Chapter 1: Approach to the Patient

Table 1–1 lists abnormalities that often require an evaluation by a hematologist.

The care of a patient with a hematologic disorder begins with eliciting a medical history and performing a thorough physical examination. Certain parts of the history and physical examination that are of particular interest to the hematologist are presented here.

• Estimation of the "performance status" helps establish the degree of disability and permits assessment of the effects of therapy (Tables 1–2 and 1–3).

• Drugs and chemicals often induce or aggravate hematologic diseases; drug use or chemical exposure, intentional or inadvertent, should be evaluated. One should inquire about professionally prescribed and self-prescribed drugs, such as herbal remedies. Occupational exposures should be defined.

• Fever may result from hematologic disease or, more often, from an associated infection. Night sweats suggest the presence of fever. It is especially prevalent in lymphomas.

• Weight loss may occur in some hematologic diseases.

• Fatigue, malaise, lassitude, and weakness are common but are nonspecific symptoms and may be the result of anemia, fever, or muscle wasting associated with hematologic malignancy or neurologic complications of hematologic disease.

• Symptoms related to specific organ systems or regions of the body may arise because of involvement in the basic disease process, such as spinal cord compression from a plasmacytoma, ureteral or intestinal obstruction from abdominal lymphoma, or stupor from exaggerated hyperleukocytosis in chronic myelogenous leukemia.

• Hematologic disorders may be inherited as autosomal dominant, autosomal recessive, or X chromosome–linked traits (see Williams Hematology, 8th ed, Chap. 9, p. 129). The family history is crucial in such cases and should include information relevant to the disease in question in grandparents, parents, siblings, children, maternal uncles and aunts, and nephews. Careful and repeated questioning is often necessary because some important details, such as the death of a sibling in infancy, may be forgotten years later.

• Absence of a family history in a dominantly inherited disease may indicate a de novo mutation or non-paternity.

• Deviations from mendelian inheritance may result from uniparental disomy (patient receives two copies of a chromosome, or part of a chromosome, containing a mutation from one parent and no copies from the other parent) or genetic imprinting (same abnormal gene inherited from mother has a different phenotype than that inherited from father as a result of silencing or imprinting of one parent's portion of DNA) (see Williams Hematology, 8th ed, Chap. 10, p.141).

• One should obtain the history of the sexual preferences and practices of the patient.

Special attention should be paid to the following aspects of the physical examination.

• Skin: cyanosis, ecchymoses, excoriation, flushing, jaundice, leg ulcers, nail changes, pallor, petechiae, telangiectases, rashes (e.g., lupus erythematosus, leukemia cutis, cutaneous T-cell lymphoma).

• Eyes: jaundice, pallor, plethora, retinal hemorrhages, exudates, or engorgement and segmentation of retinal veins.

• Mouth: bleeding, jaundice, mucosal ulceration, pallor, smooth tongue.

• Lymph nodes: slight enlargement may occur in the inguinal region in healthy adults, and in the cervical region in children. Enlargement elsewhere, or moderate to marked enlargement in these regions, should be considered abnormal.

• Chest: sternal and/or rib tenderness.

• Liver: enlargement.

• Spleen: enlargement, splenic rub.

• Joints: swelling, deformities.

• Neurologic: abnormal mental state, cranial nerve abnormalities, peripheral nerve abnormalities, spinal cord signs.

The blood should be evaluated, both quantitatively and qualitatively. This is frequently achieved using automated equipment.

• Normal blood cell values are presented in Table 1–4.

The normal total leukocyte and differential leukocyte counts are presented in Table 1–5.

• Hemoglobin concentration is measured photometrically after conversion to a stable derivative, usually cyanmethemoglobin.

• Packed cell volume (hematocrit) may be measured directly by high-speed centrifugation of anticoagulated blood. Automated instruments derive the hematocrit from the product of erythrocyte count and the mean red cell volume.

• Mean cell volume (MCV) is determined directly in automated counters, or may be calculated by using the formula:

  

• The units are femtoliters (fL) or cubic micrometers per cell.

• Mean cell hemoglobin (MCH) is calculated as follows:

  

• The units are picograms per cell.

• Mean corpuscular hemoglobin concentration (MCHC) is calculated as follows:

  

• The units are grams of hemoglobin per deciliter (dL) of erythrocytes, or a percentage.

• Red cell distribution width (RDW) is calculated by some automatic counters and reflects the variability in red cell size. The term "width" in RDW is misleading; it is a measure of coefficient of variation of the volume of the red cells, and not the diameter. It is expressed as a percent.

  RDW = (Standard deviation of MCV ÷ mean MCV) × 100.

  — Normal values are 11 to 14 percent.

  — The presence of anisocytosis may be inferred from an elevated RDW value.

• Enumeration of erythrocytes, leukocytes, and platelets can be performed by manual methods by using diluting pipettes, a specially designed counting chamber, and a light microscope, but an electronic method provides much more precise data and is now used nearly universally for blood cell counts.

• Leukocyte differential count can be obtained from stained blood films prepared on glass slides. Normal values for adults are given in Table 1–5. The identifying features of the various types of leukocytes are summarized in Williams Hematology 8th ed, Chap. 2, p. 11; Chap. 59, p. 875; Chap. 67, p. 989; Chap. 74, p. 1079.

• Electronic methods that provide rapid and accurate classification of leukocyte types based largely on the physical properties of the cells have been developed and are in general use. For example, one system classifies cells based on size and peroxidase activity, while other systems classify the cells on the basis of volume, or a combination of volume, conductivity, and light scatter as described in Williams Hematology, 8th ed, Chap. 2, p.15.

• Properly stained blood films also provide important information on the morphology of erythrocytes and platelets as well as leukocytes. Examination of the blood film may suggest the presence of a number of diseases of the blood. These are listed in Table 1–6.

Infancy and Childhood

• Some components of the blood count in infancy and childhood differ significantly from those in adults.

• Hemoglobin levels are high at birth (19.3±2.2 (s.d.) g/dL) but fall over the first 12 weeks of life to reach levels that persist throughout childhood (11.3±0.9 (s.d.) g/dL). Adult levels in males are achieved after puberty. Red cell values for infants during the first 12 weeks of life are given in Williams Hematology, 8th ed, Chap. 6, Table 6–2, p. 91.

• The mean leukocyte count is high at birth (18 × 10⁹/L); neutrophils comprise about 60 percent of the cells. The leukocyte count falls over the next 2 weeks or so, to reach levels that persist throughout childhood. Lymphocytes are the predominant cell type for the remainder of the first 4 years of life (45–55%). Further details can be found in Williams Hematology, 8th ed, Chap. 6, Table 6–3, p. 93.

• Platelet counts are at adult levels throughout childhood.

• Leukocyte function may be depressed in normal infants in the newborn period.

• Reference values for coagulation factors in neonates and infants may be found in Williams Hematology, 8th ed, Chap. 6, Table 6–6, p. 98, and for coagulation factor inhibitors in neonates and infants in Table 6–7, p. 99.

Effects of Aging

• See Williams Hematology, 8th ed, Chap.8, p. 115.

• Blood count and cell function may also vary with advanced age.

• The hemoglobin levels of men older than 60 years of age are statistically lower than those of younger men, even in the absence of a demonstrable cause for anemia, but are not sufficiently low to warrant use of specific normal values for older men. Anemia in an older person warrants careful evaluation before concluding it is the anemia of aging.

• The hemoglobin level in women does not change significantly with advancing age.

• Total and differential leukocyte counts also do not change significantly with advancing age.

• Leukocytosis in response to infection (e.g., appendicitis or pneumonia) is the same in older individuals as in people younger than age 60, but special studies indicate that the marrow granulocyte reserve may be reduced in the older person.

• Both cellular and humoral immune responses are reduced in older patients.

• The erythrocyte sedimentation rate increases significantly with age.

• Aging is associated with a net proagulant propensity and an increased risk of venous thrombosis.

Utility of the Blood Film in Diagnosis

• The blood film is invaluable in developing the differential diagnosis or the specific diagnosis of a blood cell disorder. Table 1–6 lists several situations in which the blood film can be important or decisive.

The Marrow

• Examination of the marrow is important in the diagnosis and management of a variety of hematologic disorders.

• All bones contain hematopoietic marrow at birth.

• Fat cells begin to replace hematopoietic marrow in the extremities in the fifth to sixth year of life.

• In adults, hematopoietic marrow is limited to the axial skeleton and the proximal quarter of the humeri and femora.

• Hematopoietic marrow cellularity is reduced in the elderly, falling after age 65 from about 50 percent to 30 percent, roughly in inverse proportion to age.

• Marrow is obtained by aspiration and/or needle biopsy. The most frequently utilized site is the iliac crest at the posterior superior iliac spine. The Jamshidi needle is most often used for biopsy and provides excellent material for study.

• Aspirated marrow may be evaluated after preparation of thin or thick films on glass slides and appropriate staining.

• Marrow biopsies are examined after fixation, sectioning, and staining. Touch preparations provide useful information and should be made at the time of biopsy.

• Interpretation of marrow films and biopsy sections is discussed in Williams Hematology 8th ed, Chap. 3, p. 25 and under specific diseases for which a marrow is usually performed. Williams Hematology, 8th ed, Table 3–1, p. 30 contains the normal differential count of cells in the marrow.