Extern conference

1. Extern conference 5 July 2007

3. History • An 11-year-old boy without known underlying disease • CC : Continuous bleeding at traumatic wound 9 days

4. Present history An 11-year-old boy was in his usual state of good health. 10 days PTA, he had a bicycle accident. He suffered from abrasions at his right elbow without bleeding. Film Rt. Elbow suggested a right supracondylar fracture of humerus. The fracture was fixed by using slab and arm sling. He got ibuprofen tid for relieving pain (10 days).

5. Present history 9 days PTA, he has had a continuous bleeding from his traumatic wound so the wound was dressed once daily. 3 days PTA, he was referred to provincial hospital for proper management. CBC : Hb 8.9 g/dl, Hct 28%, WBC11400/ul, (N73% L17% E14%)Plt 72,000/ul. The initial diagnosis was ITP Thus, he was refered to Siriraj hospital for further diagnosis and treatment.

6. History • PMH: No history of abnormal bleeding. No previous hospitalization, no prior surgery. • FH: 2nd child. No family history of bleeding disorder. No family history of hereditary disease. • No anticoagulant drug use.

7. Physical examination • V/S : T 36.8ºc, RR 40/min, PR 96/min, regular, BP 100/56 mmHg • BW 40.8 kg (P75),Height 151.5 cm (P90) • GA : A 11-year-old Thai boy. good consciousness, mildly pale, no jaundice, • Skin : no petechiae, purpura or ecchymosis

8. Physical examination • HEENT : pharynx and tonsils not injected, TM intact both ears, no mucosal bleeding. • RS : normal breath sounds, no adventitious sound • CVS : normal S1&S2 , no murmur • Abdomen : soft, no distension, active bowel sounds, no mass, liver& spleen not palpable, bimanual palpation negative

9. Physical examination • NS : muscle power grade V all extremites, normotonia, no sensory deficit DTR 2+ all, no stiff neck • Extremities: Rt arm: abrasion at medial side of right elbow, size 1x2 cm, active bleeding, swelling from elbow to fingers

10. Right arm

11. No purpura

12. No petechiae

13. Problem list • Moderate bleeding symptom at abrasion site at right elbow 9 days • Supracondylar fracture of right humerus from bicycle accident S/P slab 10 days

14. Bleeding disorder

15. Bleeding Patient • Clinical Evaluation • History taking • Physical examination • Clinical Evaluation • History taking • Physical examination • Laboratory Investigation • Diagnosis and treatment

16. Bleeding disorder Local vs. systemic defect Location: single vs. multiple sites Severity: Spontaneous? Appropriate to trauma? Hereditary vs. acquired disorder Onset Family history Underlying disease Medication Primary vs. secondary hemostatic disoder

17. Primary Hemostasis vessel • Platelet • Adequate number • Normal function • Blood vessel • von Willebrand factor platelet platelet

18. Secondary Hemostasis • Initiation • Propagation • Fibrin clot formation

19. Secondary Hemostasis Primary Hemostasis • Onset • Sites • Skin • Mucosal • Others • Immediate • Superficial • Petechiae, superficial ecchymosis • Common • Rare • Delayed • Deep • Deep ecchymosis, hematoma • Rare • Retroperitoneal Hematoma, hemarthrosis

20. Primary hemostatic disorder

21. Secondary Hemostatic defect

22. In this patient Local vs. systemic defect Location: single vs. multiple sites Severity: Spontaneous? Inppropriate to trauma Hereditary vs. acquired disorder Onset: 11 years old Family history: none Underlying disease: none Medication: Ibuprofen for 1 day Primary vs. secondary hemostatic disoder

23. Secondary Hemostasis Primary Hemostasis • Onset • Sites • Skin • Mucosal • Others • Immediate • Superficial • Petechiae, superficial ecchymosis • Common • Rare • Delayed • Deep • Deep ecchymosis, hematoma • Rare • Retroperitoneal Hematoma, hemarthrosis

24. Bleeding Patient • Clinical Evaluation • History taking • Physical examination • Laboratory Investigation • Diagnosis and treatment

25. Investigation • CBC at Siriraj hospital: Hb 7.1g/dL, Hct 23%, MCV 81 WBC 8880 /mm3, N 44.2%, L28.2%, Mo 7.7%, Eo19.4%, Ba 0.5% Platelet : 144,000/mm3 • CBCat provincial hospital, 9 day ago: Hb 8.9 g/dl, Hct 28%, WBC11400/ul, (N73% L17% E14%) Plt 72,000/ul.)

26. Investigation Interpretation of CBC : normochromic normocytic anemia Eosinophilia (>500/ ul) normal platelet count (150,000-400,000/ul) > 100,000/uLBleeding unlikely < 20,000/uL ↑ risk for spontaneous bleeding

27. Investigation • UA : pH 7, Sp.gr. 1.015, WBC 0-1/HPF, RBC 0 /HPF, • Coagulogram: PT 13.5 sec aPTT 27.5 sec PT-INR 1.17 • Interpretation of coagulogram: no significant prolongation of coagulogram

28. Primary Hemostatic Disorders Platelet disorder Thrombocytopenia Platelet dysfunction Blood vessel disorder von Willebrand disease

29. Bleeding tendency Hx, PE Primary hemostatic disorder Secondary hemostatic disorder CBC + platelet count CBC + platelet count+ coagulogram Normal decreased Bleeding time pancytopenia isolated thrombocytopenia Normal prolonged

30. Bleeding Time

31. Bleeding Time: Interpretation Normal value* : 2-7 min: in this patient is >30min Prolonged bleeding time: Thrombocytopenia/ anemia (Hct < 20%) Hereditary platelet dysfunction von Willebrand disease Severe hypofibrinogenemia Blood vessels disorders Uremia Myeloproliferative disorders Medication: Aspirin, NSAIDs, other antiplatelets

32. Bleeding Time • Limitation • Screening test for platelet function • Increased yield in patient suspected of bleeding disorder • - Operator dependent • - Not very sensitive nor • specific in general • population • - Poor predictor of • surgical bleeding

33. Differential diagnosis 1. Acquired platelet dysfunction with Eosinophilia 2. von Willebrand Disease (vWD) 3. Drug induced platelet dysfunction

34. Blood smear

35. Blood smear

36. Diagnosis Acquired platelet dysfunction with Eosinophilia (APDE)

37. APDE • A syndrome characterized by • Reversible spontaneous hemorrhagicdiathesis. • Platelet: bizarre shape, varying in size, pale staining and poor granulation. • Eosinophilia • First described by Mitrakul, 1975. • “Allergic vascular purpura” or “Non-thrombocytopenic purpura with eosinophilia” • Most common bleeding diathesis in children in Thailand (Suvatte, 1979).

38. Clinical manifestation in children with APDE

39. Age distribution of children with APDE

41. Platelet function studies in children with APDE

42. Platelet aggregation test • High ADP     12.5 %     (55.0-90.0) Low ADP     0.0  %(5.0-15.0)       Epinephine     0.0  %   (60.0 - 100.0)  Collagen   7.5  %   (70.0 - 100.0)   Arachidonic acid 52.5 %   (70.0 - 100.0)   Ristocetin     67.5  %   (50.0 - 100.0) 

43. Laboratory findings in children with APDE

44. Number of children with APDE by month when first seen

45. Parasitic infection in children with APDE

46. Proposed pathophysiology of APDE (Lim, 1989 and Laosombat, 2001) Parasitic infection Eosinophilia + IgE level & IgM production (Hathirat, 1993) Ag-Ab cpx bound plt PAF released from mast cell Plt activation Plt degranulation Storage Pool Deficiency

47. Storage Pool Deficiency

48. Certain facts of APDE • Clinical course can intermittently last from a few days to 1 year. • Self-limiting course and spontaneous recovery within 6-12 months. • Recurrence is apparently rare once resolved. • No correlation among number of eosinophil, IgE level and severity of bleeding.

49. Diagnostic investigation • CBC: • normal plt count, decreased granules, pale giant pltand no aggregation. • eosinophilia • Prolonged bleeding time. • Normal coagulogram and clot retraction. • Abnormal plt aggregation test.

50. Treatmentin APDE • No specific treatment • Treatment of parasitic infestation. • Symptomatic and supportive treatment • If severe bleeding occurred, platelet transfusion should be performed : 0.4-0.6 u/kg/dose of plt conc every 2-3 d as guided by bleeding time (Hathirat, 1982). • Oral vitamin C supplement.