Haematology Flashcards
Anaemia = Hb < ?
<130 M
<120 F
Causes of Anaemia
Microcytic (5)
Normocytic (5)
Macrocytic (6)
Microcytic = TAILS (thalassemia, anaemia of chronic disease, iron deficiency, lead poisoning, sideroblastic)
Normocrytic= AAA-SH (aplastic, acute blood loss, anaemia of chronic disease, sickle cell disease, haemolytic)
Macrocytic= FATRBC (folate deficiency, alcoholism/CLD, hypothyroidism, reticulocytosis, B12 deficiency, cytotoxic drugs/anti-folate drugs)
Iron deficiency anaemia is a microcytic hypochromic anaemia from increased blood loss, reduced iron intake and malabsorption.
List 5 presenting features, 2 main investigations + inv considerations and 3 mngmnt options.
Findings from FBC (Transferrin, ferritin, TIBC)
- Angular chelitis, atrophic glossitis, brittle hair, koilonychia, pica
- FBC, blood film, iron studies
- FBC - Low ferritin, low transferrin, raised TIBC
- Blood film - target cells, poikolocytes (pencil)
- investigate underlying cause (ca- colonoscopy?, OGD, bone marrow biopsy)
- iron tables (Ferrous sulfate), iron infusion (IV Cosmofer), blood transfusion
2WW Guidelines for suspected malignancy in iron defiency anaemia
- Which people would you refer for endoscopy urgent review
Men Hb <11
Post menopausal women <10
Finding on blood film - iron def anaemia
Poikolocytes (pencil)
Thalaessemia (autosomal recessive) - types of alpha (4) and beta (2)
Alpha - gene deletions
* silent - affects 1 copy of alpha globin chain
* trait - “ 2
* HbH disease - “3
* fetal hydrops (Bart’s) - “4
* Beta- gene mutations
* minor trait
* major
Inv for thalaessemia = FBC, heamoglobin electrophoresis & genetic testing.
What are the findings from hb electrophoresis for beta thalessemia (3)
Increased HbA2 and HbF
Reduced/absent HbA
HbA is the most common form of Haemoglobin (made from 2x alpha chains, 2 x beta chains.)
Note in alpha thalassemia- hb electrophoresis is typically normal.
Mngmnt thalaessemia
Iron chelation - Desferroxamine
Blood transfusion
prevents the iron overload from repeated blood transfusions
Sideoblastic anaemia:
* type
* mechanism
* cause
* blood film finding
* iron, ferritin and transferrin sats?
* bone marrow finding?
treatment supportive/underlying cause or Pyroxidine
- hypochromic microcytic
- RBCs fail to incorporate iron into haem - ring of iron forms around nucleus; biosynthesis in mitochondrion
- congenital or acquired (chemo, alcohol, myeloproliferative)
- basophilic stippling of RBCs
- high ferritin
- high iron
- high transferrin concentration
- prussion blue staining shows ringed sideroblasts
raised iron because it is not being incorporated into haem (loose)
What causes basophilic stippling (in general)
typical causes
Presence of basophils within the RBC cytoplasm –>
Disturbed erythropoeisis
Can contain fragments of DNA/mitochondria
causes
thalassemia
sideroblastic anaemia
megaloblastic anaemia
lead poisoning
etcetc
Lead poisoning
- presentation
- blood film
- fbc
- mx
- differential
- microcytic anaemia presenting with abdominal pain, peripheral neuropathy and blue stained gingiva.
- also neuropsychotic features, constipation and fatigue
- blood film = basophilic stippling and clover-leaf
- FBC: microcytic anaemia
- reqs chelation (DMSA, EDTA etc)
- acute porphyria - also presents with abdominal pain and neurological signs (but normally raises delta aminolaevulinic acid levels)
Normocytic anaemias - AAASH.
Aplastic anaemia occurs due to a problem within the bone marrow itself. What are its two main presentations?
PRCA
Pancytopenia
Aplastic can be acquired or inherited.
2 types of inherited and 2 causes of acquired?
- Diamond Blackfan & Fanconi syndrome
- Drugs (cytotoxics, antibiotics), infections (EBV, HIV), toxins (benzene).
Features of Fanconi syndrome (inherited aplastic anaemia) (6)
- Facial & skin abnormalities (e.g. microcepahly, cafe au lait spots)
- Absent thumb
- Horsehoe kidney & prox tubule dysfunction
- Aplastic anaemia - pancytopenia
- Intellectual disablity
- Short stature
General sx of haemolytic anaemia
Anaemia + jaundice + splenomegaly
?gall stones
Haemolytic anaemia can be hereditary (affecting membrane, metabolism & haemoglobin) and acquired (immune or non-immune). List 5 causes of hereditary haemolytic anaemia.
- Spherocytosis
- Elliptocytosis
- G6PD deficiency
- Thalassemia
- Si ckle Cell Disease
Key fact for
spherocytosis
- splenomegaly, jaundice & gallstones
- often presents in aplastic crisis during parvovirus inf
Key fact for
elliptocytosis
mostly asx
Triggers for H6PD deficiency (3) acute haemolytic episodes
Meds - sulfonylureas (Gliclazide), CIprofloxacin, and anti-malarials
key facts for
G6PD deficiency:
- genetics
- ethnicity
- haemolysis triggered by (3)
- findings on blood film (main + 3 others)
- reduced NADPH results in..
- ix: blood film & what else?
- management
- X linked, affected African/Medit. newborn babies (M)
- fava beans, certain drugs, infeection
- Heinz bodies (+ ghost, bite, blisters)
- reduced NADPH –> oxidative damage to RBC
- test using G6PD assay and repeat after 3 months
- treat underlying infection, avoid precipitants, transfusion may be needed
key facts for
Sickle cell anaemia
- autosomal recessive
- malaria protective
- presentation = SICKLED: note splenomegaly, priapism and dactylitis (under 3)
- crises & complications
- req tranfusion, imms, hydroxycarbamide (increased fetal hb) long term for pain and prophylaxis for crises
point mutation for SCD, on chr 11
glu- val on beta globin gene
findings on blood film for SCD
Howell-Jolly bodies (sign of hyposplenism) & target cells
presentation: SCD
Splenomegaly
Infarction
Crises
Kidney disease
Liver & lung disease
Erection (priapism)
Dactylitis
Sickle cell crises (4)
General management
1. Thrombotic “vaso-occlusive”
2. Acute Chest Syndrome
3. Sequestration crisis
4. Aplastic
General
Analgesia + O2 + IV Fluids
1. Blockage in organs (lungs, brain, hip)
2. Blockage in pulmonary microvasculature –> infarction in lung parenchyma. Treat with O2, analgesia, Abx
3. Splenic sequestration - sickling of the blood causing pooling within spleen(or lungs) - acute emergency, fall in retics.
4. Triggered by parvovirus infection: fall in Hb, fall in retics
4 - note elliptocytosis can also present like this
The acquired haemolytic anaemias can be classed as immune (Coombs +ve) and non-immune (Coombs -ve).
Name 2 types of each.
Immune
* Cold, occurs <10degrees
* Warm, more common, at >37 degrees
* Non-immune
* Paroxysmal noctural haemaglobinuria
* Microangiopathic (e.g. 2ndary to HUS)
Feature of PNH (paroxysmal nocturnal haemaglobinuria)
A type of acquired haemoltyic anaemia (non-immune, Coombs -ve)
Red urine in morning
Macrocytic anaemias can be megaloblastic (folate & B12 deficiency) and non-megaloblastic.
Folate & B12 deficiency can be caused by malnutrition, malabsorption (Crohn’s, coeliac) or autoantibodies (pernicious).
In pernicious anaemia what antibodies are present? (2)
What Ca does it increase your risk of 3x?
- Auto-abs against gastric parietal cells & intrinsic factor.
- reduced IF and reduced HCl.
- Gastric adenoca
B12 requires intrinsic factor to be absorbed
Presentation of B12 deficiency (3)
- Peripheral neuropathy
- Visual changes - reduced colour vision
- Mood changes (e.g. irritability)
- Anaemia sx - note glossitis
B12 deficiency can lead to SACDC. What tracts does this affect, and how does it present?
- Combined = both lateral corticospinal and dorsal columns.
- Sensory loss but preserved pain/temperature sensation
- Mixed UMN and LMN signs (e.g. spastic paresis)
Treatment for B12 deficiency
Can it reverse SACD?
- B12 supplementation (hydroxycobalamin - parenteral, or cyanocoblamin - oral)
- No.
Main difference between acute & chronic leukaemias
Acute - present with acute symptoms, with cytopenia
Chronic - often asx initially and gradual onset, with cytosis
Where are folate and B12 absorbed from?
Small intestine:
folate (prox jejenum)
B12 (term ileum)
Acute Leukaemias
* what is the main pathophysiology resulting in bone marrow failure in ALL and AML?
* 3 features of bone marrow failure
- impaired differentiation
- excessive proliferation of immature cells (blast cells)
- which compete with healthy bone marrow cells
- resulting in cytopenia
E.g. - AML - myeloblasts, thrombocytopenia
- ACL - lymphoblasts, neutropenia
Features of BMF - Anaemia - pallor, fatigue, Neutropenia - frequent infections, Thrombocytopenia - easy bruising, bleeding. Bone marrow failure affects all blood cells except lymphocytes (which are formed in the thymus/bone marrow and mature in lymph nodes).
AML
* age affected?
* risk factors (2)?
* prognosis?
* blood film findings (2)?
- Adults - most common adult leukaemia
- myelodysplastic syndrome and myeloproliferative disroder
- worst
- blast cells & auer rods
ALL
* age affected?
* risk factors (2)?
* prognosis?
* blood film findings (2)?
- children - most common childhood cancer
- Down’s syndrome, Philedelphia chromosome (in some)
- 3/4 children complete recovery
- blast cells
Chronic leukaemias
Mechanism behind the cytosis seen on blood film
- Excess proliferation of (more) mature cells (further down the line) than acute leukaemias.
- the mature cells have partial functionality
- but because more mature, no competiton in bone marrrow
- aka on blood film - absence of blast cells
- also anaemia due to myelofibrosis
CML - ALL CML have the philedelphia chromsome
Philedelphia chromosome translocation?
what does it code for?
what drug targets it?
- t(9:22)
- results in BCR:ABL gene
- codes for tyrosine kinase
- Imatinib - tki, for CML
CML
* age affected?
* risk factors (2)?
* prognosis?
* blood film findings (2)?
- adult
- Philedelphia chrom(95% of CML have it)
- poor
- excess cells from myeloid lineage: thrombocytosis + increase in granulocytes at different stages of maturation (eosniophilia and basophilia)
- and anaemia
CLL
* age affected?
* risk factors (2)?
* prognosis?
* blood film findings (2)?
* complications (2)
hint (sudden transformation, type of anaemia, reccurent infections)
- Adults - most common of all leukaemias
- TP53, Trisomy 13
- good
- smudge cells
- Richter transformation (to NHL), hypogammaglobulinaemia, warmAIHA
Lymphoma = Hodgkin’s-
most common subtype: nodular sclerosing
- blood film finding
- age
- risk factors (2)
- common presenting symptom
- rx
- Reed-Sternberg cells
- 20s and 60s (bimodal)
- infection (EBV) and autoimmune
- tender lymphadenopathy after alcohol
- chemo (ABVD) and radio x
Which is more common - HL or NHL?
NHL
Lymphoma - Non-Hogkins - subtypes:
B cell
* Slow growing mass, often multiple sites?
* similarto above
* Common childhood cancer worldwide, causing “starry sky appearance on biopsy”, and associated with EBV?
* Associated with H.pylori?
T cell
* As?sociated with Coeliac disease?
- Diffuse large B cell
- Follcular
- Burkitt’s
- MALT
- T cell lymphoma of intestine
note starry sky als a finding on renal biopsy for post-strep GN
Investigation = typical haem ones like FBC & blood film. What other lymphoma specific inv are of use? (3)
+ Treatment (HL/NHL)
- Lymph node biopsy, PET scan (extra-nodular disease), CT-TAP/Neck for staging
- Chemo/radio
- HL- ABVD
- NHL - R-CHOP
What is myeloma, describe its hallmark feature, and how it presents (CRABBI)?
- cancer of the plasma cells (type of b cell that produced Abs & cytokines)
- proliferation of monoclonal antibodies (IgG or IgA)
- hypercalcaemia, renal failure, anaemia, bone pain/#s - back. bleeding, recurrent infection
- also causes hypercoaguable stae (risk of stroke) - due to inflammation from cancer and from paraproteinaemia (clot aggregation)
hypercalcaemia and bone lesions due to cytokines –> osteoclastic activity, mobilisation of calcium from bone to blood
Myeloma investigations
* electrophoresis:
1. urine
2. serum
* Bloods - serum immunoglobulins; U&E, Calcium, FBC
* Blood film
* Bone marrow aspiration
* Imaging - what is first line?
* what finding may be present from xrays?
Diagnostic criteria: 1 major and one minor or 3 minor.
Major = bone marrow aspiration shows plasmacytoma (biopsy) and >30% plasma cells; and raised M proteins (serum electrophoresis)
Minor - 10-30% plasma cells, minor elevations of M protein, osteolytic lesions, low levels of other antibodies (non-cancerous) in blood
- Bence-Jones proteins
- M protein
- monoclonal paraprotein (IgG and IgA); renal failure, hypercalcaemia, anaemia, thrombocytopenia
- roleaux formation (stacked RBCs)
- confirms diagnosis - excess plasma cells
- whole body MRI
- rain drop skull (similar to pepperport skull of hyperparathyroidism)
Both are due to light chain deposition
Myleoma - management (4)
- Chemo
- Bisphosphonates
- Radio - bone lesions
- Autologous stem cell transplant
Myeloproliferative disorders are when there is chronic prolfieration in the myeloid cell lines (RBCs, granulocytes, thromboyctes).
Which leukaemia are they risk factors for?
Acute myeloid leukaemia (AML)
What condition is caused by proliferation of the following cells:
- RBC
- Megakaryocyte
- Thrombocyte
- Polycythaemia vera (=erythrocytosis)
- Myelofibrosis
- Primary thrombocythaemia
Primary polycythaemia vera mutation
JAK-2
What condition presents with massive hepatosplenomegaly, and 1 in 2 patients are JAK 2 +VE?
What is this caused by?
What accompanies this?
Massive –>
mega (karyocyte) proliferation –>
primary myelofibrosis
. Note DRY TAP!
Myelofibrosis= scar tissue develops in bone marrow –> extra-medullar haematopoesis –> splenomegaly
Symptoms of hypermetabolism - weight loss/ night sweats
Patients with PV and thrombocythaemia have increased risk of thrombosis and erythromelagia - what is this?
Sudden burning pain in hands and feet + red skin
What are MDS (myelodysplastic syndromes)?
Risk factors?
Like myeloproliferative disorders what can they also progress to?
How do they present?
Blood film shows blasts; bone marrow biopsy diagnostic.
Mx - supportive, immunosuppressive, disease modifying therapy, growth factors, or haemaotopeotic stem transplant
- Ineffective haematopoeisis due to mutations in haematopoetic stem cells.
- Age; chemo/radio. 90% primary, 10% secondary to chemo/radio therapy.
- Risk of progression to AML
- Sx of bone marrow failure
Amyloidosis (a paraproteinanaemia) - key points(3)
- depositon of amyloid protein in multiple organs (kidneys, heart, nerves, GIT)
- problem within bone marrow due to dysfunction in plasma cells –> production of light chains
- congo-red staining?
- sx depend on which organ is affected
- similar treatment to myeloma
Bleeding disorders
Factors involved in the
- intrinisic pathway
- extrinsic pathway
- final common pathway
of the clotting cascade
- Intrinsic = 12, 11, 9, 8
- Extrinsic = 7
- Common = 10 (Factor X), 5, 2 (prothrombin), 1 (thrombin)
Coagulation tests
APTT
PT
- APTT: detects problems in clotting factors in the intrinsic cascade + final common pathway (12, 11, 9, 8 + 10, 5, 2, 1)
- PT: extrinsic + FCP (7 + 10, 5, 2, 1)
Von-Willebrand disease is the most common acquired clotting disorder.
- What is the function of the VWF protein?
- how do the three types of VWD differ from eachother?
- Majority of VWD are autosomal recessive or dominant?
- VWF stabilises Factor 8 (intrinsic pathway) and promotes platelet adhesion
- Types 1-3 from least to most severe VWF is either reduced, abnormal or absent.
- Majority are autosomal dominant (types 1 and 2)
Blood findings from coag screen for VWD
- Increased APTT (dysfunctional intrinsic pathway)
- Increased bleeding time (PFA-100)
Bleeding disorders can be classified broadly into vascular, platelet, and coagulation (clotting factor) disorders.
Name 3 types of inherited coagulation disorders and 2 acquired?
Inherited:
* VWF disease (technically affects clotting factors AND platelets)
* Haemophilia A - Factor 8 deficiency (intrinsic)
* Haemophilia B - Factor 9 deficiency (intrinsic)
Acquired
* Liver disease
* Vitamin K deficiency
* Warfarin/anticoagulant use
List 4 types of vascular disorders
- Ehlers-Danlos
- Vitamin C deficiency
- Hereditary haemorrhagic telangiectasia (HHT)
- Infection, steroids, vasculitis
- Senile purpura
4 diagnostic features of HHT
- Epistaxis
- Telangiectases at multiple sites
- Visceral lesion (e.g. GI bleed or AVM)
- FHx
Classify platelet disorders and give 2 examples for each
-
Reduced quantity: ITPP, essential thrombocytopenia, dilutional, bone marrow failure (aplastic anaemia/drugs), megaloblastic anaemia, auto-immmune processes
Reduced quality - congenital causes (rare) e.g. Gp1b deficiency (Bernard-Souler) or GPIIb (Glanzmann’s)
Which clotting factors do haemophilia A and B affect?
How does haemophilia A (more common) present?
A - Factor 8 - haemarthroses, post-op bleeding
B -Factor 9
Rx for VWD/haemophilia (3)
Desmopressin
Tranexamic acid
Infusion of VWF/F8
What is disseminated intravascular coagulation (DIC)?
Finding on blood film?
Finding on FBC/coags?
What is its medical treatment?
Example patient: pt presents with episataxis post op, low plt and fibrinogen, raised APTT/INR, raised D-dimer
- Extensive clot production AND bleeding triggered by trauma/surgery/infection
- low plt, prolonged pt/aptt, low plasma fibrinogen, elevated d dimer
- Schistocytes: due to microangiopathic haemolytic anaemia
- Caused by sepsis, malignancy, trauma, obs etc
- Main contributor is tissue factor (TF)
- Reqs FFP/Plt & heparin
Typical blood picture for DIC
- PT and APTT
- FIbrinogen
- Fibrinogen degradation products
Thrombin time = fibrinogen function
- Increased
- Decreased (as being used to make fibrin)
- Increased
What is thrombophilia?
A disorder predisposing to (venous) thrombosis, inh/acq
Most common cause of inhr thrombophilia
Factor V Leiden (deactivation of 5 and 8)
Prevalence of thrombosis with Factor V Leiden disease (heterozygous form)
5%
(homozygous 0.05%)
acquired cause of thrombophilia (2)
- anti-phospholipid syndrome
- progesterone in OCPs
Complications of haematological malignancies
The umbrella term for conditions causing:
A raised RBC/Hct >05
Raised WCC >100
Raised plasma proteins
Hyperviscosity syndrome:
e.g. polycythaemia vera
leukaemia
myeloma/Waldenstrom’s
Complications of haem malignancies
- caused by chemotherapy (rarely- steroids) or lymphoma/leukaemia without chemo
- breakdown of tumour releases chemicals
- raised K+, raised PO4-, AKI evidence from Urea&Cr
- prevent: Iv Rasburicase and IV fluids or Allopurinol
-
Tumour lysis syndrome
What is the MOA for the DOACS Rivaroxaban/Apixaban/Edoxaban?
How can they be reversed (except Edoxaban)?
- Factor Xa Inhibitors
- Andexanet alfa (recombinant human form factor xa)
MOA of Dabigatran (DOAC) &
Reversal agent
Direct thrombin inhibitor
Idarucizumab
Indication/contra-indication for different blood products
1. Packed Red Cells
2. Fresh Frozen Plasma
3. Cryoprecipitate
4. VWF concentrate
5. Platelets
6. SAG-Mannitol blood
- Anaemia; malignancy (solid tumour). When a smaller volume of blood is rewd (to prevent CVS compromise).
- Contains clotting factors, Immunoglobulins and albumin. Corrects coagulopathies; e.g. liver disease/malnutrition.
- Supernantant of FFP. Contains Factor VIII and fibrinogen; for Haemophilia A or severe Fibrinogen deficiency.
- For VWF deficiency
- For thrombocytopenia (acute leukaemia/chronic low plt). Does not require cross-matching. Risk of NHFR. Highest risk of bacterial contamination ((e.g. contraindicated if immunocompromised).
- Serum removed; red cells washed and replaced in solution ( sodium chloride, adenine, mannitol etc). Long shelf life / pts at risk of severe allergic reactions?
Blood transfusion reactions
1. Non-hemolytic febrile reaction
2. Minor allergic reaction
3. Anaphylaxis
4. Acute haemolytic reaction
5. TACO
6. TRALI
What is the main difference between TACO and TRALI?
- Temp rise during administration of product. Due to host’s antibodies against WC fragments in donor blood; and leaked cytokines. Slow/stop/monitor.
- Due to foreign plasma proteins. Pruritus & urticaria. Slow/stop/monitor.
- Type 1 hypersensitivty. Stop/IM adrenaline.
- Due to ABO incompatability. Fever, abdo pain, hypotension. Stop, identity check, send blood for Coombs test.
- Transfusion associated circulatory overload - due to rapid rate of transfusion or exisitng HF. Stop –> ?furosemide.
- Transfusion related acute lung injury - non-cardiogenic lung injury; host neurtrophils –> increased vascular permeability. Stop infusion - titrate O2, give IV fluids and consider escalation of care. Bilateral coarse crepitations =noncardiogenic pulmonary oedema.
TACO = raised BP, requires diuretics. TRALI = low BP - hypotension, requires IV fluids, O2
patients with NHL must receive what to prevent taGVHD?
irradiated blood products
Signs of hyposplenism -e.g. post splenectomy, coeliac disease
Target cells
Howell-Jolly bodies
Pappenheimer bodies
Siderotic grtanules
Acanthocytes
Myelofibrosis
a myeloproliferative disorder
Blood findings:
- FBC
- Blood film
- Bone marrow biopsy (alternative?)
- Urate levels and LDH
- Anaemia
- high WCC and thrombocytosis
- tear drop poikolocytes
- dry tap - need trephine biopsy
- raised urate and raised LDH (high bone turnover)
