Haematology / Oncology Flashcards
Vit K dependent clotting factors
II
VII
IX
X
Presentation of ALL
- Bone pain at night
- Weight loss, fever
- Recurrent sore throat
- Petechial rash
- Pancytopenia
Complication of chronic transfusions
Iron overload - no mechanism for excretion of excess iron
Causes of microcytic anaemia
Iron deficiency
Thalassaemia
Anaemia of chronic disease
Causes of normocytic anaemia
Bleeding
Haemolysis
BM failure
Anaemia of chronic disease
Renal failure - reduced EPO
Transient erythroblastopenia of childhood
Causes of macrocytic anaemia
B12/ folate deficiency
Diamond-Blackfan
Liver disease
Hypothyroid
Blood results in iron deficiency anaemia
Low Iron / ferritin
High Transferrin
Hypochromic, microcytic anaemia
Causes of red cell aplasia
LOW RETICULOCYTES
- Diamond Blackfan anaemia
- Transient erythroblastopenia of childhood around 2y, triggered by infection.
- Parvovirus B19 induced aplastic anaemia (esp if already have haemolysis)
Genetics and features of Diamond-Blackfan Anaemia
Dominant. Mutation RP519.
- Macrocytic anaemia as young infant
- Low reticulocytes
- 50% physical abnormalities - craniofacies, cleft, thumb abnormalities, growth restriction
- BM - low erythroid precursors. Other cell lines normal.
- High HbF and eADA
- Tx: steroids, RBC Tx, HSCT
Acquired causes of haemolysis
- AI - idiopathic, SLE, JIA
- Microangiopathic - HUS
- Infection - malaria, sepsis
- Hypersplenism
- Burns
- Poisoning - lead, arsenic
- Allo-immune - haemolytic disease of the newborn
What does positive Direct Coomb’s Test mean?
Immune mediated haemolytic anaemia
Features of G6PD deficiency
X-linked recessive. More African, Asian, Mediterranean.
Eps of haemolysis triggered by oxidising agent eg broad bean, moth ball, co-trimoxazole, nitrofurantoin
Ix - G6PD enzyme assay, ‘bite cells’
Features of hereditary spherocytosis
Dominant. Defect spectrin. More caucasian.
Defective spherical RBC –> destroyed –> gallstones, splenomegaly, jaundice
Ix: Film = spherocytes
Tx: folic acid. Splenectomy >5y following vaccines
Features of AI haemolytic anaemia
50% idiopathic. Other causes: lymphoma, leukaemia, SLE, UC, mycoplasma
Destruction of RBC due to auto-Ab
Warm / cold - temp at which Ab reacts
Tx: Steroids, immunosuppression, remove cause
Features of pyruvate kinase deficiency
Recessive. Rare.
Rigid cells –> haemolysis
Film - prickle cells
Pyruvate kinase assay
Tx - splenectomy
Features of alpha thalassaemia
Alpha globin deletion Ch 16. Deletion 3 copies = HbH disease, 4 copies –> hydrops / death
Presents: Microcytic hypochromic anaemia, splenomegaly, jaundice
Ix: Film with brilliant cresyl blue stain / liquid chromatography
Features of beta thalassaemia
Trait - 1 copy affected, Major - both copies affected.
Presents 12-18m. Severe anaemia, frontal bossing / maxillary swelling, hepatosplenomegaly
Ix: Microcytic hypochromic anaemia, target cells, nucleated RBC
Tx: Tx + desferrioxamine, ?splenectomy, BM transplant
Genetics of sickle cell disease
Point mutation of beta-globin gene
Recessive. More African, Caribbean, Middle East, India
- Sickle cell anaemia - Homozygous mutation (HbSS)
- HbSC disease - Single beta cell mutation, HbC mutation
- S Beta thalasseamia - Beta globin and beta thalassaemia mutations
Features of sickle cell associated with increased risk of painful crisis
High haematocrit
Low levels of HbF
Presentations of sickle cell diseases
Chronic haemolytic anaemia and sickle cell crisis:
- Painful veno-occlusive eps eg dactylitis
- Sickle chest crisis
- Splenic / hepatic sequestration
- Aplastic crisis secondary to Parvovirus B19
- Cerebral infarction
- Increased risk infection - hyposplenism
Management of sickle cell
- Avoid precipitants - cold, dehydration, exercise
- BD penicillin prophylaxis and Imms
- Folic acid
- Blood Tx and iron chelation
- Crisis: Hydration, analgesia, ABx, O2
Causes of BM failure / pancytopenia
- Inherited: Fanconi’s Anaemia, Schwachman-Diamond syndrome
- Infection eg HIV, EBV, CMV, Hep C/E
- Chemicals / radiation
- AI
- Acute leukaemia
- BM infiltration lymphoma / solid tumours
- Drugs - chemo
- Ostepetrosis
Features of Fanconi Anaemia
Recessive. Mutation FANC / BRCA 2
DNA repair disorder, more cancer
BM failure
Short, microcephaly
Hyperpigmentation
Anomalies - upper limb, renal, genital
Ix: Chromosomal breakage test
Features of Leukaemia
ALL - Lymphoid. Boys >girls. More common.
AML - Myeloid. Boys=Girls. Auer Rods.
Presentation:
- BM failure
- Tissue infiltration - bone pain, hepatosplenomegaly, lymphadenopathy, soft tissue lumps, englarged testes, mediastinal mass
- BM / CSF blasts
Genetic syndromes with increased risk of leukaemia
Down’s
Fanconi anaemia
NF1
Noonan
Wiskott-Aldrich
Tumour lysis syndrome features
Hyperkalaemia
Hyperphosphataemia
High urate
Hypocalcaemia
Leukaemia - rapid breakdown of blast cells
Definition of polycythaemia and significance
Haemocrit >65% 00> hyperviscosity
What does PT test?
EXRINSIC pathway. Play Tennis outside.
Clotting factors II, V, VII, X
Abnormalities: Liver disease, DIC, Vit K deficiency, warfarin
What does APTT test?
INTRINSIC pathway. Play Table Tennis inside.
II, V, VII, IX, X, XII, XI
Abnormalities: Lupus anticoagulant, VWD, Haemophilia, heparin, antiphospholipid
Pathophysiology of Haemophilia
X-linked recessive. Females have mild Sx.
- Haemophilia A = Factor VIII deficiency (more common)
- Haemophilia B = Factor IX deficiency
Presentation of Haemophilia
Neonates - IVH, bleeding
Mod - severe bleeding
Spontaneous bleeding into joints / muscles –> arthritis
Bleeding with procedures
Bleeding easily
Markedly deranged APTT, normal PT
NB clotting factor assays
Treatment of Haemophilia
Recombinant factor concenentrates
Desmopressin
Normal function of von Willebrand factor
- Platelet adhesion
- Bind and stabilise factor VIII - protect from proteolytic degredation
Pathophysiology and presentation of Von Willebrand Disease
Dominant / recessive. Mutation Ch 12 –> reduced production of VWF / abnormal VWF
Presents:
- Menorrhagia
- Bruising
- Excessive bleeding from procedures
- Epistaxis
- Prolonged APTT, PT normal
- Low factor VIII - disrupted VWF binding
- Abnormal VWF ristocetin cofactor assay
Management of Von Willebrand Disease
Mild - TXA
Severe - desmopressin prophylaxis (increased factor VIII / platelet aggregation), VWF concentrate, esp prior to surgery
Pathophysiology / presentation / Tx DIC
- Trigger (eg sepsis, malignancy, trauma) –> excessive and unregulated activation of clotting system –> fibrin clots and consumption of clotting factors / platelets.
- Presents: Bleeding ++, thromboembolic complications
- Ix: Prolonged PT and APTT, high fibrinogen, low platelets
- Tx: Cause, transfusion
What is lupus anticoagulant?
Ab that develops following infection (measles, adenovirus, mycoplasma)
Prolonged APTT, normal PT. APTT with 50:50 mixing –> remains abnormal in LA
Usually self-resolves.
Pathophysiology / features / Tx of ITP
- AI destruction of platelets.
- Presents: Petechiae, purpura, epistaxis, superficial bleeding
- Tx: Pred, IV immunoglobulin, Plt Tx
Chronic >6m –> Rituximab / monoclonal AB
Causes of thrombosis in children (rare)
- Central line
- Malignancy
- DIC
- SLE / sickle cell
- Trauma
- Polycythaemia
- Chickenpox (low protein S)
- Inherited deficiency of anticoagulants: Antithrombin, Protein C, Protein S
- Factor V Leiden mutation - prevents protein C from binding
What are naturally occurring anticoagulants and where do they act?
Antithrombin - Thrombin, factor V
Protein C - Factor VI, VIII
Protein S - enhance protein C
What is Li-Fraumeni Syndrome?
Cancer pre-disposition syndrome
Mutation and loss of function p53 tumour suppressor gene.
FHx breast / brain cancer, sarcoma
