1. 報告 : R3 李廣祚

2. Name 傅 x x Age30 years old Genderfemale Number8xxxxxx

3. Amenorrhea, under hormone therapy and induced menstruation in Gyn OPD since 2009 Pregnancy GA 14+ weeks

4. LMP : 2011-07-20 (induced) 2011/08 Icon (+), stop E2 and P supplement Then, she received first time CBC exam in 2011/10

5. WBC 5.2 1000/uL RBC 4.39 million/uL Hemoglobin 12.2 g/dL Hematocrit 36.1 % MCV 82.2 fL MCH 27.8 pg/Cell MCHC 33.8 gHb/dL RDW 13.7 % Platelets 45 1000/uL

6. Intermittent low grade fever for 3-4 weeks Multiple petechiae and ecchymosis at trunk and limbs.

7. No travel history within recent months No URI symptom, productive cough, dysuria, diarrhea, dysuria, or abdominal pain No tarry stool No hypertension No general or lower limbs edema No self medication or herb usage

8. WBC 7.7 1000/uL RBC 2.54 million/uL Hemoglobin 7.4 g/dL Hematocrit 21.3 % MCV 83.9 fL RDW 17.4 % Platelets 5 1000/uL

9. Nucleated RBC 0.9 /100 WBC Atypical-Lympho 1.0 % Myelocyte 1.0 % Segment 84.0% Lymphocyte 6.0 % Monocyte 8.0 %

10. P.T 10.7 sec Nor.plasma mean10.5 sec INR 1.0 APTT 31.9 sec Nor.plasma mean28.5 sec

11. Creatinine(B) 0.46 mg/dL D.Bilirubin 0.4 mg/dL Total Bilirubin 1.7 mg/dL AST/GOT 45 U/L ALT/GPT 39 U/L Na(Sodium) 134 mEq/L K(Potassium) 3.7 mEq/L LDH 887.0 U/L

12. Then, blood smear was done, and steroid therapy had been started in ER Prednisolone 5mg/tab2 PC QID However, progressive anemia occurred on 11/05:

13. WBC 9.6 1000/uL RBC 1.84 million/uL Hemoglobin 5.5 g/dL Hematocrit 16 % RDW 20.7 % Platelets < 5 1000/uL Reticulocyte 9.1

14. Fibrinogen 191 D-dimer 2120 LDH 1422.0 Urinalysis : No proteinuria

15. Then, RBC 2u transfusion was done, and she had been admitted in Hematology ward since 11/05

16. Conscious: clear Pale conjunctiva No palpable lymph node No palpable spleen or liver Petechiae and ecchymosis over bil. lower limb and upper limb

17. Hyperprolactinemia without definite diagnosis, under regular following up in Meta OPD till 2008/12 No previous pregnancy record

18. Under-production Nutritional deficiency Abnormalities within bone marrow Increased peripheral destruction Hypersplenism Immune-mediated destruction Non-immune-medicated destruction

19. Nutritional deficiency Not favored by history and onset time Bone marrow abnormalities Absent leukoerythroblastic picture No leukopenia

20. Hypersplenism No palpable spleen Immune-mediated destruction Autoimmune disorder : possible Systemic infection : less likely Idiopathic thrombocytopenia : less likely due to concurrent severe anemia

21. Non-immune-medicated destruction Pre-eclampsia, HELLP : possible TTP : possible DIC No evidence of sepsis or metastatic malignancy No coagulopathy

22. Severe thrombocytopenia with anemia, possibly : Pre-eclampsia or HELLP syndrome Thrombotic thrombocytopenic purpura Systemic lupus erythematosus or other autoimmune disorder Bone marrow disorder

23. Steroid was titrated up to Methylprednisolone 40mg 1pc IV Q12H since 11/05, and blood test was followed on 11/07 :

24. WBC 8.962 1000/uL RBC 1.59 million/uL Hemoglobin 5.2 g/dL Hematocrit 14.1 % MCV 83.9 fL RDW 21.6 % Platelets 3 1000/uL Reticulocyte22.5

25. ANA ( 1:640 ) (Speckled) A-DSDNA < 40.5 (Negative) C3, C4 (not decreased) D-COOMBS Negative Anti-CardiolipinNegative Bilirubin (D)0.4 Bilirubin (T)0.5 LDH1920

27. Schistocytes

29. Impresssion Microangiopathic hemolytic anemia Markedly thrombocytopenia

30. Severe thrombocytopenia with anemia, possibly : Pre-eclampsia or HELLP syndrome Thrombotic thrombocytopenic purpura Systemic lupus erythematosus or other autoimmune disorder Bone marrow disorder

31. Hb 5.5=5.2=8.4 Platelet <5000=3000= AST 66=59=47 Bilirubin 1.4=1.5=1.7 LDH 1422=1920=1850 Plasma Exchange

32. No obvious response to steroid, start plasma exchange, QOD x 5 course (9, 11, 14, 16, 18)

33. Hb =8.5==8.9 Platelet =22000==100000 AST =21=== Bilirubin =0.8=== LDH =646=== Plasma Exchange

36. 11/0711/15

37. Hb ==8.6=9.3 Platelet ==71000=39000 AST ===== Bilirubin ==0.6== LDH ==198== Plasma Exchange

38. The response to plasma exchange was not consistently. The dosage was titrated up to QD since 11/20 - 11/24.

39. Hb =9.5==10.3 Platelet =67000==148000 AST ====18 Bilirubin ====0.3 LDH ====157 Plasma Exchange

40. 11/28 Hb 10.8 Platelet 207000 Plasma Exchange was tapered to QOD: 11/28, 11/30, 12/02, 12/04 Steroid was tapered (12/05) From Methylprednisolone 40mg IV Q12H, To Methylprednisolone 4mg/tab 4PC QID

43. WBC8400 Segment83% Lymphocyte10% Hb11.6 RDW15.5 Platelet179000 Bilirubin (T)0.3 AST15 LDH182

44. Pregnancy-related Thrombotic Thrombocytopenic Purpura

45. Since plasma exchange might be harmful to pregnant woman and fetus, how could we improve our decision making ?

46. Pathogenesis and definition of TTP ? TTP and pregnancy ? Some diseases which mimic TTP during pregnancy; how to differentiate them ?

48. ADAMTS13 deficiency (A Disintegrin And Metalloprotease with a ThromboSpondin type 1 motif, member 13) Low plasma level Presence of Autoantibody or Inhibitor Endothelial injury, increased platelet aggregation, and genetic factors … Thrombotic microangiopathies MOAKE. Thrombotic microangiopathies. N Engl J Med, Vol. 347, No. 8·August 22, 2002

50. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor Mannucci PM, Canciani MT, Forza I, Lussana F, Lattuada A, Rossi E. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood. 2001 Nov 1;98(9):2730-5.

54. high levels of estrogens The protein seems to be infuenced by high levels of estrogens because plasma levels decreased progressively from the first trimester of pregnancy.

56. Pre-eclampsia / Eclampsia HELLP syndrome Sepsis Exacerbation of SLE …

57. Abnormalities in the development of placental vasculature placental underperfusion/hypoxia/ischemia Abnormalities in the development of placental vasculature early in pregnancy may result in relative placental underperfusion/hypoxia/ischemia, which then leads to release of antiangiogenic factors into the maternal circulation that alter maternal systemic endothelial function and cause manifestations of the disease.

60. Unknown etiology; probably severe form of preeclampsia Microangiopathic hemolytic anemia Platelet count ≤100,000 cells/microL Total bilirubin ≥1.2 mg/dL Serum AST ≥70 IU/L

61. The onset of TTP tends to be earlier in gestation First trimester : 12 percent Second trimester : 56 percent Third trimester/postpartum : 33 percent Preeclampsia-HELLP does not occur before 20 weeks of gestation and most cases are diagnosed in the third trimester Martin JN Jr, Bailey AP, Rehberg JF, Owens MT, Keiser SD, May WL. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol. 2008 Aug;199(2):98-104. Epub 2008 May 23.

62. HELLP is associated with thrombocytopenia, and in severe cases, there may be DIC with the attendant prolongation of the PT and aPTT. percentage of schistocytes The percentage of schistocytes on peripheral smear is often higher in TTP (2 to 5 percent) than in HELLP (less than 1 percent) Stella CL, Dacus J, Guzman E, Dhillon P, Coppage K, How H, Sibai B. The diagnostic dilemma of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in the obstetric triage and emergency department: lessons from 4 tertiary hospitals. Am J Obstet Gynecol. 2009 Apr;200(4):381.e1-6. Epub 2008 Dec 25.

64. Imitators of severe pre-eclampsia Sibai BM. Imitators of severe pre-eclampsia. Semin Perinatol. 2009 Jun;33(3):196-205.

66. Pre-eclampsia / HELLP Almost all women spontaneously recovered platelet count > 100000 by 5 days after delivery HELLP All recovered by postpartum day 11

67. If thrombotic microangiopathy : First and Second trimester < GA 20w Consider TTP Second trimester > GA 20 More consideration Third trimester Evaluate the possibility of successful delivery Observe course after delivery

68. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura- hemolytic uremic syndrome during pregnancy. McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura- hemolytic uremic syndrome during pregnancy. J Clin Apher. 2001;16(4):202-9.

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