Haematology Flashcards
Worst prognostic factor in AML
Age > 60
Who has higher recurrence rates post VTE - men or women?
Men
Which vaccines should someone with no spleen have? 4
Haemophilus influenza B (HiB)
Influenza (annual)
Meningococcus
Pneumococcus
Which 5 clotting factors are contained in cryoprecipitate
Fibrinogen
vWF
XIII
Fibronectin
VIII
What class of drugs can cause a false positive dilute roussel venom viper test?
Anti-Xa drugs
What are the types of Haemoglobin?
Hb A (adults) - Two alpha, two beta
Hb F (babeh) - Two alpha, two gamma
Hb S
- Mutant beta chain
Wells criteria for PE
- *3.0 points - C**linical signs and symptoms of DVT (swelling, tender calves)
- *3.0 points -** Other Dx less likely than PE
- *1.5 points - P**ulse >100
- *1.5 points -** Surgery in previous 4 weeks or immobilisation (>3 days)
- *1.5 points - P**revious DVT/PE
- *1.0 point - H**aemoptysis
- *1.0 point** - Malignancy
Traditional Wells criteria
-High > 6.0
-Moderate 2.0 to 6.0
-Low <2.0
Modified Wells criteria
-PE likely >4.0
-PE unlikely <4.0
Warfarin reversal WITH bleeding
- lifethreatening and INR > 1.5
- clinically significant but not life threatening, INR > 2.0
- any INR with minor bleeding
Warfarin Reversal in someone who is NOT bleeding
- INR <4.5 =
- INR 4.5 to 10 =
- INR > 10 =
Waldenstrom Macroglobulinaemia
- Genetic mutation
- clinical presentation
- treatment
von Willebrand Factor
Vitamin K
Typical coagulation profiles
Typical CLL Immunophenotype
TTP
- define
- what is the cause of the hereditary form
- pathogenesis
- describe symptoms
- Ix findings
- 3 components of treatment
- prognosis with and without treatment
Treatment of Waldenstrom Macroglobulinaemia
Treatment of ITP
Treatment of Hodgkin Lymphoma
Two different chemotherapy approaches
-
ABVD (every 14 days in 28 day cycles). Cures:
- 90-95% Early Stage patients, and
- 60-70% with Advanced Stage Disease
-
Escalated BEACOPP (every 21 days) – MORE TOXIC BUT
- Cures more but much more intensive, (can’t use in older patients), much higher incidence of sterility, more premature menopause, and long term risk MDS/AML unresolved
Diminishing role of radiotherapy - Advanced disease: no overall survival difference
New agents:
- Brentuximab: Anti-CD30 conjugated with MMAE a tubulin toxin, very promising, AE reversible peripheral neuropathy. 75% respond, 2yr OS 65%
- PD-1 Checkpoint Inhibitors –Pembrolizumab : similar ORR, autoimmune toxicities
- Both approved in Australia for double relapsed / refractory patients.
Treatment of Haemochromatosis
Treatment of CLL
When to treat CLL? – ONLY When it threatens trouble.
-
Rituximab (anti-CD20 antibody), Fludarabine and Cyclophosphamide: R-FC in <60yr.
- ↑ CR, PFS & OS (69% at 6yrs)
UNLESS:
- 17pdel or TP53 mutation (these patients have a known short term response to other therapies) – Ibrutinib compassionate access in Aust, Venetoclax funded in NZ
- Obinutuzumab (Type II anti-CD20 with enhanced ADCC) + chlorambucil current frontline treatment for frail elderly (Must have CrCl>30, and cumulative illness rating scale, CIRS>6, or CrCl<70)
-
Oral enzyme inhibitors –for patients with relapsed disease
- Bruton’s tyrosine kinase inhibitor: Ibrutinib Works very well so long as you stay on it.
- bcl2 inhibitor: Venetoclax –potential to obtain CR and cease therapy after ≤ 2 years
Because the more effective enzyme inhibitors are not available for most patients in 1st line there is now a tendency to watch closely for intolerance or poor response with a lower threshold for moving to second-line therapies.
Ibrutinib - MoA and indication/useage
- BTK –Bruton Tyrosine Kinase –plays a crucial role in B cell maturation.
- Ibrutinib oral BTK inhibitor, well tolerated
- Blocks BTK = blocks BCR signalling / activation. Induces apoptosis, blocks migration / adherence
- 71% response rate in 85 patients with refractory CLL.
- Redistribution lymphocytosis (reduced by giving with Rituximab – but no additional benefit of adding rituximab)
- Prolonged duration of response even if del17p
- PBS listed for pts with Rel/Ref CLL unsuitable for purine analogue (fludarabine). Strict criteria for suitability based on age/frailty and also 17p del disease by FISH
- Now available on compassionate basis for 1L del 17p
- S/E: bruising ++ (withhold 7 days prior to and after major surgery, 3d for minor procedures), diarrhea, fatigue, AF in 7%
- No clear benefit from adding rituximab except dampens the lymphocytosis.
Treatment algorithm for newly diagnosed MM
Side effects
- Bortezomib/Thalidomide –neuropathy
- Lenalidamide/Pomalidomide-cytopenias
- Carfilzomib –cardiac probs
TRALI
- Which products are highest risk
- Describe the presentation and the time course
- What is the 2 hit mechanism
- Management
- Single most important prevention strategy
Target Hct in PCV?
0.40 to 0.45 (aka 40% to 45%)
NEJM 2013
TACO vs TRALI (Blood transfusion)
Synthesis and Regulation of Thromboxane A2
- *Summary of platelet activation**
- Adhesion
1. GPIb-V-IX receptor complex binds to what?
2. GP VI and GPIa/IIa receptors bind to what? - Secretion
- What do alpha granules contain
- What do dense granules contain
Adhesion
- GP Ib-V-IX receptor complex binds to vWF immobilized on collagen
- GP VI and GP Ia/IIa receptors bind to exposed collagen
Secretion
- alpha granules - contain fibrinogen, vWF, and factor V
- dense granules - contain ADP
Aggregation
- platelet activation triggers conformational change in GP IIb/IIIa from inactive to active state
- fibrinogen and vWF function as bridges between GP IIb/IIIa rceptors on neighboring activated platelets
Suggested duration of therapy to prevent recurrent VTE
- New trials demonstrating that a finite period of full dose NOACs and then transitioning to prophylactic dose of NOAC demonstrates the same benefit as full dose with less SE of bleeding
- High risk patients probably unlikely but may be a suitable approach in appropriate patient
Subtype of Hodgkin Lymphoma that is/has
- Best prognosis
- Worst prognosis
- Most common
Best prognosis - Lymphocyte predominant (rare)
Worst prognosis - Lymphocyte depleted
Most common - Nodular sclerosing
Some causes of low and high hepcidin
Smoldering MM - definition
Sickle Cell Anaemia - Cause, Epi and Pathophys
Role of compression stockings in DVT
- -Graduated compression stocking reduce incidence and severity of post thrombotic syndrome = use in all patients
- -Must provide 30 - 40mmHg pressure at ankle and extend to level of the knee
- -Wear stockings up to 18 months and indefinitely if post thrombotic syndrome is present
Risks of Autologous HCT
Risks of allogenic HCT
Risk Factors for GVHD
Reversal agent for Rivaroxaban/Apixaban
- how does it work
- main ADR
Andexanet alfa
- modified factor X fragment which acts as a decoy
- ADR = thrombosis
- NOT AVAILABLE IN AUS
Reversal agent for Dabigitran
Idarucizumab
- humanised monoclonal antibody fragment (Fab) that binds to dabigatran with very high affinity (340x fold more than dabigatran binds to thrombin).
Reptilase is normal with
HEPARIN THERAPY!
Investigation of patients with a prolonged Thrombin time (clotting). Assists in differentiating the effect of heparin, presence of FDP / D Dimer and dysfibrinogenaemia. A prolonged Thrombin time result will correct to normal using reptilase if this is due to heparin.
Red Blood Cells
Prothrombin Time
INR is derived from this = (pts PT/control PT) ^ ISI
-ISI = international sensitivity index
Prognostic Factors in B cell lymphoma - APLES
Age
Performance status
LDH
Extra nodal involvement
Stage
Preferred imaging modality for staging of Hodgkin lymphoma
FDG-PET/CT - chest/abdomen and pelvis
PNH
- gene mutation
- classic Sx
- leading cause of death
- Rx (requirements to be on this treatment)
- Other therapies (3)
- Definitive therapy
Platelet disorders vs Coagulation Disorders
-comparison of clinical consequencesd
Phenotype/Genotypes of Alpha Thalassaemia
Chromosome 16!
Pathophysiology of Alpha Thalassaemia
Overview of vWD
- Function of vWF
- Classification
- Epi
- Presentation
- Types of tests
- Treatment
Optimal agent to continue on to prevent recurrent VTE
Low dose rivaroxaban - superior to aspirin, and placebo
With non inferior rates of major bleeding and non-life threatening bleeding
Obinutuzomab - target
CD20
Normal Haemoglobin
- Describe the structure of HbA, when does it predominate
- Describe the structure of HbA2, when does it predominate
- Describe the structure of HbF, when does it predominate
Myeloma Diagnostic Criteria
Asymptomatic Myeloma = Smoldering Myeloma
Myeloid vs Lymphoid CDs (5 each)
Multiple Myeloma Diagnostic Criteria
Most signicant APLS antibody - ie conveys greatest risk of thrombosis?
Lupus anticoagulant
Weakest = anti-cardiolipin (may have a role in pregnancy)
Most sensitive test for the presence of Rivaroxaban/Apixaban?
Anti-Xa
Must specify which agent you think patient is on to get a reference range
Most sensitive test for the presence of Dabigitran?
TCT
in higher concentrations APTT will also start to prolong
Can the do a hemaclot specific assay
If TCT and APTT are both negative - excellent NPV
Most common reason for major blood ABO incompatibility
Most common cause for acute haemolytic reatcions in Australia =** **INCORRECT PATIENT IDENTIFICATION
- Failure to obtain pre-transfusion sample from the correct patient
Most common genetic mutations in Polycythemia Rubra Vera
JAK2v617F (most common) - 95%
JAK2 exon 12 (second most common) - 4%
Most common genetic mutations in essential thrombocytosis and primary myelofibrosis
- *1. JAK2 = most common**
2. CALR = second most common
3. MPL`
Mixing Study
MUST correct to normal and stay normal - otherwise there’s an inhibitor
MGUS - definition and significance
Mechanism of Action of Cancer Drugs - just read
Mastocytosis
Management of Sickle Cell Disease
Management of Follicular Lymphoma
Management of Antiphospholipid syndrome
Major Components of Haemostasis
Main Mechanism of Renal Disease in Multiple Myeloma
Main glycoprotein receptors on platelets
Lymphoma CD markers
Lab findings of the different coagulopathies
ITP
- define
- describe pathogesis
- common precipitant
- risk factors for severe bleeding
- Ix findings
- Mx of severe bleeding
- Second line options
Iron and Hepcidin
Initiation Phase of Coagulation Cascade
Inhibitors of Fibrinolysis
Induction therapy for transplant eligible patients with multiple Myeloma
Lenalidomide + Bortezomib + Dexamethasone
Usually 4 months prior to cell transplant
In young patients treated with radiotherapy what is the most likely **malignancy they will develop in the next 10 years
- Women
- Men**
Women - breast cancer
Men - thyroid cancer
Important causes of aplastic anaemia
- Telomere diseases
- Fanconi anaemia - describe the phenotype, gene involved, pathophys
- GATA2 deficiency - describe the phenotype
- CTLA4 deficiency - describe the phenotype
Intravascular vs Extravascular Haemolysis
Immunophenotypes of CLL
Suspect whenever CD19 and CD5 are co-expressed = CLL
If your blood causes _____ you should never donate again
TRALI
-Transfusion related acute lung injury
Hydrops Fetalis (Alpha thalassaemia)
Hodgkin Lymphoma - defining features and age distribution
Hodgkin Lymphoma
- Cell line
- Classic type - what CDs are expressed and not-expressed
- Classic presentation
- Pathogenomic pathology finding
- Best test of staging
- What staging system is used and how does it work?
Hodgkin Lymphoma
-Ann Arbor staging system (describe)
A or B - if presence of B symptoms (fever, drenching night sweats, LOW)
X - bulky disease
E - extra-nodal involvement
High Risk Features of Multiple Myeloma that convey poor prognosis (4)
Heyde’s syndrome
Aortic Stenosis + Acquired VWD + GI bleeding
-patient can develop angiodysplasia in GI tract
= severe and intractable bleeding
HbH Disease (alpha thalassemia)
Haemolytic uraemic syndrome
- What is the cause
- What is the classic triad
- What is the mainstay of therapy?
GPIIb/IIIa inhibitors:
Genetic Mutation of APML
Remember - mutation in t(15:17) = GOOD prognosis
Frequency of Monoclonal proteins of multiple myeloma
Follicular Lymphoma
- Cell type
- Genetic mutation
- Presentation
- What determines tumour grade
- Risk of transformation into what
Final Common Pathway of Coagulation
Fibrinolysis
Factors which Terminate Coagulation Cascade
Factors included in Prothrombinex (Prothrombin Complex)
II, IX, X
ie 2, 9, and 10
Some countries also include factor VII (7)
Endothelial elements inhibiting thrombus formation
Drugs which are SAFE in the Rx of HITTS (4)
Direct thrombin inhibitors - Argatroban, Bivalirudin
Heparinoids - Danaparoid, Fondaparinux
NOT Warfarin as this will decrease level of protein C = risk of venous limb gangrene
Drugs and Coagulation Cascade
Dipyridamole
Diffuse Large B Cell Lymphoma
- Important epi fact
- How does it present
- What are the B symptoms
- Most common primary, extra-nodal site?
- Most common immunophenotype
- Treatment of limited stage
- Treatment of advanced stage
- Prognosis without therapy
Different Morphology of AML and ALL
DIC pathogenesis
Diagnostic Criteria of CLL
In CLL: lymphocytes CD5+, CD19+, CD23+
Smudge cells on film.
SLL - small lymphocytic lymphoma = nodal counterpart, same approach
FISH in CLL
Genetic aberrations can be detected in >80%
Unfavourable more commonly seen in advanced disease
- 17p deletion -median 3yr survival
- 5% in newly diagnosed,
- 30% relapsed/refractory
- Mutation/del p53 → resistance to traditional chemo (e.g. F+C)
Favourable
- del 13q –median 12yr survival
Diagnostic Criteria for Anti-phospholipid syndrome
Diagnosis of Polycythemia
WHO criteria - must fit all 3 major criteria and minor
Major criteria
●Increased hemoglobin level (>16.5 g/dL in men or >16.0 g/dL in women), hematocrit (>49 percent in men or >48 percent in women), or other evidence of increased red cell volume
●Bone marrow biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size)
●JAK2 V617F or JAK2 exon 12 mutation
Minor criterion
●Serum erythropoietin level below the reference range for normal
Defining feature of acute leukaemia on BM
Presence of >20% blasts on BM morphology
Daratumumab - target
CD38
Used in MM
D-dimer
Criteria for accelerated phase CML
>20% basophils in peripheral blood
Clinical Features of Multiple Myeloma in order of prevalence
Causes of secondary polycythemia (6)
-key examination feature
- High altitude
- COPD
- Smoking
- Sleep Apnoea
- Drugs - EPO, testosterone
- Other - Renal, hepatic tumours, hereditary
Causes of Prolonged TCT (thrombin clotting time) (4)
All other causes of prolonged TCT will prolong reptilase time
Heparin/Enoxaparin will have a normal reptilase time
Causes of Prolonged PT/INR (out of proportion to APTT) (3)
Causes of Prolonged APTT and PT (in proportion) (3)
Causes of Low Protein C and S
Protein C and S
-Drugs: Warfarin, L asparaginase
-Liver disease, vitamin K deficiency, DIC
_______________
Protein S alone
- OCP
- Breast feeding and pregnant women
Causes of an Isolated Prolonged APTT (5)
Anticoagulation test elevated in dabigatran use?
Thrombin Time
APTT >PT also elevated,
Coagulation study elevated in anti-Xa agents ie apixaban, rivaroxaban?
Prothrombin Time!
APTT normal or slightly up
NO EFFECT on thrombin time
Brentuximab - target
CD30
Used in refractory NHL
Blinatumomab - target
CD3 on T cells /19 on B cells
used in Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukaemia.
Beta Thalassaemia pathophysiology and manifestations
Beta Thalassaemia - predictors of disease severity
Beta Thalassaemia - genotypes and phenotypes
Benefits of Tranexamic Acid in adult trauma patients
Reduced all cause mortality
Reduced bleeding mortality
with less MI events but no difference in rate of DVT/PE/stroke
No benefit in
- death due to head injury
- amount of transfused blood products
- Benefit lessened if given after 3 hours*
- *As per CRASH-2 trial**
- *Atypical HUS**
- define and how is it different from typical
- most common gene mutation
- novel Mx, how does it work, serious SE
- Other options
- Definitive Mx
aPTT general principles
INTRINSIC PATHWAY
Approach to VTE prophylaxis in pregnant women with inherited thrombophilias
Approach to Bridging Therapy
APML
- defining gene mutation
- strong association with which disorder
- treatment
- SE of treatment, management of this syndrome
- Prognosis without treatment
- Prognosis with treatment
- Main cause of death
Aplastic anaemia
- Describe 3 features of BM aspirate
- What is the ideal treatment?
Antiphospholipid antibodies
Lupus anticoagulant
Anticardiolipin antibodies
Anti-beta2 glycoprotein I antibodies
Amplification Phase of Coagulation Cascade
AML treatment
AML
- 2 Good Prognostic features
- 4 Poor Prognostic features (“CAMP”)
Acute Complications of Blood Transfusion
FNHTR = febrile non haemolytic transfusion reaction
- Common, diagnosis of exclusion
- More common in platelet transfusion than RBC
- Frequency decreased with leukoreduced products
- Pathogenesis - mediated by release of cytokines from the products WBCs
- Presentation - fever +/- chills with no systemic features
- Treatment - symptomatic
AHTR = acute haemolytic transfusion reaction
7 Unfavourable Prognostic Factors in Hodgkin’s Lymphoma
4 main factors which activate inactivated platelets
Synthesis and Regulation of Thromboxane A2
