1. H .S.P. &I. T. P Dr:Fatma Ali AlTamimi .
Pediatric rheumatology consultant.

2. Objectives
1- Outline an appropriate evaluation for apatient with thrombocytopenia. 2-Explain the pathogenesis, clinical features and treatment of ITP and H S P. 3-Identify the indications for platelet transfusion for I TP.

3. Introduction
Estimated overall annual incidence of new cases of vasculitis is 53.3 per 100,000 children under 17 years of age The most common vasculitides are Henoch-Schönlein purpura (HSP) , with estimated annual incidence of 20 per 100,000 in children less than 17 years of age Reported geographical variations in vasculitis may reflect an environmental influence A number of factors have been reported to be associated with the development of vasculitis, including infections, drugs, allergy and vaccination .

4. CONT…..
Purpura may result from disruption in vascular integrity [trauma ,infection,vasculitis ,collagen disorders] or due to abnormalities in primary or secondary hemostasis[thrombocytopenia , abnormal platelet function ,or clotting factor defeciency]. Asystematic approach to the evaluation of achild with purpura helps guide the work up and identify the appropriate treatment. [algorithm].

6. HENOCH SCHONLIEN PURPURA

7. Definition:
Vasculitides are disorders defined by the presence of inflammation in a blood vessel wall (vasculitis). The inflammation may occur as a primary process or secondary to an underlying disease.

8. Clinical symptoms depending upon
the types and location of the vessels involved.
the extent of inflammation.
and subsequent vessel wall damage with associated hemodynamic changes.

9. Disruption of the vessel wall with hemorrhage into tissue
Vasculitis = Inflammation of the Blood Vessel
Blood vessel damage
Thickening of vessel wall Attenuation of vessel wall
Luminal narrowing
or occlusion
Vessel wall thinning
Aneurysm formation or
Disruption of the vessel wall
with hemorrhage into tissue
Tissue or organ ischemia

10. Vasculitis: Histological and Clinical Correlation
Courtesy of Carol A. Langford
Copyright © The McGraw-Hill Companies, Inc. All rights reserved.
Disruption of the vessel wall with
red blood cell extravasation into tissue
Palpable Purpura

11. Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis
Small vessel vasculitis
Wegener’s granulomatosis
Churg-Strauss syndrome
Microscopic polyangiitis
Henoch-Schonlein purpura
Essential cryoglobulinemic vasculitis
Cutaneous leukocytoclastic angiitis
Medium-sized vessel vasculitis
Polyarteritis nodosa
Kawasaki disease
Large-vessel vasculitis
Giant cell (temporal) arteritis
Takayasu arteritis 11

13. Henoch-Schonlein Purpura
Most common systemic vasculitis in children affecting between 10 and 20 per hundred thousand children every year..
Immune mediated
Deposition of IgA immune complexes.
Occurs more often in fall, winter, and spring.
Rare in the summer.
About 50% of cases are preceded by URI’s.
Streptococcus is often implicated.
Vaccines, insect bites, viruses have also been reported as triggers.

14. PATHOGENESIS
Immunological; IgA vasculitis associated with [IgA] deposition ,C3, and fibrin depsition. Immunologic, genetic, and environmental factors play arole. The characterstic finding of HSP is leukocytoclastic vasculitis accompanied by IgA immune complexes within affected organ.Tpredominant cell typeswithin the inflammatory infiltrate are neutrophils and monocytes.

17. Clinical Presentation
* 50% of cases present before the age of five. Classic tetrad
Palpable purpura (100%)
In absence of thrombocytopenia or coagulopathy
Arthritis or arthralgia (75%)
Abdominal pain (50%)
Renal disease (21-50%)

21. Gastrointestinal symptoms
Occur in 50% of HSP patients. Range from mild ;nausea ,vomiting, abdominal pain , transient paralytic ileus to more significant findings;gastrointestinal hemorrage,bowel ischemia and necrosis, intussusception,and bowel perforation. Intussusception is the most common gastrointestinal complication %;small bowel can be detected by ultrasonography of abdomen.

22. Renal disease 20- 54% of HSP patients.
The most common presentation is hematuria with or without red cell casts and no or mild proteinuria.
The finding in renal biopsy are identical to IgAnephropathy.
Urine analysis should be done in all patients.

23. The A C R CRITERIA OF H S P
Palpable purpura Age at onset < 20 years Acute abdominal pain Biopsy showing granulocytes in the walls of small arterioles and or venules.

24. Laboratory studies - Complete blood count
. Nonspecific
- Complete blood count
- Erythrocyte sedimentation rate (ESR)
- C-reactive protein
. Organ involvement
- Creatinine
- Urinalysis – Liver enzymes
- Electrocardiogram - Echocardiogram
- Creatinine phosphokinase
- Chest roentgenogram
- Sinus roentgenograms
- Electromyography/nerve conduction studies
Angiography
Biopsy

25. Treatment:
Often a self-limited disease. simple medicines like paracetamol and or ibuprofen are helpful for relief from fever, joint and abdominal pain. . Those with severe abdominal pain, once the clinician is happy that there is not a severe complication called intussusception, may benefit from a short course of prednisolone.

26. Supportive care;
Adequate hydration Rest Pain killer.

27. HOspitalization
Inability to maintain adequate hydration . Sever abdominal pain. Significant G I bleeding Changes in mental status. Sever joint involvement with limitation of movement. Renal insufficiency , hypertention ,nephrotic syndrome.

28. Pitfalls in the diagnosis and management of HSP
The trick is identifying which children have severe renal involvement, so that more aggressive treatment can be given earlier , younger children tend to have a better outcome than older children and adults. .
Another common pitfall is to diagnose "atypical" HSP when in fact much more aggressive treatment is required Clinicians should be alert to the possibility of more aggressive forms of vasculitis in children with unusually severe presentation of what initially looks like HSP.

29. IDIOPATHIC THROMBOCYTOPENIA
I T P
IDIOPATHIC THROMBOCYTOPENIA

30. THROMBOCYTOPENIA Decreased production Increased destruction
Sequestration
Pseudothrombocytopenia

31. PSEUDOTHROMBOCYTOPENIA
Artifactually low platelet count due to in vitro clumping of platelets
Usually caused by antibodies that bind platelets only in presence of chelating agent (EDTA)
Seen in healthy individuals and in a variety of disease states
Diagnosis:
Marked fluctuations in platelet count without apparent cause
Thrombocytopenia disproprotionate to symptoms
Clumped platelets on blood smear
"Platelet satellitism" - platelets stuck to WBC
Abnormal platelet/leukocyte histograms
Platelet count varies with different anticoagulants

32. DECREASED PLATELET PRODUCTION
Marrow failure (pancytopenia)
aplastic anemia, chemotherapy, toxins
B-12, folate or (rarely) iron deficiency
Viral infection
Drugs that can selectively reduce platelet production
Alcohol
Estrogens
Thiazides
Chlorpropamide
Interferon
Amegakaryocytic thrombocytopenia
myelodysplasia (pre-leukemia)
immune? (related to aplastic anemia)
Cyclic thrombocytopenia (rare)
Inherited thrombocytopenia

33. INCREASED PLATELET CONSUMPTION
Immune destruction
Intravascular coagulation (DIC or localized)
Microangiopathy
Damage by bacterial enzymes, etc

34. IMMUNE PLATELET DESTRUCTION
Autoimmune (ITP)
Childhood
Adult
Drug-induced
Heparin
Quinine, others
Immune complex (infection, etc)
Alloimmune
Post-transfusion purpura
Neonatal purpura

35. ITP Childhood form (most < 10 yrs old)
May follow viral infection, vaccination
Peak incidence in fall & winter
~50% receive some treatment
≥75% in remission within 6 mo
Adult form
No prodrome
Chronic, recurrences common
Spontaneous remission rate about 5%

37. DEFINITION; Isolated immune mediated thrombocytopenia.
Peripheral blood platelet count< 100,000/microl.
It is an aquired benign disorder.
Primary I .T .P.

38. pathogenesis
Autoantibodies usually Ig G directed against platelet membrane antigens; glycoprotein I Ib/IIIa complex . The antibody coated platelets have shortened half life because of accelerated clearance by tissue macrophages in the spleen. The same antibodies may inhibit platelet production. Tcell mediated cytotoxicity.

39. EPEDMIOLOGY
Annual incidence between 1 and 6.4 cases per 100,000 children.
Peak incidence between 2 and 5 years.
Peak in the spring and early summer.

40. CLINICAL MANIFESTATIONS
Sudden appearance of petechial rash, bruising and or bleeding in otherwise healthy child.
HISTORY;
60/. History of prior infection within the past month.
6WKs post MMR vaccine 2.6per 100,000 doses.
If other symptoms present another cause of thrombocytopenia should be considered.

41. PHYSICAL FINDING; Cutaneous bleeding[ dry purpura ]; petechiae , purpura, and ecchymoses ;60%. Mucosal bleeding[ wet purpura]; 40%. Serious hemorrhage;3% Intracranial hemorrhage; % ;25% mortality.

42. LABORATORY FINDINGS: PLT count< 100,000/microl.
Peripheral blood smear to rule out morphological abnormalities in the RBC s or WBCs.
PLTs size are normal.

43. DISEASE COURSE
Newly diagnosed I T P ; 3 M Persistent I T P ;3- 12M Chronic I T P; > 12 M

44. DIAGNOSIS
It is adiagnosis of exclusion characterized by isolated thrombocytopenia. INITIAL EVALUATION; CBC , Retic ,Direct coombs test, Immunoglobulins level.

45. DIAGNOSTIC CRITERIA;
P L T COUNT <100,000 microl. Otherwise normal CBC Retics Normal peripheral blood smear. No clinically apparent associated conditions that may cause thrombocytopenia.

46. MANAGEMENT;
Supportive care; Restrict physical activities with risk of trauma. Avoid medication with antiplatelet activity; Aspirin ,ibuprofen, N S AI D Ss, anticoagulants. Monitor the disease course until full recovery is assured.

47. Indication for pharmacological intervention
The guidelines of the American Society of Heamatology[A S H];
No pharmacologic intervention for children with no bleeding regardless of platelet count.
Pharmacologic intervention for any child with sever bleeding ;.I V IG; 1 g/ kg, Glucocorticoids, Anti –D immunoglobulin.

48. ITP IN CHILDREN Management Platelets > 20-30 K, no bleeding: no Rx
30-70% recover within 3 weeks
Platelets < 10K, or < 20K with significant bleeding: IVIg or corticosteroids
prednisone, 1-2 mg/kg/day
single dose IVIg 0.8-1g/kg as effective as repeated dosing
Splenectomy reserved for chronic ITP (> 12 mo) or refractory disease with life-threatening bleeding
pre-immunize with pneumococcal, H. influenzae and meningococcal vaccines

49. Intravenous immunoglobulin therapy
ITP
Intravenous immunoglobulin therapy
Possible mechanisms of action:
Slowed platelet consumption by Fc receptor blockade
Accelerated autoantibody catabolism
Reduced autoantibody production
Dose: 0.4 g/kg/d x 5 days (alternative: 1 g/kg/d x 2 days)
About 75% response rate, usually within a few days to a week
Over 75% of responders return to pre-treatment levels within a month
Advantages: rapid acting, low toxicity
Disadvantages: high cost, short duration of benefit, high relapse rate
Indications: Lifethreatening bleeding; pre-operative correction of platelet count, steroids contraindicated or ineffective

51. Life threatening bleeding;
Rare in children. I C H in 0.5% Associated with head trauma and P L T count<10,000. Management by; P L T transfusion and IVIG and methylprednisolone together.