TTP-HUS 2014년 8월 13일 R1 황규환

Overview Thrombotic thrombocytopenic purpura (TTP) Hemolytic uremic syndrome (HUS) systemic disorders endothelial injury with small vessel platelet-rich th rombi 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 O157:H7)

TTP-HUS Comprehensive term Distinction between these entities 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.

ADAMTS13 Von Willebrand factor is assembled in larger than are present in normal plasma. -> platelet aggregation, and the platelet thrombi ADAMTS13 : a specific von Willebrand factor-cleaving protease (or cleaving metalloproteinase) Reduced ADAMTS13 activity Antibody to ADAMTS13 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 ADAMTS13 supplies the missing ADAMTS13 -> 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 Adult diarrheal HUS TTP-HUS without an obvious inciting event, such as diarrheal illne ss, 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 ADAMTS13 Rituximab 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/m2 administered during a course of plasma exchan ge Cyclosporine has generally not been used

Case 873900 M/79

Present illness 79세 남자환자 내원 6일 전 melena 로 송도병원에서 Upper GI bleeding 보여 입원치료 권유받았으나 이틀만 에 자의퇴원했던 분으로, 당시 GFS, CFS 소견으로는 small bowel bleeding이 의심되며 또한 당시에 7/30일 시행한 serum Cr.은 0.8이었음 한달전 Compression Fx. of L3, L5로 진통제와 수면제 꾸 준히 복용하던 분으로, 내원 전날 저녁에 수면제(stilnox포 함) 20여알을 한꺼번에 복용하였고 내원 당일 general weakness, Loose stool 있어 본원 ER 내원함 ER에서 DRE는 negative였고 L-tube에서는 old clot 양상 의 내용물이 나왔으나 active bleeding소견은 아닌것으로 보이고 Lab에서 BUN/Cr이 101.6/8.91로 높아 신장내과 입원함

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 General appearance Chest Abdomen BP : 190/90 mmHg BT : 36.2℃ PR : 64 회/min 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 : 13900-7.8/22.3-52k Albumin 3.1, OT/PT 62/65, Bil,total 0.7 LDH 2708 Amylase 95, Lipase 27 BUN/Cr 101.6/8.91 (eGFR 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 aBGA 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 #2 AKI HTN HAD #3 * Hb/Hct 9.1/26.7 Plt 49k - 내원당일 Hydration하고 Lasix 투여하였으나 호전 없음 - 금일 perm catheter insertion하고 HD 시작함 (2시간, 1Kg) - 금일 abd. USG 상 Rt. kidney는 8.8cm, Lt. kidney는 8.9cm으로 측정 HTN - 평소 HTN medication 안했었으나 입원하여 BP 180/80이상으로 높음 - Hydralazine 투여 HAD #3 * Hb/Hct 9.1/26.7 Plt 49k - 금일 HD 시행함 (3시간) PC 8개 수혈함 - 금일 Kidney Bx. 시행함

HAD #4 * Hb/Hct 6.5/19.4 Plt 137 * BUN/Cr 45.1/5.59 LDH 1631 tB/dB 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, pRBC 2개 수혈 - 내일 아침 Lab결과에 따라 plasmapheresis 시행 예정 HTN - 평소 HTN medication 안했었으나 입원하여 BP 180/80이상으로 높음 - Hydralazine 투여

* (post PEx) Hb/Hct 5.6/16.8 Plt 94k * LDH 1543 TTP-HUS AKI HAD #5 * (post PEx) Hb/Hct 5.6/16.8 Plt 94k * LDH 1543 TTP-HUS AKI - plasmapheresis 시행함 (FFP 10개) - 어제 pRBC 2개 수혈함 - 금일 Filtered RBC 2개 수혈함 HAD #6 * Hb/Hct 7.9/23.1 Plt 107k * LDH 1227 - 어제 plasmapheresis 시행함 - 금일 HD함

* (post PEx) Hb/Hct 7.9/24.1 Plt 73k * LDH 1268 TTP-HUS AKI HAD #7 * (post PEx) Hb/Hct 7.9/24.1 Plt 73k * LDH 1268 TTP-HUS AKI - 2차 plasmapheresis 시행함 (FFP 14개) HAD #8 * Hb/Hct 7.4/22.5 Plt 76k * BUN/Cr 36.0/4.60 LDH 910 - 어제 plasmapheresis 시행함 - 금일 HD함