Types of anaemia

MICROCYTIC
Iron deficiency (IDA)
e17-3: hypochromic
microcytic anaemia
e17-4: IDA next to
normal RBCs

Thalassaemia

Aetiology

Blood loss
Poor diet
Malabsorption (e.g.
coeliacs)
Hookworm (GI bleeding;
most common cause in
tropics)

Genetic disease of
unbalanced Hb
synthesis
o Underproductio
n (or none) of
one globin
chain
-thalassaemias

Mainly by gene
deletions
-thalassaemias

Usually caused by point

mutations in -globin
genes on hCh11
+
chain production ( ) or
0
its absence ( )

Clinical Features
Chronic:

Koilonychia (spoon nails)

Atrophic glossitis (smooth tongue)

Angular cheilosis (inflammation of one/both

corner(s) of mouth)

Post-cricoid webs (rare)

Investigations

-thalassaemia

All 4 genes deleted (/ (--/--) death in

utero (Barts hydrops)

3 deleted (--/-) moderate anaemia and

features of haemolysis (hepatosplenomegaly, leg
ulcers and jaundice)

2 deleted (--/ or -/-) asymptomatic carrier

state, with MCV

1 deleted normal clinical state

-thalassaemia
(minor/trait):

Well-tolerated anaemia (>9g/dL)

May worsen with pregnancy

Often confused with IDA

(intermedia):

Moderate anaemia

Similar picture to sickle cell anaemia

(major; Cooleys anaemia)

Abnormalities in both -globin genes

Severe anaemia and failure to thrive (in first year)

Skull bossing and hepatosplenomegaly,

osteopenia

Management

Microcytic, hypochromic anaemia

tested with anisocytosis (unequal
RBC size) and poikilocytosis
(abnormally sized RBCs)
GI blood loss: gastroscopy,
sigmoidoscopy, barium enema or
colonoscopy, stool microscopy
for ova if hookworm

Oral iron, e.g. ferrous sulphate

(for 3 months to replenish
stores)
o Hb should rise by
1g/dL/week, with
modest reticulocytosis

FBC, MCV, film, iron, HbA2, HbF,

Hb electrophoresis
MRI can monitor myocardial
siderosis from iron overload

Promote fitness; healthy diet

Folate supplements
Regular life-long transfusions to
keep Hb >9g/dL
Iron-chelators to prevent iron
overload (deferiprone +
desferrioxamine)
Ascorbic acid urinary
excretion of iron

Sideroblastic
anaemia

Consider this when

microcytic anaemia is
not responding to iron

Ineffective erythropoiesis iron absorption, iron

loading in marrow haemosiderosis (endocrine,
liver and heart damage due to iron deposition)

Ferritin, film (hypochromia) and

marrow

Remove cause
Pyridoxine may help repeated
transfusion for severe anaemia

Chronic disease

Associated with many

diseases, including
chronic infection, e.g.
TB, osteomyelitis,
vasculitis, rheumatoid
arthritis, malignancy and
renal failure

Cytokine-driven inhibition of red cell production

Milk normocytic anaemia (e.g. Hb

>8g/dL)
Ferritin normal or

Treat underlying disease

Erythropoietin is effective in
raising Hb levels in cases of
renal failure that causes
erythropoietin deficiency

NORMOCYTIC
Aplastic

Aetiology

Haemolysis
e17-6: macrocytosis
e17-8: spherocytosis
e17-14: elliptocytosis
e17-22: Heinz bodies

Sickle cell anaemia

e17-12: sickle cells
e17-13: target cells

Rare stem cell disorder

~5 cases per million/year
Most cases are autoimmune,
triggered by drugs, or by viruses
(e.g. parvovirus)
May be inherited, e.g. Fanconi
anaemia

Acquired:

Immune-mediated: drug-induced,
autoimmune haemolutic anaemia,
paroxysmal cold haemoglobinuria

Direct antiglobulin/Coombs

Microangiopathic haemolytic
anaemia

Infection: malaria

Paroxysmal nocturnal
haemoglobinuria (rare acquired stem
cell disorder)
Hereditary:

Enzyme defect: G6PD deficiency

(chief RBC enzyme defect), pyruvate
kinase deficiency (ATP production
RBC survival)

Membrane defects: hereditary

spherocytosis, hereditary
elliptocytosis

Haemoglobinopathy: sickle cell

disease, thalassaemia

AA substitution in gene coding for

chain (GluVal at position 6)
production of HbS rather than HbA

Clinical Features

Investigations

Pancytopenia (deficiency of all

3 cellular components of blood;
red cells, white cells and
platelets)
Hypoplastic marrow (marrow
stops making cells)
Features of anaemia (Hb),
infection (WCC) or bleeding
(platelets)

Premature breakdown of RBCs

before their normal life span of
~120d
In sickle cell anaemia, life span
can be as short as 5d

Vaso-occlusive painful crisis:

due to micro-vascular occlusion
o Triggered by cold,
dehydration, infection
or hypoxia
Aplastic crisis: due to
parvovirus B19, with sudden
reduction in marrow production,

Management

Marrow examination for diagnosis is

needed

FBC, reticulocytes, bilirubin, LDH,

haptoglobin, urinary urobilinogen
Thick and thin films for malaria screen if
history of travel, which may show
polychromasia and macrocytosis due to
reticulocytes
Hypochromic microcytic anaemia =
thalassaemia
Sickle cells = SCA
Schistocytes = microangiopathic
haemolytic anaemia
Abnormal cells in haematological
malignancy
Spherocytes = hereditary spherocytosis
or autoimmune haemolytic anaemia
Elliptocytes = hereditary elliptocytosis
Heinz bodies (bite cells) = G6PD
deficiency

Hb 6-9g/dL, reticulocytes 10-20%,

bilirubin
Film: sickle cells and target cells
Positive sickle solubility test
Hb electrophoresis (confirmed diagnosis
and distinguishes between SS and AS
states and other Hb variants)

Support blood count

Neutropenic regimen for the
asymptomatic patient
Allogeneic marrow
transplantation for young
patients from an HLAmathced sibling
Immunosuppression with
ciclosporin and antithymocyte
globulin may be effective
(although not curative)

Hydroxycarbamide if frequent
crises
Splenic infarction leads to
hyposplenism
Febrile children risk
septicaemia - repeated
admission may be avoided by
outpatient ceftriaxone

Acute blood loss

Bone marrow failure

Aplastic anaemia
Paroxysmal nocturnal
haemoglobinuria (RBCs break apart
prematurely)

Polycythemia vera (bone marrow

makes too many RBCs)

Diamond-blackfan anaemia
(congenital erythroid aplasia
RBCs)

Essential thrombocytosis
(overproduction of platelets by
megakaryocytes in bone marrow)
Autoimmune causes:
0

1 atrophic hypothyroidism: diffuse

lymphocytic infiltration of thyroid
atrophy

Hashimotos thyroiditis: goitre due to

lymphocytic and plasma cell
infiltration
Other causes:

Iodine deficiency (chief cause

worldwide)

Post-thyroidectomy or radioiodine
treatment

Drug-induced: antithyroid drugs,

amiodarone, lithium, iodine

Subacute thyroiditis

e17-32: aplastic
anaemia bone marrow

Hypothyroidism

especially RBCs
Sequestration crisus: mainly
affects children as spleen has
not yet undergone atrophy;
pooling of blood in spleen
liver, with organomegaly,
severe anaemia and shock

Low blood counts

Low platelets count
spontaneous bleeding in skin
and mucous membranes
Netropenia risk for serious
infections
Weakness and fatigue as a
result of anaemia
Pallor and/or congestive heart
failure

Fatigue, lethargy, mood

Cold-disliking
weight
Constipation
Menorrhagia
Hoarse voice

Bone marrow transplant can

be curative, but remains
controversial

Red cells morphologically normal

Reticulocyte count less than 1% ( lack
of RBC production)
platelet count

TSH
T4
Cholesterol and triglyceride
Macrocytosis

Blood transfusion of specific

cell that is deifiency
Bone marrow transplantation
(younger than 55yo w severe
diseased and matched,
related donor)

Levothyroxine (T4; healthy

and young)
Lower dose in elderly or those
with ischaemic heart disease

MACROCYTIC
Megaloblastic
e17-13: target cells
e17-37: megaloblastic
erythropoiesis

Aetiology
The presence in the bone marrow of
developing RBCs with delayed
nuclear maturation relative to that of
the cytoplasm

Defective DNA synthesis

WC (leukopenia)
platlets (thrombocytopenia)

Clinical Features

Mild jaundice due to combination of

anaemia and increased indirect
bilirubin levels
Glossitis with cobalamin deficiency
Hyperpigmentation of skin and
abnormal hair pigmentation due to
increased melanin synthesis
Irritability and peripheral neuropathy

Causes: B12/folate deficiency; drugs

(hydroxycaramide/ hydroxyurea)

Investigations
Blood film

Hypersegmented polymorphs in B12 and

folate deficiency

Target cells if liver disease

Management

Other tests

LFT

TFT

Serum B12

Serum folate (or red cell folate)

Bone marrow biopsy

Megaloblastic

Normoblastic marrow (e.g. liver disease,

hypothyroidism)

Abnormal erythropoiesis (e.g.

sideroblastic anaemia, leukaemia, aplasia)

erythropoiesis (e.g. haemolysis)

Pernicious anaemia

Vitamin B12
deficiency

Folate deficiency

Autoimmune atrophic gastritis

achlorhydria (absence of HCl) and
lack of gastric intrinsic factor
secretion B12absorption
(Associated with other autoimmune
conditions, e.g. thyroid, vitiligo,
Addisons)
Diet

Veganism (no animal products)

Impaired absorption

Pernicious anaemia

Gastrectomy (no IF from

terminal ileum)

Ileal disease/resection; coeliac

disease
Poor intake

Old age

Poverty

Anorexia
Malabsorption

Coeliac disease

Tropical sprue
Excess utilisation

Consideration: pernicious anaemia

has a very slow progression
(therefore hard to diagnose)
Fatigue/tiredness
Bright red, smooth tongue
Tingling/numbness of hands and feet

Symptoms of anaemia
Lemon tinge to skin due to pallor
(anaemia) + mild jaundice
(haemolysis)
Glossitis
Angular cheilosis (aka stomatitis)

Often, patient presents with history

of excessive alcohol intake w
concurrent poor diet
Glossitis
Angular stomatitis (cheilitis)
o Occurs when anaemia is
severe enough to cause
megaloblastic anaemia

Hb (3-11g/dL), MCV, WCC & platelets

(if severe)
serum B12
reticulocytes
Hyposegmented polymorphs
Megaloblasts in marrow
Serum homocysteine (normal range 5-16
mmol/L)
Serum methymalonic acid (normal range
70-270 mmol/L)

Serum folate (normal range 2.5-20

ng/mL)
Serum homocysteine (normal range 5-16
mmol/L)
RBC folate levels

Folic acid (never w/o B12

unless patient known to
have normal B12 levels)
Pregnancy: prophylactic
doses of folate to help
prevent spina bifida and
anaemia

Pregnancy; lactation;
prematurity
Chronic haemolytic anaemia;
malignant and inflammatory
diseases
Dialysis

Myelodysplastic
syndromes

May present w GI symptoms, e.g.

nausea, vomiting, abdominal pain,
and diarrhoea
Anorexia common weight loss
Cognitive impairment, dementia,
depression
Manifestations overlap with those of
B12 deficiency

May develop secondary to

chemotherapy or radiotherapy

e17-39: ringed
sideroblasts

Pancytopenia with reticulocyte count

Marrow cellularity due to ineffective
haematopoiesis
Ring sideroblasts in marrow

Multiple transfusions of red

cells or platelets as needed
Erythropoietin human
granulocyte colony
stimulating factor (G-CSF)
may lower transfusion
requirements
Immunosuppressives, e.g.
ciclosporin or antithymocyte
globulins
Curative allogeneic stem
cell transplantation

Others: liver disease/alcoholism, reticulocytosis, cytotoxics (chemo etc)

Leukaemia

Malignancy of lymphoid cells

Affecting either B or T lymphocyte cell lines, arresting maturation and promoting uncontrolled proliferation of immature blast cells, with bone marrow failure and tissue infiltration

Thought to develop from combination of genetic susceptibility (e.g. with translocations, and gains and losses of whole chromosomes) w an environmental trigger

Acute lymphoblastic leukaemia (ALL) - as an example of leukaemia

Classification
Signs and symptoms
Morphological

Marrow failure

FAB system (French, American and

o Anaemia (Hb)
British)
o Infection (WCC)

Divides all into three types: L1, L2, L3 by

o Bleeding (platelets)
microscopic appearance

Infiltration

Provides limited information

o Hepato- and splenomegaly
Immunological
o Lymphadenopathy (superficial

Surface markers used to classify all into:

or mediastinal)
precursor B-cell ALL, T cell ALL, B-cell
o Orchidomegaly
ALL
o CNS involvement (e.g. cranial
Cytogenic
nerve palsies, meningism

Chromosomal analysis

Common infections

Abnormalities detected in up to 85%

o Especially chest, mouth,
which are often translocations
perianal and skin
o Bacterial septicaemia, zoster,

Useful for predicting prognosis, e.g. poor

prognosis with Philadelphia chromosome
CMV, measles, candidiasis,
Pneumocystic pneumonia
and for detecting disease recurrence

Investigations

Characteristic blast
cells on blood film and
bone marrow; WCC
usually high
CXR and CT scan to
look for mediastinal and
abdominal
lymphadenopathy
Lumbar puncture
should be performed to
look for CNS involvment

Treatment

Education and motivate

Support
o Blood/platelet transfusion
o IV fluids
o Allopurinol: prevents tumour lysis syndrome
Infections
o Dangerous due to neutropenia caused by disease
and treatment
o Immediate IV antibiotics for infection
o Start neutropenic regimen: prophylactic antivirals,
antifungals and antibiotics
Chemotherapy
o Patients entered into national trials
o Typical programme involves: remission induction,
consolidation, CNS prophylaxis, maintenance
Matched related allogeneic marrow transplantations
o Best option in standard-risk younger adults

Treatments and anticoagulation therapies

Main indications
o Therapeutic: DVT and PE
o Prophylactic: prevention of DVT/PE in high-risk patients, e.g. post-op; prevention of stroke, e.g. in chronic AF or prosthetic heart valve
Heparin
Low molecular weight heparin (LMWH)

Given subcutaneously, e.g. dalteparin, enoxaparin, tinzaparin

Inactivates factor Xa (but not thrombin)

Half life is x2-4 longer than standard heparin and response to more predictable so only needs to be given once/twice daily

Not laboratory monitoring usually required

Replaced unfractionated heparin (UFH) as preferred option in prevention & treatment of DVT and in acute coronary syndrome

Accumulates in renal failure: lower doses are used for prophylaxis, or UFH for therapeutic doses
Unfractionated heparin (UFH)

Given IV or SC

Glycosaminoglycan

Binds antithrombin (an endogenous inhibitor of coagulation) increase ability to inhibit thrombin, factor Xa and IXa

Rapid onset and has short half life

Side effects:

Bleeding - at operative site, GI, intracranial

Heparin-induced thrombocytopenia

Osteoporosis with long-term use

Warfarin

Used orally once daily as long-term anticoagulation

Therapeutic range is narrow, varying with condition

being treated
o Measured as a ratio compared with standard
INR (international normalised ratio)

Warfarin inhibits reductase enzyme responsible for

regenerating the active form of vitamin K state
analogous to vitamin K deficiency
Contraindications:

Peptic ulcers

Bleeding disorders

Severe hypertension

Pregnancy