HAEMATOLOGY

Answers to case study questions
Chapter 5
Case Study 5.1 We find a 50-year-old woman with long-term Crohn’s disease, on various treatments and with an abdominal surgical history. Her blood tests were requested following a routine GP visit, when she complained of some lethargy, fever and diarrhoea. (p. 125) 1 The results outside the reference range are haemoglobin, MCV and ESR. This result, along with the history, is sufficient to confer the diagnosis of anaemia. With the MCV below the bottom of the reference range, we can extend the diagnosis to microcytic anaemia. The abnormal ESR adds little to the diagnosis as it is the likely consequence of the anaemia. 2 Having given the patient a diagnosis, a treatment must be initiated. However, this is not yet possible as the basis of the microcytic anaemia must be defined. As the two major causes of microcytic anaemia are iron deficiency and haemoglobinopathy, the blood is tested for iron. A level below the bottom of reference range extends the diagnosis to iron-deficient microcytic anaemia. The reason for the vitamin B12 request is unclear, but as the result is within the reference range, then malnutrition as a cause seems unlikely. The diagnosis is not entirely unexpected given the history— Crohn’s disease being an inflammatory disorder of the intestines known to lead to malabsorption. Indeed, the inflammation may well contribute to the abnormal ESR. The referral to surgery may well have been to remove a section of diseased intestine. 3 The next step is to initiate treatment. This is likely to be subcutaneous, intra-muscular or intravenous iron. Perhaps a month or six weeks later a follow-up FBC and ESR should show some response. However, Crohn’s is a chronic inflammatory disease, so that there may also be a suppression of erythropoiesis that may need immunosuppression to rectify. Case Study 5.2 This case study describes a 75-year-old woman complaining of slowly developing fatigue causing her difficulty in getting out of her house. On examination, there is a swollen and painful tongue, and she complains of becoming forgetful, with occasional ‘tingling’ of her fingertips and numbness in her toes. (p. 135) 1 Results outside the reference range are haemoglobin, MCV and ESR. This result, along with the history, is sufficient to confer the diagnosis of anaemia. With the MCV above the top of the reference range, we can extend the diagnosis to macrocytic anaemia. The abnormal ESR adds little to the diagnosis as it is the likely consequence of the anaemia. 2 The key result is the low serum vitamin B12, which provides the most likely cause of the disease and symptoms. Indeed, the symptoms are typical. Normal iron levels seem likely to count against malnutrition. One could proceed to determine the precise cause of the deficiency, which, if found to be autoantibodies to gastric parietal cells or IF, will confer the diagnosis of pernicious anaemia. In most clear cases (such as this), examination of the bone marrow (to search for megaloblasts) seems unnecessary. 3 The next step will be treatment with parenteral vitamin B12, with monitoring after several weeks to confirm its effect on the full blood count. Case Study 5.3 An 82-year-old man complains of being tired and lethargic. On examination, he is pale and there is a distended and painful abdomen. He also complains of periodic diarrhoea and constipation and recalls that he has lost perhaps a stone in the past year. (p. 139) 1 The abnormalities are low haemoglobin and raised ESR. This, coupled with the history (being pale and complaining of tiredness and lethargy) is sufficient to give a diagnosis of anaemia. With an MCV within the normal range, we describe a normocytic anaemia. 2 If the anaemia is normocytic then we are likely, at this stage, to eliminate failure to provide micronutrients to the bone marrow. It is also unlikely that there is a haemoproliferative disease within the bone marrow (such as leukaemia) as the white blood cell count and platelet count are both within the reference range. This, however, still leaves numerous possible reasons, such as haemolysis, and other tests could be used to exclude some diagnoses, such as a direct or indirect antiglobulin test for autoimmune or other antibody-mediated haemolytic anaemia. 3 In many cases, non-laboratory information can be useful, and the history can provide clues. There is loss of weight over a year, and gastrointestinal symptoms. This is indicative of several possible diagnoses, bowel malignancy among them. If this is the cause of the anaemia, one mechanism may be loss of blood into the faeces, which would normally be undetectable. This can be tested with the test ‘faecal occult blood’.

Chapter 6
Case Study 6.1 In case study 1 (p. 176), the patient is a young woman from the Far East with a history of tiredness and lethargy but few other symptoms of note. Abnormalities include a low haemoglobin, MCH, MCV and MCHC, and a raised red blood cell count, reticulocytes and ESR. The Hct is borderline low. These, linked with the history, lead to a diagnosis of anaemia. Because the MCV is low, we can further qualify the diagnosis in describing the condition as microcytic anaemia. The leading causes of microcytic anaemia are iron deficiency and haemoglobinopathy. The former is easy to diagnose with iron studies, principally transferrin and ferritin. Diagnosis of the two major haemoglobinopathies, sickle cell disease and thalassaemia, is also

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ANSWERS TO CASE STUDY QUESTIONS

relatively simple with tests such as the sickle solubility test, electrophoresis, and HPLC. Case study 2 (p. 176) is a series of electrophoresis patterns (Figure 6.11, p. 167). The pattern in Sample 1 is identical to that of AS and AD, therefore additional tests are required in order to differentiate between the two and so make a final diagnosis. The Sample 2 pattern matches that of SC, providing a confident diagnosis. The pattern of Sample 3, of three distinct bands, does not match that of any of the controls. There is a line that corresponds with A, another that matches S and a third that could be either C or E. One explanation for this anomaly is contamination, but another is that the sample is from a patient who has recently had a transfusion. Sample 4 has a line that corresponds to haemoglobin S, but there is a second line which has migrated a small distance further towards the cathode. As there is no control sample that matches up to this line, we are unable to identify it from the existing panel. It may therefore be due to a minor haemoglobin species, and will demand more complex analyses to define its identity. Sample 5 has only a single line in the same position as the AA control, thus defining its diagnosis.

with a normal platelet count makes a primary haemostatic disorder unlikely. The severity of the bleed together with the results above and the patient’s gender suggest a haemophilia and further investigation would begin with assays for FVIII and FIX. Case Study 14.2 The first set of follow-up results suggest heparin contamination. The second set indicate severe DIC and would be accompanied by elevated levels of fibrin degradation products.

Chapter 15
Case Study 15.1 The only abnormal result here is a reduced functional protein C level. This is consistent with a type II protein C deficiency.

Chapter 16
Case Study 16.2 Almost all antibiotics can potentiate the effect of warfarin by inhibiting the intestinal flora that produce vitamin K. Any patient started on antibiotics needs to have their INR tested frequently and their warfarin dose adjusted appropriately to reduce the risk of bleeding.

Chapter 14
Case Study 14.1 The isolated elevated APTT that corrects on mixing indicates an intrinsic pathway defect. The lack of bleeding from minor trauma