Haematology Flashcards
Acute Promyelocytic leukaemia
Young patients in 20’s
t (15:17) creating RARA oncogene
Auer Rods
Rx with all-trans retinoid acid (ATRA)
Progressive DIC and fatal
Best prognosis for AML given high treatment response to ATRA
Common mutation in AML
FLT3 - most common
Deletion Chromosome 5 - poorest prognosis - 5q syndrome
Translocation 15:17 (RARA) - best prognosis
Management of AML
Cytarabine + Anthracycline (Daunorubicin or Idarubicin)
Plus
Midostaurin (TK inhibitor) if FLT3 positive
Differentiation syndrome post-ATRA (All-Trans Retinoic Acid)
Fever, oedema, lung infiltrates, renal and hepatic dysfunction
Stop ATRA and give dexamethasone
Treatment indications for chronic lymphocytic leukaemia
- Anaemia or Pl < 100
- Massive splenomegaly or abdominal pain
- Progressive/painful lymphadenopathy
- Lymphocyte doubling time over 6 months
- Autoimmune complications that are not controlled with steroids (autoimmune anaemia, thrombocytopenia)
B symptoms - extreme fatigue, inability to carry out ADLs, night sweats > 1 month, weight loss > 10%/6 months, fevers > 2 weeks
NOT WCC!
Cells present in CLL
Smudge cells
Cell markers in CLL
CD 19
CD20
CD 23 (differentiates from Mantle Cell Lymphoma)
CD 5 (normally a T cell marker)
Treatment CLL
- Rituximab
- Ibrutinib - if 17p deletion with p53 mutation
- Venetoclox - BCL 2 antagonist - for relapse- if 17p deletion with p53 mutation
Ibrutinib
Brutons tyrosine kinase inhibitor
For 17p deletion -> p53 mutations
Causes AF and Bleeding as side effects
Used in CLL and Mantle cell lymhoma
Chronic myeloid leukaemia mutation
Translocation 9:22 (philidelphia chromosome) -> BCR-ABL tyrosine kinase mutation
Rx
- Imatinib
- Dasatinib
- Nilotinib
Imatanib VS. Ibrutinib
Imatanib targets - t (9,22) BCR-ABL TK in CML
Ibrutinib targets - 17q, p53 mutation in CLL
5q minus syndrome
Myelodysplastic syndrome - Deletion involving Chromosome 5
Triad;
- Hypoplastic anaemia
- Atypical megakaryocytes
- Elevated platelet count
Mangement
- Lenalidomide
Prognostic score CML
APS-BEB
Age
Platelet count
Spleen size
Basophils
Eosinophils
Blasts
Imatanib resistance
Mutations in BCR-ABL TK
Amyloid associated with MM
AL (light chain) Amyloid
Poor prognostic indicator for MM
B2 - microglobulin
Poor prognostic indicator for MM
B2 - microglobulin
Cell markers on Reed-Sternberg cells
Lost ALL B cell markers, express CD15 and CD30 instead
Risk factor VWF deficiency
“A’s”
- Ageing
- African
- Antigen negative blood group (O-type blood)
- Adrenaline
- Antenatal and other increases in oestrogen
Investigations VWF
- Prolonged APTT (intrinsic pathway)
- Factor 8 levels
Rx VWF deficiency
- DDAVP - desmopression; causes released of stored VWF
- Factor 8 replacement
- Transexamic acid for bleeding
Types VWF
Type 1 - most common, partial deficiency
Type 2 - selective deficiency i.e. in Factor 8
Type 3 - autosomal recessive, complete deficiency, rare and associated with type 1 diabetes
Extrinsic pathway
Factor 3 (Tissue Factor)
Factor 7
PT
Intrinsic pathway
Factor 8
Factor 9
Factor 11
Factor 12
APTT (two T’s look like a house “inside” for intrinsic)
Common pathway
Factor 10
Factor 5
Thrombin (Factor 2)
Thrombin time (TT)
If prolonged APTT - next test?
Mixing test, will correct prolonged APTT and confirm factor deficiency
Rx Anti-phospholipid syndrome
Warfarin lifelong for patients who have thrombosis
BUT if pregnant/to reduce miscarriage - Aspirin and LMWH
Factor V leiden pathophysiology
Factor V Leiden causes a mutant form of Factor 5 which cannot be inhibited by Protein C, therefore this increases common pathway in clotting cascade leading to increased clotting risk
Anti-thrombin 3 deficiency and Heparin use
Lack of anti-thrombin
Heparin will NOT work in Anti-thrombin 3 deficiency as Heparin requires Anti-thrombin 3 potentiation to work.
Pathologies causing a prolonged APTT and TT
DIC with low fibrinogen
Heparin (UFH)
Mechanism of Warfarin skin necrosis in protein C deficiency
Depletion of Vitamin K dependent production of Protein C -> inability of protein C to block Factor 5 -> increased clotting and skin necrosis
Multiple Myeloma Dx
- > 10% clonal plasma cells in BM
PLUS
- CRAB
OR
- Serum free light chains > 100
- > 1 MRI foci > 5mm
- > 60% clonal plasma cells in BM
Smouldering myeloma
> 10% clonal plasma cells in BM
- >3g/dl (30g/L) M protein in serum or >500mg/day urine bence jones protein
- NO CRAB
Dx Polycythemia Vera
Jak2 positive
Hb > 165 in men
Hb > 160 in women
HCT > 49% in men
HCT > 48% in women
Rx for intra vs. extravascular haemolysis
Intravascular = haemoglobinuria
Warm agglutination haemolytic anaemia
Coombs +
IgG
Spherocyte +
Causes;
- Autoimmune, SLE
- Lymphoma
- CLL
- Carcinomas
- NSAIDs
- Methyldopa
- Antibiotics
- IFN
Cause of Haemolytic Uraemic Syndrome
Enterohaemorrhagic E.Coli producing shiga toxin
HbH
Beta tetramer which is formed in Alpha Thalassaemia HbH disease (3 x alpha mutations)
Barts Hb
Gamma tetramer; occurs in the foetus when it switches from gamma-kappa to gamma-alpha (absence of alpha forms gamma tetramer)
Hydrops Fetalis
Hb alpha 2
In beta thalassaemia. Made up of two alpha and two delta chains.
When the body is depleted of beta globin chain tetramers, it compensates by producing a different form of hemoglobin with delta chains
Low = alpha thal
High = beta that
Chromosomes of a and b thalassaemia
Alpha - Ch 16, 2 genes, 4 alleles
Beta = Ch 11, 1 gene, 2 alleles
Different haemoglobins in Thalassaemia
HbA - Normal - a2b2
HbH - alpha thal - b2b2
HbF - fetal - a2g2
HbA2 - Beta thal - a2d2
Barts - g2g2
Management essential thrombocytosis
If low risk - FBC every 3 months
If intermediate risk ; JAK2 +, > 60 years, CVD - for Aspirin
If high risk; Pl > 1500, splenomegaly, prior thrombosis; for hydroxyurea + Aspirin
If pregnant; For IFN-alpha + Aspirin (hydroxyurea teratogenic)
Haemophilia
Haemophilia A - Factor 8 deficiency
Haemophilia B - Factor 9 deficiency
Haemophilia C - Factor 11 deficiency
Types of Hodgkin Lymphomas
Nodular sclerosing - most common
Mixed cellularity
Lymphocyte predominant - best prognosis
Lymphocyte deplete - least common, worse prognosis
Causes of Cold autoimmune haemolytic anaemia
- EBV (mononucleosis)
- Mycobacterium
Types of sickle cell crisis
Thrombotic
Sequestration
Aplastic due to parvovirus
Haemolytic
Mechanism of paroxysmal nocturnal haemoglobinuria
Lack of complement inhibitor receptors on RBC (glycosyl-phosphatidyl-inositol (GPI) proteins) which leads to inability to block complement dependent haemolysis
Test for paroxysmal nocturnal haemoglobinuria
Hams Test
Flow cytometry for glycosyl-phosphatidyl-inositol (GPI) protein CD 55 and 59 (low levels in PNH meaning complement cannot be inhibited -> Increased complement-mediated haemolysis)
G6PD deficiency
Inability to protect RBC from oxidative stress
Coombs negative
Bite/blister cells
Most common mutation Burkitt Lymphoma
translocation 8:14, causing alteration in c-myc oncogene
Smudge cells
Present in CLL
Disorder associated with Heparin resistance
Antithrombin 3 deficiency
Treatment of vWF
DDAVP/Desmopression - induces release of stored vWF
Sex with highest rates of DVT re-occurance
males!
Sign of intravascular haemolysis
haemoglobinuria
Causes intravascular and extravascular haemolysis
Intravascular
- Cold autoimmune haemolytic anaemia
- Paroxysmal nocturnal haemoglobinura
- DIC
- Mismatched blood transfusions
- G6PD
Extravascular
- Haemoglobinopathies - sickle cell, thalassaemia, hereditary spherocytosis
- Warm autoimmune haemolytic anaemia
JAK2 inhibitor
Ruxolitinib, for myelofibrosis
- Can cause Tb, Hepatitis and Mycobacterium reactivation
Also used pre-transplant to reduce splenomegaly
Viruses and association with Lymphoma
Burkitts - EBV
B cell lymphoma - HIV
T celllymphoma - HTLV-1 (Human T lymphotrophic Virus)
Polycythaemia Rubra Vera - Dx
Hb > 165 male, > 160 female
HCT > 49% male, > 48% female
Low EPO levels
JAK2 positive
Splenomegaly
Hypercellular BM
Dohle Bodies
Present in Leukaemoid reaction
Differentiates Leukaemoid reaction from CML
Due to immature cells spilling into peripheral blood with over-expansion of BM cells (i.e. high turnover with massive haemorrhage) or metastatic infiltration
Tear Drop poikilocytes
Seen in myelofibrosis
Stages Myelofibrosis
** myeloproliferative disorder of megakaryocytes which produce fibroblast growth factor and increase fibroblast proliferation **
Pre-fibrotic - mimics essential thrombocytosis with increased platelet count
fibrotic - thrombocytosis, leukoerythroblasts and tear drop RBC on blood film, Dry BM, anaemia, splenomegaly
Ann Arbor
- One lymph node
- 2+ lymph node one side of diaphragm
- Above and below diaphragm
- Extranodal
Causes of Bone Marrow suppression in Hereditary Spherocytosis
Parvovirus with aplastic crisis
Mutation in Mantle Cell lymphoma
t (11:14)
Has CD19, CD20, CD5, but no CD23 - differentiates from CLL
Drug induced thrombocytopenia
Gp2b/3a inhibitors- Tirofiban, Abciximab
ITP antibodies are against..
Glycoprotein 2a/3b (which is why inhibitors like tirofiban and abciximab can cause thrombocytopenia)
Ibrutinib is treatment for..
- CLL
- Waldenstroms Macroglobinaemia
- Mantle Cell Lymphoma
Dx vWF
Mimics platelet disorder with petechiae
Slightly prolonged APTT
Reduced Factor 8
