Haem Flashcards
1
Q
Signs/Symptoms of Bone Marrow Failure
A
o Anaemia – fatigue, pallor, SOB
o Neutropenia – infections
Can be severe + life threatening – septic shock, renal failure, DIC
Pneumonia, impetigo, necrotising fasciitis
o Thrombocytopenia – bleeding, bruising
+ DIC in acute promyelocytic leukaemia
2
Q
Microscopic features of Acute Myeloid Leukaemia
A
o Circulating blasts (in peripheral blood film) - granules
o Auer rods!!
3
Q
Supportive Tx in Acute Leukaemia
A
- Red cells
- Platelets
- FFP / cryoprecipitate if DIC
- Antibiotics if infections/sepsis
- IV Long line
- Allopurinol (uric acid is released from dying leukaemic cells when started on Tx)
- Fluid + electrolyte balance
4
Q
Local infiltration in AML vs ALL
A
AML: Splenomegaly Hepatomegaly Gum infiltration (monocytic disease) Lymphadenopathy (occasional) Skin CNS (monocytic)
ALL: Lymphadenopathy +/- thymic enlargement splenomegaly Hepatomegaly Testes CNS Kidneys Bone - causing pain in children (not adults)
5
Q
Negative prognostic factors in AML
A
-5. Del 5
7q, 3q-. 11q23
Complex karyotype
+ Patient characteristics e.g. comorbidities, age
Response to Tx
6
Q
Negative prognostic factors in ALL
A
o T(4;11) o Hypodiploidy o ?t(9;22) - Philadelphia Chr - used to be bad prognostic indicator but now improved with tyrosine kinase inhibitors
+ Patient characteristics e.g. comorbidities, age
Response to Tx
7
Q
Causes of thrombocytopaenia (+ most common)
A
Most common = immune mediated
o Idiopathic / Auto ITP – most common immune type!
o Drug-induced – Quinine, rifampicin, vancomycin
o Connective tissue disease – SLE, Rheumatoid
o Lymphoproliferative disease – CLL, lymphoma
o Sarcoidosis
Non immune mediated
o DIC
o Microangiopathic haemolytic anaemia (MAHA)
8
Q
Haemophilia Pathophysiology
A
Congenital deficiency if Factor 8 (A) or 9 (B)
X linked recessive
9
Q
Pathophysiology of bleeding in Vitamin K deficiency
A
Vit K acts as co-enzyme for gamma protein carboxylase
Required for synthesis of:
- Factors 2, 7, 9, 10
- Protein C, S, Z
Causes: o Most common cause = Warfarin o Malnutrition o Biliary obstruction o Malabsorption o (Broad spectrum) Abx - kills intestinal flora that generates Vit K
10
Q
Ix results in DIC
A
Prolonged aPTT Prolonged PT Prolonged TT Decreased fibrinogen High FDP Low platelets Schistocytes on blood film
11
Q
Von Willebrand pathophysiology
A
Autosomal dominant
3 types:
o 1 = partial quantitative deficiency
o 2 = qualitative deficiency
o 3 = total quantitative deficiency
Outcome = platelets cannot adhere (via Glycoprotein Ib) to exposed subendothelial connective tissue to form primary platelet plug
12
Q
Most thrombogenic (genetic) condition?
A
Anti-thrombin deficiency
Familial deficiency usually presents in 20s with thrombosis Sx
13
Q
MOA of anticoagulant drugs: Heparin Rivaroxaban/Apixaban/Edoxaban Dabigatran Warfarin
A
Potentiate antithrombin
Direct acting anti Xa
Direct acting anti IIa
Vitamin K antagonist - prevents recycling of vitamin K
* Procoagulant factors 2, 7, 9, 10 fall
* NOTE: anticoagulant protein C and S also fall but NET effect = anticoagulant
14
Q
Thromboprophylaxis regimen
A
LMWH
o E.g., Tinzaparin 4500u / Enoxaparin 40mg OD
15
Q
Treatment regiments after thrombosis due to:
- Surgery
- COCP, trauma, flight
- No trigger
A
After surgical precipitant = VERY LOW risk of recurrence
-No need for long term Tx
After minor precipitants e.g., COCP, flight, trauma = moderate risk of recurrence
- 3-month Tx usually adequate
- Longer duration may be needed if other thrombotic/haemorrhagic RF
After idiopathic VTE (no circumstantial reason) = HIGH risk of recurrence
- Long term anticoagulation needed
- DOAC
16
Q
Features of Leucoerythroblastic blood film
A
Teardrop RBCs - aniso, poikilocytosis
Nucleated RBCs
Immature myeloid cells
17
Q
Causes of leucoerythroblastic anaemia
A
Malignancy
- Haem: leukaemia, lymphoma, myeloma
- Non haem: metastatic breast, bronchus, prostate
Myelofibrosis
Severe infection
- Miliary TB
- Severe fungal infection
18
Q
Key features of Acquired Immune mediated Haemolytic anaemia
A
Spherocytes on blood film
DAT+
Agglutination
19
Q
Key features of Acquired Non-immune mediated haemolytic anaemia
A
RBC fragments ‘schistocytes’
Thrombocytopaenia
DAT-
20
Q
Reactive vs malignant neutrophilia
A
Reactive (infection): toxic granulation, no immature cells, vacuoles in neutrophils
Malignant:
Neutrophilia + basophilia + immature cells (myelocytes) + splenomegaly –> CML
Neutrophilia + even more immature cells (myeloblasts) –> AML
21
Q
Causes of Secondary polycythaemia
A
Appropriately increased EPO:
- High altitude
- Hypoxic lung disease
- Cyanotic heart disease
- High affinity haemoglobin
Inappropriately increased EPO:
- Renal disease – cysts, tumours, inflammation
- Uterine myoma
- Other tumours - liver, lung
22
Q
Features of polycythaemia vera
A
Asymptomatic - raised Hb and Hct on routine FBC
Hyperviscosity Sx:
- Headaches, light headedness, stroke
- Visual disturbance
- Fatigue
- Dyspnoea
Increased histamine release
- Aquagenic pruritis (after hot bath/shower)
- Peptic ulceration
Variable splenomegaly?
23
Q
Features of Essential thrombocythaemia
A
Asymptomatic - incidental thrombocytosis >600 on FBC in 50%
Thrombosis – arterial or venous
o CVA, gangrene, TIA
o DVT, PE
Bleeding – mucous membranes, cutaneous
Headaches, dizziness, visual disturbance
Modest splenomegaly
24
Q
Clinical features of Primary Myelofibrosis
A
Asymptomatic - Incidental finding in 30%
Related to bone marrow failure / cytopenias
o Anaemia – pallor, SOB
o Thrombocytopenia – bruising, bleeding
Thrombocytosis
(Hepato)Splenomegaly – massive
o Budd-Chiari syndrome
Hypermetabolic state – weight loss, fatigue, dyspnoea, night sweats, hyperuricaemia (causing gout)
25
Clinical features of CML
* Lethargy, hypermetabolism
* Thrombotic event
* Monocular blindness (CVA)
* Bruising, bleeding
* Massive splenomegaly +/- hepatomegaly
26
CML Treatment
1st line = Oral 1st gen TKI e.g. Imatinib
No complete response at 1 year OR acquire resitance --> 2nd line = 2nd gen TKI e.g. Dasatinib OR 3rd gen TKI e.g. Bosutinib
+/- Allogeneic stem cell transplant
27
Treatment of Ph Chr -ve Myeloproliferative disease
PCV = Venesection, aspirin, hydroxycarbamide
ET = Aspirin, Hydroxycarbamide - reduce platelet count +/- anagrelide (rare)
PM
Supportive:
- RBC & platelet transfusion
Symptomatic:
hydroxycarbamide (but may worsen anaemia), JAK 2 inhibitor e.g. Ruxolotinib
Curative: allogenic stem cell transplant
28
Primary genetic events in Multiple myeloma
Hyperdiploidy - 60% of cases
- E.g. trisomy 1, 9
IGH rearrangements involving Chr14q32
- E.g. t(4;14) IGH/FGFR3
29
Natural History of Multiple Myeloma
```
MGUS
Smouldering myeloma
Symptomatic myeloma
Remitting-relapsing
Refractory
Plasma cell leukaemia
```
30
Diagnostic Features of Multiple Myeloma
10% or more plasma cells in bone marrow PLUS 1+ of the following:
CRAB
Hypercalcaemia - >2.75mmol/L
Renal disease – creatinine >177umol/L or eGFR <40ml/min
Anaemia – Hb <100g/L or drop by 20g/L
Bone disease – 1 or more lytic lesions on imaging
MDE
Bone marrow plasma cells 60+%
Involved: uninvolved FLC ratio >100
>1 focal lesion in MRI (>5mm)
31
Clinical Features of AL Amyloidosis
```
Nephrotic syndrome - proteinuria, peripherla oedema
Unexplained heart failure
Sensory neuropathy
Abnormal LFTs
Macroglossia
```
32
Microscopic features of AL Amyloidosis
Congo Red stain
Apple green birefringence (under polarised light)
Fibrils are solid, non branching, randomly arranged and 7-12nm diameter.
33
Chromosome translocations in lymphoma
Follicular NHL - IgH;BCL2
Mantle Cell Lymphoma - IgH;cyclinD
Burkitt Lymphoma - IgH;c-MYC
34
Specific mechanisms of Lymphomagenesis
1. (Constant antigenic stimulation) secondary to Chronic bacterial infection
- B cell non-Hodgkin lymphoma marginal zone sub type (MZL)
- H. Pylori --> Gastric MALToma of stomach
2. (Constant antigenic stimulation) secondary to AI disorders
- B cell non-Hodgkin lymphoma marginal zone sub types (MZL)
• Hashimoto’s --> MZL of thyroid
• Sjogren’s syndrome --> MZL of salivary glands
- Coeliac disease --> small intestinal enteropathy-associated T cell non-Hodgkin lymphoma (EATL)
3. Direct viral integration
- HTLV1 retrovirus infects T cells via vertical transmission
- Risk of adult T cell leukaemia lymphoma(ATLL) – a subtype of T cell non Hodgkin lymphoma = 2.5% at 70 years
4. EBV driven proliferation (with immunosuppression)
- NORMALLY EBV infects B lymphocytes --> healthy carrier state where proliferating B cells targeted and killed by EBV specific cytotoxic T cells
- LOSS of T cell function can --> failure to eliminate EBV-driven proliferation of B cells:
• HIV infection --> B NHL
• Transplant immunosuppression --> Post-transplant lymphoproliferative disorder (PTLD)
N
35
Key Histological features of B cell Non Hodgkin's Lymphomas
B cell types
- Burkitt's = starry sky appearance
- Small lymphocytic lymphoma = small lymphocytes, naive or post-germinal centre cells, CD5+CD23+
- Follicular lymphoma = follicular pattern, CD10+bcl6+
- Diffuse large B cell lymphoma = sheets of large lymphoid cells, germinal centre (good) or post-germinal centre cells
- Mantle cell = pre-germinal centre cells, cyclin D1, aberrant CD5
- Marginal zone = post-germinal centre memory cells
36
Key Histological features of T cell Non Hodgkin's Lymphomas
- Peripheral T cell lymphoma NOS = large T cells + EOSINOPHILS
Cutaneous T cell lymphomas = CD4+ T cells infiltrating epidermis
- Anaplastic large cell lymphoma = large epithelioid lymphocytes, T cell or null phenotype
37
Key Histological Features of Hodgkin's Lymphoma
Classical type
- Reed Sternberg cells!
- Hodgkin cells - large nuclei, prominent nucleoli -> 'Owl's eye' appearance
- Eosinophils
Non classic / Lymphocyte predominant
- B cell rich nodules
- Scattered L & H cells
38
Immunophenotype of B cells in CLL
```
CLL = Aberrant expression of CD5
Will also have:
o CD23+
o FMC7-
o CD79b +/-
o SmIG +/-
o CD19+
```
Normal peripheral B cell = CD3- CD5- CD19 +
39
Ann Arbor staging system for Lymphoma
FDG-PET-CT
* I - one group of nodes
* II - >1 group of nodes, same side of diaphragm
* III – nodes above and below diaphragm
* IV - extra-nodal spread
+ A - no constitutional Sx or B = any constitutional symptom
40
Poor prognostic factors in CLL
Tp53 mutation - del17p
IgH mutation status - unmuated = worse (8 year survival vs 25 years)
+ extent of disease (IPI score)
41
Diagnostic findings in CLL
* Lymphocytosis 5-300 x109/L
* Smear cells
* Normocytic normochromic anaemia
* Thrombocytopenia
* Bone marrow lymphocytic replacement of normal elements
+ malignant cells on immunophenotyping e.g. aberrant expression of CD5 in peripheral B cells
42
Acute Adverse Blood Transfusion Reactions
Acute haemolytic (ABO incompatible) - severe or fatal
Allergic - mild to moderate
Anaphylaxis - severe or fatal
Infection (bacterial) - severe or fatal
Febrile non-haemolytic - mild to moderate
Respiratory
- Transfusion associated circulatory overload (TACO) - moderate, severe or fatal
- Acute lung injury (TRALI) - severe or fatal
- Transfusion associated dyspnoea (TAD) - diagnosis of exclusion
43
Delayed Adverse Blood Transfusion Reactions
Delayed haemolytic transfusion reaction (Abs) - previous transfusion forms Ab to RBC antigen, next transfusion causes IgG mediated extravascular haemolysis, mild-moderate.
Infection - presents months-years later
TA-GvHD - rare, always fatal, patient tissue HLA attacked by donor lymphocytes (normally destroyed by patient immune system), immunosuppressed patients.
Post-transfusion purpura - settles in 1-4 weeks, give IV Ig, risk of life-threatening bleeding.
Iron overload - numerous transfusions (>50) accumulate iron, damage to organs e.g. liver, endocrine, heart,
44
Sensitising events in Haemolytic disease of newborn
o Delivery – if baby RhD+
o Spontaneous miscarriage (if surgical evacuation needed)
o Termination of pregnancy
o Invasive procedures in pregnancy – amniocentesis, chorionic villus sampling
o Abdominal trauma
o External cephalic version
o Stillbirth or intra-uterine death
All require dose of anti-D
- 250 iu if <20 weeks
- 500 iu if >20 weeks
- larger dose if large foetal bleed - use Kleihauer test!
45
Components of cryoprecipitate
```
o Fibrinogen
o FVIII and vWF
o Fibronectin
o fXIII
o Platelet microparticles
o IgA
o Albumin
```
46
Timeline of infections after BM transplant
Early = bacterial
Viruses
* HSV re-activation early
* BK = within first 30 days
* CMV = after first month
* EBV = late
Fungal = throughout?
* Candida early
* PCP later
* Aspergillus has early + late peak
47
HLA Types relevant to BM transplant
```
o HLA-A, -B, -C (class I) – present peptide to CD8+ cytotoxic T cells
o HLA-DP, -DQ, -DR (class II) – present peptide to CD4+ T helper cells
```
HLA-A, -B, -DR most important!
48
Possible indications for autologous + allogeneic BM transplant
```
Autologous
o Acute leukaemia
o Myeloma
o Lymphoma
o Chronic lymphocytic leukaemia
o Solid tumours
o AI disease
o Multiple sclerosis
```
```
Allogeneic
o Acute leukaemia
o Chronic leukaemia
o Myeloma – most elderly patients cannot tolerate levels of myeloablation needed!
o Lymphoma
o BM failure
o Congenital immune deficiencies
```
49
Physiological changes in FBC during pregnancy
Mild anaemia
o Red cell mass rises – 120-130%
o Plasma volume rises 150%
Macrocytosis
o Normal physiology OR Folate or B12 deficiency
Neutrophilia
Thrombocytopenia
o with increased platelet size (more immature + more active platelets released due to rapid turnover)
50
Cut offs for anaemia in pregnancy
* <110 in 1st trimester
* <105 in later trimesters
* <100 Post-partum
51
Causes of thrombocytopenia in pregnancy
* Physiological / gestational / incidental - Mechanism poorly understood (partially dilution + increased consumption), >50 sufficient to deliver, >70 sufficient for epidural, foetal + baby UNAFFECTED
* Pre-eclampsia (PET) - increased activation + consumption?, usually resolves post delivery
* ITP - hardest to distinguish from physiological, baby can be affected - check cord blood!, may continue to fall up to 5 days post delivery, Tx = IVIg or steroids (if bleeding / needed for delivery)
* Microangiopathic syndromes (MAHA) - shearing + fragmentation of RBC due to platelet deposition in vessels, includes HELLP, TTP, HUS (latter 2 not changed by delivery)
* Other - Bone marrow failure, leukaemia, hypersplenism, DIC etc.
52
Management principles of VTE in pregnancy
LMWH OD or BD (as for non pregnant)
Monitoring after 1st trimester - check anti Xa 4 hours post dose
STOP Tx for labour/planned delivery
- epidural can be given after 24 hours (12 if only prophylactic dose)
NO WARFARIN - causes chondrodysplasia punctata (but is safe to use when breastfeeding)
NO DOAC - during pregnancy or breastfeeding
53
Stages of granulocyte maturation
```
Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
Band cell
Immature --> mature neutrophil
```
54
Features of a blast cell
Large
High nuclear: cytoplasmic ratio
Diffuse / primitive chromatin pattern
Visible nucleoli
55
Microscopic/blood film features of acute promyelocytic leukaemia
classical subtype = hyper granular, multiple Auer rods
| variant = bilobed nuclei
56
Cytochemical staining in acute myeloid vs lymphocytic leukaemia
Myeloperoxidase: +AML, -ALL
Sudan black: +AML, -ALL
Non-specific esterase: +AML, -ALL
57
Definitive Ix for diagnosis of ALL
Immunophenotyping
ALL:
Precursor B cell = CD19, CD20, TdTm CD10+/-
B cell: CD19, CD20, surface Ig
T cell: CD2, CD3, CD4 or 8, TdT
AML: MPO, CD13, CD33, CD14, CD15, glycophorin (E), platelet antigens
58
Important platelet proteins/receptors
glycotprotien 1a - direct adhesion to exposed subendothelium
glycoprotein 1b - binds with assistance of vWF to exposed subendothelium (more important)
glyocpotein 2b 3a 'Fibrinogen receptor' - allows platelet aggregation
59
Clotting pathway
TF binds F7 --> F7a
TF-Factor 7a complex activates F10 and 9 --> F10a and F9a
F10a activates F5 on cell surface
F10a and F5a convert prothrombin --> thrombin (small amount)
Thrombin activates F8, F5, F11, local platelets
Factor 11a activates Factor 9
Platelets bind Factor 5, 8 and 9
Factor 9a + Factor 8a together activate more Factor 10
Activated factor 10 and 5 convert more prothrombin --> thrombin 'thrombin burst' which forms stable fibrin clot
60
Most thrombogenic quality/condition
Anti-thrombin deficiency (quantitative or qualitative)
61
Treatment of Immune-mediated Idiopathic Auto ITP
Platelets >50,000 + No Sx = no Tx
Platelets 20-50,000 + No Sx = no Tx
Platelets 20-50,000 + bleeding = steroids + IV Ig
Platelets <20,000 + No Sx = steroids
Platelets <20,000 + bleeding = Steroids, IV Ig, hospital admission
62
Factor deficiency coagulation disorders - name & defect/mechanism
Haemophilia
- congenital deficiency of Factor 8 (A) or 9 (B)
- X linked
Von Willebrand disease
- autosomal domiannt
- Type 1 = partial quantitative deficiency
- Type 2 = qualitative deficiency
- Type 3 = total quantitative deficiency
63
Affected proteins in RBC Membrane disorders
Hereditary spherocytosis
- Band 3
- Protein 4.2
- Ankyrin
- beta spectrin
Hereditary elliptocytosis
- alpa spectrin
- beta spectrin
- protein 4.1
64
Indications for Splenectomy in Haemolytic anaemia
```
Transfusion dependence
Growth delay
Physical limitation Hb <80
Hypersplenism
Age not <3 years but BEFORE 10 years - maximise prepubertal growth
```
65
Blood film features during acute episode of RBC oxidative haemolysis (G6PD deficiency)
```
Contracted cells
Nucleated RBCs
Bite cells - cytoplasm removed
Hemighosts?
Heinz bodies!!!! (using Methyl violet stain)
```
66
Morphological feature of Pyrimidine 5-nucleotidase deficiency AND lead poisoning
Basophilic stippling - fine and course
67
PROthrombotic effects in vessel wall after injury/inflammation
Anticoagulant molecules e.g. thrombomodulin DOWNregulated
tissue factor becomes expressed
Prostacyclin (anti platelet factor) production DECREASES
Adhesion molecules UPREGULATED
Von Willebrand factor release
68
Key diagnostic feature of Paroxysmal cold haemoglobinuria (PCH)
Presence of Donath-Landsteiner Ab
| Stick to RBC in cold --> complement mediated haemolysis when re-warmed
69
TTP Pentad of Signs/Sx
```
Microangiopathic haemolytic anaemia (MAHA)
Thrombocytopenia
AKI
Neurological impairment
Fever
```
70
Aetiology of TTP
Mutation in ADAMTS13
| Causes deficiency of vWF cleaving protease = fragmentation of RBCs in vessels
71
Measuring response to Tx in CML
Haematological - WBC <10
Cytogenetic (on 20 metaphases)
- Partial = 1-35% Philadelphia Chr +
- Complete = 0% Philadelphia Chr + after 6 months Tx
Molecular - measure % reduction in BCR-ABL transcripts
72
Diagnostic criteria for MGUS
Serum M protein <30g/L
BM clonal plasma cells <10%
No lytic bone lesions
No myeloma-related organ or tissue impairment
No evidence of other B cell proliferative disorder
73
Risk factors for progression of MGUS to lymphoma/myeloma
Non IgG M spike
M spike >15g/L
Abnormal serum free light chain ratio
74
Criteria for smouldering myeloma
Must meet both:
1) serum monoclonal protein (IgG or IgA) 30+ g/L OR urinary monoclonal protein 500mg + per 24 hours AND/OR clonal BM plasma cells 10-60%
2) Absence of myeloma defining events or amyloidosis
75
Risk factors for progression of smouldering myeloma
BM myeloma cells >20%
M spike >20g/L
Serum free light chain ratio >20
High risk (2+ factors) may need Tx
76
Mechanism of Myeloma kidney disease
MAIN = Cast nephropathy
- normally taken up within proximal tubule --> return to circularion
- BUT very high serum free light chains + Bence Jones proteinuria overwhelms cells
- triggers inflammatory + fibrotic pathways
- light chains able to travel further down tubule - interact with uromodulin (THP)
- block tubules --> AKI
Other causes:
- hypercalcaemia
- loop diuretics
- infection
- dehydration
- nephrotoxics
77
Treatment of myeloma kidney disease
Hydration
| Bortezomib-based therapy
78
Diagnostic workup for multiple myeloma
Immunoglobulin studies
- serum protein electrophoresis
- serum free light chain
- 24h Bence jones protein
BM aspirate + biopsy
- immunohistochemistry for CD138 - myeloma specific!
- kappa / lambda light chain staining
FISH analysis
Flow cytometry immunophenotyping
79
Multiple myeloma treatment regimen if fit + <65 years old
Induction:
- 'VTD / VRD' = proteasome inhibitor e.g. Bortezomib + immunomodulatory drug e.g. Lenalidomide + Dexamethasone
- +/- Anti CD38 mAb e.g. Daratumumab
Autologous stem cell transplant
+/- consolidation: 2 x VTD/VRD regimen
Maintenance: low dose lenalidomide 2 years
80
Multiple myeloma treatment regimen if frail and/or over 65 yrs
Lenalidomide + Dexamethasone
OR Bortezomib (proteasome inhibitor) + Cyclophosphamide (alkylator) + Dexamethasone
OR Daratumumab (anti CD38 mAb) + Bortezomib + Cyclophosphomide + Prednisolone
81
Subtypes of Classical Hodgkin's lymphoma
Nodular sclerosing
Mixed cellularity
Lymphocyte rich
Lymphocyte depleted
81
Subtypes of Classical Hodgkin's lymphoma
Nodular sclerosing
Mixed cellularity
Lymphocyte rich
Lymphocyte depleted
82
ABVD Hodgkin's Lymphoma Treatment Regimen
Adriamycin
Bleomycin
Vinblastine
DTIC (Dacarbazine)
83
R-CHOP Non-Hodgkin's Lymphoma Tx regimen
R = Rituximab (anti CD20)
CHOP:
- Cyclophosphamide
- Adriamycin
- Vincristine
- Prednisolone
84
Indications to start Tx in (indolent) follicular Non-Hodgkin's lymphoma
Nodal extrinsic compression e.g. bowel, bile duct, ureter, vena cava
Massive painful nodes
Recurrent infections
85
Active Treatment of Chronic Lymphocytic Leukaemia
Ibrutinib = bruton tyrosine kinase inhibitor, suitable for refractory p53 mutation
Venetoclax = anti Bcl-2 oral agent, suitable for refractory p53 mutation
Allogenic stem cell transplant
CAR-T - complete B cell depletion so must give IV Ig!
86
Indications for active Tx in CLL
Progressive lymphocytosis (count doubling in <6mths)
Progressive BM failure: Hb <100, Plts <100, Neutrophils <1
Massive or progressive lymphadenopathy / splenomegaly
Systemic/B symptoms
87
Staging systems for CLL prognosis
Binet
A = <3 lymphoid areas
B = >3
C = Hb or Plts <100
```
Rai
0 = lymphocytosis only
1 = lymphadenopathy
2 = hepatosplenonegaly +/- splenomegaly
3 = Hb <110
4 = Plts <100
```
88
Rank severity of Acute blood transfusion reactions
Severe/fatal
- Acute haemolytic ABO incompatibility
- Anaphylaxis
- Infection (bacterial)
- Acute lung injury (TRALI)
Moderate-severe-fatal
-Transfusion associated circulatory overload (TACO)
Mild/moderate
- Allergic
- Febrile non haemolytic
89
Severity of delayed blood transfusion reactions
Always fatal
- Transfusion associated Graft versus Host disease
Mild-moderate
- Delayed haemolytic transfusion reaction
- Infection (from donor blood)
- Post-transfusion purpura (BUT sometimes causes life-threatening bleeding)
90
Criteria for neutropenic sepsis
Temp 38+ for 1 hour OR single fever >39
| in patient with neutrophils <1.0 x 10^9/L
91
EBMT risk score Post BM transplant
Age <20=0 20-40=1 >40=2
Disease phase Early=0 Intermediate=1 Late=2
Gender of rec/donor. Female to Male =1
Time to transplant <1year=0 >1 year =1
Donor Sibling=0 VUD=1
92
Type of leukaemia seen in Down syndrome infants
Transient abnormal myelopoeisis
form of congenital leukaemia
Involves megakaryocytic lineage
Spontaneous remission common
93
Typical hypersplenism bacteria
Pneumococcus
Meningococcus
H. influenzae
94
Factors considered in WHO classification of Myelodysplastic syndrome (2016)
```
Number of dysplastic cell lineages
% blasts in BM and peripheral blood
Cytogenetic
% ringed sideroblasts
Number of cytopenias
Hb <100
Plts <100
Neutrophils <1.8
Monocytes <1.0
```
95
Outcomes of Myelodysplastic syndrome
1/3 die from infection
1/3 die from bleeding
1/3 die from transformation to acute leukaemia
96
Drugs that can cause BM failure
Dose dependent - cytotoxics
Idiosyncratic - gold salts, phenylbutazone, NSAIDs
Other:
Abx - chloramphenicol, sulphonamide
Thiazide diuretics
Carbimazole (anti thyroid)
97
Camilla Criteria for Idiopathic Aplastic Anaemia
2 out of 3:
- Reticulocytes <1% (<20 x 10^9/L)
- Neutrophils <0.5
- Platelets <20
AND BM cellularity <25%
98
Classical triad of Dyskeratosis Congenital
Skin pigmentation
Nail dystrophy
Leukoplakia
99
Key features of Fanconi Anaemia
Congenital malformations - up to 70%
- short stature
- cafe au lait spots
- thumb abnormalities
- microcephaly/hydrocephaly
- hyogonadism
+ Aplastic anaemia
