This document discusses hemostasis disease in children, specifically focusing on immune thrombocytopenia (ITP). It describes the mechanisms, clinical presentation, diagnostic evaluation, and treatment approaches for ITP. Key points include that ITP is characterized by low platelet count due to increased platelet destruction by autoantibodies, with symptoms of bruising and bleeding. Evaluation involves blood tests to confirm thrombocytopenia and exclude other causes, while treatment may include corticosteroids, IVIG, or splenectomy in severe cases.

1. Hemostasis Disease
In Children
dr. Bertha

2. Hemostatic Mechanism
• Vascular response
• Plateletadhesion
• Platelet aggregation
• Clot formation
• Clot stabilization
• Limitation of clotting (antitrombil III, Protein C,
Protein S, TFP1)
• Re-establishment of vascular potency 
Fibrinolusis & vascular healing

3. History
• Site, severity,duration of bleeding
• Age of the symtomp onset
• Spontaneous or after trauma
• Previous history or family historyof bleeding
• Does bruising (memar) occur spontaneously?
• IS there has been previous surgery or dental
procedure?
• Menstrual history

4. Physical examination
• Symptoms primarily associated with
mucous or skin (mucocutaneous bleeding)
 defects in platelet or blood vessel wall
interaction (vWF disease)
• Or muscle & joints bleeding (deep
bleeding)  clotting factor deficiency
• Presence of petechiae, ecchymoses,
hematomas, hemarthroses, or mucous
bleeding

5. Trombin time
vWF
-Platelet count
-Bleeding time
-PT / aPTT
Specific work-up

6. Laboratory
• Bleeding time (BT)
– Assesses platelet function & their interaction with vascular wall
– Platelet < 100.000/µL  prolonged BT
– Disproportionate BT  qualitative platelet defects or vWF
disease
• aPTT
– Measures the initiation of clotting (intrinsic pathway)
– doesn’t measure factor VII, XIII or anticoagulant
• PT
– Measures extrinsic pathway
– Normal in defiencies offactor VIII, IX, XI or XIII

7. Laboratory
• TT
– Measures final step of the clotting cascade
– Prolonged  reduced fibrinogen levels
• Dysfunctional fibrinogen (hypo/afibrinogenemia)
• Substances that interfere with fibrin polymerization (heparin or fibrin
split products)  reptilase time
• Mixing studies
– if there is unexplained prolongation of PT, PTT or TT
– Normal plasma + patient’s plasma  repeat lab exam
• Correction of PT/PTT by mixing  clootting factor deficiencie
• Not corrected + bleeding  inhibitor
• Not corrected, no bleeding  lupus-like-anticoagulant
• Clotting factor assays

8. Hemophilia
• Hemophilia A  Factor VIII deficiencies
(85%)
• Hemophilia B  Factor IX deficiencies (
10-15%)
• Most common & serious congenital
coagulation factor deficiencies
• Prevalence 1:5000 males
• No racial predilection
• Clinical finding  same

9. Hemophilia
• Classification
– Severe deficiency  <1% factor activity
• Spontaneous bleeding
– Moderate deficiency  1-5% factor activity
• Mild trauma to induce bleeding
– Mild deficiency  >5% factor activity
• May be asymptomatic, took years to diagnose

10. Hemophilia
• Clot formation is delayed & fragile
• When bleeding occurs in the closed space 
tamponade
• Open wound  profuse bleeding
• Bleeding symptoms may be present in utero
• Neonates  intracranial bleeding
• Easy bruising, IM hematomas, hemarthroses
• Bleeding from minor trauma of the mouth 
persist for days

12. Hemophilia
• Iliposoas bleeding  life threatening
– Inability to extend the hip
– Confirmed by UTZ or CT scan
– Aggresive therapy
• Life threathening bleeding
– CNS, Upper airways bleeding
– External bleeding
– GI bleeding

13. Hemophilia
• Prolonged PTT
• Factor assay:
– Severe def.
– Moderate def.
– Mild def.
• Inhibitor assay

15. Treatment
• Prevention of trauma
• Phychosocial
• Avoid aspirin & NSAID
• Replacement therapy
– Recombinant fact. VIII/IX
– Cryoprecipitate/ cryosupernate
• Joint bleeding:
– Ice pack
– Elevate the limb
– Immobilization of the limb
• Supportive therapy
• multidiciplinary

16. Chronic Complication
• Chronic joint destruction
• Risk of transfusions associated disease
• Development of inhibitor

17. Disseminated Intravascular
Coagulation (DIC)
• Consumptive coagulopathy
• Consumption of clotting factors, platelets &
anticoagulant protein
• Widespread intavascular deposition of
fibrin  tissue ischemic & necrosis,
generalized hemorrhagic state, hemolytic
anemia

18. DIC
• Trigger factors:
– Hypoxia
– Acidosis
– Tissue becrosis
– Shock
– Endothelial damage
– Septic shock
– Incompatible blood transfusion
– Snake bite

19. DIC
• Manifestations:
– Bleeding from surgical incision/venipuncture
(pungsi vena)petechiae, ecchymoses
– Organ damage
– Anemia microangiopathic hemolytic anemia

20. DIC
• Labs:
– Prolonged PT, PTT & TT
– Thrombocytopenia
– Hemolytic process on blood smear
– FDP, d-dimer appear in blood

21. DIC
• Treatment:
– Treat the cause
– Restore normal homeostasis
• Correct shock, acidosis, hypoxia
– Blood component transfusions
• Platelet concentrate, cryoprecipitate, FFP
– Heparin infusions
• For acute promyelocytic leukemia
• Not indicated for septic shock, snack bite, massive
head injury, incompatible transfusions

22. Platelet

23. The characteristic of platelets
• Size: 1-4 µm (younger platelets are larger)
• Mean platelet volume (MPV) : 8,9 ± 1.5 µm3
• Number : 150.000 – 400.000 / mm
• Distribution : 1/3 in the spleen, 2/3 in blood
stream
• Life span : 7-10 days
Bleeding may occur because :
• Reduce in number (thrombsytopenia)
• Defective in function

24. Thrombocytopeni based on
pletelet sized
Macrothrombocytes (MPV ↑) Microthrombocytes (MPV ↓)
• ITP or condition with increased • Wiskott –Aldrich syndrome
platelet turnover (eg. DIC)
• TAR syndrome
• Bernard-Soulier Syndrome
• Some storage pool diseases
• May Heggin anomaly and other
MYH-9-Related disease • Iron def. Anemia
• Swiss Cheese platelet syndrome Normal size (MPV normal)
• Disease with hypocellular marrow
• Montreal platelet syndrome or infiltrated with malignant
disease
• Gray platelet syndorme
• Various mucopolysaccharisoses

25. Clasification of Trombocytopenia
Incrase platelet Disorder of platelet
destruction distribution or
pooling
Thrombocyto
penia
Decrased platelet Pseudothrombocyto
production penia

26. Clasification of Trombocytopenia
Hypersplenism
(Portal hypertension,
Gaucher disease,cyanitic
Disorder of congenital, heart disease,
platelets neoplasm, infection)
distribution or
pooling
Hypothermia

27. Clasification of Drugs:
Chlorothiazide, ethanol
Trombocytopenia
Constitusional:
Hyperplasia or Rubella,…
suppresion of
megakaryocyte Ineffective Thrombopoeisis:
……..
Disorder of control
Decrase platelet mechanism:
production Trombopoetin deficiency
Acquired myelositic
disorder:
Drugs
Marrow Benign:
Infiltrative Osteoporosis
Process
Malignancy

28. Clasification of Trombocytopenia
Platelet inactivation
during bloof
collection
Pseudo-
thrombocytopenia Undercounting of
megathrombocytes
In vitro agglutination
of platelets
to EDTA

29. Clasification of Idiopathic (ITP)
Trombocytopenia
Secondary:
Immune Infection, drugs,
Thrombocytopenia SLE, etc
Neonatal:
Autoimune, Erito-
Increase platelet blastosis fetalis
destruction
Platelet
consumption
Non-immune
Thrombocytopenia Platelet
destruction:
drugs

30. Immune Thrombocytopenia
The most frequent cause of
thrombocytopenia is immune mediated
platelet destruction due to:
1. autoantibodies
2. drug-dependent antibodies
3. alloantibodies

31. Immune (Idiopathic)
Thrombocytopenic Pupura
A syndrome characterized by
thrombocytopenia :
1. Shortened platelet survival
2. Presence of antiplatelet antibody in
the plasma
3. Increase megakaryocytes in the
bone marrow

32. ITP
• The syndrome can be:
– Acute
• Platelet count return to normal within 6 month &
relaps does not occur
• Most in children
– Chronic
• Platelet count remain low beyond 6 month
• More common in adult
– Recurrent
• Platelet count decrease after having returned to
normal

33. Predisposing Factor
• 50-80% : infection (usually viral) prior to
thrombocytopenia
• About 20% : a specific infection can be
identified, eg. Rubella, measel, varicella,
pertussis, mumps, infectious mononucleosis,
CMV, parvovirus or bacterial
• Measel or smallpox vaccination

34. Clinical Manifestation
• Skin: Ecchymosess/purpira usually on the
anterior surface of lower extremities and body
prominences (ribs, scapula, shoulders, legs,
pubic)
• Mucous membranes: subconjunctival, buccal
mucosa, soft palate
• Menorrhagia
• Hematemesis & melena  infrequent
• Others: nose, gum, G.I, Kidnets (usually at the
onset of the disease

35. Clinical manifestation
• Intracranial bleeding:
– Usually preceded by:
• Headache, dizziness, acute bleeding at other
place
• Retinal hemorrage
• Middle ear  hearing impairment
• Deep muscle hematoma and hemarthrosis
• Rare, seen after i.m injection or significant trauma
• Characteristic of plasma coagulation

36. Laboratory Findings
• Low platelet count
– Always <150.000 /mm3
– Often <20.000 /mm3 in patients with severe generalized
hemorrhagic manifestations
– MPV ( N : 8.9 + 1.5 um3)
• Blood smear
– Thormbocytopenia must be confirmed by peripheral
blood examination to exclude the diagnosis
pseudothrombocytopenia, the presence of
megathrombocytes and other hematologic
manifestation
– Blood semar normal apart from thrombicytopenia
• Anemia present in proportion to amount of blood loss

37. Bone Marrow Aspiration
• Indication
– Atypical presentation
– Poor respone to therapy
– To exclude other hematologic disorder sucg as
leukemia
• Characteristic
– ↑ ,megakaryocytes, immature and asence of budding
– Nomlar erythroid and myeloid cells
– Occasionally eosinophilia
– Erythroid hyperplasia if significant blood loss

38. Intracranial Hemorrhage
• Incidence : 0,1 – 0,5 %
• Age: 13 month – 16 years
• Platelet count :
– < 10.000 /mm3 in 73% cases
– 10-20.000 /mm3 in 25% of cases
– >20.000 /mm3 in 2% of cases
• Interval between diagnosis of ITP and ICH:
– <4 wekks in 51% of cases
– 4 weeks – 9 years in 49%of cases (mean 27 weeks)

39. Intracranial Hemorrhage
• Risk Factors in 45 % cases of ICH
include:
– Head injury (29%)
– Aspirin treatment (5%)
– AV malformation (17%)
– Mucocutaneous hemorrhage (49%)
• Site of ICH:
– Intra cerebral (77%)
– Subdural hematoma (23%)
• 50 % had prior tretament with steroid
and / or IVIG
• 54% survival, most without
permanent damage

40. Supportive Treatment
• No treatment is required when platelet count
>20.000 /mm3 , asymptomatic or has mild
bruising but no evidence of mucous membrane
bleeding
• Competitive sport should be avoided
• Depoprovera or any other long-acting
progesteron in suspending menstruation for
several month
• Aspirin, Nonsteroidal antiinflammatory agents
and any other drug the interfere with platelet
function should not be given

41. Farmacological Treatment
• Treatment choice : Steroid, IVIG, and anti–D
• Indication
– Platelet count <20.000 /mm3 and significant
mucous membrane bleeding
– Platelet <10.000 /mm3 and minor purpura

42. Steroid Therapy
• Mechanisms:
– Inhibits phagocytosis of antibody coated platelet in
the spleen  prolongs platelet survival
– Improves capillary resistance and thereby improve
platelet economy
• Dose and Duration:
– Dose : 2mg/kg/day (max. 60/mg/day) in divided dose.
Tap off in 5-7 day interval and stopped at the end of
21-28 days, regardless of the response
– In severe cases methylprednisolone 30mg/kg/day
(max 1 g/day) for 3 days
• Prolonged case of steroid in undesirable:
– Worsen the thrombocytopenia and depress platelet
[rpduction
– Side effect : weight gain, caushingoid facies, fluid
retention, acne, hyperglycemia, hypertension, mood
swings, pseudotumor cerebri, cataracts, growth
retradation , avascular necrosis

43. IVIG
• Mechanism of action
– Reticuloendothelial Fc-receptor blockade
– Activation of inhibitor pathways
– Decrease autoantibody synthesis
• Indication
– Neonatal Symptomatic Immune Thrombocytopenia 
Infant less than 2 y.o are generally more refractory to
steroid treatment
– Alternative therapy to corticosteroid therapy
• Much more expensive and has significant side
effects

44. Anti –D Therapy
• Plasma derived gamma immune globulin of anti
–Rh antigen
• Mechanism action :
– Blockade of Fc receptor of reticuloendothelial cell
• Platelet is increase after 48 hours, therefore the
therapy is not appropriate for emergency
treatment
• Patients who have not undergone splenectomy
and Rh positive are more likely to respond to IV
Anti-D

45. Splenectomy
• Indication
– Severe acute ITP with acute life-threatening bleeding
and not responsive to medical treatment
– Chronic ITP with bleeding symptom or platelet count
persistently below 30.000 /mm3 an not responsive to
medical treatment for several years
– In very active patient subject to frequent trauma, early
splenectomy may be indicated
• Because the hazard of overwhelming
postsplenectomy infection (OPSI) the procedure
should be performed after clear indication

46. Splenectomy
• Indication for splenectomy are rare because of
judicious use if steroid and IVIG
• It is rarely necessary to perform splenectomy
before 2 years adter diagnosis
• Laparoscopic splenectomy is preferable to open
splenectomy
• Up to 70% have complete and long-lasting
recovery
• 40% wuth persistent thrombocytopenia after
splenectomy have acsseory spleen

47. Treatment Algorithm
Yang skema itu.. Gak keliatan di foto.. Maaf
ya kawan..

48. Live Threatening Hemorrahage
• Platelet transfusion
• Methylprednisolone 500 mg/m2 IV per day
for 3 days
• IVIG 2 /kg for 12 hours infusion
• Emergency splenecomy

49. Prognosis
• Excellent, 50 % recover within 1 month % 70-80% within
6 month
• Spontaneous remission after 1 year in uncommon, but
may occur even after several years
• When demonstration underlying cause, the prognosis is
related to the cause
• Age older than 10 years, insidious onset, female are
associated with chronic ITP
• 50-60 % chronic ITP………….. without any other therapy
and without splenectomy