 10 to 30 years of age. It is thought to be transmitted by oral contact with exchange of saliva. Discomfort, fever, sore throat, and grippelike symptoms, together with enlargement of lymph nodes and spleen, characterize the condition. The blood serum contains an antibody (sheep cell or heterophil agglutinin) that is characteristic of the disease, but antibodies against the EpsteinBarr virus itself are more specific markers of the infection. The symptoms of this disease vary in severity in different persons, but often they are mild. Recovery takes place, as a rule, within several weeks. Despite the immune response against the EpsteinBarr virus, the virus is never completely eliminated from the body. A small number of virus particles remain in latent form within B lymphocytes. In a normal person the immune system (the T lymphocytes in particular) keeps the latent viruses in check. If the natural responses of the immune system are suppressed (immunosuppression), however, the EpsteinBarr virus can emerge from its latent form and initiate a new round of infection. The EpsteinBarr virus is a member of the herpesvirus family, which also includes viruses that cause cold sores (herpes simplex type 1), genital ulcers (herpes simplex type 2), and shingles (herpes zoster) and the cytomegalovirus. All of these viruses show the property of latency, and in each case immunosuppression can lead to their activation. The most dramatic example of this can be found in acquired immunodeficiency syndrome (AIDS), which causes a pronounced deficiency of T lymphocytes. Patients with AIDS can develop severe and even fatal herpesvirus infections. Monocytosis, an increase in the number of monocytes in the blood, occurs in association with certain infectious processes, especially subacute bacterial endocarditisinflammation of the lining of the heartand malaria. Monocytosis also occurs when the bone marrow is recovering from a toxic injury. Eosinophilia, an increase in the number of eosinophilic leukocytes, is encountered in many allergic reactions and parasitic infections. It is especially characteristic of infestation by trichina larvae, which are ingested when infected and poorly cooked pork or pork products are eaten.