Haematology Flashcards
def erythema
redness of the skin or mucous membrane due to capillary congestion (inflammation, injury or infection)
General signs of anaemia
Fatigue, weakenessm pale/yellowish skin, irregular heartbeats, SoB, dizziness/light-headedness, chest pain, cold hands and feet, headache
How is vit B12 absorbed (journey from mouth to blood)
Binds to transcobalamin I/haptocorrin/R protein/R factor produced by salivary glands
Haptocorrin-vitamin B12 complex is protected from acid degradation in stomach
In duodenum: pancreatic proteases degrade haptocorrin: free vit B12 binds to intrinsic factor (IF): B12-IF complex
In terminal ileum: cubilin receptors take up B12-IF complex by endocarditis-mediated absorption
If patient has iron, folate or vit B12 deficiency anaemia, what Qs should you ask to get to the bottom of it?
- are they deficient in the diet
- are they malabsorbed
- are they producing it (renal failure, chronic diseases, bone cancers etc)
- are they losing it (nose bleeds, cutting yourself)
How do you give vit B12
Orally Injections (if issue with the stomach: intrinsic factor)
What do you do if a patient is in shock and is not anaemic
GIVE BLOOD
(May take a while for the blood to expand and dilate)
Assess clinically: pale and clammy, pulse, BP, level of consciousness
Def haematocrit
Percentage of RBC i total blood (should be approx 40%)
How is Hb concertation measured and what are normal values
Lyse of RBC and measure of Hb concentration
Men: 130-180 g/L
Women: 115-165 g/L
What does the reticulocyte count show
Amount of reticulocytes (RBC with RNA) in blood
If low: problem in production
If high: production is fine but RBC are being destroyed prematurely
Causes of hypochromic microcytic anaemia
Iron deficiency
Chronic disease (IL6 and hepcidin)
Sideroblastic anaemia
Thalassaemia
What are the haematinic deficiencies?
Iron
Folate
Vit B12
Haematinics and milk
Cows milk: contains folate but contains no iron and hinders its absorption
Goats milk: no folate but contains iron
Causes of iron deficiency anaemia
Diet
Malabsorption (coeliac disease, milk, tea)
Blood loss (menarche, GI bleeding, cancer, bleeding disorder)
(Pregnancy, rapid grow, premature birth, low birth weight)
Types of thalassaemia
Beta thalassaemia minor: one abnormal gene
Beta thalassaemia major: two abnormal genes
Alpha thalassaemia: 4 types (4 genes)
-1 gene delete:clinically silent
-2 genes deleted: alpha thalassaemia trait (mild hypochromic microcytic anaemia)
-3 gene deleted: Hb H disease (haemolytic disease)
-4 gene deleted: Bart’s Hydrops Fetalis
What does ferritin measure
Iron stores
But goes up in chronic inflammation
Signs and symptoms of iron deficiency
General symptoms of anaemiaa
Headaches (esp with activity) Pica Sore or smooth tongue Brittle nails or hair loss Koilonychia
B12 deficiency anaemia causes
- nutritional
- malabsorption
- gastric: surgery, pernicious anaemia
- intestine: iléal résections fish tapeworm
- alcohol excess
(Would get malabsorption in Crons, coeliac, CF but not bough to cause deficiency)
Folate deficiency anaemia causes
Nutritional Intestinal (coeliac, resection) Excessive requirement (pregnancy) Increase turnover (chronic haemolysis, severe skin disease) Drugs (methotrexate, anticonvulsants ) Excess loss (dyalisis) (Alcohol BUT beer good source of folate)
Specific symptoms and signs seen in B12 and folate deficiency
- insidious onset
- mild jaundice and anaemia
- Glossitis
- angular Cheilitis (inflam of corners of mouth
- neuropathy
- peripheral (folate + B12)
- sub-acute degeneration of the cord (B12)
- optic (B12)
- dementia (B12)
Iron tablet prescriptions caution and info for patient
- be careful in diverticulosis and IBD because can exacerbate diarrhoea
- can interact with antibiotics, levadopa, zinc, tetracyclins, calcium products, levothyroxins so don’t give them together (2 hour difference)
- better absorbed on empty stomach, astobic acid helps with absorption + dpn’t take it with tea, eggs and milk products
Def haemolytic anemia
Destruction of. RBC
Investigatons in haemolytic anaemia
FBC with reticulocytes (high) Blood film (macrocytic) Bilirubin/lactic dehydrogenase (goes up) Coomb’s test (DAT) (for immune haemolytic anaemia) EMA binding Glucose-6-phosphate dehydrogenase levels Haemoglobin identification
Name some Haemolytic anaemia and the defects
Congenital
- RBC membrane: hereditary elliptocytosis and sperocytosis
- RBC enzyme deficiency: G^PD, pyruvate kinase
- RBC Hb disorders: thalassaemia, sickle cell disease
Acquired:
- auto-immune haemolysis (AIHA)
- Wilson’s disease (copper deficiency)
- others
Hereditary spherocytosis:
- aetiology
- clinical presentation
- Diagnosis
- treatment
- what it looks like on blood film
Aetiology:
- autosomal dominant
- abnormalities of RBC membrane proteins Spectrin and Actin
Clinical presentation:
-neonatal jaundice
-complicated by gallstones
(Blood film: micro-spherocytes (small, round dense RBC) and polychromatic macrocytes)
Diagnosis:
- family history, FBC, reticulocyte count, blood film
- if family history but FBC and blood film are normal: EMA-binding (fluorescence would be weaker)
Treatment:
- regular folate
- possible splenctomy and cholecystectomy
Glucose-6-phosphate dehydrogenase deficiency
- aetiology
- presentation
- treatment
Aetiology:
-often family history OR history of neonatal jaundice (X linked)
Presentation
- normally well between attacks
- sudden onset of
- feeling unwell + lack of energy
- pale and jaundice + backache
- passing dark urine
Treatment
- avoid triggers :
- fava and broad beans
- anti-malarial drugs, aspirin, many other drugs
- moth balls
Sickle cell disease
- aetiology
- clinical presentation/complications
- management/prevention
Aetiology
-beta globin variant (HbSS(/HbAS)): co -dominant autosomal recessive
Clinical presentation
- Vaso-occlusive crisis (artérioles in bone)
- stroke/death
- sickle cell chest (fat emboli in lungs)
- sequestration crisis
- pulmonary hypertension
- multi organ failure
- Anaemia
Management:
Long term: keep warm, hydrated, eat well, hydroxyurea (switch to HbF)
take penicillin and folic acid, Pneumovax, Primary and secondary stroke prevention (use transcranial Doppler for detection, regular transfusions, stem cell transplant
-during crisis: analgesia, IV fluids, transfusion (severe cases)
Management of Beta thalassaemia major
Long term blood transfusion and Iron chelation (Desferrioxamine or desferasirox)
or stem cell transplantation
Autoimmune Haemolytic anaemia
- types
- causes
- diagnosis
- treatment
Types: warm and cold
Causes:
- warm: idiopathic, secondary to rheumatoid disease, lymphoma, chronic lymphatic leukaemia, drugs, ovarian teratoma
- cold: idiopathic, secondary to EBV virus, mycoplasma pneumonia, ulcerative colitis
Diagnosis: confirming haemolysis, blood film, positive Coomb’s test (IgG in warm and complement in cold)
Treatment:
-warm: steroids
Affect of hepcidin on iron
Hepcidin degrades ferroportin
Ferroportin stimulates:
- enterocyte Fe release
- marrow macrophage Fe release
High transferrin saturation, IL6 increases Hepcidin
Low TFR saturation, TMPRSS6 (liver protein), GDF15 (RBC haemolysis, hypoxia decreases Hepcidin
Why can you get iron overload in chronic haemolysis
In haemolytic anaemia, increase in levels of growth differentiation Factor 15 (GDF15): which promotes iron absorption by inhibiting hepcidin
Early sign of microcytic anaemia (esp caused by vit B12 and folic acid deficiency)
Hyper segmentation of neutrophils
Coomb’s tests:
What it is
When do you use it
Antiglobulin test: look for antibodies to RBC
- Indirect antiglobulin test: ab to parties serum (used in cross matching blood)
- Direct antiglobulin test (DAT): detects ab to own serum (used in autoimmune haemolytic anaemia)
What do you order for coagulation tests
Prothrombin time (PT) Activated partial thromboplastin time (APTT) APTT 50:50 Fibrinogen levels (Thrombin time)
Which tests measures extrinsic pathway of clotting cascade
Prothrombin Time: II V VII X TF Warfarin
Which tests measures the intrinsic pathway of clotting cascade
APTT VIII IX X XI XII VWD
More?
Factor VIII deficiency disorder
Haemophilia A
Factor IX deficiency disorder
Haemophilia B
Which factor are vit K dependent
II, VII, IX, X
Protein C and S
Diagnostic triad of bleeding disorders
- Personal history of bleeding
- bruising, epistaxis, GIT, menses, urine
- surgical and dental history, cuts and injuries - Family history of bleeding
- Known bleeding disorders
- bleeding in family members - Supportive lab tests
- platelets
- coagulation
- clot stability
What do you do for platelet tests
FBC
Microscopy
PFA (platelet function assay)
What can the APTT 50:50 test show
If prolonged PT or APTT
And with 50:50 mixture:
If correct: factor deficiency
If fails to correct: factor inhibitor
Haemophilia A
- aetiology
- clinical features
- investigations
- management
Aetiology
-Factor VIII deficiency, X linked
Clinical features (same as haemophilia B)
- severe (levels of <1 IU/dL): frequent spontaneous bleeding (into joints and muscles). Can dad to crippling joint deformity
- moderate (levels 1-5 IU/dL): sever bleeding post surgery + occasional spontaneous bleeds
- mild (>5 IU/dL): bleeding post surgery + injury
Investigations:
- personal and family history
- prolonged APTT and reduced FVIII
Management:
- RICE (rest, immobilise, cool, elevate)
- factor VIII (3 times a week)
- for mild Haemophilia: desmopressin (DDAVP): releases stores of FVIII
- tranexamix acid (anti-fibrinolytic): oral
Haemophilia B
- aetiology
- clinical features
- investigations
- management
Aetiology:
-factor IX deficiency, X linked
Clinical features (same as haemophilia A)
- severe (levels of <1 IU/dL): frequent spontaneous bleeding (into joints and muscles). Can dad to crippling joint deformity
- moderate (levels 1-5 IU/dL): sever bleeding post surgery + occasional spontaneous bleeds
- mild (>5 IU/dL): bleeding post surgery + injury
Investigations:
- personal and family history
- prolonged APTT and reduced FIX
Management:
- RICE
- FIX (twice a week)
- tranexamix acid (anti-fibrinolytic): oral
Von Willebrand’s disease
- aetiology
- types
- clinical presentation
- diagnosis
- management
Aetiology
-defective platelet function and FVIII deficiency
Types:
- 1: partial quantitative deficiency of vWF (inherited autosomal dominant)
- 2: qualitative abnormality of vWF (inherited autosomal dominant)
- 3: complete deficiency of vWF (inherited recessive)
Clinical features:
- type 1 and 2: mild features (bleeding post trauma +surgery, epistaxis and ménorragie, mucocutaneous)
- type 3: severe bleeding, rarely joint and muscle bleeds of Haemophilia (mucocutaneous)
Diagnosis:
- test FVIII, vW ag, vW activity
- VW activity:vW protein ratio
- type 1 >0.6
- type 2 <0.6
Treatment: -type 1: DDVAP + tranexamic factor -type 2: vWFactor/?DDVAP (but NOT for Type 2b) -type 3: VWFactor \+iron
Virchow’s triad what is it?
Factors that contribute to thrombosis:
Stasis of blood flow, endothelial injury and hypercoagulability
VTE prevention in hospitals
(Risk assessment tool) Early annulation 1. Mechanical -anti-embolism stockings OR -intermittent pneumatic compression sleeves (for surgery) 2. Pharmacological -LMWH (SC) -UFH (low dose unfractionated heparin) (IV) -DOACs (oral) NOT warfarin
VTE risk factors
Age, BMI, varicose veins, air travel, immobility, pregnancy, precious VTE, thrombophilia, oestrogen therapy, plasminogen deficiency
Trauma/surgery, cardiac/resp failure, malignancy, recent MI/stroke, acute illness/infection, IBD, sickle cell
DVT
- symptoms/signs
- investigations
- differential diagnosis
Symptom/signs
-unilateral painful, red/hot, swollen calf (>3cm compared to unaffected leg), engorged superficial veins, ankle oedema, present Homan’s sign, cyanotic discoloration
Investigations:
- DVT Wells score
- proximal leg vein ultrasound, if low risk or can’t be done w/in 4h do
- D-dimer, if pos: anticoagulants
Differential diagnosis:
Cellulitis, ruptured bakers’s cyst, muscle haematoma
PE
- sign/symptom
- investigations
- ECG findings/ABG
Signs and symptoms:
- asymptomatic, acute SoB, pleuritic chest pain, Haemoptysis,dizziness, syncope
- Pyrex is, cyanosis, tac hypnoses, tachycardia, hypotension, raised JVP, pleural rub/effusion
Investigations::
- two-level PE Wells score
- CT pulmonary angiogram, if can’t be carried out straight away (w/in 1h)
- anticoagulants followed by CTPA
ECG findings: sinus tachycardia, AF, right heart strai (RBBB, right axis deviation), S1Q3T3 pattern
ABG hypoxia/T1RF
VTE treatment
LMWH or fondaparinux
(If patient high risk of bleeding: UFH)
Start warfarin and when INR>2, stop LMWH
What are the different fates of thrombus
Dissolution (fibrinolysis)
Propagation
Recanaliation
Embolisation
def embolus
Material which is transported in the blood and lodged at different site
Can be gaseous or solid
Causes of normocytic anaemia
Acute blood loss Chronic disease (or decreased MCV) Bone marrow failure Renal failure Hypothyroid (or increased MCV) Haemolysis (or increased MCV) Pregnancy
Causes of macrocytic anaemia
B12/ folate deficiency Alcohol excess Reticulocytosis Cytotoxics Myelodyaplastic syndromes Marrow infiltration Hypothyroidism Anti folate drugs
what is the cell based model of haemostasis
initiation
amplification
propagation
what is disseminated intravascular coagulation
process of clotting and fibrinolysis dysregulated: widespread clotting and bleeding
how does DIC occur (pathophysiology)
release of procoagulant materials (i.e. TF) or via cytokine pathways (inflame response):
widespread coagulation activation leads to platelet and coagulation depletion + dysregulated fibrinolytic activation
causes of DIC
- malignant disease
- septicaemia
- haemolytic transfusion reactions
- obstretic causes
- trauma, burns, surgery
- liver disease
- snake bite
what is D dimer a breakdown product of?
fibrin
treatment of DIC
- keep warm
- sort out causes
- reverse drugs:
- clotting factors
- fresh frozen plasma
- platelets
- blood transfusion?
- -> TRANSFUSION PROTOCOL
what are the different levels of the neck
- submandibular triangle
sternomastoid muscle divided into 3 areas:
- skull base to hyoid bone
- hyoid bone to circa cartilage
- cricoid cartilage to clavicle
- posterior triangle
- around thyroid cartilage
what is the normal shape of a lymph node, and what is abnormal
normal: oval shaped
abnormal: football shape
when does lymphadenopathy become relevant clinically?
- adult: >1cm or 1.5 at level 2
- paediatrics: > 2cm
- any node w/ associated head neck symptoms that are persistent
what are causes of lymphadenopathy?
- inflammation (infection TB, HIV, bacterial etc)
- malignant (metastatic, lymphoma)
what imaging techniques are good for what cervival lymphadenopathy
US: thyroid and benign nodes
CT: primary disease below hyoid
MRI: primary disease above hyoid
what investigations to do in cervical lympadenopathy?
-full herd and neck exam including endoscopy
-imaging: US, CT, MRI, PET
biopsy FNA core
risk factors for tonsil and tongue cancer
smoking
drinking
HPV
salivary gland lump differentials
- stones (recurrent tender with meals
- tumour (persistent slow grown)
- malignant (rapid growth , pain)
what primary sites metastasise to cervical nodes
breast, stomach, lung, pancreas and thyroid
what diseases have bilateral hi mar lymphadenopathy
- lymphoma
- glandular fever
- TB
- disseminated malignancies
- sarcoid
- ?
presentation of tuberculous lymphadenopathy
chronic, painless mass in the neck (cold abscess)
may rupture through the skin forming chronic discharging sinus
Hodgkin’s disease: age affected
bimodal distribution
15-30
50+
types of Hodgkin’s disease by histological classification
- lymphocyte predominant
- nodular sclerosis (bands of collagen)
- mixed cellularity
- lymphocyte depleted
