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Hemostasis

Indra Wijaya
Internal Medicine
Hasan Sadikin Hospital - Medical Faculty
Padjadjaran University
HEMOSTASIS

Mechanism to stop spontaneous
bleeding and maintain blood circulation
in vessels

Including: - Coagulation system
- Fibrinolysis system

Complex process

Hemostasis Pathofisiology
Bleeding
and
fibrinolysis
Coagulation
Hemostasis
Interaction: Blood vessel thrombocyte coagulation
factors
Medical Bleeding Caused by
Defects of:
1. Blood vessel wall
Inflammation

2. Thrombocyte
Qualitative or quantitative

3. Coagulation factors
Quantitative or inhibitor

Primary Hemostasis:
Vascular (blood vessel)
Thrombocyte

Secondary Hemostasis:
Blood coagulation factors
Hemostasis Pathofisiology
Blood Vessel
Permeability, Fragility, Vasoconstriction
Release:
- Tissue Factor
- von Willebrand factor (vWf)
- Prostacyclin: Vasodilatation, Thrombocyte Aggregation
inhibitor
- Anti thrombin
Coagulation inhibitor
- Thrombomodulin
Pro - coagulation
Balancing
Coagulation Inhibition
THROMBOCYTE
Perform and stabilized thrombocyte plug

Adhesion - Aggregation - releasing

Protein S carrier
(Protein S activate protein C)
COAGULATION
Intrinsic Pathway: XII, XI, IX, VIII, PF
3
,
HMWK,
Calcium ion
HMWK
XII
a
Pre Kalikrein


Kalikrein VII

VII
a

Plasminogen Plasmin
Extrinsic Pathway: - Tissue Thromboplastin
- VII Factor
- VII
a
IX IXa
X Xa

Common Pathway:
Fibrinogen
Protrombin Thrombin


Fibrin
Coagulation Cascade
Blood cloth control
mechanism
Blood Circulation : dilution
Clearance : Hepatocyte and RES
INHIBITOR : AT III, Protein C,
Protein S,

2
Macroglobulin,

1
Antitrypsin
FIBRINOLYSIS
Fibrin destruction opening blood circulation
Fibrinolysis system : - Plasminogen
- tissue-Plasminogen Activator (t-PA)
- Plasmin Inhibitor

Plasminogen Activator: - Intrinsic (F XII a, Kalikrein)
- Extrinsic : t-PA (Endothel)
- Exogen : Streptokinase
Plasmin Inhibitor: -
2
Plasmin Inhibitor
-
2
Macroglobulin
-
1
Antitripsin
- AT III
Vasoconstriction
Primary Hemostasis
Thrombin
Fibrin Fibrinogen
Secondary Hemostasis
t-PA
Thrombomodulin
Fibrinolysis
Blocks coagulation
Anticoagulation counter-regulation
t-PA
Thrombomodulin
Fibrinolysis
Blocks coagulation
Anticoagulation counter-regulation
Clinical Difference of Vascular, thrombocyte and
coagulation system defect
Clinical
Presentation
Coagulation Disorder
Thrombocyte/
vascular Disorder
- Petechiae Rarely Characteristic
- Hematom Characteristic Rarely
- Echimosis Frequent, big,
soliter
Characteristic, small,
multiple
- Hemarthrosis Characteristic Rarely
-Occult
bleeding
Frequent Rarely
Clinical Difference of Vascular, thrombocyte and
coagulation system defect
Clinical
Presentation
Coagulation
Disorder
Thrombocyte/
vascular Disorder
- Bleeding from
superficial lesion
Minimal

Persistent, severe
bleeding is frequent
- Sex 80-90% Male Dominantly female
- Family history Frequent Rarely
Petechiae
Echimosis
Thrombositopenia
Decreasing production: Hereditary,
Bone marrow Hypoplasia
Increasing destruction:
Immune : ITP, Secondary effect diseases
Non immune : Microangiopathy, Vasculitis

Abnormal distribution: Splenomegali


Immune thrombocytopenic purpura (ITP)
Thrombositopenia due to thrombocyte destruction by
antibody

Thrombocytes surface protein stimulate autoantibody.

ANTIGEN: GP Ib/IX, GP IIb/III a
- macrophage immune complex ( Reseptor Fc )
- C 5-9 Activated and fixated
Thrombocyte Lysis
History of ITP
Acute ITP
- children and adolescent, male = female
- Viral infection 1 - 3 weeks before
- Acute bleeding symptom
- 2 - 6 weeks
- spontaneous remission 80%
Chronic ITP
- Female, menometrorhagi
- Several months to years
- Rarely spontaneous remission
- Secondary manifestation of SLE, HIV,
lymphoma

ITP symptom's
Petekhie, echimosis, hemorrhagic
vesicles or bullae
Epistaksis, gum bleeding, traumatic
bleeding etc.
Intracranial bleeding, 1 %
No Limphadenopaty
Mild Splenomegali
ITP Laboratory
Thrombositopenia, Retikulocytosis
Anemia
Prolonged Bleeding Time
Bone marrow: Agranular Megakariocyte
Other assay: ANA, Anti-dsDNA, Anti HIV
Drug induced thrombocytopenia
Acetaminophen, Alopurinol
Amiodaron, Aspirin
Penicillin, Cephalosporin
Cimetidin, Ranitidin
Diazepam, Kina, Digitalis
Rifampisin, INH, PAS
Phenitoin, furosemid, heparin
Opiat, metildopa
Cotrimoxazole
ITP Therapy
Steroid : prednisone, methylprednisolone
Danazole
Immunosupresive: Cyclofosfamid ,
Azathioprine, Cyclosporin, Vinkristin
Immunoglobulin
Splenectomy
Thrombocyte function defect
Hereditary : Mimically thrombocytopeni
Prolonged bleeding time
Normal thrombocyte count
Abnormal aggregation thrombocyte test

- Bernard-Souliers Syndrome ( Def.GP Ib/IX)
- Glanzmanns Thromboasthenia (Def.GP IIb/IIIa)

Acquired : Systemic diseases: Hematologic
diseases,
Uremia, Drugs
Thromboasthenia
Vascular Defect

A part of systemic disease:

Vasculities (eg: Henoch-Schonlein Purpura )
Telangiektasi
Collagen disease
Autoimmune disease

Henoch-Schonlein Purpura (HSP)
Allergic vascular purpura

Defect on vascular permeability in skin, joint, small
intestine, kidney, others.

Secondary from:
1. Infection
2. Drugs
3. Chemical
4. Autoimmune disease: SLE, RA
5. Malignancy
Henoch-Schonlein Purpura
Lab: normal thrombocyte, Rumple Leede (+)

Differential diagnosis:
ITP
ATP
Abdominal colic
Articular disease

Therapy : Symptomatic, Steroid

Hemophilia
Hemophilia A : f VIII deficiency
B : f IX deficiency

Bleeding depends on F VIII / IX level
Spesific assays: substitution test
Therapy : depend on type
Coagulation Disorder
Clinical Classification of Hemophilia A
Factor VIII Level Clinical Features
Severe 1% of normal
( 0.01 U/ml)
Spontaneous hemorrhage from early
infancy
Requiring clothing factor replacement

Moderate 1 5% of normal
(0.010.05 U/ml)
Hemorrhage secondary to trauma or
surgery
Occasional spontaneous hemarthroses

Mild 6 30% or
normal
(0.060.30 U/ml)
Hemorrhage secondary to trauma or
surgery
Rare spontaneous hemorrhage
Laboratory
Prolonged aPTT
Factor VIII IX activity
Therapy
General : Avoid NSAID, aspirin
No intramuscular injection
F VIII Concentrate : 50 U/kg
F IX 25 40 U/kg twice weekly
Cryoprecipitate
Transfusion : Fresh whole blood (hemophilia A)
Screening Test for Hemorrhagic Diathesis
Platelet
Prothrombine time (PT)
APTT
Bleeding time

Platelet disorder
Bleeding time
Vascular

PT
Factor deficiency
APTT
APTT : intrinsic pathway
PT: extrinsic pathway
BLEEDING
HISTORY
PHYSICAL
DIAGNOSIS
SCREENING
CBC
BT
APTT
PT
Anemia
Organomegaly
Type of bleeding
Underlying disease
VESSEL
THROMBOCYTE COAGULANT FACTORS
Palpabel Non Palpabel
Quantitative Hereditary
qualitative
Acquired
qualitative
Congenital Acquired
- Henoch-
Schnlein
- Dysproteinemia
- Primary
untaneon disease
- Unknown
- Primary
- Secondary
Pressure
Integrity
Trauma
- Glanzmann
- Bernard-Soulier
- Systemic
diseases
- Hematologic
- Drugs or foods
- vW
- Hemophilia
- Fibrinogen
- DIC
- Primary
fibrinolysis
- vW

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