Transcript Haematology Revision - Dec 2013

Haematology in 1 hour
Approach to low blood count
Consider cause
– Is it a lack of production = bone marrow
problem (intrinsic or extrinsic)
– Is it excess destruction = immune or other
causes
– Is it excess consumption = sepsis,
haemorrhage, large spleen etc
Always consider Drugs
Consider inherited vs acquired
Approach to the investigation of
Anaemia
MCV
LOW
Assess iron status
Ferritin
Iron deficiency
Define and treat
cause
Treat with Fe
Establish response
NORMAL
HIGH
Film appearance
History
-diet
-drugs
-alcohol
Normal
(or raised)
? Ethnic origin
Normal
Spherocytes
Hb screen
Raised ESR
DAT
Reticulocyte count
B thal trait
(Putative a thal trait)
Investigate for ACD
Counsel
Abnormal cell
shapes
Associated FBC
abnormalities
Liver function inc
gGT
B12/folate
Thyroid function
Treat appropriately
Refer to Haematologist for further investigation
Microcytic anaemia -questions
Is it iron deficiency or thalassaemia?
– or both?
If iron deficiency:
– what is the cause?
– what further investigations are required?
– What is the treatment?
– What if the patient fails to respond to oral
iron?
Iron deficiency
Produces a drop in MCV proportional to the degree of
anaemia
RDW increases, reflecting anisocytosis
Beware effect of acute disease in interpretation of
Ferritin and TIBC results
Beware of counteracting effect of drugs/alcohol causing
macrocytosis on MCV in iron deficiency – look at
previous results
Treatment dose is 200 mg Fe/day (=200mg tds of Feso4,
look up other Fe preparations in BNF
Failure to respond to oral iron
Insufficient dose
Thalassaemia traits
Non compliance
Continuing losses
Malabsorption (coeliac disease, post
gastrectomy)
Thalassaemia traits
Produce microcytic, hypochromic indices
Clinically asymptomatic
Mild anaemia, MCH<27pg
Look for steady state Hb in notes – will tell if additional
problem
Do not give iron unless iron deficiency proven
b thalassaemia trait causes raised Hb A2
a thal traits by exclusion of other causes
In antenatal context identification of b thal trait in women
mandates partner screening
Haemolytic anaemia questions
How is diagnosis of haemolytic anemia
made?
– Clinical – jaundice, dark urine, splenomegaly
– Lab-normocytic anemia, unconjugated
hyperbilirubinaemia, reticulocytosis
– Further tests: direct antiglobulin test
(Coombs), blood film, Hb screen
Haemolytic anaemia
Consider cause
– Inherited: haemoglobinopathy, membrane
disorder
– Acquired: drugs, transfusion reaction, immune
disorders
Treatment directed at cause
Transfuse if symptomatic (problems with
cross match)
Sickle cell disease: clinical
problems
Anaemia
Infections
Painful crises
Stroke
Leg ulcers
Visual loss
Chronic organ damage
– Kidneys, lungs, joints, heart
Sickle cell basic facts
Not exclusive to black races
Hb SS steady state Hb 7-9g/dl
Transfuse only for certain indications
Milder forms may have normal Hb so
always do Hb Screen if suspicion or pre op
% Hb S is constant and bears no relation
to acute crisis
Patients have functional asplenia,
therefore high risk of infection
Macrocytic anaemia - questions
Is it a new problem?
Is it due to alcohol?
Is it due to diet /haematinic deficiency
Is it due to drugs?
When to refer to the haematologist?
Management of low B12
History
– Diet, previous surgery, GI disease
IF antibodies
– Schilling test no longer available
Symptoms/signs - give i.m. B12 with folic acid
– levels unhelpful and unnecessary after this
Asymptomatic - ?dietary can give oral B12 and reassess
levels after a few weeks
Failure to respond to haematinics may indicate MDS
n.b. if normal Hb, MCV can take several weeks to fall
Polycythaemia
Raised haematocrit (in well hydrated
patient)
Consider cause
– primary (uncommon) v secondary
(common)
– cause of secondary
Hypoxia (respiratory disease, smoking, cardiac
disease R – L shunt)
Excessive EPO (renal /hepatic disease/tumours)
Increased thrombotic risk
Polycythaemia
Investigations, if not apparent from history
– CXR, Arterial gas, lung function, EPO level
Refer to haematology if no obvious
secondary cause
Management: Venesection to Hct as
defined for underlying cause
Chemotherapy (primary cause)
Raised WBC questions
Is it confined to one type of cell or all white
cells?
Are abnormal cells present?
What are appearances of blood film?
Common cause is reactive (neutrophilia, L
shift, in context of
infection/inflammation/malignancy)
CRP may be a pointer to reactive cause
Leukaemia
Clonal proliferations of one of more types
of white cells
Mature cells = chronic leukaemia
– CLL lymphocytes
– CML Mature + immature Myeloid cells
Immature cells = acute leukaemia
– characterised by presence of blasts and
immature cells in blood/BM
– e.g AML, ALL
Effects of leukaemia
Bone marrow failure
– anaemia
– thrombocytopenia - bleeding risk
– neutropenia - infection risk
Tissue infiltration
– Tumour deposits e.g skin, nodes, gums,CNS,
liver or spleen
Immune suppression - infection
Death usually due to infection or bleeding
How does acute leukaemia
present?
Infection
Symptoms of anaemia
Bruising/bleeding
Tissue infiltration
Blood film shows cytopenias with blasts
Confirm on Bone marrow and
immunophenotyping/cytochemistry. Chromosomes
Treatment: intensive chemotherapy
Prognosis: depends on characterisitcs and patient
comorbidity. e.g childhood ALL very good prognosis,
elderly AML, poor
Chronic leukaemia
May be incidental finding e.g CLL
Associated with symptoms/signs of marrow
infiltration
Increased infections (bacterial/fungal)
Lymphadenopathy
Autoimmune features eg AIHA in CLL
Diagnosis on film/marrow/special investigations
Treatment variable: observation only to intensive
chemotherapy
Prognosis very variable eg. CLL
What are lymphomas
neoplasms of lymphoid origin, typically
causing lymphadenopathy
leukaemia vs lymphoma
lymphomas are clonal expansions of cells
at certain developmental stages
A practical approach to lymphomas
Category
NonHodgkin
lymphoma
Hodgkin
lymphoma
Indolent
Survival of
untreated
patients
Years
Curability
To treat or
not to treat
Generally
not curable
Generally
defer Rx if
asymptomatic
Aggressive
Months
Curable in
some
Treat
Very
aggressive
Weeks
Curable in
some
Treat
All types
Variable –
months to
years
Curable in
most
Treat
Clinical manifestations
Variable
severity: asymptomatic to extremely ill
time course: evolution over weeks, months, or
years
Systemic manifestations
fever, night sweats, weight loss, anorexia,
pruritis
Local manifestations
lymphadenopathy, splenomegaly most common
any tissue potentially can be infiltrated
Other complications of lymphoma
bone marrow failure (infiltration)
CNS infiltration
immune hemolysis or thrombocytopenia
compression of structures (eg spinal
cord, ureters) by bulky disease
pleural/pericardial effusions, ascites
Staging of lymphoma
Stage I
Stage II
Stage III
A: absence of B symptoms
B: fever, night sweats, weight loss
Stage IV
Investigation of suspected lymphoma
Biopsy of affected node/mass
– ESSENTIAL as dictates treatment
and prognosis
Staging CT scans/Bone marrow
FBC, Biochemistry, LDH, etc
Three types of lymphoma you will
most commonly meet
Follicular lymphoma
Diffuse large B-cell lymphoma
Hodgkins lymphoma
Neutropenia questions
Is it isolated or associated with other
cytopenias?
Is it recent or longstanding?
Is it associated with history of infection?
Common causes of isolated neutropenia:
– Viral infection (acute and chronic eg HIV)
– Drug related (look up list)
– Ethnic (longstanding, asymptomatic, no other
cause)
Severe neutropenia
Infection risk increased if neuts<1.0 x 109/l
High risk of infection of neuts<0.5
Risk is also related to duration of neutropenia
and neutrophil function
Consider prophylaxis of infection if neuts<0.5
Fever in Neutropenic patient is a medical
emergency – investigate and treat empirically
with broad spectrum antibiotics pending micro
results. Hospital should have a protocol.
Paraproteins
Common incidental finding, esp in elderly
Due to clonal proliferation of plasma cells
Is it significant?
Causes:
– secondary: (autoimmune disorders/infections)
– Malignant: myeloma/lymphoma
– Uncertain: MGUS (20% evolve into clonal
disorder)
Myeloma
Clinical features due to combinations of:
–
–
–
–
Marrow failure
immunsuppression
Paraprotein (renal disease)
Bone disease (pain, fractures, lytic lesions/hypercalcaemia)
Investigation of PP
–
–
–
–
–
History
FBC, Biochem, Serum electrophoresis
Bone X rays
Bone marrow
MGUS is defined by lack of evidence for malagnancy or reactive
cause.
Haemostasis and
thrombosis
Physiology of haemostasis
Bleeding disorders (congenital)
Massive blood loss
DIC
Anticoagulant drugs
Haemostasis needs…
Platelets
Vessel Wall
Clotting Factors
The starter motor……..
PT
Switched off
by Tissue Factor
Pathway
Inhibitor
Provides initial Thrombin burst
Factors measured in Prothrombin Time
The engine…………..
APTT
Thrombin from initial burst back activates “intrinsic system”
TT
Fibrin then cross linked by XIII
Natural anticoagulants
Protein C (activated by thrombin/thrombomodulin)
Protein S - cofactor for protein C
Protein C and S cleave factors V and VIII
Antithrombin inhibits Thrombin and Xa
TAT complexes removed by liver
Activity increased 000’s by heparin
Global coagulation tests
•APTT : Kallikrein, HMWK, XII, XI, IX, VIII, X, V, II, I
•“intrinsic system”
•PT : VII, X, V, II, I
•“extrinsic system”
•TT : I
•50:50 mix with normal plasma will distunguish a lack of clotting
proteins from an inhibitor of function
CAUSES OF A PROLONGED
PROTHROMBIN TIME
CONGENITAL
•Coagulation factor deficiencies: VII, X, V, II, I
ACQUIRED
•Hepatocellular disease
•Vitamin K deficiency (II, VII, IX, X): obstructive
jaundice, haemorrhagic disease of the newborn
•Disseminated intravascular coagulation (DIC)
•Massive blood transfusion
•Warfarin (monitoring test based on PT)
•Gross overheparinisation, some lupus anticoagulants
CAUSES OF A PROLONGED ACTIVATED
PARTIAL THROMBOPLASTIN TIME
CONGENITAL
•Coagulation factor deficiencies: XII, XI, IX, VIII, X,
V, II, I
ACQUIRED
•Hepatocellular disease
•Vitamin K deficiency
•Disseminated intravascular coagulation
•Massive blood transfusion
•Heparin (monitoring test based on APTT)
•Lupus anticoagulants
CAUSES OF A PROLONGED
THROMBIN TIME
CONGENITAL
•Dys/hypofibrinogenaemia
ACQUIRED
•Hepatocellular disease: dys/hypofibrinogenaemia
•Disseminated intravascular coagulation:
hypofibrinogenaemia
FDPs
•Heparin
Haemophilia
A = reduced VIII; B = reduced IX
Both sex-linked recessive
Queen Victoria
Intronic rearrangements, point mutations, gene deletions
Haemophilia A 1 in 10,000 male infants
Prolonged APTT (normal PT and TT)
Mild Rx: Tranexamic acid, DDAVP (not HB)
Severe Rx: factor replacement recombinant or pooled donor
Home prophylaxis
Past problem with HIV, now HCV ??? CJD
Von Willebrand’s Disease
Functions of VWF:
1. Sticks to platelets (GPIb)
2. Sticks to collagen in subendothelium
(Important in small blood vessel lesions; high shear stress)
3. Binds to and protects VIII (labile)
Therefore in VWD see long APTT (low VIII) and bleeding where
VWF platelet interaction important
Von Willebrand’s Disease
Treatment options
DDAVP, antifibrinolytics
NB DDAVP causes fluid retention. NOT for type 2B
Intermediate purity VIII concentrate
VWF concentrate (NB takes hours for VIII to follow so may
need to give both)
If severe bleeding consider platelet infusion and
cryoprecipitate
(NB type I may “auto-correct” in pregnancy)
Massive blood loss
Defined as loss of > one circulating volume in 24
hours
Coagulopathy is multifactorial:
Loss of factors only once 80% of volume replaced
Dilution of factors during fluid resuscitation
Inhibitory effect of some colloids on clotting factors
DIC secondary to trauma
Acidosis
Hypothermia (enzymes) (blood warmer)
Massive blood loss
Regular checks of FBC and PT,APTT,TT and Fibrinogen
Aim for platelets > 50x109/l or >100x109/l if polytrauma or CNS
injury
Aim for fibrinogen >1g/l
Aim for PT and APTT <1.5x control times
FFP 12-15ml/kg
Cryoprecipitate 1-1.5 packs /10kg if fibrinogen fails to correct
with FFP
? rVIIa
Causes of DIC
sepsis/severe infection (any organism)
trauma (e.g. polytrauma, neurotrauma, fat embolism)
organ destruction (e.g. severe pancreatitis)
malignancy
massive blood loss with inadequate fluid replacement
vascular abnormalities (e.g. Kassbach-Merrit syndrome)
severe hepatic failure
severe toxic or immunological reactions (e.g.
recreational drugs, transfusion reactions, transplant
rejection)
Management of DIC
TREAT THE CAUSE
Fluid resus as needed, antibiotics if sepsis
If bleeding or need surgery give FFP, Platelets, Cryoprecipitate
(Aim Platelets>50x109/l, PT and APTT < 1.5x normal)
If thrombotic manifestations eg. Dermal ischaemia consider low
dose heparin infusion.
Heparin
NB arterial
lines !!!!!!!
Heparin
Unfractionated
monitor with APTT (ratio 1.5-2.5 patient’s baseline)
reversal by stopping infusion and (very rapid with protamine
sulphate)
can be hard to anticoagulate children due to low antithrombin levels
bolus then continuous infusion
Low molecular weight heparin
less monitoring
once or twice daily administration
more reliable pharmacokinetics (NB renal excretion)
anti-Xa levels - 4h post dose
Treatment 0.5-1; Prophylaxis 0.1-0.3 IU/ml
Warfarin
II, VII, IX, X, protein C and S
are vitamin K dependent.
NB C and S fall first so overlap
with heparin (Warfarin induced
skin necrosis)
Therapeutic range within 3-5
days
Monitor in anticoagulant clinic
using INR
Most indications target INR 2-3
Bleeding on warfarin
Treatment based on assessment of bleeding risk and
INR
Usually enough to stop and monitor INR daily until in
therapeutic range
Reversal with Vitamin K (6-8 hours) – large doses may
render subsequent antico difficult)
Emergency use Plasma or clotting factor concentrates
Hospital should have protocol