Bleeding disorders

Dairion Gatot, Soegiarto Gani, Savita Handayani

Div Hematology-Medical Oncology, Dept of Internal Medicine

School of Medicine, Sumatera Utara Unversity
2009
HEMOSTASIS, (Virchow’s Triad)
Kerjasama 3 komponen : pembuluh darah, aliran
darah dan darah
Function of HEMOSTASIS

• ARREST BLEEDING
• MAINTAIN BLOOD IN FLUID STATE
HOMEOSTATIC HEMOSTASIS adalah mekanisma
fisiologis yang mempertahankan darah dalam bentuk
cairan di dalam sirkulasi, yang menggambarkan suatu
kesetimbangan yang baik antara perdarahan dan
pembekuan
Hemostatic Balance

PAI-1 Prot. S

Antiplasmin Prot. C

Tissue factor* TFPI

Fibrinolytic
Clotting Factors System
ATIII

Procoagulant Anticoagulant
 HEMOSTASIS
• Primary Hemostasis
– Blood vessel contraction
– Platelet Plug Formation
• Secondary Hemostasis
– Activation of Clotting Cascade
– Deposition & Stabilization of Fibrin
• Tertiary Hemostasis
– Dissolution of Fibrin Clot
– Dependent on Plasminogen Activation
 Hemostasis Lab Tests
•CBC-Plt
BV Injury •BT,(CT)
•PT
Tissue •PTT
Neural Platelet Factor
Adhesion
and
Activation

Blood Vessel Platelet Coagulation

Constriction Aggregation Cascade
Primary hemostatic plug

Reduced
Fibrin
Blood flow formation

Plt Study
Morphology
Stable Hemostatic Plug
Function
Antibody
 The primary haemostatic system:
haemostasis and platelet plug formation

Primary haemostasis
Platelet aggregation

trombosit
Adhesion
endothelial cells
Activation
sub endothelial tissue

Vascular Aggregation
injury
White clot

Formation of
platelet plug

exposed sub
endothelial tissue
 The haemostatic system:
secondary haemostasis and clot formation

Prothrombin Thrombin Activation of the

Factor coagulation cascade
Intrinsic
Xa
Extrinsic Fibrinogen Fibrin
leads to generation of
pathway pathway thrombin and, in turn,
fibrin

Coagulation cascade
leads to clot formation

Clot
growth
Fibrin threads
 The haemostatic system:
Tertiary haemostasis and clot formation
 Coagulation balance:
endogenous activators : the core role of factor Xa
Intrinsic system Extrinsic system
XII XIIa

XIa Cellular
XI thromboplastin
VIIa VII
IX IXa Ca2+
VIIIa
Ca2+
PL
Xa X
Xa
Va
Ca2+
Thrombin
PL
II IIa

XIIIa
Fibrinogen Soluble fibrin Fibrin (clot)
Boneu B, et al. Sang Thrombose Vaisseaux 1998; 10:291–313.
 Coagulation cascade
Hemophilia A 
(classic)is due to 
reduced amount or 
reduced activity of 
Hemophilia B  Factor VIII
(Christmas
Disease) results 
from  Thrombomodulin 
deficiency of factor  binds to thrombin, 
IX
making it an 
Heparin is a cofactor  anticoagulant which
that allows  then activates anti­
antithrombin III to  coagulant protein C.
inactivate thrombin  Protein C cleave 
and Factor Xa factors Va and VIIIa
Clinical Manifestation of Hemostatic
defect
• Ptechia
• Purpura
• Echymosis
• Haematoma
• Haematemesis
• Melena
• Haemathrosis
• Haematophysis
• Hematuria
• Epistaxis
• Petechia : a minute, rounded spot of haemorrhage on a
surface, such as skin, mucous membrane, serious
membrane
• Purpura : a condition in which haemorrhage occur in the
skin
• Ecchymosis: extravasasion of blood into the
subcutaneous tissue. It is marked by purple discoloration
of the skin, the color gradually changing to brown green
and yellow
• Hematemesis : the vomiting blood
• Hemoptysis : the spitting of blood from larynx ,pharynx,
trachea, bronchi or lung
• Hematoma : a focalized extravasation of blood which
soon clot to form a solid mass and readily became
encapsulated by connective tissue
• Melena : the discharge of stool colored black by altered
blood
• Hemathrosis : extravasation of blood into a joint
• Hematuria : the discharge of urine containing blood
• Epistaxis : bleeding from nose
• Hematoschezia : the discharge of stool colored red or
brown
 Disorders of Hemostasis
• Vascular disorders –
– Scurvy, easy bruising, Henoch-Schonlein purpura.
• Platelet disorders
– Quantitative - Thrombocytopenia
– Qualitative - Platelet function disorders – Glanzmans
• Coagulation disorders
– Congenital - Haemophilia (A, B), Von-Willebrands
– Acquired - Vitamin-K deficiency, Liver disease
• Mixed/Consumption: DIC
VASCULAR
 Vascular
• Purpura, echymosis
• Connective tissue  Ehler-Danlos Syndrome
• Aging process  senile purpura (Bateman’s disease)
• Infectious
 Meningococcus  Rocky Mountain’s syndrome
typhoid fever  Roseola spot
• Vit C deficiency  scurvy
• Immunologic Henoch-Schonlein purpura
• ↑ fragility capillary  infectious, vasculitis
Senile Purpura
Petechiae in
Vasculitis
(Rocky Mountain Spotted Fever)
 Henoch-Schonlein purpura

20y Male, fever, painful symmetric polyarthritis for a day. During the next two days,
edema and palpable purpura developed.
 Henoch-Schonlein purpura
• Immune disorder
• Children
• Follows infection
• Petechiae with
edema and
itching.
 Vascular
• Non palpable purpura
 senile purpura
 scurvy
 use corticosteroid
• Palpable purpura  Henoch-Schonlein
syndrome
THE ROLE OF PLATELET IN
HEMOSTASIS
THE ROLE OF PLATELET IN
HEMOSTASIS
 Platelet dysfunction:
Inherited Disorders:
– Bernard-Soulier disease
• large platelets, failure of adhesion
– Glanzmann’s thrombasthenia
• normal size, failure of aggregation
Acquired Disorders:
– Drugs : Aspirin
– Alcohol
– Uremia,
 Platelet dysfunction

• Quantitatif : - thrombocytemia
- ITP
- aplastic anemia
- DHF
- acute leukemia
- hypersplenism
Platelet Disorders - Features:

• Mucocutaneous bleeding
• Petechiae, Purpura, Ecchymosis.
• Spontaneous bleeding after trauma
• CNS bleeding (severe,  plt)
• Prolonged bleeding time (BT)
Dengue Hemorrhagic fever

Platelet deficiency..
 Petechiae
(typical of platelet disorders)

Do not blanch with

pressure
(cf. angiomas)
Not palpable
(cf. vasculitis)
 Idiopathic Thrombocytopenic
Purpura (ITP)
• Acute - children (post infection)
• Chronic - adults ( females, 20-40 yrs)
• autoimmune disorder
• antiplatelet antibodies (IgG)
• IgG coated platelets removed by spleen
• Usually  megakaryocytes in BM
 Coagulation disorders:
• Deficiencies of Clotting factors
• Onset - delayed after trauma
• Deep bleeding
– Into joints - Hemarthroses
– Into deep tissues – Hematoma
– large skin bleed – Ecchymoses
Ecchymoses
(typical of
coagulation factor
disorders)
 Coagulation Disorders
• Laboratory findings:
• Normal bleeding time & Platelet count
• Prolonged prothrombin time (PT)
– deficiencies of II, V, VII, X
• Prolonged time (aPTT)
– all factors except VII, XIII
• Mixing studies - normal plasma corrects PT or
aPTT
 Factor VIII Deficiency
• Classic hemophilia (hemophilia A):

• X-linked disorder (affects 1º males)

• Most common - severe bleeding
• Spontaneous hematomas < 1, 5, 75%
• Abnormal aPTT – Intrinsic path.
• Diagnosis - factor VIII assay
• Treatment - factor VIII concentrate
• Cryoprecipitate (less desirable)
 Factor IX Deficiency
• Christmas disease (Hemophilia B):

• X-linked recessive disorder

• Indistinguishable from classic hemophilia (F VIII)
• Requires evaluation of factor VIII and IX activity
levels to diagnose
• Treatment - factor IX concentrate
• Cryoprecipitate if factor IX unavailable
Von-Willebrand Disease:
• Coagulation + PLT disorder:

• Congenital disorder
• Deficiency of vWF molecule
• Part of FVIII,
• Mediates platelet adhesion
• Prolonged Bleeding time
• Low Factor VIII & long aPTT
• Mucocutaneous bleeding
• Von-Willebrand Disease:

• vWF: F-VIII & Plt function.

• Defective Platelet Adhesion
• Skin Bleeding
• Prolonged Bleeding time.
• Low Factor VIII levels.
Secondary Hemostatic Disorders

Acquired coagulation disorder:

 Vitamin K deficiency
- neonates - decreased intestinal
flora and dietary intake
- oral anticoagulants (coumadin)
- fat malabsorption syndromes

 Required for factors II, VII, IX, X

 Prolonged PT and aPTT
Combined Primary and Secondary
Hemostatic Disorders

Severe Liver Disease:

 Primary - dysfunctional platelets and/or

thrombocytopenia ( BT)
 Secondary - decrease in all coagulation factors

except vWF ( PT, aPTT)

 Vitamin K will promote synthesis of factors II, VII,

IX, X
 Clinical Features of Bleeding
Disorders
Platelet Coagulation
disorders factor disorders

Skin Deep in soft tissues

Site of bleeding Mucous membranes (joints, muscles)
(epistaxis, gum,
vaginal, GI tract)
Petechiae Yes No
Ecchymoses (“bruises”) Small, superficial Large, deep
Hemarthrosis / muscle bleeding Extremely rare Common
Bleeding after cuts & scratches Yes No
Bleeding after surgery or trauma Immediate, Delayed (1-2 days),
usually mild often severe
 Platelet Coagulation

Petechiae, Purpura Hematoma, Joint bl.

Summary