1. Dairion Gatot, Soegiarto Gani, Savita Handayani
Bleeding disorders
Dairion Gatot, Soegiarto Gani, Savita Handayani
Div Hematology-Medical Oncology, Dept of Internal Medicine
School of Medicine, Sumatera Utara Unversity
2009

2. HEMOSTASIS, (Virchow’s Triad) Kerjasama 3 komponen : pembuluh darah, aliran darah dan darah

3. Function of HEMOSTASIS
ARREST BLEEDING
MAINTAIN BLOOD IN FLUID STATE

4. HOMEOSTATIC HEMOSTASIS adalah mekanisma fisiologis
HOMEOSTATIC HEMOSTASIS adalah mekanisma fisiologis yang mempertahankan darah dalam bentuk cairan di dalam sirkulasi, yang menggambarkan suatu kesetimbangan yang baik antara perdarahan dan pembekuan

5. Hemostatic Balance Procoagulant Anticoagulant PAI-1 Prot. C
Prot. S
Prot. C
Antiplasmin
TFPI
Tissue factor*
Fibrinolytic System
Clotting Factors
ATIII
Procoagulant
Anticoagulant

6. HEMOSTASIS Primary Hemostasis Secondary Hemostasis Tertiary 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

7. Stable Hemostatic Plug
Lab Tests
CBC-Plt
BT,(CT) PT
PTT
Hemostasis
BV Injury
Platelet
Aggregation
Blood Vessel
Constriction
Coagulation
Cascade
Stable Hemostatic Plug
Fibrin formation
Reduced
Blood flow
Tissue Factor
Primary hemostatic plug
Neural
Platelet Adhesion
and
Activation
Plt Study
Morphology
Function
Antibody

9. The primary haemostatic system: haemostasis and platelet plug formation
Slide A8
Primary haemostasis
Platelet aggregation
trombosit
Adhesion
Activation
Aggregation
White clot
endothelial cells
sub endothelial tissue
Vascular
injury
Formation of
platelet plug
exposed sub
endothelial tissue

10. The haemostatic system: secondary haemostasis and clot formation
Slide A9
Prothrombin
Thrombin
Activation of the coagulation cascade leads to generation of thrombin and, in turn, fibrin
Factor Xa
Intrinsic
pathway
Extrinsic
pathway
Fibrinogen
Fibrin
Coagulation cascade
leads to clot formation
Clot
growth
Fibrin threads

11. The haemostatic system: Tertiary haemostasis and clot formation

12. Cellular thromboplastin
Coagulation balance: endogenous activators : the core role of factor Xa
Intrinsic system
Extrinsic system
XII
XIIa
Cellular thromboplastin XI
XIa
VIIa
VII IX
IXa
Ca2+
VIIIa
Ca2+ PL Xa X Xa Va PL
Ca2+
Thrombin
IIa II
XIIIa
Fibrinogen
Soluble fibrin
Fibrin (clot)
Boneu B, et al. Sang Thrombose Vaisseaux 1998; 10:291–313.

13. Coagulation cascade
Hemophilia A (classic)is due to reduced amount or reduced activity of Factor VIII
Hemophilia B (Christmas
Disease) results from
deficiency of factor IX
Thrombomodulin binds to thrombin, making it an anticoagulant which
then activates anti-
coagulant protein C.
Protein C cleave factors Va and VIIIa
Heparin is a cofactor that allows antithrombin III to
inactivate thrombin and Factor Xa

15. Clinical Manifestation of Hemostatic defect
Ptechia
Purpura
Echymosis
Haematoma
Haematemesis
Melena
Haemathrosis
Haematophysis
Hematuria
Epistaxis

16. 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

17. 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

18. 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

19. VASCULAR

20. Vascular ↑ fragility capillary  infectious, vasculitis
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

21. Senile Purpura

22. Petechiae in
Vasculitis
(Rocky Mountain Spotted Fever)

23. Henoch-Schonlein purpura
20y Male, fever, painful symmetric polyarthritis for a day. During the next two days, edema and palpable purpura developed.

24. Henoch-Schonlein purpura
Immune disorder
Children
Follows infection
Petechiae with edema and itching.

29. Vascular Non palpable purpura  senile purpura  scurvy
 use corticosteroid
Palpable purpura  Henoch-Schonlein syndrome

30. THE ROLE OF PLATELET IN HEMOSTASIS

31. THE ROLE OF PLATELET IN HEMOSTASIS

32. 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,

33. Platelet dysfunction Quantitatif : - thrombocytemia - ITP
- aplastic anemia
- DHF
- acute leukemia
- hypersplenism

34. Platelet Disorders - Features:
Mucocutaneous bleeding
Petechiae, Purpura, Ecchymosis.
Spontaneous bleeding after trauma
CNS bleeding (severe,  plt)
Prolonged bleeding time (BT)

35. Dengue Hemorrhagic fever
Platelet deficiency..

36. (typical of platelet disorders)
Petechiae
(typical of platelet disorders)
Do not blanch with pressure (cf. angiomas) Not palpable (cf. vasculitis)

37. Idiopathic Thrombocytopenic Purpura (ITP)
Acute - children (post infection)
Chronic - adults ( females, yrs)
autoimmune disorder
antiplatelet antibodies (IgG)
IgG coated platelets removed by spleen
Usually  megakaryocytes in BM

38. Coagulation disorders:
Deficiencies of Clotting factors
Onset - delayed after trauma
Deep bleeding
Into joints - Hemarthroses
Into deep tissues – Hematoma
large skin bleed – Ecchymoses

40. (typical of coagulation factor disorders)
Ecchymoses
(typical of coagulation factor disorders)

41. 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

42. 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)

43. 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

44. 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

45. Von-Willebrand Disease:
vWF: F-VIII & Plt function.
Defective Platelet Adhesion
Skin Bleeding
Prolonged Bleeding time.
Low Factor VIII levels.

46. 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

47. 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

48. Combined Primary and Secondary Hemostatic Disorders (DIC)
Disseminated Intravascular Coagulation:
Major pathologic processes -
obstetric complications, neoplasms, infection (sepsis), major trauma
Primary - platelet consumption
( bleeding time,  platelets)
Secondary - factor consumption
( PT, aPTT)

49. 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

50. Platelet Coagulation
Petechiae, Purpura Hematoma, Joint bl.

51. Summary