1 st Student Teleconference Yeungnam Univ. – Kyushu Univ. 26 th March, 2012

1. 1st Student Teleconference • Yeungnam Univ. – Kyushu Univ. • 26th March, 2012

2. Case 1: Petechiae on both forearms & lower legs JeongHeo(M 6, YU medical college)

3. Chief complaint • Petechiae on both forearms & lower legs

4. Present illness • 6 years old female complaint petechiae on both arms & legs • Past medical history • Complete regular vaccination • No prior disease • Drug : Ibuprofen for 5 days • due to URI 2wks ago • No previous operation • No transfusion history • Atopic dermatitis

5. Family history • Older brother (9 years old) has atopic dermatitis • Social history • N-S

6. Review of system • General weakness(+) • Sweat(-) • Headache (-) • Gum bleeding (+) • Oynophagia (-) • Hemoptysis (-) • PND (-) • Anorexia (+) • Abd. discomfort (-) • Melena (-) • Stool color change (-) • Frequency (-) • Fatigue (+) • Wt. loss (-) • Dizziness (+) • Sorethroat (-) • Cough (-) • Cyanosis (-) • Palpitation (-) • Nausea (-) • Constipation (-) • Hematochezia (-) • Tenesmus (-) • Dysuria (-) • Fever (+) • Skin rash (-) • Tinnitus (-) • Neck pain (-) • Sputum (-) • DOE (-) • Chest pain (-) • Vomitting (-) • Diarrhea (-) • Bowel habit change (-) • Incontinence (-) • Polydipsia (-) • Chill (-) • Itching sensation (-) • Vertigo (-) • Dysphagia (-) • Dyspnea (-) • Orthopnea (-) • Chest discomfort (-) • Abd. pain (-) • Hematemesis (-) • Stool caliber change (-) • Nocturia (-) • Temperature tolerance (-)

7. Physical examinations • General appearance • Relatively well being appearance • Alert mentality • Vital sign • BP 125/80 • PR 103/min • RR 20/min • BT 37°C • Weight 27kg (97%) • Height 123.5cm (97%) • Head&Eye&ENT • Icteric sclera • Pale Conjunctiva • No engorgemented neck vein • Gingival bleeding • Chest • Regular heart beat without murmur • Symmetric & clear breath sound with resonance

8. Abdomen • Inspection • Not distended • Auscultation • Normoactive • Palpitation • Soft without tenderness • No splenomegaly & hepatomegaly • No palpable mass • Percursion • Resonance • Back & Extremity • No pitting edema • Petechiae (+)

9. Problem list?? • Differential diagnosis???

10. Platelet disorder • Platelet agenesis • Idiopathic thrombocytopenic purpura • Drug • Aspirin, clopidogrel • von-Willebrand disease

11. Coagulation factor disorder • Hemophillia • Vitamin K deficiency • Liver disease • Anticoagulation drug

12. Vascular disorder • Thrombotic thrombocytopenic purpura • Hemolytic uremic syndrome • Vasculitis • Systemic lupus erythematosus • Henoch-Schonleinpurpura

13. Anemia • Malnutrition • Auto-immune Hemolytic anemia • Iron deficiency anemia • Aplastic anemia • Megaloblastic anemia • Leukemia • Bone marrow suppression

14. Other impression?? • Physical abuse • Next step??

15. CBC • Hb 6 g/dL/ WBC 5.5K / Plt 13,000 /uL • MCV 92.3 fL / MCH 33.5 pg/cell / RDW 16.2% • Reticulocyte 13.05%

16. PB smear

17. Total & Direct Bilirubin • 2.5 mg/dL / 0.4 mg/dL

18. Coomb's Test • Direct (+) / Indirect (+)

19. Iron study • Serum Iron 103 ug/dL / TIBC 310 ug/dLFerritin 20 ug/dL

20. Serologic test • Antinuclear Ab (-) • Lupus anticoagulant (-) • Factor VIII Ab (-) • Factor IX Ab (-) • AntiplateletAb • Platelet-associated IgG (+) • Platelet glycoprotein Ab (+) • Anti-dsDNAAb (-) • Anti-SmAb (-)

21. Urinalysis • No hematuria • No proteinuria • No pyuria • Urobilinogen (+) • Ketone (-)

22. Coagulation screening test • BT 11min / PT 11 / aPTT 24 / PT INR 1.1

23. Coagulation factor assay • Normal • vWF test • Normal

24. Liver function test • AST 52 U/L / ALT 74 U/L / LDH 1283 U/L • GGT 13 U/L / TP 5.91 g/dL / Alb 3.73 g/dL

25. Bone marrow examination

26. Final diagnosis????

27. Evan’s syndrome • Autoimmune disease • Idiopathic hemolytic anemia • Idiopathic thrombocytopenic purpura

28. Treatment • IV immunoglobulin 1g/kg/d IV for 2days • Methylprednisolone 30mg/kg/d IV for 2-3days • Platelet transfusion

29. If not response? • Splenectomy • Vaccines for Pneumococcus, H. influenzae, Meningococcus

30. Splenectomy failure patients?? • Search for accessory spleen • Diagnosis and eradication of Helicobactor pylori infection • IV immunoglobulin • Anti-D • High-dose dexamethazone • Danazol • Vincristine • Vinblastine • Cyclophosphamide • Azathioprine • Rituximab • Cyclosporine A

31. More information??

32. Disease review : Approach to Bleeding disorder Yeungnam – Kyushu Teleconference Hyun Jung Chung, YUMC

33. Components of hemostasis • Vascular endothelium • Platelet • Coaguation factor

35. Vascular endothelium Antithrombotic Prothrombotic Von Willebrand factor Tissue factor Fibrinolysisinhibitors • Antiplatelet effects • Anticoagulant properties • Fibrinolytic properties

36. Platelet • Adhesion • To ECM after vascular injury with vWF • Secretion • Release of calcium and ADP. • Calcium : coagulation cascade • ADP : platelet aggregation • Aggregation • Via glycoprotein IIb/ IIIa • Primary hemostatic plug. • Secondary plug • Platelet contraction + fibrin

37. Coagulation factor (-) surface charge Tissue injury Most critical step

38. Bleeding? Platelet and vessel wall Coagulation pathway ↑Prothrombin time(INR>1.2) Extrinsic pathway Vt. K deficiency WarfarinTx Liver disease ↑activated partial thromboplastin time(>22-38s) Intrinsic pathway Heparin therapy Hemophila A, B ↑Both Liver disease(advanced) DIC • ↑Bleeding time (>2-7min) • Henoch-Schonleinpurpura • Immune Thrombocytopenic Purpura • Von Willebrand’s disease • Multiple myeloma

40. Platelet disorders • Thrombocytopenia = Reduced platelet number • Causes • Decreased production of platelets • vitamin B12 or folic acid deficiency • Decreased platelet survival • Immunologic or Nonimmunologic etiology • Sequestration : Hypersplenism • Dilutional • Massive transfusions

41. Idiopathic (Immune) Thrombocytopenic Purpura • Thrombocytopenia • Absence of other blood cell abnormalities • No clinically apparent conditions causes thrombocytopenia • Incidence of 22 million/year in one study

42. Clinical Manifestations • May be acute or insidious onset • MucocutaneousBleeding • petechiae, purpura, ecchymosis • epistaxis, gum bleeding • Menorrhagia • GI bleed, CNS bleed : rare

45. Etiology of ITP • Often after infection >80% • Preceding URI history • Theories • Antibody cross-reactivity • Cross-react to PLT antigens • Secondary PLT clearance • H. pylori • Some strains, induce PLT aggregation • Bacterial lipopolysaccharides • LPS adherence to PLT • Secondary PLT clearance • Adults • Lesser clear than children • No prodrome. • Chronic, recurrent form

46. Childhood (acute) ITP Extravascular destruction Adult (chronic) ITP

47. Diagnosis • “Diagnosis of exclusion” • Rule out other causes: • PLT clumping : Pseudothrombocytopenia • Drug : Acetaminophen, Bactrim, Quinidine • Infections : HIV, Hepatitis C • Thyroid : hyper/hypo • Autoimmune disease : SLE • Destructive-consumptive : TTP-HUS • Bone marrow disease : Leukemia, MDS

48. P/E : no splenomegaly, lymphadenopathy • Bleeding time prologation • PT, aPTT : Within normal limits • Peripheral blood smear • Normal RBC, WBC • Normal or slightly enlarged PLT • Bone marrow study • Ix : >60yo, refractory, suspicious other hematologic disorder (AA, leukemia, MDS) • Megakaryocyte : increased • Confirmatory study • Serum antiplatelet antibody assay • Antiplatelet glycoprotein antibodies • Confirmatory test is not necessary in typical cases!

49. ITP : Relatively BENIGN DISEASEA PROSPECTIVE STUDY OF ITP IN 245 ADULTS • Only.. • 12% Bleeding • 12% Needed splenectomy • 1.6% died • 28% Asymptomatic • 18% needed no treatment • 63% remission(PLT>100K) • 87% at least partial remission(PLT>30K, Asx.)

50. Management • Indications of treatment • Platelet < 20K & persistent bleeding • High risk of severe bleeding : wet purpura, retinal bleeding • Chronic bleeding >6mon • PLT< 20K or PLT < 50K + mucocutaneous bleeding • Management for children • 30-70% recover within 3 weeks • Single dose IVIg 0.8-1g/kg as effective as repeated • Vaccination schedule : delay 8-11 mon • Splenectomy • Chronic ITP (> 12 mo) • Refractory with life-threatening bleeding • Vaccination : encapsulated bacteria • Pneumococcal, H. influenzae and meningococcal vaccines