Haematology Flashcards
1
Q
What is leukaemia?
A
- Cancer of a partivular line of STEM CELLS in the BONE MARROW
2
Q
What does leukaemia cause the unregulation of?
A
- Certain types of blood cells
- Uncontrolled proliferation of IMMATURE BLAST CELLS (precursor of WBC, RBC, platelets) → build up in the blood
3
Q
What are the 4 types of leukaemia?
A
- Acute myeloid leukaemia
- Chronic myeloid leukaemia
- Acute lymphoblastic leukaemia
- Chronic lymphocytic leukaemia
4
Q
Which blood cell does acute myeloid leukaemia (AML) start?
A
Myeloblast
5
Q
Which blood cell does chronic myeloid leukaemia (CML) start?
A
- Basophils
- Eosinophils
- Neutrophils
6
Q
Which blood cell does acute lymphoblastic leukaemia (ALL) start?
A
Lymphoblast
7
Q
Which blood cell does chronic lymphocytic leukaemia (CLL) start?
A
B lymphocyte
8
Q
What is the mnemonic for the ages at which the different leukaemias start?
A
ALLCeLLmates haveCoMmonAMbitions
- Under 5 and over 45 –acutelymphoblasticleukaemia (ALL)
- Over 55 –chroniclymphocyticleukaemia (CeLLmates)
- Over 65 –chronicmyeloid leukaemia (CoMmon)
- Over 75 –acutemyeloid leukaemia (AMbitions)
9
Q
Leukaemia is cancer of what?
A
Cells in the bone marrow
(Genetic mutation in one of the precursor cells in the bone marrow → EXCESSIVE PRODUCTION of a single type of ABNORMAL WHITE BLOOD CELL )
10
Q
What is pancytopenia in leukaemia?
A
The excessive production of a single type of cell can lead to suppression of the other cell lines causing underproduction of other cell types → pancytopenia
11
Q
A patient has leukaemia, and have developed pancytopenia. What do their FBC look like?
A
Low:
* RBCs (aneamia)
* WBCs (leukopenia)
* Platelets (thrombocytopenia)
12
Q
General cytopenia puts the patinet at risk of what complications?
A
Infection + bleeding
(Progenitors cannot mature → too many blasts)
13
Q
What is the difference between the differentiation in acute and chronic leukaemia?
A
- Acute → cells don’t differentiate at all
- Chronic → cells partially differentiate
14
Q
What are the signs to the skin that are present in leukaemia?
A
- Bleeding under the skin → brusing + petechiae
- = caused by thrombocytopenia (low platelets)
- Petechiae = non-blanching rash
- Pallor (due to anaemia)
15
Q
What are the symptoms of leukaemia?
A
Non-specific
* Fatigue
* Fever
16
Q
What are the signs of leukaemia?
A
- Failure to thrive (children)
- Pallor (anaemia)
- Petechiae + abnormal bruising (thrombocytopenia)
- Abnormal bleeding
- Lymphadenopathy
- Hepatosplenomegaly
Children or young adults with ptechiae or hepatosplenomegaly = should be referred immediately to hospital
17
Q
What are the first line Ix for leukaemia?
A
- URGENT FBC (within 48 hours)
-
Blood film
- Look for abnormal cells + inclusions
- Lactate dehydrogenase (LDH) (elevated) → non-specific
-
CXR
- Show infection
- Show mediastinal lymphadenopathy
-
Lymph node biopsy
- Assess lymph node involvement
- Investigate for lymphoma
18
Q
What is the gold standard (diagnostic) Ix for leukaemia?
A
-
Bone marrow biopsy
- Analyse the cells in the bone marrow
19
Q
What are the types of bone marrow biopsy?
A
-
****Bone marrow aspiration****
- Taking a liquid sample full of cells within the bone marrow
-
Bone marrow trephine
- Solid core sample of bone marrow
- Better assesssment of the cells + structure
-
********Bone marrow biopsy**********
- Usually taken from iliac crest
- Samples from bone marrow aspiration can be examined straight away
20
Q
What other Ix can you request for leukaemia?
A
CT, MRI, PET
* Staging + assessing for lymphoma and other tumours
21
Q
What is seen on a blood film for ALL?
A
Blast cells
22
Q
What is seen on a blood film for CLL?
A
Smear/smudge cells
23
Q
What is seen on a blood film for AML?
A
Blast cells with Auer rods
24
Q
What is seen on a blood film for CML?
A
High proportion of blast cells
25
Which two leukaemias have the Philidelphia (9:22) translocation?
ALL and CML
| 'CAM' Loves Philidelphia
26
What are some complications of chemotherapy?
* Failure to thrive
* Stunted growth and development in children
* Infections due to immunodeficiency
* Neurotoxicity
* Infertility
* Secondary malignancy
* Cardiotoxicity
* Tumour lysis syndrome
27
What is tumour lysis syndrome caused by?
The release of **uric acid** from cells that are being destroyed by chemotherapy
28
How can chemotherapy cause an AKI?
Tumour lysis syndrome
The uric acid = can form crystals in the intersitial tissue + tubules of the kidneys
29
What medications are given in tumour lysis syndrome to reduce the high levels of uric acid?
* Allopurinol
or
* Rasburicase
30
What is the most common leukaemia in children?
Acute lymphoblastic leukaemia (ALL)
31
What leukaemia is associated with Down's syndrome?
Acute lymphoblastic leukaemia (ALL)
32
Acute lymphoblastic leukaemia (ALL) causes the excessive proliferation of which blood cell?
B lymphocytes (usually)
(Causes pancytopenia)
33
Chronic lymphocytic leukaemia (CLL) cause the chronic proliferation of which blood cell?
Well differentiated B lymphocytes
34
How can CLL present?
* Often **asymptomatic**
* Infections
* Anaemia
* Bleeding
* Weight loss
35
Chronic lymphocytic leukaemia (CLL) can transform into high-grade **lymphoma**, what is the transformation called?
Richter's transformation
36
What does CLL look like on a blood film?
Smear/smudge cells
(fragile WBCs = rupture when prepping the film)
37
Which leukaemia is associated warm haemolytic anaemia?
CLL
38
What are the 3 phases of CML?
* Chronic (often asymptomatic)
* Accelerated
- Become more symptomatic
- Develop anaemia + thrombocytopenia
- Become immunocompromised
* Blast
- Even higher proportion of blast cells (>30%)
- Severe symptoms
- Pancytopenia
- Often fatal
39
What is the Philidelphia chromosome?
Translocation of genes between chromosome **9** and **22**
40
What is the most common acute leukaemia in adults?
AML
41
What can cause AML?
Transformation from a **myeloproliferative disorder**
(e.g. polycythaemia ruby vera or myelofibrosis)
42
What does a blood film look like for acute myeloid leukaemia (AML)?
* High proportion of blast cells
* Blast cells = have Auer rods in their cytoplasm
43
A 5 y/o patient with Down's presents with petechie, abnormal brusing and fatigue. Possible diagnossis?
Acute lymphoblastic leukaemia (ALL)
43
What are the results of Ix for ALL?
* FBC: Pancytopenia
* Blood film: Increased lymphoblasts (blast cells)
* BM biopsy (>20% lymphoblasts) = diagnostic
44
Treatment options for ALL?
Chemotherapy
Allopurinol (for tumour lysis syndrome)
45
What is the general management of leukaemia?
First line:
* Chemotherapy
* Steroids
Other:
* Radiotherapy
* Bone marrow transplant
* Surgery
46
Typical presentation: 70% men w/ general anaemia, with lymphadenopathy (non-tender) and hepatosplenomegaly. Which leukaemia is his most likely to have?
Chronic lymphocytic anaemia (CLL)
47
A patient has chronic lymphocytic leukaemia (CLL). What do the Ix come back as?
* FBC: Pancytopenia (except leukocytosis), elevated WBCs
* Blood film: Smudge cells
* Immunoglobulin levels: Hypogammaglobinaemia (patient has reccurrent infections)
| Hypogammaglobinaemia as B cells dont prolif to plasma cells (no Igs)
48
What is an additional treatment for CLL?
IV Igs for hypogammaglobinaemia
49
What is a major complication of CLL?
**Richter transformation (high-grade lymphoma)**
* B cells = massively accumulate in lymph nodes → massive lymphadenopathy
* Transformation from CLL to aggressive lymphoma
50
What are some specific Sx of Acute Myeloid Leukaemia (AML)?
* Association with Down's + radiation
* Gum infiltration (gingival enlargement)
* Hepatosplenomegaly
51
A patient has AML what would their Ix return back as?
* FBC: pancytopenia
* Blood film: Myeloblast cells with Auer rods
* BM biopsy: > 20% myeloblasts
52
What is a slightly more specific Sx of chronic myeloid leukaemia (CML)?
General leukaemia Sx + MASSIVE HEPATOSPLENOMEGALY
53
A patient with CML has Ix, when they return what would they look like?
* FBC: Pancytopenia (but **granulocytosis**)
* Blood film: Increases granulocytes (B.E.N)
* Genetic testing: Philidelphia chromosome
54
What is the treatment for CML?
Chemotherapy + **imatinib**
(Imatinib = tyrosine kinase inhibitor)
55
What is a complication/risk of CML if left untreated?
Risk of progression to AML
56
What type of cancer is lymphoma?
Cancer that affects the LYMPHOCYTES inside the LYMPHATIC SYSTEM
(The cancerous cells = PROLIFERATE INSIDE the LYMPH NODES → lymph nodes = become abnormally large → LYMPHADENOPATHY)
57
Name 3 areas of lymphandenopathy in lymphoma
* Cervical
* Axillary
* Inguinal
58
Define Hodgkin's lymphoma
Haematological malignancy arising from **mature B cells**
59
What cells is Hodgkin's lymphoma characterised by?
Presence of Hodgkin's cells + **Reed-Sternberg cells**
60
What age group is primarily affected by Hodgkin's lymphoma?
BIMODAL AGE DISTRIBUTION
Peaks: **20** and **70** years
(Teens and elderly)
61
What are some Rx for Hodgkin's lymphoma?
* HIV
* **Epstein-Barr virus (50%) immunodeficiency/suppression**
* Autoimmune conditions (RA, sarcoidosis)
* Family history
62
Describe the lymphadenopathy with Hodgkin's lymphoma
(Location, characteristics)
* Neck, axilla (armpit) inguinal (groin)
* Non-tender + rubbery
63
What happens to the lymphadenopathy in Hogdkin's after drinking alcohol?
PAINFUL after drinking alcohol
64
What are the signs and symptoms of Hodgkin's lymphoma?
* B symptoms
* Lymphadenopathy (painful after drinking alcohol)
* (Reccurent infection)
65
What are the B symptoms?
* Night sweats
* Unintentional weight loss
* Fever
66
What are the first line and gold-standard investigations for Hodgkin's lymphoma?
* First line: ↑LDH, ↑ESR ↓Hb
* Gold standard: Lymph node biopsy (diagnostic)
- Reed-Sternberg cells present
- (Excisional lymph node biopsy or core biopsy)
67
What are Reed-Sternberg cells?
Present in Hodgkin's lymphoma
Abnormally large B cells
(Have multiple nuclei - that have nucleoli inside of them)
Face of an **OWL with eyes**
68
What Ix can you perform to stage Hodgkin's lymphoma?
**Contrast-enhanced CT (neck, chest, abdomen, pelvis)** → enlarged lymph nodes and other sites of disease
(Or MRI, PET)
* To see the extent of the disease
* **Biopsy** = used to confirm the diagnosis
69
What staging system is used in Hodgkin's and Non-Hodgkin's lymphoma?
Ann Arbor Staging
| Importance on whether the affected nodes are above or below diaphragm
70
Give the stages of Ann Arbor staging system
* Stage 1: **One region** of lymph nodes
* Stage 2: **2 or more regions** - on the **same side of the diphragm**
* Stage 3: Lymph nodes **above and below** the diaphragm
* Stage 4: **Extranodal organ spread** (spread to non-lymphatic organs e.g. lungs or liver)
Prefixed with A or B:
* A - absence of B symptoms
* **B - presence of B symptoms**
71
What is the treatment of Hodgkin's lymphoma?
* Chemotherapy + ABVD
* A - Adriamycin
* B - Bleomycin
* V - Vinblastine
* D - Dacarbazine
72
What are some complications of chemotherapy anf radiotherapy?
* Chemotherapy: Risk of leukaemia + infertility
- Alopecia, N+V, myelosuppression + BM failure, INFECTION
* Radiotherapy: Risk of cancer, damage to tissues, **hypothyroidism**
73
Hodgkin's lymphoma typically presents to clinic like what?
- **Hodgkin's lymphoma (HL) most commonly presents with painless cervical and/or supraclavicular lymphadenopathy in a young adult.**
- **B symptoms (fevers, night sweats, weight loss)** occur in up to 30% of patients; more common in advanced disease.
74
What is Non-Hodgkin's lymphoma?
Heterogenous group og malignancies of the lymphoid system
75
Name a few types of Non-Hodgkin's lymphoma
* **Burkitt lymphoma** (associated with EBV, malaria, HIV)
* **MALT lymphoma** (associated with H. pylori infection)
* **Diffuse large B cell lymphoma** (presents as a rapidly growing painless mass in patients over 65 years) - (80%)
75
Name a few types of Non-Hodgkin's lymphoma
* **Burkitt lymphoma** (associated with EBV, malaria, HIV)
* **MALT lymphoma** (associated with H. pylori infection)
* **Diffuse large B cell lymphoma** (presents as a rapidly growing painless mass in patients over 65 years) - (80%)
76
Pathophysiology of Non-Hodgkin's lymphoma
* Malignant cloncal expansion of lymphocytes at different stages of lymphocyte development
* Majority are B-cell origin (80%)
* ABSENCE OF REED-STERNBERG CELLS
77
What is an occupational risk factor for Non-Hodgkin's lymphoma?
Exposure to pesticides with trichloroethylene
78
Sx of Non-Hodgkin's lymphoma
* **B symptoms +** **PAINLESS RUBBERY LYMPHADENOPATHY** (**NOT** affected by alcohol), splenomegaly
* (Sx similar to Hodgkin's - only biopsy will differentiate)
* (More varied than Hodgkin's as more subtypes)
79
Ix for Non-Hodgkin's lymphoma
* First line: FBC (anaemia, ↑WBC or thrombocytopenia, ↑ESR)
- ↑WBC or thrombocytopenia = suggests B cell involvement
* Diagnostic: Lymph node biopsy (no RS cells/popcorn cell)
- Confirms subtype (e.g. Burkitt's = 'starry sky' biopsy)
- Staging: CT/MRI chest, abdomen, pelvis (Ann Arbour staging 1-4)
80
What is the Tx for Non-Hodgkin's lymphoma?
R-CHOP Chemotherapy:
* R - Rituximab
* C - Cyclophosphamide
* Hydroxy-daunorubicin
* O-Vincristine
* Prednisolone
| Rituximab = monoclonal antibody (targets CD20 on B cell)
81
Myeloma is a cancer of what?
Neoplastic **monoclonal** proliferation of a **plasma cell**
* Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced
82
In more than 50% of myelomas, which immunoglobulin (monoclonal paraprotein) is significantly produced?
IgG
83
In myeloma, what are the abnormally produced antibodies called?
Monoclonal paraproteins
84
What are 'Bence Jones proteins'?
**Light chains** of an antibody found in the **urine** of patients with **myeloma**
85
Bone marrow infiltration of cancerous plasma cells in myeloma can cause what?
Pancytopenia
* Anaemia (low RBCs)
* Neutropenia (low neutrophils)
* Thrombocytopenia (low platelets)
86
Myeloma bone disease causes increased activity of oestoblast or osteoclast?
What does it result in?
* **Oestoclast** (+ suppresses osteoblast activity)
* Results in **osteolytic lesions** → pathological fractures
* Calcium = reabsorbed in to the blood → **hypercalcaemia**
87
What is the 'typical' patient with myeloma?
70 y/o Afro-carribean male
88
What are the signs and symptoms of myeloma?
**Old CRAB:**
* **Old** → 70+
* **C** - **Hypercalcaemia** (↑osteoclast bone reabsorption)
* **R** - **Renal failure**
- Hypercalcaemia → calcium oxalate renal stones
- Immunoglobulin light chain kappa deposition → Bence Jones protein in urine
* **A** - **Anaemia** (BM failure)
* **B** - **Bone lesions** (BM failure = painful. New onset back pain in elderly)
89
Myeloma can result in hyercalcaemia. What is the mnemonic for the presentation of hypercalcaemia?
* Bones (weak bones)
* Stones (kidney stones)
* Abdo moans
* Psychiatric groans
90
Ix for myeloma?
* FBC (anaemia, low WBC)
* **U&Es (hypercalcaemia), urea/creatinine → renal failure**
* ESR (raised)
* Blood film: Normocytic normochromic, rouleaux fomration
* ** Urine electrophoresis: Bence Jones protein**
* **Serum electrophoresis**: Ig 'paraprotein M spike'; hypergammagobulin for that specific IgG
Imaging:
* **Skeletal survey (x-ray of ull skeleton)** → 'raindrop skull', punched out/lytic lesions
* **Whole body MRI/CT**
**BM biopsy → >10% plasma cells**
91
Management of myeloma?
* Chemotherapy (bortezomid, thalidomide, dexamethasone)
* Bisphosphonates (alendronate) - (suppress osteoclast activity)
* Stem cell transplant
92
What type of virus is HIV?
RNA Retrovirus
93
Which cells does HIV enter and destroy?
CD4 T helper cells
94
How does HIV cause immunodeficiency?
HIV replicates with CD4 cells → over time dicimates theor population → causing immunodeficiency
95
What are the two markers used to monitor HIV infection?
(important in prognosis)
* CD4 cell count
* HIV viral load
96
How does acute HIV present ?
(Symptoms usually start within 2-4 weeks of infection)
Similar to **glandular fever/flu**
Non-specific symptoms:
* Fever
* Sore throat
* Myalgia
* Rash
(Others: Vomiting + diarrhoea, headache, lymphadenopathy, wt loss)
97
If a patient presents with fever, rash and non-specific symptoms, what should you ask/think about?
* Ask about sexual history
* Think about HIV seroconversion
98
In the clinical latency period of HIV, what S may the patient present with?
No symptoms!
**Persistant generalised lymphadenoapathy**
(enlarged lymph nodes, involving at least 2 areas of the body for at least 3 months)
| Clinical latency periods can be about 8 years
99
Name some conditions that someone with early symptomatic HIV (immunocompromised) might present with?
* Shingles (in HIV more severe and can be multidermatomal)
* Candida (thrush) - oral or genital
* Oral hairy leucoplakia
* Molluscum contagiosum (strain of poxvirus)
100
When should you think about doing a HIV test?
When a common problem:
* In an unexpected patient
* Is recurring
* Has no clear underlying cause
101
Define AIDS
AcquiredImmune Deficiency Syndrome
**AIDS** = **CD4 <200** or **'AIDS defining illness'** present
102
What fungal pneumonia is common in HIV/AIDS?
How does it present?
**Pneumocystis pneumonia (PCP)** = most common AIDS defining illness
* Fevers
* SOB
* Dry cough
* Pleuritic chest pain
* **Exertional drop in oxygen saturations**
103
What do you treat pneumocytis pneumonia with?
**Co-trimoxazole**
+/- predisolone (if hypoxic)
104
What do you treat pneumocytis pneumonia with?
**Co-trimoxazole**
+/- predisolone (if hypoxic)
105
What is the most common opportunistic infection in HIV/AIDS?
Pneumocystis pneumonia (PCP)
106
Name some AIDS-defining illnesses
* PCP
* Oesophageal candida (oral is not)
* Kaposi's sarcoma
* TB
* CMV
107
What does a late diagnosis of HIV lead to?
* Increased transmission
* Increased morbidity
* Increased mortality
108
TB in HIV at any CD4 count is what?
AIDS-defining
109
All patients with TB require which test?
HIV test
110
The is a low threshold for which investigation for a patient with HIV and a headache?
Lumbar puncture
(Cryptococcal Meningitis)
111
HIV increased the risk of which cancers?
Any cances that is a associated with a virus:
* Kaposi's sarcoma (Human Herpesvirus 8)
* Lymphomas Epstein Barr Virus)
* Cervical (Human Papilomavirus)
(These are all AIDS-defining cancers)
112
What is the treatment regime for HIV?
Highly Active Anti-Retroviral Therapy
* Usually 3+ antiretroviral drugs
**NRTI + NRTI + Other**
NRTI = Neucleoside reverse transcriptase inhibitor
113
HIV treatment: Good adherence + avoidace to drug interactions are key to what?
* Suppress HIV replication
* Avoid drug resistance
114
Read: General facts about HIV
* HIV = causes progressive immunoprogression
* Early symptomatic HIV = may present with a range of conditions seen in normal hosts, but more frequently + more severity
* As the CD4 count drops below 200, a range of opportunistic infections and cancers can occur
* HAART = very effective in suppressing viral replication - resulting in a good prognosis
115
What are the types of HIV?
* HIV-1 (majority) - most virulent
* HIV-1 - less virulent
116
Rx for HIV
* MSM
* Sharing needles
* Needle stick injury
* Unprotected anal sex
117
What is the pathology of HIV infection?
* HIV gp120 binds to CD4 on Th cells
* ENDOCYTOSIS RNA + ENZYMES
* Reverse transcriptase; RNA → DNA
* Integrase; viral DNA integrated into host's
* PROTEIN SYNTHESIS
* VIRAL PROTEINS + RNA EXOCYTOSE + take part of CD4
- ↑viral copies
- ↓CD4+ (Th) cells
118
What are the stages of HIV (?natural history)?
* Infection: CD4+ dip then 'set point'
* Clinical latency (YEARS!)
* Sx: Constitutional Sx (fever, diarrhoea, night sweats, minor opportunistic infections e.g. oral candida, shingles)
* AIDS: CD4+ <200/mm3
- AIDS-defining conditions:
- CMV (e.g. colitis → owl eyes)
- PCP
- TB
- Kaposi sarcoma
- Lymphomas
119
Ix for HIV
* History
* Serum HIV enzyme-linked immunosorbent assay (ELISA)
- p24 Antibody
* Monitor progression
- Serum viral load (HIV RNA)
- CD4 count
