TTPHUS 2014 8 13 R 1 Overview Thrombotic

TTP-HUS 2014년 8월 13일 R 1 황규환

Overview � Thrombotic thrombocytopenic purpura (TTP) � Hemolytic uremic syndrome (HUS) ◦ systemic disorders ◦ endothelial injury with small vessel platelet-rich thrombi ◦ microangiopathic hemolytic anemia �Schistocyte, Reticulocytosis, nucleated RBCs ◦ Thrombocytopenia ◦ Neurologic and/or Renal abnormalities.

Schistocyte � marked red cell fragmentation ◦ TTP, HUS, DIC, Cardiac valve prosthesis, Eclampsia, Malignant HTN, Kidney graft rejection

TTP � Severe thrombocytopenia � Microangiopathic hemolytic anemia � Fever � Neurologic symptoms and signs ◦ Headache, mental disorder, confusion, seizure, aphagia etc. � Renal function abnormalities ◦ Proteinuria, Hematuria, Azotemia ◦ ARF is minimal or not present

HUS � Acute renal failure � Microangiopathic hemolytic anemia � Thrombocytopenia � Children � Shiga toxin-producing E. coli (usually E. coli O 157: H 7)

TTP-HUS � Comprehensive term ◦ more appropriate for most sporadic cases in adults � Distinction between these entities ◦ less clear ◦ the treatment choice is not dependent upon the presumed underlying etiology � Children without renal failure may also be diagnosed as having TTP-HUS

Adult TTP-HUS syndromes � Drug induced ◦ Immune mediated : Quinine is most common ◦ Dose-dependent toxicity : Cancer chemotherapy(mitomycin C, gemcitabine, possibly others) : Immunosuppressive agents (cyclosporine, tacrolimus, sirolimus) Following bloody diarrhea caused by Shiga toxin-producing E. coli � Pregnancy or postpartum � Congenital � Autoimmune disorders � : Patients may have both TTP-HUS and SLE. � Acquired autoimmune TTP : Due to autoantibody inhibition of ADAMTS 13 activity.

ADAMTS 13 Von Willebrand factor is assembled in larger than are present in normal plasma. -> platelet aggregation, and the platelet thrombi � ADAMTS 13 : a specific von Willebrand factor-cleaving protease (or cleaving metalloproteinase) � � Reduced ADAMTS 13 activity Antibody to ADAMTS 13 � Severe sepsis, DIC, severe liver disease, Pregnancy �

Pathology � � Thrombi composed primarily of platelet in affected organs Kidney thrombi in the glomeruli and arterioles subendothelial deposit of fibrin-like material intimal thickening and onion-skin hypertrophy(healing) (malignant nephrosclerosis, preeclampsia, scleroderma, chronic rejection)

Plasma exchange � The mainstay of Tx. � removal of Pt’s plasma by pheresis and replacement with donor plasma ◦ depletes the circulating autoantibody to ADAMTS 13 ◦ supplies the missing ADAMTS 13 -> Reverse the microvascular thrombus formation � should be initiated even if there is uncertainty about Dx. � mortality 90% (prior to use of plasma exchange) ◦ <25% (treated with plasma exchange)

Plasma exchange � Idiopathic TTP-HUS ◦ TTP-HUS without an obvious inciting event, such as diarrheal illness, other infection, or new medication ◦ fatal, medical emergency ◦ plasma exchange without delay! � Adult diarrheal HUS ◦ caused by enteric infection with Shiga toxin-producing E. coli or other organisms ◦ observational study: mixed results ◦ plasma exchange can be used � Exceptions to the use of plasma exchange ◦ postdiarrheal HUS in children ◦ cancer, chemotherapy, hematopoietic cell transplantation ◦ Pneumococcal infection in children

Immunosuppression � Glucocorticoids : autoantibody to ADAMTS 13 ◦ idiopathic TTP-HUS � prednisone (1 mg/kg per day by mouth) � methylprednisolone (125 mg IV twice daily) ◦ platelet not increase within several days of Plasma exchange ◦ thrombocytopenia recurs when PEx diminished � Rituximab ◦ more severe course and more neurologic abnormalities ◦ 375 mg/m 2 administered during a course of plasma exchange � Cyclosporine has generally not been used

Case 873900 M/79

Review of system � General weakness (+) � Dyspnea (-) Cough (-) Sputum (-) � Abd. Pain (-) Nausea (-) Vomiting (-) � Loose stool(+) Melena (+) Hematochezia (-) � Lower back pain (+) � Purpura (+) ◦ 양쪽 팔, 다리

Physical examination � Vital sign ◦ BP : 190/90 mm. Hg ◦ PR : 64 회/min � BT : 36. 2℃ RR : 18 회/min General appearance ◦ Acute ill-looking appearance with alert mental state � Chest ◦ Normal breathing sound ◦ Wheezing (-), Rale (-) � Abdomen ◦ Tenderness/Rebound tenderness(-/-) � Back & Extremities ◦ Pretibial pitting edema(-/-) ◦ Rash (-) ◦ Purpura (+)

� Lab ◦ ◦ ◦ ◦ CBC : 13900 -7. 8/22. 3 -52 k Albumin 3. 1, OT/PT 62/65, Bil, total 0. 7 LDH 2708 Amylase 95, Lipase 27 BUN/Cr 101. 6/8. 91 (e. GFR 5. 1) Electrolyte: 130 -5. 6 -96 -12 CRP : 3. 65 RUA : Protein trace, Blood 4+ � RBC many/HPF, WBC 5 -9/HPF, Squamous 1 -4/HPF ◦ FENa 10. 6 ◦ a. BGA 7. 312 -24. 5 -119 -12. 4, 98%

Problem list � � � AKI Hyperkalemia d/t AKI Pulmonary edema ◦ Hydration하고 Lasix 투여 ◦ 호전되지 않거나 acidosis 진행할 경우 HD 또는 CRRT � r/o Small bowel bleeding ◦ General condition 호전 후 GFS, CFS 시행 � Known COPD ◦ 증상 호소 없어 경과 관찰

HAD #4 * Hb/Hct 6. 5/19. 4 Plt 137 * BUN/Cr 45. 1/5. 59 LDH 1631 t. B/d. B 1. 3/0. 7 ◦ TTP-HUS � ◦ AKI - Purpura 양 하지 전체로 악화 - POD #3 시행한 PB morphology 상 Moderate thrombocytopenia, schistocytes 10% 소 견 보이고 Kidney Bx. 의 중간결과를 검토한 결과 Hemolytic uremic syndrome 가능성 - 금일 MH 전과, p. RBC 2개 수혈 - 내일 아침 Lab결과에 따라 plasmapheresis 시행 예정 ◦ HTN - 평소 HTN medication 안했었으나 입원하여 BP 180/80이상으로 높음 - Hydralazine 투여

� HAD #5 * (post PEx) Hb/Hct 5. 6/16. 8 Plt 94 k * LDH 1543 ◦ TTP-HUS ◦ AKI - plasmapheresis 시행함 (FFP 10개) - 어제 p. RBC 2개 수혈함 - 금일 Filtered RBC 2개 수혈함 HAD #6 * Hb/Hct 7. 9/23. 1 Plt 107 k * LDH 1227 ◦ TTP-HUS ◦ AKI � - 어제 plasmapheresis 시행함 - 금일 HD함

� HAD #7 * (post PEx) Hb/Hct 7. 9/24. 1 Plt 73 k * LDH 1268 ◦ TTP-HUS ◦ AKI - 2차 plasmapheresis 시행함 (FFP 14개) HAD #8 * Hb/Hct 7. 4/22. 5 Plt 76 k * BUN/Cr 36. 0/4. 60 LDH 910 ◦ TTP-HUS ◦ AKI � - 어제 plasmapheresis 시행함 - 금일 HD함