Williams Hematology




Drugs and Chemicals

General Symptoms

Specific Symptoms

Family History

Sexual History
Physical Examination

Chapter References

Ideally, the physician’s goal is to prevent illness, and many opportunities exist for hematologists to prevent the development of hematologic disorders. These opportunities include identification of individual genetic risk factors and either avoidance of situations that may make a latent disorder manifest or actual prophylactic therapy, as for example in avoiding venous stasis in patients heterozygous for protein C deficiency or administering prophylactic subcutaneous heparin after major surgery in such patients. Hematologists may also prevent disease by participating in public health and community medicine efforts, such as eliminating sources of environmental lead that may result in childhood anemia. Prenatal diagnosis of hematologic disorders can provide information to families in which a fetus is affected with a hematologic disorder.
When preventive opportunities are not available or fail, the care of a patient begins with a systematic attempt to determine the nature of the illness by eliciting an in-depth medical history and performing a physical examination. The physician should identify the important symptoms and obtain as much relevant information as possible about their origin and evolution and about the general health of the patient by appropriate questions designed to explore the patient’s recent and remote experience. Reviewing previous records may add important data for understanding the onset or progression of illness. Hereditary and environmental factors should be carefully sought and evaluated. The physician follows the medical history with a physical examination to obtain data on the patient’s general health and to permit a careful search for signs of the illnesses suggested by the history. Additional history is obtained during the physical examination, as findings suggest an additional or alternative diagnosis. Thus, the history and physical examination should be considered as a unit, providing the basic information with which further diagnostic information is integrated.
Primary hematologic diseases are uncommon, while hematologic manifestations secondary to other diseases occur frequently. For example, the signs and symptoms of anemia and the presence of enlarged lymph nodes are common clinical findings that may be related to hematologic disease but occur even more frequently as secondary manifestations of disorders not considered primarily hematologic. A wide variety of diseases may produce signs or symptoms of hematologic illness. Thus, in patients with metastatic carcinoma, all the signs and symptoms of anemia may be elicited and lymphadenopathy may be pronounced, but additional findings are usually present that indicate primary involvement of some system besides the blood and lymph nodes. In this discussion, therefore, emphasis is placed on the clinical findings resulting from either primary hematologic disease or the complications of hematologic disorders in order to avoid presenting an extensive catalog of signs and symptoms encountered in general clinical medicine.
In each discussion of specific diseases in subsequent chapters, the signs and symptoms that accompany the particular disorder are presented, and the clinical findings are covered in detail. In this chapter a more general systematic approach is taken.

Acronyms and abbreviations that appear in this chapter include: PS, performance status.

HISTORY1,2,3 and 4
Drug therapy, either self-prescribed or ordered by a physician, is extremely common in our society. Drugs often induce or aggravate hematologic disease, and it is therefore essential that a careful history of drug ingestion, including beneficial and adverse reactions, be obtained from all patients. Drugs taken regularly often become a part of the patient’s way of life and are often forgotten or are not recognized as “drugs.” Agents such as aspirin, laxatives, tranquilizers, medicinal iron, vitamins, other nutritional supplements, and sedatives belong to this category. Further, drugs may be ingested in unrecognized form, such as antibiotics in food or quinine in tonic water. Specific, persistent questioning, often on several occasions, may be necessary before a complete history of drug use is obtained. It is very important to obtain detailed information on alcohol consumption from every patient. The four “CAGE” questions—about cutting down, being annoyed by criticism, having guilt feelings, and needing an eye-opener—provide an effective approach to the history of alcohol use. Patients should also be asked about the use of recreational drugs. The use of “alternative medicines” and herbal medicines are common, and many patients will not consider these medications or may actively withhold information about their use. Nonjudgmental questioning may be successful in identifying agents in this category that the patient is taking.
In addition to drugs, most people are exposed regularly to a variety of chemicals in the environment, some of which may be potentially harmful agents in hematologic disease. Similarly, occupational exposure to chemicals must be considered. When a toxin is suspected, the patient’s daily activities and environment must be carefully reviewed, since significant exposure to toxic chemicals may occur incidentally.
Vaccinations can be potent triggers of exacerbations of immune thrombocytopenia.
Nutrition information can be useful in deducing the possible role of dietary deficiency in anemia. The avoidance of certain food groups, as might be the case with vegans, or the ingestion of uncooked fish or meat can be clues to the pathogenesis of anemia.
Performance status (PS) is a useful concept in establishing the seriousness of the patient’s disability at the outset and in evaluating the effects of therapy.2 A well-founded set of criteria for evaluating performance status is presented in Table 1-1.


Weight loss is a frequent accompaniment of many serious diseases, including primary hematologic entities, but it is not a prominent accompaniment of most hematologic disease. Many “wasting” diseases, such as disseminated carcinoma or tuberculosis, cause anemia, and pronounced emaciation should suggest one of these diseases rather than anemia as the primary disorder.
Fever is a common manifestation of the lymphomas or leukemias, usually because of secondary infection but sometimes as a result of the disease itself. In patients with “fever of unknown origin,” leukemia or lymphoma, and particularly Hodgkin’s disease, should be considered. Myelofibrosis and chronic lymphocytic leukemia may also cause fever. In rare patients with severe pernicious anemia or hemolytic anemia, fever may be pronounced. Chills may accompany severe hemolytic processes and the bacteremia that may complicate the immunocompromised or neutropenic patient. Night sweats suggest the presence of low-grade fever and may occur in patients with lymphoma or leukemia.
Fatigue, malaise, and lassitude are such common accompaniments of both physical and emotional disorders that their evaluation is complex and often difficult. In patients with serious disease, these symptoms may be readily explained by fever, muscle wasting, or other associated findings. Patients with anemia frequently complain of fatigue, malaise, or lassitude, and these symptoms may accompany the hematologic malignancies. Fatigue or lassitude may occur also with iron deficiency even in the absence of sufficient anemia to account for the symptom. In slowly developing chronic anemias, the patient may not recognize reduced exercise tolerance, etc., except in retrospect, after a remission has been induced by appropriate therapy. Anemia may be responsible for more symptoms than has been traditionally recognized, as suggested by the remarkable improvement in quality of life of most uremic patients treated with erythropoietin.3
Weakness may accompany anemia or the wasting of malignant processes, in which cases it is manifest as a general loss of strength or reduced capacity for exercise. The weakness may be localized as a result of neurologic complications of hematologic disease. In pernicious anemia there may be weakness of the lower extremities, accompanied by numbness, tingling, and unsteadiness of gait. Peripheral neuropathy also occurs with dysproteinemias. Weakness of one or more extremities in patients with leukemia, myeloma, or lymphoma may signify central or peripheral nervous system invasion or compression. Myopathy secondary to malignancy occurs with the hematologic malignancies and is usually manifest as weakness of proximal muscle groups. Foot drop or wrist drop may occur in lead poisoning, amyloidosis, systemic autoimmune diseases, or as a complication of vincristine therapy. Paralysis may occur in acute intermittent porphyria.
Headache may be due to a number of causes related to hematologic diseases. Anemia or polycythemia may cause mild to severe headache. Invasion or compression of the brain by leukemia or lymphoma, or infection of the central nervous system by Cryptococcus or tuberculosis, may also cause headache in patients with hematologic malignancies. Hemorrhage into the brain or subarachnoid space in patients with thrombocytopenia or other bleeding disorders may cause sudden, severe headache.
Paresthesias may occur because of peripheral neuropathy in pernicious anemia or secondary to hematologic malignancy or amyloidosis. They may also result from therapy with vincristine.
Confusion may accompany malignant or infectious processes involving the brain, sometimes as a result of the accompanying fever. Confusion may also occur with severe anemia, hypercalcemia, or glucocorticoid therapy. Confusion or apparent senility may be a manifestation of pernicious anemia. Frank psychosis may develop in acute intermittent porphyria or with glucocorticoid therapy.
Impairment of consciousness may be due to increased intracranial pressure secondary to hemorrhage or tumor in the central nervous system. It may also accompany severe anemia or polycythemia, or it may be due to hyperviscosity secondary to a paraprotein in the plasma.
Visual disturbances may be manifestations of anemia, polycythemia, leukemia, or macroglobulinemia. Occasionally blindness may result from retinal hemorrhages secondary to anemia and thrombocytopenia or severe hyperviscosity. Diplopia or disturbances of ocular movement may occur with orbital tumors or paralysis of the third, fourth, or sixth cranial nerves because of compression by tumor.
Vertigo, tinnitus, and “roaring” in the ears may occur with marked anemia, polycythemia, or macroglobulinemia-induced hyperviscosity.
Epistaxis may occur with any bleeding disorder. Anosmia or olfactory hallucinations occur in pernicious anemia. The nasopharynx may be invaded by a malignant tumor, with the symptoms dependent on the structures invaded. Sore tongue occurs in pernicious anemia and may accompany iron deficiency or vitamin deficiencies. Macroglossia occurs in amyloidosis. Bleeding gums may occur with bleeding disorders. Infiltration of the gingiva with leukemic cells occurs in acute monocytic leukemia. Ulceration of the tongue or oral mucosa may be severe in the leukemias or in patients with neutropenia. Dryness of the mouth may be due to hypercalcemia, secondary, for example, to plasma cell myeloma. Dysphagia may be seen in patients with severe mucous membrane atrophy associated with chronic iron-deficiency anemia.
Painless swelling in the neck is characteristic of lymphoma but may be due to a number of other diseases as well. Occasionally, the enlarged lymph nodes of lymphomas may be tender or painful because of secondary infection or rapid growth. Diffuse swelling of the neck and face may occur with obstruction of the superior vena cava due to lymphoma.
Both dyspnea and palpitations, usually on effort but occasionally at rest, may occur because of anemia. Congestive heart failure may supervene, and angina pectoris may become manifest in anemic patients. The impact of anemia on the circulatory system depends in part on the rapidity with which it develops, and chronic anemia may become severe without producing major symptoms; with acute blood loss, the patient may develop shock with a nearly normal hemoglobin level. Cough may result from enlarged mediastinal nodes. Chest pain may arise from involvement of the ribs or sternum with lymphoma or multiple myeloma, nerve-root invasion or compression, or herpes zoster; the pain of herpes zoster usually precedes the skin lesions by several days. Tenderness of the sternum may be quite pronounced in chronic myelogenous or acute leukemia, in myelofibrosis, or if the sternal marrow is invaded by lymphoma or myeloma.
Dysphagia has already been mentioned under “Nasopharynx.” Anorexia frequently occurs but usually has no specific diagnostic significance. Hypercalcemia and azotemia cause anorexia, nausea, and vomiting. A variety of ill-defined gastrointestinal complaints grouped under the heading “indigestion” may occur with hematologic diseases. Abdominal fullness, premature satiety, belching, or discomfort may occur because of a greatly enlarged spleen, but such splenomegaly may also be entirely asymptomatic. Abdominal pain may arise from intestinal obstruction by lymphoma, retroperitoneal bleeding, lead poisoning, ileus secondary to therapy with the Vinca alkaloids, acute hemolysis, allergic purpura, the abdominal crises of sickle cell disease, or acute intermittent porphyria. Diarrhea may occur in pernicious anemia. It also may be prominent in the various forms of intestinal malabsorption, although significant malabsorption may occur without diarrhea. Malabsorption may be a manifestation of small-bowel lymphoma. Gastrointestinal bleeding related to thrombocytopenia or other bleeding disorder may be entirely occult but often is manifest as hematemesis or melena. Constipation may occur in the patient with hypercalcemia or in one receiving treatment with the Vinca alkaloids.
Impotence or bladder dysfunction may occur with spinal cord or peripheral nerve damage due to one of the hematologic malignancies or with pernicious anemia. Priapism may occur in leukemia or sickle cell disease. Hematuria may be a manifestation of any of the bleeding disorders. Red urine may also occur with intravascular hemolysis (hemoglobinuria), myoglobinuria, or porphyrinuria. Injection of anthracycline drugs or ingestion of drugs such as pyridium regularly causes the urine to turn red. Beeturia also occurs as a benign genetic trait. Amenorrhea may accompany any serious disease. It may also be induced by certain drugs, such as antimetabolites or alkylating agents. Menorrhagia is a common cause of iron deficiency, and care must be taken to obtain an accurate history of the extent of menstrual blood loss. Semiquantification can be obtained from estimates of the number of days of heavy bleeding (usually 1 to 2), the number of days of any bleeding (usually 5 to 7), number of tampons or pads used, degree of blood soaking, and clots formed. Menorrhagia may occur in patients with bleeding disorders.
Back pain may accompany acute hemolytic reactions or be due to involvement of bone or the nervous system in malignant disease. It is one of the commonest manifestations of myeloma.
Arthritis or arthralgia may occur with gout secondary to increased uric acid production in patients with hematologic malignancies, myelofibrosis, or hemolytic anemia. They also occur in the plasma cell dyscrasias, acute leukemias, and sickle cell disease without evidence of gout, and in allergic purpura. Arthritis may accompany hemochromatosis. Hemarthroses in patients with severe bleeding disorders cause marked joint pain. Autoimmune diseases may present as anemia and/or thrombocytopenia, and arthritis appears as a later manifestation. Shoulder pain on the left may be due to infarction of the spleen and on the right from gall bladder disease associated with chronic hemolytic anemia such as hereditary spherocytosis. Bone pain may occur with bone involvement by the hematologic malignancies or metastatic tumor; it is common in the congenital hemolytic anemias, such as sickle cell anemia, and may occur in myelofibrosis. In patients with Hodgkin’s disease, ingestion of alcohol may induce pain at the site of any lesion, including those in bone. Edema of the lower extremities, sometimes unilateral, may occur because of obstruction to veins or lymphatics by enlarged lymph nodes. Leg ulcers are a common complaint in sickle cell anemia and occur rarely in other hereditary anemias.
Skin manifestations of hematologic disease may be of great importance; they include changes in texture or color, itching, and the presence of specific or nonspecific lesions. The skin in iron-deficient patients may become dry, the hair dry and fine, and the nails brittle. In hypothyroidism, which may cause anemia, the skin is dry, coarse, and scaly. Jaundice may be apparent with pernicious anemia or congenital or acquired hemolytic anemia. The skin of patients with pernicious anemia is said to be “lemon yellow” because of the simultaneous appearance of jaundice and pallor. Jaundice may also occur in patients with hematologic diseases as a result of liver involvement or biliary tract obstruction. Pallor is a common accompaniment of anemia, although some severely anemic patients may not appear pale. Widespread erythroderma occurs in cutaneous T-cell lymphoma and in some cases of chronic lymphocytic leukemia or lymphocytic lymphoma. The skin is often involved, sometimes severely, in graft-versus-host disease following marrow transplantation. Patients with hemachromatosis may have bronze or grayish pigmentation of the skin. Cyanosis occurs with methemoglobinemia, either hereditary or acquired; sulfhemoglobinemia; abnormal hemoglobins with low oxygen affinity; and primary and secondary polycythemia. Cyanosis of the ears or the fingertips may occur after exposure to cold in individuals with cryoglobulins or cold agglutinins.
Itching may occur in the absence of any visible skin lesions in Hodgkin’s disease and may be extreme. Mycosis fungoides or other lymphomas with skin involvement may also present as itching. A significant number of patients with polycythemia vera will complain of itching after bathing.
Petechiae and ecchymoses are most often seen in the extremities in patients with thrombocytopenia, nonthrombocytopenic purpura, or nonthrombocytopenic bleeding disorders. Unless secondary to trauma, these lesions usually are painless, although the lesions of psychogenic purpura and erythema nodosum are painful. Easy bruising is a common complaint, especially among women, and when no other hemorrhagic symptoms are present, usually no abnormalities are found after detailed study. This symptom may, however, indicate a mild hereditary bleeding disorder, such as von Willebrand’s disease or one of the platelet disorders.
Infiltrative lesions may occur in the leukemias and lymphomas and are sometimes the presenting complaint. Necrotic lesions may occur with intravascular coagulation, purpura fulminans, warfarin-induced skin necrosis, or rarely with exposure to cold in patients with circulating cryoproteins or cold agglutinins.
A carefully obtained family history may be of great importance in the study of patients with hematologic disease. In the case of hemolytic disorders, questions should be asked regarding jaundice, anemia, and gallstones in relatives. In patients with disorders of hemostasis or venous thrombosis, particular attention must be given to bleeding manifestations, and clots in family members. In the case of autosomal recessive disorders such as pyruvate kinase deficiency the parents are usually not affected, but a similar clinical syndrome may have occurred in siblings. It is particularly important to inquire about siblings who may have died in infancy, since these may be forgotten, especially by older patients. When sex-linked inheritance is suspected, it is necessary to inquire about symptoms in the maternal grandfather, maternal uncles, male siblings, and nephews. In patients with disorders with dominant inheritance, such as hereditary spherocytosis, one may expect to find that one of the parents and possibly siblings and children of the patient have stigmata of the disease. Ethnic background may be important in the consideration of certain diseases such as thalassemia, sickle cell anemia, glucose-6-phosphate dehydrogenase deficiency, or other inherited disorders that are concentrated in geographic areas.
Because of the epidemic of infections with the human immunodeficiency viruses, it is important to ascertain the sexual preferences and risk factors of patients.
A detailed physical examination should be performed on every patient, with sufficient attention paid to all systems to obtain a full evaluation of the general health of the individual. Certain body areas are especially pertinent to hematologic disease and therefore deserve special attention. These are the skin, eyes, tongue, lymph nodes, skeleton, spleen and liver, and nervous system.
The color of the skin is due to the pigment contained therein and to the blood flowing through the skin capillaries. The component of skin color related to the blood may be a useful guide to anemia or polycythemia, since pallor may result when the hemoglobin level is reduced and redness when the hemoglobin level is increased. The amount of pigment in the skin will modify skin color and may mislead the clinician, as in individuals with pallor due to decreased pigment, or make skin color useless as a guide because of the intense pigmentation present.
Alterations in blood flow and in hemoglobin content may change skin color; this too may mislead the clinician. Thus emotion may cause either pallor or blushing. Exposure of the skin to cold or heat may similarly cause pallor or blushing. Chronic exposure to wind or sun may lead to permanent redness of the skin, and chronic ingestion of alcohol to a flushed face. The degree of erythema of the skin can be evaluated by pressing the thumb firmly against the skin, as on the forehead, so that the capillaries are emptied, and then comparing the color of the compressed spot with the surrounding skin immediately after the thumb is removed.
The mucous membranes and nail beds are usually more reliable guides to anemia or polycythemia than the skin. The conjunctivae and gums may be inflamed, however, and therefore not reflect the hemoglobin level, or the gums may appear pale because of pressure from the lips. The gums and the nail beds may also be pigmented and the capillaries correspondingly obscured. In some individuals, the color of the capillaries does not become fully visible through the nails unless pressure is applied to the fingertip, either laterally or on the end of the nail.
The palmar creases are useful guides to the hemoglobin level and appear pink in the fully opened hand unless the hemoglobin is 7 g/dl or less. Liver disease may induce flushing of the thenar and hypothenar eminences of the palm, even in patients with anemia.
The detection of cyanosis, like the detection of pallor, may be made difficult by skin pigmentation. Cyanosis is a function of the total amount of reduced hemoglobin, methemoglobin, or sulfhemoglobin present. The minimum amounts of these pigments that cause detectable cyanosis are about 5 g of reduced hemoglobin, 1.5 to 2.0 g of methemoglobin, and 0.5 g of sulfhemoglobin per deciliter of blood.
Jaundice may be observed in the skin of individuals who are not otherwise deeply pigmented or in the conjunctivae or the mucous membranes. The patient should be examined in daylight rather than under incandescent or fluorescent light, because the yellow color of the latter masks the yellow color of the patient. Jaundice is due to actual staining of the skin by bile pigment, and bilirubin glucuronide (direct-reacting or conjugated bilirubin) stains the skin more readily than the unconjugated form. Jaundice of the skin may not be visible if the bilirubin level is below 2 to 3 mg/dl. Yellow pigmentation of the skin may also occur with carotenemia, especially in young children.
Petechiae are small (1 to 3 mm), round, red or brown lesions resulting from hemorrhage into the skin and are present primarily in areas with high venous pressure, such as the lower legs. These lesions do not blanch on pressure, and this can be demonstrated most readily by compressing the skin with a glass microscope slide or magnifying lens. Petechiae may occasionally be elevated slightly, i.e., palpable; this finding suggests vasculitis. Ecchymoses may be of various sizes and shapes and may be red, purple, blue, or yellowish green, depending on the intensity of the skin hemorrhage and its age. They may be flat or elevated; some are painful and tender. The lesions of hereditary hemorrhagic telangiectasia are small, flat, nonpulsatile, and violaceous. They blanch with pressure.
Itching may be intense in some hematologic disorders such as Hodgkin’s disease, even in the absence of skin lesions. Excoriation of the skin from scratching is the only physical manifestation of this severe symptom.
Open ulcers or scars from healed ulcers are often found in the region of the internal or external malleoli in patients with sickle cell anemia and, rarely, in other hereditary anemias.
Detection of pallor or rubor by examining the nails was discussed earlier. The fingernails in chronic, severe iron-deficiency anemia may be ridged longitudinally and flattened or concave rather than convex. The latter change is referred to as koilonychia and is uncommon in present practice.
Jaundice, pallor, or plethora may be detected from examination of the eyes. Jaundice is usually more readily detected in the sclerae than in the skin. Ophthalmoscopic examination is also essential in patients with hematologic disease. Retinal hemorrhages and exudates occur in patients with severe anemia and thrombocytopenia. These hemorrhages are usually the typical “flame-shaped” hemorrhages, but they may be quite large and elevate the retina so that they may appear as a darkly colored tumor. Round hemorrhages with white centers are also often seen. Dilatation of the veins may be seen in polycythemia; in patients with macroglobulinemia, the veins are engorged and segmented, resembling link sausages.
Pallor of the mucosa has already been discussed. Ulceration of the oral mucosa occurs commonly in neutropenic patients. In leukemia there may also be infiltration of the gums with swelling, redness, and bleeding. Bleeding from the mucosa may occur with a hemorrhagic disease. A dark line of lead sulfide may be deposited in the gums at the base of the teeth in lead poisoning. The tongue may be completely smooth in pernicious anemia and iron-deficiency anemia. Patients with an upper dental prosthesis may also have papillary atrophy, presumably on a mechanical basis. The tongue may be smooth and red in patients with nutritional deficiencies. This may be accompanied by fissuring at the corners of the mouth, but fissuring may also be due to ill-fitting dentures.
Lymph nodes are widely distributed in the body, and in disease any node or group of nodes may be involved. The major concern on physical examination is the detection of enlarged or tender nodes in the cervical, supraclavicular, axillary, epitrochlear, inguinal, or femoral regions. Under normal conditions in adults, the only readily palpable lymph nodes are in the inguinal region, where several firm nodes 0.5 to 2.0 cm long are normally attached to the dense fascia below the inguinal ligament and in the femoral triangle. In children, multiple small (0.5 to 1.0 cm) nodes may be palpated in the cervical region as well. Supraclavicular nodes may sometimes be palpable only when the patient performs the Valsalva maneuver.
Enlarged lymph nodes are ordinarily detected in the superficial areas by palpation, although they are sometimes large enough to be seen. Palpation should be gentle and is best performed with a circular motion of the fingertips, using slowly increasing pressure.
Nodes too deep to palpate may be detected by radiologic examination, including computerized tomography, magnetic resonance imaging, radiographic lymphangiography, isotopic lymphangiography, or by ultrasound.
Increased rib or sternal tenderness is an important physical sign often ignored. Increased bone pain may be generalized, as in leukemia, or spotty, as in plasma cell myeloma or in metastatic tumors. The superficial surfaces of all bones should be examined thoroughly by applying intermittent firm pressure with the fingertips to locate potential areas of disease.
SPLEEN5,6,7 and 8
The normal adult spleen is usually not palpable on physical examination but occasionally may be felt. Palpability of the normal spleen may be related to body habitus, but there is disagreement on this point. Enlarged spleens may be detected by percussion, palpation, or a combination of these two methods. Some enlarged spleens may be visible through the abdominal wall.
The normal spleen weighs about 150 g and lies in the peritoneal cavity against the diaphragm and the posterolateral abdominal wall at the level of the lower three ribs. As it enlarges it remains close to the abdominal wall, while the lower pole moves downward, anteriorly, and to the right. Spleens enlarged only 40 percent above normal may be palpable, but significant splenic enlargement may occur and the organ still not be felt on physical examination. A good but imperfect correlation has been reported between spleen size estimated from radioisotope scanning or ultrasonography and spleen weight determined after splenectomy or at autopsy. Although it is common to fail to palpate an enlarged spleen on physical examination, palpation of a normal-sized spleen is unusual, and therefore a palpable spleen is usually a significant physical finding.
In examining for an enlarged spleen, it should be remembered that the organ lies just beneath the abdominal wall and that it is identified by its movement during respiration. The splenic notch may be evident if the organ is moderately enlarged. During the examination the patient lies in a relaxed, supine position. The examiner, standing on the patient’s right, gently palpates the left upper abdomen with the right hand while exerting pressure forward with the palm of the left hand placed over the lower ribs posterolaterally. If nothing is felt, the palpation should be performed repeatedly, moving the examining hand about 2 cm toward the inguinal ligament each time. It is often advantageous to carry out the examination initially with the patient lying on the right side with left knee flexed and to repeat it with the patient supine.
It is not always possible to be sure that a left upper quadrant mass is spleen; masses in the stomach, colon, kidney, or pancreas may mimic splenomegaly on physical examination. When there is uncertainty regarding the nature of a mass in the left upper quadrant, imaging procedures will usually permit accurate diagnosis.
LIVER7,8,9,10 and 11
Palpation of the edge of the liver in the right upper quadrant of the abdomen is commonly used to detect hepatic enlargement, although the inaccuracies of this method have been demonstrated. It is necessary to determine both the upper and lower borders of the liver by percussion in order to properly assess liver size. The normal liver may be palpable as much as 4 to 5 cm below the right costal margin but is usually not palpable in the epigastrium. The height of liver dullness is best measured in a specific line 8, 10, or 12 cm to the right of the midline. Techniques should be standardized so that serial measurements can be made. The vertical span of the normal liver determined in this manner will range about 10 cm in an average-size man and about 2 cm smaller in women. Because of variations introduced by technique, each physician should determine the normal area of liver dullness by his or her own procedure. Correlation of radioisotope imaging data with results from routine physical examinations indicates that often a liver of normal size is considered enlarged on physical examination and an enlarged liver is considered normal. Imaging procedures are useful in demonstrating localized infiltrative lesions.
A thorough evaluation of neurologic function is necessary in many patients with hematologic disease. Vitamin B12 deficiency impairs cerebral, olfactory, spinal cord, and peripheral nerve function, and severe chronic deficiency may lead to irreversible neurologic degeneration. Leukemic meningitis is often manifested by headache, visual impairment, or cranial nerve dysfunction. Tumor growth in the brain or spinal cord compression may be due to malignant lymphoma or plasma cell myeloma. A variety of neurologic abnormalities may develop in patients with various leukemias and lymphomas as a consequence of infiltration, bleeding, or infection.
Deformities of the knees, elbows, ankles, shoulders, wrists, or hips may be the result of repeated hemorrhage in patients with hemophilia A, hemophilia B, or severe factor VII deficiency. Often, a target joint is prominently affected.

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Sackett DL: A primer on the precision and accuracy of the clinical examination. JAMA 267:2638, 1992.

Enelow AJ, Forde DL, Brummel-Smith K: Interviewing and Patient Care, 4th ed. Oxford University Press, Oxford, 1996.

Arkles LB, Gill GD, Nolan MP: A palpable spleen is not necessarily enlarged or pathological. Med J Aust 145:15, 1986.

Barkun AN, Camus M, Green L, et al: The bedside assessment of splenic enlargement. Am J Med 91:512, 1991.

Halpern S, Coel M, Ashburn W, et al: Correlation of liver and spleen size: determinations by nuclear medicine studies and physical examination. Arch Intern Med 134:123, 1974.

Downey MT: Estimation of splenic weight from ultrasonographic measurements. Can Assn Rad J 43:273, 1992.

Castell DO, O’Brien KD, Muench H, Chalmers TC: Estimation of liver size by percussion in normal individuals. Ann Intern Med 70:1183, 1969.

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Copyright © 2001 McGraw-Hill
Ernest Beutler, Marshall A. Lichtman, Barry S. Coller, Thomas J. Kipps, and Uri Seligsohn
Williams Hematology


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    A couple component e-cigarette includes the car battery component including a cartridges. Here the atomizer is definitely protected inside of the cartridges (often known as cartomizer). Some Three component e-cig includes the car battery component, a powerful atomizer including a cartridges.

    Some component 3 component

    Each cartridge/cartomizer incorporates a clean and fresh atomizer built-in.
    No headaches regarding hygiene or atomizer efficiency diminish in the future.
    No require to ever in your life shop for a completely new atomizer.

    Atomizer is definitely about better not to mention has service contract.
    Refill tubes are cheaper (a handful of simply by more than 50%).
    New atomizer fees regarding $10. And that means you could a whole new atomizer by means of almost every 8 tubes nevertheless make big savings.
    Recommended to the who want to once again install tubes.

    Some component e-cig

    Some component sauna vapor smoke

    3 component e-cig

    Three component sauna vapor smoke

    free electronic cigarette starter kit

    Stock up e-Cigarette Capsules
    You should purchase smoke veggie juice not to mention once again install tubes to save money. If you are hoping in order to once again install tubes only then do we encourage the Three component e-cig. Atomizers through Some component ecigs are not made to carry on.

    Watery vapor Volume levels
    The amount sauna you can jump on 1 drag is a big bargain for the majority of people who smoke ,. Typically, additional size implies an increasingly acceptable not to mention genuine tobacco smoking working experience. Specialist smells start in this quick drag in order to cook the atomizer accompanied by a lengthier move.

    Subject material ? most desirable e-cig flavor? E cigs tubes include several styles. All e-cig manufacturers give tobacco not to mention menthol tasting tubes. For anybody who is in to a fairly particular flavor afterward pick out a type as required or look at re-filling tubes by means of smoke veggie juice owning your flavor.

    light red e-cigarette
    E-cigarettes for female
    Many ladies intend their particular e-cig for being stylish or cute as being a fashion accessory. They prefer ecigs by means of colorings that include light red, pink, or eco-friendly. In addition, they adore the people using a stone ravenscroft crystal Encouraged. A number of retailers give as an illustration light red ecigs and a couple of market people with ravenscroft crystal LEDs. Take a look at all of our e-cigs for women site to determine what retailers give stylish, cute, not to mention brilliant e-cigarettes not to mention essential accessories.

    Ladies moreover have a preference for their particular e-cig for being less heavy not to mention tinier. Your please just click url above to get details.

    The cost
    Costs for the purpose of e-cig employee products range on manufacturers through regarding $60 to over $200. But the starter kit sole tells a initial fee. Over time you must obtain once again install tubes. There you’ll want to look at the fee each cartridges but more grasp how long the cartridges endures. The numerous e-cig manufacturers do a comparison of their particular tubes to your selection of customary using tobacco or totes. Such as, for more cartridges even compares to an authentic carry, this cartridges presents several cigarette smoking as the customary carry may have. Your e-cig assessments on this internet site turn out this: the top e-cigarette won’t have for being the highest priced 1!

    Please normally check all information listed here to the brand’s blog.

    free electronic cigarette starter kit

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