Haemolytic Crash Course Flashcards
Which of these is the most concerning for an acute leukaemia:
A. Neutrophil count of 12
B. 10cm splenomegaly
C. Microcytic anaemia
D. Blast cells present on blood film examination
E. Cervical lymphadenopathy
D. Blast cells present on blood film examination
What can cause a high platelet count? (5)
- Acute infection
- Chronic inflammation
- Malignancy (5-10%)
- Essential thrombocytopenia
- Polycythaemia rubra vera
Patients who are well with no inflammation or infection should be investigated
Which of these blood differentials is most in keeping with CML?
1
Chronic leukaemias always have a high WCC (excluding 3 + 4)
With CML would expect a high neutrophil count (excluding 2)
High platelet, eosinophil + basophil count is in keeping with CML
Rank these in order of Ann-Arbor staging (top stage 1- bottom stage 4)
A. Cervical lymphadenopathy + BM infiltration
B. Mediastinal + axillary lymphadenopathy
C. Inguinal + Cervical lymphadenopathy
D. A single enlarged lymph node in the axilla
D. Single enlarged LN in axilla
B. Mediastinal + axillary lymphadenopathy
C. Inguinal + Cervical lymphadenopathy
A. Cervical lymphadenopathy + BM infiltration
A patient with newly diagnosed Burkitt Lymphoma has these blood results 6h after chemotherapy
Creatinine 200 (baseline 90) Urea 14.4 (baseline 6) K+ 7.1 (3.5-5.5) Na+ 140 (135-145) Ca2+ 1.81 (2.2-2.6) Phosphate 1-1.6) Uric acid 800 (<400) What is the diagnosis? What is the treatment?
Diagnosis: Tumour lysis syndrome
Tx: Resburicase (depletes uric acid levels), treat K+, renal replacement therapy
Use Allopurinol to prevent this or Resburicase in high risk patient
What investigations are needed for a patient with an IgG lambda paraprotein of 25g/l discovered on a routine blood test?
Anyone with a IgA paraprotein >10 or IgG paraprotein >15 get referred to haematology clinic
Imaging to look for bone lesions + BM biopsy
55M with no PMH presents with fatigue to his GP. Bloods show
WCC 7 Hb 90 MCV 95 Na 140 K 4.0 Creatinine 90 Calcium 2.5 Serum electrophoresis shows an IgG kappa paraprotein of 37g/l Full body MRI shows no lytic lesions BM aspirate shows a clonal population of plasma cells, 15% of marrow cells What is the most likely diagnosis? A. Acute Leukaemia B. Multiple Myeloma C. Smouldering Myeloma D. MGUS E. Waldenstrom’s Macroglobulinaemia
B. Multiple Myeloma
Paraprotein >30 means it can only be multiple myeloma or smouldering myeloma
CRAB Sx: fatigue and Hb of 90 (with no other cause) confirms dx of MM
55M presents with 2/52 hx of fatigue and easy bruising to his GP. Bloods show
WCC 27 Hb 90 Plt 30 Na 140 K 4.0 Creatinine 90 Calcium 2.5 Blood film shows presence of blasts, with 27% blasts in marrow Flow cytometry shows a clonal population of cells expressing CD34, CD19 + TdT Cytogenic analysis shows the presence of t(9;22) What is the most likely diagnosis? A. Acute Myeloid Leukaemia B. Acute Lymphoblastic Leukaemia C. Mixed Phenotype Acute Leukaemia D. Adult T-cell Leukaemia-lymphoma E. Burkitt’s lymphoma
B. Acute lymphoblastiic leukaemia
Any % >20% blasts in BM defines acute leukaemia
CD19: B cell marker
TdT: Lymphoid precursor marker
t(9;22): seen in CML, but also ~1/3 cases of ALL
- 55M presents with 2/52 hx of fatigue and easy bruising to his GP. Bloods showWCC 27Hb 90Plt 30Na 140K 4.0Creatinine 90Calcium 2.5Blood film shows presence of blasts, with 27% blasts in marrowFlow cytometry shows a clonal population of cells expressing CD34, MPO
What is the most likely diagnosis?
A. Acute Myeloid Leukaemia
B. Acute Lymphoblastic Leukaemia
C. Mixed Phenotype Acute Leukaemia
D. Adult T-cell Leukaemia-lymphoma
E. Burkitt’s lymphoma
Acute Myeloid Leukaemia
Auer Rod
MPO: myeloid cell marker
25M presents to GP after 4/52 hx of intermittent fevers + drenching night sweats. Blood results show:
WCC 7 Hb 120 Plt 300 Na 140 K 4.0 Creatinine 90 Calcium 2.5
Examination reveals cervical lymphadenopathy , which is biopsied. On biopsy there are multinucleated cells. What is the diagnosis?
A. Mantle Cell lymphoma B. Disseminated tuberculosis C. Chronic Lymphocytic Leukaemia D. Hodgkin’s Lymphoma E. Burkitt’s Lymphoma
D. Hodgkin’s lymphoma
Reed Sternburg cell on biopsy
- A 50F presents to GP with left sided abdominal pain. Examination reveals palpable splenomegaly. Blood tests:WCC 30Hb 110Platelets 500Neutrophils 20Monocytes 0.7 (<1)
A blood film shows left shifted granulocytes.
Urgent FISH shows presence of BCR-ABL1 fusion gene. What is the most likely diagnosis?
A. Chronic Myeloid Leukaemia B. Chronic Myelomonocytic Leukaemia C. Myelodysplastic syndrome D. Essential Thrombocythaemia E. Myelofibrosis
CML
Left shifted granulocytes and BCR-ABL1 fusion gene
Give 3 clinical manifestations of BM failure
Anaemia: SOB, Chest pain on exertion, fatigue
Thrombocytopenia: easy bruising, petechial rashes, spontaneous bleeding e.g. epistaxis
Neutropenia: frequent or severe infections inc. opportunistic infections
In which type of leukaemias is splenomegaly more common?
LESS common in ACUTE than chronic leukaemias (as takes a long time for spleen to enlarge that much)
Give 5 potential features of AML on presentation
Bone pain
Occassional mild lymphadenopathy
Fevers from disease
Rarer: gum infiltrates, skin
Pancytopenia: May have elevated WCC- but low neutrophil count
In which type of leukaemia is there less burden in the BM?
Chronic
Slower proliferation
(thus less anaemia, thrombocytopenia + neutropenia, but will develop eventually given enough time)
How may chronic leukaemias be differentiated on examination?
CLL: Lymphadenopathy + Splenomegaly
CML: Splenomegaly
How may chronic leukaemias be differentiated on examination?
CLL: Lymphadenopathy + Splenomegaly
CML: Splenomegaly
What is leukostasis? What can this result in? (4)
Haematological emergency
High WCC causes blood to be viscous + end organ damage:
Retinopathy
Pulmonary infiltrates
Bleeding
Thrombosis
What is the treatment for leukostasis?
Leukaphoresis or chemo/ steroids
Give 6 features that may present in a question about ALL
- Often 2-5y
- Hepatosplenomegaly
- Bone pain/ limp
- Fevers
- CNS Sx (up to 10%)
- Testicular swelling (rare but specific)
How would ALL present in an adult?
BM failure
Bone pain, splenomegaly
Lymphadenopathy
What will be seen on a blood test in acute lymphoid leukaemia?
High WCC (but not always)
Anaemia
Thrombocytopenia
Some analysers flag blasts as lymphocytes
What will be seen on blood film in ALL?
High nuclear : cytoplasmic ratio
Lymphoblasts larger than RBCs (normal lymphocytes same size as RBCs)
Blasts often have tails/ blebs of cytoplasm
What can be used to distinguish between ALL and AML?
Immunophenotyping (looking at markers expressed)
Give 2 markers of immaturity which are seen in ALL
CD34
TdT
Which markers are expressed by B cells in ALL?
CD19
CD20
CD22
Which markers are expressed by T cells in ALL?
CD3
CD4
CD8
Which mutation may be associated with ALL? What % of adults have this? Which targeted treatment can be used against this?
BCR-ABL1 t(9;22)
20-30% of ALL in adults
(same mutation that causes CML)
Imatinib
What is the chemo treatment for ALL?
Induction: chemo + steroids
Consolidation: high dose, multi-drug
Maintenance: 2y in F + adults, 3y in M
Consider allo-SCT if high risk of relapse
Name 3 targeted treatments in ALL
Nelarabine (T-ALL)
CAR-T cells
Blinatumumab (B-ALL)
Give 5 poor prognostic factors for ALL
Age < 2y or > 10y
WBC > 20 * 10^9/l at dx
T or B cell surface markers
Non-Caucasian
Male sex
What supportive treatment is given in ALL?
Blood products
Abx prophylaxis
Allopurinol, Fluid + Electrolytes to prevent TLS
Give 4 features to look for in a question about AML
- Incidence INCREASES with age
- Might have had pre-existing myelodysplastic syndrome (MDS)
- Sx of cytopenias
- May have hx of chemotherapy, though mostly idiopathic
What will be seen on blood test in AML? (6)
- Anaemia: due to BM suppression
- Leukocytosis: high no. circulating white cells
- Thrombocytopenia: due to BM suppression
- Neutropenia: lack of mature white cells due to excess of blasts
- High no. circulating blasts
- Normal INR: normal for AML
What may be seen on a blood film in AML?
AUER RODS
A single Auer rod is enough to diagnose AML (or MDS), but sometimes there are lots
Not all AML patients have Auer rods
Granules
What markers are expressed in AML? (4)
MPO = myeloid cells
CD13
CD33
CD117
Which marker is expressed in both ALL and AML? What is this indicative of?
CD34
Precursor/ stem cells
What targeted treatment can be used for acute promyelocytic leukaemia? What is the MOA?
ATRA
All-trans-retinoic acid
Forces cells to differentiate, stops proliferation
Which chemotherapy drugs are often used in AML?
Induction: Daunorubicin + Cytarabine
Consolidation: Cytarabine
Consider allo-SCT if high risk of relapse
Which drugs may be used in older patients with AML?
Azacytidine
+/-
Venetoclax
Name 3 targeted treatments in AML
Midostaurin: FLT3 mutations Gemtuzumab: CD33 immunotherapy Enasidenib: IDH mutations
What are 4 types of myeloproliferative neoplasm?
Essential Thrombocytopenia
Polycythaemia Vera
Myelofibrosis
Chronic Myeloid Leukaemia
Give 3 features of essential thrombocytopenia
Platelet count >450 consistently with no other cause
Increased risk thrombotic events (arterial + venous)
Small risk of transformation to myelofibrosis or AML
Give 3 mutations seen in essential thrombocytopenia
JAK2
CALR
MPL
What treatment is required for essential thrombocytopenia?
Aspirin (reduce stroke risk)
Hydroxycarbamide (to lower count)
What is seen on blood film in essential thrombocytopenia?
Large platelets + megakaryocyte fragments
