Haematology Investigations Flashcards
Anaemia & Multiple Myeloma
You’re a medical intern on your first rotation. Your consultant thinks your patient has anaemia and wants them to be checked for it.
* Which blood test will check for anaemia?
What accompanying test can also be ordered?
FBC
Blood film
What is found on an FBC?
RBC and Haemoglobin values (HCT, MCV, MCH, MCHC, RDW)
WBC
Platelets
Neutrophils
Lymphocytes
Monocytes
Eosinophils, basophils
Here is an example of an FBC, what is the definition of each test name in the red box?
RBC=number of red blood cells per litre
* HB=amount of haemoglobin per decilitre
* HCT=percentage of red cells by volume
* MCV=mean cell volume=average(mean) size of the red blood cell
* MCH=mean cell haemoglobin=average haemoglobin per red blood cell
* MCHC=mean cell haemoglobin concentration=average haemoglobin per
red blood cell corrected by red cell size
* RDW=red cell distribution width=difference in size between the largest and
smallest red blood cells
Is anaemia a diagnosis?
No, the cause of it is
Define anaemia for males and females
Anaemia is the reduction in Hb concentration
Male: below 13
Female: below 12
What values on the FBC would tell you the colour (e.g. hypochromic)
MCH/MCHC
Give the morphological classification of anaemia and tell me the MCV, MCH, and blood film results expected for each
- Hypochromic Microcytic Anaemia
– Reduced MCV
– Reduced MCH
– Small cells on blood film - Normochromic Normocytic Anaemia
– Normal MCV
– Normal MCH
– Normal size cells on blood film - Macrocytic Anaemia
– Increased MCV
– Increased MCH
– Large cells on blood film
Give the 3 main causes of Hypochromic Microcytic Anaemia
Deficiency: Fe-deficiency anaemia
Genetic: Thalassaemia
Acquired: Sideroblastic anaemia
Half of patients presenting with microcytic anaemia have it due to Fe-deficiency. What are your differentials in this case?
Blood Loss: GI, Uterine,
Haematuria
Malabsorption: Coeliac disease,
Gastrectomy, Inadequate diet
Increased Demands: Pregnancy
Is sideroblastic anaemia microcytic, normocytic or macrocytic?
Genetic Sideroblastic anaemia is normocytic
Acquires sideroblastic anaemia is either microcytic or macrocytic (mostly microcytic)
A patient with Hypochromic Microcytic Anaemia is in the ward. Sideroblastic anaemia with no known genetic component to it was determined to be the cause. What are the causes of acquired sideroblastic anaemia
Alcohol abuse
Isoniazid/B6 deficiency
Trientine (used in Wilson’s as an alternative to penicillamine)
Cu deficiency
Zinc Deficiency
Lead poisoning
What type of anaemia is anaemia of chronic disease?
What is meant by that and what are some examples?
Mostly normocytic but may be microcytic as well
Malignancy
Chronic infection e.g. Tb
Chronic inflammation e.g. RA
Chronic kidney disease (reduced EPO production)
Other chronic conditions (CKD->EPO, crohn’s, HF, COPD…)
Haemolysis is one of the main causes of anaemia. What type of anaemia would haemolysis typically cause?
haemolysis can be divided into intravascular and extravascular causes. Give the Intravascular causes
Extravascular causes can be further subdivided into intrinsic and extrinsic to the RBC. Give 2 intrinsic and 2 extrinsic causes
How would you differentiate between an intravascular or extravascular cause of haemolysis?
What is the significance of a Coomb’s test in a case of haemolysis? What is another term for it?
Normochromic normocytic anaemia but may also less likely cause macrocytic, non-megaloblastic anaemia
Intravascular causes:
DIC
TTP (thrombotic thrombocytopenic purpura)
Malaria
Prosthetic valve degradation
ABO incompatibility
Extravascular causes:
Intrinsic: Sickle Cell Anaemia, G6PD deficiency
Extrinsic: Autoimmune, Hypersplenism!, Drug-induced, vasculitis
Ordering a blood film can differntiate between intravascular and extravascular causes of haemolysis:
Intravascular: Fragmented (schistocytes)
Extravascular: Tear-drop shapes (Extra-vascular)
Coombs or (Direct antiglobulin test) is used to determine if it is an immune or non-immune cause of haemolysis
Your consultant approaches you asking you to investigate a patient just admitted to the ward for “Bone Marrow infiltration”. You note it is a cause of anaemia. What type of anaemia?
Give 3 ddx
Normochromic normocytic anaemia
Leukemia
Multiple Myeloma
Metastatic disease
Myelofibrosis
What infectious diseases are known to cause pancytopenia? Give 3
HIV/AIDS
Viral hepatitis (B&C)
EBV
Parvovirus B19 (mostly reduced RBC)
Bone Marrow infiltration can cause pancytopenia. In an FBC showing pancytopenia, what would be your differential diagnoses?
1) Bone Marrow Infiltration => Leukemia, myelofibrosis, metastatic disease, Multiple Myeloma
2) Bone marrow aplasia: Aplastic anaemia, Nutritional deficiencies (B12, Folate)
3) Blood cell destruction (DIC/TTP) or sequestration (Hypersplenism)
4) Infectious diseases: HIV, Hep B&C, EBV
What is multiple myeloma?
Haematological malignancy characterized by the uncontrolled proliferation of malignant plasma cells in the bone marrow leading to the overproduction of a monoclonal Ig protein => BM infiltration causing Anaemia, Renal damage (raised creatinine), Bence Jones Proteinuria, lytic Bone lesions and hyperCalcemia.
What is meant by Bence-Jones Proteinuria
negative on urine dipstick despite evidence of acute kidney injury typically seen in multiple myeloma
Give 10 causes of Normochromic normocytic anaemia (you must categorize properly for 5/5)
a) Anaemia of chronic Disease
Malignancy
Chronic infection e.g. Tb
Chronic inflammation e.g. RA
Chronic kidney disease (reduced EPO production)
+ Genetic Sideroblastic anaemia
b) Acute/subacute blood loss
c) Haemolysis:
Intravascular causes:
DIC
TTP (thrombotic thrombocytopenic purpura)
Malaria
Prosthetic valve degradation
Extravascular causes:
Intrinsic: Sickle Cell Anaemia, G6PD deficiency
Extrinsic: Autoimmune, Hypersplenism!, Drug-induced
d) BM infiltration: Leukemia, Multiple Myeloma, Myelofibrosis, and metastatic disease
Macrocytic Anaemia can be megaloblastic or non-megaloblastic. What are the 2 main causes of megaloblastic anaemia?
B12/Folate deficiency
A 35 year old woman presents to her general practitioner with a 3 month history of fatigue and pre- syncope. She has no past medical history and is otherwise healthy. On examination she is pale with no other abnormality identified. A full blood count is performed which demonstrates a haemoglobin (Hb).
What type of anaemia is this?
What are your differentials?
What additional tests will you order?
Hypochromic microcytic anaemia
Fe-deficiency anaemia Blood Loss: GI, Uterine, Haematuria
Malabsorption: Coeliac disease,
Gastrectomy, Inadequate diet
Increased Demands: Pregnancy
Thalassaemia
Sideroblastic disease (alcohol abuse, copper deficiency, zinc toxicity, isoniazid/B6 deficiency, lead poisoning)
Blood film
Iron studies
A 60 year old man with a history of well controlled epilepsy is brought to the emergency department following a witnessed mechanical at home. On arrival he is orientated with GCS of 15. Vital signs are within normal limits. There is no evidence of bleeding. His FBC comes back as follows:
What type of anaemia is this?
What are your differentials?
What additional tests will you order?
Macrocytic anaemia. Given the history of epilepsy, the patient may be on anticonvulsants => Folate deficiency => Megaloblastic anaemia
Other differentials
B12: Deficiency: Vegan diet, pernicious anaemia, gastrectomy, crohn’s, ileal resection
Folate: Alcoholism, methotrexate, anticonvulsants
Non-megaloblastic:
Haemolysis
ethanol abuse
Hypothyroidism
aplastic anaemia
Myelodysplastic syndromes
Additional tests: Blood film, B12 levels, folate levels
A 75 year old woman presents to ED with a fall at
home. She admits a longstanding history of SOB, fatigue and weight loss.
What type of anaemia is this?
What are your differentials?
Reticulocytes are normal despite the anaemia + RDW is large => this is a mixed anaemia (the average size is normal but theyre made up of both microcytic and macrocytic cells)
=> differentials would be all the causes of microcytic and macrocytic and the workup would be for both as well
What is shown in this image
Blood film showing Schistocytes or Fragmented RBCs
A 70 year old man is referred by his GP with a 2/12 history of fatigue, dyspnoea and weakness. He denies any history of weight loss, bleeding, or altered bowel habit. He has a past hx of mechanical aortic valve placement 18 years ago. His blood results are as follows: Low Hb, Normal folate and B12, raised bilirubin, and schistocytes on blood film.
Physical Exam: Yellow tinge to his
sclera, no other abnormalities.
What is the most likely cause of the yellow sclera?
What type of anaemia is it?
What additional tests are essential to order?
Jaundice caused by haemolysis due to the prosthetic heart valves 18 years ago => it is degrading now
Normocytic anaemia due to intravascular haemolysis
Coombs test (Direct Antiglobulin test) to determine whether the haemolysis is caused by an immune or non-immune process. In this case it should be DAT-ve
also LDH may be ordered
A 57 year old woman presents with worsening fatigue, and intermittent night sweats. On examination she is jaundiced and has generalised lymphadenopathy with moderate hepatosplenomegaly. She is a non-smoker and does not drink alcohol. She has noticed a 5kg weight loss over the past year. She has no known medical conditions.
What type of anaemia is this?
What is the most likely underlying diagnosis?
Normocytic anaemia
There is a raised WCC but normal neutrophils with a blood film showing lymphocytosis => increased lymphocytes specifically
Bilirubin is also raised indicating haemolysis
Lastly a positive coomb’s test tells us it is immune-mediated.
With the history showing B symptoms including night sweats and weight loss, the most likely diagnosis is chronic lymphocytic leukemia as autoimmune hemolytic anaemia occurs in 55-66% of cases
An 87 year old lady presents with a 6 week history of worsening fatigue, shortness of breath on exertion, and weight loss. She reports that her friends have commented that she looks very pale. She has noticed multiple bruises on forearms and lower legs occurring frequently over the past 2 months. Her only significant past medical history is that she has had 3 urinary tract infections in the past few months but prior to this had otherwise been well. Her blood results are as follows:
What type of anaemia is this?
Give your differentials?
Normocytic anaemia
Differentials for pancytopenia
1) Bone Marrow Infiltration => Leukemia, myelofibrosis, metastatic disease, Multiple Myeloma
2) Bone marrow aplasia: Aplastic anaemia, Nutritional deficiencies (B12, Folate)
3) Blood cell destruction (DIC/TTP) or sequestration (Hypersplenism)
4) Infectious diseases: HIV, Hep B&C, EBV
An 88 year old lady presents to the ED complaining of acute onset headache, with blurred vision and lethargy, worsening over the past 2 weeks. Her
husband reports that she had been slightly confused in the past 24 hours. Upon further questioning, the patient reports worsening chronic back pain
over the past 2-3 months and some intermittent episodes of constipation, for which she has started taking laxatives
On examination: BP was 108/63 mmHg, HR 88 beats per minute, mild pitting oedema of the ankles, scattered fine bi-basal crepitations on auscultation.
What type of anaemia is this?
What is the most likely diagnosis?
What is the reason behind her worsening chronic back pain? How will you confirm
What is the reason she is having blurred vision, ankle oedema, headache, and bibasal creps?
Normocytic anaemia
Anaemia + AKI (raised creatinine) + Hypercalcaemia => Multiple myeloma
Reminder of Definition of Multiple Myeloma: Haematological malignancy characterized by the uncontrolled proliferation of malignant plasma cells in the bone marrow leading to the overproduction of a monoclonal Ig protein => BM infiltration causing Anaemia, Renal damage (raised creatinine), Bence Jones Proteinuria, lytic Bone lesions and hyperCalcemia.
Her worsening back pain/bone pain may be due to osteolytic lesions => must be confirmed with a skeletal survery including Xray of the feet, leg, femur, pelvis, spine, and skull
These additional symptoms are consistant with Hyperviscosity syndrome which is a complication of multiple myeloma.
Reminder of Definition of Multiple Myeloma: Haematological malignancy characterized by the uncontrolled proliferation of malignant plasma cells in the bone marrow leading to the overproduction of a monoclonal Ig protein => BM infiltration causing Anaemia, Renal damage (raised creatinine), Bence Jones Proteinuria, lytic Bone lesions and hyperCalcemia. What is meant by a plasma cell?
What are the main diagnostic investigations to confirm the diagnosis of Multiple Myeloma?
What supportive investigations will you perform to further increase your confidence in your diagnosis?
A plasma cell is a fully differentiated B-lymphocyte that produces a single type of antibody => one of the Igs will be disproportionately raised compared to the rest
Diagnosis via:
1) BM Aspirate: showing >10% plasma cells
2) BM Biopsy
3) SPEP/UPEP (serum/urine electrophoresis) showing M protein band
4) Skeletal survey: Evidence of lytic lesions
CRABBB:
C: Serum calcium - Hypercalcaemia
R: Renal U&E showing creatinine clearance <40ml/min
A: Anaemia: Hb <10 on FBC
B: Bone lytic lesions on skeletal survey
B: Bence-Jones proteinuria Urine dipstick negative for protein
B: Blood film showing Rouleaux formation
Others: Elevated LDH and ESR + MRI spine for spinal cord compression
What tool is used to obtain a bone marrow biopsy?
Trephine
