The haematological history

The haematological examination

Haematological assessment does not depend only on the microscopic examination of the blood constituents. Physical signs, followed by examination of the blood film, can give vital clues about underlying disease. Haematological disease can affect the red blood cells, the white cells, the platelets and other haemostatic mechanisms as well as the mononuclear-phagocyte (reticuloendothelial) system.

Examination anatomy

An important part of the examination involves assessment of all the palpable groups of lymph nodes. As each group is examined its usual drainage area must be kept in mind (Figure 8.1). It follows that whenever an abnormality is discovered anywhere that might be due to infection or malignancy its draining lymph nodes must be examined.

Figure 8.1 Usual drainage areas of lymph nodes

Adapted from Epstein O et al, Clinical Examination, 4th edn, Edinburgh: Mosby, 2008.

The hands

The detailed examination begins in the usual way with assessment of the hands. Look at the nails for koilonychia—these are dry, brittle, ridged, spoon-shaped nails, which are rarely seen today. They can be due to severe iron deficiency anaemia, although the mechanism is unknown. Occasionally koilonychia may be due to fungal infection. They may also be seen in Raynaud’s phenomenon. Digital infarction (Figure 8.2) may be a sign of abnormal globulins (e.g. cryoglobulinaemia). Pallor of the nail beds may occur in anaemia but is an unreliable sign. Pallor of the palmar creases suggests that the haemoglobin level is less than 70 g/L, but this is also a rather unreliable sign.¹

Figure 8.2 Digital infarction

Note any changes of rheumatoid or gouty arthritis, or connective tissue disease (Chapter 9). Rheumatoid arthritis, when associated with splenomegaly and neutropenia, is called Felty’s syndrome^b: the mechanism of the neutropenia is unknown, but it can result in severe infection. Felty’s syndrome can also be associated with thrombocytopenia (Figure 8.3), haemolytic anaemia, skin pigmentation and leg ulceration. Gouty tophi and arthropathy may be present in the hands. Gout may be a manifestation of a myeloproliferative disease. Connective tissue diseases can cause anaemia because of the associated chronic inflammation.

Figure 8.3 Thrombocytopenic purpura

Now take the pulse. A tachycardia may be present. Anaemic patients have an increased cardiac output and compensating tachycardia because of the reduced oxygen-carrying capacity of their blood.

Look for purpura (Figure 8.3), which is really any sort of bruising, due to haemorrhage into the skin. The lesions can vary in size from pinheads called petechiae (from Latin petechia ‘a spot’) (Table 8.4) to large bruises called ecchymoses (Table 8.3).

TABLE 8.4 Causes of petechiae

Thrombocytopenia Platelet count <100 x 109/L Increased destruction Immunological: • immune thrombocytopenic purpura (ITP) • systemic lupus erythematosus • drugs, e.g. quinine, sulfonamides, methyldopa • Non-immunological: • damage, e.g. prosthetic heart valve • consumption, e.g. disseminated intravascular coagulation (DIC) • loss, e.g. haemorrhage Reduced production Marrow aplasia, e.g. drugs, chemicals, radiation Marrow invasion, e.g. carcinoma, myeloma, leukaemia, fibrosis Sequestration Hypersplenism

Platelet dysfunction

Congenital or familial

Acquired:

• myeloproliferative disease

• dysproteinaemia

• chronic renal failure, chronic liver disease

• drugs, e.g. aspirin

^* Eduard Henoch (1820–1910), professor of paediatrics, Berlin, described this in 1865, and Johannes Schönlein (1793–1864), Berlin physician, described it in 1868.

If the petechiae are raised (palpable purpura), this suggests an underlying systemic vasculitis, where the lesions are painful, or bacteraemia.

The forearms

If thrombocytopenia or capillary fragility is suspected, the Hess test^c can be performed.^d

Epitrochlear nodes

These must always be palpated. The best method is to flex the patient’s elbow to 90 degrees, abduct the upper arm a little and then place the palm of the right hand under the patient’s right elbow (Figure 8.4). The examiner’s thumb can then be placed over the appropriate area, which is proximal and slightly anterior to the medial epicondyle. This is repeated with the left hand for the other side. An enlarged epitrochlear node is usually pathological. It occurs with local infection, non-Hodgkin’s lymphoma^e or rarely syphilis. Note the features and different causes as listed in tables 8.5 and 8.6. Certain symptoms and signs suggest that lymphadenopathy may be the result of a significant disease (Good signs guide 8.1).

Figure 8.4 Feeling for the epitrochlear lymph node

TABLE 8.5 Characteristics of lymph nodes

TABLE 8.6 Causes of localised lymphadenopathy

GOOD SIGNS GUIDE 8.1 Factors suggesting lymphadenopathy is associated with significant disease

From McGee S, Evidence-based physical diagnosis, 2nd edn. St Louis: Saunders, 2007.

Axillary nodes

To palpate these, the examiner raises the patient’s arm and, using the left hand for the right side, pushes his or her fingers as high as possible into the axilla. The patient’s arm is then brought down to rest on the examiner’s forearm. The opposite is done for the other side (Figure 8.5).

Figure 8.5 Feeling for the axillary lymph nodes

There are five main groups of axillary nodes: (i) central; (ii) lateral (above and lateral); (iii) pectoral (medial); (iv) infraclavicular; and (v) subscapular (most inferior) (Figure 8.6). An effort should be made to feel for nodes in each of these areas of the axilla.

Figure 8.6 The main groups of axillary lymph nodes

A = central; B = lateral; C = pectoral; D = infraclavicular; E = subscapular.

The face

The eyes should be examined for the presence of scleral jaundice, haemorrhage or injection (due to increased prominence of scleral blood vessels, as in polycythaemia). Conjunctival pallor suggests anaemia and is more reliable than examination of the nail beds or palmar creases.³ In northern Europeans the combination of prematurely grey hair and blue eyes may indicate a predisposition to the autoimmune disease pernicious anaemia, where there is a vitamin B₁₂ deficiency due to lack of intrinsic factor secretion by an atrophic gastric mucosa.

The mouth should be examined for hypertrophy of the gums, which may occur with infiltration by leukaemic cells, especially in acute monocytic leukaemia, or with swelling in scurvy. Gum bleeding must also be looked for, and ulceration, infection and haemorrhage of the buccal and pharyngeal mucosa noted. Atrophic glossitis occurs with megaloblastic anaemia or iron deficiency anaemia. Multiple telangiectasiae may appear around the mouth or in the mouth in patients with hereditary haemorrhagic telangiectasia. Look to see if the tonsils are enlarged. Waldeyer’s ring^f is a circle of lymphatic tissue in the posterior part of the oropharynx and nasopharynx, and includes the tonsils and adenoids. Sometimes non-Hodgkin’s lymphoma will involve Waldeyer’s tonsillar ring, but Hodgkin’s disease rarely does.

Cervical and supraclavicular nodes

Sit the patient up and examine the cervical nodes from behind. There are eight groups. Attempt to identify each of the groups of nodes with your fingers (Figure 8.7). First palpate the submental node, which lies directly under the chin, and then the submandibular nodes, which are below the angle of the jaw. Next palpate the jugular chain, which lies anterior to the sternomastoid muscle, and then the posterior triangle nodes, which are posterior to the sternomastoid muscle. Palpate the occipital region for occipital nodes and then move to the postauricular node behind the ear and the preauricular node in front of the ear. Finally from the front, with the patient’s shoulders slightly shrugged, feel in the supraclavicular fossa and at the base of the sternocleidomastoid muscle for the supraclavicular nodes. Causes of lymphadenopathy, localised and generalised, are given in Table 8.7. Note that small cervical nodes are often palpable in normal young people.^4,5

Figure 8.7 Cervical and supraclavicular lymph nodes

1 = submental; 2 = submandibular; 3 = jugular chain; 4 = supraclavicular; 5 = posterior triangle; 6 = postauricular; 7 = preauricular; 8 = occipital.

TABLE 8.7 Causes of lymphadenopathy

The detection of lymphadenopathy should lead to a search of the area drained by the enlarged nodes. This may reveal the likely cause (see Table 8.6).

Bone tenderness

While the patient is sitting up, tap over the spine with the fist for bony tenderness. This may be caused by an enlarging marrow due to infiltration by myeloma, lymphoma or carcinoma, or due to malignant disease of the bony skeleton. Also gently press the sternum and both clavicles with the heel of the hand and then test both shoulders by pushing them towards each other with your hands.

The abdominal examination

Lay the patient flat again. Examine the abdomen carefully, especially for splenomegaly⁶ (Table 8.8, Good signs guide 8.2), hepatomegaly, para-aortic nodes (rarely palpable), inguinal nodes and testicular masses. Remember that a central deep abdominal mass may occasionally be due to enlarged para-aortic nodes. Para-aortic adenopathy strongly suggests lymphoma or lymphatic leukaemia. The rectal examination may reveal evidence of bleeding or a carcinoma.

TABLE 8.8 Causes of splenomegaly

Note: Secondary carcinomatosis is a very rare cause of splenomegaly.

^* Phillipe Charles Ernest Gaucher (1854–1918), who described this in 1882, was physician and dermatologist at the Hôpital St-Louis, Paris.

GOOD SIGNS GUIDE 8.2 Splenomegaly

From McGee S, Evidence-based physical diagnosis, 2nd edn. St Louis: Saunders, 2007.

Assessment of the patient with suspected malignancy is presented in Table 8.9.⁷

TABLE 8.9 Assessing the patient with suspected malignancy

Inguinal nodes

There are two groups—one along the inguinal ligament and the other along the femoral vessels. Small, firm mobile nodes are commonly found in otherwise normal subjects (Figure 8.8).

Figure 8.8 The groups of inguinal lymph nodes, their drainage areas and the position of the spleen

Adapted from Epstein O et al, Clinical Examination, 4th edn, Edinburgh: Mosby, 2008.

The legs

Inspect for any bruising, pigmentation or scratch marks. Palpable purpura over the buttocks and legs are present in Henoch-Schönlein purpura^g (Figure 8.9). Leg ulcers may occur above the medial or lateral malleolus in association with haemolytic anaemia (including sickle cell anaemia and hereditary spherocytosis), probably as a result of tissue infarction due to abnormal blood viscosity. Leg ulcers can also occur with thalassaemia, macroglobulinaemia, thrombotic thrombocytopenic purpura and polycythaemia, as well as in Felty’s syndrome. Chronic use of hydroxyurea for myeloproliferative disorders can cause malar ulcers.

Figure 8.9 Henoch-Schönlein purpura

From McDonald FS, ed., Mayo Clinic images in internal medicine, with permission. © Mayo Clinic Scientific Press and CRC Press.

Very occasionally, popliteal nodes may be felt in the popliteal fossa.

The legs should also be examined for evidence of the neurological abnormalities caused by vitamin B₁₂ deficiency: peripheral neuropathy and subacute combined degeneration of the spinal cord. Vitamin B₁₂ is an essential cofactor in the conversion of homocysteine to methionine; in B₁₂ deficiency, the lack of methionine impairs methylation of myelin basic protein. Deficiency of vitamin B₁₂ can also result in optic atrophy and mental changes. Lead poisoning causes anaemia and foot (or wrist) drop.

The fundi

Examine the fundi. An increase in blood viscosity, which occurs in diseases such as macroglobu, myeloproliferative disease or chronic granulocytic leukaemia, can cause engorged retinal vessels and later papilloedema. Haemo may occur because of a haemostatic disorder. Retinal lesions (multiple yellow-white patches) may be present in toxoplasmosis (see Figure 16.5) and cytomegalovirus infections (see Figure 16.6).

Examination of the peripheral blood film

This is a simple and useful clinical investigation.

A properly made peripheral blood film is one of the simplest, least invasive and most readily accessible forms of ‘tissue biopsy’, and can be a very useful diagnostic tool in clinical medicine. An examination of the patient’s blood film can (i) assess whether the morphology of red cells, white cells and platelets is normal; (ii) help to characterise the type of anaemia; (iii) detect the presence of abnormal cells and provide clues about quantitative changes in plasma proteins—e.g. paraproteinaemia; and (iv) help to make the diagnosis of an underlying infection, malignant infiltration of the bone marrow or primary proliferative haematological disorder. The following pages present illustrated examples of some clinical problems diagnosed by examination of the blood film (Figures 8.10 to 8.22).

Figure 8.10 Iron-deficiency anaemia

Red cells show varying shape and size and are generally hypochromic.

Figure 8.11 Megaloblastic anaemia

Red cells are macrocytic with many oval forms and the neutrophil is hypersegmented.

Figure 8.12 Spherocytic anaemia

Hereditary spherocytosis or autoimmune haemolytic anaemia. The numerous red blood cells which are small, round and lack central pallor are spherocytes (the big red blood cells are probably reticulocytes).

Figure 8.13 Autoagglutination

Cold haemagglutinin disease. Film shows clumping of red cells (low power).

Figure 8.14 Microangiopathic haemolysis (e.g. disseminated intravascular coagulation)

Frequent fragmented (bitten) red cells.

Figure 8.15 Sickle cell anaemia

Film shows several sickle-shaped cells with target cells probably secondary to the ‘autosplenectomy’ that occurs in this disease.

Figure 8.16 Leucoerythroblastic film

Film indicative of bone marrow infiltration. Shows circulating nucleated red blood cells and immature white cells.

Figure 8.17 Myelofibrosis

Film shows a dysplastic nucleated red blood cell, frequent tear-drop poikilocytes and a primitive granulocyte.

Figure 8.18 Postsplenectomy picture

Film shows several Howell-Jolly bodies, target cells and crenated cells.

Figure 8.19 Malaria

The two red cells in the centre show the trophozoite.

Figure 8.20 Viral illness (e.g. infectious mononucleosis)

Film shows two atypical or ‘switched-on’ lymphocytes.

Figure 8.21 Bacterial infection (e.g. pneumonia, infective endocarditis)

The white cell in the centre is a band form with prominent ‘toxic’ granules.

Figure 8.22 Acute leukaemia

The film shows two very primitive white cells with prominent nucleoli.

Correlation of physical signs and haematological disease

Signs of a severe anaemia of any cause include pallor, tachycardia, wide pulse pressure, systolic ejection murmurs due to a compensatory rise in cardiac output, and cardiac failure if myocardial reserve is reduced. There may be signs of the underlying cause.

Pancytopenia

Acute leukaemia

Leukaemia is a neoplastic proliferation of one of the blood-forming cells. Acute leukaemia presents with marrow failure from progressive infiltration of the marrow with immature cells. The course is rapidly fatal without treatment. Acute leukaemias can be divided into two main types: acute lymphoblastic leukaemia and acute myeloid leukaemia.

Chronic leukaemia

This is a haematological malignancy in which the leukaemic cell is at first well differentiated. These have a better prognosis untreated than acute leukaemia. There are two main types: chronic myeloid leukaemia and chronic lymphocytic leukaemia.

Myeloproliferative disease

This is a group of disorders of the haematopoietic stem cell. These include polycythaemia rubra vera, primary myelofibrosis, chronic myeloid leukaemia and essential thrombocythaemia. Overlapping clinical and pathological features occur in these disorders. Therefore, patients may have signs of one or more of the conditions. Any of them may progress to acute myeloid leukaemia.

Lymphoma (Figure 8.23)

This is a malignant disease of the lymphoid system. There are two main clinicopathological types: Hodgkin’s disease (with the characteristic Reed-Sternberg cellⁱ) and non-Hodgkin’s lymphoma. Signs of lymphoma depend on the stages of the disease (Table 8.12).

Figure 8.23 Cervical lymph node enlargement in a patient with lymphoma

From Mir MA, Atlas of Clinical Diagnosis, 2nd edn. Edinburgh: Saunders, 2003, with permission.

TABLE 8.12 Staging of lymphoma: Ann Arbor classification

Hodgkin’s disease often presents in stage I or II, while non-Hodgkin’s lymphoma usually presents in stage III or IV.

Multiple myeloma

This is a disseminated malignant disease of plasma cells.

Summary

The haematological examination: a suggested method (Figure 8.24)

This will be a targeted examination during follow-up consultations but should be completed in full for the first visit.

Figure 8.24 Haematological system examination

Lying flat (1 pillow)

1. General inspection

Weight (normal, reduced, increased)

Bruising (thrombocytopenia, scurvy etc)

• Petechiae (pinhead bleeding)

• Ecchymoses (large bruises)

Pigmentation (lymphoma)

Rashes and infiltrative lesions (lymphoma)

Ulceration (neutropenia)

Cyanosis (polycythaemia)

Plethora (polycythaemia)

Jaundice (haemolysis)

Scratch marks (myeloproliferative diseases, lymphoma)

Racial origin

2. Hands

Nails—koilonychia, pallor

Palmar crease pallor (anaemia)

Arthropathy (haemophilia, secondary gout, drug treatment etc)

Pulse

3. Epitrochlear and axillary nodes

4. Face

Sclera—jaundice, pallor, conjunctival suffusion (polycythaemia)

Mouth—gum hypertrophy (monocytic leukaemia etc.), ulceration, infection, haemorrhage (marrow aplasia etc.); atrophic glossitis, angular stomatitis (iron, vitamin deficiencies)

Tongue—amyloidosis

5. Cervical nodes (sitting up)

Palpate from behind

6. Bony tenderness

Spine

Sternum

Clavicles

Shoulders

7. Abdomen (lying flat) and genitalia

Inguinal nodes

Detailed examination

8. Legs

Vasculitis (Henoch-Schönlein purpura—buttocks, thighs)

Bruising

Pigmentation

Ulceration (e.g. haemoglobinopathies)

Neurological signs (subacute combined degeneration, peripheral neuropathy)

9. Other

Fundi (haemorrhages, infection etc)

Temperature chart (infection)

Urine analysis (haematuria, bile etc)

Rectal and pelvic examination (blood loss)

Position the patient as for a gastrointestinal examination. Make sure he or she is fully undressed, in stages and with a gown for women. Look for bruising, pigmentation, cyanosis, jaundice and scratch marks (due to myeloproliferative disease or lymphoma). Also note the presence of frontal bossing and the racial origin of the patient.

Pick up the patient’s hands. Look at the nails for koilonychia (spoon-shaped nails, which are rarely seen today and indicate iron deficiency) and the changes of vasculitis. Pale palmar creases may indicate anaemia (typically the haemoglobin level has to be lower than 70 g/L). Evidence of arthropathy may be important (e.g. rheumatoid arthritis and Felty’s syndrome, recurrent haemarthroses in bleeding disorders, secondary gout in myeloproliferative disorders).

Examine the epitrochlear nodes. Note any bruising. Remember, petechiae are pinhead haemorrhages, while ecchymoses are larger bruises.

Go to the axillae and palpate the axillary nodes. There are five main areas: central, lateral (above and lateral), pectoral (most medial), infraclavicular and subscapular (most inferior).

Look at the face. Inspecting the eyes, note jaundice, pallor or haemorrhage of the sclerae, and the injected sclerae of polycythaemia. Examine the mouth. Look for peri-oral telangiectasiae. Note gum hypertrophy (e.g. from acute monocytic leukaemia or scurvy), ulceration, infection, haemorrhage, atrophic glossitis (e.g. from iron deficiency, or vitamin B₁₂ or folate deficiency) and angular stomatitis. Look for tonsillar and adenoid enlargement (Waldeyer’s ring).

Sit the patient up. Examine the cervical nodes from behind. There are eight groups: submental, submandibular, jugular chain, supraclavicular, posterior triangle, postauricular, preauricular and occipital. Then feel the supraclavicular area from the front. Tap the spine with your fist for bony tenderness (caused by an enlarging marrow—e.g. in myeloma or carcinoma). Also gently press the sternum, clavicles and shoulders for bony tenderness.

Lay the patient flat again. Examine the abdomen. Focus on the liver and spleen. Feel for para-aortic nodes. Don’t forget to feel the testes, and to perform a rectal and pelvic examination (for tumour or bleeding). Spring the hips for pelvic tenderness. Palpate the inguinal nodes. There are two groups—along the inguinal ligament and along the femoral vessels.

Examine the legs. Note particularly leg ulcers. Examine the legs from a neurological aspect, for evidence of vitamin B₁₂ deficiency or peripheral neuropathy from other causes. Remember, hypothyroidism can cause anaemia and neurological disease.

Finally, examine the fundi, look at the tempera chart, and test the urine.