This document discusses bleeding disorders in children, focusing on immune thrombocytopenic purpura (ITP). ITP is characterized by thrombocytopenia caused by autoantibodies against platelets. It most commonly presents as bruising and bleeding in otherwise healthy 1-4 year olds after a viral infection. Diagnosis is based on low platelet count and the absence of other causes. Most cases resolve spontaneously within 3-6 months without treatment.

1. DR SUJIT SHRESTHA
MD PEDIATRICS,NEONATOLOGY
NMCTH
Bleeding Disorder in Children

2. HEMOSTASIS
1. VASCULAR PHASE- damaged Blood vessel,
vasoconstriction.
2. PLATELET PHASE- clump to white plug
3. COAGULATION PHASE- fibrinogen to fibrin-
fibrin plug
4. FIBRINOLYTIC PHASE- Anticlotting
Mechanism- lysis of clot and repair BV

3. HEMOSTASIS
DEPENDENT UPON:
1. Vessel Wall Integrity
2. Adequate Numbers of Platelets
3. Proper Functioning Platelets
4. Adequate Levels of Clotting Factors
5. Proper Function of Fibrinolytic Pathway

4. Coagulation cascade
Vitamin K dependant factors
XIIa
IIa
Intrinsic system (surface contact)
XII
XI XIa
Tissue factor
IX IXa VIIa VII
VIII VIIIa
Extrinsic system (tissue damage)
X
V Va
II
Fibrinogen Fibrin
(Thrombin)IIa
Xa

5. LABORATORY EVALUATION
1. Platelet Count
2. Bleeding Time (BT)
3. Prothrombin Time (PT)
4. Partial Thromboplastin Time (pTT)
5. Thrombin Time (TT)

6. Laboratory Evaluation of the Coagulation
Pathways
Partial thromboplastin time(PTT) Prothrombin time(PT)
Intrinsic pathway Extrinsic pathway
Common pathwayThrombin time
Fibrin clot

7. Laboratory Evaluation of the Coagulation
Pathways
 PT - prolonged in extrinsic and common pathway
 APTT- prolonged in intrinsic and common
pathway
 PT &APTT – prolonged in common pathway ,liver
dysfunction ,DIC
 DIC – thrombin time is also prolonged
 Factor XIII deficiency – platelet ,APTT,PT,BT-
Normal

8. Diagnostic Approach
Increased BT
a) Platelet decreased – ITP
b) Platelet normal – anaphylactoid purpura
Increased CT
a) only PT prolonged – Factor VII deficiency
b) only APTT prolonged – factor – VIII,IX,XI,XII and
von willebrand’s disease

9. Diagnostic Approach
Both PT & APTT prolonged –
1. Vitamin k deficiency
2. Severe liver disease
3. Cong deficiency of factor V, X.
4. Fibrinogen deficiency
5. DIC

10. PLATELET COUNT
 NORMAL 100,000 - 400,000 CELLS/MM3
< 100,000 Thrombocytopenia
50,000 - 100,000 Mild Thrombocytopenia
< 50,000 Severe Thrombocytopenia

11. BLEEDING TIME
PROVIDES ASSESSMENT OF PLATELET COUNT
AND FUNCTION
NORMAL VALUE
2-8 MINUTES

12. PROTHROMBIN TIME
Measures Effectiveness of the Extrinsic
Pathway
NORMAL VALUE
10-15 SECS
International Normalized Ratio- INR

13. PARTIAL THROMBOPLASTIN TIME
Measures Effectiveness of the Intrinsic
Pathway
NORMAL VALUE
25-40 SECS

14. THROMBIN TIME
Time for Thrombin To Convert
Fibrinogen Fibrin
A Measure of Fibrinolytic Pathway
NORMAL VALUE
9-13 SECS

15. Causes Bleeding Disorders
Vessel defects
Platelet disorders
Factor deficiencies
Other disorders

16. VESSEL DEFECTS
Vascular purpuras
 Infection – meningococcal meningitis, hge measles,
typhoid
 Drugs – aspirin ,indomethacin, phenytoin , quinine
 Anaphylactoid purpura – Henoch-schonlein
Purpura
 Metabolic – uremia, scurvy

17. PLATELET DISORDERS
Thrombocytopenia

18. THROMBOCYTOPENIA
CONGENITAL - TAR syndrome
- Fanconi’s anemia
- Wiskott Aldrich syndrome
ACQUIRED -Aplastic anemia
- BM replacement/depression

19. DECREASED PRODUCTION:-
A) IMMUNE THROMBOCYTOPENIC PURPURA(ITP)
B) INFECTIONS - EBV
- HIV
- HBV
- RUBELLA
- PARVO-B19
- CMV
- TB,TYPHOID

20. C .Drug induced - NSAID, ATT, AED, QUININE,
SULFA,PENICILLIN, FRUSEMIDE, HEPARIN,
D . Autoimmune Disorders -SLE, hyperthyroidism
E . Malignancy - ALL, AML, Lymphoma,
Neuroblastoma
F. Aplastic anemia

21. Others
- DIC
- Microangiopathic Hemolytic Anemia- HUS
-Liver disease
- Neonatal thrombocytopenia – toxoplasmosis,
CMV, herpes simplex, ITP

22. Qualitative disorders
 Inherited disorders
 Glanzmann syndrome
 Bernard soulier syndrome
 Gray platelet syndrome
 Wiscott Aldrich syndrome
 Acquired disorders
 Medications- aspirin
 Chronic renal failure

23. DEFINITION : IS CHARACTERISED BY
-THROMBOCYTOPENIA < 100.000/CM
-SHORTENED PLT. SURVIVAL
-PRESENCE OF ANTIPLATELET ANTOBODY IN THE
PLASMA.
-INCREASED MEGAKARYOCYTES IN BM
IDIOPATHIC / IMMUNE
THROMBOCYTOPENIC
PURPURA

24. BACKGROUND
 Most common causes of symptomatic thrombocytopenia
in children.
 Incidence - 1 cases per 20,000 children
 Before a diagnosis of ITP – R/O other common causes of
thrombocytopenia (concurrent infection , autoimmune
disorders , malignancy , bone marrow failure)
A recent viral illness is identified in 50-65% cases.

25. CLASSIFICATION
1.Acute ITP (children)- Platelets returns to normal
value before 6 mths.
2.Chronic ITP (adults) - Platelets remains low after
6mth. > 12 MONTHS- As per Nelson
3.RECURRENT:-PLT count decreases after
becoming normal

26. ETIOLOGY
Usually benign transient immune-mediated
thrombocytolytic condition
Autoantibodies (usually IgG) directed against
platelet membrane antigens (especially
glycoprotein complex IIb/IIIa) are present
Thrombocytopenia results from phagocytosis of
antibody-coated platelets by the
reticuloendothelial system

27. ROLE OF SPLEEN
1.Auto-antibody production
2.Platelet destruction
3.Platelet storage

29. CLINICAL PRESENTATION
1. 1 to 7 years- OPGhai, peak 1-4 years: Nelson
2. Patients < 1 years or > 10 years at presentation
are atypical
3. No seasonal variation
4. History of a preceding infection (1-4 wks back)
5. Post-vaccination cases also have been reported
( MMR )

30. Clinical Manifestations
Previously healthy child
Sudden onset
Bruises and dots, petechiae and purpura
Gum and mucus membrane bleeds
Splenomegaly, lymphadenopathy, bone pain, pallor
rare ( ? Leukemias)

31. CLINICAL PRESENTATION
 Previously healthy child - sudden skin and
mucous membrane bleeds - Petechiae, purpura
ecchymosed, Gingival bleeding and epistaxis ,
gastrointestinal , genitourinary
Conjunctival and retinal hemorrhages may occur
Life-threatening bleeding, (ICH), - is very rare,
occurring with an incidence of 0.1 to 1.0 %

32. According to severity
 1. No symptoms
 2. Mild symptoms- bruising , petechie, occasional
minor epistaxis, very little interefence with daily life
 3. Moderate: more severe skin and mucus lesions,
troublesome epistaxis , menorrhagia
 4. Severe: Bleeding episodes-menorrhagia, epistaxis,
melena– requiring trasfusion or hospitalization,
seriously affects quality of life.

33. Petechiae
Do not blanch with
pressure

34. CLINICAL PRESENTATION
 No other systemic symptoms - fever, anorexia,
weight loss, or bone or joint pain
 No significant enlargement of lymph nodes,
liver, or spleen is present
Insidious onset and adolesecents – Chronic ITP,
SLE

35. LABORATORY STUDIES
For the typical case of ITP :
CBC – Hb normal, wbc normal unless
bleed.
Platelet count < 20,000- common
Peripheral blood smear (often large
platelet forms are seen )
Mean Platelet Volume increased
Bleeding time prolonged
PT/ APTT normal
Platelet antibodies in 70-90 %

36. Fewer Platelets than normal.

37. LABORATORY STUDIES
For the atypical case of ITP :
Viral antibody titers (including HIV)
Coombs' test
Reticulocyte count
Studies for collagen vascular : ANA , Anti
ds-DNA, ANCA etc
Studies for rheumatoid disorders: RF

38. Platelet Auto-antibodies
Platelet
Antigens

39. LABORATORY STUDIES
 BONE MARROW EXAMINATION (BME)
In the past, BME was performed routinely in
children with suspected ITP
BME are unnecessary in the "typical" case of
childhood ITP
Bone marrow aspiration and biopsy is reserved for
- atypical presentation
BME - who initially was diagnosed as ITP but
subsequent clinical course is inconsistent with the
natural history of acute ITP

40. DIFFERENTIAL DIAGNOSIS
Aplastic anemia
Leukemia ( ALL )
Autoimmune disease (SLE)
HSP
Infection - hepatitis, HIV
Drug exposure - heparin, quinidine, sulfonamides

41. MANAGEMENT
80 to 90 % of cases recover spontaneously within a few months
(3-6 months) even without treatment
Restriction of activity and avoidance of medications with
antiplatelet activity (aspirin , ibuprofen ,NSAID)
Guidelines suggest :
 Platelet counts >20,000 no symptom to mild symptoms
– no treatment
 Platelet counts <20,000 with symptoms – treatment

42. THERAPY
Intravenous immunoglobulin (IVIG)
Anti-Rho(D) immune globulin
Steroid

43. IVIG
interferes with macrophage Fc receptor clearance
Rapid improvement in platelet numbers - 95%
patients within 48 hrs
Dose - 400 mg/kg per day for five days
- 1 gm/kg for one to two days
The higher, shorter dosage schedules appear to be
preferable

44. IVIG
The side effects include :
1. Nausea and vomiting (63 %)
2. Headache (56 %)
3. Fever (19 %)
4. Neutropenia (absolute neutrophil count <1500/microL)
30 %
Cost must be considered in the selection of
therapy for ITP

45. ANTI-D IMMUNE GLOBULIN (Anti-
Rho(D)
MoA: anti-D results in blockade of Fc receptors by
antibody coated RBCs in place of antibody coated
platelets
Dose - single dose of 50 µg/kg
80-85 % patients show rise in platelets within 48 hrs
Given to children with a Hb > 10 g/dl
One to two weeks after administration, a fall in the Hb
level of 1 to 1.5 grams - as a result of mild hemolysis of
the patient's Rho(D)-positive red cells

46. CORTICOSTEROIDS
Steroids reduce the risk of symptoms by
1. Improving vascular integrity
2. Diminishing antibody affinity for
the platelet membrane
3. Reducing antibody production
4. Reducing reticuloendothelial
system phagocytosis of antibody-
coated platelets

47. Dosage regimens
Prednisone 1-4 mg/kg per day for 2 to 3 weeks
 Pulse IV methylprednisolone for 3 to 7 days
Occasionally, a second course of treatment may be
necessary if significant hemorrhagic symptoms again
develop

48. CORTICOSTEROIDS
Chronic administration of steroids - Avoided
Alternative therapies - IVIG or Anti-D should be
considered who need prolonged or repeated
corticosteroid therapy

49. OUTCOME
80 % -90% - recovers spontaneously within three
months of presentation, with or without therapy
15 to 20 % - have moderate or major hemorrhage
0.1 to 1 % - Life-threatening bleeding(ICH) is rare
<5 % with acute ITP have recurrent acute
thrombocytopenia

50. CHRONIC ITP
Definition - persistence of thrombocytopenia
beyond six months from the time of diagnosis
More than 12 months - Nelson
20 % of patients with typical ITP will have chronic
ITP
Patients who have atypical features at
presentation are more likely to have chronic
disease

51. CHRONIC ITP ( Management )
Aim of treatment - should focus on minimizing the
risk for bleeding
Many patients will require no treatment
Even after years, a significant proportion of such
patients will improve

52. CHRONIC ITP ( Management )
CORTICOSTEROIDS
 Periodic short courses or pulses of corticosteroids
 For steroid dependent patients - alternate day dosing
may be effective in preventing bleeding while reducing
side effects

53. CHRONIC ITP ( Management )
Immunoglobulin therapy :
IVIG or anti-Rho(D)- effective in chronic
ITP who are resistant to steroids
All of these strategies offer temporary relief
of symptoms and improvement in platelet
numbers
Very costly

54. CHRONIC ITP ( Management )
Splenectomy
Effective in 60 to 90 % of children with chronic ITP
Overwhelming post-splenectomy infection
Presplenectomy immunizations and subsequent penicillin
prophylaxis are necessary for all age groups

55. CHRONIC ITP ( Management )
Splenectomy :
No universally accepted standards for the timing
of splenectomy in chronic ITP
Guidelines recommend waiting until at least 12
months after diagnosis
8)Immunosupressive agents - Cyclophoshamide

56. Newer drugs
 Rituximab- monoclonal anti-b cell antibody
Stimulate Thrombopoeisis
 Romiplastin
 Eltrombopag

57. Mostly children
Male/Female = 1:1
Acute onset
Plt. Count mostly
<20,000/mm3
Spontaneous
remission frequent
Mortality : 0.5-1.5 %
Duration – 2-6 wks
Mostly adults
Male/Female = 1:3-4
Usually gradual onset
Plt. Count 20 – 50000/mm3
Spontaneous remission rare
Chronic recurrent course
Duration - mo -yrs
Acute ITP Chronic ITP

58. Neonatal thrombocytopenia
Systemic illness
1.Cong infections – rubella, CMV, toxoplasmosis,
syphillis
2.Gram –ve sepsis

59. Neonatal thrombocytopenia
Due to transfer of maternal antibodies
directed against fetal platelets
1. Neonatal alloimmune TP-(NATP) – development
of maternal antibody against antigens present on
fetal platelets
- develops symptoms in first few days of life
- No maternal thrombocytopenia

60. Neonatal thrombocytopenia
2. Baby of ITP mother-
 Symptoms in perinatal period
 Resolves within 2-4 months
 IVIG & steroids

61. TTP
 Thrombotic Thrombocytopenic purpura
 Pentad – fever, microangiopathic hemolytic anemia,
thrombocytopenia,impaired renal function ,CNS
changes
 Usually adolescents & adults
 Treatment – plasmapheresis – 80-95% effective
 Steroids & splenectomy