DATA INTERPRETATION FOR MEDICAL STUDENTS

Second Edition

Paul K Hamilton BSc(Hons), MB BCh BAO(Hons) MRCP(UK) MD Consultant Physician Belfast Health and Social Care Trust Belfast United Kingdom Ian C Bickle MB BCh BAO(Hons), FRCR Consultant Radiologist RIPAS Hospital Brunei Darussalam

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CONTENTS

Contents

Preface to second edition Acknowledgements Normal values 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Haematology Biochemistry Endocrinology T oxicology Pleural and peritoneal fluid analysis Microbiology Neurology Immunology Imaging Cardiology Pathology Genetics Respiratory medicine Interpreting bedside chart data Miscellaneous Complete clinical cases Index

vi vii viii 1 55 139 167 189 213 221 239 245 341 395 401 419 451 493 509 597

HAEMATOLOGY

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HAEMATOLOGY
One of the most frequently requested tests in medicine is the full blood picture (FBP). This contains a wealth of information about the components of blood. The typical constituent parts of the FBP are as shown in the box.

FULL BLOOD PICTURE A typical FBP comprises the following tests: Haemoglobin concentration (Hb) Mean cell volume (MCV) Mean corpuscular haemoglobin (MCH) Packed cell volume (PCV) Red cell distribution width (RDW) White cell count (WCC) incorporating a differential white cell count Platelet count Reticulocyte count

Abnormalities with red blood cells

Anaemia
Anaemia describes a low level of haemoglobin. It is usually defined by an arbitrary cut-off haemoglobin concentration (eg 13 g/dl in men aged >15 years, 12 g/dl in non-pregnant women aged >15 years and 11 g/dl in pregnant women), below which a patient is deemed to be anaemic. Before deciding on the particular subtype of anaemia present in a patient, it is worth looking at the other cell types described on the full blood picture. If there are problems with red cells, white cells and platelets, then the major problem is likely to be a disease of the bone marrow, and the test most likely to give the diagnosis would be a bone marrow biopsy.

DATA INTERPRETATION FOR MEDICAL STUDENTS

Abnormal white blood cells

ABNORMALITY
Hypersegmented neutrophils T oxic granulation of neutrophils Auer rods Smear cells

FOUND IN
Megaloblastic anaemias, chronic infections Bacterial infection, poisoning, burns, chemotherapy Acute myeloid leukaemia Chronic lymphocytic leukaemia

Leukoerythroblastic blood film

This is a term used to describe the overall appearance of a blood film in which immature red and white blood cells are seen in peripheral blood. There are several causes. CAUSES OF A LEUKOERYTHROBLASTIC BLOOD FILM

Coagulation disorders
Haemostasis (the process of stopping bleeding) is a complex process. It involves the interplay of blood vessel walls, platelets and clotting factors. The common tests used to assess coagulation are as follows:

COMMON TESTS OF COAGULATION

HAEMATOLOGY

Prothrombin time
The PT is dependent on clotting factors I, II, V, VII and X. In clinical practice, it is most commonly measured to assess the synthetic function of the liver (eg in liver failure), or to monitor the effects of warfarin therapy.

International normalised ratio

T o allow comparison of coagulation results between laboratories, the PT is often converted to the INR, by applying a correction factor. This takes into account differences in laboratory methods, and means that the patients INR should be the same regardless of the laboratory used to measure it. The INR is the parameter most commonly used to monitor the effects of warfarin. In a patient with normal coagulation, the INR will be close to 1.0 before warfarin is commenced. As warfarin is introduced, the INR rises. The higher the INR, the less coagulable the blood becomes (ie the more difficult it will be for the blood to clot). Target INRs are set, and warfarin dosing must be adjusted to aim for these targets.

DISEASE
Deep venous thrombosis (DVT) Pulmonary embolism (PE) Atrial fibrillation Mechanical prosthetic heart valve Recurrent DVT/PE in a patient with a therapeutic INR

TARGET INR
2.5 2.5 2.5 2.5 3.5

The essence of warfarin prescribing involves increasing the dose if the INR is too low, reducing the dose if the INR is too high, and omitting it if the INR is dangerously high or the patient is bleeding. An example of a warfarin prescribing chart is shown on page 486.

Activated partial thromboplastin time

The APTT depends on all clotting factors except factor VII. In clinical practice, the APTT is used most commonly in patients receiving an infusion of heparin. The APTT is monitored frequently, and the rate of the heparin infusion adjusted to achieve the desired level of anticoagulation. With the common prescribing of low-molecular-weight heparin, in preference to unfractionated heparin, this process is now performed infrequently. A frequent cause of concern relates to elevated APTT s in patients with central venous catheters. The proximal end of

DATA INTERPRETATION FOR MEDICAL STUDENTS such catheters are often filled with heparin to keep the lumina patent when they are not being used. A spuriously high APTT will be obtained if blood is withdrawn from one such lumen. If the APTT is tested on a sample of blood tested peripherally, the true value will be obtained.

Coagulation correction testing

In cases of deranged coagulation, laboratories will often perform a coagulation correction test. This is performed to detect problems in coagulation arising because of a low level of a particular clotting factor. Essentially, normal plasma (containing normal clotting factors) is mixed with the patients sample. If the patient is deficient in clotting factors, a deranged coagulation profile would be expected to normalise. There will be no change, however, if an inhibitor of coagulation is present. Specialised assays for individual clotting factors are also available.

Bleeding time
Bleeding time is measured directly at the bedside. A sphygmomanometer cuff is inflated around the patients arm to 40 mmHg. A specially designed blade is then used to make a small puncture in the arm. Blood is removed from the area at fixed time intervals (eg 15 s) using a piece of filter paper to soak it up. The time taken for bleeding to stop is recorded. Elevated bleeding times indicate defective platelet function or low platelet numbers. This test should not be performed if the patient is known to have severe thrombocytopenia. Bear in mind that patients with abnormal numbers or deranged function of platelets may also have abnormal bleeding. Patients with von Willebrand disease may have normal coagulation profiles.

DONT FORGET
Patients with von Willebrand disease may have normal coagulation profiles.

Disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC) is a disease of two apparently conflicting problems. On the one hand, fibrin deposition in various organs results in areas of micro-infarction. On the other hand, the bodys supplies of clotting factors become used up because of all the clotting, leaving the patient prone to bleeding.

HAEMATOLOGY

DISSEMINATED INTRAVASCULAR COAGULATION

A disease in which clotting and bleeding cause problems simultaneously.

Typical laboratory findings in DIC are as follows:

Raised PT and APTT Reduced fibrinogen Raised D-dimer Since clotting factors are reduced Due to widespread fibrin formation Due to the bodys attempt to break down the excess fibrin deposits

D-dimer
D-dimer is the most commonly measured fibrinogen/fibrin degeneration product. It is detected following clot formation in the vasculature, as the bodys fibrinolytic system attempts to break the clot down. D-dimer levels are often tested in cases of suspected deep venous thrombosis and pulmonary embolism, and in the majority of cases will be raised. However, D-dimer levels are also raised in many other conditions, and a raised level should always be interpreted in light of the clinical scenario.

Laboratory findings in bleeding disorders

PT
Warfarin treatment Heparin treatment Haemophilia A or B Liver disease DIC Increased Normal (or increased) Normal Increased Increased

APTT
Normal (or Increased) Increased

FIBRINOGEN
Normal Normal

Increased Increased Increased

Normal Normal Reduced

DATA INTERPRETATION FOR MEDICAL STUDENTS

Plasma cell dyscrasias

Diseases of plasma cells are common, and their investigation is often a cause for confusion. They represent a spectrum of disorders, with multiple myeloma being the most important at the undergraduate level, and monoclonal gammopathy of unknown significance (MGUS) being the most common. The hallmark of these conditions is that plasma cells secrete M protein in excess. The effects of multiple myeloma can be far-reaching, and can lead to the following features: Anaemia Renal impairment Low levels of normal immunoglobulins with resultant infections Bone involvement, causing bony pain, hypercalcaemia, lytic lesions and problems if bones collapse Hyperviscosity of the blood.

The conditions should be suspected if any of the following abnormalities are present: Elevated ESR Hypercalcaemia Anaemia Renal impairment Abnormal M-protein detected on plasma protein electrophoresis Abnormal quantities of immunoglobulin light chains in the serum (with an abnormal ratio) Low levels of immunoglobulins Lytic lesions on X-ray of bones Detection of Bence Jones protein in the urine (this represents immunoglobulin light chains) Abnormal plasma cells seen on bone marrow biopsy Elevated 2-microglobulin.

HAEMATOLOGY

Case 1.1
A 48-year-old retired civil servant is concerned with her pale colour and feelings of faintness that have occurred over the past 4 weeks. She had felt well before this and enjoyed regular trips to southern France. Brief clinical examination reveals pallor. Her blood tests come to your attention.

Hb MCV Plt WCC Serum iron Ferritin TIBC Vitamin B12 Folate

8.7 g/dl 64.5 fl 556 109/l 7.7 109/l 6 mol/l 10 g/l 90 mol/l 221 ng/l 8.2 g/l

1.

How would you interpret these results?

2. How would you proceed with investigation?

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DATA INTERPRETATION FOR MEDICAL STUDENTS

Answer 1.1

Low Hb MCV Plt WCC Serum iron Ferritin TIBC Vitamin B12 Folate 8.7 g/dl 64.5 fl 556 109/l 7.7 109/l 6 mol/l 10 g/l 90 mol/l 221 ng/l 8.2 g/l

Low High Low Low High

1. This patient has a microcytic anaemia. Her iron profile is in keeping with iron deficiency with a low iron, low ferritin and high TIBC. There is a mild thrombocytosis which may indicate active bleeding. 2. The most common cause for these findings in young women is menorrhagia. In an older female or male of any age, investigations should be carried out to exclude a sinister cause in particular an occult gastrointestinal tract malignancy. Investigations should begin with a thorough history and clinical examination which should include rectal examination. The next line of investigation usually involves gastrointestinal tract endoscopy.

HAEMATOLOGY

Case 1.2
A 57-year-old woman attends her GP complaining of tiredness. The GP knows her medical history well as she also suffers from Graves disease. A full blood count was analysed as well as haematinics.

Hb MCV Plt WCC Serum iron Ferritin TIBC Vitamin B12 Folate

9.9 g/dl 104.5 fl 199 109/l 6.7 109/l

21 mol/l 50 g/l 60 mol/l 22 ng/l 9.8 g/l

1.

Interpret these blood results.

Following these results the GP also requests another test shown below.

Anti-parietal cell antibody Anti-intrinsic factor antibody

Titre 1:220 Positive

2. What is the diagnosis?

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DATA INTERPRETATION FOR MEDICAL STUDENTS

Answer 1.2

Low Hb MCV Plt WCC Serum iron Ferritin TIBC Vitamin B12 Folate 9.9 g/dl 104.5 fl 199 109/l 6.7 109/l

High

21 mol/l 50 g/l 60 mol/l 22 ng/l 9.8 g/l

Low

Anti-parietal cell antibody Anti-intrinsic factor antibody

Titre 1:220 Positive

Abnormal Abnormal

1. The haemoglobin is low with an elevated mean cell volume. This patient has a macrocytic anaemia. Haematinics show a low vitamin B12 level. Iron studies and folate level are within normal limits. 2. The positive antibodies to gastric parietal cells and intrinsic factor indicate that the likely underlying cause of the anaemia is pernicious anaemia. You will note that the patient was already known to have an autoimmune disease Graves disease. Always remember that patients with one autoimmune disease are prone to developing another. A Schilling test would have been useful in this case. The initial test would show low levels of radiolabelled vitamin B12 in the urine. Once the patient was given oral intrinsic factor, urine vitamin B12 excretion would be expected to return to normal.

HAEMATOLOGY

Case 1.3
A 49-year-old woman with systemic sclerosis complains of malaise and palpitations. Her disease has been quiescent for 2 years and she is not on any immunosuppressant medications. She has a balanced diet and has had no previous surgery. Her rheumatologist requests the following tests:

Hb MCV Plt WCC Serum iron Ferritin TIBC Vitamin B12 Folate

8.2 g/dl 109.4 fl 169 109/l 6.2 109/l

23 mol/l 49 g/l 62 mol/l 31 ng/l >10 g/l Titre < 1:120 Negative

Anti-parietal cell antibody Anti-intrinsic factor antibody Schilling test

Without oral intrinsic factor: 0.03 g radioactive vitamin B12 in 24-h urine sample (3% of oral dose) With oral intrinsic factor: 0.03 g radioactive vitamin B12 in 24-h urine sample (3% of oral dose) Early peak in hydrogen excretion

Hydrogen breath test

1.

What would you infer from these results?

2. What is the reason for performing a hydrogen breath test?

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DATA INTERPRETATION FOR MEDICAL STUDENTS

Answer 1.3

Hb MCV Plt WCC Serum iron Ferritin TIBC Vitamin B12 Folate

8.2 g/dl 109.4 fl 169 109/l 6.2 109/l

Low High

23 mol/l 49 g/l 62 mol/l 31 ng/l >10 g/l

Low Less than 10% of oral dose excreted in urine

Anti-parietal cell antibody Anti-intrinsic factor antibody Schilling test Less than 10% of oral dose excreted in urine Hydrogen breath test

Titre < 1:120 Negative

Without oral intrinsic factor: 0.03 g radioactive vitamin B12 in 24-h urine sample (3% of oral dose) With oral intrinsic factor: 0.03 g radioactive vitamin B12 in 24-h urine sample (3% of oral dose) Early peak in hydrogen excretion Abnormal result

1. This patient has a macrocytic anaemia. Vitamin B12 is the only deficient haematinic, but the autoantibodies for pernicious anaemia are negative. The history states that the diet is balanced and no surgery has taken place on the bowel to interfere with the absorption of vitamin B12. The Schilling test is abnormal. Normally, at least 10% of the oral dose of radiolabelled vitamin B12 is excreted in the urine. In this case, the excreted dose is low, and supplementation with intrinsic factor makes no difference. The likely pathology is therefore in the ileum. 2. The abnormal hydrogen breath test result points to the cause of anaemia small bowel bacterial overgrowth. Patients with systemic sclerosis are prone to developing this condition. Definitive testing for bacterial overgrowth involves culturing small bowel contents. One would expect a normal Schilling test after an adequate course of appropriate antibiotics.

HAEMATOLOGY

Case 1.4
A 34-year-old accountant with a 15-year history of Crohns disease attends for outpatient review. He feels reasonable, although has not yet been able to hold down full employment after numerous hospital admissions and surgery over the past 10 years. His last surgery involved small bowel resection and anastomosis after further failure of medical therapy. The doctor in the clinic requests the following tests.

Hb MCV Plt WCC RDW Serum iron Ferritin TIBC Vitamin B12 Folate

8.9 g/dl 94.5 fl 399 109/l 9.7 109/l 20%

9 mol/l 10 g/l 80 mol/l 12 ng/l 1.8 g/l

What is your interpretation of these tests?

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DATA INTERPRETATION FOR MEDICAL STUDENTS

Answer 1.4

Low Hb MCV Plt WCC RDW Serum iron Ferritin TIBC Vitamin B12 Folate 8.9 g/dl 94.5 fl 399 109/l 9.7 109/l 20%

Normal

Raised Low Low High Low Low

13 mol/l 10 g/l 80 mol/l 12 ng/l 1.8 g/l

This man has a normocytic anaemia. He is deficient in iron, vitamin B12 and folate. The red cell distribution width (RDW) is raised, indicating a wide variation in the size of circulating red cells. The patient is likely to have a dimorphic blood picture, with small red cells resulting from iron deficiency, and large cells resulting from deficiencies of vitamin B12 and folate. Crohns disease is an inflammatory bowel disease involving the whole gastrointestinal tract so has the potential to cause deficiencies in all three haematinics. In this case, multiple operations have left him with a very short small bowel (short gut syndrome).

HAEMATOLOGY

Case 1.5
A 55-year-old woman with essential hypertension attends the medical clinic. Her blood pressure remains elevated despite treatment with four drugs. Her consultant commences her on methyldopa. Four weeks later she attends the accident and emergency department feeling generally unwell. The A&E doctor sends off a variety of blood tests, which are shown here.

Hb MCV Plt WCC Serum iron Ferritin TIBC Vitamin B12 Folate T otal bilirubin AST ALT GGT ALP

9.2 g/dl 93.4 fl 376 109/l 7.2 109/l

25 mol/l 154 g/l 65 mol/l 198 ng/l 6.5 g/l 45 mol/l 25 IU/l 22 IU/l 15 IU/l 98 U/l

She is admitted to the medical unit, and several other tests are requested.

Urinary urobilinogen Blood film Direct antiglobulin test

Positive Large numbers of reticulocytes Positive

1.

Interpret the results above

2. What is the likely diagnosis?

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