Haematology 2.

Pathology of Red Blood Cells

C. Riedinger

Chapter 2

Pathology of Red Blood Cells

Following Handout on pages 50, podcast content formatted in Arial.

Haematology 2. Pathology of Red Blood Cells

C. Riedinger

Table of Contents
Chapter 2......................................................................................................................0
Pathology of Red Blood Cells.....................................................................................0
Table of Contents........................................................................................................1
1. Deficiency of RBCs/Hb: Anaemia [1-4]..............................................................2

a)
b)

1.1. Clinical Manifestations of Anaemia..................................................................2

1.2. Laboratory Investigations of Anaemia..............................................................3
1.3. Causes of Anaemia............................................................................................5
1.3.1. Decreased production................................................................................5
1.3.2. Increased destruction.................................................................................5
1.3.3. Loss...........................................................................................................5
1.4. Microcytic Anaemia Anaemia of diminished Erythropoiesis.........................6
1.4.1. Causes of Microcytosis.............................................................................6
1.4.2. Iron Deficiency Anaemia...........................................................................6
1.4.3. Anaemia of chronic disease.......................................................................8
1.4.4. Thalassaemia (also a haemolytic anaemia)...............................................9
1.4.5. Sideroplastic anaemia..............................................................................10
1.5. Normocytic Anaemia.......................................................................................10
1.6. Macrocytic/Megaloblastic Anaemia................................................................11
1.6.1. Causes of Macrocytic Anaemia...............................................................12
Folate deficiency anaemia...........................................................................................12
Vitamin B12 Deficiency Anaemia (+ Pernicious Anaemia).......................................13
1.7. Haemolytic Anaemias......................................................................................14
1.7.1. Thalassaemia (also a microcytic anaemia)..............................................16
1.7.2. Sickle cell anaemia..................................................................................18

2. Excess of RBCs - Polycythaemia Rubra Vera [2]...............................................23

Bibliography..............................................................................................................27

Haematology 2. Pathology of Red Blood Cells

C. Riedinger

1. Deficiency of RBCs/Hb: Anaemia [1-4]

-

Reduction of the total circulating red cell mass below normal limits
decreasing the oxygen-carrying capacity of the blood

Epidemiology of anaemia:
o 10% in developed countries
o 25-50% in developing countries
o Of this iron deficiency most common

1.1.
-

Clinical Manifestations of Anaemia

Acute
o SOB
o Organ failure
o shock

Chronic
o pallor (pale skin, mucosal linings, nail beds, skin creases)
o fatigue
o + haemolysis: jaundice and gallstones
o + ineffective erythropoiesis: iron overload, heart and endocrine failure
o severe and congenital: growth retardation, bone deformities due to
reactive marrow hyperplasia
o related - signs of iron deficiency:

can be mild or asymptomatic

koilonychias (in long-standing anaemia)

dizziness

hair loss

irritability

weakness

pica, pagophagia

Haematology 2. Pathology of Red Blood Cells

C. Riedinger

Plummer Vinson syndrome (atrophy of pharyngeal mucous

membranes)

1.2.
-

Restless leg syndrome

Laboratory Investigations of Anaemia

FBC (low, high, changed either way)

o

WBC

RBC

Hb

Haematocrit

Platelets

MPV (mean platelet volume)

MCV (mean corpuscular volume) => micro, normo, macrocytic!

MCH (mean corpuscular Hb)

MCHC (mean corpuscular c(Hb))

Iron tests
o

Serum iron

Limited routine value

Best for iron overload and acute iron poisoning

Transferrin iron transporter in blood

Made by liver, therefore look at liver values too!!

Liver problem, proteins low, transferrin (AOCD)

Transferrin if iron low

TIBC (total iron binding capacity), often measured instead of

transferrin, as cheaper

UIBC = Serum iron TIBC (unsaturated iron binding capacity)

Transferrin saturation normally 30%, low in iron deficiency,

high in overload

Serum ferritin IC iron storage protein

Its value reflects the amount of iron stored

Haematology 2. Pathology of Red Blood Cells

C. Riedinger

Ferritin => clear iron deficiency, but need to look at CRP as well,
as infection increases ferritin can mask iron deficiency

Red cell protoporphyrin carrier of divalent cations, porphyrin precursor

Ferroportin iron absorption in gut (basolateral TM protein)

Hepcidin ferroportin regulator (antagonist)

Overview of different constellations on iron profile:

Condition

Serum Iron

Iron
deficiency
anaemia
Anaemia
of chronic
disease
Pregnancy

Low

Transferrin,
TIBC
High
(compensates)

Transferrin
saturation
Low

Ferritin

Hepcidin

Low

Low

Normal

High

High

Normal

High

Low

Protoporphyrin
High

LFTs
o

Indicate existence, extent and type of liver damage

Also look at serum albumin => livers synthetic capacity

Billirubin total, i.e. conjugated and unconjugated

Iron containing porphyrin

Unconjugated bound to albumin

Conjugated (in the liver) free

Aminotransferases

Raised values indicate acute liver damage

AST Asp aminotransferase, raised in MI, heart failure, hepatic

necrosis

ALT Ala aminotransferase, more specific to liver disease

Alkaline phosphatase

Raised in response to cholestasis

Also present in bone, small intestine, placenta (3rd trimester) and

kidney

Increased activity is an indicator of osteoblast activity = bone

formation as in Pagets Disease for example!

Gamma-glutamyltranspeptidase

Haematology 2. Pathology of Red Blood Cells

C. Riedinger

Alcoholic liver disease

Can also include INR, total protein, antibodies, viral markers

CRP to assess status of infection and interaction with ferritin levels

1.3.
1.3.1.
-

Causes of Anaemia
Think decreased production or increased destruction! (and more)
Decreased production
Bone marrow aplasia => aplastic anaemia
o

Drugs

Radiotherapy

Radiation

Autoimmune conditions

Post viral infection

Bone marrow hyperplasia, non-functional bone marrow => megaloblastic

anaemia

Folate/Vitamin 12 deficiency

Congenital

Cytotoxic drugs

Bone marrow infiltration

o

Cancer

Leukaemias

Myelodysplasia ineffective production of myeloid cells

Myeloproliferative disorders

1.3.2.

Myelofibrosis

Polycythaemia rubra vera

Essential thrombocytosis

Increased destruction

Hypersplenism

Spherocytosis

Sickle cell anaemia

Haematology 2. Pathology of Red Blood Cells

C. Riedinger
1.3.3.

Thalassaemia
Loss

Acute: Trauma, surgery

Prematurity (frequent blood sampling!!)

Menstruation

Chronic: GI lesions, gynaecological disturbances, parasitic infections

=> iron deficiency anaemia

Dilution:
o

Hypervolaemia

Pregnancy

1.4.

Microcytic Anaemia Anaemia of diminished Erythropoiesis

Anaemia characterised by small RBCs, also known as microcythaemia.

Small RBCs with MCV

1.4.1.
-

1.4.2.

Causes of Microcytosis
Childhood:
o

Iron deficiency anaemia

Thalassamia

Adulthood:
o

Iron deficiency anaemia

AOCD (also this also causes normocytic anaemia!)

Sideroplastic anaemia

Lead poisoning

Iron Deficiency Anaemia

Reduction in Hb concentration due to inadequate iron supply

Epidemiology
o

Most common cause of anaemia

10% in developed countries

25-50% in developing countries

Of this iron deficiency most common

Haematology 2. Pathology of Red Blood Cells

C. Riedinger
-

80% of functional body iron in Hb

20% of iron in storage

iron balance maintained by regulating the absorption of iron

Aetiology
o

western world:

chronic blood loss

peptic ulcer

colorectal carcinoma (have to rule out in adult with

IDA!!!)

diverticular disease

gynaecological

malabsorption (e.g. celiac disease)

increased blood loss means increased RBC production =>

stores depleted

developing world:

low iron intake

poor bioavailability

parasitic disease: hookworm infection

increased demands not met: pregnancy or infancy

malabsoroption in celiac disease or after

Pathogenesis
o

If insufficient iron, haem group of Hb cannot be synthesised

Disruption of final step in haem synthesis

Investigations
o

FBC

Iron tests

LFTs

CRP

Blood film

Clinical features
o

May be asymptomatic

Haematology 2. Pathology of Red Blood Cells

C. Riedinger

Symptoms and signs, see above

blood film: microcytic and hypochromic

Hb low

MCV low

Serum ferritin and iron low

Transferrin saturation low

TIBC high (because depleted?)

Platelet count often elevated for unknown reasons

Erythropoietin high

Marrow cellularity only slightly increased

Microscopic features
o

Microcytic (small) and hypochromic (pale) red cells

Variation in RBC size (anisocytosis) and shape (poikilocytosis)

Pencil cells: long elyptical cells

Bone marrow: erythroid hyperplasia and absence of stainable iron

From podcast:
o

Normal 2/3 haemoglobinised, abnormal red ring only 1/3

Confirm by measuring ferritin as representer of iron stores but also a

marker of acute inflammation

1.4.3.
-

Treat by treating underlying cause

Anaemia of chronic disease

Reduction in Hb concentration related to chronic inflammatory
disorders, infection and malignancy.

Epidemiology
o

Most common form of anaemia in hospitalised patients

2nd most common cause of anaemia

Aetiology
o

chronic infections

chronic inflammatory disorders

neoplasms

Pathogenesis

Haematology 2. Pathology of Red Blood Cells

C. Riedinger
o
o

Complex, not fully understood

Cytokine-driven inhibition of RBC production in marrow

Inflammatory cytokines such as IL-6 cause reduced sensitivity

of bone marrow to erythropoietin

Failure to incorporate iron into RBCs

Reduced iron absorption from intestine

Reduced activity of iron transport via ferroportin across

membrane

Hepcidin inhibits ferroportin (reduces transport of iron into

erythrocytes)

Hepcidin is raised in AOCD, therefore iron deficiency

develops

transported in the blood by transferrin

If transferrin saturated, then iron stays bound to epithelium,

which renews every 3-4 days and means that the iron will be
lost

Microscopic Features
o

Normal to small RBCs

No other features

Bone marrow: normal with stainable iron

Clinical Features
o

1.4.4.

Similar to iron deficiency anaemia, but

ferritin elevated

TIBC reduced

MCV normal or low

Diagnosis
o

Look at ferritin, transferrin, transferrin saturation, and hepcidin

Best method of assessing iron levels is bone marrow or liver biopsy

Thalassaemia (also a haemolytic anaemia)

Genetic disease of unbalanced Hb synthesis

Epidemiology
o Alpha is prevalent in the Far East

Haematology 2. Pathology of Red Blood Cells

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10

o Beta is prevalent in the Mediterranean

-

Aetiology
o Genetic

point mutations in the b-globin genes on chromosome 11 =

beta

mutations (usually deletions) in the a-globin genes on

chromosome 16 = alpha

o different severities

minor/trait = heterozygous

major = homozygous

Pathogenesis
o One Hb chain is underproduced
o Other Hb chain precipitates => haemolysis via RBC membrane
damage
o Occurs while cells still in the bone marrow

Clinical Features
o If minor/trait then asymptomatic or minor anaemia, exacerbation
during pregnancy
o If major

Presents in 1st year of life

Severe anaemia and FFT

Characteristic head shape with skull bossing

osteopenia

o Iron accumulation
o ferritin increased
-

Treatment
o Promote healthy lifestyle and diet
o Folate supplements
o Iron chelators to prevent iron overload
o Lifelong transfusions if major trait

Haematology 2. Pathology of Red Blood Cells

C. Riedinger
1.4.5.
-

1.5.

11

Sideroplastic anaemia
BM produces sideroblasts instead of RBCs
Genetic or part of myelodysplastic syndrome
Inability to incorporate iron into Hb

Normocytic Anaemia

Simply not enough RBCs.

Causes

AOCD

Acute blood loss

Pregnancy due to increase in plasma volume, but occasionally microcytic

iron deficiency or macrocytic vitamin B12 deficiency anaemia

Bone marrow failure

renal failure (EP?)

cancer

Sometimes several cytic anaemias can arise at the same time!

1.6.
-

Macrocytic/Megaloblastic Anaemia

In megaloblastic anaemia, there is an overall decrease in the circulating

mass of RBCs due to impaired DNA synthesis and the appearance of
megaloblasts, enlarged erythroid precursors that give rise to abnormally
large red cells (macrocytes).

Epidemiology
o

Autoimmune gastritis 1/1000

F>M

Aetiology
o

Vitamin B or folate deficiency (see below) due to alcoholism, poor diet or

malabsorption

o
-

Autoimmune gastritis => pernicious anaemia

Pathogenesis
o

Impaired DNA synthesis as insufficient building blocks

Haematology 2. Pathology of Red Blood Cells

C. Riedinger
o

12

DNA duplication fails => arrest of development => immature

megaloblastic RBCs in bone marrow => macrocytes in the blood

Microscopic Features
o

Megalocytes are produced as a result of a defect in DNA synthesis that

impairs nuclear maturation and cell division and results in:

Delayed nuclear maturation

Hypersegmented neutrophils (more nuclear lobes)

Nuclear cytoplasmic asynchrony (RNA synthesis and protein

synthesis occur at a faster rate)

Anisocytosis

Poikilocytosis

Large oval macrocytes

Nucleated RBCs

Bone marrow:

Hypercellular

Megaloblasts

Presentation
o

Symptoms of anaemia

Mild jaundice

Neurological symptoms if related to B12 deficiency

1.6.1.

Causes of Macrocytic Anaemia

B12 deficiency and folate deficiency

Liver disease

Alcohol abuse, but can just cause macrocytosis without anaemia

Certain drugs, e.g.

o

chemotherapy reagents

antifolate drugs

Severe hypothyroidism

Haemolytic anaemia/reticulocytosis

Liver disease

Myeloproliferative disease

Pregnancy

Haematology 2. Pathology of Red Blood Cells

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-

Chronic exposure to benzene

Haemolytic anaemia

a)

Folate deficiency anaemia

Folate = carbon donor in purine synthesis, i.e. DNA building blocks

Folate contained in green veggies and liver and cereal

o

Absorbed in small intestine (less specialised than B12)

main site of absorption in upper 1/3 of small intestine

Pregnancy => folate deficiency => neural tube defects

Marginal folate stores not uncommon

Aetiology
o

poor diet

elderly

pregnant women

people with haemolytic anaemias

drugs

Phenytoin (antiepileptic) inhibits folate absorption

Methotrexate inhibits folate metabolism

Malabsorption

Inflammatory bowel conditions

Celiac disease

Clinical Features
o

Non-specific symptoms at onset

Potential deficiency of other vitamins, especially in alcoholics

Alimentary tract symptoms can occur as quick turnover of epithelial cells

impaired by lack of folate

13

Detect in blood smear and bone marrow aspirate

Measure serum and red cell folate and B12 levels to distinguish

Treatment
o

Best sources uncooked foods as destroyed after 15min of cooking

Nutritional supplements (400ug/d)

Acidic foods prevent absorption

Haematology 2. Pathology of Red Blood Cells

C. Riedinger
b)

14

Vitamin B12 Deficiency Anaemia (+ Pernicious Anaemia)

Vit B12 required for folate recycling

B12 absorbed via intrinsic factor which is produced in parietal cells by stomach,
then absorbed in terminal ileum

intrinsic factor aids absorption of B12 in small intestine (first B12 binds to
haptocorrin in the stomach, at higher pH to intrinsic factor)

Aetiology
o

Usually long standing malabsorption

Diet usually provides enough B12 unless vegan

Pernicious anaemia: autoimmune reaction against parietal cells and

intrinsic factor => gastric mucosal atrophy

After gastrectomy

poor diet

gastrectomy, removal or inflammation of terminal ileum

Clinical Features
o

Non-specific signs of anaemia

May include mild jaundice due to increased destruction of erythroid

progenitors

GI symptoms similar to folate deficiency

Low serum B12

Normal or elevated folate levels

Serum antibodies to intrinsic factor

Moderate to severe megaloblastic anaemia

Leukopenia with hypersegmented granulocytes

Dramatic reticulocytic response (within 2-3d) to parenteral adminstration

of vit B12

Neuro abnormalities: demyelination of peripheral nerves! These often

dont resolve even after B12 administration

Complications
o

Neuritis

Dementia

subacute combined degeneration of the spinal cord

Haematology 2. Pathology of Red Blood Cells

C. Riedinger

1.7.
-

15

Haemolytic Anaemias

Is an anaemia due to haemolysis, i.e. abnormal breakdown of RBCs either

intra- or extravascularly.

RBCs have decreased lifespan (120d normally)

Aetiology look at three RBC components

o

1. Problems with Hb

Thalassaemia

Sickle cell anaemia

Lead poisoning

2. Problems with the RBC Membrane

Aetiology

Hereditary spherocytosis (autosomal dominant)

o

RBCs lack a membrane protein => turned into

spherocytes upon first passage through spleen,
later lysed

Autoimmune haemolytic anaemia AIHA

o

autoantibodies cause lysis and spherocytosis

caused by IgG (warm AIHA)

by IgM (cold AIHA)

because of their oxygen binding temperature

Warm are affected more in summer, cold in winter

Drug-induced autoimmune reactions

o

e.g. ABs to penicillin

immune complexes as reaction to quinine

Alloimmune reactions
o

acute transfusion reaction leading to rapid

haemolysis

more ACQUIRED causes!

Pathogenesis

reduced surface area of RBCs

loss

of

biconcave

SPHEROCYTOSIS

shape

=>

spherocyte

Haematology 2. Pathology of Red Blood Cells

C. Riedinger

16

Oxygen diffusion less efficient as surface to volume

smaller

If more rigid => lysis in splenic sinusoids turns RBCs into

spherocytes

3. Problems with RBC Metabolism

defects in pentose-phosphate pathway

or glycolysis (not mitochondria)

Glucose-6-phosphate dehydrogenase deficiency (X-linked)

Enzyme in pentose-phosphate pathway essential in RBCs

Acute oxidative crises with anaemia and jaundice

ROS are not removed

Precipitated by illness, drugs such as aspirin, fava beans!

Other hereditary metabolic causes

More HEREDITARY

4. Misc

Infections

Malaria causes lysis by mechanical disruption

= MicroAngiopathic Haemolytic Anaemias (MAHA)

Group of haemolytic anaemias caused by small vessel pathology,
haemolysis caused by fibrin depositin, mechanical disruption and
platelet aggregatin.

Haemolytic

uraemic syndrome

HUS,

see histopath

chapter 6.10.

Thrombotic thrombocytopenia purpura TTP

Disseminated intravascular coagulation DIC

Severe hypotension, e.g. in pre-eclampsia

Prostetic heart valves

-

Miscoscopic Features
o

immature RBCs (reticulocytes, with blue granules of RNA in the cp, of

greater volume)

o
-

possible presence of spherocytes (sphere-shaped RBCs)

Clinical Features

Haematology 2. Pathology of Red Blood Cells

C. Riedinger
o

17

Breakdown intravascular => excess Hb in the blood => filtered in the

kidneys => Hb-uria

Breakdown extravascular

in reticuloendothelial system (macrophages or liver, spleen and

marrow): splenomegaly, splenic hypertrophy

prehepatic jaundice (unconjugated billirubin is not degraded by

the liver to conjugated billirubin)

Erythropoietin increased

Iron recycling increased

Erythroid hyperplasia of bone marrow

Investigations
o

Include direct antiglobulin tests to check for antibodies and rule out
immune haemolytic anaemia

1.7.1.

Thalassaemia (also a microcytic anaemia)

Genetic disease of unbalanced Hb synthesis

Epidemiology
o Alpha is prevalent in the Far East
o Beta is prevalent in the Mediterranean

Aetiology
o Genetic

point mutations in the b-globin genes on chromosome 11 =

beta

mutations (usually deletions) in the a-globin genes on

chromosome 16 = alpha

o different severities

minor/trait = heterozygous

major = homozygous

Pathogenesis
o One Hb chain is underproduced
o Other Hb chain precipitates => haemolysis via RBC membrane
damage

Haematology 2. Pathology of Red Blood Cells

C. Riedinger

18

o Occurs while cells still in the bone marrow

-

Clinical Features
o If minor/trait then asymptomatic or minor anaemia, exacerbation
during pregnancy
o If major

Presents in 1st year of life

Severe anaemia and FFT

Characteristic head shape with skull bossing

osteopenia

o Iron accumulation
o ferritin increased
-

Treatment
o Promote healthy lifestyle and diet
o Folate supplements
o Iron chelators to prevent iron overload
o Lifelong transfusions if major trait

1.7.2.
o

Sickle cell anaemia

Epidemiology

of west-africans and 1/10 afro-caribbeans carry the sickle cell gene

o

Aetiology
B-chain abnormality = Hb-S

If combined with thalassaemia, significant sickleing events

life expectancy is reduced:

QuickTime and a
decompressor
are needed to see this picture.

causes of death
-

lung complications

stroke

infections

Haematology 2. Pathology of Red Blood Cells

C. Riedinger
-

19

splenic sequestration

- chronic organ damage or failure

In children causes vary according to age (infection,

stroke, therapy complications, emboli, sequestration,
organ failure)

Infections most common most of death in

all child age groups

0-2y: infection and sequestration of blood in

an organ

~16y: stroke peaks, can be prevented with

modern techniques

early detection of Hb-S is important to

prevent infection by prophylactive penicillin
V and pneumococcal vaccines can be
initiated from 3 months onwards.

Death from infection due to autoinfarction of the spleen

Results in poorly or non-functional spleen rendering children more prone

to infections

Difficult to establish prognosis (see figure below)

WCC, degree of anaemia and dactylitis have some predictive power

High WCC predisposes to higher occurrence of sickling

QuickTime and a
decompressor
are needed to see this picture.

Acute complications of sickle cell anaemia in children

Termed sickle cell crises
Can be vaso-occlusive, haemolytic, aplastic or to do with sequestration
painful vaso-occlusive crises: (distressing symptom)

Variable in severity, may need opiate analgesia

Haematology 2. Pathology of Red Blood Cells

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20

Underlying pathophysiology is bone marrow ischaemia, avascular

necrosis

With increasing age, as bone marrow becomes more axial rather

than peripheral, the pain becomes more central with age

Treatment: analgesia, fluids, antibiotics

Dactylitis (vaso-occlusive) can be first clinical manifestation of

sickle cell anaemia
o

extremely painful and tender

treatment is analgesia, hydration and antibiotics if

fever

Girdle syndrome (presumed vaso-occlusive)

Painful crisis affecting the abdomen

Can be silent distended abdomen and extreme pain, can mimic

acute surgical abdomen, need to distinguish

Also prone to producing gall stones => can be cholecystitis

CNS events (vaso-occlusive)

Ischaemia, acute infarction, stroke

Occurs in up to 7% in children

Incidence 0.7%/y for first 20y

Peak incidence at 5-10y

Stroke can happen in isolation or post crisis

Management of stroke in children

Exchange transfusion

MRA, cerebral dopplers

Untreated 20% mortality

High instance of permanent motor disability

70% recurrence of stroke in 3 years of first event

national recommendation is that children from 2-16 are

screened with transcranial Doppler on temple to measure
MCA blood flow to predict risk of stroke, if risk high then
blood transfusions to reduce risk

Priapism (vaso-occlusive)

Haematology 2. Pathology of Red Blood Cells

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21

Can occur in 40-50% of young men

If lasting >6h can cause permanent damage resulting in erectile

dysfunction

Can occur acutely fulminant or stuttering, i.e. recurring short

episodes, but self-limiting

Commonly start in sleep or early morning

Need urgent treatment

Fluids, analgesia, catheter

If does not settle then contact urologist for potential surgical

intervention, injections of phenylephrine

Exchange transfusions are controversial but still performed,

effectiveness limited
Sickle cell chest crisis (vaso-occlusive)

Sickling is the result of poor oxygenation in consolidated

areas of the lungs

Can come on extremely fast

In context of upper or lower resp tract infection that then

progresses

CXR of patient with fever, raised RR, normal sats

Within 12h bilateral basal shadowing of both lung fields

Extremely unwell, intubation and ventilation

=> any child with Hb-S and respiratory symptoms needs to be

treated rapidly with

IV fluids

Hydration

IV antibiotics

Oxygen therapy to maintain sats above 95%

transfusion

CXR changes can occur very rapidly

If any reason to suspect sickling in chest then emergency

measures and exchange transfusion
Acute sequestration crisis

Most coming affects children <2 and spleen

Haematology 2. Pathology of Red Blood Cells

C. Riedinger
o

Spleen enlarges rapidly due to pooling of blood

Rapid Hb fall, => blood transfusion

Most commonly occurs in septic sick child

Significant mortality => prompt treatment

Post transfusion the spleen often improves rapidly but in 50%

22

recurrence => splenectomy

avascular necrosis of the femoral head!

Treatment of sickle cell anaemia in children

o

Prevention

Education of parents and children to maintain health, can cope

with minor crises at home by increasing fluid intake and
analgesia, if worse then attend hospital, teach patents how to feel
for spleen to detect splenic sequestration early

General measures in hospital such as analgesia, fluids,

antibiotics, oxygen
Multidisciplinary input, protocols

Transfusion
sometimes difficult as optimal haematocrit for O2 carriage vs
increased viscosity, if too much transfused to raise Hb to normal
levels but if viscosity too high then further complications such as
stroke
alloimmunisation also a problem, sickle cell population has
different surface antigens than blood donors => sensitisation to
red cell antigens => cross matching becomes very difficult, e.g. U
antigens, patients become almost untransfusable, therefore limit
transfusion to severe cases such as chest crises, splenic
sequestration and stroke

Hydroxyurea
Oral chemotherapy reagent for myeloproliferative disorders or
CLL
Side-effect: increased production of fetal Hb which reduces
sickling, also neutrophil reduction, which can also be beneficial

Haematology 2. Pathology of Red Blood Cells

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23

Very effective in patients with recurrent chest crises but efficacy in

preventing strokes has not been proven
o

Bone marrow transplantation

o

Limited use (300-400 patients worldwide so far)

Children <16y are referred, those with very severe

phenotypes will benefit most

Require matched sibling donor

Only a small number of patients are eligible

Outcome: 91% survival, 73% event-free survival, 18%

rejection or recurrence

=> a lot of families are reluctant to proceed with bone

marrow transplant

Haematology 2. Pathology of Red Blood Cells

C. Riedinger

24

2. Excess of RBCs - Polycythaemia Rubra Vera [2]

-

This is from the podcast on PRV, for more notes, see Chapter 5. Leukaemia and
Myeloproliferative Disorders

also called erythrocytosis

raised RBC count

picked up as increased Hb >18g/dL or 16.5dL in females

also picked up in raised haematocrit

o traditionally measured by height of RBCs after centrifugation of blood
o haematocrit = proportion of volume of RBCs in blood
o 0.46 for men, 0.38 for women
o today its calculated from other parameters of the FBC
o also called PCV, packed cell volume, even though not exactly the same

effects of polycythaemia: increased blood viscosity => risk of clotting

symptoms
o vague
o reduced blood supply to various organs as result of increased blood
supply
o dizziness
o headaches
o visual disturbance
o tinnitus
o itch in extremities after hot bath
o stroke
o DVT
o Asymptomatic

Examination
o Facial plethora
o Splenomegaly in 60% of patients

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25

o Risk of thrombosis increases along with other risk factors such as being
male, obese or older
-

Relative polycythaemia
o Plasma volume decreases, RBCs themselves not increased
o Acute from dehydration, e.g. after diuretic intake or excessive alcohol
intake
o Chronic from kidney disease, obesity, hypertension, high alcohol and
tobacco intake
o May resolve when underlying cause is addressed
o Should be reported and investigate because it may be absolute
polycythaemia

Absolute polycythaemia
o Plasma volume normal
o 1* cause: disorder of haemopoietic stem cell
o 2* cause: when RBC cell mass increases due to increased erythropoietin
production

EP rise physiological in response to hypoxia, either simply due to

living at high altitude due to diseases that cause hypoxia:
-

Chronic lung disease

Cyanotic heart disease

Excessive smoking

Reduced blood supply to the kidney by occlusion of the

renal artery

EPO can also be taken by athletes to artificially raise their

RBC count, can have fatal complications when exercising
at high altitude

EP rise pathological as in due to tumour producing erythropoietin,

i.e. non-physiological cause

Renal or hepatocellular carcinoma

Renal cysts

Uterine fibroids

Congenital causes are rare and present shortly after birth

Haematology 2. Pathology of Red Blood Cells

C. Riedinger

26

Mutations in EP receptor

Mutations of Hb that cause high oxygen affinity leading to

chronic hypoxia

Idiopathic polycythaemia

o Erythropoietin:

glycoprotein hormone involved in production of RBCs from bone

marrow

prevents apoptosis of RBC precursors

controls the amount of RBCs produced

mainly produced in peritubular fibroblasts of the kidney and some

in the liver

regulation depends on level of oxidation of the blood

hypoxia increases EP production

o polycythaemia rubra vera

myeloproliferative disorder

acquired disease

affects mainly older patients

malignant proliferation of clones of haematopoietic myeloid stem

cells

accumulate mutations that enable cells to avoid apoptosis even in

the presence of erythropoietin

e.g. JAK2 gene, intracellular tyrosine kinase involved in growth

factor signalling pathways, absence causes excess production of
RBCs, WBCs and platelets => viscosity increased leading to
thrombotic complications

o detection/distinction

is Hb and haematocrit increased?

Relative or absolute?
-

Measure red cell mass and plasma volume:

o Label RBCs with radioactive chromium

Haematology 2. Pathology of Red Blood Cells

C. Riedinger
o Measure plasma volume by using radioactive
iodine to bind to albumin
o Measure and compare distribution of two
o Estimate red cell mass in comparison to plasma
volume

If absolute, is WCC and platelets also raised?

-

If yes, polycythaemia rubra vera

If not, think of 2* causes of polycythaemia

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Haematology 2. Pathology of Red Blood Cells

C. Riedinger

Bibliography

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