Bleeding
Primary
Vasoconstriction
Hemostasis
Platelet plug
Secondary
Blood clot Hemostasis
Normal Primary Hemostasis
Hoffbrand AV, Pettit JE, Moss PA. Essential Haematology. 4th ed. 2001
Pathogenesis of ITP
Specific platelet autoantibodies binding to the
platelets
• Autoantibody-mediated platelet destruction
• Suboptimal platelet production
Pathogenesis of ITP
Autoantibody-mediated platelet destruction
Hemophilia is a long-life
disease !!
Etiology & Pathogenesis
Hemophilia A Hemophilia B
The gene for FVIII (F8C) The gene for FIX (F9)
located within the Xq28 located within the Xq27
region; contains 2332 region; contains 415
amino acids amino acids
Normal Hemostasis
How does bleeding start and stop?
Bleeding
Primary
Vasoconstriction
Hemostasis
Platelet plug
Secondary
Blood clot Hemostasis
Normal Secondary Hemostasis
The classic coagulation cascade model
Intrinsic pathway Extrinsic pathway
Common pathway
Initiation Amplification
Propagation
Hoffman M, Dargaud Y. J Thromb Haemost 2012.
Secondary Hemostasis Disorders
Common pathway
Initiation Amplification
Propagation
Hoffman M, Dargaud Y. J Thromb Haemost 2012.
Pathophysiology of Hemophilia
Hemophilia (secondary hemostatic disorder):
• Bleeding tendency
• Most internal bleeding: joints, muscles, GIT,
genitourinary tact or intracranial
• The severity of bleeding is generally correlated with
the clotting factor level
Antibodies against
C2 domain
DiMichele DM. World Federation of Hemophilia 2008; Gringeri A, et al. Blood 2003.
Pathogenesis and
Pathophysiology of
Vitamin K Deficiency
Bleeding (VKDB)
Vitamin K
A fat-soluble vitamin that can be absorbed from the
GI tract in the presence of bile salts.
Is required for the production of coagulation factor (FII,
FVII, FIX and FX) in the liver.
Inadequate intake of vitamin K can result in
deficiency in a short period of time because of:
- the short half-life of these factors, and
- the small amounts of vitamin K that can be
stored in the body.
Several Forms of Vitamin K
• Vitamin K1 (Phylloquinone): green leafy vegetables
Vitamin K γ-glutamyl
carboxylase (GGCX)
Vitamin K Cycle
Vitamin K γ-glutamyl
carboxylase (GGCX)
Vitamin K dependent
proteins
Vitamin K Dependent Proteins
• Coagulation factors:
- Factor II (prothrombin)
- Factor VII (proconvertin)
- Factor IX (thromboplastin component)
- Factor X (Stuart factor)
• Protein C & protein S
• Protein Z
Functions of Vitamin K
Prothrombin – platelet interaction
•Carboxylated prothrombin contains two carboxylate
groups bind to Ca2+ forming prothrombin-Ca complex
•The complex then binds to phosholipids on the surface of
platelets (important for blood clotting)
•Converting prothrombin to thrombin & initiating clot
formation
Vitamin K Deficiency Bleeding
Synonym: Vitamin K Deficiency Bleeding (VKDB),
Hemorrhagic Disease of the Newborn (HDN)
Risk factors for VKDB:
• Prolonged antibiotic therapy & gastrointestinal
infections with diarrhea destroy the bacterial flora
leading to vitamin K deficiency
• Most common in newborn infants
Vitamin K Deficiency Bleeding
Why are newborns vulnerable to deficient in vitamin K ?
• Placenta transfer of vitamin K is very limited
• Vitamin K1 (Phylloquinone) levels in umbilical cord
blood is very low
• The storage of vitamin K in neonate liver is also
limited
• Breast milk is poor source of vitamin K
• GI tract is sterile at birth gut-related microbial
source of vitamin K is low
Pathogenesis of VKDB
Vitamin K γ-glutamyl
carboxylase (GGCX)
Vitamin K dependent
proteins
Pathogenesis of VKDB