Haem Flashcards
How to replace B12/folate?
1mg B12 injections 3 times per week for 2 weeks, then once every 3 months
5mg folate tablets also, but not before B12 as risks SACD
think BeFore - B before F
Causes of high ferritin without iron overload?
With iron overload?
How to tell if there is iron overload?
Without (90%):
- inflammation (acute phase protein)
- alcohol excess
- liver disease
- CKD
- malignancy
With:
- Haemochromatosis
- repeated transfusions
Normal values of transferrin saturation normally excludes iron overload (<45% females and <50% males)
Difference between direct and indirect Coombs test?
Direct (DAT):
To test for haemolytic anaemia
Patients RBC are mixed with anti-human Ig (antibodies against human antibodies)
If they are present the cells will agglutinate
Indirect:
Tests for Ig in patient’s plasma (e.g. prenatal for anti-D and before blood transfusion)
Patient’s plasma mixed with donor blood
If Ig present, these will attach to RBC surface
As before, anti-human Ig added, causing agglutination if Ig have attached to RBC surface
If suspected DVT what should you do if:
- DVT likely?
- DVT unlikely?
2 level wells score
If score 2+ (likely):
- USS doppler within 4 hours
- if cannot be done within 4 hours, D-dimer and give anticoagulation; ensure USS within 24 hours
- if scan negative but D-dimer positive, stop anticoagulation and repeat scan in 6-8 days
If score <2 (unlikely):
- D-dimer
- if neg, other diagnosis
- if pos, doppler USS within 4 hours - again if cannot be done anticoagulate in meantime
Rx for DVT?
If renal failure or anti-phospholipid syndrome?
Normally:
- DOAC (apixaban/rivaroxaban)
- LMWH
- Dabigatran
- Warfarin
If eGFR<15 or antiphospholipid syndrome:
- LMWH
- Warfarin
4 most sensitive clinical signs of PE?
Tachypnoea (96%)
Crackles (58%)
Tachycardia (44%)
Fever (43%)
If suspected PE what should you do to investigate?
PE rule out criteria (PERC)
then 2 PE level Wells score
If >4 points (likely):
- arrange immediate CTPA - if there is a delay then anticoagulate
CTPA +ve - diagnosis
CTPA -ve - leg doppler USS
If <=4 (unlikely):
- D-dimer
+ve then CTPA and anticoagulate
-ve then stop any anticoagulation and consider alternative
Apart from Wells, CTPA etc, what else should be done for suspected PE?
ECG:
- sinus tachycardia
- S1, Q3, T3 in 20%
- RBBB or RAD may occur
CXR:
- Recommended for all patients whilst waiting on CTPA to rule out other pathology
- Typically normal in PE - may show wedge-shaped opacification
Treatment of PE?
Haemodynamic instability?
Repeat PE?
Normally:
- DOAC (apixaban, rivaroxaban)
- LMWH
- Dabigatran
- Warfarin
If eGFR <15 or anti-phospholipid syndrome:
- LMWH
- Warfarin
If haemodynamically unstable:
thrombolysis
OR
thrombectomy (if facilities available)
In repeat PE, IVC filters may be used
Length of anticoagulation in DVT/PE?
If provoking factor e.g. immobilisation following surgery, COCP - this transient risk will pass:
3 months
If unprovoked or cancer:
6 months and calculate HASBLED score
Monitoring of unfractioned heparin?
Monitoring of LMWH?
aPTT
LMWH - no monitoring
Polycythaemia rubra vera:
- What is it?
- features?
- management?
- prognosis?
Clonal proliferation leading to increased red cells. May also be accompanying increased neutrophils and PLT
Features:
- itch - worse when hot
- ‘ruddy complecion’
- Splenomegaly
- hyperviscosity
- JAK2 +ve
Rx:
- aspirin
- venesection (keep Hb normal)
- chemo - hydroxyurea (slight increased risk of secondary leukaemia)
Prognosis:
- thrombotic events common
- 10% progress to myelofibrosis
- 10% progress to acute leukaemia (risk increased with chemo)
Sickle cell crises:
- thrombotic?
- sequestration?
- acute chest?
- aplastic?
- haemolytic?
Thrombotic: vaso-occlusive, caused by infection/dehydration. Clinically diagnosed from pain. Infarcts occur in various organs including bones (AVN)
Sequestration: pooling in spleen or lungs with worsening anaemia
Acute chest: chest pain, dyspnoea, bilateral infiltrates on CXR, low pO2. Commonest cause of death after childhood.
Aplastic: caused by parvovirus B19, sudden fall in Hb
haemolytic: rare, increased rate of haemolysis
Features of G6PD deficiency?
What is seen on film of G6PD deficiency?
Diagnosis?
Inheritance?
Features: intravascular haemolysis, gallstones, splenomegaly (neonatal jaundice common)
Heinz bodies
Bite cells
Blister cells
Diagnosis: G6PD enzyme assay - check levels 3 months after acute haemolysis
X-linked recessive
Hereditary spherocytosis inheritance?
features?
Diagnosis?
Management acute and long-term?
AD
Failure to thrive, jaundice, gallstones, splenomegaly, MCHC elevated
Parvovirus causes aplastic crisis
spherocytes on film
Diagnosis: EMA binding test
Management:
acute - supportive, transfusion
long term - splenectomy, folate supplements
What is seen in hyposplenism on film?
Howell-Jolly bodies
Pappenheimer bodies
Target cells
Can LMWH cause heparin-induced thrombocytopaenia?
How can it cause a PE?
Yes
Heparin/LMWH binds to a platelet factor on the surface and causes an immune response. Some people form IgG which bind to the heparin-PF4 complex, which can actually activate the platelet, causing a clot
Primary haemostasis?
Vessel wall damage exposes collagen which platelets bind to via vWF
Platelets activated and change shape, release ADP and TXA2 which stimulate aggregation,
Extrinsic pathway?
Measurement?
Most important
Tissue factor (factor 3) is released from damaged vessel walls and binds to factor 7
TF/7 converges on common pathway and activates factor 10
Measure: PTT
Intrinsic pathway?
Measurement?
Amplification of response
Exposed collaged activates factor 12
12-11-9
9a binds and activates 8
9a/8a converge on common pathway
Measure: aPTT
Common pathway?
TF/7 or 9/8 activate 10
10a binds 5a to activate prothrombin (2) to thrombin (2a)
This converts fibrinogen to fibrin
Control of haemostasis?
ATIII - protease that blocks all pathways of the cascade
Protein C/S - proteins that are on the surface of platelets and inhibit factor 5/8
Fibrinolysis - breakdown of fibrin by plasmin, which is activated from plasminogen by tissue plasminogen factor
ITP?
Autoimmune condition against platelets in adults or children
Isolated low platelets
Kids: aged 2-6, self-limiting post-infection
Adults: variable and fluctuating course
1st line - steroids
2nd - pooled IVIG
TTP:
- what is it?
- what gene?
- features?
- bloods?
- film?
- management?
Emergency characterised by thrombocytopaenia + MAHA - widespread micro-thrombi and intravascular haemolysis, caused by a trigger
ADAMTS-13
Fever, bleeding, AKI (haematuria + proteinuria), fluctuating CNS signs (drowsy, confusion, seizures)
Bloods:
profound thrombocytopaenia
MAHA: low Hb, high LDH, high bili, low haptoglobin
NORMAL COAGULATION
Film: schistocytes
Management: Plasmapheresis
Management of HUS?
Supportive - no role for abx
Causes of severe thrombocytopaenia?
Mild?
ITP
TTP
DIC
Malignancy
Mild:
- heparin-induced
- drugs - diuretics, aspirin, thiazides
- alcohol, liver disease
- hypersplenism
- pregnancy
- SLE/APS
- B12 def
Causes of thrombocytosis?
Reactive - acute phase reactant
Malignancy
Hyposplenism
Essential thrombocytosis
What is essential thrombocytosis?
Features?
Mutation?
Management?
Myeloproliferative disorder which overlaps with CML and polycythaemia rubs vera and myelofibrosis. Megakaryocyte overproduction causing increased PLT
Both arterial or venous thrombus or haemorrhage can be seen
Characteristic symptom - burning sensation in hands
JAK2 mutation
Management - hydroxyurea
aspirin
interferon a in younger people
What is seen on coag of vWD?
increased aPTT and bleeding time
low vWF and factor 8
Haemophilia A and B?
Seen on coag?
A = factor 8 def B = factor 9 def
Coag: increased aPTT
Factor infusions
Seen on coag of liver disease?
Increased PTT/aPTT
May be increased TT if production of prothrombin reduced
Causes of abnormal platelets?
Drugs: NSAIDs, aspirin, anti-platelets
Systemic: renal/liver disease
Haem: paraprotein/myeloproliferative disease
Bloods for DIC?
Management?
D dimers - high PLT - low Bleeding - high PTT, aPTT, TT - long Fibrin degradation products - high Film: schistocytes
Management:
- Treat underlying cause
- PLT transfusion
- FFP
- Cryoprecipitate
- RBC infusion
General what causes an increase in:
- PTT?
- aPTT?
- TT?
- Everything?
PTT - liver disease, warfarin
aPTT - haemophilia, vWD, heparin
TT - heparin, advanced liver disease
everything - DIC
Coag for ITP?
low PLT
Coag for TTP?
low PLT
low Hb, high LDH, low haptoglobin, schistocytes
Coag for vWD?
increased aPTT
low factor 8
Coag for haemophilia?
increased aPTT
Coag for liver disease?
Increased PTT, aPTT, late on increased TT as well
Coag for vitK def/warfarin?
Very high PTT, high aPTT
Coag for heparin?
high PTT, very high aPTT and TT
MOA heparin? Excretion? Coag? Monitoring? When to stop before surgery?
potentiates ATIII, inhibits factor Xa
(LMWH Xa only, unfractioned also 2, 9, 11 and 12)
Renal
Coag - increased PTT, very high aPTT and TT
Monitor - aPTT
Before surgery - stop the day before
Fondaparinux MOA?
Also potentiates ATIII to inhibit factor Xa
Warfarin change in coag?
When starting warfarin?
Monitoring?
When to stop before surgery?
Very high PTT, high aPTT
Cover with heparin for a couple of days
INR - modified PTT compared to international normal
2-3 = DVT, PE, AF
3-4 = VET on warfarin, APS, metallic valve
- check INR daily until within range 2 days in a row, then check twice weekly then weekly. Once stable check every 6-12 weeks
5 days before surgery
What can potentiate warfarin?
Liver disease
Cranberry juice
P450 inhibitors (cipro, amiodarone, valproate)
NSAIDs
Management of warfarin if:
- major bleeding?
- INR 5+, minor bleeding?
- INR >8, no bleeding?
- INR 5-8, no bleeding?
Major: stop warfarin, IV vit K and prothrombin complex concentrate
INR 5+, minor bleed: Stop warfarin, IV vit K, restart when INR <5
INR >8, no bleeding: stop warfarin, oral VitK using IV preparation, restart when INR <5
INR 5-8, no bleeding: withhold 1-2 doses of warfarin, reduce maintenance dose
MOA Dabigatran?
2a inhibitor
Causes of inherited thrombophilia?
Factor V leiden (protein C resistance) - most common
Prothrombin mutation - 2nd commonest
Others:
- ATIII, protein C or protein S deficiency
Causes of acquired thrombophilia?
APS
COCP
when to consider thrombophilia?
Recurrent VTE or miscarriage
VTE <40y/o
VTE in unusual place e.g. mesenteric/cerebral veins
Common lymphoid precursor produces?
Common myeloid precursor?
Common erythroid precursor?
Lymphoid: T, B and NK cells
Myeloid: granulocytes - neutrophils, basophils, eosinophils, macrophages
Erythroid: PLT, RBC
What drug can cause neutrophilia?
Steroids (due to reduced marginisation)
What are atypical lymphocytes in glandular fever?
Increase in cytoplasm and wrapping around the cell
What causes conversion to Fe3+?
Oxidative stress
What controls iron absorption via down regulation of ferroportin in response to iron load and inflammation?
Hepcidin
Iron, ferritin and TIBC in:
- haemochromatosis?
- iron deficiency anaemia?
- AOCD?
- thalassaemia?
Haem: iron and ferritin raised, TIBC low
Iron def: iron and ferritin low, TIBC high
AOCD: iron low, ferritin high, TIBC low
Thalassaemia: iron normal or high, ferritin normal or high, TIBC normal
Main 3 causes of microcytic anaemia
Iron def
Thalassaemia
AOCD
Iron replacement if uncomplicated?
200mg ferrous fumarate/sulfate TDS for a minimum of 3 months
What is seen on film with a thalassaemia trait?
Heinz bodies - accumulations of B globin tetramers
What is seen on film in HbH?
On HPLC?
Management?
Heinz bodies, target cells
HPLC - low HbA, HbA2 and HbF
High HbH - with B globin tetramers
Folic acid
Intermittent transfusions
May need splenectomy
Physical features of B thalassaemia major?
CXR?
HPLC?
Management?
Severe anaemia
Extramedullary haematopoiesis - hepatosplenomegaly, skull bossing
CXR - hair on end sign
HPLC - High HbF, HbA2, low HbA
Regular transfusions and iron chelators (desferrioxamine)
Where are folate and B12 absorbed in bowel?
Folate - duodenum
B12 - ileum
In pernicious anaemia which Ig’s are sensitive and specific?
Anti-parietal cell - sensitive, not specific
Anti-IF - specific, not sensitive
What is seen on film of B12 deficiency anaemia?
Hypersegmented neutrophils
Howel Jolly bodies
Causes of non-megaloblastic macrocytosis (may not have anaemia)?
Alcohol
Pregnancy
Hypothyroidism
Liver disease - TARGET CELLS
Marrow failure - myelodysplasia/aplastic anaemia
- unlike the others this will always cause anaemia
What causes spurious macrocytosis?
Reticulocytosis
Cold agglutination
(reticulocytosis - haemolysis, haemorrhage, treatment of anaemia, thalassaemia)
3 hallmarks of extravascular haemolysis?
Hepatosplenomegaly
Protoporphyrin release (converted to unconjugated bilirubin, causing jaundice and pigment gall stones)
Urobilinogen (normal products in excess)
Hallmarks of intravascular haemolysis?
Schistocytes
Increased LDH
Low haptoglobin
Haemoglobinaemia
Causes of extravascular haemolysis?
Thalassaemia
Sickle cell
Hereditary spherocytosis
Autoimmune haemolytic anaemia
Woman returns from Haiti 25 days ago and has fever/chills on alternating days, headache and myalgia. O/E temp 39, hepatomegaly - what is it?
Malaria
Platelet transfusion limit in active bleeding?
30 in most cases
Can be up to 100 if bleeding at critical site such as CNS
Platelet transfusion limit for pre-invasive procedure?
50 for most
50-75 if risk of bleeding
100 if surgery at a critical site
Platelet transfusion threshold if no bleeding or planned invasive procedure?
Contraindications for platelet transfusion? (4)
10
Contra:
- Chronic bone marrow failure
- ITP
- Heparin-induced thrombocytopaenia
- TTP
Atypical blood cells seen on film with hyposplenism?
Howell-Jolly bodies
Target cells
Pappemheimer bodies
Seen on film with iron-deficiency anaemia?
If combined iron deficiency/B12 deficiency?
Fe def:
- target cells
- pencil poikilocytes
- microcytic hypochromic
Mixed:
- microcytic and macrocytic (dimorphic) film - so MCV often normal
What to prescribe to people with heart failure who are receiving packed red cells?
Furosemide dose STAT - even if already on it
What can polycythaemia rub vera progress to?
AML
Myelofibrosis
Management of vWD in mild bleeding?
What can raise levels of vWF?
What else can be given if severe?
Mild - tranexamic acid
Desmopressin can raise levels of vWF by inducing release of vWF from endothelial cells
Factor VIII concentrate
Commonest ages of Hodgkin’s?
Bimodal peak - 30’s and 70’s
Types of Hodgkin’s?
Typical symptoms?
- Nodular sclerosing - most common - good prognosis
- Mixed cellularity
- lymphocyte predominant - best prognosis
- lymphocyte depleted - rare, worst prognosis
‘B’ symptoms - weight loss, fever, night sweats
Presence of B symptoms are assoc w a poor prognosis
How is tranexamic acid given in major haemorrhage?
IV bolus followed by slow infusion
Features of Waldenstrom’s Macroglobulinaemia?
Lymphoplasmacytoid malignancy characterised by secretion of monoclonal IgM paraprotein
Weight loss, lethargy
Hyperviscosity - visual disturbance, stroke etc
Hepatosplenomegaly
Cryoglobulinaemia e.g. Raynaud’s
Renal function fine
No bone lesions on skeletal survey
What is generally given 1st line in DIC after resus measures?
FFP or cryoprecipitate
Over how long is a unit of RBC transfused in non-urgent cases?
90-120 mins
What malignancy might EBV cause?
Non-hodgkins lymphoma (specifically Burkitt’s)
Apart from biopsy, what in Hx can help differentiate hodgkin’s from non-hodgkin’s?
Hodgkins get alcohol-induced pain
B symptoms typically occur later in non-hodgkins
Extra nodal disease is commoner in non-hodgkins (marrow failure, bone pain, gastric, CNS, testicular)
Ix for lymphoma?
What are good prognostic indicators?
- biopsy
- CTCAP - staging
- FBC - rule out leukaemia
Offer HIV - RF for non-hodgkin’s
LDH and ESR - prognostic indicator
Staging of lymphoma?
- one node
- more than one node on same side of diaphragm
- nodes on both sides of diaphragm
- extra-nodal disease
Commonest type of non-hodgkin’s lymphoma?
Specifically associated with immunosuppressed?
Rarest?
Other types?
Commonest - diffuse large B cell (40%) - high grade but these typically respond better to chemo
Burkitt’s - immunosuppressed, young, ‘starry-sky’, c-myc mutation
Rarest - Mantle cell
Others - follicular - low grade
Cutaneous T cell - quite rare
What DOAC should be avoided in kidney failure?
What one should be used?
Dabigatran - renally excreted
Use Apixaban - faecally excreted
(Rivaroxaban is hepatic ally excreted)
How long should cancer patients get VTE prophylaxis after DVT/PE?
6 months
Exception to the rule
Indications for cryoprecipitate use?
What is its major constituent?
Major haemorrhage and haemophilia
Major constituent = factor VIII
What leukaemia can cause raised platelets?
CML
Management of APS in pregnancy?
Aspirin as soon as pregnancy confirmed
LMWH once foetal heart is seen (around 6-7 weeks) and discontinued at 34 weeks
Are any Ix needed to be performed in sickle cell crises?
No, clinical diagnosis
What is seen on film with sickle cell disease?
Howell-Jolly bodies
Target cells
(due to hyposplenism)
How often should sickle cell patients be given the pneumococcal vaccine?
Every 5 years
Common presentation of sickle cell in late infancy?
Hand-foot syndrome - both hands and feet get swollen
Management of post-thrombotic syndrome?
Stockings
