Med D - Haemotology

Question 1

Thrombocytopenia describes a ____ ________ ________. The normal platelet count is 150-450 x 109/L. There is a long list of causes of a low platelet count. They can be split into problems with ____________ or _____________.

Answer 1

Thrombocytopenia describes a low platelet count. The normal platelet count is 150-450 x 109/L. There is a long list of causes of a low platelet count. They can be split into problems with production or destruction.

Question 2

Reduced platelet production can occur with:

Answer 2

• Certain viral infections (e.g., Epstein-Barr virus, cytomegalovirus and HIV)
• B12 deficiency
• Folic acid deficiency
• Liver failure, causing reduced thrombopoietin production by the liver
• Leukaemia
• Myelodysplastic syndrome
• Chemotherapy

Question 3

Increased platelet destruction can occur with:

Answer 3

• Medications (e.g., sodium valproate and methotrexate)
• Alcohol
• Immune thrombocytopenic purpura (ITP)
• Thrombotic thrombocytopenic purpura (TTP)
• Heparin-induced thrombocytopenia (HIT)
• Haemolytic uraemic syndrome (HUS)

Question 4

Mild thrombocytopenia may be asymptomatic and found incidentally on a full blood count.

Platelet counts below 50 x 109/L will result in easy bruising and prolonged bleeding times. It may present with:

Answer 4

• Nosebleeds
• Bleeding gums
• Heavy periods
• Easy bruising
• Haematuria (blood in the urine)
• Rectal bleeding

Question 5

Platelet counts below 10 x 109/L are at high risk for spontaneous bleeding. Particularly concerning are:

Answer 5

• Intracranial haemorrhage
• Gastrointestinal bleeding

Question 5

What is Immune Thrombocytopenic Purpura

Answer 5

Immune thrombocytopenic purpura (ITP) can also be called autoimmune thrombocytopenic purpura, idiopathic thrombocytopenic purpura and primary thrombocytopenic purpura. They all refer to the same condition.

ITP is a condition where antibodies are created against platelets. An immune response against platelets leads to their destruction and a low platelet count (thrombocytopenia).

Question 6

The clotting system creates blood clots to stop bleeding. There are several ways this system can malfunction. The top differentials of abnormal or prolonged bleeding to remember are:

Answer 6

• Thrombocytopenia
• Von Willebrand disease
• Haemophilia A and haemophilia B
• Disseminated intravascular coagulation (usually secondary to sepsis)

Question 7

Presentation of ITP

Answer 7

It characteristically presents with purpura, which are non-blanching lesions caused by bleeding under the skin.

Question 8

Management of ITP

Answer 8

Care involves monitoring the platelet count, controlling blood pressure, and suppressing menstrual periods.

Management options include:

• Prednisolone (steroids)
• IV immunoglobulins
• Thrombopoietin receptor agonists (e.g., avatrombopag)
• Rituximab (a monoclonal antibody that targets B cells)
• Splenectomy

Question 9

What is Thrombotic Thrombocytopenic Purpura

Answer 9

Thrombotic thrombocytopenic purpura (TTP) is a condition where tiny thrombi develop throughout the small vessels, using up platelets. As the problem is in the small vessels, it is described as a microangiopathy. It causes:

Thrombocytopenia
Purpura
Tissue ischaemia and end-organ damage

Question 10

Thrombi develop due to a problem with a specific protein called ADAMTS13. This protein normally:

Answer 10

Inactivates von Willebrand factor
Reduces platelet adhesion to vessel walls
Reduces clot formation

Question 11

Deficiency in the ADAMTS13 protein can be due to:

Answer 11

• An inherited genetic mutation (hereditary)
• Autoimmune disease, where antibodies are created against the protein (acquired)

Question 12

Treatment for Thrombotic Thrombocytopenic Purpura

Answer 12

Treatment is guided by a haematologist and may involve plasma exchange, steroids and rituximab.

Question 13

What is Heparin-Induced Thrombocytopenia

Answer 13

**Heparin-induced thrombocytopenia (HIT) **involves the development of antibodies against platelets in response to heparin (usually unfractionated heparin, but it can occur with low-molecular-weight heparin). Heparin-induced antibodies target a protein on platelets called platelet factor 4 (PF4).

Question 14

What is Von Willebrand disease (VWD)

Answer 14

Von Willebrand disease (VWD) is the most common inherited cause of abnormal and prolonged bleeding.

In von Willebrand disease, there is a deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factor (VWF). Von Willebrand factor is important in platelet adhesion and aggregation in damaged vessels.

Question 15

How is Von Willebrand disease (VWD) inheritied

Answer 15

autosomal dominant.

Question 16

There are three types of von Willebrand disease:

Answer 16

• **Type 1 **involves a partial deficiency of VWF and is the most common and mildest type
• Type 2 involves the reduced function of VWF
• Type 3 involves a complete deficiency of VWF and is the most rare and severe type

Question 17

VWD presentation

Answer 17

Patients present with a history of unusually easy, prolonged or heavy bleeding:

• Bleeding gums with brushing
• Nosebleeds (epistaxis)
• Easy bruising
• Heavy menstrual bleeding (menorrhagia)
• Heavy bleeding during and after surgical operations

A family history of heavy bleeding (e.g., menorrhagia) or von Willebrand disease is relevant.

Question 18

Diagnosis of VDW

Answer 18

Diagnosis is based on a history of abnormal bleeding, family history, bleeding assessment tools and laboratory investigations. Due to the various underlying causes and types, there is no single von Willebrand disease test.

Question 19

VWD management

Answer 19

Von Willebrand disease does not generally require daily treatment. Management is needed in response to significant bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding). Options include:

• Desmopressin (stimulates the release of vWF from endothelial cells)
• Tranexamic acid
• Von Willebrand factor infusion
• Factor VIII plus von Willebrand factor infusion

Question 20

VWD management of heavy mentrual periods

Answer 20

Options for heavy menstrual periods include:

• Tranexamic acid
• Mefenamic acid
• Mirena coil
• Combined oral contraceptive pill
• Norethisterone

A hysterectomy (surgical removal of the uterus) may be required in severe cases of heavy menstrual bleeding.

Question 21

WHat is haemophilia A and B

Answer 21

Haemophilia A and B are severe inherited bleeding disorders. Haemophilia A is caused by a deficiency of factor VIII. Haemophilia B (also known as Christmas disease) is caused by a deficiency in factor IX.

Question 22

How are haemohpilia inherited?

Answer 22

X-linked recessive diseases

Question 23

Who do X linked recessive conditions primarly affect

Answer 23

haemophilia A and B primarily affect males because males only have one X chromosome and require only one abnormal copy to have the disease

Question 24

How can females be affected in X-linked recessive conditions?

Answer 24

For a female to be affected, they would require an affected father and a mother who is either a carrier or affected.

Question 25

Haemophilia
Most cases present in neonates or early childhood. It can present with ________ ____________, ________________ and ______ __________ in neonates

Answer 25

Most cases present in neonates or early childhood. It can present with intracranial haemorrhage, haematomas and cord bleeding in neonates

Question 26

Spontaneous bleeding into joints (____________) such as the ankle, knee or elbow can lead to joint damage and deformity. Bleeding into the muscles can cause ___________ __________

Answer 26

Spontaneous bleeding into joints (haemarthrosis) such as the ankle, knee or elbow can lead to joint damage and deformity. Bleeding into the muscles can cause compartment syndrome.

Question 27

Diagnosis of Haemophilia

Answer 27

Diagnosis is based on bleeding scores, coagulation factor assays and genetic testing

Question 28

Management of Haemophilia

Answer 28

The affected clotting factors (VIII or IX) can be given by intravenous infusion, either regularly or in response to bleeding. A complication of this treatment is the formation of **antibodies **(called inhibitors) against the treatment, resulting in it becoming ineffective.

Question 29

The mnemonic for remembering the causes of microcytic anaemia is “TAILS”:

Answer 29

T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia

Question 30

There are 3 As and 2 Hs for normocytic anaemia

Answer 30

A – Acute blood loss
A – Anaemia of chronic disease
A – Aplastic anaemia
H – Haemolytic anaemia
H – Hypothyroidism

Question 31

Megaloblastic anaemia is caused by:

Answer 31

B12 deficiency
Folate deficiency

Question 32

Normoblastic macrocytic anaemia is caused by:

Answer 32

• Alcohol
• Reticulocytosis (usually from haemolytic anaemia or blood loss)
• Hypothyroidism
• Liver disease
• Drugs, such as azathioprine

Question 33

What is Reticulocytosis

Answer 33

Reticulocytosis refers to an increased concentration of reticulocytes (immature red blood cells). This happens when there is a rapid turnover of red blood cells, such as with haemolytic anaemia or blood loss.

Question 34

There are many generic symptoms of anaemia:

Answer 34

• Tiredness
• Shortness of breath
• Headaches
• Dizziness
• Palpitations
• Worsening of other conditions, such as angina, heart failure or peripheral arterial disease

Question 35

Symptoms specific to iron deficiency anaemia include:

Answer 35

• Pica (dietary cravings for abnormal things, such as dirt or soil)
• Hair loss

Question 36

Signs of specific causes of anaemia include:

Answer 36

• Koilonychia refers to spoon-shaped nails and can indicate iron deficiency anaemia
• Angular cheilitis can indicate iron deficiency anaemia
• Atrophic glossitis is a smooth tongue due to atrophy of the papillae and can indicate iron deficiency anaemia
• Brittle hair and nails can indicate iron deficiency anaemia
• Jaundice can indicate haemolytic anaemia
• Bone deformities can indicate thalassaemia
• Oedema, hypertension and excoriations on the skin can indicate chronic kidney disease

Question 37

Ix for anemia

Answer 37

Blood tests depend on the suspected cause. Possible blood tests include:

• Full blood count for haemoglobin and mean cell volume
• Reticulocyte count (indicates red blood cell production)
• Blood film for abnormal cells and inclusions
• Renal profile for chronic kidney disease
• Liver function tests for liver disease and bilirubin (raised in haemolysis)
• Ferritin (iron)
• B12 and folate
• Intrinsic factor antibodies for pernicious anaemia
• Thyroid function tests for hypothyroidism
• Coeliac disease serology (e.g., anti-tissue transglutaminase antibodies)
• Myeloma screening (e.g., serum protein electrophoresis)
• Haemoglobin electrophoresis for thalassaemia and sickle cell disease
• Direct Coombs test for autoimmune haemolytic anaemia

A colonoscopy and oesophagogastroduodenoscopy (OGD) are indicated for unexplained iron deficiency anaemia to exclude gastrointestinal cancer as a source of bleeding.

A bone marrow biopsy is indicated for unexplained anaemia or possible malignancy (e.g., leukaemia or myeloma).