Haematology Flashcards
Translocation associated with mantle cell lymphoma
(11;14) translocation
q13;q32) cyclin D1 (CCDN1) and immunoglobulin heavy chain (IgH
List 2 GIIB/IIIB inhbitors
abciximab
eptifibatide
Deficiency in:
- Bernard soulier
- grey platelet syndrome
- glanzmans thrombesthenia
BS - glycoprotein abnormalities
GPS - alpha granule deficiency
GT - GIIb/IIIB defect
Treatment of essential thrombocytosis
If no JAK mutation, age <60yo, no vasomotor sx or CVS risk factors, can observe
Otherwise, aspirin daily (BD if CVS risk factors)
ADD hydroxyurea if high risk (i.e. previous clots, >60YO) with target platelets <400
ADD anticoagulation if previous VTE
What conditions is eculizumab inducated for?
PNH Atypical HUS (complement mediated TMA)
Hepcidins action on iron
What effect does inflammation have on it?
Decreases serum iron
Inhibits ferroportin (major role)
- decreased recycling of iron from old RBCs/macs via the reticuloendothelial system
- decreased release of iron into the circulation at basolateral membrane of enterocytes
Inhibits intestinal iron absorption (minor role
Inflammation increases hepcidin
Common mutations in myelodysplastic syndromes
Which are associated with a poor prognosis?
TET2 SRSF2 ASXL1 DNMT3A RUNX1
SRSF2, RUNX1 and TP53 = poor prognosis
Which form of MDS does lenalidomide work best in
isolated del5q
Poor prognostic markers in MM
High beta 2 microglobulin
Low albumin
t(4;14)
Standard treatment for MM if ineligible for transplant
What can be added if high risk?
Bortezomib (proteosome inhibitor)
Melphalan (akylating agent) or lanalidomide
Prednisone
Antibodies
- antiCD38: daratunumab, isatuximab
Most common feature of MM
Anemia
Hodgkins lymphoma with best prognosis
worst prognosis?
Nodular sclerosing’
Lymphocyte depleted (worst)
What are Dohle bodies and when do they occur
Toxic granulation of neutrophils
Leukomoid rection - associated with high LAP socre and differentiating feature from CML
Features of WM
Funduscopic abnormalities Constitutional "B" symptoms Bleeding Neurologic symptoms Hyperviscosity Lymphadenopathy Hepatomegaly Splenomegaly
What does TCT test?
Name conditions where it will be prolonged
Fibrinogen conversion to fibrin (i.e. the action of thrombin)
Unfractionated heparin Direct thrombin inhibitors (dabigatran) Liver disease DIC and acquired fibrinogen disorders Hypoalbuminemia Paraproteinemia
Abelacimab mechanism of action
Factor XI inhbitor
Prolonged APTT with normal reptilase time indicates what
Heparin contamination
Test to distunguish secondary and primary polycythemia
EPO level
- low in primary
- high in secondary
Spindle cells and fibrosis on BM biopsy with elevate tryptase
Mutation?
Systemic mastocytosis
KIT mutations (D816V common)
Empiric antibiotics for patients with febrile neutropenia life threatening penicillin allergy
Non-life threatening penicillin allergy?
Life threatening:
- aztreonam OR cipro
- AND vancomycin
Non-life threatening
- cefepime (no vanc)
Empiric antibiotics for patients with febrile neutropenia and systemic compromise
As for non life threatening (pip-taz) and:
- ADD gentamycin
- ADD vanc if signs of cellulitis
If GI features and not on pip-taz/mero, need to cover for anaerobes with metronidazole
What is daratunumab?
What is the major issue?
Anti-CD38, used in MM
Interferes with pre-transfusion cross match due to CD38 markers on RBCs
Malignancy associated with “starry sky” picture on blood film
Mutation?
Burkitts Lymhoma
MYC;IgH translocation (8;14)
What is gemtuzumab and when is it used?
Major issue?
Anti-CD33, used in AML (less common now)
causes hepatic sinusoidal obstructive(veno-occliusive) syndrome
Treat with defibrotide
CML translocation
t(9;22)
APML translocation
t(15;17)
Indications for treatment in CLL
Worsening anemia/thrombocytopenia
Splenomegaly
Lymphadenopathy
Progressive lymphocytosis - doubling time <6 months OR increase >50% over 2 months
Autoimmune anemia/thrombocytopenia poorly responsive to steroids
Symptomatic/functional extranodal involvement (skin, kidney, lungs, spine)
Constitutional symptoms - unintentional LOW, fevers, fatigue, night sweats
Poor prognostic markers in CLL
BIG ONE - Del(17p)/TP53
Lymphocyte doubling time <12 months Del(11q) Unmutated IGHV Age >60 High B2 microglobulin
Best evidence for prevention of post thrombotic syndrome
Anti-coagulation
Definition of MM
> 10% clonal plasma cells + either of:
- End organ damage (1 or more) - CRAB sx
- presence of a biomarkers (1 or more) - ≥60% clonal plasma cells in BM, FLC ratio ≥100, MRI with >1 focal bone lesion
Chains in:
- HbA
- HbA2
- HBF
- HBH
- Hb Barts
HBA: 2 alpha, 2 beta (normal) HBA2: 2 alpha, 2 delta (beta thal) HBF: 2 alpha, 2 gamma HBH: 4 beta (alpha thal) Hb Barts: 4 gamma (alpha thal)
hemoglobin in sickle cell
HBS - 2 alpha, 2 beta
Mutated beta chain
Mutation in sickle cell disease
missense mutation [Glu6Val, rs334] in the β-globin gene
[HBB]
What is hemoglobin E?
When is it significant?
HbA chains (2 alpha, 2 beta) with mutated beta chain Significant when occurs with beta thalasamia; significant beta chain reduction
Features of red cell aplasia
Normochromic, normocytic anemia
elevated EPO
Absent erythroblasts and f giant pronormoblasts in the bone marrow.
Microspherocytes are associated with what
Autoimmune hemolytic anemia
Poor prognostic features in ALL
Philadelphia chromosome (9;22) Male gender Age <2 or >10 Initial WCC >100 CNS involvement Non-caucasian FAB L3 T or B cell surface markers
Good prognostic features in ALL
FAB L1
Common ALL
Pre-B phenotype
Low initial WCC
In what organ is thrombopoetin mostly produced
Liver
Small amounts produced in kidney and bone marrow
Effects of anticoagulants on coagulation studies:
- Warfarin
- Apixaban
- Rivaroxaban
- Dabigatran
- Heparin
Warfarin
- prolonged INR, variable APTT
Apixaban, rivaroxaban
- PT>APTT, TT normal
Dabigatran
- TT>APTT>PT
Heparin
- APTT>TT, normal reptilase, normal PT
Reason for increased VTE risk in malignancy
Increased tissue factor production by cancer cells –> excessive extrinsic pathway activation
