Bleeding

disorders
:Prepared and Presented by
Kholoud AL-atawi
Omnia Shaban
students should be able to At the end of, :
this seminar
1. Identify causes of bleeding disorders.
2. Discuss the tests used in initial evaluation of patients with
bleeding disorders.
3. Discuss definition and causes of thrombocytopenia.
4. Describe etiology, pathogenesis, classification, clinical
features, and laboratory diagnosis of
immune thrombocytopenic purpura (ITP).
5. Identify and classify causes of coagulation disorders.
6. Discuss types, causes, clinical features, laboratory diagnosis,
and treatment of haemophilia.
7. Discuss causes, clinical features, laboratory diagnosis, and
treatment of von-Willebrand Disease
 Hemostasis

Definition:
It is the stoppage of bleeding whenever it occurs.

There are several phases to hemostasis:

1. Vascular Phase.
2. Platelet Phase.
3. Coagulation Phase.
4. Clot retraction.
5. Fibrinolysis and resolution.
 :Normal Hemostasis Components

1. BV Vasoconstriction
2. Platelet plug formation
3. Activation of Coagulation stable fibrin
plug.
4. Activation of fibrinolysis clot dissolution.
 Clotting Factors

Clotting Factor Synonyms

Fibrinogen Factor I
Prothrombin Factor II
Tissue factor Factor III; tissue thromboplastin
Calcium Factor IV
Factor V Proaccelerin; labile factor;
factor VII Serum prothrombin conversion
accelerator
Factor VIII Antihemophilic A factor (AHF);
 Factor IX Plasma thromboplastin
Christmas factor;
antihemophilic factor B

Factor X Stuart factor;

Factor XI Plasma thromboplastin
antecedent
antihemophilic factor C

Factor XII Hageman factor- glass factor

Factor XIII Fibrin-stabilizing factor
:Hemostasis depends on three factors

Integrity of blood vessel wall

Platelets
Coagulation system

:So Excessive bleeding can result from

Increased fragility of vessels-

Platelet deficiency or dysfunction -
Defect in coagulation-
 Definition: abnormalities of hemostasis and / or coagulation,
characterized by local or extensive skin or mucocutaneous
hemorrhage derived from capillary. The bleeding is usually
spontaneous or from slight trauma
bleeding disorders: Causes of
Blood Vessel Platelet Coagulation
Disorders Disorders Disorders
Hereditary Function disorder -: :Hereditary
H.H.telangiectasia Drugs Aspirin Due to deficiency of
Marfans sy. Kidney failure: certain coagulation
. uremia :factors . As

AcquirBleeding Thrombocytopenia: hemophilia A & B-

Disorders: Immune - ITP von willebrand disease-
Scurvy, Chemotherapy
Viral Drugs, viral :Acquried
infections Infection
.Aplastic anemia Liver diseasse-
vitamin k deficiency-
 Laboratory diagnosis of bleeding disorders

Five studies are important to the diagnosis of bleeding

disorders:
Platelet conts :
normal range: (150000-400000 CELLS/MM3)
< 100,000 Thrombocytopenia
50,000 - 100,000 Mild Thrombocytopenia
< 50,000 Sev Thrombocytopenia
Bleeding time(BT):
evaluates platelet function up to the formation of
temporary platelet plug.(normal value 2-5 minutes)
Prothrombin time(PT):
test the extrinsic pathway (Factors V, VII,
X) and common pathway (prothrombin and
fibrinogen components by measuring clotting
time in response to commercial tissue factor.
(normal value 10-15 seconds)
partial thromboplastin time (APTT):
test the intrinsic pathway (Factors XI, IX, VIII,
X) and common pathway (prothrombin and
fibrinogen) components by measuring clotting
time in response to calcium and phospholipids
(normal value 21-35 seconds)
Thrombin time (TT):
Time for Thrombin To Convert -
Fibrinogen Fibrin
measure of Fibrinolytic Pathway. (normal value 10-15)

Thrombocytopenia
Thrombocytopenia

: Definition
inadquate number of platelate .less than 100,000 cell -

: Laboratory test
PT and PTT normal
prolonged Bleeding time
: Clinical manifestations
Petechiae or large ecchymoss in the skin , the mucous-
. membranes of the gastrointestinal and urinary tracts

Larger hemorrhage into the CNS in patients with -

.sever decresed platelet counts
Petechiae <3mm
Purpura <1 cm
Echymosis >1cm
 Causes of thrombocytopenia

Sequestration in the spleen Increased destruction

Immunolgic destruction:
thrombocytopenia e.g Immune
e.g Hypersplenism thromboctopenic purpura
(ITP), Drugs
Nonimmunologic-
destruction: e.g
Thrombotic
thrombocytopenic
Decreased production purpura, DID

e.g Aplastic anemia ,

Marrow infiltration as
hhhhhf
in leukemia
 Immune Thrombocytopenic Purpura (ITP)
(Idiopathic Thrombocytopenia Purpura(

: Etiology & pathogenesis

Caused by autoantibodies(IGg( directed against platelet membrane
Classification :
ITP is classified into either :
1- secondary ITP ( of known cause )
2- primary ITP ( Idiopathic) :

Two clinical subtypes of primary ( idiopathic) ITP :

1- acute primary ITP :
- self limited disorder
- commonly seen in childern following a viral infection .
2- chronic primary ITP :
- common disorder
- usually seen in adult females between 20 40 years
- May be a manifestation of systemic lupus erythematosus .
 Clinical Features of ITP
Petechiae Ecchymosis (bruises) gum bleeding

Bleeding occur spontaneously or Epistaxis

following trauma.
Skin is the most common site of
haemorrhage
Haemorrhage may in the form of
petechiae or ecchymoses, or both.
Bleeding from mucous membrane is
common.
Epistaxis, gum bleeding, menorrhagia,
melena may also occur.
 Laboratory Findings

Antiplatelet
Thrombocytopenia PTT & PT: Normal
antibody (IgG(

Decreased platelet BM:

Megakaryocytes Bleeding time (BT(:
count below are increased in prolonged
100 000 number

?? Why
 :Treatment

- Corticostteroide
- Immunoglobulin therapy
- Splenectomy : complete remission in most
patients.
 Thrombotic Thromocytopenic Purpura
( TTP)
Pathogenesis:
deficiency or inhibition
of metalloproteinase
ADAMTS13 most commonly
disabled by an autoantibody
ADAMTS13 degrades vWF
multimers
deficiency large vWF multimers
increased platelet adhesion
platelet thrombosis
Epidemiology:
female > male
most commonly in young adults
Clinical finding: : Laboratory findings
Symptoms (recall pentad) Complete blood count
thrombocytopenia anemia -
easy bleeding Thrombocytopenia -
epistaxis
neurological symptoms Peripheral blood smear
confusion schistocytes (helmet cells) -
seizures
thrombosis bleeding time
renal dysfunction
normal PT/PTT
Physical exam
fever
pallor (from anemia)
purpura/petechiae
jaundice (from hemolysis)
splenomegaly
The peripheral blood smear shows schistocytes ( arrows)
seen,in Microangiopathic Hemolytic Anemia
Superficial Deep Bleeding/
Platelet / BV Coagulation

A. Superficial & small Platelet & BV disorder

B. Deep & Big Coagulation disorder
Antibodies made in the spleen that are directed
against the cell surface antigens GpIIb/IIIa or
GpIb/IX are characteristically seen in individuals
with:
a. Cold autoimmune hemolytic anemia
b. Feltys syndrome
c. Hashimotos thyroiditis
d. Immune thrombocytopenic purpura
e. Warm autoimmune hemolytic anemia
Coagulation disorders
 Coagulation disorders

Acquried Congenital
Vitamin K Hemophilia A
Liver disease Hemophilia B
Drugs-Heparin von willebrand
disease
 :Hemophilia
Genetics- A (Classic Hemophilia)
Genetics : X-linked recessive
Caused by : Deficiency of factor VIII
Signs/symptoms:
spontaneous bleeding or bleeding following trauma or
surgery
hemoarthroses (Bleeding into joints) deformities
swollen and painful joints
easy bruising and hematoma
Diagnostics: PTT,normal PT, normal platelet count and
bleeding time
most specific test functional assay for factor VII
Treatment : Desmopressin and recombinant factor VII
concentrate.
 Hemophilia B(Christmas Disease )
Genetics : X-linked recessive
Caused by : Deficiency of factor IX
Signs/symptoms:
spontaneous bleeding or bleeding following trauma or
surgery
hemoarthroses (Bleeding into joints) deformities.
swollen and painful joints.
easy bruising and hematoma.
Diagnostics: PTT, normal PT, normal platelet count
and bleeding time.
most specific test functional assay for factor IX
Treatment : Desmopressin and recombinant factor VII
concentrate.
Von willebrand factor
 Von willebrand Disease

a common inherited bleeding disorder in which

your blood doesn't clot well.,
autosomal dominant Disease
caused by :
a deficiency or dysfunction VW

:Clinical Features
1. Excessive bleeding from an injury or after surgery or
dental work
2. Nosebleeds that don't stop within 10 minutes
3. Heavy or long menstrual bleeding
4. Blood in your urine or stool
5. Easy bruising or lumpy bruises
Laboratory Findings

Bleeding
time: PT: Normal
Prolonged

Clotting Platelet
time: count:
Prolonged Normal

Factor VIII
PTT:
assay:
Prolong
Reduced