Haematology Flashcards
Lab features of iron deficiency anaemia
microcytic, hypochromic anaemia
Lab features of red cell aplasia
low reticulocyte count, normal bilirubin, negative DAT
Lab features of a haemolytic anaemia
raised reticulocyte count, high bilirubin (unconjugated), positive DAT
What are the causes of microcytic anaemia?
IDA Anaemia of chronic disease Disorders of globin synthesis Lead poisoning Sideroblastic anaemia
How is Diamond-Blackfan anaemia inherited?
20% familial, 80% sproadic
When does Diamond-Blackfan present?
2-3 months, but can present at birth
What other anomalies can patients with Diamond-Blackfan anaemia have?
Short stature
Abnormal thumbs
Cleft palate
Microcephaly
How is Diamond-Blackfan anaemia treated?
Steroids
Transfusion
What is Diamond-Blackfan anaemia?
Inability of bone marrow to produce red cells
What causes ABO incompatibility?
Antibodies in recipient’s plasma are directed against donor antigens
In what circumstance is ABO incompatibility usually most severe?
Group A blood transfused into Group O recipient
What are the consequences of ABO incompatibility?
○ Haemolysis
DIC
Renal failure
Possible complement mediated cardiovascular collapse
How does a TRALI present?
Acute SOB and non productive cough
Bilateral infiltrates on CXR
What causes TRALI?
Donor antibodies reaction with recipient’s leucocytes
What causes a non-haemolytic febrile transfusion reaction?
production of cytokines by donor leucytes in the transfused blood, or interaction between leucocyte and anti-leucocyte antibodies in the recipient
Which blood product is usually the culprit in a non-haemolytic febrile reaction?
Platelets
What are the symptoms of a non-haemolytic febrile transfusion reaction?
Fever
Chills
Rigors
What counts as a massive transfusion?
replacement of more than half of patient’s blood volume at once, or entire blood volume within 24h
What are the features of a massive transfusion reaction?
Coagulopathy Volume overload Hypothermia Hypokalaemia Hypocalcaemia
What is the defect in sickle cell disease?
HbS, forms due a point mutation in codon 6 of the beta globin gene (glutamine changes to valine)
HbS is insoluble and forms crystals when exposed to low oxygen tension
What are the four main types of sickle cell disease?
Sickle cell anaemia (HbSS) - homozygous
HbSC disease - HbC is due to a different point Sickle beta talassaemia - HbS from one parent, and beta thal trait from the other, similar symptoms to HbSS
Sickle trait: heterozygous, usually asymptomatic
What are the possible complications of sickle cell disease?
Splenic or liver sequestration Infection Cerebrovascular accidents Kidney disease Lung disease Eye disease e.g. proliferative retinopathy Crises: painful or infarctive Priapism Limb effects including osteomyelitis and aseptic necrosis Leg ulcers
How is sickle cell disease managed?
Penicillin V prophylaxis against encapsulated organisms e.g. strep pneumoniae and Hib
Immunisation
Folic acid
Hydroxyurea for some - cytotoxic which increases the concentration of HbF
Bone marrow transplant in most severely affected children
Why should sickle cell patients have periodic eye checks?
For proliferative retinopathy
What are the two main types of beta thalassaemia?
§ Major: HbA cannot be produced because of the abnormal beta globin gene
Intermedia: milder, small amount of HbA and/or HbF can be produced
What are the clinical features of beta thalassaemia?
Severe anaemia
Failure to thrive
Extramedullary haemopoiesis, which can cause hepatosplenomegaly and bone marrow expansion
How is beta thalassaemia managed?
Monthly blood transfusion
Iron chelation with desferrioxamine SC or oral
Bone marrow transplant is the only cure
What is the defect in alpha thalassaemia?
Alpha globin - usually there are 4 globin genes and any number of them can be defective
What are the three main types of alpha thalassaemia?
Major/Hb Barts (deletion of all 4 chains)
HbH (deletion of 3)
Trait (deletion of 1 or 2)
What is the management in alpha thalassaemia major?
Needs monthly intrauterine transfusions and lifelong monthly transfusion for any chance of survival
How severe is HbH?
Mild-moderate; may be transfusion dependent
How severe is alpha thalassaemia trait?
Usually asymptomatic
What are some causes of non-midline neck lumps?
Branchial cyst Cystic hygroma Vascular tumours Sternomastoid tumour Recurrent parotitis with sialectitis
What are the causes of a midline neck lump?
Thyroglossal cyst
Ectopic thyroid
Dermoid cyst
What are the features of branchial cysts and how are they managed?
Transilluminates, fluid filled
Can get infected, so are excised
What are the features of a cystic hygroma?
○ Macrocystic lymphatic malformation
Can be simple or complex; complex ones can infiltrate local structures and cause airway obstruction
Usually anterior triangle, transilluminate, fluctuant
What is an example of a vascular neck tumour?
Haemangioma
What is a particular feature of a vascular neck tumour?
Can have a thrill or bruit
What are the features of a sternomastoid tumour?
Only in neonates
Non-tender and very firm
Can be associated with angulation of the head
What are the features of a sialectitis due to recurrent parotitis?
Young children affected
Episodic swelling and pus from parotid gland
What are the features of a thyroglossal cyst?
Cyst moves up with the tongue is protruded
Moves with swallowing
Often close to the hyoid bone
What should you inspect for when there is an ectopic thyroid?
A lingual thyroid
What are the features of a dermoid neck cyst?
Do not transilluminate as they are filled with sebaceous fluid
No not move with swallowing or tongue protrusion
How is Fanconi anaemia inherited?
AR
What are the associated congenital anomalies with Fanconi anaemia?
Short stature Abnormal radii and thumbs Renal malformations Microphthalmia Pigmented skin lesions
When does Fanconi anaemia usually present?
5-6 years
How can Fanconi anaemia be diagnosed before the anaemia?
demonstrating increased chromosomal breakage of peripheral blood lymphocytes
What is the prognosis in Fanconi anaemia?
High risk of death from bone marrow failure or transformation to acute leukaemia
How is Fanconi anaemia managed?
BMT
What is the defect in Fanconi anaemia?
Inability to repair DNA damage, leading to bone marrow failure and pancytopenia
How is Schwachman-Diamond inherited?
AR
What are the characteristics of Schwachman-Diamond?
Bone marrow failure
Signs of pancreatic exocrine failure
Skeletal abnormalities
What is the defect in Schwachman-Diamond?
Mutation in SBDS gene
What is the most common haematological problem in Schwachman-Diamond?
Isolated neutropenia or mild pancytopenia
What is the possible consequence of Schwachman-Diamond?
Risk of transforming to acute leukaemia
How is haemophilia inherited?
X-linked recessive
2/3 have family history
1/3 sporadic
What are the defects in haemophilia A and B?
A = factor VIII deficiency B = factor IX deficiency
What are the clinical features of haemophilia?
Depends on % of normal factor:
Severe disease (<1%): recurrent spontaneous bleeding into joints and muscles
Moderate (1-5%): bleeding after minor trauma
Mild(>5-40%): bleeding after surgery
What will a coagulation screen show in haemophilia?
Tests: prolonged APTT, low factor levels - all else normal
How is haemophilia managed?
Recombinant factor where there is bleeding
Desmopressin in mild haemophilia (stimulates endogenous release of factor VIII and vWF)
What does vWF do?
Facilitates platelet adhesion to damaged endothelium
Acts as carrier protein for factor VIII, protecting it from inactivation and clearance
What is the defect in von Willebrand disease?
Quantitative or qualitative deficiency of vWF
How is vWD inherited?
Usually AD
What are the clinical features of vWD?
Bruising
Excessive, prolonged bleeding after surgery
Mucosal bleeding e.g. epistaxis and menorrhagia
Uncommon to have joint or muscle bleeding like in haemophilia
What are the three main types of vWD?
1: most common, partial deficiency of vWF
2: abnormal function of vWF
3: complete absence of vWF
What will the clotting screen show in vWD?
Normal PT
Prolonged or normal APTT
Low or normal factor VIII
How is vWD managed?
Depends on type and severity
DDAVP
Most severe types may need FVIII concentrate
What is the commonest cause of thrombocytopenia in children?
ITP
What is the pathophysiology of ITP?
Usually caused by destruction of platelets by anti-platelet IgG
May have compensatory increase of megakaryocytes in the bone marrow
Who gets ITP?
Usually presents between 2 and 10 years, 1-2 weeks after a viral infection
What are the clinical features of ITP?
Petechiae or purpura
Superficial bruising
Can cause epistaxis or mucosal bleeding
Profuse bleeding is uncommon
How is ITP diagnosed?
Diagnosis of exclusion
Bone marrow examination should be done if the child will be treated with steroids, as this could mask ALL
What is the prognosis in ITP?
Usually acute, benign and self limiting within 6-8 weeks
How is ITP managed?
Most children don’t need treating unless there is evidence of bleeding that is serious or affecting daily activities, can include: Oral prednisolone, Intravenous anti D, IVIG
Platelet transfusion is reserved for life threatening haemorrhage as it only raises the platelet count for a few hours
Avoid trauma and contact sports
What is chronic ITP?
When Plt remains low 6 months after diagnosis
How is chronic ITP managed?
Treatment is supportive
Specialist care is needed for the rare cases with significant bleeding, which may include rituximab or thrombopoietic growth factors
What is the pathophysiology of DIC?
Coagulation pathway activation leads to diffuse fibrin deposition in the microvasculature and consumption of coagulation factors and platelets
What are the causes of DIC?
Severe sepsis
Shock
Can be acute or chronic
What lab features should make you think of DIC?
Thrombocytopenia Prolonged PT and APTT Low fibrinogen Raised fibrinogen degradation products Raised D dimer Microangiopathic haemolytic anaemia Usually a marked reduction in protein C and S
How is DIC managed?
Treat the underlying cause
May need FFP, cryoprecipitate and platelets
What are the most common inherited thrombotic disorders?
Protein C deficiency Protein S deficiency Antithrombin deficiency Factor V Leiden Prothrombin gene G20210A mutation
What do protein C and S do?
Both natural anticoagulants
How are protein C and S deficiencies inherited and how does this affect the clinical picture?
AD
Heterozygotes are also predisposed to thrombosis
Homozygotes are very rare and present with life threatening thrombosis with widespread haemorrhage and purpura fulminans in the neonatal period
What is factor V Leiden?
inherited abnormality in coagulation protein factor V, which makes it resistant to degradation by activated protein C.
What are the acquired causes of thrombosis?
Catheter-related DIC Hypernatraemia Polycythaemia Malignancy SLE
