18

Haemolytic anaemias

Anaemias due to shortened life span of RBCs

Moderate hemolysis (RBCs life span 20-40 days)
Severe hemolysis (RBCs life span 2-20 days)

Pathology (Destuction of RBCs leading to)

1-  I. Bil., since the liver can  capacity of conj. (8-10) folds so
jaundice may not occur of may be mild.
2- Anaemias, but B.M. can  RBCs production up to 8 folds so
some cases presented with out evident An. (compensated
hemolytic state).
3- Hb become free in blood so is attached to habtoglobin
(globulin) & haemopexin (Beta glob.)

Complex taken up by RES

Reduced hemopexin & haptoglobin

4- Excessive Haemolysis with saturated haptoglobin

Haemoglobinuria

General features of haemolytic Anaemia

1- Features of haemolytic An. + Mongloid features
2- Features of H. Jaundice Lemon yellow skin.
Tinge of jaundice in sclera.
Dark stool.
Nr. Urine ?! (Acholuric Jaundice)
3- Liver & Spleen ++ (Extramedullary erythropoiesis)
4- Leg ulcers surrounded by pig. Due to deposition under skin.
5- Gall stone CBD J. (pigment stone).

N.B. Causes of Jaundice in H. An

- Haemolysis - Haemosedrosis.
- Viral hepatitis. - Gall stone.

6- Haemolytic crises Fever, rigors (pyrogen from RBCs)

Pallor, Jaundice
Dark urine (Hb).
Bony pains due to active B.M.
Abdominal pain
 19

7- Hyporegenerative crisis (a plastic crises)

Attacks of  capacity of B.M. to replicate. It my be due to folic
A.  or viral infection e.g paravirus. Here An.  without
deepening of Jaundice, this can be avoided by folic acid therapy

Investigations for Haemolytic Anaemia

1- Bl. picture
 Microcytic hypochromic thalasaemia.
 Normocytic normochr. A.
 Mcrocytic AN. Due to folic A 
 WBCs & plat.  (B.M. hyperactivity).
 Brisk reticulocytosis.
2- B.M. (hyperactive) = erythroid hyperplasia.
Normoblasts.(the usual)
Megaloblastic.(in cases of folate deficiency)
3- S. bilirubin  (indirect)
4-  haptoglobin, heamopexin.
5- Urine & stools  urobilinogen,  sterocobilin.
6- Special investigtions
 Bl. film Spherocytosis.
Target cell (th.)
 Hbelectrophoresis Hb F (TH).
Hb S (S.A.)
 Osmotic fragility  in spherocytosis.
 Sickling test. For sickle cell anaemia.
 Ham’s test (P.N.H.).
 Coomb’s test for autoimm. H. A.

Causes of Haemolytic Anaemia

Intrinsic (Intracorpuscular) Inherited.
+ve F.H.
Since childhood.
1- Membrane defect Spherocytosis.
Parocysmal nocturnal haemoglobinuria.
(Acquired)
2- Haemoglobinopaties sickle cell An.
3- Defect in globin synthesis thalassaemia.
4- Enzyme  (G 6 PD).
 20

Extrinsic (Extracorpuscular) Acquired.

-ve F. H.
Adult.
1- Autoimmune H.A.
2- Mechanical haemolysis e.g. prothestic valve.
3- Infection malaria, clostridia.
4- Chemical e.g. drugs or snake venum.
5- Hypersplenism.

Hereditary Spherocytosis
It is autosomala dominant, there is  in a lipoprotein of cell membran.
(Spectrin) with resultant 3 defects.
ㄱ  permeability to H2O & Na.
ㄴ Cells become spherocytes
ㄷ ++ RBCs rigidity.
So haemolysis here is extravascular. (in spleen – RES).

C\P G. features of A.
F. H. +ve
Onset : early childhood
Gallstones of pegment type are common even in childhood

Investigations: G. investig. Of An.

Blood film spherocytes.
Osmotic fragility test.
MCV is normal or slightly 
NCHC 

Early tubes with serial

Haemolysis dilution of saline
= membr. D. 0.7 0.6 0.5 0.4 0.3 0.2 0.1

normal
Red cell survival studies with cr show destruction of red cell in the spleen

Treatment 1- Splenectomy Stricking, permanent

improvement,
better after age of 4 yrs
2- Bl. Transfusion
3- Folic A. 5 mg /d.
 21

ㄱ Splenctomy advised when there is severe An, severe H. crises

or other members of the family have died from the disease.
ㄱ Following splenectmoy penicillin, 250 mg/12hr for at last 5 yrs.
ㄱ Rare relapses, due to splenic autotransplants or to hyperplasia of
secondary spleens.

Hereditary elliptocytosis

ㄱ It is a cell membrane disorder, autosomal dominant. RBCs are

elliptical in shape. Clinically similar to hereditary spherocytosis.
ㄱ Minority of patients has anaemia and only occasional patients
require splenectomy.

Hereditary stomacytosis

Also it is a cell membrane defect. It is an inherited disease but it

may be associated with alcohol intake.

Thalassaemias

This is an autosomal codominant D.

Beta thalassaemia
 production of beta chains which are replaced by gamma chains
2 types:

◘ Homozygous ◘ Heterozygous

◘ TH. Major ◘ TH. Minor (similar to iron↓ An.)

◘ ↑ Hb F markedly
70% - 90% ◘ Mild anaemia,
microcytichypochromic An.
◘ ++ spleen
◘ It needs no
◘ Sevre sympt. ◘ Hb F is raised (10%)
 22

Alpha thalasaemia
There is  production of alph chains gamma 4 Hp.
Homozygos Heterozygos

Incompatile with life mild Anaemia

(Hydrops) ◘ No specific therapy
Fetalis ◘ Avoid iron therapy
◘ Folic acid if necessary

Anemias with secondary iron loading

ㄱ Sideroblastic anemia
ㄱ Trnsfusionl themochromtosis e.g.:-
1- thalassemia major 2- aplastic anemia

Cooley An. = TH Major = target cell

An.
Aetiology Abnormal gene is inherited from both parents
↑Hb F (70%-80%). (Defect in the switch of  chains to B chains)

C/P 1- Starts in childhood.

2- G. features of H.A.
3- Mongloid features +ve due to marked expansion of B.M.
4- Marked ++ hepatospleenomegaly
5- Patients have peculiar skin color due to combination of icterus,
pallor and increased melanin deposition.

Investigations
1- General investigations for H. An.
2- Blood film target cells.
3- Hb electrophoresis Hb F
4- X-ray skull hair on end
Long bone thin cortex wide medulla.
5- MCV , MCHC normal, saturated iron binding capacity and
high serum ferritin level.
6- Prenatal diagnosis by DNA analysis of chronic villus biopsy.

TTT  Blood transfusion.  Desferal

 Folic A.  B.M. trnsplantation
 23

 Splenectomy value ?! indication.

Cellular pathogenesis of the major

There is excess oduction of & chain these free & chains
membrane permeability abnormalities + destruction of RBCs by
the mononuclear agocytic system. Since these abnormalities
starting in the RBCs pre cursors intramedullary destruction of
RBCs and short life span of circulating red blood cells that emerge
from B.M. So there is extramedullary hematopoiesis in the liver
and spleen.

Sickle cell Anaemia

Aetiology Aut. Codminant disorder with abnormal HbS

SS SA
Sickle cell an. trait
Manifested Asympt. sickling may occur with
severe hypoxia
e.g during anaesthesia

Pathology Substitution of valine for

Glutamic at 6 position in
beta chain

HbS Hypoxia RBCS become sickle shaped

Haemolysis Vascular obstr (vasocclusive)

Microinfarcts macroinfarcts
Painful crises organ damage
C/P
1- Features of h. An.
2- Vascular occlusion (organ failure or pain crises).

Dactylitis mesentric  renal infarction splenic liver

 nephragenic D.I.
Acute abdomin autosplenectomy infarcts
Penis bone cerebral heart retina
priapism pain hemiplegia sickling in the  infarcts
 24

myocardium retinal detachment

3- long term problems:
ㄱ susceptibility to infections.
ㄱ Chronic leg ulcers due to ischaemia.
ㄱ Gall stones (pigment stones).
ㄱ Aseptic necrosis of bone particularly of femoral head.
ㄱ Chronic renal disease.
ㄱ Blindness.

Investigations
 G. invest. For An. Normocytic normochromic Anaemia
 Electrophoresis HbS.
 Sickling test (blood + Na bisulphite)

+ve test in hypoxia

SS SA

 Sickle C disease 50 % HbS + 50% HC

mild to moderate anaemia
Spleen ++, retinal detachment
nearly normal life span.
 Sickle beta thalassemia;- 70% HbS + 30% HbS there is
splenomegally – longer life span.

Treatment:
1- Blood transfusion.
2- Crises (pain) analgesic.
O2 – fluids.
Na HCO3
Fresh blood
3- G. counselling.
4- Drugs that  Hb F as this  sickling of Hb S.

Drugs hydroxy urea. These drugs have

Erythropoietin unacceptable toxicity

5- Autosplenectomy ; give pneumococeal vaccine or penicillin V

(250 mg/d).
 25

G6pD = glucose 6 phosphate

dehydrogenase 
This enzyme is involved in the pentose shunt which is the source of
NADPH+ which is essential to  reduced glutathione that resist
oxidizing stress. It is an X linked disease.
C/P:1- Manifestation in blacks, enzyme 155, pt Nr. But when subjected
to oxidative stress e.g. antimalarial
they will suffer haemolysis sulpha
infection
4- other populations, enzyme ≤ 5%, where pt C/O of moderate H.A.
↑↑ with oxidative stress.
5- Favism. 2 genes are present  G 6 P D
Abnormal metabolism
Beans oxidant
Investigations
 G6PD activity of the red cell measured but this may be entirely
accurate if there is marked reticulocytosis
 Hienz bodies in blood film
Treatment
 Removal of toxic agent. Splenectomy is of no value.
 Blood transfusion during the attack.

N.B Other enzymopathies anaemia e.g. pyrurate kinase enz 

(Aut. R) , RBCs deficient in ATP hemolysis due to  RBCs
rigidity + spleenomegally.
 26

Auto immune H.A.

Pt 45 yrs old with jaundice
History jaundice
Dark stool.
Reddish urine.
Suspect H.Jaundice
Ask for S. bilirubin
 I. Bilirubin
suspect haemolysis
(blood picture)
Brisk reticulocytosis
Coomb’s test
If + ve
= autoimmune H.A.
type of Ab cold
warm
Search for the cause e.g. SLE, lymphoma

1) Autimmune H. An. Due to warm Ab

2) i.e Ab attaches best to red cells at 37c

Causes Lupus 1- Idiopathic.

Leuk. 3L 2- Chr. Lymphocytic leuk
Lymph. 3- Lymphoma - SLE
4- Alpha - methyl D.
C/P ▪ A. An.
▪ Cause.
Investig □ Comb’s test +ve
□ Spherocyte
□ Ab (IgG)

N.B. When IgG attack RBCs Stimulate splenic phagocytic

Activity haemolysis

Treatment ◘ Steroid. If no response splenectomy.

 27

2) Autoimmune H. A. due to cold Ab

i.e Ab attaches best to RBCs at Temp. lower than 37c

Causes ◙ Viral infection. E.g. infections mononucleosis.

◙ Mycoplasm.
C/P ◘ H. An.
◘ Cause.
Investig IgM
TTT (keeping the extremities warm)
1- Steroids.
2- Splenectomy is of n value
3- Immunosuppressive therapy  Ab

N.B. Paroxysmal cld hemoglobinuria = Ab that cause haemolys is

in cold temp. e.g. in $. It is due to IgG Ab which attack RBCs
(Donath – landsteiner Ab)

Drugs causing haemolysis

1- Direct interaction in cell membr. amphotericine.
2- Imm. Reaction ♪ Autoimm. e.g. aldomet.
It induces Ab attack RBCs
♪ Hapten drug act s (H) as penicilline.
♪ Innocetn by stander (sulfa)
(drug + plasma pr.) Ag + Ab

Ag – Ab – C attack RBCs
3- Drugs causing hemolysis in G6PD  e.g. antimlarial, sulfa,
nitrofurantoin
 28

Mechanical haemolysis

1- March haemoglobinaemia with prolonged marching or running.

2- Prothetic valve haemolysis
3- Micro - angio - pathic H. A.

small Bl. V. diseased

Causes 1- DIC
HCQ/ 2- T.T.P
3- Haemolytic uraemic $
4- Malig H – Scleroderma.
Diagnosis. Blood film shistocytes
TTT Causes

fibrin thrombbus

Toxic causes of haemolysis

 Malaria  Clostridium welchi

 Pneumococci  Staph
 Smoke venom  Spider venom
 Copper :- It has ad direct effect on RBCs e.g. wilson’s disease.

Paroxymal nocturnal haemglobinuria

It is an acquired defect at the level of stem cell (mother cells) So defect

in RBCs – plat RBCs. It may be associated with a plastic anaemia.

Pathology
RBCs : There is absence of specific protein in cell membr.
Leading to activation of C3 against RBCs esp. during
sleep (PH). The deficient protein (glyxosyl
phosphatidinositol).
Plat. : Aggregation thrombus.
WBCs : P.N.L. dysfunction infection
 29

C/P
1- H. An. (noctunal) why?! (intravascular H. An).
2- Vascular occlusion e.g. budd – chiari, cerebral
3- Recurrent infections.

Investigations
1- +ve Ham’s test blood + acidic medium (PH of 6.2)

Haemolysis
2- Leukopenia.
3- Thrombocytopemia.

Treatment
ㄱ Steroids 25mg prednisone only on alternate day.
ㄴ Thrombolytics , anticogulant for thecombosis.
ㄷ Antithymocyte globulin to treat B.M a plasia.

Q: Sickle cell syndromes sickle cell An – sickle cell

Sickle cell Beta. Trait thalssaemia
Sickle C disease.

Q: Thalassaemia syndromes Th. Major – th. Minor

Th. Intermedia
Sickle cell beta th.

Alloimmune H. An due to :- Bo, Rh in compatibility

 30

The Leucocytes
 Normal 4.000 – 11.000 / c.mm (adult).
 In newborn TLC 10.000 - 26,000 /c.mm

Leucocytes classified into:

Granular leucocytes non granular

WBCs contain specific granules  Lymphocytes

 Monocytes.
Neutrophils eosinophils basophils

Development of WBCs
Hemocytoblast

Granuloblast Monoblst Lymphoblast

Pro – myelocyte pro- monocyte pro-lymphocyte

Myelocyte monocyte lymphocyte

 basophil.
 Neutrophil.
 Eosinophil

 There is immature WBCs in peripheral blood < 3% .

 Shift to the left = immature WBCs > 3%.
 This occurs in severe infection.
severe hge.
severe haemolysis.
 31

Neurtophils
They constiute about 40-75% of TLC
The absolute count = 2000 -7000/c.mm
Function phagocytosis.
Chemotoxis (chemical attraction to the site of invasion)

Neutrophilia Neutropenia
> 7000 / C.mm < 2000 / C.mm
 Physiological exercise Inf  Typhid fever.
preg.  Viral infection
 Path: BM   A plastic An.
ㄱpyogenic infection  Agranulcytsis.
ㄱTissue damage (burns)  Hypersplenism
ㄱPolyctthemia vera.  Cyclic
ㄱLeuk (chr. Myeloid) Imm  SLE
ㄱRh. Fever – M. infarct drugs  Drugs  of B.M
ㄱDrugs as cortisone  Some antibiotics.
ㄱAcute he or hemolysis.

Eosinophils

Normally 1-5% or 40-400/c.mm

Function;phagocytosis – role of Ab production. – release neurotoxin to
kill the parasites.
Cause of easinophilia; Allergy
Parasitic – malignancy (lymphoma)
Addison’s D.
Lymphoma – familial.
Some types of vasculitis.
Hypereosinophilic syndrome.
Eosinophilic leukaemia.
Pulmonary eosinophilia.
 32

Basophils

Normally < 2% or 10 –100/c.mm

Function they combine with Ig E causing release of histamine.

Causes of basophilia:
 chronic myeloid leuk  T.B.
 polycyth. Vera.  influenza
 myelosclerosis  hypothyroidism

Lymphocytes
Normally 20-45% (1500-3500/c.mm)
Origin Central origin B.M.
Thymus.
Peripheral spleen – L.N.
All lymphocytes are originally supplied by B.M but proliferate in the L.N

Types B- lymphocytes (humoral imm.)

T- lymohocytes (cellular imm.).

Lymphocytosis > 3.500/c.mm Lymphocytopenia

Viral inf. (IMN – CMV)  Cortisone
 Leuk (lymphatic leuk)  Immunodeficiency
Chr. Inf. (T.B. brucellosis  B. M.
 Lymphoma  HIV
Atypical lymphoctosis

Infectious lymphoma viral

Mononuckosis leukemia hepatitis.
 33

Monocytes
Normally 2-9% or 200-800/c.mm
They originate in the B.M. circulate in the blood

Then they leave the circulation to the tissues

Converted into macrophages.

Function  phagocytosis of Bact., virus and immune complex
 Activation of lymphocytes
Monocytosis:
 T.B. - typhoid F. – sarcoidosis
 protozoa ( malaria).
 Viral inf. Mononucl.
 Monocytic leuk – lymphoma – SLE – inflammatory B.D.

N.B. Plasma cells appear in blood

 m.m.
 Plasma cell leuk.
 G. measles.
 Chicken pox.

Value of B.M. examination

Diagnosis:
m.m. myelofibrosis aleuk. Leuk a plastic An. Sideroblastic
amoenia
Confirmation:
Leuk  iron An megaloblastic I. T.P
Anaemia
Site of B.M. puncture
1- Sternum aspiration.
2- ASIS trephine (as in myelofibrosis it gives dry tap with
B.M. aspiration.)
 34

Q Leukmoid reaction
It is blood picture with TLC simulating leuk
Criteria
ㄴusually there is a cause e.g. infection
ㄷTLC usually not > 50.000, v. rare > 100.000
ㄹBlast cells never > 5 %
ㅁPlatelets normal.
ㅂRBCs normal or mild .
ㅅB.M. proliferation (normal) no blasts.
ㅇLeucocytic alk. Phosphatase 

Q Value of Bl. Picture in pt with fever

 inf. T.B. – viral – Brrucella
pyogenic inf.
 Malig. Leuk. – lymphoma.
 Collagen D SLE,…

Q How can you diff. Bet. Leucocytosis due to

infection or steroids.
infection WBCs showing toxic grannulation i.e.
vacules in cytoplasm of WBCs.

Q Anaemia of chronic disease

Criteria
ㄷ It is due to chronic inf. Chronic inflamm, or neokplasia.
ㄹ The An is not related to bleeding, hemolysis or B.M.
infiltraion.
ㅁ The An is generally mild + normal MCV but up to 25% with
 MVC.
ㅂ The serum iron is low buy iron stores are normal or
increased ( ferritin).
Path (failure of iron utilization).
ㄷ Anormal iron metabolism and erythropoiesis.
ㄹRecent interest is centred on the role of the inhibitory affect of
interleiukin I.
TTT
ㄱ ttt of the cause.
ㄴ No response to iron therapy.
Q Leukoerythroblastic reaction?
 35

i.e presence of immature WBCs or RBCs in peripheral blood due

to B.M infiltration e.g myeloma, leuk, myelofibrosis, hge and
haemolysis.