Hemat Flashcards
1
Q
? ml blood has 1 mg iron
A
2ml blood = 1mg iron
Daily requirement = 1-2mg
2
Q
Iron chelation drugs
A
- Deferoxamine (IV/SC)
- Deferiprone
- Deferasirox
3
Q
Deferoxamine (aka Desferrioxamine)
A
- Deferoxamine
- IV/SC
- Prefer: Slow SC infusion over 8-12h
- SE: Local skin reactions, infection (Yersinia, Klebsiella), Growth retardation, skeletal abnormalities in children, hearing, visual problems
4
Q
Deferiprone
A
- Deferiprone
- Oral
- 75mg/kg/day given tds
- Better cardiac function than Desferoxamine
- SE: Agranulocytosis (0.2/100 in 1y; CBC weekly at least in first 3 months), Arthropathy
- 1st line in thal major (but not in other transfusion dependent patient)
- Switch to Deferasirox if agranulocytosis
5
Q
Deferasirox
A
- Deferasirox
- Oral, long half-life
- Once daily 20-30mg/kg
- SE: GI disturbance, reversible rise in creatinine
- CI in renal failure
6
Q
Mx of thal major
A
- Confirm Dx with Hb pattern and thalassemia genotype; Screen family members
- Extend RBC Ag typing before transfusion to safeguard development of alloautoAb in future
- Check HBV, HCV, HIV before transfusion
- Give Rh C, c, E, e, Kell Ag compatible blood to minimize alloimmunization
- Aim pre-transfusional Hb at 9, Usual transufsion interval 3-4 wk
- Give WBC reduced, fresh packed cells
- Perform full pre-transfusion compatibility test and Ab screening before each transfusion
- Splenectomy only if Sx of splenomegaly or transfusion requirement >200ml/kg/yr as result of hypersplenism
7
Q
Monitor iron overload
- Serum ferritin
A
- Monitor ferritin every 3m
- Iron chelation to keep ferritin <2500mg/L (preferably 1000)
- Persistent >2500 –> increased cardiac risk, mortality
- Ferritin monitoring often underestimates degree of iron overload in Thal intermediate
8
Q
Tumor lysis syndrome
A
Hyper
-uric acid, K, phosphate, LDH
Hypo
-Ca
Tx
- Aggressive hydration (beware of fluid overload)
- Alkalinzation of urine (may worsen RFT due to Ca phosphate deposition)
- Allopurinol, Febuxostat (Xanthine oxidase inhibitor)
- Rasburicase (Recombinant urate oxidase in Aspergillus flavus, avoid in G6PD deficiency)
- Renal replacement therapy
- Monitor WBC, tumor size, fluid intake, urine output, body weight, electrolytes, RFT, LDH, pH, PT/APTT
9
Q
LDH
A Lie
A
Lactate dehydrogenase
- Located in inner surface of cell membrane
- Converts lactate to pyruvate
- Anaerobic reaction
10
Q
Bite cells
A
G6PD
aka Degmacyte
>=1 semicircular portions removed from the cell margin
Bites: due to removal of denatured Hb by MQ in the spleen
G6PD: uncontrolled oxidative stress causes Hb to denature and form Heinz bodies
11
Q
Schistocyte
A
Fragmented part of RBC
In DIC, TTP, artificial heart halves
12
Q
Hypersplenism 4 cardinal features
A
- Pancytopenia
- Hyperplastic BM
- Corrected by splenectomy
- Splenomegaly
13
Q
Lab features of Hemolytic anemia
A
- Anemia - usu mild macrocytic, with reticulocytosis
- ↑Unconjugated bilirubin, LDH, methemalbumin
- ↓Serum haptoglobin
- Blood film
- Polychromasia
- Spherocytes (hereditary spherocytosis, immune hemolytic anemia)
- RBC fragmentation (microangiopathic hemolysis)
- RBC agglutination (cold agglutinin disease) - Direct antiglobulin test (Direct Coomb’s test) – positive in immune hemolytic anemia
14
Q
AI hemolytic anemia
A
Warm (IgG), Cold (IgM)
- Both can be due to secondary cause
- Warm: Drug (e.g. Methyldopa), SLE, CLL
- Cold: infection e.g. Mycoplasma, IM, lymphoproliferative disorders
15
Q
Tx of AIHA
A
- Transfusion if needed
- Folate supplement
- Decrease further hemolysis: steroid, avoid certain drugs, keep warm for cold hemagglutinin disease, splenectomy
- Treat underlying causes e.g. lymphoproliferative disorders
16
Q
Dx of AIHA
A
- ↑Reticulocytes
- Blood film showing microspherocytes
- ↑Unconjugated bilirubin, LDH, methemalbumin
- ↓Haptoglobin
- Specific tests: Direct antiglobulin test (aka Direct Coombs’ test)
17
Q
Aplastic anemia, clinical features
A
- Pancytopenia resulting from BM hypoplasia or aplasia
- Can be Congenital/Acquired (Acquired: Idiopathic/Secondary)
- Can be pure red cell aplasia, e.g. Diamond-Blackfan syndrome, or asso w/ large granular lymphocytosis
Clinical features
- Symptoms of pancytopenia
- No lymphadenopathy
- No hepatosplenomegaly
- Look for congenital physical abnormalities in young patients (inherited BM failure syndromes)
18
Q
Etiology of Aplastic anemia
A
Idiopathic (70-80%)
- Pathogenesis (for idiopathic)
- Immune mediated T cell destruction of BM stem cells (IL-17 CD4, TH-17)
- Over-expression of HLA-DR2
- Polymorphism in perforin gene / TNF-alpha gene
- ∴Tx is by immunosuppressant
Congenital: Fanconi anemia, Shwachman-Diamond syndrome, Dyskeratosis congenita
Drugs: Gold, alcohol, diclofenac acid, indomethacin, chloramphenicol, anti-convulsants
Infection: Non-A/B/C hepatitis (Seronegative hepatitis)
Environmental: Benzene, pesticide
19
Q
Tx of Aplastic anemia
A
- Supportive
- Cyclosporin A
- Anti-thymocyte globulin + Cyclosporin
- 1st line = Allogeneic HSCT (for young patients with matched sibling donors)
- Eltrombopag (high dose) – for relapse/refractory cases
20
Q
Ix of Aplastic anemia
A
- CBC: Pancytopenia, macrocytic anemia (not as big as blasts), low reticulocyte
2, Blood film - AI markers
- Vit B12 and folate levels
- BM: Trephine biopsy to assess cellularity
- Specialized tests
- Ham tests/flow cytometry to rule out PNH (Paroxysmal Nocturnal Hemoglobinuria)
- Chromosome breakage with diepoxybutane (to screen for Fanconi anemia)
21
Q
Hereditary spherocytosis, clinical features
A
- Presence of Spherocytes
- Hemolytic anemia
- AD inheritance
- 60% due to a defect in ankyrin-spectrin complex or vertical interaction
Features
- Jaundice
- Splenomegaly
- Gallstones
- Aplastic crisis (Primary parovovirus B19 infection – more prone + because of the reduced RBC half-life, more likely to have severe anemia)
- Extravascular hemolysis
- Blood film showing Spherocytes
- MCHC often raised
22
Q
Specific test for Hereditary spherocyotsis
A
- Osmotic fragility test
2. Eosin-5-maleimide binding (↓binding in HS)
23
Q
Tx for Hereditary spherocytosis
A
- Folic acid supplement
- If compensated hemolysis – no specific tx
- Cholecystectomy if symptomatic gallstone
- Splenectomy if severe hemolysis
24
Q
Anticoagulation scheme for DVT
A
- 1st week: Heparin (overlaps Warfarin @ Day 3-7)
- 3rd day to 3-6 months: Warfarin
- Reason for not starting Warfarin at once: Protein C and S is also vitamin K dependent
25
G6PD
- X-linked recessive
- HK: 4.5% in M; 0.5 in F
- Type B refers to wild type
- 4 classes; Class 1 most severe
- Intravascular hemolysis with hemoglobinuria – acute/chronic (not common)
- Precipitated by infection or acute medical illness. drugs, Fava beans
- Drugs: Sulphonamide, Anti-malarial
- Blood film: Polychromasia, ghost / hemi-ghost cells
- G6PD assay maybe normal during acute phase as young RBC and reticulocytes may have normal G6PD levels
Tx
- Supportive
- Blood transfusion
- Folic acid
- Stop and avoid offending agents
26
R-CHOP
```
Rituximab
Cyclophosphamide
Doxorubicin
Vincristine
Prednisolone
```
27
Cx of Iron overload
1. Cardiomyopathy (HF is 1st cause of death)
2. Hormonal deficiency: Hypogonadism, DM, HypoT, HypoPTH, GH deficiency, etc
* Untreated Thal Major can lead to Slow Growth and Puberty delay too
3. Liver Fibrosis and Cirrhosis (Uncommonly Severe enough to cause Cirrhosis)
4. Hyperpigmented due to deposition on skin
28
Ix for Leukemia
1. CBC w/ D
2. PBS
3. BM exam
4. Morphology (Auer rods in AML)
5. Cytochemistry (Myeloperoxidase in Myeloid lineage)
6. Immunophenotyping
7. Genetic tests
- Cytogenetics (Chromo)
- FISH (genes)
- PCR (genes, mRNA)
29
Induction for AML
Cytarabine x7d
| Daunorubicin x3d
30
Induction for ALL
```
Cyclophosphamide
Daunoubicin
Vincristine
Prednisolone
L-asparaginase
?Dexamethasone
?MTX
?Cytarabine
?Doxorubicin
```
31
CNS prophylaxis for ALL
Intrathecal MTX
+
Cranial irradiation
32
Consolidation
2-6m, about 1 course/month
33
Indication for HSCT in AML
- 2nd complete remission for HLA identical donors, or MUD available
- 1st complete remission for intermediate/high risk AML for suitable donor available
34
Tx for APML
All-trans retinoic acid
Arsenic trioxide
Chemo: Cytarabine, Daunorubicin
35
Translocation for ALL
t(9;22)
| Can add TKI (Imatinib, Dasatinib)
36
International prognostic index (IPI) for NHL
1. Tumor stage (Ann-Arbor system)
2. Serum LDH (represents tumor bulk)
3. No. of extranodal disease stage
4. Performance status (Ambulatory > Bed-ridden)
5. Age
37
Principle of Mx of Lymphoma
1. Chemo = main tx
2. Anti-CD20 Ab for B cell lymphoma on top of chemo
3. RT – for consolidation, relieve of obstruction, palliative tx
- Also used for Low-grade lymphomas, but always recur (chemo not given), RT to prevent local recurrence
- Consolidation tx for >10cm, i.e. bulky, high risk of local recurrence
- Relief obs - SVCO, brain obs
- Good palliative tx for chemo refractory cases
4. Surgery – for tumor bleeding and obs; localized and indolent lymphoma (e.g. eyelid lymphoma)
5. Symptomatic tx and psychosocial support
38
Ann Arbor system for Hodgkin lymphoma
- Stage 1: 1 group of LN
- Stage 2: 2 groups of LN on same side of diaphragm (i.e. either above or below)
- Stage 3s: Across diaphragm (either top to below or below to top; s means spleen)
- Stage 4: Involves non-lymphatic organ
Each stage can be categorized into A (Asymptomatic) or B (Constitutional symptoms)
*Difficult to apply in Non-Hodgkin lymphomas (NHL), but still used because no better classification
39
Lymphoma - other considerations
1. Cx that require urgent attention
- Bleeding (ulcerative lymphoma in stomach --> GIB)
- Infection
- Obstruction (SVCO can be fatal)
2. Hepatitis status
- HBV occult carriers may have flare-ups if given intensive chemo, causing reactivation
- HCV: always find out underlying reason for HCV infection (transfusion, IV drug addicts)
3. HIV
- HIV test is routine for patients with lymphoma
- Need HIV tx tgt with lymphoma tx because need CD4 to work
4. Ig pattern / Serum protein immuno-electrophoresis
- Positive monoclonal band as marker to monitor progress
5. CVS function
- Anthracycline (e.g. Doxorubicin) leads to cardiac toxicity
6. Lung function
- Methotrexate, Bleomycin lead to lung toxicity
7. LRFT
- For baseline
40
Reed-Sternberg cells
- Hodgkin’s lymphoma
| - Owl’s eye appearance (symmetric mirror image bilobed nucleus)
41
Histological exam for Lymphoma
1. Morphology
- Follicles: Enlargement vs Effacement抹消
- Diffuse large B-cell lymphoma shows no follicles, effaced, replaced by sheets of large cells
- Follicular lymphoma shows enlarged follicles
2. Immunostaining
- Determine B or T cell *CD-20 for B cell
3. Clonality study
B cells (lymphoma vs reactive)
- Neoplasm = Clonal, arise from 1 type of lymphoid cell only
- B cell lymphoma: from same B cell lineage / 1 single clone, express only lamba OR kappa chain but not both
- Reactive: Some cells lambda, some kappa
T cells
- T cell receptor gene rearrangement
- PCR to see if cells belong to same clone
- Sharp band (gene rearrangement) instead of smearing/shadow = more suggestive of T cell lymphoma
42
Ix for Lymphoma
1. CBC
2. BM examination
- BM aspiration or trephine biopsy for histological Dx
3. Imaging
- CXR – may present w/ SOB, shows mediastinal LN involvement
- CT: Gold standard
- PET/CT: see if aggressive --> look for anatomical imaging + metabolic activity of lesion (high grade shows high metabolic activity; low shows low)
- MRI: when CT is not clear
4. Excisional biopsy of LN for histological examination
43
CML does not present with lymphadenopathy!
>_>
44
B cell lymphoma grades
High grade
- Diffuse large B cell lymphoma
- Burkitt lymphoma
- -> Dangerous, may die in short, but highly curable if early tx by intensive chemotherapy
Low grade
- Follicular lymphoma
- MALT lymphoma (indolent, no need to rush)
- -> Safe, can be untreated for months, but not curable (always recur), requires less aggressive tx
*MALT: Mucosa associated lymphoid tissue
45
Clinical manifestations of Lymphoma
- Enlargement of LN (Nodal) / extranodal organs (Extranodal)
| - Systemic symptoms: fever, night sweats, weight loss (>10% in 6 months)
46
CML
- Cytogenic analysis - t(9;22); philadelphia chromosome
- Molecular analysis (BCR-ABL1 fusion gene)
>_>
47
JAK2 mutation in other Myeloproliferative disorders
| Esp Polycythemia vera
>_>
48
Triphasic for CML
Chronic phase
Accelerated phase
Blast phase
49
Specific tx for CML
Cytotoxic chemotherapy
- Hydroxyurea, Busulphan, Thioguanine
Biological agent
- Interferon-alpha (now rarely used)
Signal transduction (Tyrosine kinase) inhibitors
- 1st gen: Imatinib, 2nd gen: Dasatinib, Nilotinib
- 1st line tx = 2nd gen TKI
- Target level = IS (international scale) ratio of <0.1% (from BCR-ABL/ABL ratio, PCR)
Allogeneic HSCT
- For failed TKI
50
Complications of HSCT
1. Infection
2. Hemorrhage
3. Veno-occlusive disease of liver (VOD)
4. Graft-versus-host disease (GVHD) (allo HSCT)
5. Graft rejection (i.e. host-versus-graft) (allo HSCT)
6. Cataract (mainly due to total body irradiation (TBI))
7. Immunodeficiency
8. Endocrine dysfunction & infertility
9. Secondary malignancy
10. Relapse of disease
51
2nd gen TKI for CML / ph+ ALL
Dasatinib
| Nilotinib
52
TTP pentad
```
Fever
Changes in mental status
Thrombocytopenia
Abnormal RFT
Microangiopathic hemolytic anemia
```
