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Objectives
1. To understand normal physiologic
hemostasis in infant and children.
2. List the most common hemostatic
abnormalities in infant and children.
3. To describe diagnostic approach and
management of bleeding in infant and
children.
Hemostasis
is series of physiological processes which
arrest bleeding at the site of injury and
initiate repair of the blood vessel.
Involving:
1.
2.
3.
4.
Blood vessels
Platelets
Coagulation cascade
Fibrinolytic system
Nathan and Oskis Hematology of Infancy and Childhood. Sixth edition. Philadelphia, WB Saunders Company, 2003,
Hillman RS, Ault KA, Rinder HM. Hematology in clinical practice. Fourth edition. New York: McGraw Hill; 2005.
Anticoagulant
Vessel contraction
Coagulation factor production
Protein C inhibitor
Factor VIII
Factor Von Willebrand
Fibronectin
Activation antigen expression
p-selectin
Platelet inhibition
Nitric oxide
Prostacyclin
ADPase
Clot inhibition/lysis
Heparans
Thrombomodulin
Tissue factor pathway inhibitor
Plasminogen activator
Hillman RS, Ault KA, Rinder HM. Hematology in clinical practice. Fourth edition. New York: McGraw Hill; 2005.
Platelets
Structure:
Function :
plasma membrane
cytoplasmicgranules
surface-connected
canalicular system
peripheral band of
microtubules
cytoplasmic microfilaments
dense tubular system
platelet adhesion
the platelet shape
change
platelet release reaction
platelet aggregation
platelet procoagulant
activities
Furie B, Furie BC. Molecular and cellular biology of blood coagulation. N Engl J Med 1992;326;800.
Platelet activation
Vascular damage
1. Adhesion
1 2 sec
ADP Release
2. Loose aggregation
Thrombin formation
on platelet plug surface
3. Firm aggregation
2 4 min
Coagulation
4. Fibrin formation
5 10 min
Platelet retraction
5. Clot retraction
1 2 hrs
Thrombin formation
www.irvingcrowley.com
Coagulation factors
Components of coagulation factor:
fibrinogen
prothrombin
tissue factor (thromboplastin)
Ca-ion (Ca++)
pro-accelerin (labile factor)
pro-convertin (stable factor)
anti-hemophilic factor
Christmas-factor
Stuart-Prower factor
plasma thromboplastin antecedent
Hageman factor
fibrin stabilizing factor(Laki-Roland)
factor
factor
factor
factor
factor
factor
factor
factor
factor
factor
factor
factor
I
II
III
IV
V
VII
VIII
IX
X
XI
XII
XIII
Hutton RA, Laffan MA, Tuddenham EGD. Normal Hemostasis. In : Postgraduate Hematology.4th edition, 1999.
www.irvingcrowley.com
Hutton RA, Laffan MA, Tuddenham EGD. Normal Hemostasis. In : Postgraduate Hematology.4th edition, 1999.
Fibrinolysis
Components of the fibrinolytic system:
- Plasminogen and plasmin
Plasminogen activators:
- tissue plaminogen activator (tPA)
- urinary plaminogen activator (uPA)
- exogenous plasminogen activators
(streptokinase)
Hutton RA, Laffan MA, Tuddenham EGD. Normal Hemostasis. In : Postgraduate Hematology.4th edition, 1999.
Furie B, Furie BC. Molecular and cellular biology of blood coagulation. N Engl J Med 1992;326;800.
Hutton RA, Laffan MA, Tuddenham EGD. Normal Hemostasis. In : Postgraduate Hematology.4th edition, 1999.
Inhibitors of fibrinolysis
~ plasminogen-activator inhibitor type-1
~ plasminogen-activator inhibitor type-2
~ inhibitor of plasmin
alpha-2-anti-plasmin
lipoprotein A
Inhibitors of fibrinolysis
Hutton RA, Laffan MA, Tuddenham EGD. Normal Hemostasis. In : Postgraduate Hematology.4th edition, 1999.
Hutton RA, Laffan MA, Tuddenham EGD. Normal Hemostasis. In : Postgraduate Hematology.4th edition, 1999.
www.irvingcrowley.com
Normal
fibrinolysis
Inhibitor of
fibrinolysis
Inhibitor of
coagulation
hemostasis
Inhibitor of
fibrinolysis
Bleeding
fibrinolysis
Inhibitor of
coagulation
fibrinolysis
Thrombosis
hemostasis
Inhibitor of
fibrinolysis
Inhibitor of
coagulation
Bleeding
Mild
Severe
intervention
stopped
continues
prolonged
Platelet disorder
delayed
Coagulation disorder
Spontaneous bleeding
(without injury)
superficial, multiple
petechiae,
purpura,
ecchymoses
platelet disorder
deep, solitary
hematoma,
hemarthrosis
coagulation disorder
Vascular abnormalities
Vasculitis
Platelet disorder
Most common : ITP
Characterized by:
1.
2.
3.
4.
Patophysiology of ITP
Fab portion, IgG
Fc portion, IgG
Fc portion
Fc receptors
Nathan and Oskis Hematology of Infancy and Childhood. Sixth edition. Philadelphia, WB Saunders Company, 2003, .
Nathan and Oskis Hematology of Infancy and Childhood. Sixth edition. Philadelphia, WB Saunders Company, 2003, .
Allen GA, Glader B. Approach to the bleeding child. Pediatr Clin N Am 2002;49:1239-1256.
Leung AKC, Chan KW. Evaluating the child with purpura. Am Fam Physician 2001;64:419-428.
Coagulation disorders
Hereditary :
Hemophilia A & B
von Willebrand disease
Acquired :
Vitamin K deficiency
Liver disease
Renal disease
DIC (infection/sepsis, shock, severe head
injury)
World Federation of Hemophilia. Guidelines for the management of Hemophilia. Canada: World Federation of Hemophilia; 2005.
Djajadiman Gatot. Penyakit von Willebrand. In : Permono B, Sutaryo, Ugrasena IDG, Windiastuti E, Abdulsalam M, eds. Buku Ajar
Hematologi Onkologi Anak. Jakarta: BP IDAI; 2005.
Levi M, ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999;341:586.
Neonatal hemostasis
Neonatal hemostatic system is functionally
immature.
Coagulation system: factors concentration 50%
Fibrinolytic system: relatively hypofibrinolytic state
Platelets: normal count, hypofunction
The hemostasis system matures within weeks to
months and the concentration of most hemostatic
proteins are near to adult values by 6 months of
age
Nuss R, Manco-Johnson M. Bleeding disorder in the neonate. NeoReviews 2000;1:e196-e200.
Neonatal Hematology. First edition. Cambridge, University Press, 2005.
Neonatal bleeding
Clinical considerations are important in the
investigation of a neonate with hemorrhagic
problem
Apparently well neonate, suggestive of:
inherited coagulation disorder
an immune thrombocytopenia
Sick neonate (i.e. severe infection or sepsis),
consumptive coagulopathy i.e. DIC
Neonatal bleeding
Thrombocytopenia
Fetal thrombocytopenia
Immune thrombocytopenia
Neonatal allo-immune thrombocytopenia (NAIT)
Thrombocytopenia in the sick neonate (severe perinatal
infection, DIC, NEC)
Coagulation disorders:
Inherited - in apparently well neonate:
+ hemophilia, von Willebrand disease
+ rare coagulation disorders (deficiency I, VII, X, XIII)
Acquired - in unwell neonate: DIC
Vitamin K deficiency bleeding (VKDB)
Nuss R, Manco-Johnson M. Bleeding disorder in the neonate. NeoReviews 2000;1:e196-e200.
Neonatal Hematology. First edition Cambridge, University Press, 2005.
Finding
Type of disorder
Vascular
Platelet
Coagulation
History
Hereditarity
gender
rare
rare
common
Delayed bleeding
rare
rare
frequent
Prolonged bleeding
frequent
mainly
rare
Type of disorder
Finding
Vascular
Platelet
Coagulation
Clinical:
Petechiae
typical
typical
rare
Ecchymoses
typical
typical
present
Hematoma
rare
rare
typical
Hemarthrosis
rare
rare
typical
Laboratory:
Peripheral blood
normal
low p.c.
Bleeding time
prolonged
prolonged
normal
Clotting time
normal
normal
abnormal
Tourniquet test
Clot retraction
(+)
normal
(+)
abnormal
normal
(-)
normal
Hillman RS, Ault KA, Rinder HM. Hematology in clinical practice. Fourth edition. New York: McGraw Hill; 2005.
Management
ITP :
Self-limiting disease
Indications for treatment:
Severe bleeding
Mucosal bleeding
Generalized cutaneous bleeding
Platelet count < 20,000/ul
Treatment :
Management
Coagulation deficiency disorders
Vitamin K deficiency:
Thank You
Terima Kasih