Haematology/Haem-oncology

Question 1

What is Gilbert’s syndrome?

Answer 1

Genetic Disorder that affects metabolism of bilirubin. Causing a raised UNCONJUGATED bilirubin.

Mostly asymptomatic.
Can get Jaundice

Is common, up t o 5% of a population

Question 2

What would “CRAB” symptoms indicate
Hypercalcemia, Renal insufficiency, Anaemia, Bone lesions?

Answer 2

Plasma Cell Disorder

MGUS (monoclonal gammopathy of undetermined significance)
Multiple Myeloma

Question 3

What might you find on bloods/serology for someone you suspect of MM?

(3)

Answer 3

Anaemia
Low eFGR, raised ACR
Elevated protein levels
Hypercalcemia

Question 4

What is the general clinical presentation of someone with Multiple Myeloma?

4 main general types

Answer 4

Quite vague, you need a high index of suspicion.

1. Can range from completely asymptomatic (with abnormal lab results)
   to
2. Non specific symptoms: weight loss, fatigue, nausea, recurrent infections (which you’d investigate for appropriately)
   to
3. Bone issues (pain, fractures)
4. Random symptoms; neuropathy, spinal cord compression, bleeding, unexplained thrombotic event.

Question 5

What tests to order for suspected Multiple Myeloma/MGUS?

Answer 5

Apart from
FBC
Calcium and creatinine renal function (EUC)
ESR (if not already done)

Also
-Peripheral blood smear
-Serum protein Electrophoresis and immunofixation
-Urine protein electrophoresis and immunofixation
-Serum Free light chain assay

Question 6

What is the most common cause for macrocytic anaemia?

Answer 6

Alcohol misuse

Question 7

What is the most common cause of megablastic anaemia, and what is megablastic anaemia?

Answer 7

Megaloblastic anaemia is a type of macrocytic anaemia when the bone marrow makes immature red cells, which are inherently larger than the eventual form.

Most common cause it’s pernicious anaemia. Inability to absorb B12 due to an autoimmune issue.

Question 8

What tests would you order for pernicious anaemia to help confirm the diagnosis?

Answer 8

Intrinsic factor antibodies. Only present half the time but highly sensitive

Parietal cell antibodies are present in 90% of people with pernicious anaemia but also in 22% of healthy people

Question 9

What else should you order when you suspect pernicious anaemia?

Answer 9

Serum B12 assay
Serum and red cell folate assay
If B12 deficient then proceed to antibodies testing

Question 10

Causes of macrocytic anaemia?

Answer 10

Alcohol

Megaloblastic anaemia: b12 deficient in diet, pernicious anaemia, gastrectomy, folate deficiency due to diet, anticonvulsants or Coeliac disease

Drugs. MTX, chemotherapy, azothioprine, anticonvulsants

Liver disease

Haemolytic anaemia

Myelodysplasia

Question 11

What are three main types of Haemoglobulinopathies?

Answer 11

1. Alpha Thalassaemia
2. Beta Thalassaemia
3. Sickle cell disease

Question 12

How does thalassaemia lead to anaemia?

Answer 12

The thalassaemia cause inclusions (bits of material) to build up in the red blood cell. This then triggers them for degradation by the spleen leading to anaemia.

Question 13

Treatment for thalassaemia may involve splenectomy and lifelong blood transfusions, what complication can arise from blood transfusions and what are its result sequelae.

Answer 13

iron overload

Can be treated with chelating agents, but there is still a risk of iron build up in organs: pituitary, heart, liver, pancreas leading to diabetes, endocrine issues, liver cirrhosis, cardiomyopathy

Question 14

What can cure thalassamia?

What are the risks?

Answer 14

Bone marrow transplant

Significant risk of mortality and complications

Question 15

With Alpha thalassaemia you essentially inherit 4 genes.

aa/aa is normal, what about the others and when is tranfusion needed and what is not viable with life.

1. aa/a-
2. a-/a- or aa/–
3. a-/–
4. –/–

Answer 15

1. aa/a-
   healthy, silent carrier
2. a-/a- or aa/–
   alpha thalassaemia minor, carier trait, may see changes in haematology results (mild hypochromic, microcytic anaemia)
3. a-/aa
   Mild to severe haemolytic anaemia
   HbH disease
   May require blood transfusions

4.–/–
Haemoglobin barts. hydrops fetalis. No live birth.

Question 16

In beta thalassaemia you (opposed to alpha) you only inherit 2 copies of the gene B/B

However you can have
B = normal
B+ = mutated and slightly functional
B0 = doesn’t work

B0/B0 would be called Beta thalassaemia major. result in severe anaemia, causing jaundice, splenomegaly, iron overload, bone deformities. What about the other combinations?

Answer 16

Clearly you only need one functioning B gene.

B+/B0 is also Beta thalassemia major

Question 17

at what age would you expect symptoms of beta thalassamia to manifest, and what would they be?

Answer 17

usually 6-12 months after birth

Pallor
Lethargy
Failure to thrive
irritability
Poor appetite
Difficulty settling
Developmental delay

might get
fractures
leg ulcers
bone deformities

Question 18

What is sickle cell disease?

Answer 18

this is when the structure of the B-globin chain is altered.

The disease is present only if homozygous, hence its autosomal recessive.

It leads to a chronic haemolytic anaemia when RBC form an irreversible sickle shape after repeated cycles of deoxygenation

Question 19

What are the three high risk categories, in which genetic screening should be offered?

What should screening start with?

Answer 19

1. Family history of anaemia, thalassaemia or other haemoglobin variant
2. Ethnicity: Southern Europe, middle east, africa, South east asia, Indian subcontinent, Pacific islanders, NZ (maori), South America and some Western Australian and Northern Territory Aboriginal communities.
3. Haemotology blood results
   MCV <80
   or
   MCH <27

Order
FBC
Haemoglobin electrophoresis
Iron Studies
Take blood for DNA studies

Question 20

Clotting disorders- what are the three main groups of them, and what do they cause?

Answer 20

Group one: lack of an anticoagulant protein. NOTE: ANTICOAGULANT protein
-remember that clot break down is a balance between thrombegnic and thrombocytic factors
(e.g. Protein C and protein S deficienc)

Group two: mutations in coagulant proteins that cause clotting
(e.g. factor V lieden)

Group three: abnormal fibrinolysis

ALL can lead to thrombosis.

Question 21

When is screening for thrombophilias (increased clotting) recommended?

Answer 21

a DVT < 50

Spontaneous thrombosis in absence of recognised risk factors

recurrent thrombosis

Family history of thrombosis

Thrombosis in unusual sites (eg. central nervous
system, abdominal veins, upper limb).

Question 22

Is there a role for primary prophylaxis in those with a thrombophilia?

What about travel?

What about Contraception?

Answer 22

No there is no recommendation for anticoagulant use, as the risk of anticoagulation complications outweigh the benefits at this stage

There are no recommendations for long distance driving, but you can follow the guidelines for air travel. Regular movement, compression stockings, avoidance of alcohol and sedatives.

Combined Oral Contraceptive pills are contraindicated

Question 23

What is the von willebrand disease?

Answer 23

This is NOT problem with increased clotting and thrombosis (vWD is NOT a thrombophilia)

vWD it is the opposite - a bleeding disorder. It is when there is a lack of von willebrand factor which normally helps PLATELETS aggregate.

It is the most common inherited bleeding disorder affecting 0.1 - 1% of the population

Different levels of it

1 (reduced levels) - mild bleeding
2 (several variants of abnormal structure, rare) - variable bleeding
3 (Near absence of vWF) - similar to haemophilia

Question 24

What are risk factors for a VTE?

Answer 24

Surgery < 1 month (especially if for a malignancy or hip/knee surgery)

Recent trauma< 1 month

Prolonged immobility > 3days

Cancer

Moderate to severe congestive heart failure

History of prior VTE

Family history of VTE

Thrombogenic cases: Factor V leiden, anti-thrombin/protein S or protein C deficiency

OCP use, HRT, tamoxifen

Obesity(BMI>30)

acute medical illness

pregnancy and post partum peroid

Older age > 70

(note smoking and even air travel are not part of this list)

Question 25

What are medical options for DVT/VTE prophylaxis?

Answer 25

Enoxaparin 40mg S/C, daily or 20mg if CrCl <30 Dalteparin 5000IU, S/C daily if CrCl > 30 Apixaban 2.5mg , orally, 12 hourly Rivoroxaban 10mg, orally, daily

Question 26

What is the prescription for mechanical therapies in VTE prophylaxis?

Answer 26

Graduated compression stockings that provide 16-20mmHg at the ankle level and fitted by a professional. Pneumatic compression devices.

Question 27

For patients with spontaneous superficial thrombophlebitis, especially if the thrombus involves thigh veins, consider treatment with...?

Answer 27

Dalteparin (CrCl 30 mL/min or more) 5000 units subcutaneously, once daily OR Enoxaparin CrCl 30 mL/min or more: 40 mg subcutaneously, once daily CrCl less than 30 mL/min: 20 mg subcutaneously, once daily

Question 28

Which scoring system would you use in a suspected DVT to determine the likelihood and therefore further investigation/treatment?

Answer 28

Wells Criteria for DVT

Question 29

What are the options to treat a DISTAL DVT

Answer 29

1. U/S monitoring IF significant bleeding risk 2. Apixaban 5mg, orally, 12 hourly for 6 weeks if provoked or at least 3 months if unprovoked (not exact guide when to stop)

Question 30

What is ITP? How is it treated?

Answer 30

Idiopathic Thromocytopenia Purpura Can occur in adults or children There is a low level of platelets, usually <100. Cause is not known, but thought to be triggered by viral infection- at least in children. It doesn't always need treatment. But would fall under specialist management to guide either prednisolone, IVIG or maybe splenectomy.

Question 31

What education should you provide to a family in a child that has idiopathic thromocytopenia purpura? (5)

Answer 31

Provide written information and letter to document diagnosis Restrict activities to minimise the risk of head injury: avoid contact sports (eg footy, rugby, soccer, hockey and martial arts) limit activities that have a risk for traumatic injury (eg horse-riding, riding a scooter, skate-board or bike, climbing on play-ground equipment) Avoid anti-platelet, non-steroidal and anticoagulant medications. Avoid intramuscular injections Monitor for significant bleeding symptoms and go immediately to the emergency department if they occur. e.g: epistaxis. Monitor for signs of ICH and go immediately to the emergency department if head injury or severe headache

Question 32

What is the main difference between leukemia and lymphoma?

Answer 32

Leukemia think of as lemonade- its liquid. affects cells in the bone marrow and the blood. Lymphoma. - think of as a lemon. It involves solid masses of lymphoid tissue. Can be lymph nodes or other lymph tissue like MALT. There is some crossover however. some leukemias can have a lymphoma component and vice versa.

Question 33

What are the subtypes of leukemia? (4)

Answer 33

myleoid vs. lymphoid Chronic vs acute leukemia can affect cells from the myeloid or lymphocyte lines. it doesn't refer to whether or not the lymph nodes are affected.

Question 34

What are the two types of lymphoma and how is is differentiated?

Answer 34

Hodgkins. vs. non-hodgkins lymphoma Reed-Sternberg cells are large, abnormal lymphocytes (a type of white blood cell) that may contain more than one nucleus. These cells are found in people with Hodgkin lymphoma.

Question 35

Chronic Lymphocytic Leukemia is the most common type of lymphoproliferate disease. What are some 4 categories of signs and symptoms? (4 categories)

Answer 35

* cytopenias – anaemia – leukopenia/neutropenia, with increased risk of infections * thrombocytopenia, with increased risk of bleeding * lymphadenopathy and splenomegaly * constitutional symptoms of malignancy (eg weight loss >10% in six months, fevers, night sweats).

Question 36

What is the most common cancer in children?

Answer 36

ALL acute lymphoblastic leukemia

Question 37

what is the difference between acute and chronic leukemias?

Answer 37

Yes acute leukemias tend to affect younger patients more and chronic tend to affect older patients more. However it comes down to the type of cell in the bone marrow. blasts= immature=acute cytes=more mature- takes more time hence chronic. If > 10% of 'blasts' then it is immature cells hence an acute leukemia if the blast cells are < 10% then you have more '-cyte' cells and this means it's more chronic as the cells have had time to mature. usually will see smudge cells in CLL.

Question 38

CLL is usually diagnosed on blood test before patients have symptoms. What cells may you find on peripheral blood smear?

Answer 38

Smudge cells

Question 39

What are signs of ALL? Acute lymphocytic leukemia?

Answer 39

Children with leukaemia can present with a variety of symptoms, most commonly pallor, lethargy, fever, easy bruising, pain in the bones or joints, swollen glands and/or weight loss.

Question 40

What white blood cells would you expect to be affected in MYELOID leukemia?

Answer 40

Neutrophils Monocytes Basophils Eosinophils

Question 41

What is this demonstrating?

Answer 41

Mainly mass confusion. There is considerable overlap between different haematological disorders. You have 1. proliferative disorders; myeloid vs. lymphoid 2. malignancies: myeloid vs. lymphoid and MM 3. marrow failure disorders including myelodysplastic syndrome 4. benign reactions such as to an infection raising lymphocytes or neutrophils.

Question 42

What is the difference between myeloproliferative disorders and myelodysplastic syndrome?

Answer 42

Myoloproliferative disorders are when myeloid cells are in over production. 4 types of these disorders -Polycythemia Vera -CML -Essential thrombocytosis -Primary Myelofibrosis Myeldyspastic syndromes are usually when there is abnormal maturation of cells, causing cytopenias.

Question 43

Given the great confusion caused by haematological proliferative disorders, when should a GP consider referral?

Answer 43

persistent cytosis (raised) on peripheral blood count without a clear alternative cause unexplained arterial or unusual site venous thrombosis regardless of FBE parameters evidence of elevated blood counts or anaemia with constitutional symptoms. Performing genetic testing for driver mutations such as BCR-ABL1 and JAK2 while awaiting haematology review may help in expediting the diagnosis. However this is not covered by MBS for GPs.

Question 44

This is abit over the top but.. In polycythaemia vera, microvascular-related symptoms such as ....(list 6)....may be evident.

Answer 44

headaches, dizziness, visual disturbances, plethora, erythromelalgia (intense erythema and burning pain in response to heat stimuli) and aquagenic pruritus (generalised pruritus experienced after exposure to water, typically during a hot bath)

Question 45

Three categories of causes for thromboytopenia?

Answer 45

1. Decreased platelet production: chemo, chronic alcohol use, infections (HIV, HCV, HBV, CMV, parvovirus), rare genetic things, myelodysplastic syndromes 2. Increased platelet consumption: drug induced, ITP, infections (as above), auto-immune destruction 3. Sequestration/other Alcohol Splenomegaly Chronic Liver Disease Gestational Basically anything that persists, or anything with symptoms should be referred to haematology