Haematology Flashcards
Blood film - splenectomy
- Howell-Jolly bodies - nuclear fragments in RBC
- Acanthocytes - spur cells, thorn/spicules at irregular intervals on surface of RBC
- Target cells - central density with halo of pallor in RBC
Blood film - iron deficiency anaemia (IDA)
- Microcyctic (small) RBC
- Hypochromic (thin rim of pink) RBC
- Poikilocytosis - abnormal shaped RBC, eg. “pencil” shaped cells
Blood film - hypothyroidism
- Normocytic, normochromic, hypoproliferative, anaemia
- In chronic autoimmune thyroiditis - pernicious anaemia (macrocytic, marrow megaloblastosis)
Blood film - B12 and folate deficiency
- Macrocytosis - macro-ovalocytes, occasional megaloblast
- Teardrop cells
- Hypersegmented neutrophils
Coagulation studies - acquired factor VIII inhibitor
Prolonged APTT
Mixing test - corrects initially, no correction in 2 hour incubation (characteristic)
Haemophilia A
Congenital factor VIII deficiency
Haemophilia B
Congenital factor IX deficiency
Most common haemophilia bleeding sites
Haemarthrosis (70-80%) - primarily knee and elbow
Muscle / soft tissue (10-20%)
Other major bleed (5-10%)
CNS bleed (rare, less than 5%)
Most common Von Willebrand disease bleeding sites
Bruising
Skin bleeding
Mucosal bleeding
Coagulation studies - disseminated intravascular coagulation (DIC)
Prolonged APTT
Prolonged PT/INR
Low fibrinogen
High d-dimer
Coagulation studies - heparin
Prolonged TCT (thrombin clotting time) Normal reptilase
Coagulation studies - dysfibrinogenaemia
Prolonged TCT
Prolonged reptilase test
Lugano classification (for non-Hodgkin’s lymphoma)
Stage I - disease on one side of diaphragm
Stage II - more than one area same side diaphragm
Stage III - lymph nodes above and below diaphragm
Stage IV - extranodular disease
E = extranodal contiguous extension
Choice of treatment modality in non-Hodgkin’s lymphoma
Based on Lugano classification:
Stage I - radiotherapy (curative in 50%)
Stage II - consider radiotherapy if low bulk and within field, otherwise treat as advanced
Stage III/IV (advanced) - chemooimmunotherapy ± radiotherapy, for symptom control
Intravascular haemolysis - investigations
Presence of urine haemosiderin - most specific
Increased LDH
Increased bilirubin
Decreased haptoglobin
Most common lymphoproliferative disorders associated with Epstein-Barr virus (EBV)
Hodgkin’s lymphoma
Burkitt’s lymphoma
Cytogenetics - follicular lymphoma
t(14;18) - bcl-2 / IgH
overexpression of BCL-2, an anti-apoptosis protein
Cytogenetics - diffuse large B-cell lymphoma (DLBCL)
No single typical abnormality.
BCL-6 - chromosome 3, numerous alterations seen
t(14;18) - bcl-2 (30%)
t(8;14) - c-MYC (5-15%)
Cytogenetics - mantle cell lymphoma
t(11;14) - cyclin D1 / IgH
abnormal dysregulated expression of cyclin D1 in B lymphocytes, involved in control of G1 phase of cell cycle
Cytogenetics - Burkitt lymphoma
t(8;14) - 80%, c-MYC / IgH
t(2;8) and t(8;22) - also seen
(c-MYC dysregulation driven by IgH enhancer)
Cytogenetics - acute myeloid leukaemia (AML)
Recurrent genetic abnormalities in 11% of cases.
t(8;21) - 7% adults, most frequent in children
t(16;16), inv(16) - 5% adults, chromosome 16 abnormality
Cytogenetics - acute promyeloid leukaemia (APL)
t(15;17) - PML-RARA fusion protein
aberrant retinoid receptor with altered DNA binding and transcriptional regulatory properties
Cytogenetics - acute lymphocytic leukaemia (ALL)
Hyperdiploidy - more than 46 chromosomes
t(9;22) - confers worse prognosis
Cytogenetics - chronic myeloid leukaemia (CML)
t(9;22) - Philadelphia chromosome
bcr-abl leads to increased PO4 of TK residues on substrates, switches on signalling pathways
Cytogenetics - chronic lymphocytic leukaemia (CLL)
del(17p) - 7-10%, worse prognosis
del(11q) - 17-20%, worse prognosis
TP53 mutation - 10-47%, worse prognosis
del(13q) - 45-55%, favourable prognosis
Blood film - primary myelofibrosis
- Teardrop cells (dacrocytes)
- Poikilocytosis - abnormal shaped RBC
- Nucleated RBC
- Leukopenia/ thrombocytopenia (can have leukocytosis/ thrombocytosis)
Most common myeloproliferative disorder associated with Budd Chiari syndrome
Polycythaemia rubra vera (PCV)
Blood film - myelodysplasia
- Anaemia (with anisocytosis)
- Leukopenia
- Thrombocytopenia
(can transform to AML)
Polycythaemia rubra vera (PRV) - diagnostic criteria
WHO critera - 2 major + 1 minor, or 1 major + 2 minor
Major:
- Hb more than 185 men, 165 women
- JAK2 mutation present
Minor:
- Bone marrow biopsy (hypercellularity, trilineage growth)
- Serum EPO level low
- Endogenous erythroid colony formation in vitro
Myelodysplastic syndrome (MDS) - treatment
Azacitidine
Lenalidomide - in deletion 5q
Blood film - autoimmune haemolytic anaemia (AIHA)
- Spherocytes - dark red, sphere shaped RBC (rather than biconcave)
- Microspherocytes - dark red, small spherocyte
Blood film - microangiopathic haemolytic anaemia (MAHA)
- Schistocytes - fragmented RBC including helmet cells, triangle cells
- Helmet cells - RBC shaped as bicycle, combat or football helmets
(Seen in TTP, HUS)
Blood film - thalsassaemia
- Target cells - central density with halo of pallor
- Hypochromia
- Microcytosis
- Teardrop cells
- Basophilic stippling - blue granules on RBC
Blood film - liver disease
- Target cells - central density with pale halo (due to membrane excess)
Thrombotic thrombocytopenic purpura (TTP) - presentation
- Microangiopathic haemolytic anaemia
- Thrombocytopenia
- Fever
- Neurological manifestations
- Minimal renal abnormalities
Haemolytic uraemic syndrome (HUS) - presentation
- Microangiopathic haemolytic anaemia
- Thrombocytopenia
- Acute kidney injury
- Bloody diarrhoea - in typical (secondary) HUS
ADAMTS13 (A Disintegrin And Metalloprotease with a ThromboSpondin type 1 motif, member 13) deficiency
- Causes TTP
- Activity level <10%
- Due to ADAMTS13 gene mutation, or inhibitory antibodies
Plasma exchange / plasmapheresis - indications
- Guillain-Barre syndrome
- ANCA RPGN
- Anti-GBM (Goodpasture’s)
- CIDP
- Cryoglobulinaemia
- FSGN
- Atypical HUS
- TTP
- Wilson’s disease
- Hyperviscosity in monoclonal gammopathy
- Renal or liver transplantation - desensitization, Ab rejection
- Myasthenia gravis
- PANDAS
- Paraproteinemic polyneuropathy
Promoter of neutrophil production
G-CSF (granulocyte colony stimulating factor)
Promoter of platelet production
TPO (thrombopoietin)
Heparin - mechanism of action
- Binds and activates anti-thrombin III
- Activated ATIII inactivates other factors (mainly Xa)
- Simultaneous binding of ATIII and thrombin to inactivate thrombin (LMWH cannot do this)
Protein C - mechanism of action
- Activated by thrombin-thrombomodulin complex
- Protein S is co-factor for activation
- Activated protein C (APC) inactivates factor V and VIII
