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DATA INTERPRETATION
FOR MEDICAL
STUDENTSSecond Edition
Paul K HamiltonBSc(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 RadiologistRIPAS Hospital
Brunei Darussalam
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Contents
Preface to second edition vi
Acknowledgements vii
Normal values viii
1. Haematology 1
2. Biochemistry 55
3. Endocrinology 139
4. Toxicology 167
5. Pleural and peritoneal fluid analysis 189
6. Microbiology 213
7. Neurology 221
8. Immunology 239
9. Imaging 245
10. Cardiology 341
11. Pathology 395
12. Genetics 401
13. Respiratory medicine 419
14. Interpreting bedside chart data 451
15. Miscellaneous 493
16. Complete clinical cases 509
Index 597
CONTENTS
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HAEMATOLOGY1
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One of the most frequently requested tests in medicine is the full blood
picture (FBP). This contains a wealth of information about the components ofblood. The typical constituent parts of the FBP are as shown in the box.
Abnormalities with red blood cells
AnaemiaAnaemia describes a low level of haemoglobin. It is usually defined by anarbitrary 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 isworth looking at the other cell types described on the full blood picture. Ifthere are problems with red cells, white cells and platelets, then the majorproblem is likely to be a disease of the bone marrow, and the test most likelyto give the diagnosis would be a bone marrow biopsy.
HAEMATOLOGY
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
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DATA INTERPRETATION FOR MEDICAL STUDENTS
Hypersegmented neutrophils
Toxic granulation of neutrophils
Megaloblastic anaemias, chronic infections
Bacterial infection, poisoning, burns, chemotherapy
Auer rods Acute myeloid leukaemia
ABNORMALITY FOUND IN
Abnormal white blood cells
Leukoerythroblastic blood film
This is a term used to describe the overall appearance of a blood film in whichimmature red and white blood cells are seen in peripheral blood. There areseveral causes.
CAUSES OF A LEUKOERYTHROBLASTIC BLOOD FILM
Coagulation disorders
Haemostasis (the process of stopping bleeding) is a complex process. Itinvolves the interplay of blood vessel walls, platelets and clotting factors.The common tests used to assess coagulation are as follows:
COMMON TESTS OF COAGULATION
Smear cells Chronic lymphocytic leukaemia
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HAEMATOLOGY
Prothrombin timeThe PT is dependent on clotting factors I, II, V, VII and X. In clinical practice, itis most commonly measured to assess the synthetic function of the liver (eg inliver failure), or to monitor the effects of warfarin therapy.
International normalised ratioTo allow comparison of coagulation results between laboratories, the PT isoften converted to the INR, by applying a correction factor. This takes intoaccount differences in laboratory methods, and means that the patients INRshould be the same regardless of the laboratory used to measure it.
The INR is the parameter most commonly used to monitor the effects ofwarfarin. In a patient with normal coagulation, the INR will be close to 1.0before warfarin is commenced. As warfarin is introduced, the INR rises. The
higher the INR, the less coagulable the blood becomes (ie the more difficult itwill be for the blood to clot). Target INRs are set, and warfarin dosing must beadjusted to aim for these targets.
DISEASE TARGET INR
Deep venous thrombosis (DVT)
Pulmonary embolism (PE)
Atrial fibrillation
Mechanical prosthetic heart valve
Recurrent DVT/PE in a patient with
a therapeutic INR
2.5
2.5
2.5
2.5
3.5
The essence of warfarin prescribing involves increasing the dose if the INR istoo low, reducing the dose if the INR is too high, and omitting it if the INR isdangerously high or the patient is bleeding. An example of a warfarinprescribing chart is shown on page 486.
Activated partial thromboplastin timeThe 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 adjustedto achieve the desired level of anticoagulation. With the common prescribing of
low-molecular-weight heparin, in preference to unfractionated heparin, thisprocess is now performed infrequently. A frequent cause of concern relates toelevated APTTs in patients with central venous catheters. The proximal end of
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such catheters are often filled with heparin to keep the lumina patent when theyare not being used. A spuriously high APTT will be obtained if blood iswithdrawn from one such lumen. If the APTT is tested on a sample of bloodtested peripherally, the true value will be obtained.
Coagulation correction testingIn cases of deranged coagulation, laboratories will often perform a coagulationcorrection test. This is performed to detect problems in coagulation arisingbecause of a low level of a particular clotting factor. Essentially, normal plasma(containing normal clotting factors) is mixed with the patients sample. If thepatient is deficient in clotting factors, a deranged coagulation profile would beexpected to normalise. There will be no change, however, if an inhibitor ofcoagulation is present. Specialised assays for individual clotting factors are alsoavailable.
Bleeding timeBleeding time is measured directly at the bedside. A sphygmomanometer cuffis inflated around the patients arm to 40 mmHg. A specially designed blade isthen used to make a small puncture in the arm. Blood is removed from the areaat fixed time intervals (eg 15 s) using a piece of filter paper to soak it up. Thetime taken for bleeding to stop is recorded. Elevated bleeding times indicatedefective 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 ofplatelets may also have abnormal bleeding. Patients with von Willebranddisease may have normal coagulation profiles.
DATA INTERPRETATION FOR MEDICAL STUDENTS
DONT FORGET
Patients with von Willebrand disease may have normal coagulation profiles.
Disseminated intravascular coagulationDisseminated intravascular coagulation (DIC) is a disease of two apparentlyconflicting problems. On the one hand, fibrin deposition in various organsresults in areas of micro-infarction. On the other hand, the bodys supplies ofclotting factors become used up because of all the clotting, leaving thepatient prone to bleeding.
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HAEMATOLOGY
DISSEMINATED INTRAVASCULAR COAGULATION
A disease in which clotting and bleeding cause problems simultaneously.
Typical laboratory findings in DIC are as follows:
D-dimerD-dimer is the most commonly measured fibrinogen/fibrin degenerationproduct. It is detected following clot formation in the vasculature, as thebodys fibrinolytic system attempts to break the clot down. D-dimer levels areoften tested in cases of suspected deep venous thrombosis and pulmonaryembolism, and in the majority of cases will be raised. However, D-dimer levelsare also raised in many other conditions, and a raised level should always beinterpreted in light of the clinical scenario.
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
Laboratory findings in bleeding disorders
PT APTT FIBRINOGEN
Warfarin treatment Increased Normal (or Increased) Normal
Heparin
treatment
Normal (or
increased)
Increased Normal
Haemophilia A or B Normal Increased Normal
Liver disease Increased Increased Normal
DIC Increased Increased Reduced
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DATA INTERPRETATION FOR MEDICAL STUDENTS
Plasma cell dyscrasiasDiseases of plasma cells are common, and their investigation is often a causefor confusion. They represent a spectrum of disorders, with multiple myelomabeing the most important at the undergraduate level, and monoclonalgammopathy 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 thefollowing 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 arepresent:
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 representsimmunoglobulin light chains)
Abnormal plasma cells seen on bone marrow biopsy
Elevated 2-microglobulin.
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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 wellbefore this and enjoyed regular trips to southern France. Brief clinicalexamination reveals pallor. Her blood tests come to your attention.
HAEMATOLOGY
Hb 8.7 g/dlMCV 64.5 fl
Plt 556 109/l
WCC 7.7 109/l
Serum iron 6 mol/l
Ferritin 10 g/l
TIBC 90 mol/l
Vitamin B12 221 ng/l
Folate 8.2 g/l
1. How would you interpret these results?
2. How would you proceed with investigation?
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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 bloodcount was analysed as well as haematinics.
HAEMATOLOGY
Hb 9.9 g/dl
MCV 104.5 fl
Plt 199 109/l
WCC 6.7 109/l
Serum iron 21 mol/l
Ferritin 50 g/l
TIBC 60 mol/l
Vitamin B12 22 ng/l
Folate 9.8 g/l
Anti-parietal cell antibody Titre 1:220
Anti-intrinsic factor antibody Positive
Following these results the GP also requests another test shown below.
1. Interpret these blood results.
2. What is the diagnosis?
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Answer 1.2
DATA INTERPRETATION FOR MEDICAL STUDENTS
Hb 9.9 g/dl
MCV 104.5 fl
Plt 199 109/l
WCC 6.7 109/l
Serum iron 21 mol/l
Ferritin 50 g/lTIBC 60 mol/l
Vitamin B12 22 ng/l
Folate 9.8 g/l
Anti-parietal cell antibody Titre 1:220
Anti-intrinsic factor antibody Positive
Low
High
Low
Abnormal
Abnormal
1. The haemoglobin is low with an elevated mean cell volume. This patient hasa macrocytic anaemia. Haematinics show a low vitamin B
12
level. Iron studiesand folate level are within normal limits.
2. The positive antibodies to gastric parietal cells and intrinsic factor indicatethat the likely underlying cause of the anaemia is pernicious anaemia. Youwill note that the patient was already known to have an autoimmunedisease Graves disease. Always remember that patients with oneautoimmune disease are prone to developing another.
A Schilling test would have been useful in this case. The initial test would showlow levels of radiolabelled vitamin B12in the urine. Once the patient was given
oral intrinsic factor, urine vitamin B12excretion would be expected to return tonormal.
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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 anyimmunosuppressant medications. She has a balanced diet and has had noprevious surgery. Her rheumatologist requests the following tests:
HAEMATOLOGY
1. What would you infer from these results?
2. What is the reason for performing a hydrogen breath test?
Hb 8.2 g/dlMCV 109.4 fl
Plt 169 109/l
WCC 6.2 109/l
Serum iron 23 mol/l
Ferritin 49 g/l
TIBC 62 mol/l
Vitamin B12 31 ng/l
Folate >10 g/l
Anti-parietal cell antibody Titre < 1:120
Anti-intrinsic factor antibody Negative
Schilling test Without oral intrinsic factor: 0.03 g radioactive vitamin
B12in 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)
Hydrogen breath test Early peak in hydrogen excretion
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Hb 8.2 g/dl
MCV 109.4 fl
Plt 169 109/l
WCC 6.2 109/l
Serum iron 23 mol/l
Ferritin 49 g/lTIBC 62 mol/l
Vitamin B12 31 ng/l
Folate >10 g/l
Anti-parietal cell antibody Titre < 1:120
Anti-intrinsic factor antibody Negative
Schilling test Without oral intrinsic factor: 0.03 g radioactive vitamin
B12in 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)
Hydrogen breath test Early peak in hydrogen excretion
Low
Low
Abnormal result
Less than 10% of
oral dose excreted
in urine
Less than 10% of
oral dose excreted
in urine
High
1. This patient has a macrocytic anaemia. Vitamin B12is the only deficienthaematinic, but the autoantibodies for pernicious anaemia are negative. Thehistory states that the diet is balanced and no surgery has taken place onthe bowel to interfere with the absorption of vitamin B12. The Schilling testis abnormal. Normally, at least 10% of the oral dose of radiolabelled vitaminB12is excreted in the urine. In this case, the excreted dose is low, andsupplementation with intrinsic factor makes no difference. The likelypathology 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 proneto developing this condition. Definitive testing for bacterial overgrowth
involves culturing small bowel contents. One would expect a normalSchilling test after an adequate course of appropriate antibiotics.
Answer 1.3
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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 holddown full employment after numerous hospital admissions and surgery over thepast 10 years. His last surgery involved small bowel resection and anastomosisafter further failure of medical therapy. The doctor in the clinic requests thefollowing tests.
HAEMATOLOGY
Hb 8.9 g/dl
MCV 94.5 fl
Plt 399 109/l
WCC 9.7 109/l
RDW 20%
Serum iron 9 mol/l
Ferritin 10 g/l
TIBC 80 mol/lVitamin B12 12 ng/l
Folate 1.8 g/l
What is your interpretation of these tests?
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Answer 1.4
DATA INTERPRETATION FOR MEDICAL STUDENTS
Hb 8.9 g/dl
MCV 94.5 fl
Plt 399 109/l
WCC 9.7 109/l
RDW 20%
Serum iron 13 mol/l
Ferritin 10 g/l
TIBC 80 mol/l
Vitamin B12 12 ng/l
Folate 1.8 g/l
This man has a normocytic anaemia. He is deficient in iron, vitamin B12andfolate. The red cell distribution width (RDW) is raised, indicating a widevariation in the size of circulating red cells. The patient is likely to have adimorphic blood picture, with small red cells resulting from iron deficiency, andlarge cells resulting from deficiencies of vitamin B12and folate. Crohns diseaseis an inflammatory bowel disease involving the whole gastrointestinal tract sohas the potential to cause deficiencies in all three haematinics. In this case,multiple operations have left him with a very short small bowel (short gutsyndrome).
Low
Normal
High
Raised
Low
Low
Low
Low
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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. Herconsultant commences her on methyldopa. Four weeks later she attends theaccident and emergency department feeling generally unwell. The A&E doctorsends off a variety of blood tests, which are shown here.
HAEMATOLOGY
She is admitted to the medical unit, and several other tests are requested.
Hb 9.2 g/dl
MCV 93.4 fl
Plt 376 109/l
WCC 7.2 109/l
Serum iron 25 mol/l
Ferritin 154 g/l
TIBC 65 mol/l
Vitamin B12 198 ng/l
Folate 6.5 g/l
Total bilirubin 45 mol/l
AST 25 IU/l
ALT 22 IU/l
GGT 15 IU/l
ALP 98 U/l
Urinary urobilinogen Positive
Blood film Large numbers of reticulocytes
Direct antiglobulin test Positive
1. Interpret the results above
2 Wh t i th lik l di i ?