Haematology Flashcards
1
Q
What is Thalassaemia?
A
Thalassaemia = genetic defect in the protein chains that make up haemoglobin
2
Q
What inheritance pattern does alpha + beta thalassaemia follow?
A
Autosomal recessive
3
Q
Defects in the alpha chains in haemoglobin production lead to….
A
Alpha thalassaemia
4
Q
Defects in the beta chains in haemoglobin production lead to….
A
Beta thalassaemia
5
Q
What are the red cells like in patients with thalassaemia?
A
The RBCs are more fragile + break down more easily
6
Q
What happens to the spleen in thalassaemia?
A
Splenomegaly
(Spleen = acts like a sieve to filter blood + remove older RBCs → spleen collects all the destroyed RBCs → splenomegaly)
7
Q
What bone changes occur in thalassaemia and why do they occur?
A
Pronounced forehead + malar eminences (cheekbones)
* Bone marrow = expands to produce more RBCs → to compensate for chronic anaemia
* Casuses susceptibility to fractures + prominent features → pronounced forehead + malar eminences
8
Q
An infant presents with:
* Fatigue
* Pallor
* Jaundice
* Gallstones
* Splenomegaly
* Poor growth and development
* Pronounced forehead and malar eminences
On his blood tests: microcytic anaemia (low MCV).
Possible diagnosis?
A
Thalassaemia
9
Q
What investigations do you request when you suspect thalassaemia?
A
- FBC → shows microcytic anaemia
- Haemoglobin electrophoresis → diagnoses globin abnormalities
- DNA testing → looks for genetic abnormality
Pregnant women = offered a screening test for thalassaemia
10
Q
What test is used to diagnose globin abnormailities?
Used in thalassaemia
A
Haemoglobin electrophoresis
11
Q
What is a major complication with thalassaemia?
A
Iron overload
(causes similar effects to haemochromatosis)
12
Q
Why does iron overload occur in thalassaemia?
A
As a result of:
* Faulty creation of RBCs
* Recurrent transfusions
* Increased absorption of iron in gut (response to anaemia)
13
Q
What blood test is required and monitored for iron overload in thalassaemia patients?
A
Serum ferritin
14
Q
How do you manage iron overload in thalassaemia patients?
A
- Limiting transfusions
- Iron chelation
15
Q
What are the effects of iron overload in thalassaemia?
A
- Fatigue
- Liver cirrhosis
- Infertility
- Impotence
- Heart failure
- Arthritis
- Diabetes
- Osteoporosis and joint pain
16
Q
What is alpha thalassaemia caused by?
A
Defects in the alpha globin chains coded on chromosome 16
17
Q
What is the management for alpha-thalassaemia?
A
- Monitoring the full blood count
- Monitoring for complications
- Blood transfusions
- Splenectomy may be performed
- Bone marrow transplant can be curative
18
Q
What is beta-thalassaemia caused by?
A
Defective beta globin chains coded on chromosome 11
19
Q
What are the 3 types of beta thalassaemia?
A
- Thalassaemia minor
- Thalassaemia intermedia
- Thalassaemia major
20
Q
What genotype is Thalassaemia Minor?
A
One abnormal gene + one normal gene
(Patients with beta thalassaemia minor = carriers of abnormally functioning beta globin gene
21
Q
What does thalassaemia minor cause?
A
Mild microcytic anaemia
22
Q
What is the genotype for thalassaemia intermedia?
A
2 abnormal copies of beta globin gene
* 2 defective genes
* One defective gene + one deletion gene
23
Q
```
~~~
What does thalassaemia intermedia cause?
A
A more significant microcytic anaemia
(compared to thalassaemia minor)
24
Q
What is the geneotype for thalassaemia major?
A
Homozygous for the deletion genes
(no functioning beta globin genes at all)
25
How does thalassaemia present in early childhood?
* Severe anaemia
* Failure to thrive
26
What thalassaemia major cause?
* Severe microcytic anaemia
* Splenomegaly
* Bone deformities
27
What is the management for thalassaemia minor, intermedia, major?
* Thalassaemia Minor → monitoring + no active treatment
* Thalassaemia Intermedia → occassional blood transfusions + iron chelation
* Thalassaemia major → regular transfusions + iron chelation + splenectomy + bone marrow (curative)
28
What is Von Willebrand disease (VWD)?
An inhereited deficiency, absence or malfunctioning of a **glycoprotein** called **von Willebrand factor (VWF)** → Causes **abnormal + prolonged bleeding**
29
What is von Willebrand factor used for?
Platelet adhesion + aggregation in damaged vessels
30
What are the 3 types of von Willebrand disease?
* Type 1 → **partial deficiency** of VWF (most common, mildest)
* Type 2 → **reduced function** of VWF
* Type 3 → **complete deficiency** of VWF
31
What is are the clinical manifestations of von Willebrand disease?
Patients usually present with a Hx 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
32
What is the key question that you should ask in a family history when thinking about von Willebrand disease?
Any family history of **heavy bleeding (e.g. menorrhagia) or von Willebrand disease itself
33
What are the investigations for von Willebrand disease?
**No single von Willebrand disease test**
Diagnosis based on:
* History of abnormal bleeding
* FHx
* Bleeding assessment tools
* Laboratory investigations
34
When do you only manage Von Willebrand disease?
In response to:
* Significant bleeding
* Trauma (to stop bleeding)
* In preparation to operations (to prevent bleeding)
35
Name some forms of management for von Willebrand disease
* **Desmopressin** (stimulates the release of vWF from endothelial cells)
* **Von Willebrand factor** infusion
* **Factor VIII + von Willebrand factor** infusion
* **Tranexamic acid**
For heavy menstrual periods:
* Tranexamic acid
* Mefenamic acid
* **Mirena coil**
* Hysterectomy
36
What is immune thrombocytopenic purpura (ITP)?
ITP = a condition where **antibodies** are created **against platelets** → leads to their **destruction** + **low platelet count (thrombocytopenia)**
37
How does ITP usually present?
**Purpura**
(**non-blanching lesions** caused by bleeding under the skin)
38
What is the managment for ITP?
Management:
* **Prednisolone (steroids)**
* **IV immunoglobulins**
* Thrombopoietin receptor agonists (e.g., avatrombopag)
* **Rituximab** (a monoclonal antibody that targets B cells)
* Splenectomy
39
What is Haemophilia (A and B)?
**Severe inherited bleeding disorders**
40
What is haemophilia **A** caused by?
**Haemophilia A** = caused by a deficiency of **factor VIII**
## Footnote
A = Ayyyyyyy-tt
41
What is haemophilia **B** caused by?
**Haemophilia B** = caused by a deficiency in **factor IX**
## Footnote
B 9 (be mine)....trying
42
What inheritence pattern does haemophilia A and B follow?
**X-linked recessive diseases**
(**All** X chromosomes need to have the **abnormal gene** to have haemophilia)
Since X-linked:
* **Males → when they inherit 1 copy → affected**
* Females → inherit 1 copy → asymptomatic carrier; inherit 2 copies → symptomatic
43
Since haemophilia is X-linked recessive, what gender does the condition affect more?
**Haemophilia** = affects primarily **males**
44
Most cases of haemophilia present in **neonates** or **early childhood**. How does haemophilia occur in neonates?
* Intracranial haemorrhage
* Haematomas
* Cord bleeding
45
What can happen to the joints and muscles in people with haemophilia?
Bleeding into the:
* **Joints** (**haemarthrosis**) e.g. ankle, knee, elbow → **joint damage + deformity**
* **Muscles** → causes **compartment syndrome**
46
What are patients with haemophilia at risk of?
## Footnote
Very basic question
* Excess bleeding in response to minor trauma
* **Sponatenous bleeding** without trauma
47
Apart from the joints and muscles, where can bleeding occur in patients with haemophilia?
* Oral mucosa
* Nosebleeds (**epistaxis**)
* Gastrointestinal tract
* Urinary tract → **haematuria**
* Intracranial haemorrhage
* Surgical wounds
48
What investigations do you request for haemophilia?
* Bleeding scores
* Coagulation factor assays
* Genetic testing
49
What is the management for haemophilia A and B?
Regularly or in response to bleeding (via IV):
* Haemophilia A → factor VIII
* Haemophilia B → factor IX
## Footnote
A complication is the formation of **antibodies (inhibitors)** against the treatment → resulting in it becoming **ineffective**
50
What is sickle cell anaemia?
Genetic condition that causes **sickle** (cresent) shaped RBCs
51
What does sickle cell anaemia do to the RBCs?
Sickle shaped → more **fragile** → **easily destroyed**
Causing **haemolytic anaemia**
52
What type of anaemia does sickle cell anaemia cause?
**Haemolytic anaemia**
53
What are patients with sickle cell anaemia prone to?
**Sickle cell crises**
54
When in gestation does production of fetal haemoglobin (HbF) decrease and adult haemoglobin (HbA) increase?
32-36 weeks gestation
(Gradual transition from HbF to HbA)
55
At birth what percentage of HbF is left?
5O% HbF
(50% HbA)
## Footnote
At 6 months very little HbF is left
56
What variant of haemoglobin is present in sickle cell anaemia?
Abnormal variant called **haemophilia S (HbS)**
(results in sickle-shaped RBCs)
57
What inheritance pattern does sickle cell anaemia follow and which chromosome?
**Autosomal recessive**
Affects the gene for **beta-globin**
**Chromosome 11**
58
Since sickle cell anaemia is autosomal recessive, what happens when people inherit one or two copies of HbS?
* 1 copy → sickle cell trait → usually asymptomatic carriers
* 2 copies → sickle-cell disease
59
Why is the sickle cell trait more common in area like Africa, India, Middle East and the Caribbean?
There is a **selective advantage** → having the **sickle cell trait** makes them **more likely to survive MALARIA** → it is then more likely to be passed on
60
When is sickle cell anaemia screened for?
* **Newborn blood spot** (around 5 dats of age)
* **Pregnant women** at high risk of being carriers of HbS are offered testing
61
Name 4 complications of sickle cell anaemia
* Anaemia
* Increased risk of infection
* Chronic kidney disease
* Sickle cell crises
* Acute chest syndrome
* Stroke
* Avascular necrosis in large joints such as the hip
* Pulmonary hypertension
* Gallstones
* Priapism (painful and persistent penile erections)
62
What are sickle cell crises?
A spectrum of **acute exacerbations** caused by sickle cell disease
(mild to life-threatening)
63
What are sickle cell crises caused by?
* Spontaneously
Or triggered by:
* Dehydration
* Infection
* Stress
* Cold weather
64
What is the treatment for a sickle cell crisis?
**No sepcifc treatment** → managed **supportively**
* Low threshold for admission to hospital
* **Treating infections** that may have triggered the crisis
* **Keep warm**
* Good hydration (**IV fluids** may be required)
* **Analgesia** (NSAIDs should be avoided where there is renal impairment)
65
What is a vaso-occlusive crisis (VOC)?
AKA **Painful crisis** in sickle cell anaemia
* Sickle-shaped RBCs = **clog capillaries** → causing **distal ischaemia**
Typically presents as:
* **Pain + swelling** in **hands + feet** (also chest, back, other areas)
* Can be asssociated with **fever**
66
What is the urological emergency caused by a vaso-occlusive crisis in a patient with sickle cell anaemia?
**Priapism**
* Trapping of blood in the penis → causing **persistent + painful erection**
* Treated by aspirating blood from the penis
67
What is a splenic sequestration crisis?
In a patient with sickle cell anaemia → RBCs blocking the blood flow within the spleen → emergency
Presents as:
* **Acutely enlarged + painful spleen**
Blood pooling in the spleen → can lead to **severe anaemia + hypovolaemic shock**
68
What is the management for splemic sequestration crisis?
**Blood transfusions + fluid resuscitation**→ to treat **anaemia + shock**
**Splenectomy** → preventative, used in recurrent cases
69
What are the complications of splenic sequestration crisis?
Splenic sequestration crisis → **splenic infarction** → **hyposlenism** → **susceptibility to infections** (particularly **encapsulated bacteria)** (**Streptcoccus pneumoniae + Haemophilus influenzae**)
70
What is an aplastic crisis in a patient with sickle cell anaemia?
The **temporary absence** of the **creation of new RBCs**
71
What **virus** usually triggers an **aplastic crisis** in a patient with **sickle cell anaemia**?
Parvovirus B19
72
What does aplastic crisis lead to?
How is it treated?
Aplastic crisis:
* Leads to significant **anaemia** (**aplastic anaemia**)
* Management → supportive (blood transfusions if necessary) → usually resolces spontaneously within a week
73
What is acute chest syndrome in sickle cell anaemia?
**Acute chest syndrome** = vessels in the **lungs** become **clogged with RBCs** → medical emergency (high mortality)
Presents:
* **Fever**, **SOB**, **chest pain**, cough, hypoxia
74
What will a CXR show in an acute chest syndrome in a person with sickle cell anaemia?
**Pulmonary infiltrates**
75
What is the management for an acute chest syndrome in a person with sickle cell anaemia (a sickle cell crisis)?
* **Analgesia**
* **Good hydration** (IV fluids may be required)
* **Antibiotics** or **antivirals** for infection
* **Blood transfusions** for anaemia
* **Incentive spirometry** using a machine that encourages effective and deep breathing
* **Respiratory support** with oxygen, non-invasive ventilation or mechanical ventilation
76
What is the general management for sickle cell disease?
* **Avoid triggers for crises**, such as dehydration
* **Up-to-date vaccinations**
* **Antibiotic prophylaxis** to protect against infection, typically with **penicillin V** (phenoxymethylpenicillin)
* **Hydroxycarbamide** **(stimulates HbF)**
* **Crizanlizumab**
* **Blood transfusions** for severe anaemia
* **Bone marrow transplant can be curative**
77
What drug stimulates the production of HbF in sickle cell anaemia?
**Hydroxycarbamide**
HbF does not lead to sickling (unlike HbS)
It **reduces vaso-occulsive crises** → improves anaemia + extends lifespan
78
What drug (a monoclonal antibody) targets P-selectin (adhesion molecule) on endothelial cells + platelets used in sickle cell anaemia to prevent the RBCs sticking to blood vessels → reducing vaso-occulsive crises?
Crizanlizumab
79
What is haemolytic disease of the newborn?
The **incompatibility** between the **rhesus antigens** on the surface of RBCs of the mother + fetus
Causes **haemolysis** (RBCs breaking down) + **jaundice** in the neonate
80
What is the most important **antigen** within the rhesus blood group system?
**Rhesus D antigen**
81
What happens when a mother who is rhesus D negative carries their first fetus that is rhesus D positive?
Fetal blood finds its way into her bloodstream → fetal RBCs display rhesus D antigen → mothers immune system will recognise it as foreign → produce **antibodies** against it
Mother becomes **sensitised** to rhesus D antigens
(Does not usually causes problems)
82
Why is a second pregnancy when the mother is rhesus D neg and the baby is rhesus D positive a problem?
The **mothers anti-D antibodies** (acquired suring sensitisation during first pregnancy) → can cross the **placenta into the fetus** → is fetus is rhesus D positive → these antibodes = attach themselves to the fetal RBCs → causing the fetus' immune system to attack its own RBCs
Leads to **haemolysis** → causing **anaemia + high bilirubin levels ** → leading to **haemolytic disease of the newborn**
83
What is the investigation used to test for **immune haemolytic anaemia** → testing for haemolytic disease of the newborn?
**Direct Coombs test (DCT)**
84
# =
What is the management for the 3 types of beta thalassaemia?
* Thalassaemia Minor: monitoring + no active treatment
* Thalassaemia Intermedia: blood transfusions + iron chelation
* Thalassaemia major: regular transfusions + iron chelation + splenectomy + bone marrow (curative)
85
What is fanconi anaemia?
Rare **inherited genetic disorder** that primarily affects the **bone marrow** → leading to **decreased production of all blood cells**
86
Does fanconi anaemia result in pancytopenia?
Yes! Decreased production of:
* RBCs (**anaemia**)
* WBCs (**leukopenia**)
* Platelets (**thrombocytopenia**)
Results in **fatigue, increased susceptibility to infections, easy bruising/bleeding **
87
What are the clinical manifestations for fanconi anaemia?
* **Thumb, arm, kidney malformations **
* **Short stature**
* **Skin pigmentation changes**
* **Skeletal abnormalities**
88
A patient has fanconi anaemia, what cancers are they at higher risk of developing?
* **Acute myeloid leukaemia (AML)**
* Head + neck cancer
* GI cancer
* Gynaecological cancers
89
What are the management options for fanconi anaemia?
* **Bone marrow transplant (haematopoietic stem cell transplant)** → replace defectove bone marrow cells
* **Medications** (symptoms + complications) → growth factors to stimulate blood cell production + antibiotics to prevent infections
* **Androgens** → stimulates RBC + platelet production → alleviates some symptoms of anaemia + thrombocytopenia
90
A young child has a malformation with his thumb, he is short, is looking quite pale. You suspect he has fanconi anaemia, what investigations should you request?
* Complete blood count (**CBC**) → **pancytopenia**
* **Bone marrow aspiration + biopsy**
* **Gold standard: Chromosome breakage test** → FA will show increased chromosome breakage
* **Genetic testing** → most common genes **FANCA**, FANCC, FANCD2
* Cancer screening
