Bleeding Disorders

Dr. Ahmed Mansour , PhD

Professor of Haematology
Mansoura University Pediatric Hospital
Mansoura Faculty of Medicine
 Bleeding Disorders
Haemostasis depends on 3 factors:
 Blood vessels: Through contraction of wall of vessels.
 Platelets: Normal count 150.000– 400.000/mm3
Coagulation mechanism: Which depends on interaction between 13
clotting factors to form the blood clot.
Thus, for bleeding to occur, there must be at
least one of three disorders.

Vascular disorder Coagulation disorder

Platelet disorder

Number disorder Function disorder

Platelets < 150.000/cmm

Thrombocytopenia Thrombasthenia
Blood vessel
Vasoconstriction Vascular
injury
phase

Platelet Consolidation
Platelet Platelet
aggregation Platelet plug
adhesion formation phase

Prothrombin

Tissue Plasma
thrompoplastin factors

Thrombin Plasma
phase

fibrinogen Fibrin

Concept of hemostasis
 Vessel injury Vasoconstriction

Endothelial lining disruption

Collagen exposure Von Willebrand

factor
Platelet adhesion

Release reaction ADP

Thromboxane A2
Platelet aggregation
Serotonin
Platelet clump

Thrombin
Platelet plug

Primary hemostatic mechanism

 I- Vascular Purpura
Definition

Bleeding disorder due to defect in

blood vessels.
Causes: It may be either acquired
or congenital.
 I- Vascular Purpura
A- Acquired:
Anaphylactoid purpura (Henoch Schonlein P.).
Scurvy
Scurvey (vit C deficiency).
-Bleeding tendancy
Mechanism:
- Gum Hypertrophy

Platelet function -defect.
Poor wound healing

Vascular defect -because Vit. (Cause????)
Tender Bone C is essentialSub-periosteal
for formation of
cement substance that link epith cells of Bl. V. together.
haemorrahge
ttt → vit C 200-500mg/day oral.

DD
Steroid Purpura: of Racjhitic rosaries
Due to prolonged

use of
- Rickets: corticosteroids
enlarged either systemic
costochondral juction or
topical → thining of wall of
- Marsmus: blood vessel.
rounded , normal sized
May be in cushing syndrome (Endogenous ↑ ).
costochondral juncion, not tender
Fat Embolism:-Achondroplasia: angulation , angle downword (V)

As in fracture-Scurvey: tender
of long Bones.
 I- Vascular Purpura
Traumatic Asphyxia: as:

Severe chronic cough e.g. Whooping cough.
Epileptic fits.

Crushing injuries of the thorax.

Severe infections:
Subacute bacterial endocarditis, Typhoid fever, menigococcal
septicemia → Due to vasculitis.
Uremia.
Diabetes Mellitus.
Drugs: Penicillin, sulfa, INH, mercurials….etc.
Due to hypersensitivity to drug
Purpura Facticia: “Self inflected”.
Usually in the areas within reach.

More common in females.
 I- Vascular Purpura
B) Congenital:
Congenital Amyloidosis.
Heriditary telengiactasia (Rendu-Osler-Weber disease).
Autosomal dominant disease.
Thin walled dilatations in the wall of blood capillaries. These

dilatations lack the muscle layer so, if injured they can not
contract like other normal BI.v. → severe bleeding.
 Ehlers- Danlos Syndrome:
Autosomal dominant disease characterised by:
↑ Skin Elasticity.
↑ Range of movement of joints ( Hyper extensibility of joints).
↑ Fragility of blood vessels.
Anaphylactoid Purpura
Definition
Allergic disorder similar to
Rheumatic fever in which the
allergic reaction occurs in wall of
blood vessels.
 Etiology
May be 2ry to infection with group A B
hemolytic streptococci.
Or
Other infections.
Insect bites.
Food or drug allergy.
 Clinical Picture
It can affect one or more of 4 systems:-
 Skin: 100%
Youmaculopapular
Urticarial can’tMedical
Diagnose Causes
rash anaphylactoid
present of Acute Abdomen:-
manily on lower limbs,
-Diabetic Buttocks & Extensor surface of
Ketoacidosis
upperpurpura
limbs. without skin Manifestations
-Sickle cell crisis
Ecchymosis & purpuric
-Rh fever(eruption.
activity)
Angioneurotic edema is common.
-Anaphylactoid
Joints: 75%
purpura ( mesentric vasculitis)
-Basal pleurisy
Migratory polyarthritis or arthralgia similar to that of
rheumatic fever but-Uraemia
the joints are not tender.
-Familial
Gastro-intestinal Mediterranean fever
tract: 50%
Severe abdominal-Porphyria
pain.
Diarrhea. Mesentric Vasculitis
-Inferior wall infarction DD from
Bloody stools.

Renal: 25% Appendicitis
It may be in the form of asymptomatic proteinuria and
hematuria or nephrotic syndrome.
Clinical Picture
Clinical Picture
 Complications
Intussusception.
Subarachinoid or cerebral hemorrhage.
 Investigations
All investigations of bleeding tendency
are normal except Hiss test may be +ve.
Diagnosis depends on clinical
So, diagnosis depends on clinical
manifestationsmanifestations
with:

1- Investigations for streptococcal infection:
* ESR * ASO Titer
2- Urine analysis:
Technique
* To detect of Hiss
renal affection Test?
(worst prognosis) because
50% of cases → chronic renal failure.
3- Stool analysis: for occult blood.
4- Serum IgA: may be elevated.
 Treatment
This disease is self limited but recurrence can
occur at least within 6 months.
Pencillin:
If the condition is 2ry to streptococcal infection.
And if not try to detect the cause and avoid it as drugs or
insect bites.
For Arthritis:
Acetyl salicylic acid as for rheumatic arthritis.

For GIT manifestations:
Corticosteroids: Prednisone 1-2mg/kg/day oral.

For renal Affection:
Immuno suppressive drugs as: Endoxan, and
azothioprine.
 II- Platelet Disorder
Platelets are essential for Haemostasis by:
Their number.
Their function:
 Platelet aggregation .

Platelet adhesiveness.
Clot retraction.

Platelet factor 3 production.

 Char
acte
rs of
plate
lets
Size: 1-4 µm (younger platelets are larger)

Mean platelet volume (MPV): 7.1 fl

Number: 150,000-400,000/mm3

Distribution: One-third located in spleen; two-

thirds circulate in the blood stream
A- Platelet number defect: Thrombocytopenia:

Definition:
(Normal
Platelet platelet count
count <150.000/mm3
= 150.000–
400,000 /mm3).
Causes:
Divided into 2groups according to
Megakaryocyte in the bone marrow:

1- Decrease Megakaryocyte in B.M:
MostAplastic
Common anemia.
causes of thrombocytosis in Egypt?
Malignent diseases:
a- 1ry in bone marrow e.g leukemia.
-Splenectomy
b- 2 ries e.g neuroblastoma.

 Metabolic disorders infilterating bone marrow:

 Gaucher’s disease.
A- Platelet number defect: Thrombocytopenia:

Normal or ↑ Megakaryocyte in B.M:

ITP “Immune Thrombocytopenic pupure”
Drug induced thrombocyto penia. e.g Quinidine
Hyper splenism
Infection e.g. Measle & German Mensis
Collagen ds:
SLE
Juvenile rheumatoid arthritis

Megaloblastic Anemia
DIC
Repated Transfusion of stored Bl.

N.B: Thus for patients with thrombocytopenia the most important

investigation is bone marrow examination.
Immune Thrombocytopenic Purpura (ITP)

Definition:
Anti-platelet Ab is IgG
Immune disorder due to destruction of the
prepheral platelets by antibodies. Usually it
-Specie specific
follows viral upper respiratory
-Can cross tract thrombocytopenia
placenta causing infection by 2
-Active against homologous and
weeks. autologus platelets
Usually it is acute & self limiting but if it persist
>6 months it chronic.
Incidence:
The most common cause of thrombocytopenia
Female= male
Common from 2 – 8 years
 Char
a c te
rs of
ITP

Thrombocytopenia: (Platelet count <100,000/ml)

Shortened platelet survival

Presence of antiplatelet antibody in plasma

Increased megakaryocytes in bone marrow

Types:((according to onset, Duration
Acute: Disappear in < 6 m
Chronic: Disappear in >6 m
Recurrent : Disappear in < 6 m but re-
occur again
 Clinical Picture
Petehcial & purpuric euption over any site of the body.
Ecchymosis: mainly over medial aspect of tibia.
Epistaxis & bleeding Gums are common
manifestations.
Orificial bleeding but less common.
Big Haematomas.
Intracranial hemorrhage: the most serious
complication and occurs especially if bleeding
manifestations more in upper pant of body.
Spleen may be enlarged if enlarged never hugely
enlarged.
Clinical Picture
Role of splenomegaly in ITP
Site of formation of anti-platelet Ab.
Site of distruction of Ag (platelets)-Ab complex.
Splenin I & II  B.M depression decrease platelet
production.
 Acute Chronic
- <6m - >6m
- More common in children -More common in Adult
- Male= female - female >Male
- Seasonal variation -Any time
(spring)
- Platelet count < - Platelet count>
400.00/mm3 400.00/mm3
- Very high dose of anti- -High Ig A
platelet Ab -Better prognosis
- Good response to
corticosteroids
 Age
and
ITP
ITP occurs in great frequency:
between 2-8 years old age
Infants less than 2 years old (infantile ITP)
have the following features:
--More abrupt onset.
--More severe clinical course.
--Platelet count < 20,000/mm3
--Poor response to treatment
--Higher incidence of chronicity
Intracranial haemorrhage
Usually occurs within 10 days of attack by ITP.
So patient must be observed for 10 days in hospital.
Occur in 10% of cases.
Occur when platelet count < 10.000 / mm3

Value of Faucial examination in ITP

Peticial haemorrhage in soft palate usually followed by IC

hge so we can predict IC he.
 Congenital
Hemorrhagic telangiectasia
Ehler-Danlos syndrome
Vascular
:Acquired
Drug-steroids
Normal platelet count Henoch-Schollein purpura
(Nonthrombocytopenia) Purpura factitia
Purpura fulminans
(Vasculitis (e.g. SLE

Platelet
dysfunction
Congenital
Petechiae
Purpura
Ecchymosis
Neonates Acquired
Low platelet count Infants
(Thrombocytopenia) Children

Clinical approach to Petechiae, Purpura

and Ecchymosis based on platelet count
 Investigation
Prolonged Bleeding time (< Normal = 2 – 4 min >).
Normal
Mostclotting Coaggvlation
important single test time.
for ITP Anti-platelet Ab
+ veMost
Hess Test (fragility
important test).
single test for thrombocytopenia B.M
Examination
Thrombocylopenia:

Platelet count <150.000/mm3”. In severe cases the count
is usually below 50.000/cmm.
Detection of antiplatelet antibodies, which present up
to 65% of chronic cases. So, it is good diagnostic test
B.M. Examination:
The most important diagnostic test.
↓ Projection or budding or surface of megakariocytes.

Due to rapid release of blood platelets to peripheral

circulation.
 Treatment
Conservation treatment: Because the disease is
self-limiting, the patient is put under observation
for fear of intracranial hemorrhage.
Corticosteroid:
Prednisone→ 60mg/m2/day, oral, for 2-3weeks & then


withdraw the drug even if there is no response.

Indication:

Orifascial bleeding: epistaxis or menorrhagia.

Extensive Purpura & Eahymosis.

Intracranial hemorrhage.

Chronic cases.
 Treatment
Immuno suppressive drugs:
- Azo thoprive. - Vincristine. -
Vinblastine.
- Cyclophosphomid .
 High dose of I.V Immunoglobulins:
Block the receptor site of surface of Bl. platelets → competitive
inhibition of antiplatelet antibodies.
Anti-Rh D:
Dose → 75µ g/kg IV infusion over 3-5 minutes period.
The patient must be Rh D +ve for this mode therapy to be beneficial.

Blood & Platelet transfusion:

Blood transfusion → to compensate Bl. Loss.
Platelet transfusion → in life threatening conditions e.g. I.C.Hege → to

stop bleeding .

But it has temporary effect bec. it will be destructed by antiplatelet Abs

 Treatment
Splenectomy: It is indicated in:
Severe acute cases non-responsive to medical
treatment.

Chronic cases with bleeding e.g menorrhagia.

Pneumococcal vaccine or longatine penicillin must be
given to prevent septicemia.

Exclusion of collagen diseases as SLE must be done
before splenectomy.
Danazol:

It is an androgen shown to increase platelet count. 300-
400mg/m2/day orally for 2-3 months.
B- Platelet Function Defect
It may be either congenital or
acquired.
Congenital: e.g:
Glanzmann thrombasthenia
Hemorrhagic thrombocythemia.
Wiskott-aldrich syndrome.
Von-Willebrand disease.
B- Platelet Function Defect
Acquired:
Drugs:
Anti-inflammatory drugs: Acetyl salicylic acid i)aspirin), I
buprofen.
Antibiotics: Ampicillin, Gentamycin.

Anaesthetics: Procaine, Xylocaine.

Cardiovascular: Theophylline, papaverine.

Duiretics: Furosemide, Ethacrynic acid.

Chronic renal failure.

Chronic liver disease.
Scurvey (vit c deficiency).
Paraprotenemia: abnormal protein coating blood platelets.
 Congenital vascular disorder
Congenital Hemorrhagic telangiectasia
or Acquired Ehler-Danlos syndrome
Adhesion
defect Abnormal
Normal
Platelet
aggregation Platelet aggregation
defect ADP
Abnormal Epinephrine
Defects in Collagen
Normal

release Ristocetin
reactions

Platelet Bleeding
time
count
Acquired vascular condition
Henoch-Schollein purpura
Normal Purpura factitia
Clinical approach to nonthrombocytopenic Purpura
based on bleeding time
 Clot formation results from interaction
between 13 coagulation factors

Factor I Fibrinogen

Factor II Prothrombin
The Coagulation factors are
Factor III Thromboplastin

.
Factor IV Calcium
Factor V Labile factor((Proaccelerin

Factor VI Activated labile factor

Factor VII Stable factor((Procovertin

Factor VIII Anti hemophilic globulin

Factor IX Christmas factor

Factor X Stuart prower factor

Plasma thromboplastin
Factor XI
antecedent factor

Factor XII Hageman factor

Factor XIII Fibrin stabilizing factor

 Mechanism of blood
coagulation

It occurs through
3 phases
 Phase I

Concerned with formation of

thromboplastin (factor III) which
occurs through 2 pathways

1. Intrinsic pathway
2. Extrinsic pathway
 w a y
a t h
i c p
r i n s
I n t
--Resposible for formation of plasma
thromboplastin.

--It depends on factors VIII, IX, XI and XII.

--Its specific diagnostic test is

activated partial thromboplastin time
(APPT): normally 25-40 seconds.
 w ay
at h
i c p
r i n s
E x t
--Resposible for formation of tissue
thromboplastin.

--Depends on factors calcium, V, VII and X

--Its specific diagnostic test is

prothrombin time (PT): normally 12-20 seconds.
Extri VII
nsic
path
way VIIa TTP,++Ca
Platelet
plug
Loose

X Xa Platelet
aggregation
XIII
V, Va, Ca++ , PF3
Prothrombin Thrombin

Fibrin Fibrin
Fibrinogen monomers polymers

Fibrino peptides A & B ++

Ca XIIIa
Stable fibrin clot

Secondary haemostatic mechanism

Intrin Prekal HMK
sic XIIa
KAL
path Kal XII
way XIa XI Collagen

IXa IX Platelet
plug
V, Va, Ca++ , PF3 Loose

X Xa Platelet
aggregation
XIII
VIII, VIIIa, Ca++ , PF3

Prothrombin Thrombin

Fibrin Fibrin
Fibrinogen monomers polymers

Fibrino peptides A & B

++
Ca
XIIIa
Stable fibrin clot

Secondary haemostatic mechanism

 Phase II

Concerned with formation of

thrombin through the action of
thromboplastin
Prothrombin ------------ Thrombin

It i s s p e c i f i c
p ro t h r o m b i n
test for
time
 Phase III

-- Concerned with formation of fibrin

through the action of thrombin
-- Formed fibrin is stabilized by factor XIII
Fibrinogen ------------ Fibrin

It is specific
t f o r t hr o m b in
tes
:(Time (TT
Normally
c o n d s 1 5 - 2 0
se
 Hemophilias

There are 3 types

A, B and C
 Hemophilia A

Commonest hereditary coagulation disorder

Due to deficiency of factor VIII (Anti-hemophilic

globulin) which is composed of 2 parts:
-- Antigenic part
-- Coagulation part
p hi l i c p a t i e n ts
,In hemo o n l y
a n t pa r t
the coagul
is deficient
It is inherited as X-linked recessive.

So,
-- it affects males only
--females are carriers

Degrees:
Severe -------- Factor VIII < 1%
Moderate ------- Factor VIII 1-5%
Mild -------- Factor VIII 5-25%
 Clinical Picture
1. Bleeding from:
Umbilical stump
CNS hemorrhage in neonates.

2. Skin bleeding (ecchymosis):

Spontaneous
After minor trauma.
 Clinical Picture

3. Excessive bleeding after minor

surgical procedures:
Tooth extraction.
Circumcision.

4. Large intramuscular hematomas

and orificial bleeding:
Epistaxis
Bleeding gums
GIT bleeding
 Clinical Picture

5. Hemoarthrosis (bleeding in joint cavity)

of big joints
knee, ankle and elbow

limping
limitation of movement due to ankylosis

Joint will be:

hot, red, tender and painful
Clinical Picture
 Investigations
1. Prolonged coagulation time (CT).

2. Prolonged activated partial thromboplastin

time (APTT).

3. Deficient factor VIII by specific factor assay.

4. Radiologic examination of joints with

hemoarthrosis.

5. Prenatal diagnosis by amniocentesis or

chorionic villus sampling
 Treatment

General
Replacement
measures Hemoarthrosis
therapy
 Treatment

1. General measures:
--- Avoid
---Trauma
---I.M injections
---Surgical procedures.
--- Local measures
---Pressure bandage
---Cold compresses
---Application of thrombin
preparations on small wounds
 Treatment

2. Hemoarthrosis:

--Rest of the join

--Cold packs
-- Physiotherapy (passive) to avoid ankylosis
--Corticosteroids for recurrent cases
--Aspiration of the joint can be done
by a meticulous hand.
 Treatment
3. Replacement therapy
Increase level of factor VIII in plasma
(prevent hemorrhage)

1. Fresh frozen plasma 10-15 ml/kg/12h.

keeps factor VIII level between 10-20% of normal

2. Cryoprecipitate.
Each unit contain 80-100 IU of factor VIII.

3. Factor VIII concentrate:

Each vial (25 ml) contains 250-1500 IU of factor VIII.
 Treatment
4. Fresh blood transfusion
because factor VIII is unstable
for correlation of blood loss: 10-20 ml/kg.

5. Desmopressin (DDAVP): Deamino-8-D-

arginine vasopressin
--given in mild and moderate cases
-- dose: 0.3-0.4 µg/kg in 50 ml normal saline
I.V over 15-20 minutes.
--Concentrated form can be given intranasally.
--It increases plasma level of factor VIII 4 folds
 Hemophilia B

Also is X linked recessive disease.

Due to deficiency of factor IX

(Christmas factor)

o a r t hr os i s is
He m
le s s c o m m o n
e
Than in A typ
 Hemophilia C

Autosomal recessive disease.

Due to deficiency of factor XI

(Plasma thromboplastin antecedent factor)
Sto Can b
red e t
s is r
r t h ro s i Fa bloo eate
o a o n cto dt dw
He m m m rX ran ith
t c o pe I is sfu
no n A t y sta sio
i
Than ble n
 Von Willebrand disease
Pseudo-hemophilias

Congenital disorder comprises both

coagulation and platelet function
defects

X- linked recessive
(inherited like hemophilia A)
Characterized by:

1. +ve family history.

2. Prolonged bleeding time with normal

coagulation time.
(only coagulation disorder with Prolonged
bleeding time).

3. Deficiency in factor VIII activator (vW

factor)
So, factor VIII activity decreases to about
65%.
4. Defective platelet aggregation by
restocetin.

5. Defective platelet adhesiveness.

6. The preferred treatment is factor VIII

concentrate containing high levels of
vW factor.
 T
H
A
N
K
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