Hemostasis & Bleeding disorders

Dairion Gatot, Savita Handayani

Divisi Hematology -Onkology Medic

Internal Departement of Medical Faculty of North
Sumatera University /
Haji Adam Malik General Hospital,
Medan 2011
HEMOSTASIS, (Virchow’s Triad)
Function of HEMOSTASIS

• ARREST BLEEDING
• MAINTAIN BLOOD IN FLUID STATE
 HOMEOSTATIC HEMOSTASIS
Fisiologic funtion Maintain blood in fluid state
 Hemostatic Balance
Hemostasis an equilibrium of physiological activators and
inhibitors of coagulation
The equilibrium is fragile and several
causes put patient at risk

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
 Lab Tests
Hemostasis •CBC-Plt
•BT,(CT)
BV Injury •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 Xa coagulation cascade
Intrinsic 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
Clinical Manifestation of
Hemostatic defect
• Ptechia
• Purpura
• Echymosis
• Haematoma
• Haematemesis
• Melena
• Haemathrosis
• Haematophysis
• Hematuria
• Epistaxis
• Gum bleedeing
• 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
 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.
9 Maret 2004
9 Maret 2004
9 Maret 2004
9 Maret 2004
 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
 Coagulation Disorders
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
 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)
• Concentrat factor VIII Koate
• Recombinat factor VIII
 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
Symptom Platelet Coagulation
Petechiae Yes No

Sites Skin & Deep Tissue

Mucosa
Time Immediate Delayed

Ecchymoses Yes Yes

/Hematomas