Haematology Flashcards
(256 cards)
1
Q
Adverse effects of imatinib?
A
Weight gain
Oedema
Nausea
Vomiting
2
Q
Which 1 of the 3 antiphospholipid test confers the most risk of clotting events?
A
- Lupus anticoagulant
- anti-B2 glycoprotein 1
- IgM anticardiolipin antibody
3
Q
Which agent reduces mortality in trauma patients at risk of bleeding?
A
Prothrombinex
4
Q
What are the indications for Vitamin K warfarin reversal in a patient with an INR:
4.5
>4,5 -10 + high risk of bleeding
>10
A
4.5:
stop warfarin until INR approaches therapeutic range and then resume dose
Check INR in 24 h
> 4.5 - 10 - high risk of bleeding: Cease warfarin Give 1-2 mg PO or 0.5-1 mg IV Check INR in 24 h
> 10: cease Vit K3-5 mg PO or IV Prothrombinex (FII, IX, X)if bleeding risk high. Check INR after 12-24h.
5
Q
17p deletion good or poor prognosis?
A
Always poor.
17 p in CLL
6
Q
Rivaroxaban is CI in pts with eGFR
A
False.
Use with caution.
CI if eGFR
7
Q
Co-administration of posaconazole with Rivaroxaban will increase risk of bleeding. T/F
A
True, Posa inhibits CYP3A4
8
Q
MOA Rivaroxaban? How to monitor?
A
Anti-Xa inhibitor. No reversal agent.
Assay by anti-Xa testing
9
Q
When do you stop Rivaroxiban/apixiban prior to elective Sx?
A
Elderly - 2-3 days prior, clearance 44-52 h
Young - 1-2 d prior, clearance 20-36 h
10
Q
Predictors of recurrence after DVT?
A
+ve D-dimer 2 weeks after cessation of warfarin
Heritable thrombophilias and low protein C levels are low risk
11
Q
What are the strong RF for recurrence after DVT?
A
PE/DVT
> 2 thrombotic events
Male sex
Residual vein thrombus
Vena cava filter
Continued oestrogen use
Cancer
12
Q
What is the role of hepciden?
A
Negative regulator of Fe, blocks feroportin and the free movement of Fe across cells
13
Q
What happens to hepciden in anaemia?
A
decreases hepciden
14
Q
What happens to hepciden in inflammation?
A
Increases transcription of hepciden through IL6 via Stat3, LPS
15
Q
What are the disease associations for the following haemoglobinopathies?
Thalassemia
B-thalassaemia
a-thal
Haemoglobinopathies
Sickle cell anaemia
Abnormal Hb
High affinity Hb
A
Thalassemia - micorcytic anamia +normal ferritin
B-thalassaemia - Hb electrophoresis demonstrates increased HbA2
a-thal - molecular test for a-chain deletion
Haemoglobinopathies - abnormal Hb molecules
Sickle cell anaemia - Vascular complications
Abnormal Hb - Anaemia Hb D, O, C, S
High affinity Hb - Polycythemia. Dx ABG paO2
16
Q
Hydroxyurea has been shown to reduce acute on chronic complication of SCD. T/F
A
True
CI in pregnancy
17
Q
What is the commonest inherited bleeding disorder?
A
vWD, 1 in 100.
Deficient or defective vWF
18
Q
How does vWF bind to sub endothelium? Role of vWF?
A
primary binding site on platelets is GP1b-IX-V
required for platelet adhesion, aggregation and stabilises FVIII
19
Q
What are the types of vW disease?
A
Type 1-reduced levels, partial reduction in vWF (80% of pts). AD
Type 2- mutations in vWF functional (binding sites) defect, abnormal form of vWF
Type 3 – severe deficiency, total lack of von willebrand factor (AR)
20
Q
How do you dx Waldenstrom’s macroglobulinaemia?
A
Presence of any size serum IgM paraprotein
Bone marrow aspirate: inflitration with snake lymphocytes demonstrating plasmacytoid/plasma cell differentiation
Immunophenotype (flow cytometry) - B cell lymphoma, IgM CD19/20+, CD10 and CD5
21
Q
What feature do you see on film with lead poisoning?
A
Basophilic stripping
22
Q
What feature do you see on blood film with Fe def anaemia?
A
Target cells
23
Q
Tx for ITP?
Plts 30, no bleeding
A
Plts 30 and no bleeding
- observation
IVIG can be used instead of steroids when a more rapid increase in plt count is requiored
24
Q
APTT is a measure of intrinsic pathway (FXI, IX, VIII). T/F
A
True
25
APTT does not correct on mixing and no bleeding diathesis. Aetiology?
Lupus anticoagulant most common
FXII and HMWK/Prekalikrein antibody rare
26
APTT does not correct and bleeding diathesis. Aetiology?
FVIII inhibitor (time dependent)
FIX inhibitor
FXI inhibitor (rare)
27
Which NOAC can be removed with dialysis?
Haemodiaylsysis works for dabigatran as low protein binding, not for other NOACs as has high protein binding
28
Does 5q deletion indicate good or poor prognosis in myelodysplastic syndrome?
Good prognosis
29
Tx for myelodyplastic syndrome?
Supportive care and iron chelating therapy
Azacitadine
Lenolidamide
30
What are the RF for myelodysplastic syndrome?
DNA damage from previous CTx or radiation, inherited defects in DNA repair
Down syndrome
31
What drug has been shown to improve survival in Myelodysplasia?
Azacitidine
| - a DNA hypomethylating agent
32
What does the film morphology show in Myelodysplasia?
Anisopoikilocytosis
tear drop cells
oval macrocytes
occasional nucleated red blood cells
33
What complement change is PNH associated with?
decrease in CD59
34
What complement change is mesangiocapillary glomerulonephritis associated with?
Production of C3 nephritic factor
35
How do you diagnose haemochromatosis?
What levels do you aim for phlebotomy?
Risk of progressing to fibrosis?
Tranferrin saturations >60% in M, >50% in F, most sensitive test
Liver Bx provides definitive Dx
- Serum ferritin
- acute phase reactant
- can be elevated by EtOH, steatosis, viral overlaid
- a level of >1000 in absence of above used to indicate the need for biopsy
- the negative predictive value of a normal transferrin saturation and serum ferritin is 97%.NO FURTHER TESTING.
- Liver biopsy
- grade 3 hepatocyte Fe accumulation with an acinar distribution pattern consistent with homozygous genetic haemochromotosis
- stained with Perl’s prussian blue
Phlebotomy
- Aim serum ferritin maintain levels
36
What is the mutation in haemochromatosis?
HFE gene located on chromosome 6.
2 missense mutations: C282Y (85%) and H63D (20%)
37
When if FFP indicated?
To replace coagulation factors
Used when PT/PTT supratherapeutic
38
When is cryoprecipitate indicated?
Contains fibrinogen, vWF, FVIII, FXIII, Fibronectin (5Fs)
Its a plasma component enriched with fibrinogen.
Used in DIC to replace fibrinogen
39
What is cerebral venous thrombosis? Presentation? Dx?
Rare, presents in immediate post part period.
Clinical:
Headache
Vomiting
Focal or generalised seizures
Confusion
Blurred vision
Focal neurological deficits
Altered consciousness
Dx:
MRI
40
What is the hallmark of Factor VII inhibitor?
Bleeding that is first noted after a surgical procedure.
APTT is prolonged
PT is normal
41
Is there a prolonged APTT in antiphospholipid syndrome?
Yes however thrombosis is the common presentation
42
What is the most common inherited hypercoagulable state? Which hypercoagulable state is most likely to clot?
Factor V Leiden mutation and prothrombin gene mutation account for 50-60% of cases
patients with defects in Protein C,S and antithrombin are more likely to clot
43
Mechanism of Factor V mutation leading to thrombosis?
Causes a resistance to the normally inhibitory effects of protein C
Heterozygosity for the factor V Leiden mutation increases the lifetime risk for thrombosis 7-fold
Homozygosity raised the risk 20 fold
44
Mechanism of Prothrombin gene mutation leading to thrombosis?
A gain of function mutation resulting in elevated levels of prothrombin.
Heterozygous carrier have increased risk of 3-4 fold of venous and possibly arterial thrombosis
45
Which antiphospholipid abs has the strongest RF for thrombosis? Lupus, anticardiolipin or B2-glycoprotein?
Lupus anticoagulant - highest risk of thrombosis and adverse pregnancy outcomes after 12 weeks gestation
46
Is Hepcidin increased or decreased in anaemia of chronic disease?
Increased in order to prevent further iron release into the blood
47
Myelodyplasia: what therapy has prolonged survival compared with supportive care? Therapy fro 5q sydnrome?
Azacitdine
5q syndrome indicates good prognosis. Responds to Lenalidomide, reduces risk of transformation to AML.
48
GVHD. What is the key cell type involved?
T cell mediated disease. The principle antigenic targets of the T cells of the graft are the host MHC molecules if the patient and donor MHC molecules differ.
49
What diseases are associated with each of the cryoglobulinaemia?
Type 1 - Waldenstrom’s or MM, produces few complement abnormalities
Type 2 - persistent viral infections, HCV, HIV
Type 3 - systemic rheum conditions
50
PT high, aPPT normal. Cause?
Problem with FVIII, IX, XI, XII
Heparin the most common
Factor VIII inhibitor if bleeding present
Antiphospholipid syndome in clotting patient
vWD
Haemophilia
51
PT high, aPPT high. Cause?
Defect in the common pathway e.g. def prothrombin, fibrinogen, factor V or X.
Combined factor deficiencies.
most common cause is RHF with liver congestion, very high PT!
Medications
- abx, not as elevated as RHF
- Warfarin
- Liver disease, Vit K def, excess heaprin, DIC
52
Which thalassaemia combination gives the highest risk of having a child with a severe form of thalassaemia?
Trait + Trait
53
What does a normal Hb electrophoresis pattern contain?
HbA 97%
HbA2
54
Genetic defect in B thal? Types?
defect in B-genes
Normal Hb contains 2 alpha and 2 beta
B-thalassaemia minor (deletion of 1 B-globin gene)
- mild microcytic anaemia or no anaemia.
- Asymptomatic.
- 2-3 fold elevation of HbA2, slight increase in HbF on Hb electrophoresis.
B-thal major (deletion of both B-globin genes):
Resulting severe anaemia -> elevated EPO levels
Hb electrophoresis shows high HbF and HbA2
Fetus and newborn not affected as a2y2 until y switches to beta -> severe anaemia, pallor, growth retardation and heptosplenomegaly due to extramedullary haemopoiesis.
B- thal intermedia (homozygous)
- not all pts with homozygous have full clinical severity
- modulating defects include minor qualitative defects of the B-globin, coinheritance of a-thal trait and increased prod of HbF
55
What is the best way to prevent post thrombotic syndrome after DVT? What is post thrombotic syndrome?
Exercise training.
Is the development of S&S of chronic venous insufficiency following a DVT
56
HITS, what are the 4Ts? Score numbers?
Presentation
Ix
Tx
Thrombocytopenia, PLT count fall > 50%
Timing of PLT count fall, 5-10 days (HITs type 2, type 1 is in 1-2 d and recovers spontaneously)
Thrombosis or other sequel
Other cases for thrombocytopenia present
0-3 = low probability
4-5 = intermediate
6-8 = high probability
Presentation:
Fever, chills, dyspnoea, chest pain
THROMBOEMBOLISM (large vessel venous or arterial) is the most common manifestation
Ix:
Immunoassays identify antibodies against heparin/platelet factor 4 (PF4) complexes.
Functional assays measure the platelet-activating capacity of PF4/heparin-antibody complexes.
Functional assays have greater specificity than immunoassays but are time-consuming and not widely available; many institutions offer only immunoassays
Tx:
Heparin cessation
Tx with non heparin anticoagulant:
Danaparoid (LMWH), Fondaparinux (synthetic Factor Xa inhibitor) lepirudin (direct irreversible thrombin inhibitor), argatroban (direct thrombin inhibitor)
Bivalirudin is indicated only in pats with HIT or at risk for HIT undergoing acute cardiac interventions.
Lepirudin is renally cleared.
Argatroban is cleared through liver.
Dx of Pure red cell aplasia?
A very low reticulocyte count,
57
DDx of microcytic anaemia?
Fe def
Thalassaemia
Less common
- anaemia of chronic disease
- myelodyplasia
- sideroblastic anaemia
- hyperthyroidism
- heavy metal poisoning
58
What are the 2 major causes of non-restricted Fe def anaemia?
1. Absolute Fe def - absent stores
2. Functional Fe def - insufficient availability of Fe in the setting of normal to increased Fe stores e.g. anaemia of chronic disease, erythropoietin therapy
59
What factors are involved in the Fe cycle?
Duodenal enterocytes - absorb
Erythroid precursors - utilise
Reticuloendothelial macrophages - Fe storage and recycling
Hepatocytes - Fe storage and endocrine regulation
60
What form of Fe do duodenal enterocytes absorb? How does Fe exit enterocyte?
Ferrous Fe2+
Ferroportin exports Fe into the plasma
61
What is the role of transferrin and transferrin receptor?
Transferrin carries Fe in the plasma
Transferrin receptor mediates uptake into cells
62
What is the role of Hepcidin in Fe absorption? When does it increase/decrease?
Binds to ferroportin and induces its degradation
Hepcidin increases in Fe overload
Hepcidin decreases in Fe def
63
What is the major cause of Fe def anaemia in affluent countries?
Blood loss
- GI bleeding e.g. ulcers, malignancy, diverticulitis
- Menstruation
- Diet
- Coeliac disease, partial gastrectomy, PRV etc
64
What do the Fe studies show in Fe def? Soluble transferrin receptor?
Ferritn reduced
Transferrin increased
TIBC increased
Transferrin saturation reduced
Soluble transferrin receptor increased (derived from bone marrow erythroid precursors and directly proportional to erythropoietic rate
65
Causes of elevated Ferritin?
Inflammation
Liver disease
Infection
Malignancy
66
What is the 1st/2nd/3rd line Mx of Fe def? How do you monitor response?
1st Orals
2nd IV
3rd IM
Monitoring Hb and reticulocyte count
67
What are the causes of anaemia of chronic disease?
Infectious
Neoplastic
Inflammatory
Have an inappropriately low reticulocyte count
68
What are the mechanisms of anaemia of chronic disease?
- Altered/abnormal Fe homeostasis e.g. reduced absorption, trapping of Fe in macrophages
- Reduced RBC production by the bone marrow e.g. toxicity of erythroid precursors, cytokine mediated effects
- Blunted response to erythropoietin e.g. blunted production, reduced receptors, reduced responsiveness
- Shortened red cell survival e.g. erythrophagocytosis, cytokine and free radical damage
69
How do you Dx anaemia of chronic disease?
Ferritin normal
Transferrin saturation reduced
Transferrin reduced to normal
Soluble transferrin receptor normal
70
How can you differentiate between anaemia of chronic disease and Fe def anaemia?
Soluble transferrin receptor is increased in Fe def anaemia, normal in ACD
Cytokine levels increased of ACD
71
How do you Mx ACD?
Tx underlying cause
If mild, no intervention
Measure erythropoietin level to guide
Fe replacement therapy if Fe def and with erythropoietin therapy
Supportive care - transfusion warranted for severe symptomatic anaemia
72
What are the strongest RF for VTE?
What is the strongest RF for VTE?
Previous VTE
Fracture of LL
Hip/knee replacement
Hospitilisation for HF or AF/flutter within previous 3 months
Major trauma
MI within 3 months
Spinal cord injury
73
Which malignancies have the highest risk fro VTE?
Brain
GI
Haem
Lung
Pancreas
74
Which cytokines are involved in haem disease?
IL -3,7,9,11 - odd number
75
What is the Tx for ATRA syndrome?
Stop ATRA and give dexamethasone 10 mg IV BD
76
What is ATRA syndrome due to? S&S?
Cytokine release following differentiation of APL cells.
Causes fluid retention and capillary leak.
Occurs in 1/3 of patients.
Lower rates of ATRA syndrome if chemo is commenced with ATRA.
77
What are the RF for ALL?
```
Male- incidence 30% higher in males
Children 2-5 y
Caucasion
Down’s syndrome – 20 x risk for leukemia
Radiation exposure
```
78
What is the best CTx for Philadelphia +ve ALL?
Imatinib
79
What is the MOA of Imatinib? What is the main transporter of Imatinib?
Blocks abl function by interfering with ATP binding.
OCT-1 (organic Cation Transporter 1).
Pts with suboptimal response have lower OCT-1 activity.
80
What is the most effective Tx of MDS with chromosome 5q syndrome (5q31 deletion)?
Lenalidomide.
| Can reduce transfusion requirements and reverse cytologic and cytogenic abnormalities.
81
What is the HASFORD prognostic score?
```
Measures the response post interferon a Tx in CML. Prognostic score for survivial.
APS BEB
Age
Platelets
Slpeen size
Basophils
Eosinophils
Blasts
```
82
What is the Tx for chronic phase CML?
Imatinib
Hydroxyurea bulk reduction
IFNa +/- ARA-C
Bone marrow transplant remains the only known curative therapy=sibling allograft (ALLOGENIC)
83
What are the features of complete haematological response in the Tx of CML?
Complete normalization of peripheral blood
No immature cells in peripheral blood
No S&S of disease including disappearance of splenomegaly
No Philadelphia chromosome
84
What are the AE of imatinib?
```
Weight gain
Odema
Muscle cramps
Nausea
Deranged LFTs
Porphyria-rash
```
85
What is the main mechanism of imatinib resistance in CML?
Mutations of BCR-ABL kinase domain.
| Outgrowth of leukemic subclones secondary to BCR-ABL mutation.
86
What is the next line of Tx if a pt with CML is intolerant to Imatinib?
Dasatinib.
Induces cytogenic and haematoligcal response in pts with CML or Philadelphia +ve ALL who cannot tolerate or are resistant to Imatinib.
87
What is Hodgkin’s lymphoma? Histological classification and prognosis of each?
A malignant proliferation of lymphocytes characterised by the presence of Reed Sternberg cell.
Lymphocyte predominant – best prognosis
Lymphocyte deplete – worst prognosis
Mixed cellular –good prognosis
Nodular sclerosing – most common, good prognosis
88
What are the poor prognostic factors for Hodgkin’s lymphoma?
```
Lymphocyte deplete
B symptoms
Weight loss > 10% in last 6 months
Age> 45y
Stage IV
Hb 15, 000/uL
```
89
What is the most common inherited bleeding disorder?
Von Willebrand’s disease
| AD
90
What are the types of VWD?
Type 1-partial reduction in vWF (80% of pts)
Type 2- abnormal form of vWF
Type 3 – total lack of von willebrand factor (AR)
91
What is the role of vWF?
Large glycoprotein which forms massive multimers up to 1, 000, 000 Da in size and promotes platelet adhesion to damaged endothelium.
Carrier molecule for factor VIII.
92
What is the treatment for vWD?
Tranexamic acid for mild bleeding
Desmopressin (DDAVP) to raise levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
Factor VIII concentrate
93
What is the main AE of DDVAP (vasopressin)?
Hyponatraemia
94
What is a leukamoid reaction?
Describes the presence of immature cells such as myeloblasts, promyelocytes and nucleated red cells in the peripheral blood. May be due to infiltration of the bone marrow causing the immature cells to be pushed out or sudden demand for new cells.
Causes are severe infection, severe haemolysis, massive haemmorhage, metsatic can with bone marrow infiltration.
95
How can you differentiate leukamoid reaction from CML?
Leukamoid reaction
-high leucocyte alkaline phosphatase score
toxic granulation (Dohle bodies) in the white cells
Left shift of neutrophils i.e. three or less segments of the nucleus.
CML
-low leucocyte alkaline phosphatase score.
96
What are the features of amyloid light chain amyloidosis?
```
Nephrotic range proteinuria
Acquired factor X def leading to high INR
Postural hypotension
Macroglossia
Low grade plasma dyscrasia
```
97
What is the purpose of a mixing study?
To asses if the pt has a factor def or an clotting factor inhibitor present.
If the mixing study corrects, pt has factor def.
If it does not correct, pt has a clotting factor inhibitor present.
98
What factors are involved in the extrinsic pathway?
Tissue factor III
VII
PT checks extrinsic pathway.
99
What factors are involved in the intrinsic pathway?
```
XII (Prekallikrein)
HMWK
VIII
IX
XI
XII
APTT checks intrinsic pathway
```
100
Which pathway does the thrombin clotting time check?
The common pathway (Factor X)
101
What is romiplostim?
A fusion protein analogue of thrombopoietin, a hormone that regulates platelet production.
Romiplostim stimulates the patient’s megakaryocytes to produce platelets at a more rapid than normal rate thus overwhelming the immune system’s ability to destroy them.
102
what are the AE of romiplostim?
Myalgia
Joint and extremity discomfort
Insomnia
Thrombocytosis ->clots and bone marrow fibrosis
103
Which medications will enhance the effects of warfarin? Which will reduce the effects of warfarin?
Warfarin is a CYP3A4 substrate
CYP3A4 inhibitor-erythromycin, other macrolides, protease inhibitors (ritonavir, indinavir, nelfinavir), azole antifungals, aprepitant and verapamil. Will inhibit metabolism of warfarin.
CYP3A4 inducer- Carbamazepine and phenytoin, increase metabolism of warfarin and reduce effects.
104
How do you diagnose antiphospholipid syndrome?
Persistently positive test (at least 2 positives, 6 weeks apart)
- Anticardiolipin test
- Lupus anticoagulant test
- Anti-beta2 glycoprotein I test
105
How do you treat antiphospholipid syndrome? Non pregnant vs pregnant
No hx of thrombosis – no Tx
If SLE, CTD, Hx of miscarriage – low dose aspirin
Previous VTE – life long warfarin
If pregnant- aspirin and unfractionated heparin may reduce chance of miscarriage.
106
What is the most common cause of familial thrombophilia?
Factor V leiden (activated protein C resistance)
107
Which coagulation abnormality is resistant to the effect of heparin?
Anti-thrombin deficiency as anti-thrombin required
108
Which 2 conditions will have a raised APTT and TCT?
Heparin
DIC (raised D-dimer, low fibrinogen)
Liver disease
109
Which clotting factor is found in cryoprecipitate?
Factor VIII
110
List the myeloproliferative disorders
Polycythemia Essential thrombocythaemia
Myelofibrosis
Myelodyplasia
111
What are the secondary causes of polycythaemia?
```
Due to appropriate increase in erythropoietin
-High altitiude
-Lung disease
-CVD: R-L shunt
-Heavy smoking
-Increased affinity of Hb e.g. familial polycycthaemia
Due to inappropriate increase in erythropoietin
-renal disease e.g. RCC, Wilm’s tumour
HCC
Adrenal tumours
Cerebella haemangioblastoma
Massive uterine fibroma
```
112
How do you Dx PCV?
Presence of both major and one minor criteria or the presence of 1st major criteria and 2 minor criteria.
Major:
-Hb > 185 in M, >165 in F
-presence of JAK2 tyrosine kinase V617F or other functionally similar mutation such as JAK2exon 12 mutation
Minor
-bone marrow Bx showing hypercellularity for age witgh trilineage growth with prominent erythroid, granulcytic and megakaryocytic proliferation
-serum erythropoietin level below the reference range for normal
Endogenoous erythoid colony formation in vitro
Ix:
Elevated platelets
113
What are the clinical features of PCV.
| Tx
```
HT
Angina
Intermittent claudication
Tendency to bleed
Severe itching after a hot bath
Gout
Peptic ulceration
```
Tx:
Low dose aspirin to reduce thrombotic events.
VENESECTION best overall survival
- perform once or twice weekly until HCT is 40-45%.
Fe def will develop.
>60y + previous thrombotic event
- hydroxyurea + phlebotomy to decrease subsequent risk of thrombosis
114
What lab features distinguish between primary and secondary PCV?
Primary-low EPO
| Secondary- normal or raised EPO
115
What is Gaisbock’s syndrome (AKA stress erythrocytosis)? What are the features?
An apparent rise of the erythrocyte level in the blood.
Features
-normal RCV
-reduced plasma volume
- often caused by loss of body fluids through burns, dehydration and stress.
116
What are the lab features of ET?
Normal Hb and WCC
Platelet count ~600, may be as high as 2000
JAK2 mutation in 50% of pts
117
What are the lab features of myelofibrosis?
WCC>100
Platelet count may be very high but in later stages thrombocytopenia occurs
Bone marrow aspiration often unsuccessful
Bone marrow trephine demonstrates markedly increased fibrosis
Increased numbers of megakaryocytes
Leucocyte alkaline phosphatase score is normal or high
High serum urate
Low serum folate levels
Philadelphia chromosome ABSENT
118
Which lab investigation will help you distinguish between myelofibrosis and CML?
Bone marrow appearance
| Absence of Philadelphia chromosome in myelofibrosis
119
What are the lab features of myelodysplasia?
Pancytopenia
-anaemia
neutropenia
monocytosis
thrombocytopenia
Bone marrow usually shows increased cellularity despite pancytopenia
Ring sideroblasts are present in all types
120
What is the value for an elevated HCT in M and F?
M=>60%
| F = >57%
121
What sign is classically seen in pts with protein c def commenced on warfarin?
Skin necrosis
122
How is MM Dx?
Presence of at least 10% clonal bone marrow plasma cells and serum or urinary monoclonal protein
123
What is the most common presentation of MM?
Bony lesions 80%
Anaemia 73%- related to bone marrow infiltration or renal dysfunction
Bone pain -58%
Renal impairment – 20-40% due to tubular damage from excess protein load, dehydration, hypercalcaemia and use of nephrotoxic medications
124
Warfarin exerts anti-thrombotic effects via depletion of which factor?
FII (prothrombin) is converted to thrombin.
| Warfarin inhibits Vit K dependent synthesis os II,VII,IX,X
125
What is the commonest cause of activated protein C resistance?
Factor V leiden mutation. Accounts for 40-50% of inherited thrombophilia in Caucasians.
126
What is myeloid metaplasia?
A complication of PCV.
Caused by progressive fibrosis of the bone marrow and shift hematopoisesis from marrow to the liver and spleen. Some of the largest spleens seen are in MM and agnogenic myeloid metaplasia (AMM).
127
What do you see on the blood film in myeloid metaplasia?
Tear drop cells and leukoerythrocytoblastic picture are characteristic.
128
What Ix result is most suggestive of intravascular haemolysis? What is the mechanism?
Urinary haemosiderin.
| Free Hb released in intravascular haemolysis. Free Hb is excreted in urine as haemoglobinuria, haemosiderinuria
129
Which karyotypes are favourable in AML?
t(8:21)
t(15:17)
Inv (16)
130
Why is cytogenentics important?
Predicts prognosis.
•Good - t(15:17), t(8:21), inv(16)
* Intermediate (Normal karyotype, Y-
* Poor - del7, del5q, inv(3), t(3:3), t(6:9), t(9:22), 11q23, complex cytogenetics >=3 abn
131
What is the strongest adverse prognostic factor in AML?
Age > 60 y. CTx has not been shown to improve survival
132
What is the strongest good prognostic factor in ALL?
Paediactric age group is the strongest good prognostic factor
133
What is the 1st line Tx for CLL?
Chlorambucil
| 2nd line Tx- Fludarabine
134
List the myeloproliferative disorders under heading BCR-ABL +ve and BCR-ABL –ve.
BCR-ABL +ve -> CML
| BCR-ABL –ve -> PCV, Essential thrombocythemia, Myelofibrosis
135
List the plasma cell dyscrasias
MGUS monoclonal gammopathy uncertain significance
MM
Amyloidosis (like MGUS with attitude)
136
Causes of microcytic anaemia
Fe def
Thalassaemia
Anaemia of chronic disease
Sideroblastic anaemia
137
Causes of macrocytic anaemia (megaloblastic)?
Megaloblastic
- Vit B12 def
- folate def
- pervicious anemia
- drugs e.g. hyroxyurea, azathioprine, zidovudine
- congenital enzyme def in DNA synthesis e.g. orotic aciduria
- myelodysplasia due to dyserythropoiesis
138
Causes of macrocytic anaemia (Normoblastic)?
Pregnancy
Alcohol
increased Reticulocytes e.g. haemolysis, haemmorhage
Liver disease
Hypothyroidism
Drug therapy e.g. azathioprine
Cold agglutins due to autoagglutination of red cells
139
Causes of normocytic anaemia
```
Blood loss
Anaemia of chronic disease
Renal failure
AI rheumatic disease
Marrow infiltration/fibrosis
Endocrine disease
Haemolytic anaemias
```
140
What is PNH characterized by?
Intravascular haemolysis
Venous thrombosis
Haemoglobinuria
141
What is the defect in alpha thalassaemia due to?
Gene deletion
142
What is the defect in beta thalassaemia due to?
Point mutation resulting in decreased beta globin synthesis
143
Is the INR useful to determine liver function?
No. PT is a better indicator.
144
What are the causes of an elevated PT and normal APTT?
```
VII def
VII inhibitor
Vit K def
Liver disease
Warfarin
```
145
What are the causes of a normal PT and elevated APTT?
Inhibitors
Lupus anticoagulant
Heparin -elevated TT and reptilase normal
146
What are the causes of and elevated PT and APTT?
```
Inhibitors
Liver disease
DIC
Heaprin and warfarin
V, X, II and fibrin def
Combined factor def
```
147
What results would you expect in regards to haemostatic function for the Haem A/B?
PT normal, aPPT elevated, TT N, Fib N, Plt N, Platelet function analysis (PFA) N
148
What results would you expect in regards to haemostatic function for the vWD?
PT N, aPPT elevated, TT N, Fib N, plt N, PFA A
149
What results would you expect in regards to haemostatic function for the DIC?
PT elevated, aPPT elevated, TT elevated, Fib low, Plt low, PFA A
150
What results would you expect in regards to haemostatic function for the TTP?
PT N, aPPT N, TT N, Fib N, plt low, PFA A
151
What results would you expect in regards to haemostatic function for the decreased Plts ?
PT N, aPPT N, TT N, Fib N, plts low, PFA A
152
What results would you expect in regards to haemostatic function for the Abn platelet?
Pt N, aPPT N, TT N, Fib N, Plt N, PFA A
153
What results would you expect in regards to haemostatic function for the CTD/VD?
PT N, aPPT N, TT N, Fib N or elevated, Plt N, PFA N
154
What are the thresholds for transfusion of blood components?
Platelets Spontaneous bleeding
Fibrinogen 1.5
APTT no data
155
What are the indications for prothrombinex?
warfarin reversal
156
What does prothrombinex contain?
Conc FII, IX, X and low levels of VII
157
Complication of prothrmobinex?
PE
158
What is the indication for recombinant FVIIa?
Control of bleeding or procedural prophylais in pts with inhibitrs to coagulation factors VIII or IX
159
What is the haem indication for desmopressin (DDAVP)?
Mild vWD
MDS
Enhance haemostasis in platelet dysfunction defects e.g vWD
Increases vWF and FVIII levels
Effect within 30-60 minutes and sustained for 6-12 hours
160
What are the complications of desmopressin?
Hyponataemia and tachyphylaxis
161
What are the causes of HTR?
Febrile = RED
•Donor RBC Ag reacting with recipients pre-existing alloantiboes.
•Can occur with other products FFP, IVIG
•Usually due to clerical/procedural error
•High risk patients are:
repeated transfusions
multiparous
162
What are the symptoms of HTR?
* Fevers, back pain due to renal blockage, pain at infusion site
* Anaemia
* Jaundice
* ATN
* DIC
163
Dx of HTR?
* DAT
* Repeat X-match done and recipient
* Urine
* FBC-Hb
* Used packs
* BC
164
What is the cause of NFHTR?
• Recipients Ab reacts with donor white cells
165
What are the immunological causes of delayed/chronic TF reactions?
```
Delayed HTR (5-10 days later)
GVHD
TRIM
Alloimmunisation from repeated transfusions
Post transfusion purpura
```
166
What is the mechanism of GVHD?
Occurs after stem cell or BM transplant
Recipient cannot amount an immune response to the donor lymphocytes (DL) due to HLA one-way compatibility or immunosupresion
167
What is the clinical presentation of GVHD?
* Occur 2-30 days post TF
* Rash- erythmeatous with macules and papules —> erythroderma
* Fever
168
Tx of GVHD?
* Acute: High dose methylpred
| * Chronic: Prednisone
169
What are the viral causes of transfusion reactions?
```
aHIV
HBV
HCV
HTLV
Creuztfeldt-Jakob Disease
```
170
What factors make up the Well’s score?
```
Prior Hx TE 1.5
HR > 95 bpm 1.5
Recent Sx/immob in previous 4 weeks 1.5
Haemoptysis 1
Active malignancy 1
Clinical signs of a DVT (pain palpation/oedema) 3
Unlikely alternative Dx 3
>4 = PE likely
```
171
What factors make up the Geneva Score?
```
Age>65y 1
Prior TE 3
HR >95 5
HR 75-94 3
Recent Sx/limb immbolisation 2
Haemoptysis 2
Active malignancy 2
Clinical signs DVT 3
Pain on palpation/oedema 4
>5 = PE likely
```
172
How do you monitor LMWH?
Anti-XA levels
renal function ml/min 48h
Normal >60 - nor required
173
Which NOACs target Xa and their half-life?
Apixiban 8-15 h, CYP 450 15%
Rivaroxiban 9-13 h, CYP 450 32%
Edoxaban 10-14 h, CYP 450 30% (not available in Australia)
Renal excretion 25-35% for above
Above drugs inhibit, not deplete factors therefore replacement of factors only effective if able to bypass or overwhelm inhibition of Xa or thrombin
174
Which NOACs target IIa?
Dabigatran 12-14h
| No Cyp450 activity
175
Indications for dabigatran (PBS)?
Prevention of TE in pts who have undergone major orthopaedic lower limb Sx
Stroke prevention in non-valvular AF
176
Indications for rivaroxiban (PBS)?
Prevention of TE in pts who have undergone major orthopaedic lower limb Sx
Stroke prevention in non-valvular AF
Tx of acute symptomatic DVT without symptomatic PE and to prevent recurrent VTE
Tx of acute PE to prevent recurrent VTE
177
Are NOACs inferior or non-inferior to warfarin fro the prevention of stroke/embolism in AF, Tx of DVT/PE?
Non inferior
178
What are the differentiators between the NOACs Dabigatran, Apixiban and Rivaroxiban?
Dabigatran 150 mg was associated with a reduction in ischameic stroke
Rivaroxiban OD was associated with a lower rate of fatal bleeding
Apixiban was associated with a reduction in all cause but not CV mortality
179
How long do you continue Tx for a 1st episode VTE after 3 months of Tx with NOAC?
•VTE associated with temporary RF e.g. Sx
stop anticoagulation
•Cancer associated VTE
complete 6 months of Tx
If ongoing cancer therapy Tx then cont for another 6 months
If no more Cancer Tx than stop
•Unprovoked VTE
stop anticoagulation
risk assessment for recurrent VTE, if high risk and low risk bleeding than complete 12 months of Tx. If low recurrence risk and high bleeding risk than stop.
180
What is the impact of oral and non-oral hormones on VTE?
* 2-6 fold increased risk of VTE
* limited data on non oral hormones
* Family Hx TE -> 2-4 fold increase risk TE
* Prior Hx of TE -> recurrence rate 3% per year if OCP continued
* Hormone releasing IUD better than oral preparations
* increased risk with thrombophilia
181
What is eculizumab?
A C5 monoclonal antibody used in the treatment of PNH?
182
What is the leading cause of death in beta thalassaemia major?
Heart failure secondary to a severe iron induced cardiomyopathy in poorly chelated patients.
183
What globins do the following contain: HbA (normal), HbA2 (minor) and HbF (fetal)?
```
Normal HbA (a2b2)
Minor HbA2 (a2,delta2)
Fetal HbF (a2, y2)
```
184
List the classifications of alpha thalassaemia’s?
Silent carrier state = a-/aa, 1 gene deletion, normal Hb
Alpha thalassemia trait = a-/a- or aa/--. 2 gene deletions, HbA -> mild anaemia
Hb H = --/-a, 3 gene deletions, HbH -> moderate anaemia
Hb Barts = --/--, 4 gene deletions, fetal hydrops
185
Which haem disorder provide protections from plasmodium falciparum?
G6PD def
Sickle cell trait
Alphal thal
186
Transfusions transmitted infections are most likely to occur with which blood product?
Platelets
187
What is the cause of a haemolytic transfusion reactions?
ABO incompatibility
Donor RBC antigens reacting with recipients pre-existing allo-antibody
Mx: DAT, repeat Xmatch
188
What is the cause of a febrile non-haemolytic transfusion reaction (FNHTR)?
Recipient Antibodies against the donor’s leucocytes
| Mx: Self limiting without complications
189
What is the cause of TRALI?
Donor’s antibody reacting to recipients leucocytes (opposite of Febrile non haem transfusion reaction)
Mx by informing public health and donor to stop donating.
190
What is the cause of Delayed transfusion reactions (GVHD)?
```
Recipient unable to mount an immune response to donor’s lymphocyte.
High mortality (>85%)
Mx by using irradiated products.
```
191
What is the Tx for ITP?
Prednisone
192
What is the Tx for Thrombotic Thrombocytopenic Purpura?
Plasma exchange
193
Leucodepletion reduces the risk of which transfusion associated infection?
CMV
194
What is the most appropriate Tx for prevention of Fe overload in transfusion dependen pts?
Desferroxamine
195
How do you prevent FNHTR in a pt requiring regular transfusions?
Leucodepletion
196
What is the Tx for HITS?
Stop heparin
| Commence Danaparoid
197
What is the risk of acquiring HIV, HCV, HBV, HTLV and malaria from a screened blood transfusion due to the infectious window period of HIV?
```
HIV- 1 in 5, 000, 000
HCV 1 in 2.7 million
HBV 1 in 739 000
HTLVI and II is 1 in 17.5 milliom
Malaria 1 is 1 in 4.9-10 million
```
198
What type of anaemia does RBC aplasia produce?
Normochromic normocytic anaemia with elevated EPO levels
| Erythroblasts will be absent in the bone marrow therefore diminished reticulocytes
199
which factors are Vitamin K dependent?
2,7,9,10, Protein C and S
F7 and Protein C have the shortest half life and therefore decrease first
Vit K def manifest with prolonged PT time first then aPTT prolonged in severe def
200
What are the major causes of Vit K def?
Dietary intake
Intestinal malabsortpion
Liver disease
201
What do you expect to see on a peripheral blood smear of a pt with AIHA?
Microspherocytes
202
What do you expect to see on a peripheral blood smear of a pt with B12 def?
Macrocytosis and PMN with hypersegmented nuclei
203
What do you expect to see on a peripheral blood smear of a pt with MAHA (TTP/HUS)?
Schistocytes
204
What do you expect to see on a peripheral blood smear of a pt with Sickle cell disease?
Sickle cells
205
What do you expect to see on a peripheral blood smear of a pt with thalassaemia or liver disease?
Target cells
206
Which malignancies are associated with pure red cell aplasia?
Thymomas and lymphomas
207
How do you manage asymptomatic essential thrombocytosis?
FBC q 3 months
Group patients into low, intermediate or high risk
-intermediate: regular RBC q 3 months and low dose aspirin for mild vasomotor symptoms
-high – hydroxyurea and aspirin
If neutropenia from hydroxyurea than Anegralide which reduced shedding of platelets from megakaryocytes.
Hydroxyurea has superior benefit.
-pregnant and high risk – interferon alpha 2b and anti-plt Tx
208
What is the MOA of anagrelide?
Inhibitor of cAMP phosphodiesterase III that reduces plt production and at higher doses inhibits plt aggregation
209
Indications for platelet transfusion
* I bag of platelets = 60 ml = 4 Unit = 20-30 platelet rise.
* Thrombocytopenia
* Defective pleatelt function
* Surgical pt platelets
210
Indications for FFP?
* contains all coagulation factors
* used for correction of bleeding where multiple co-agulation factor
* deficiencies are present
* DIC
* liver dysfunction
* dilutitional coag
* TTP to replace DAMTS-13 enyme
* effects immediate and not sustained
* number to correct ?15 ml/kg
211
What does cryoprecipitate contain?
| Indications for cryoprecipitate? (5Fs)
* contains 5Fs: fibrinogen, vWF, FVIII, FXIII, Fibronectin (5Fs)
* 10-15 ml = 200 mg Fib
* Average bag 30 ml (20-40 ml)
* 150 ml = 2 g ->raise level of fibrinogen 0.7 g/L
* Fibrinogen defi
* dysfinrinogenaemia
* DIC
* can be used in vWD
* used in any condition that gives you low fibrinogen
212
Indications for Prothrombinex?
Contains Vitamin K dependent factors and used in warfarin reversal
213
Indications for Recombinant Factor VIIa?
consist of activated FVII
Used to control bleeding or procedural prophylaxis with patients with inhibitors to coagulation FVIII or IV (Haemophilias)
214
Indication for Desmopressin?
increase vWF and FVIII levels in vWD
215
Indication for tranexamic acid?
Displaces plasminogen from fibrin and inhibits fibrinokysis
| Used for mucosal bleeding
216
Treatment for Hodgkin lymphoma?
ABVD for 2 -3 cycles and RTx
217
Spherocytes strongly suggestive of?
AIHA
218
Schistocytes and helmet cells suugetive of?
Microangiopathic contribution of haemolytic anaemia
219
tear drop shaped erythrocytes, nucleated erythrocytes and immature granulocytes strongly suggestive of?
Primary myelofibrosis
220
JC virus. What, cause, clinical, Dx, Tx?
Lytic lesions of oligodendrocytes and astrocytes resulting in multiple areas of demyelination in the CNS
PML lesions are assymetrical demyelinated plaque areas with irregular borders surrounded by macrophages and irregular astrocytes with large, multiple nuclei.
Cause:
Human polymavirus - JC virus
5% of the world is infected with the JC virus however they remain asymptomatic and virus remains quiescent in the kidneys, bone marrow and lymphoid tissue)
```
Clinical:
Muscle weakness
Sensory deficit
Cognitive dysfunction
Language impiaremnet
Co-ordination and gait difficulties
```
Dx:
JC virus DNA in CSF by PCR
or JC virus DNA or proteins by insitu hybridization of immunohisto on brain Bx sample
Tx:
Supportive
Cease or decrease immunosuppression
No specific anti-viral drugs for JC virus
Recovery of immune system can trigger IRIS. In HIV neg pats with PML-IRS Tx with corticosteroids
221
CLL: What, Epid, Aet, Ix, Dx, Tx, Complications?
a monoclonal disorder characterised by a progressive accumulation of functionally incompetent lymphocytes.
Incurable.
Epid:
Commonest haem malignancy
65-70 y
M:F 1:1
Aet:
Unknown
Genetics
```
Causes?
Clinical:
SOB
Fatigue
Lymphadenopathy
Splenomegaly
B-symptoms
```
```
Ix:
FBC - Hb 5000/microlitre
Blood film - smudge/smear cells
Flow cytometry - CD5, CD19, CD23
BM Bx - MB infiltration by leukaemic cells
```
Dx:
Following criteria:
Absolute lymphocyte count in the peripheral blood ≥ 5000/microL [5 x10(9)/L], with a preponderant population of morphologically mature-appearing small lymphocytes.
Demonstration of clonality of the circulating B lymphocytes by flow cytometry of the peripheral blood.
A majority of the population should express the following pattern of monoclonal B-cell markers: extremely low levels of Sm Ig and either kappa or lambda (but not both) light chains, expression of B-cell associated antigens (CD19, CD20, CD21, CD23, and CD24), and expression of the T-cell associated antigen CD5.
Prognosis:
Depends on clinical stage and rate of disease progression:
lymphocyte doubling time and serum β2-microglobulin level, immunophenotyping, cytogenetic studies, fluorescence in situ hybridization testing, and mutational gene assessment (del(17p13) (p53)
Tx:
Observation if asymptomatic
Symptomatic/advanced
1st - Fludarabine CR combination with Ritux or single agent Cx.
Adjunct allogenic SCT
- Allogeneic HSTC is the only curative treatment but is associated with a high risk of morbidity and mortality
Poor ECOG - Obinutuzumab + chlorambucil or mono therapy with chlorambucil or Ritux
```
Cx:
Febrile neutropenia
TLS
Hypogammaglobulinaemia
AIHA
ITP
Richter transformation - NHL
Fludarabine induced interstitial lung disease
```
222
What is the most common peripheral aneurysm? Presentation? Complication?
Popliteal artery aneurysms
At presentation 50-80% are symptomatic (thrombosed or embolising distally)
Rupture rates are
223
What is erythromyelgia?
Condition characterized by intense burning pain, erythema and increased skin temperature primarily of feet and hands.
Symptoms vary between pts, can flare up or be continuous.
Bilateral involvement.
UL can be involved- fingers.
Classic description of erythromyelgia is red, painful, warm hands and feet bought on by warming or hanging the limb downward and relieved with cooling and elevation.
224
What is Buerger's disease (thromboangiitis obliternas)?
A rare disease of the arteries and veins in the arms and legs.
Blood vessels become inflamed, swell and can become blocked with blood clots.
This can lead to infection and gangrene.
All patients are smokers!!
First affects hands and feet and may affect larger areas of arms and legs.
225
Pt with ITP post splenectomy has moderate thrombocytopenia and Howells jolly bodies. A symptomatic. Next step?
Watch and wait as no symptoms.
| Howell jolly bodies suggest functional a splenic.
226
What is CML due to?
chromosomal translocation between chromosomes 9 and 22. Results in abnormal BCR-ABL fusion gene -> unregulated proliferation.
227
What is the MOA of hydroxyurea?
Causes inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor. An S-phase specific.
228
What do you expect in the BM and peripheral cell counts with Myeloproliferative neoplasm vs. myeloproliferative syndrome?
MPN
- hypercellular BM (except MF)
- increased peripheral cell countse.g. ER, CML, PRV
MDS
- hypercellular BM (except hypoplastic MDS) and peripheral cytopenias
Both have risk of transforming to AML
229
Aplastic anaemia. What, pathophys, Dx, Tx
BM fails to produce blood cells resulting in a hypocellular BM and pancytopenia.
Acquired or Congenital (20%).
Most common congenital form is Fanconi anaemia, AR or X-linked.
Pathophys:
In acquired, immune dysfunction and abnormal expression of suppressor T cells if often present.
Small PNH clones identified in 50% of pts with aplastic anaemia (Dx by absence of CD 55 and CD59).
```
Dx:
Bone marrow aspitate and Bx
- hypocellualr BM with increased fat space and decrease in hamatopoietic elements.
- reticulocytes LOW
- DAT is -ve
```
Tx:
HLA compatible sibling allogenic HSCT as initial therapy. Cure rate of 75-90%.
Non HSCT candidates:
- antithymocyte globulin and cyclosporine therapy which has resulted in long term suvival in 60-85%
230
What is the immediate Mx to reduce the risk of perioperative bleeding in a pt with ITP, plt count 30 who underwent an urgent procedure ?
Platelet transfusion
Adjunct Tx with high dose glucocorticoids or 100 mg and IVIG also appropriate.
Prednisone is used in Tx but takes time to work.
231
MM. Dx?
> 10% clonal malignant plasma cells on BM and serum or urinary monoclonal paraprotein e.g. IgG kappa.
232
MM. When to Tx?
CRAB symptoms or any 1 of the following biomarkers of malignancy consider Tx:
clonal bone marrow plasma cell > 60% or >1 lytic lesion on MRI
233
Dx of MGUS?
| Tx?
No symptoms
| low paraprotein,
234
Dx of smouldering/asymptomatic myeloma?
high paraprotein > 30 g/L
>10% plasma cells in bone marrow
No CRAB features
10% pa will progress in the 1st 5 years
Tx:
Close FU blood test +/- xr
235
Indication for Bortezumab in MM?
| AE?
Relapsed or 1st line with steroids for pts with renal failure
AE:
Peripheral neuropathy severe, takes years to resolve
236
MM. 1st line therapy?
Autologous SCT - best overall survival
Initial induction CTx. Standard therapies consist of:
Proteasome inhibitor e.g. bortezomib OR
immunomodulatory agent e.g. thalidomide or lenalidomide PLUS
alkylating agent cyclophosphamide or melphalam
PLUS
Steroid (Dex/Pred)
237
When is Lenolidamide indicated? AE?
Second line therapy for failed Tx with Thalidomide.
More myelotoxicty.
Less neuropathy.
Risk of secondary primary malignancies.
238
What is a common complication of HL after mantle therapy (RTx to lymph nodes of neck, chest and axillar, sometimes upper abdomen)?
Hypothyroidism most common after neck irradiation
Takes place in 1st 5 years but some take place beyond 10 years
239
What is the most common cause of ACQUIRED Protein C resistance?
Pregnancy
Factor V Leiden is the most common cause of INHERITED
240
CML:
What
Clinical
Ix
```
Disorder characterised by myeloid proliferation
Consist of:
chronic
accelerated
blast phase -> AML 80% or ALL 20%
```
```
Clinical:
Asymptomatoc
Fatigue
Night sweats
weight loss
abdo pain
early satiety
bleeding
Splenomegaly most common finding
```
```
Ix:
9:22 translocation or
BCR-ABL fusion transcript
Bone marrow: hypercellular with myeloid hyperplasia
Chronic phase:
- WCC high
Hb low or normal
Plts normal or high
Blood film = neutrophilia and left shifted granulopoiesis and basophilia
```
Tx:
All patients treated, even if asymptomatic.
Chronic phase: Imatinib 1st line
More potent BRC-ABL inhibitors, Nilotinib and Dasatinib are used in pts intolerant or have disease resistant to imatinib.
HSCT is reserved for eligible patients in accelerated or blast phase of disease or disease resistance to BCR-ABL inhibitor regardless of phase.
The best chance of long term survival is ALLOGENIC BMT
241
```
Myelodyplastic syndrome:
What
Presentation
Ix
Tx
```
Clonal haemotopoietic stem cell disease characterised by cytopenia, dysplasia, ineffective haematopoiesis and increased risk of development to AML
Presentation:
Fatigue
Easy bleeding
Infections due to neutropenia- common cause of death
Ix:
Normocytic or macrocytic anaemia
Blood film: dysplastic changes such as nucleated erythrocytes and hypolobated, hypogranular neutrophils
BM: Hypercellular and dypslasia identified in affected line
Tx:
Supportive with transfusions and GCSF when septic
Azacitidine (DNA hypomethylating agent) improves survival
242
Key distinguishing points in myeloproliferative disorders.
CML = BRA ABL +ve
ET = platelet count > 600 x109/L (600, 000/uL) on 2 separate occasions 1 month apart
PCV = increase Hb, JAK 2 +ve
Myelofibrosis = WCC>100, high leucocyte ALP
Myelodysplasia = pancytopenia
243
AML:
proliferative leukaemic cells leading to accumulation of blast cells.
Presentation:
fatigue
bruising
infection
Ix:
pancytopenia
Cytogenetics:
FLT3 poor prognosis
KIT = poor
NPM1 = reduce risk of relapse, improved CR
Age> 60 biggest predictor of poor prognosis
Tx:
7:3 Ida in elderly
APML presents with DIC.
244
APML:
characterised by translocation of retinoic acid receptor on Ch17.
t (15:17) most common translocation, >98%
Presentation:
DIC
Tx:
ATRA and anthracyclines = complete remission in >90% of cases and cure in >80%
Complication:
Differentiatio syndrome - pul infiltration by diff APML blasts. Tx with steroids.
245
ALL:
accumulation of malignant immature lymphoid cells
Most common in children
Epid:
Bimodal, 4-10 y and then >50y
Presentation:
Non specific
pancytopenia
Bone pain, splenomegaly and lymphadenopathy common
Dx:
FISH - t(9:22), philadelphia chromosome = poor prognosis
Tx:
Imatinib if positive t(9:22) PLUS
anthracyclines, corticosteroids and vincristine
intrathecal MTx to prevent CNS relapse
Pts in first remission should be considered for allogenic BMT due to high relapse rate.
246
Waldenstrom hyperviscosity syndrome.
| Initial Ix and Mx.
Ix:
Plasma viscosity measurement to Dx and Tx
Tx:
plasmaphoresis
then cytoreductive therapy
247
```
drug-induced neutropenia or agranulocytosis:
Presentation
Dx criteria
Ix
Tx
```
Presenation:
fever, mouth sores, or gingival disease inflammation -> suggest BM failure.
Dx:
The diagnosis is confirmed when all of the following are present:
●Low to absent absolute neutrophil count
●Absence of anemia and thrombocytopenia
●A hypocellular bone marrow that shows normal erythropoiesis and megakaryocytopoiesis, but few if any granulocytic precursors.
●Return of the neutrophil count to normal when the offending agent is stopped, with or without the concomitant use of a granulocyte colony-stimulating factor
Ix:
BM unless clear source of offending drug
Tx:
Stop drug
GCSF if pt ill from infection or evidence of BM suppression
248
AIHA: Abs associated.
Antibodies are IgG = 80% or IgM = 20%
249
Warm AIHA
Caused by IgG abs that bind erthrocyte Rh antigens at 37 degrees.
Can be Idiopathic or associated with other AI, lymphoproliferative, malignant or drug related.
Haemolysis is caused by clearance of antibody -coated erythorcytes to the Fc receptor on splenic macrophages. Partial phagocytsois leads to sphercytes which become entrapped and removed by the spleen.
Presentation:
Rapid or more insidious symptoms of anaemia or jaundice.
Mild splenomegaly.
Blood film: SPHEROCYTES
DAT +ve for IgG and NEGATIVE or weakly positive for COMPLEMENT.
TX:
CORTICOSTEROIDS
Splenectomy for non responders.
250
Cold AIHA
Caused by binding of IgM abs to erythrocytes antigens, typically I or i at temperatures below 37 degrees with max activity at 4 degrees.
Aetiology:
Few weeks after EBV infection or mycoplasma.
IgM abs fix COMPLEMENT to erthythrocyte membrane -> erythrocyte clearance by DIC or binding to macrophages in the liver.
Ix:
Anaemia is mild, moderate and chronic.
Cold agglutination leads to falsely elevated MCV.
Blood film- clumping or AGGLUTINATION of erythrocytes
IgG negative, strongly positive for C3
Tx:
Avoidance of cold temperatures
Chlorambucil, cyclophosphamide, and, more recently, rituximab, have shown benefit.
corticosteroids and splenectomy are INEFFECTIVE!
251
G6PD:
Congenital haemolytic anaemia
MOST COMMON ERYTHROCYTE ENZYME DEFECT.
Mutations on X chromosome.
Inability of erthrocyte to generate (NADPH) and maintain glutathione in a reduced state.
Epid:
M>F
African
Heterozygous def protects against P. falciparum
Causes:
African variant leads to episodic haemolysis in response to Infection, Drugs e.g. dapsone, bactrim ad nitrofuratoin,
Mediteraanean variant leasd to chronic haemolysis associated with favism.
Ix:
Blood fils:
bite cells
A brilliant cresyl blue stain may reveal Heinz bodies (denatured oxidosed Hb)
In African american variant, check G6PD levels a few months after the episode as may be elvated
Tx:
Supportive during acute crisis.
Stop drug, treat infection.
252
Sickle cell disease (HbS):
Results from point mutation leading to a single amino acid substitution at the 6th position of the B-globin chain.
Sickle cell trait = HbAS, 8-9% of blacks. Benign condition mostly.
```
Genotypes:
Homozygous SS (HbSS)
- moderate to severe anaemia
-frequent painful crisis
- reduced life expectancy
```
Sickle - Bo thalassaemia (HbSB0)
- may closely mimic HbSS
Sickle B+thal (HbSB+) and
- less severe anaemia and lower crisis
HbSC disease (HbSC)
- less severe anaemia and lower crisis
- higher frequency of ocular complications and bony infarcts has been noted in Hb SC disease because of increased blood viscosity
Phenotypic differences exist amongst these genotypes.
REFER to evernote table
Mx:
Hydroxyurea - decreased mortlaity (teratogenic)
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Erythrocyte transfusion:
Acute indications:
stroke
symptomatic anemia
acute chest syndrome, and surgical interventions
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Erythrocyte exchange transfusion: indicated for:
acute ischemic stroke
acute chest syndrome with significant hypoxia and
multiorgan failure/hepatopathy,
as well as in individuals in whom simple transfusion would raise the hemoglobin level to greater than 10 g/dL (100 g/L).
Chronic transfusions may decrease stroke recurrence but may be associated with Fe overload and vascular difficulties and alloumminisation,i ncreased risk for a delayed hemolytic transfusion reaction.
Can lead to moyamoya syndrome.
253
Complications of SCD
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Pain crisis:
due to vasococclusion
Tx:
- hydration
- non oipoid and oipoid
- incentive spiro to reduce chest syndrome
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Stroke
- Tx erythrocyte exchange transfusion to reduce HbS concetration to
254
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Blood films:
Acanthocyte (spur cell)
Basophilic stipping
Bite cell
Elliptocyte
Macro-ovalocyte
Ringer sideroblast
Schistocyte (helmet cell)
Spherocytes
Teardrop
Target cell
Heinz body
Howell jolly bodies
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Acanthocyte (spur cell)
- liver disease
Basophilic stipping
- lead poisoning
Bite cell
- G6PD def
Elliptocyte (long oval shaped)
- herid elliptocytsois
Macro-ovalocyte
- megaloblastic anaemia
- marrow failure
Ringer sideroblast
- sideroblastic anaemia
Excess Fe in mitochondria
Schistocyte (helmet cell)
- TTP/ITP/HUS/HELLP
- heart valve prsothesis
Spherocytes
- herid spherocytosis
- drug and infection-induced hemolytic anemia.
Teardrop
- Bone marrow infiltration (e.g.,
myelofibrosis) .
Target cell
- HbC disease, Asplenia, Liver
disease, Thalassemia (HALT).
Heinz body
-G6PD deficiency; Heinz
body–like inclusions seen in
α-thalassemia
Howell jolly bodies
- Basophilic nuclear remnants
found in RBCs
- functional hyposplenia or asplenia
255
Amyloid deposits: which protein is universally present?
Serum amyloid P (SAP)
256
Heparin with prolonged aPPT. Coagulation test corresponding to heparin?
Increased aPPT
Increased TT - measures final step of coag cascade, conversion of fibrinogen to fibrin.
Normal reptilase test
