CHAPTER 20

The haematological history

The blood is the generative part, the fountain of life, the first to live, the last to die and the primary seat to the soul.

William Harvey (1578–1657)

Haematological disorders

The range of haematological disorders includes the following:

• Abnormalities of red cells—for example, anaemia (too few red cells), polycythaemia (too many red cells) and haemoglobinopathies (abnormal haemoglobin molecules).

• Abnormalities of platelets—for example, thrombocytopenia (reduced platelet numbers), thrombocytosis (increased platelet numbers) and reduced platelet function, for example as a result of the use of anti-platelet drugs.

• Abnormalities of clotting factors—for example, haemophilia (clotting factor deficiency) and increased tendency to clotting (e.g. Factor V Leiden).

• Abnormalities of white cells—for example, neutropenia (reduced neutrophil numbers) and leukaemia (increased numbers of lymphocytes).

• Reductions in bone marrow production of white or red cells, or both (e.g. myelofibrosis, bone marrow infiltration).

• Cancers of lymph nodes (lymphoma).

• Abnormalities of immunoglobulin production—for example, myeloma (monoclonal overproduction) and immunoglobulin deficiencies.

Presenting symptoms

Major presenting symptoms are outlined in List 20.1.

LIST 20.1   Haematological history

Major symptoms

SYMPTOMS OF ANAEMIA

• Weakness

• Tiredness

• Dyspnoea

• Fatigue

• Postural dizziness

The patient may be aware of a problem that is associated with anaemia:

• bleeding (menstrual, gastrointestinal, after dental extractions)

• iron (microcytic anaemia; page 283) and vitamin B12 or folate deficiency (macrocytic anaemias; page 283)

• bone marrow abnormalities (e.g. infiltration, myelofibrosis, leukaemia)

• chronic disease

• haemoglobinopathy

• malaria.

SYMPTOMS OF CLOTTING ABNORMALITIES

• Easy bruising

• Purpura

• Bleeding into joints (haemophilia)

• Thrombotic tendency

The patient may know of previous problems with:

• coagulation (e.g. haemophilia)

• platelets (e.g. thrombophilias [a low platelet count], anti-platelet drugs)

• an increased risk of clotting (e.g. previous deep vein thrombosis [DVT], inherited clotting abnormality).

SYMPTOMS OF ABNORMALITIES OF WHITE CELLS

• Recurrent infections (e.g. neutropenia, myeloma, bone marrow suppression)

• Fever or jaundice

• Mouth ulcers

SYMPTOMS OF LYMPHOMA

• Lymph gland enlargement

• Malaise, loss of weight, fever, tiredness

SYMPTOMS OF MYELOMA

• Recurrent infections (e.g. pneumonia)

• Bone pain

• Symptoms of hypercalcaemia

• Enlargement of the tongue from secondary amyloidosis

RED CELL ABNORMALITIES

The numerous causes of anaemia make a careful history important in helping to work out the aetiology (see Questions Box 20.1). Patients with anaemia may present with weakness, tiredness, dyspnoea, fatigue or postural dizziness. Angina and heart failure may be precipitated by anaemia. Anaemia due to iron deficiency is often the result of gastrointestinal blood loss, or sometimes recurrent heavy menstrual blood loss, so these symptoms should be sought. The anaemia of chronic disease occurs as a result of bone marrow suppression associated with chronic illness such as infective endocarditis and chronic kidney disease. Ask about other illnesses. In much of the world chronic malarial infection or intestinal parasitic infection is the cause of chronic anaemia. Polycythaemia may be associated with pruritus and headache. Ask about chronic lung disease (hypoxia), which can be a cause. Excessive alcohol intake is associated with macrocytic anaemia and some vegan diets can lead to B12 deficiency. Previous resection of the stomach or terminal ileum can lead to B12 deficiency, and serious gastrointestinal disease can cause folate and iron deficiency because of malabsorption.

Questions box 20.1

Questions to ask the patient with anaemia

1. How was the problem diagnosed? (Routine tests or symptoms)

2. What symptoms have you had (e.g. tiredness, dyspnoea, angina)?

3. Have you noticed any bleeding from the bowel, or vomited any blood?

4. Have you noticed black bowel motions?

5. Have you had problems with stomach ulcers or inflammation of the bowel (colitis) or previous bowel operations?

6. Have you been taking arthritis tablets or blood-thinning tablets?

7. Have you had a recent operation or procedure? (Blood loss)

8. Have you had heavy periods?

9. What is your diet like? Do you drink much alcohol?

10. Do you take iron or vitamin supplements?

11. Have you had problems with your kidneys or a chronic severe arthritis? (Anaemia of chronic disease)

12. Have you ever needed a blood transfusion?

13. Have been generally unwell or had problems with recurrent infections or ulcers?

14. Is there a history of anaemia in the family? (Haemoglobinopathy) Do you know what the cause was?

PLATELETS

Disorders of platelet function may present with easy-bruising or bleeding problems. Ask about drug treatment; anti-platelet drugs are commonly prescribed for vascular disease. Reduced platelet numbers (thrombocytopenia), which is sometimes associated with increased bleeding risk, can occur as a result of autoimmune disorders (idiopathic thrombocytopenic purpura, ITP). Ask about previous traumatic or surgical splenectomy, which can result in increased platelet numbers (thrombocytosis).

RECURRENT INFECTION

Recurrent infection such as pneumonia may be the first symptom of a disorder of the immune system, including leukaemia, myeloma or HIV infection. The patient may have noticed lymph node enlargement, which can occur with lymphoma or leukaemia. Not all lumps are lymph nodes: consider the differential diagnosis (see List 20.2). Ask about fever, its duration and pattern. Lymphomas can be a cause of chronic fever, and viral infections such as cytomegalovirus and infectious mononucleosis are associated with haematological abnormalities and fever.

LIST 20.2   Differential diagnosis of suspected lymphadenopathy

1. Lipoma—usually large and soft; may not be in lymph node area

2. Abscess—tender and erythematous, may be fluctuant

3. Sebaceous cyst—intradermal location

4. Thyroid nodule—forms part of thyroid gland

5. Secondary to recent immunisation

Treatment history

Anaemia may have been treated with iron supplements or vitamin B12 injections. Anti-inflammatory drugs or anticoagulants may be the cause of bleeding. Supportive treatment for anaemia due to myelofibrosis or bone marrow failure may have included regular blood transfusions.

Polycythaemia or haemochromatosis (page 284) may have been treated with regular venesections.

Treatment for leukaemia, myeloma or lymphoma may have involved chemotherapy, radiotherapy, or both; or bone marrow transplant. Ask about the effects these complicated treatments have had on the patient’s life.

Splenectomy may have been performed for thrombocytopenia or lymphoma.

Past history

A history of gastric surgery or malabsorption may give a clue regarding the underlying cause of anaemia. Anaemia in patients with systemic disease such as rheumatoid arthritis or uraemia can be multifactorial.

Social history

A patient’s racial origin is relevant. Thalassaemia is common in people of Mediterranean or southern Asian origin. Rarely, very strict vegetarian diets can result in vitamin B12 deficiency. Find out the patient’s occupation and whether he or she has had work exposure to toxins such as benzene (risk of leukaemia). Ask whether the patient has had previous chemotherapy for a malignancy (drug-related development of leukaemia). Find out whether the patient drinks alcohol.

Family history

There may be a history of thalassaemia or sickle cell anaemia in the family. Haemophilia is a sex-linked recessive disease, while von Willebrand’sa disease is autosomal dominant with incomplete penetrance (see List 20.3).

LIST 20.3   Causes of purpura

Trauma

Thrombocytopenia or platelet dysfunction

Coagulation disorders

ACQUIRED

Vitamin K deficiency (leading to factor II, VII, IX and X deficiency)

Liver disease (impaired synthesis of clotting factors)

Anticoagulants (e.g. heparin, warfarin, proteins with anticoagulant activity)

Disseminated intravascular coagulation

CONGENITAL (RARELY CAUSE ECCHYMOSES AND USUALLY PRESENT WITH HAEMORRHAGE)

Haemophilia A (factor VIII deficiency)

Haemophilia B (factor IX deficiency, Christmas disease)

Von Willebrand’s disease (an inherited abnormality of the von Willebrand protein, which is part of the factor VIII complex and causes a defect in platelet adhesion)

Senile ecchymoses (due to loss of skin elasticity)

T&O’C essentials

1. Haematological symptoms are often not specific: many haematological and other diseases cause tiredness and malaise.

2. Anaemia is most often diagnosed on a routine blood test, not physical examination, but taking a careful history from patients can often give clues about its aetiology and help direct further tests.

3. Many medications can cause haematological problems and patients do not always appreciate these medications as being relevant (e.g. over-the-counter aspirin). Careful questioning is important to identify possible drug side effects as a cause of haematological disease.

4. Recurrent infection should arouse suspicions about underlying acute or chronic haematological disease.


aEA von Willebrand (1870–1949), Swedish physician, described this in 1926.