Haem Flashcards
Risk a child will be a carrier of beta-thalassaemia trait if both parents are carriers?
50%
Risk a child will have beta-thalassaemia trait if both parents are carriers?
25%
Risk a child will be unaffected if both parents are carriers beta-thalassaemia trait?
25%
Macrocytosis, anaemia, and hypersegmented polymorphonuclear cells on blood film, peripheral neuropathy and glossitis
Pernicious anaemia
Abnormally large and oval-shaped RBCs
Pernicious anaemia
Normochromic-normocytic haemolytic disorder
Sickle cell anaemia
Microcytic and hypochromic anaemia. High transferrin, ferritin and serum iron is low
Iron deficiency anaemia
Hypochromic, microcytic red cells
Additional pencil cells
Occasional target cells
Iron deficiency anaemia
Heinz bodies (denatured haemoglobin secondary to oxidative damage) and bite cells (erythrocytes with an irregular membrane caused by splenic macrophages attempting to remove Heinz bodies)
G6PD
Acute kidney injury, microangiopathic haemolytic anaemia and thrombocytopenia
Escherichia coli
A negative Coombs test indicates…
Non-immune cause of haemolytic anaemia
Macrocytosis and anaemia
Vitamin B12 or folate deficiency, or rarely, pernicious anaemia
Reticulocytosis and macrocytosis but haemoglobin levels are usually normal or increased
Haemolytic anaemia
Non-megaloblastic macrocytic anaemia
Hypothyroidism
High total iron binding capacity (TIBC) with low ferritin
Iron deficiency anaemia
Pancytopenia along with hypocellular bone marrow and absence of haematopoietic cells
Aplastic anaemia
Antiphospholipid syndrome triad
Venous and arterial thromboses, recurrent fetal loss and thrombocytopenia
Mx for APS in pregnancy
Aspirin once pregnancy confirms on urine test
LMWH once fetal heart seen on US until 34 weeks
Most common inherited bleeding disorder?
Von Willebrand’s disease
How is VWD inherited?
Autosomal dominant
VWD behaves like a..
Platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare
3 roles of VWF
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
3 types of VWF
1: partial reduction in vWF (80% of patients)
2: abnormal form of vWF
3: total lack of vWF (autosomal recessive)
Defective platelet aggregation with ristocetin
VWF
Mx for VWF
Tranexamic acid for mild bleeding
Desmopressin
Factor VIII concentrate
Function of Desmopressin (DDAVP)
Raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
Fever, chills
Red cell transfusion (1-2%)
Platelet transfusion (10-30%)
Non-haemolytic febrile reaction
What is Non-haemolytic febrile reaction?
Antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage - normally due to white blood cell HLA antibodies
Mx for Non-haemolytic febrile reaction
Slow or stop the transfusion
Paracetamol
Monitor
Pruritus, urticaria
Minor allergic reaction
What causes minor allergic reaction?
Thought to be caused by foreign plasma proteins
Mx for Minor allergic reaction
Temporarily stop the transfusion
Antihistamine
Monitor
Hypotension, dyspnoea, wheezing, angioedema
Anaphylaxis
What causes Anaphylaxis?
Patients with IgA deficiency who have anti-IgA antibodies
Mx for Anaphylaxis
Stop the transfusion
IM adrenaline
ABC support - Oxygen, fluids
What is acute haemolytic reaction?
ABO-incompatible blood e.g. secondary to human error - red blood cell destruction by IgM-type antibodies.
Fever, abdominal pain, hypotension
Acute haemolytic reaction
Mx for Acute haemolytic reaction
Stop transfusion
Confirm diagnosis:
check the identity of patient/name on blood product
send blood for direct Coombs test, repeat typing and cross-matching
Supportive - fluid
What is Transfusion-associated circulatory overload (TACO)?
Excessive rate of transfusion, pre-existing heart failure
Pulmonary oedema, hypertension
Transfusion-associated circulatory overload (TACO)
Mx for Transfusion-associated circulatory overload (TACO)
Slow or stop transfusion
Consider intravenous loop diuretic (e.g. furosemide) and oxygen
Hypoxia, pulmonary infiltrates on chest x-ray, fever, hypotension
Transfusion-related acute lung injury (TRALI)
What is Transfusion-related acute lung injury (TRALI)?
Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood
Mx for Transfusion-related acute lung injury (TRALI)
Stop the transfusion
Oxygen and supportive care
Often the result of sensitization by previous pregnancies or transfusions
Non-haemolytic febrile reaction
Simple urticaria should be treated in allergic/anaphylaxis reaction by..
Discontinuing the transfusion and with an antihistamine
Once the symptoms resolve, the transfusion may be continued with no need for further workup
Severe sx in allergic/anaphylaxis reactions should be treated by..
Transfusion should be permanently discontinued
IM should be administered and supportive care
Antihistamine, corticosteroids and bronchodilators should also be considered for these patients
Infective transfusion reactions is normally due to..
vCJD
Blood film anisopoikilocytosis, target cells, ‘pencil’ poikilocytes
IDA
Who should be considered for further gastrointestinal investigations with a further gastrointestinal investigations?
Post-menopausal women with a haemoglobin level <100
Men with a haemoglobin level <120
A high TIBC reflects..
Low iron stores
Isolated rise in GGT in the context of a macrocytic anaemia
Alcohol excess
Megaloblastic causes of macrocytic anaemia
Vit B12 deficiency
Folate deficiency
Secondary to methotrexate
Normoblastic causes of macrocytic anaemia
Alcohol
Liver disease
Hypothyroidism
Pregnancy
Reticulocytosis
Myelodysplasia
Drugs: cytotoxics
Precipitated by infection, dehydration, deoxygenation (e.g. high altitude)
Infarcts occur in various organs including the bones (e.g. avascular necrosis of hip, hand-foot syndrome in children, lungs, spleen and brain)
Thrombotic crises
Painful crises
Vaso-occlusive crises
Vaso-occlusion within the pulmonary microvasculature → infarction in the lung parenchyma
Dyspnoea, chest pain, pulmonary infiltrates on chest x-ray, low pO2
Acute chest syndrome
Mx of acute chest syndrome
Pain relief
Respiratory support
Antibiotics
Transfusion
Sudden fall in Hb
Reduced reticulocyte count
Aplastic crises
Aplastic crises is caused by infection with..
Parvovirus
Sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia
Sequestration crises
Sequestration crises is associated with increased/decreased retic count
Increased
Admit all people with clinical features of a sickle cell crisis to hospital unless they are..
A well adult who only has mild or moderate pain and has a temperature of 38°C or less
A well child who only has mild or moderate pain and does not have an increased temperature
When is Fresh frozen plasma used?
In patients undergoing invasive surgery where there is a risk of significant bleeding
The universal donor of FFP is..
AB blood
PT or aPTT ratio required for FFP
> 1.5
What is Cryoprecipitate?
Made from FFP and is repeatedly thawed to produce concentrated factor VIII:C, von Willebrand factor, fibrinogen, Factor XIII and fibronectin
Cryoprecipitate is most commonly used to replace..
Fibrinogen
Examples of cases where cyro is used
DIC
Liver failure
Hypofibrinogenaemia secondary to massive transfusion
Emergency situation for haemophiliacs and vWF
When is Prothrombin complex concentrate used?
Emergency reversal of anticoagulation in patients with either severe bleeding or a head injury with suspected intracerebral haemorrhage
Polycythaemia vera causes an increase in RBC volume, often accompanied by..
Overproduction of neutrophils and platelets
Polycythaemia vera has a peak incidence in the sixth decade, with typical features including..
Hyperviscosity, pruritus and splenomegaly
Mx for PV
Aspirin
Venesection
Hydroxyurea and phosphorus-32 therapy
Where is rivaroxaban metabolised?
Liver
Where is apixaban released?
A stands for Ass = Apixaban is fecal excretion
Where is Dabigatran excreted?
Kidney
Dabigatran starts with D = Vit. D (most important organ related to Vit D is kidney)
Vit B12 is absorbed after binding to _______
Intrinsic factor (secreted from parietal cells in the stomach)
Vit B12 is actively absorbed in _________
Terminal ileum
Causes of Vit B12 deficiency
Pernicious anaemia
Post gastrectomy
Vegan diet
Disorders/surgery of terminal ileum (site of absorption). Crohn’s: either diease activity or following ileocaecal resection
Metformin (rare)
Mx for Vit B12 deficiency
If no neurological involvement:
1mg IM hydroxocobalamin 3 times each week for 2 weeks, then once every 3 months
if a patient is also deficient in folic acid then it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord
What is B-thalassaemia major
Absence of beta globulin chains on chromosome 11
HbA2 & HbF raised
HbA absent
Beta-thalassaemia major
Mx for Beta-thalassaemia major
Repeated transfusion
Iron overload → organ failure so iron chelation therapy important (e.g. desferrioxamine)
Target cells
Howell-Jolly bodies
Pappenheimer bodies
Siderotic granules
Acanthocytes
Hyposplenism e.g. post-splenectomy, coeliac disease
Target cells
‘Pencil’ poikilocytes
Iron-deficiency anaemia
‘Tear-drop’ poikilocytes
Myelofibrosis
Schistocytes
Intravascular haemolysis
Hypersegmented neutrophils
Megaloblastic anaemia
↓ platelets
↓ fibrinogen
↑ PT & APTT
↑ fibrinogen degradation products
DIC
Schistocytes due to microangiopathic haemolytic anaemia is normally seen in..
DIC
Prolonged PT/aPTT
Prolonged bleeding time
Low platelet count
DIC
Prolonged prothrombin
Normal aPTT
Normal bleeding time
Normal platelet count
Warfarin administration
Normal prothrombin
Normal aPTT
Prolonged bleeding time
Normal platelet count
Aspirin administration
Often normal (may be prolonged) prothrombin
Prolonged aPTT
Normal bleeding time
Normal platelet count
Heparin
Normocytic anaemia, leukopenia and thrombocytopenia
Aplastic anaemia
Aplastic anaemia causes
Idiopathic
Fanconi anaemia, dyskeratosis congenita
Cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
Benzene
Infections: parvovirus, hepatitis
radiation
Disproportionate microcytic anaemia
Beta-thalassaemia trait
Which factors are prevented in Heparin?
2,9,10,11
Which factors are prevented in Warfarin?
2,7,9,10
Which factors are prevented in DIC?
1,2,5,8,11
Which factors are prevented in Liver disease?
1,2,5,7,9,10,11
aPTT increased
PT normal
Bleeding time normal
Haemophilia
aPTT increased
PT normal
Bleeding time increased
von Willebrand’s disease
aPTT increased
PT increased
Bleeding time normal
Vitamin K deficiency
Tense, swollen joint without any history of trauma are consistent with a haemarthrosis (bleeding into a joint space)
Haemophilia
Transfusion threshold for patients without ACS
70 g/L
Transfusion threshold for patients with ACS
80 g/L
Target after transfusion for patients without ACS
70-90 g/L
Target after transfusion for patients with ACS
80-100 g/L
In a non-urgent scenario, a unit of RBC is usually transfused over..
90-120 minutes
Serum iron <8
TIBC high
Transferrin low
Ferritin low
Iron deficiency anaemia
Serum iron <15
TIBC low
Transferrin low
Ferritin high
Anaemia of chronic disease
History of a normal haemoglobin level associated with a microcytosis but not at risk of thalassaemia
Polycythaemia rubra vera
TTP = nasty fever ruined my tubes
N = neurological abnormalities
F = fever
R = renal failure
M = microangiopathic haemolytic anaemia
T = Thrombocytopaenia
Hydroxycarbamide makes red blood cells bigger, stay rounder and more flexible. This is achieved by increasing a special kind of haemoglobin called..
Haemoglobin F.
T or F: Hydroxycarbamide should not be used in pregnancy
True - increases risk of infections
HbAA
Normal haemoglobin
HbAS
Sickle cell trait
HbSS
Homozygous sickle cell disease
HbSC
Some patients inherit one HbS and another abnormal haemoglobin (HbC) resulting in a milder form of sickle cell disease
In SCA, polar amino acid ________ is substituted by non-polar ________ in each of the two beta chains (codon 6). This decreases the water solubility of deoxy-Hb
In SCA, polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains (codon 6). This decreases the water solubility of deoxy-Hb
HbAS patients sickle at pO2 _____kPa
2.5 - 4
HbSS patients sickle at pO2 ___kPa
5 - 6
Definitive diagnosis of sickle cell disease is by..
Haemoglobin electrophoresis
Differentiate between G6PD deficiency and hereditary spherocytosis
Heinz bodies
Bite/blister cells
G6PD deficiency
Common triggers for G6PD deficiency
Fava beans
Soy
Viral hep
Pneumonia
Common drug triggers for G6PD deficiency
Primaquine
Ciprofloxacin
Sulph-group drugs
Mx for DIC
Clotting studies and a platelet count should be urgently requested and advice from a haematologist
Up to 10 units of cryoprecipitate 4 units of FFP and may be given whilst awaiting the results of the coagulation studies
Autosomal dominant defect of red blood cell cytoskeleton
Hereditary spherocytosis
Acute mx for hereditary spherocytosis
Treatment is generally supportive
Transfusion if necessary
Long term mx for hereditary spherocytosis
Folate replacement
Splenectomy
Venous thromoboembolism - length of anticoagulation
Provoked (e.g. recent surgery): 3 months
Unprovoked: 6 months
An important differential in a poorly patient with hereditary spherocytosis would be..
Splenic rupture
Abdominal pain, constipation, neuropsychiatric features, basophilic stippling
Lead poisoning
Microcytic anaemia. Blood film shows red cell abnormalities including basophilic stippling and clover-leaf morphology
Lead poisoning
Which drugs are used to reverse heparin?
Protamine
Which drugs are used to reverse warfarin?
Vitamin K and fresh frozen plasma
Which drugs are used to reverse dabigatran?
Idarucizumab
Which drugs are used to reverse Rivaroxaban?
Andexanet alfa (recombinant form of human factor Xa protein)
Which drugs are used to reverse Apixaban?
Andexanet alfa (recombinant form of human factor Xa protein)
Ix for Hereditary spherocytosis
EMA binding test and the cryohaemolysis test
Ix for Hereditary spherocytosis if an atypical presentation
Electrophoresis analysis of erythrocyte membranes
Patients with sickle cell disease and hyposplenism are at increased risk of severe infections from encapsulated organisms. Examples include..
Streptococcus pneumoniae, Pseudomonas aeruginosa and Haemophilus influenzae.
Pappenheimer bodies
Sideroblastic anaemia
Alcohol is not a cause of mixed upper and lower motor neuron signs. Instead it causes a..
Sensory polyneuropathy
Essential thrombocythemia risks
Low-risk = age ≤60 years, no thrombosis history, JAK2 mutation-positive
Intermediate-risk = age >60 years, no thrombosis history, JAK2 mutation-negative
High-risk = thrombosis history at any age OR age >60 years and JAK2 mutation-positive
Translocation between chromosomes 8 and 14
Burkitt’s lymphoma
Translocation between chromosomes 11 and 14
Multiple myeloma
Translocation between chromosomes 9 and 22
CML
Translocation between chromosomes 14 and 18
Follicular lymphoma
Generalised lymphadenopathy. Biopsy reveals atypical lymphoid cells with an irregular nucleus and a high mitotic rate
Non-Hodgkin’s lymphoma
BCR-ABL polymerase chain reaction positive
CML
Serum protein electrophoresis reveals IgG paraprotein spike
Multiple myeloma
‘Dry tap’ on attempt of bone marrow aspiration
Myelofibrosis
Bone marrow aspiration reveals 20% blasts and Auer rods
AML
Bone marrow aspiration reveals lymphoblastic infiltration and marrow hypercellularity
ALL
Most common paraprotein in multiple myeloma
IgG
2nd most common paraprotein in multiple myeloma
IgA
Plasma cell (post-germinal B cell) dyscrasia, arising from post-germinal B cells in the lymph nodes
Multiple myeloma
Leukaemic lymphoblastic cells
ALL
Mature myeloid cells
CML
Smudge cells
CLL
EBV
Hodgkin’s and Burkitt’s lymphoma, nasopharyngeal carcinoma
HTLV-1
Adult T-cell leukaemia/lymphoma
HIV-1
High-grade B-cell lymphoma
Warm AIHA is caused by which antibody?
IgG
Cold AIHA is caused by which antibody?
IgM
Causes of warm AIHA
Idiopathic
Autoimmune - SLE
Neoplasia
Lymphoma
Chronic lymphocytic leukaemia
Methyldopa
Causes of cold AIHA
Neoplasia: e.g. lymphoma
Infections: e.g. mycoplasma, EBV
Mx warm AIHA
Steroids (+/- rituximab)
Relative causes of Polycythaemia
Dehydration
Stress: Gaisbock syndrome
Primary causes of Polycythaemia
Polycythaemia rubra vera
Secondary causes of Polycythaemia
COPD
Altitude
OSA
Excessive erythropoietin: cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids
Hereditary causes: membrane
Hereditary spherocytosis/elliptocytosis
Hereditary causes: metabolism
G6PD deficiency