Acquired platelet dysfunction with eosinophilia

1. Acquired platelet dysfunction with eosinophilia ผศ.พญ.พัชรี คำวิลัยศักดิ์ ภาควิชากุมารเวชศาสตร์ มหาวิทยาลัยขอนแก่น

2. Case เด็กชายอายุ 5 ปี มาด้วยเรื่อง จุดฟกช้ำที่ขาและแขน มาประมาณ 3 วัน ก่อนหน้านี้เด็กสบายดี ไม่เคยมีจุดจ้ำเลือดมาก่อน ไม่มีเลือดออกที่บริเวณใดๆ ประวัติครอบครัว ไม่เคยมีใครมีเลือดออก ตรวจร่างกาย no pale, no jaundice, no hepatosplenomegaly, normal chest and heart, superficial ecchymoses both legs and arms

5. Laboratory Findings • CBC: Hb 12 g/dL, Hct 36% WBC 12,000 cells/cumm, Eo 8%, N 75 %, L 17 %, platelet count 230,000 cells/cumm • Coagulogram: PT 10 secs, PTT 30 secs

7. Acquired platelet dysfunction with eosinophilia • the most common cause of bleeding diathesis in children in Thailand • previously known in Thailand as ‘allergic vascular purpura’ • first recognized: by Mitrakul in 1974 • name by Suvatteet al. in 1974 as nonthrombocytopenicpurpura with eosinophilia • internationally accepted to be ‘acquired platelet dysfunction with eosinophilia’ on 9 January 1979

8. Acquired platelet dysfunction with eosinophilia • The majority of patients with acquiredplatelet dysfunction with eosinophilia (APDE) were reported from Thailand and Southeast Asia

9. Clinical Manifestations Laosombat V, Platelet (2001) 12;5-14

10. Age Distribution Laosombat V, Platelet (2001) 12;5-14

11. Clinical Manifestations Laosombat V, Platelet (2001) 12;5-14

12. Clinical Manifestations Laosombat V, Platelet (2001) 12;5-14

13. Clinical Manifestations Laosombat V, Platelet (2001) 12;5-14

14. Acquired Platelet Dysfunction with Eosinophilia in Thai Children: 4 years prospective cohort study • 18 patients with APDE were identified. The mean age at diagnosis was 5.7 years (range 2 to 12 yrs). M:F=1.6:1 • Most children presented with spontaneous purpuraall over the body (94.5%) but only 1 case (5.6%) presented with severe bleeding: subgaleal hematoma after minor head trauma. • The absolute eosinophil count range 1.2-13.2 x109/L. • The mean of platelet count was 223,056 /mm3. All patients had pale-stained. Sosothikul D,et al. International Congress on Tropical Pediatrics 2011

15. Laboratory Findings Laosombat V, Platelet (2001) 12;5-14

16. Acquired Platelet Dysfunction with Eosinophilia in Thai Children: 4 years prospective cohort study • 18 patients with APDE were identified. The mean age at diagnosis was 5.7 years (range 2 to 12 yrs). M:F=1.6:1 • Most children presented with spontaneous purpura all over the body (94.5%) but only 1 case (5.6%) presented with severe bleeding: subgaleal hematoma after minor head trauma. • The absolute eosinophil count range 1.2-13.2 x109/L. • The mean of platelet count was 223,056 /mm3. All patients had pale-stained. Sosothikul D,et al. International Congress on Tropical Pediatrics 2011

19. Platelet Function Test Laosombat V, Platelet (2001) 12;5-14

20. Acquired Platelet Dysfunction with Eosinophilia in Thai Children: 4 years prospective cohort study • The bleeding time were prolonged in all cases. Coagulogram were normal in all cases. • Parasitic infestations were detected in 50% (Hook worm eggs 5/9 cases and ascaris eggs 4/9 cases). • The whole blood platelet aggregation tests were abnormal in all cases. Collagen, ADP, and Arachidonic acid induced platelet aggregation test were abnormal in 83.3,72.2 and 44.4% of cases, respectively but ristocetin induced platelet aggregation tests were normal in all cases. • The transmission electron microscopy were studies in 4 cases and all showed decrease of dense granule. SosothikulD,et al. International Congress on Tropical Pediatrics 2011

21. Platelet Function Test Laosombat V, Platelet (2001) 12;5-14

22. Acquired Platelet Dysfunction with Eosinophilia in Thai Children: 4 years prospective cohort study • The bleeding time were prolonged in all cases. Coagulogram were normal in all cases. • Parasitic infestations were detected in 50% (Hook worm eggs 5/9 cases and ascaris eggs 4/9 cases). • The whole blood platelet aggregation tests were abnormal in all cases. Collagen, ADP, and Arachidonic acid induced platelet aggregation test were abnormal in 83.3,72.2 and 44.4% of cases, respectively but ristocetin induced platelet aggregation tests were normal in all cases. • The transmission electron microscopy were studies in 4 cases and all showed decrease of dense granule. SosothikulD,et al. International Congress on Tropical Pediatrics 2011

27. Platelet Function Test Laosombat V, Platelet (2001) 12;5-14

28. ATP release

29. Acquired Platelet Dysfunction with Eosinophilia in Thai Children: 4 years prospective cohort study • The bleeding time were prolonged in all cases. Coagulogram were normal in all cases. • Parasitic infestations were detected in 50% (Hook worm eggs 5/9 cases and ascaris eggs 4/9 cases). • The whole blood platelet aggregation tests were abnormal in all cases. Collagen, ADP, and Arachidonic acid induced platelet aggregation test were abnormal in 83.3,72.2 and 44.4% of cases, respectively but ristocetin induced platelet aggregation tests were normal in all cases. • The transmission electron microscopy were studies in 4 cases and all showed decrease of dense granule. SosothikulD,et al. International Congress on Tropical Pediatrics 2011

30. Electron Microscopy Study Laosombat V, Platelet (2001) 12;5-14

31. Electron Microscopy Study SosothikulD,et al. International Congress on Tropical Pediatrics 2011

32. Parasitic Infection in Children with APDE Laosombat V, Platelet (2001) 12;5-14

33. Acquired Platelet Dysfunction with Eosinophilia in Thai Children: 4 years prospective cohort study • The bleeding time were prolonged in all cases. Coagulogram were normal in all cases. • Parasitic infestations were detected in 50% (Hook worm eggs 5/9 cases and ascaris eggs 4/9 cases). • The whole blood platelet aggregation tests were abnormal in all cases. Collagen, ADP, and Arachidonic acid induced platelet aggregation test were abnormal in 83.3,72.2 and 44.4% of cases, respectively but ristocetin induced platelet aggregation tests were normal in all cases. • The transmission electron microscopy were studies in 4 cases and all showed decrease of dense granule. SosothikulD,et al. International Congress on Tropical Pediatrics 2011

35. Proposed Pathophysiology of APDE

36. IgE level and Ig M production Ag-Ab complex bound platelets PAF released from mast cells Platelet Activation Platelet degranulation Storage pool deficiency

37. Treatment The majority of patients did not receive anytreatment Patients with severe bleeding, excessive bleeding after tooth extraction or large hematoma were treated by platelet transfusion to stop bleeding and packed red cell transfusion to correct anemia from blood loss All of the patients had good responses

38. Outcome

39. Summary • APDE is transient with no serious bleeding manifestations • APDE has a benign clinical course • The hallmark includes spontaneous bruising, normal hematocrit, normal number of platelets, normal coagulogram, eosinophilia, prolonged bleeding time, abnormal platelet adhesiveness, and associated parasitic infection • Remission is spontaneous

40. Future Direction • Epidemiologic study; incidence • Multicenter or Registry from Thai Hematology Society