This document provides information on hemophilia and idiopathic thrombocytopenic purpura (ITP). It discusses the history, pathophysiology, inheritance, classification, clinical manifestations, management, and treatment of hemophilia. It also discusses the triggers, classification, prognosis, laboratory findings, differential diagnosis, and treatment of ITP. The key points are that hemophilia is an inherited bleeding disorder caused by a lack of specific clotting factors, while ITP is an immune-mediated platelet disorder caused by autoantibodies against platelets. Management involves factor replacement or immunosuppressive therapies depending on the condition.

1. HEMOPHILIA
&
ITP
Dr M.Sanjeevappa
M.D.(Paeds)
Asst.Professor,
Dept. of Paediatrics
Govt.Medical College
Ananthapuramu.

4. HISTORY OF HEMOPHILIA
 Best known of the hereditary bleeding disorders
since 2nd century AD.
 First coined by Schonlein in 1820s.
 Originally termed “HAEMORRAPHILIA”
i.e. love for haemorrhages but over
time contracted to HEMOPHILIA.
 Hemophilia is often called the DISEASE OF KINGS.

5. PATHOPHYSIOLOGY
 Activated factor IX complexes with factor VIIIa, calcium,
and phosphatidylserine on physiologic membranes to
generate factor Xa, which subsequently participates in
formation of the prothrombinase complex.
 Thrombin is crucial for platelet aggregation, fibrin
generation, clot retraction, and activation of factor XIII.
 The propagation phase of coagulation is impaired, and
clot formation is delayed and is not robust and is often
friable.

6. DEMOGRAPHICS
 Incidence : approximately 1 in 5000 males.
 HEMOPHILIA A : 80% to 85%
 HEMOPHILIA B : 10% to 15%
 No racial predilection

7. INHERITANCE OF HEMOPHILIA

8. CLASSIFICATION
 One IU of factor VIII = amount of factor found in 1
ml of normal plasma.
 Normal F VIII activity = 50-150% (> 30%).
 Severe - < 1%
Modrate - 1% to 5%
Mild - > 5%

9. CLINICAL MANIFESTATIONS
Severity F VIII activity Clinical manifestations
Severe <1% Spontaneous hemorrhage from
early infancy
Post circumcision bleeding
Frequent spontaneous
hemarthrosis
Moderate 1-5% Hemorrhage sec to trauma or surgery
Post circumcision bleeding .
Occasional spontaneous
hemarthrosis
Mild >5% Hemorrhage sec to trauma or surgery
Rare spontaneous bleeding

10. CLINICAL MANIFESTATIONS
History of Hemorrhage :
 Post circumcision bleeding
 Epistaxis
 Oral mucosal hemorrhage, hemoptysis
 Prolonged bleeding after minor trauma/surgery
 Prolonged bleeding after tooth extraction
 Spontaneous bleeding in joint

11. MUSCULOSKELETAL BLEEDING
 The hallmark of hemophilia is deep bleeding into
joints and muscles.
 Hemarthrosis – target joint.
 Intramuscular hemorrhage.

12. LIFE-THREATENING HEMORRHAGES
 central nervous system (CNS) bleeding.
 bleeding into and around the airway.

13. LABORATORY EVALUATION
 Hb/Hct Normal / low
 PT Normal
 aPTT Prolonged
 Platelets Normal
 B.T Normal
 C.T Prolonged
 Factor VIII levels Decreased
Inhibitor levels :
 Low titer 0-10 Bethesda U
 High titer > 10 Bethesda U

14. IMAGING STUDIES FOR ACUTE BLEEDS
 Ultrasonography
 MRI
 CT Scan

15. MANAGEMENT
 Prevention of trauma
 Avoid high-impact contact sports and other
activities with a significant risk of trauma
 Avoid Aspirin/NSAIDs
 No I.M injections.
 Short nails
 Immunization (given S/C)
 Factor VIII replacement
 Fresh blood, Cryo-PPT, FFPs (if needed)

16. MANAGEMENT
 FFPs.
 Cryoprecipitates.
 1ml FFP = 0.7 unit factor VIII.
 FFP: 10-20 ml / kg will increase factor level 20 -
30%
 1 bag Cryoprecipitates = 75 unit factor VIII

17. MANAGEMENT
REPLACEMENT THERAPY : HEMOPHILIA - A
 ‘‘Factor VIII” replacement
 1unit factor VIII → raises 2 % activity of factor level.
 Factor VIII concentrates 1 vial=250 units
 Dose : desired factor level% x Wt(kg) x 0.5
-For life threatening bleeding 80-100% factor level
-For mild-moderate bleeding 40 % factor level

18. MANAGEMENT
REPLACEMENT THERAPY : HEMOPHILIA - B
 ‘‘Factor IX” replacement
 1unit factor IX → raises 1% activity of factor level
 Dose : desired factor level% x Wt(kg) x 1.2
-For life threatening bleeding 80-100% factor level
-For mild-moderate bleeding 40 % factor level

20. MANAGEMENT
DESMOPRESSIN : synthetic vasopressin analogue
 The dose of intranasal desmopressin is 150 μg (1 puff) for
persons weighing less than 50 kg and 300 μg (1 puff in each
nostril) for persons weighing more than 50 kg.
ANTIFIBRINOLYTIC THERAPY:
Aminocaproic acid
 The oral dose of aminocaproic acid is 100 to 200 mg/kg
initially(maximum dose, 10 g), followed by 50 to 100 mg/kg
per dose every 6 hours (maximum dose, 5 g).
Tranexamic acid :
 The dose of tranexamic acid is 25 mg/kg every 6 to 8 hours.

21. IDIOPATHIC (AUTOIMMUNE)
THROMBOCYTOPENIC PURPURA(ITP)

22. ITP
 The most common cause of acute onset of thrombocytopenia
in an otherwise well child.
 Estimated about 1 in 20,000 children.
 A recent history of viral illness is described in 50-65% of
cases of childhood ITP.
 The peak age is 1-4 yr.
 ITP seems to occur more often in late winter and spring

23. PATHOPHYSIOLOGY
 An autoantibody directed against the platelet surface
develops with resultant sudden onset of thrombocytopenia.
 After binding of the antibody to the platelet surface,
circulating antibody-coated platelets are recognized by the
Fc receptor on splenic macrophages, ingested, and
destroyed.

24. TRIGGERING FACTORS
 Most common viruses have been described in
association with ITP, including Epstein-Barr virus.
 Helicobacter pylori infection.
 rarely following the MMR vaccine.

25. CLINICAL MANIFESTATIONS
 The classic presentation of ITP is a previously
healthy 1-4 yr old child who has sudden onset of
generalized petechiae and purpura with profound
thrombocytopenia (platelet count <10 × 109/L).
 Bleeding from the gums and mucous membranes
may be seen.
 Findings on physical examination are normal,
other than the finding of petechiae and purpura

27. CLASSIFICATION OF ITP
 Depending on the basis of symptoms and signs, but
not platelet count.
 Class 1: No symptomes.
 Class 2: Mild symptoms:
–Bruising and petechiae
–Occasional minor epistaxis
–Very little interference with daily living.

28. CLASSIFICATION OF ITP
 Class 3: Moderate:
– More severe skin and mucosal lesions
– More troublesome epistaxis and menorrhagia.
 Class 4: Severe:
– Bleeding episodes—menorrhagia, epistaxis,
melena — requiring transfusion or
hospitalization
-Symptoms interfering seriously with the quality
of life

29. PROGNOSIS
 Severe bleeding is rare (<3% of cases).
 In 70-80% of children who present with acute
ITP, spontaneous resolution occurs within 6months.
 Fewer than 1% of patients develop an intracranial
hemorrhage.
 20% of children who present with acute ITP go on to
have chronic ITP

30. LABORATORY FINDINGS
 Severe thrombocytopenia(plateletcount<20,000/cmm).
 platelet size is normal or increased.
 Hb ,TC ,DC should be normal.
 Bone marrow examination shows normal granulocytic
and erythrocytic series, with characteristically normal
or increased numbers of megakaryocytes.
 A direct antiglobulin test (Coombs) should be done
1.to rule out Evans syndrome (autoimmune hemolytic
anemia and thrombocytopenia)
2. Before instituting therapy with IV anti-D.

31. DIFFERENTIAL DIAGNOSIS
 Autoimmune thrombocytopenia may be an initial
manifestation of :
1. SLE
2. HIV infection
3. Common variable immunodeficiency
4. Lymphoma(rarely)

32. TREATMENT
 Platelet transfusion in ITP is contraindicated unless
life-threatening bleeding is present.
 No therapy other than education and counseling of
the family and patient for patients with minimal, mild,
and moderate symptoms.
 Intravenous immunoglobulin (IVIG):
 IVIG at a dose of 0.8- 1.0 g/kg/day for 1-2 days
induces a rapid rise in platelet count(usually
>20,000/cmm) in 95% of patients within 48 hr.
 IVIG induce a response by downregulating Fc-
mediated phagocytosis of antibody-coated platelets.

33. TREATMENT
 Intravenous anti-D therapy:
- For Rh positive patients.
- IV anti-D at a dose of 50-75 μg/kg causes a rise in
platelet count to >20,000/cmm in 80-90% of patients
within48-72 hr.
 Prednisone :
- Doses of prednisone of 1-4 mg/kg/24 hr and
continued for 2 - 3 wk or until a rise in platelet count
to >20,000/cmm has been achieved.

34. TREATMENT
Splenectomy in ITP should be reserved for 1 of the
following circumstances.
1. The older child (≥4 yr) with severe ITP that has
lasted >1 yr (chronic ITP)
2. Life-threatening hemorrhage (ICH) complicates acute ITP
3. Platelet count cannot be corrected rapidly with
transfusion of platelets and administration of IVIG
and corticosteroids

35. THANK YOU