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Title: Haematology for Medical Finals
Description: Haematology notes aimed at medical students preparing for their final examinations. Produced by a 6th year medical student, University of Oxford, United Kingdom
Description: Haematology notes aimed at medical students preparing for their final examinations. Produced by a 6th year medical student, University of Oxford, United Kingdom
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Haematology
Iron Deficiency Anaemia:
Haematological features
Iron studies
Further investigation
Prescription of iron therapy
Anaemia: defined as a Hb concentration below the reference range for the age and sex of the individual
...
5 – 20
...
0 – 23
...
0 – 14
...
0 – 15
...
0 – 17
...
0 – 15
...
0 – 14
...
-‐ Renal EPO is responsible for translating tissue hypoxia into increased RBC production
...
Blood loss
2
...
Congenital defects e
...
sickle cell disease, hereditary spherocytosis
b
...
g
...
Impairment of red cell formation
a
...
Ineffective erythropoiesis
4
...
Increased plasma volume e
...
splenomegaly, pregnancy
Haematology
Morphological classification
1
...
Macrocytic = high mean cell volume
3
...
Normal mean cell volume (MCV): 82 – 99 fL
b
...
Normal mean cell Hb concentration (MCHC): 32 – 36g/dL
Type
MCV
Microcytic and hypochromic, or microcytic
Low
Normocytic or normochromic
Normal
Macrocytic
High
Causes
Fe deficiency
Thalassaemia syndromes
Some cases of anaemia of chronic disorders
Acute blood loss
Chronic renal failure
Aplastic anaemia
Leucoerythroblastic anaemia
Anaemia of chronic disease
Alcoholism
Folate deficiency
B12 deficiency
Some haemolytic anaemias
Iron Deficiency Anaemia (microcytic anaemia)
Normal iron metabolism:
-‐ The body has no mechanism for up-‐regulating iron excretion, and excess iron is potentially toxic
...
o Iron absorption can be maximised when stores are low or if there is a need to increase erythropoiesis
o No excess iron is absorbed when stores are good
-‐ Normal Western diet contains 10-‐20mg of iron/day = around 5-‐10% is absorbed (0
...
-‐ Once the iron crosses the basolateral membrane into the plasma it is converted from Fe2+ to Fe3+ by ferroxidase
enzymes
...
-‐ Iron bound to transferrin will enter erythroid cells by interacting with the transferrin receptor 1
...
At this point the haem is recycled and the Fe released from the haem ring is bound to
transferrin to be redelivered to the bone marrow or stored as ferritin
...
o Iron itself also directly affects production of DMT1 – by binding iron-‐response proteins to iron-‐response
elements in 5’ untranslated region of the mRNA for the gene
...
g
...
How can we confirm the diagnosis of iron deficiency?
Serum ferritin (how much in the stores)
Serum iron (how much going around in the blood)
Transferrin (how hard your body/liver is trying to work to transport iron around)
o Ferritin:
§ The main storage protein for iron
§ For concentrations <4000microg/L it roughly correlates with the amount of tissue-‐storage iron
§ Ferritin levels are therefore low in iron deficiency anaemia
• *Ferritin is also an acute phase reactant, therefore it can be raised in infection and
inflammation
• May therefore get normal serum ferritin levels in the presence of reduced iron stores in
patients with acute and chronic infections and in malignancy
...
If transferrin is high, for example due to Fe deficiency and the body
trying to shift iron around, then the TIBC will also be high
...
§ A reticulocytosis is expected in response to treatment
§ Rise of Hb level of 2g/dL over 3/52 is expected
§ One Hb concentration and red cell indices are normal:
• Continue for 3/12 to replenish iron stores, then stop
• Monitor the person’s FBC ever 3 months for 1 year
• Re-‐check after a further year, or again if symptoms of anaemia develop
o Alternative options: e
...
for patients who cannot tolerate iron orally, or in whom substantial blood loss
continues/have severe malabsorption syndromes
§ Parenteral iron preparations
• Iron sucrose = Venofer
• Low molecular weight iron dextran = CosmoFer
o Adverse effects: anaphylaxis, fever, arthropathy
...
It should be
§ Have malabsorption
taken on an empty stomach if possible
...
§ Are undergoing haemodialysis
§
§
§
-‐
-‐
Other causes of a microcytic hypochromic anaemia?
1
...
Sideroblastic anaemia
a
...
Can be inherited (X-‐linked) or acquired
i
...
Acquired can be due to myelodysplasia, excessive alcohol consumption, certain drugs (e
...
isoniazid, chloramphenicol), lead poisoning
...
Pyridoxal phosphate is required for both enzyme activity and stability, some patients will
respond to high doses of pyridoxine given orally
...
§ Signalling through the receptor is blunted
§ Response to exogenous erythropoietin is also limited
o Inflammatory cytokines (IL-‐6, TNF-‐alpha) increase hepcidin synthesis
§ Limits iron absorption
§ Reduces the amount of stored iron released from macrophages and made available for
erythropoiesis (as the release from these stores requires ferroportin)
• Iron studies:
o Serum iron concentration = low
o Ferritin = normal/high
o Transferrin = low
Other causes of normocytic anaemia:
-‐ Blood loss
-‐ Bone marrow infiltration
-‐ Anaemia associated with renal disease (reduction in EPO secretion in response to hypoxaemia)
Haematology
Vitamin B12 and Folate Deficiency
Differential diagnosis of macrocytic anaemia
Autoantibodies to diagnose B12 deficiency
Macrocytic Anaemia:
-‐ Causes can be divided into those showing megaloblastic erythropoiesis and those with normoblastic
erythropoiesis
...
antipurines (mercaptopurine, azathioprine), antipyrimidines
(fluorouracil, AZT)
o Orotic aciduria
• Myelodysplastic syndromes (can sometimes also be normoblastic)
• Congenital dyserythropoietic anaemias
o Normoblastic = normal appearance of RBC maturation, but may still have macrocytosis in the peripheral
blood
§ Causes:
• Chronic alcoholism – both due to toxicity and due to associated malnourishment
• Chronic liver disease – due to phospholipid deposition in the RBC membranes
• Hypothyroidism
• Therapy with anticonvulsant drugs
• Haemolytic anaemia
• Hypoplastic and aplastic anaemia
• Myeloma
• Normal neonates (physiological)
• Normal pregnancy
Vitamin B12 and Folate Deficiency:
-‐ Folic acid is needed for the enzymatic reaction to convert dUMP to dTTP: this is essential for synthesis of
thymidine, one of the pyrimidine bases in DNA
...
-‐ How does someone become deficient?
o Folate in Western diet: found in meat and vegetables
...
§ Deficiency due to poor intake can be seen in frail elderly people and in the context of alcoholism
...
§ Absorption is principally in the duodenum and jejunum, therefore coeliac disease can impair
absorption
...
Therefore vegan diets are likely to be
deficient
...
g
...
§ It is then bound to haptocorrin proteins
§ The bound B12 passes to the duodenum, where it is then cleaved from haptocorrin and bound to
the glycoprotein Intrinsic Factor
• Intrinsic factor is essential for B12 absorption
• It is highly resistant to enzymatic digestion
• It transports B12 to the ileum where the B12/IF complex then binds its receptor, cubilin,
and is endocytosed – disease in the terminal ileum can therefore prevent the complex
being taken up into the enterocytes
...
Sensitivity is 50-‐75% and
specificity is nearly 100%
...
o Anti-‐parietal cell antibodies associated with gastric atrophy and failure of IF
secretion
...
Good for ruling it out if absent, but not so good
for ruling in if they are present
...
This means if they are not
present it is a good test to rule out PA, but if they are present the lack of
specificity means you cannot be sure of PA being the cause
...
•
§
Causes of folate deficiency:
1
...
Malabsorption
3
...
Increased loss
5
...
Inadequate intake
2
...
Inadequate secretion of IF
4
...
Diphyllobothrium latum
6
...
-‐ If severe, can get a mild jaundice
o Destruction of poorly matured erythroid precursors releases bilirubin
-‐ B12 deficiency can cause neurological symptoms:
o Peripheral neuropathy – particularly proprioception and vibration sense
o Demyelination of the dorsal and lateral columns of the spinal cord
§ Pyramidal picture = subacute combined degeneration of the cord (can be irreversible)
• Increased tone
• Extensor plantars
Haematology
o
• Sensory ataxia
GI tract e
...
glossitis
Diagnosing B12 or folate deficiency:
-‐ Macrocytic anaemia with megaloblastic erythropoiesis
-‐ Blood film:
o Oval macrocytes
o Hypersegmented neutrophils
o Reticulocyte count will be low for the degree of anaemia
-‐ Bone marrow aspirate:
o Nulcear-‐cytoplasmic dyssynchrony
o Giant metamyelocytes
-‐ Mild increase in bilirubin and LDH: due to destruction of the defective erythroid cells in the bone marrow
...
§ If there is doubt about an assay, can measure the levels of the substrates of the cobalamin-‐
requiring enzymes e
...
homocysteine and methylmalonic acid levels will be high in true B12
deficiency
...
o For the second stage you give additional oral intrinsic factor with the radiolabelled B12, and the IM B12
...
Treatment:
-‐ Oral folic acid supplementation if folate defiency – although must be careful that a coincident B12 deficiency is not
missed
o If it was missed, the folic acid supplementation would temporarily alleviate the haematological and
physical signs, but can make the B12-‐associated neurological pathology worse
-‐ Oral B12 supplements if there is simple dietary deficiency
-‐ Parenteral vitamin B12 administration by IM injection if pernicious anaemia
...
Fe-‐deficiency
1
...
Sideroblastic
2
...
B12/folate deficiency
3
...
Anaemia of chronic disease
2
...
Renal failure
3
...
BM failure
Non-‐megaloblastic:
4
...
Myelodysplasia
6
...
Reticulocytosis
Haematology
Thalassaemia Trait
Diffferential diagnosis of microcytic anaemia
Beta-‐thalassaemia trait:
• One normal and one abnormal beta-‐globin gene
• Hb electrophoresis is normal
• HbA2 (a HB subtype with no known function) is increased = from 2% to 4-‐6%
o Two functional alpha chains + two functional beta chains = HbA (makes up 97% of Hb normally)
o If one beta globin gene is abnormal: two functional alpha chains + one functional beta + one delta chain =
HbA2 (usually makes up <2%)
• Partners of those with beta-‐thalassaemia trait should be tested, as trait carriage by both could lead to offspring
with thalassaemia major
...
Cataracts
o Splenectomy may improve situation
2
...
Nerve d eafness
Alpha-‐thalassaemia trait:
• There are 4 alpha globin genes – severe disease only occurs if 3 or 4 of them are deleted
...
• Hb electrophoresis is normal
• HbA2 levels are normal
• Microcytic anaemia
• Diagnosis = exclude beta-‐thalassaemia, exclude iron deficiency anaemia
Alpha-‐thalassaemia major:
• Deletion of all 4 alpha-‐globin genes
• Hydrops fetalis
• Intrauterine death if not diagnosed early – intrauterine blood transusions can be life saving
• Treatment:
o Require life-‐long blood transfusions
Thalassaemia intermedia:
• Between trait and major
• By definition does not require transfusions
• Beta-‐thalassaemia intermedia = where one or both genes still produce small amounts of HbA
• Alpha-‐thalassaemia intermedia = deletion of 3 or 4 of the alpha-‐globin genes
• Splenectomy – can improve the anaemia
Haematology
Sickle Cell Anaemia
Complications, management of painful crises and acute chest syndrome
...
g
...
2
...
Haemoglobin abnormalities
Sickle cell disease
Thalassaemia
HbC and HbE erythroids
1
...
3
...
• Malignancy of the plasma cells in the bone marrow
...
Black > white
...
o Bence-‐Jones protein – deposited in kidney, interferes with function
• Normal immunoglobulin production is suppressed = immunoparesis
• Anaemia is common, due to:
o Tumour infiltration of the BM
o Cytokine-‐mediated anaemia of chronic disease
o Coexistent renal impairment
• Renal failure:
o Renal failure affects 50% of patients
o Due to renal deposition of Bence-‐Jones protein (the light chains of an immunoglobulin molecule)
o Can also be due to hypercalcaemia, sepsis, drugs or dehydration
• Hypercalcaemia:
o Found in 25% of patients at diagnosis
o Myeloma cells release cytokines – stimulate osteoclasts – cortical bone erosion – release of Ca into blood
Clinical features:
Monoclonal gammopathy of uncertain significance
• Mean age presentation 65-‐70 yo
• Monoclonal paraprotein but no other features
• History and examination:
of melanoma
o Anaemia and cachexia of chronic disease
• Risk o f developing myeloma or similar
symptoms
disorder is 1 % per year
§ Leads to tiredness, SOB, fatigue
o Hypercalcaemia symptoms
§ Nausea
§ Thirst and polyuria
§ Constipation
§ Confusion – can also be due to hyperviscosity syndrome or infection
o Renal impairment symptoms
§ Malaise
§ Anorexia
o Hypogammaglobulinaemia/immunoparesis
§ Bacterial infection
o Osteoporotic fractures and bone pain
§ Hip, ribs, skull, back
...
Electrophoresis = monoclonal immunoglobulin band, depression of other immunoglobulins
2
...
Blood = Freelite assay can detect free light chains in the blood, low Hb, low albumin
4
...
End-‐organ damage related to the plasma cell disorder (CRAB):
i
...
75mM/L
ii
...
Anaemia = Hb<10g/dL
iv
...
o Thalidomide + dexamethasone initially, disease control in 2/3rd
...
e
...
g
...
The transfused platelets have a
lifespan of 24-‐48 hours and repeated transfusions can lead to antibody development, therefore it is
reserved for treating haemorrhage only, or pre or peri-‐operatively
...
Myeloproliferative disorders are group of 4 disease caused by clonal proliferation of haematopoietic stem cells:
1
...
Myelofibrosis
3
...
Essential thrombocythaemia
Haematopoietic stem cells reside in the bone marrow; clonal expansion leads to increases in some or all of stem cells, RBC,
WCC, and platelets
...
• Clonal expansion of stem cells
o Growth factors, cytokines – marrow fibrosis – decreased space for normal elements
§ Get extramedullary haematopoiesis by the spleen
§ Get marrow failure = decreased Hb, decreased WCC, decreased platelets
• Clonal expansion of RBCs
o High Hb
o Polycythaemia rubra vera
• Clonal expansion of platelets
o High platelets
o Essential thrombocythaemia
• Clonal expansion of WCCs
o High WCC
o Chronic myeloid leukaemia
Myelofibrosis:
• Typically 60 yo
• Clonal proliferation of the haematopoietic stem cells
• Release of growth factors (platelet-‐derived GF) and cytokines – leads to polyclonal marrow fibrosis
• Clinical features:
o Anaemia
o Splenomegaly – painful due to infarcts
o Weight loss
o Fever
• Investigations:
o Blood count
§ Anaemia
§ WCC and platelets may be normal or high
o Blood film
§ Leukoerythroblastic change (immature WCC and RBCs)
§ Tear drop RBCs
o Bone marrow
§ Often inaspirable due to fibrosis
§ Trephine biopsy = hypercellular, increased fibrosis
• Treatment:
o Not very effective
o Often get progressive anaemia – may need blood transfusion, anabolic steroids, or EPO
...
o Hydroxycarbamide – can control a high WCC and reduce spleen size, no impact on fibrosis
...
o Median survival: 4 years
...
• ½ patients will have increased platelets and/or WCC too
• 40% have marrow karyotypic abnormality
...
Chronic hypoxia e
...
COPD, lung disease, cyanotic heart disease, high altitude
a
...
Lung function tests
2
...
g
...
Renal ultrasound
b
...
Gaisbock’s syndrome: an apparent polycythaemia where the red cell mass is normal, but the plasma
volume is reduced = found in hypertensive men who are heavy smokers
...
g
...
Essential thrombocythaemia:
• Typical age 50-‐80yo
• Peripheral platelet count >600X10(9)/L
• Differential diagnosis: (reactive thrombocytosis)
o Post-‐splenectomy
o Chronic bleeding
o Sepsis (particularly chronic abscesses)
o Inflammatory diseases e
...
IBD, RA
o Malignancy
• Clinical features:
o Most diagnosed incidentally
o Thrombotic events – risk increased by factors e
...
HTN, diabetes, smoking
o Haemorrhage/bruising – increased risk as there is impaired platelet function
• Investigations:
o 40% have JAK2 mutation, giant platelets in the peripheral blood
o Exclude other myeloproliferative diseases and reactive causes
• Treatment:
o Elderly patients with count >1000, other thrombotic RFs or previous thrombotic event = treatment
§ Hydroxycarbamide 1st line, interferon-‐alpha or anagrelide 2nd line
o Young patients with count <1000, no additional RFs = observation/aspirin
• Prognosis: 70% survive >10 years, 5% develop AML
Haematology
Thrombophilia
Congenital and acquired factors predisposing to thrombosis
...
1
...
Serine protease inhibitor (serpin)
b
...
Antithrombin forms 1:1 complexes with them and thus inhibits their activity
d
...
Neutralizes thrombin
ii
...
Protein C pathway
a
...
Protein C is activated by thrombin in the presence of an endothelial cell cofactor,
thrombomodulin
...
Action:
i
...
To do this, protein C needs it’s own cofactor, protein S
iii
...
Inherited thrombophilia
• Common, affect 5-‐7% of the population overall
...
• Heterzygous protein C, protein S or antithrombin deficiency:
o 50% of normal levels of activity
o At risk of thrombosis
• Homozygous protein C or S deficiency:
o Neonatal purpura fulminans
• Homozygous antithrombin deficiency:
o Fatal in utero
• Investigations:
o Any patients with unprovoked VTE, positive FHx, or young with children/siblings
o Relatives of a patient with proven VTE and identified heritable thrombophilia
Factor V Leiden:
• Point mutation in factor V at the site where protein C inactivates it = leads to resistance to activated protein C
(APC)
• Discovered in Leiden, in the Netherlands
...
• This leads to higher levels of prothrombin
• Associated with a 4x increased risk of VTE
Haematology
Acquired Thrombophilias
Antiphospholipid syndrome:
• Presence of antiphospholipid antibodies, leading to thrombosis in the venous or arterial systems
...
g
...
g
...
g
...
• Causes:
o Atheroma
o Heart disease e
...
AF, heart failure
o Malignancy
o Polycythaemia
o Thrombocythaemia
o Antiphospholipid antibody syndrome
o Sickle cell disease
o Homocystinuria – abnormal metabolism of methionine, leads to accumulation of homocystine
...
g
...
• Causes:
o Smoking
o Malignancy
o Oral contraceptive pill
o Polycythaemia
o Thrombocythaemia
o Antiphospholipid syndrome
o Nephrotic syndrome
Haematology
Chronic Lymphocytic Leukaemia
Prognosis, features on blood film, complications including haemolytic anaemia
...
Pale
1
...
Hepatomegaly
performed for another reason
3
...
Recurrent sepsis: from hypogammaglobulinaemia
4
...
Anaemia: due to BM infiltration or autoimmune
painless
haemolysis (may be triggered by infection)
4
...
§ Patients with mutation of Ig heavy chain genes has better prognosis than patients with un-‐
mutated genes
...
0
<100
<5 years
*Areas include cervical, axillary or inguinal nodes, spleen or liver
...
Causes of haemolytic anaemia
Congenital/hereditary
Acquired
Membrane defects:
Immune:
• Hereditary spherocytosis
• Warm AIHA
• Cold haemagluttinin disease
Enzyme defects:
• Paroxysmal cold haemoglobinuria
• Glucose-‐6-‐phosphate dehydrogenase deficiency
• Pyruvate kinase deficiency
Non-‐immune:
• Infection
Globin defects:
• Burns
• Sickle cell disease
• Hypersplenism
• Thalassaemia
Drugs/chemicals/venoms:
• Oxidant drugs and chemicals e
...
arsine, lead,
copper
• Certain snake and spider venoms
Mechanical trauma to cells:
Abnormalities of the heart and large blood vessels
• Aortic valve prostheses, severe valve disease
Microangiopathic haemolytic anaemia:
• HUS
• TTP
• Metastatic malignancy
• Malignant hypertension
• DIC
General clinical and laboratory features:
• Haemolytic anaemia is anaemia due to a reduction in the lifespan of RBCs
• General features include:
o Pallor
o Jaundice
§ Usually no itching – as unconjugated hyperbilirubinaemia
o Variable degrees of splenomegaly
o Pigment gallstones – can occur if chronically hyperbilirubinaemic, if obstruct the CBD you can get
obstructive jaundice with itching, as it will be conjugated hyperbilirubinaemia
...
Haemosiderinuria: occurs with chronic IV haemolysis, Hb filtered in kidneys is reabsorbed in the proximal convoluted tubule
...
When the tubule cells slough off with the haemosiderin, they are excreted in the
urine, seen 3-‐4 days after onset of haemolysis
...
Can test for presence with Perls’ Prussian Blue stain
...
These are cells under haemolytic attack
...
§ Need prophylactic penicillin
...
G6PD Deficiency:
• G6PD acts to catalyse glucose-‐6-‐phosphate to generate NADPH – this is essential for the maintenance of functional
Hb and prevention of oxidative attack
...
• Occurs due to a variety of mutant alleles of the G6PD structural gene
...
• Gene is X-‐linked = G6PD deficiency more common in males
• Can have mild (African type) or severe (Mediterranean type)
• Clinical features
o Most are asymptomatic until an acute haemolytic episode occurs
o Triggers = infection, drugs e
...
sulphonamides, primaquine, ingestion of fava beans
...
• Diagnosis
o Bloods: Hb 4
...
coli O157
• Characterized by:
o Microangiopathic haemolytic anaemia
o Thrombocytopaenia
o Renal impairment
• Similar lab features to TTP
• Treatment
o Supportive
o May require dialysis
o Plasmapheresis – although less effective than for TTP
o Most recover, some have persistent renal impairment
...
Immune
Warm antibody-‐mediated haemolysis:
• IgG binding to red cells = splenic phagocytosis = complete or partial (produces spherocytes)
• Also get some complement-‐mediated death
• Causes
o Idiopathic
o Lymphoproliferative diseases e
...
CLL, non-‐Hodkin’s lymphoma
o Autoimmune disease e
...
SLE
o IBD
o Drugs e
...
methyl-‐dopa, mefenamic acid, penicillin
• Investigations:
o Positive direct antiglobulin test (Coombs’ test)
• Treatment:
o Prednisolone
o Blood transfusions if severe, symptomatic anaemia – while waiting for the steroids to work
o Splenectomy if steroids fail
o Rituximab – CD20 antibody
Haematology
Cold antibody-‐mediated haemolysis:
• IgM antibodies against the red blood cells
...
g
...
• Paediatrics: acute transient form associated with viral infection e
...
influenza, mumps, EBV
• Adults: usually a chronic form, associated with syphilis
...
• CD55 and CD59 are two of the proteins that depend on this anchor – these proteins are critical regulators of the
complement pathway
...
Damaged
Trauma
endothelial surface
APTT
PT
Heparin – via
antithrombin 3
Activated Partial Thromboplastin Time (APTT): normal range 26 – 37 seconds
• Intrinsic system (slower clotting system)
• Estimates the activity of factors: 12, 11, 9, 8, 10, 5, 2 and fibrinogen
...
5 – 13
...
Prolongs APTT
Prolongs PT
Prolong both APTT and PT
1
...
Warfarin (called INR)
1
...
Contact factor deficiency e
...
pre-‐
K dependent factors are 2, 7,
kallikrein deficiency
9, 10
...
Acquired clotting factor inhibitors –
2
...
g
...
4
...
Acquired dysfibrinogenemia
phospholipid, PT also requires
4
...
g
...
Disseminated intravascular
the lupus anticoagulant
...
Dilutional coagulopathy e
...
prolongs APTT, but in vivo it is
massive blood transfusion
actually a pro-‐coagulant and
7
...
deficiencies e
...
5, 2,
5
...
o Average time that elapses until bleeding ceases is measured
...
• PFA-‐100
o In vitro estimation of haemostasis using a PFA-‐100 machine
...
• Platelet aggregation studies
o Light transmission aggregometry
o Studies the aggregation after addition of ADP, epinephrine, arachidonate, collage and ristocetin to
platelet-‐rich plasma
...
o Aggregation causes an increase in light transmitted through the sample
...
o Inactivates the coagulation factors thrombin (2a) and 10a
...
o LMWH is used subcut, inactivates 10a to a greater extent than 2a, and has a longer biological halflife
...
g
...
o Fondaparinux induces AT3 specifically to inhibit 10a
...
• Administration = subcut or IV
• Safety in pregnancy: does not cross the placenta
LMWH
Standard/unfractionated heparin
Treating thrombus or embolism
• Given subcut once a day
• Bolus of 5000 units IV
• Continuous IV infusion of 15-‐
25 units/kg/h
• Monitor APTT, maintain at
1
...
5x normal
Preventing venous thrombosis in
• Subcut once a day
hospitalized patients at risk
Preventing post-‐operative thrombosis
• Subcut once a day
• 5000 units subcut pre-‐
operatively
• 5000 units subcut 8-‐12 hourly
post-‐operatively
LMWHs are associated with a predictable dose–response and have fewer non-‐haemorrhagic side-‐effects
...
When then started on warfarin – continue the heparin for at least 5 days, or until the INR has been therapeutic for at least
24 hours, whichever is longest
...
Side effects of heparin:
1
...
Stop the heparin
b
...
Heparin-‐induced thrombocytopenia d ue to antibodies
3
...
Alopecia
5
...
• However, factor 7 has the shortest half-‐life – so when you give Warfarin this is the first factor to decrease
...
You would not want to wait until the APTT becomes affected and prolonged before adjusting the patient’s dose, as
by then they may be over anti-‐coagulated
...
o Prescribe 5 or 10mg on the first day, subsequent doses based on the INR
o Therapeutic INR range: 2-‐3
o Recurrent DVT, PE, prosthetic heart valves – INR range: 3-‐4
Haematology
• Causes of loss of control of warfarin therapy:
o Drugs that affect warfarin metabolism e
...
anything that affect cytochrome P450
o Changes in dietary vitamin K
• Safety in pregnancy: crosses the placenta and can cause developmental abnormalities e
...
chrondrodysplasia,
microcephaly, blindness
...
FFP only used if PCC unavailable
Non-‐major bleeding – stop warfarin, 1-‐3mg IV vit K
Non-‐bleeding INR > 5 – hold 1-‐2 doses of warfarin, reduce maintenance dose
Non-‐bleeding INR > 8 – 1-‐3mg oral vit K
PCC is more quickly available than FFP, as it doesn’t have to be warmed
...
Direct oral thrombin inhibitors and direct oral Xa inhibitors:
• Oral thrombin inhibitors = Dabigatran, Etexilate
• Oral Xa inhibitors = Rivaroxaban, Apixaban, Edoxaban
• Alternative to warfarin in treating VTE and AF
• Given as fixed dose
• Don’t require monitoring
• No antidote, but relatively short half-‐life (9-‐17 hours)
Haematology
Febrile reaction – due to antibodies against recipient leucocytes
...
Haematology
Haematology
Haematology
Haematology
Title: Haematology for Medical Finals
Description: Haematology notes aimed at medical students preparing for their final examinations. Produced by a 6th year medical student, University of Oxford, United Kingdom
Description: Haematology notes aimed at medical students preparing for their final examinations. Produced by a 6th year medical student, University of Oxford, United Kingdom