Haematology Flashcards
Aplastic crises
- caused by?
- lab findings?
- caused by infection with parvovirus
- sudden fall in haemoglobin
- bone marrow suppression causes a reduced reticulocyte count
Sequestration crises:
- seen in?
- clinical findings?
- lab findings?
- seen in sickle cell anemia
- sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia
- associated with an increased reticulocyte count
- known sickle cell anaemia presents with abdominal pain, splenomegaly and anemia
CML is associated with
Philadelphia chromosome - t(9:22)
Philadelphia chromosome is associated with
CML
The Philadelphia translocation is seen in around 95% of patients with chronic myeloid leukaemia. Around 25% of adult acute lymphoblastic leukaemia cases also have this translocation.
It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of normal.
What is the chromosomal abnormality in Philadelphia chromosome?
- t(9:22)
t(9;22) - Philadelphia chromosome is a poor prognostic indicator in
ALL
What is a poor prognostic indicator for ALL?
Philadelphia chromosome
Hereditary Spherocytosis is diagnosed by
- the osmotic fragility test previously
- the British Journal of Haematology (BJH) guidelines state that ‘patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes) do not require any additional tests
- if the diagnosis is equivocal > EMA binding (Eosin-5€²-maleimide (EMA) binding test) test and the cryohaemolysis test
- for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice
Lab Findings of Hereditary Spherocytosis
- spherocytes
- raised mean corpuscular haemoglobin concentration [MCHC],
- increase in reticulocyte
Hereditary Spherocytosis vs G6PD
- Hereditary Spherocytosis is inherited in a ———– fashion
- seen mostly in which ethnicity?
- Autosomal Dominant
(Male + female) - Northern European descent
- G6PD is inherited in a ——— manner.
- seen mostly in which ethnicity?
- X Liked recessive(Male only)
- African+Mediterranean descent
Key Blood film in G6PD
Heinz Body
Key Blood film finding in Hereditary spherocytosis
Spherocytes (round, lack of central pallor)
Follicular lymphoma is characterised by ———— translocation
t(14:18) translocation
Follicular lymphoma is driven by a translocation involving Ig heavy chain on chromosome 14 and BCL2 on chromosome 18.
Lymphoma classification
Lymphoma is the malignant proliferation of lymphocytes which accumulate in lymph nodes or other organs. Lymphoma may be classified as:
- Hodgkin’s lymphoma (a specific type of lymphoma characterized by the presence of Reed-Sternberg cells)
- non-Hodgkin’s lymphoma (every other type of lymphoma that is not Hodgkin’s lymphoma). may affect either B or T-cells and can be further classified as high grade or low grade.
- Non-Hodgkin’s lymphoma is much more common than Hodgkin’s lymphoma
- Low-grade non-Hodgkin’s lymphoma has a better prognosis
- High-grade non-Hodgkin’s lymphoma has a worse prognosis but a higher cure rate
Investigation of choice for Lymphoma
Excisional node biopsy is the diagnostic investigation of choice
-certain subtypes will have a classical appearance on biopsy such as Burkitt’s lymphoma having a ‘starry sky’ appearance
- CT chest, abdomen and pelvis (to assess staging)
- HIV test (often performed as this is a risk factor for non-Hodgkin’s lymphoma)
- FBC and blood film (patient may have a normocytic anaemia and can help rule out other haematological malignancy such as leukaemia)
- Prognostic indicator ESR, LDH (LDH is marker of cell turnover)
- Other investigations can be ordered as the clinical picture indicates (LFT’s if liver metastasis suspected, PET CT or bone marrow biopsy to look for bone involvement, LP if neurological symptoms)
Clinical Presentation of Lymphoma
- Painless lymphadenopathy (non-tender, rubbery, asymmetrical)
- Constitutional/B symptoms (fever, weight loss, night sweats, lethargy)
- Extranodal Disease - gastric (dyspepsia, dysphagia, weight loss, abdominal pain), bone marrow (pancytopenia, bone pain), lungs, skin, central nervous system (nerve palsies)Rre
Clinical difffernetiation between Hodgkin vs Non-Hodgkin Lymphoma
- Biopsy mainly
- Lymphadenopathy in Hodgkin’s lymphoma can experience alcohol-induced pain in the node
- ‘B’ symptoms typically occur earlier in Hodgkin’s lymphoma and later in non-Hodgkin’s lymphoma
- Extra-nodal disease is much more common in non-Hodgkin’s lymphoma than in Hodgkin’s lymphoma
Risk factors for Non-Hodgkin Lymphoma
A- Autoimmune disease (SLE, Sjogren’s, coeliac disease)
B- History of viral infection (specifically Epstein-Barr virus)
C- Caucasians, chemical agents (pesticides, solvents), History of chemotherapy or radiotherapy
D- ImmunoDEFICIENCY (transplant, HIV, diabetes mellitus)
E- Elderly
F- Family history
which test used to investigate to cause of anaphylaxis?
Radioallergosorbent test (RAST) - is used for Anaphylaxis
Burkitt’s lymphoma has a _______ appearance in LN Biopsy
‘starry sky’ appearance
Prognostic indicator of Lymphoma?
ESR
LDH
Which type of non-Hodgkin’s lymphoma has a better prognosis?
Low-grade non-Hodgkin’s lymphoma has a better prognosis
How to assess allergies?
Skin prick is used for ——
Skin prick is contraindicated in ———
Skin patch is used for ——-
Radioallergosorbent test (RAST) - is used for ———
Skin prick is used for food allergies and pollen.
Skin Prick is Contraindicated in anaphylaxis and patients on oral antihistamine
Skin patch is used for contact dermatitis
Radioallergosorbent test (RAST) - is used for Anaphylaxis ( Useful for food allergies, inhaled allergens (e.g. Pollen) and wasp/bee venom). Determines the amount of IgE that reacts specifically with suspected or known allergens, for example IgE to egg protein. Results are given in grades from 0 (negative) to 6 (strongly positive)
What is Philadelphia chromosome?
It is due to a translocation between the long arm of chromosome —– and —– ?
It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of normal.
First line Rx for CML
Imatinib is now considered first-line treatment
inhibitor of the tyrosine kinase associated with the BCR-ABL defect
Management of CML
Hint:
IHIA
IHIA
I- Imatinib is now considered first-line treatment
inhibitor of the tyrosine kinase associated with the BCR-ABL defect
very high response rate in chronic phase CML
H- Hydroxyurea
I - Interferon-alpha
A - Allogenic bone marrow transplant
Von Willebrand’s disease types and inheritence
- most common inherited bleeding disorder.
- characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare
type 1: partial reduction in vWF (80% of patients)
type 2*: abnormal form of vWF
type 3**: total lack of vWF (autosomal recessive)
Majority is Autosomal Dominant
Type 3 is Autosomal recessive.
What is VWF
Role of von Willebrand factor:
- large glycoprotein which forms massive multimers up to 1,000,000 Da in size
- promotes platelet adhesion to damaged endothelium
- carrier molecule for factor VIII
Rx of VW Disease
- Tranexamic acid for mild bleeding
- Desmopressin (DDAVP): a synthetic analogue of the antidiuretic hormone vasopressin. It stimulates the release of von Willebrand factor (vWF) from Weibel-Palade bodies within endothelial cells, thereby elevating vWF levels. VWF then facilitates haemostasis by enhancing platelet adhesion to damaged endothelium and stabilising factor VIII. Desmopressin should be the initial treatment choice for both therapeutic and prophylactic interventions in minor spontaneous, traumatic, or surgical bleeding episodes associated with von Willebrand’s disease. Nevertheless, caution is needed when using desmopressin during childbirth due to potential risks such as fluid retention and hyponatraemia. Factor VIII concentrates, which contain both factor VIII and vWF, might also be utilised in severe cases where there is a significant deficiency or when desmopressin is not effective.
- factor VIII concentrate
Lab findings of VW Disease
Prolonged bleeding time
APTT may be prolonged
Factor VIII levels may be moderately reduced defective platelet aggregation with ristocetin
Acute Intermittent Porphyria presentation
4ps=painful abdomen, polyneuropathy, psyciatric symptoms, port wine urine=symptoms of AIP
Rx of Acute Intermittent Porphyria
Management
- avoiding triggers
- acute attacks:
1. IV haematin/haem arginate
2. IV glucose should be used if haematin/haem arginate is not immediately available
Acute Intermittent Porphyria Genetics
rare autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem
How to diagnose Acute Intermittent Porphyria
Diagnosis
- classically urine turns deep red on standing
- raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks)
- assay of red cells for porphobilinogen deaminase
- raised serum levels of delta aminolaevulinic acid and porphobilinogen
Skin patch testing is used for
COntact dermatitis
Name the anti-estrogen drugs
- Selective oEstrogen Receptor Modulators (SERM)
: Tamoxifen is a SERM which acts as an oestrogen receptor antagonist and partial agonist. It is used in the management of oestrogen receptor-positive breast cancer. - Aromatase inhibitors:
Anastrozole and letrozole are aromatase inhibitors that reduces peripheral oestrogen synthesis. This is important as aromatisation accounts for the majority of oestrogen production in postmenopausal women and therefore anastrozole is used for ER +ve breast cancer in this group.
APS in Pregnancy RX
Management
low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing
low molecular weight heparin once a fetal heart is seen on ultrasound. This is usually discontinued at 34 weeks gestation
Aplastic Anemia RX
- Immunosuppressive therapy with anti-thymocyte globulin (ATG) and ciclosporin is the treatment of choice for older patients with severe aplastic anaemia or those without a suitable stem cell donor
Ultimate Rx-
Allogenic Stem Cell Transplant
Drugs causing AIHA
Methyldopa
B Thalassemia Major Pathology
absence of beta globulin chains
chromosome 11
Hyposplenism Blood picture:
Hyposplenism e.g. post-splenectomy, coeliac disease (occurs in around 30% of coeliac patients)
target cells
Howell-Jolly bodies
Pappenheimer bodies
siderotic granules
acanthocytes
Acute Hemolytic Reaction is caused by
ABO-incompatible blood e.g. secondary to human error
What is used to replace Fibrinogen
Cryoprecipitate
Most common tumour causing bone metastases
Most common tumour causing bone metastases (in descending order)
prostate
breast
lung
Pure Bony Lesion
Wiskott-Aldrich syndrome
- combined B- and T-cell dysfunction. It is inherited in a X-linked recessive fashion and is thought to be caused by mutation in the WASP gene.
Features
- recurrent bacterial infections (e.g. Chest)
- eczema
- thrombocytopaenia
- low IgM levels
Wiskott-Aldrich syndrome Pathology
Mutation in the WAS gene affecting cytoskeletal regulation
How does Desmopressin work in VWF
desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
Drugs risk factors for VTE
- combined oral contraceptive pill: 3rd generation more than 2nd generation
- hormone replacement therapy: the risk of VTE is higher in women taking oestrogen + progestogen preparations compared to those taking oestrogen-only preparations
- raloxifene and tamoxifen
- antipsychotics (especially olanzapine) have recently been shown to be a risk factor
Tumour Lysis SYndrome Bloods
- Laboratory TLS:
High Potassium
High Phosphate
Low Calcium
High uric acid - Clinical TLS: laboratory TLS + one or more of the following:
- increased serum creatinine (1.5 times upper limit of normal)
- cardiac arrhythmia or sudden death
- seizure
Drugs used for prevention of TLS
- High Risk: Rasburicase
- Low Risk: Allopurinol
M/A of Rasburicase
a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin.
TXA M/A
Tranexamic acid is a synthetic derivative of lysine. Its primary mode of action is as an antifibrinolytic that reversibly binds to lysine receptor sites on plasminogen or plasmin. This prevents plasmin from binding to and degrading fibrin.
Rx of Essestial Thrombocytosis
- Hydroxyurea (hydroxycarbamide) is widely used to reduce the platelet count
- interferon-α is also used in younger patients
- low-dose aspirin may be used to reduce the thrombotic risk: for patients under 60 years old without previous thrombotic events but with platelet counts over 450 × 10⁹/
SVC Obstruction most commonly associated with
. It is most commonly associated with lung cancer.
Urgent Rx of SVC Obstruction
Urgent endovascular stenting of the superior vena cava is the treatment of choice for rapid symptom relief in patients with superior vena cava (SVC) obstruction
common causes of SVC Obstruction
common malignancies: small cell lung cancer, lymphoma
How is Sickle Cell Anemia managed Longer terms
Hydroxyurea
increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes
sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years
Aplastic Crisis vs
Sequestration Crisis
Aplastic crisis = AHHH where have my reticulocytes gone?
Sequestration crisis = So many reticulocytes
Drugs causing Hemolysis in G6PD
Some drugs causing haemolysis
- anti-malarials: primaquine, Dapsone
- ciprofloxacin
- sulph- group drugs: sulphonamides, sulphasalazine
- sulfonylureas
- Nitrofurantoin
G6PD seen mostly in
+
Genetics
is more common in people from the Mediterranean and Africa and is inherited in an X-linked recessive fashion.
What is Factor 5 Leiden
mutation in the Factor V Leiden results in protein C resistance:
Increased resistance of factor V to inactivation by activated protein C
Who should receive VTEP during pregnancy?
According to UK guidelines, women with a previous VTE and a documented thrombophilia such as Factor V Leiden heterozygosity should receive prophylactic LMWH throughout pregnancy and for at least six weeks postpartum to reduce the risk of recurrent VTE.
Which scoring is used as a performance status to decide if a patient is a good or poor candidate for future oncological therapi
ECOG Score
6 points (0-5)
0= fully active
5= Dead
Drugs Causing Pancytopenia
Drug causes of pancytopaenia
- cytotoxics
- antibiotics: trimethoprim, chloramphenicol
- anti-rheumatoid: gold, penicillamine
- carbimazole*
- anti-epileptics: carbamazepine
- sulphonylureas: tolbutamide
M/A of Hydroxyurea (hydroxycarbamide)
Hydroxyurea (hydroxycarbamide) Inhibits ribonucleotide reductase, decreasing DNA synthesis
M/A Cyclophosphamide
Cyclophosphamide is an alkylating agent used in the management of cancer and autoimmune conditions. It works by causing cross-linking of DNA
Cyclophosphamide adverse effect
- Haemorrhagic cystitis: incidence reduced by the use of hydration and mesna
- Myelosuppression
- Transitional cell carcinoma
Which subtypes of HPV virus are carcinogenic
Human papilloma virus (HPV) infection is the most important risk factor for developing cervical cancer. Subtypes 16,18 & 33 are particularly carcinogenic.
Carcinogens and their association:
Aflatoxin - –?
Aniline dyes—-?
Asbestos—- ?
Nitrosamines —?
Vinyl chloride—-?
AL (aflatoxin-liver) can’t remember his
AB (aniline dyes- Bladder) Cs at 7
AM (asbestos, mesthelioma + bronchial carcinoma) before breakfast. He got
NO (nitrosamines, oesophageal and gastric cancer) time to complete his
CV (vinyl chloride, hepatic angiosarcoma)
Most important screening test for Hereditary Angioedema
Hereditary angioedema - C4 is the best screening test inbetween attacks
Most common cause of Neutropenic Sepsis
coagulase-negative, Gram-positive bacteria are the most common cause, particularly Staphylococcus epidermidis
Type of Lymphoma with:
Best Prognosis?
Worst Prognosis?
Most common?
Best Prognosis- Lymphocyte predominant
Worst Prognosis- Lymphocyte Depleted
Most common- Nodular sclerosing
Mainstay of Rx of Hodgkin Lymphoma
Chemo
An Arbor staging of Hodgkin Lymphoma
Ann-Arbor staging
The Ann-Arbor staging system was historically the main way patients with Hodgkin’s lymphoma were staged.
Stage
I: single lymph node
II: 2 or more lymph nodes/regions on the same side of the diaphragm
III: nodes on both sides of the diaphragm
IV: spread beyond lymph nodes
Lymphoma is confirmed by presence of —- cells. what does the cell look like?
ells that are either multinucleated or have a bilobed nucleus with prominent eosinophilic inclusion-like nucleoli (thus giving an ‘owl’s eye’ appearance)
PNH Gold standard investigations
Flow cytometry of blood to detect low levels of CD59 and CD55 has now replaced Ham’s test as the gold standard investigation in PNH
A 55-year-old man presents to the Emergency Department with sudden onset of severe abdominal pain and vomiting over the past 12 hours. He has recently been feeling depressed and reports experiencing palpitations and sweating. On examination, he is hypertensive with a blood pressure of 160/100 mmHg and tachycardic with a heart rate of 115 bpm. His abdomen is soft and non-tender. Neurological examination is normal.
The patient’s severe abdominal pain, vomiting, psychiatric symptoms (depression), autonomic disturbances (palpitations, sweating, hypertension, tachycardia), and normal initial investigations are classic features of an acute porphyria attack, specifically acute intermittent porphyria (AIP).
Poor prognostic markers for Myeloma
- B2-microglobulin is a useful marker of prognosis - raised levels imply poor prognosis
- Low levels of albumin are also associated with a poor prognosis
Causes of Intra and Extravascular Hemolysis
Intravascular haemolysis: causes
mismatched blood transfusion
G6PD deficiency*
red cell fragmentation: heart valves, TTP, DIC, HUS
paroxysmal nocturnal haemoglobinuria
cold autoimmune haemolytic anaemia
Extravascular haemolysis: causes
haemoglobinopathies: sickle cell, thalassaemia
hereditary spherocytosis
haemolytic disease of newborn
warm autoimmune haemolytic anaemia
(Hot-HHH and Warm)
Hereditary angioedema caused by a deficiency of
Hereditary angioedema is caused by deficiency of C1 esterase inhibitor
