혈소판감소증및고혈소판증 2010. 03. 21. 분당서울대학교병원혈액종양내과방수미 Warming-up 다른목적으로검사를진행한환자의혈소판이 25K (130~350K) 로체크되었다면우선취할조치는? 1. 재검 2. 재검 (citrate bottle) 3. 말초혈액도말 4. 골수검사 5. 출혈증상확인 증례 1. ( 여자 /43) 주소 : 3주전팔과다리등에빨간반점이생겼고 2주전부터는허벅지에커다란멍이들었고외상은없었음 과거력 : 현재의 9살자녀를출산하기전 2회의자연유산 약물복용이나술, 담배 : 가끔두통등에복용하는타이레놀외에는모두부인 동반질환 : 없음 동반증상 : 최근두달동안생리량이증가하고간격도짧아짐
신체검진 환자의우측바깥쪽허벅지의멍 (purpura) 검사소견 CBC: WBC 6,510/μL, Hb 12.6g/dL, PLT 3K LFT: ALP 76 U/L, protein/albumin 7.8/4.3g/dL, t-bilirubin 0.7mg/dL, AST/ALT 22/15 U/L HBs Ag /Ab (-/+), HCV Ab (-) U/A: blood/protein(-/-) PBS : PBS
문항 1 이환자에서확진을위해추가해야하는검사는무엇인가? 1. Antinuclear Ab 2. Lupus anticoagulant 3. Anti-HIV Ab 4. Bone marrow biopsy 가. 1, 2, 3 나. 1, 3 다. 2, 4 라. 4 마. 1, 2, 3, 4 혈소판감소증의기전 Decreased marrow production of megakaryocytes Marrow infiltration with tumor, fibrosis Marrow failure - aplastic, hypoplastic anemias, drug effects Increased destruction of circulating platelets Nonimmune destruction Vascular prostheses, cardiac valves Disseminated intravascular coagulation Sepsis Vasculitis Immune destruction Autoantibodies to platelet antigens (ITP) Drug-associated antibodies Circulating immune complexes (SLE, AIDS, sepsis) Splenic sequestration Splenic congestion d/t portal hypertension (HBV. HCV, alcohol) Splenic enlargement d/t tumor infiltration 문항 2 추가검사에서이상소견이없다면환자의정확한진단명은?
문항 3 환자의초치료방침으로적절한것은? 1. Observation 2. Steroid 3. Danazol 4. Splenectomy 5. TPO * receptor agonist * TPO; thrombopoietin Thrombopoietin (TPO) Ligand for TPO-R on megakaryocyte Stimulate megakaryocyte differentiation and platelet production 투여후 5~14일째말초혈액혈소판이상승 제한점 : 중화항체의발생으로인한이차성혈소판감소증 => TPO-R agonist의개발로이어짐 Romiplastim versus placebo 63명의비장절제환자 연구목표 : 8주동안혈소판 50k 목표달성율 : 38.1% versus 0% No neutralizing Ab 반응율 : 78.6% versus 0% 2006, NEJM Elthrombopag versus placebo 반응기준 : 6 주후혈소판 50k 반응율 : 28/70/81% versus 11% 비장절제술을받은환자에서의반응율 :47% 2007, NEJM
증례 2. ( 여자 /43) 주소 : 검사중진행하는혈소판감소증 동반증상 : 생리과다및치질출혈 과거력 : 고막성형술 (2회) 동반질환 : (1) 1997년궤양성대장염진단후 42개월치료하며호전되어중단, 다시재발하여 mesalamine 32개월째복용중 (2) 3개월전당뇨약 (metformin/pioglitazone) 복용시작, 위장장애로 1달전pioglitazone 로변경 검사결과 : 혈소판 68k 94k 90k 124k 108k 175k (mesalamine 복용직전 ) 문항 1 가장의심되는진단은? Criteria for DIT 1. Drug administration preceded thrombocytopenia; recovery from thrombocytopenia complete and sustained after drug discontinued 2. Other drugs administered prior to thrombocytopenia were continued or reintroduced after discontinuation of the suspected drug 3. Other etiologies of thrombocytopenia excluded 4. Re-exposure to the drug resulted in recurrent thrombocytopenia Definite: all 4 criteria met, Probable: criteria 1 3 met, Possible: criterion 1 met, Unlikely: criterion 1 not met
http://www.ouhsc.edu/platelets/ Drug (brand name) Definite evidence Probable evidence Abciximab (ReoPro) 6 7 Acetaminophen (Tylenol, Panadol, and others) 3 4 Carbamezapine (Tegretol) 0 10 Chlorpropamide (Diabinese) 0 5 Cimetidine (Tagamet) 1 5 Danazol (Danocrine) 3 4 Diclofenac (Cataflam and Voltaren) 2 3 Efalizumab (Raptiva) 0 6 Eptifibatide (Integrilin) 2 7 Gold (Ridaura, Solganal, and others) 0 11 Hydrochlorothiazide (Aquazide-H, Esidrix, and others) 0 5 Interferon- (Roferon-A and Intron A) 1 6 Methyldopa (Aldomet) 3 3 Nalidixic Acid (NegGram) 1 5 Quinidine (Quinaglute, Cardioquin, and others) 26 32 Quinine (Quinamm, Quindan, and others) 14 10 Ranitidine (Zantac) 0 5 Rifampin (Rifadin, Rimactane) 5 5 Tirofiban (Aggrestat) 2 6 Trimethoprim/sulfamethoxazole (Bactrim, Septra, and others) 3 12 Vancomycin (Vancoled) 3 4 DRUGDEX DIT 치료원칙 약제중단 수혈 [ 생명을위협하는출혈 ] 면역글로불린 [ 중증감소 ] 스테로이드등의면역억제제 [ 중증감소 ]
증례 3. ( 여자 /69) 주소 : 2007. 10. 좌측새끼발가락의염증이진행하여수술예정으로혈소판이 950k나와의뢰되심 과거력 : 50세넘어진후발생한대퇴경부골절로고관절치환술후 63세때재수술받으심 동반질환 : 고혈압으로 9년째투약중 동반증상 : 6개월전부터바깥에나가면손가락끝이파래지고주무시는중에는붓고빨갛다 신체검진 추가검진및검사 과거병력 : 6년전관절재수술당시혈소판이최고 717k로상승하여골수검사등을시행하고수술후 572k로감소하여반응성고혈소판증으로잠정진단 신체검진 : 간이나비장비대는없음 CBC: 12,330-14.4-950k LD: 382 (100~225) BM aspiration and biopsy: normocellular marrow with increased mature megakaryocytes (cellularity 41-50%)
반응성고혈소판증 Inflammation Malignancy ET, essential thrombocythemia; RARS, refractory anemia with ringed siderolasts Infection Myeloproliferative disorders other than ET Myelodysplastic syndorme: RARS Postsplenectomy Hemorrhage and iron deficiency anemia Surgery Reboud: correction of megaloblastic anemia Hemolysis Familial: TPO overproduction 진성고혈소판증 (WHO 2001) 문항 1. 최종진단은? 혈소판 > 600k BM : increased mature megakaryocytes JAK2 V617F mutation (heterozygote)
Erythromelalgia 만성골수증식성질환 (WHO 2001) Common 1. Chronic myelogenous leukemia (CML) 2. Polycythemia vera (PV) 3. Essential thrombocythemia (ET) 4. Chronic idiopathic myelofibrosis (CIM) Uncommon 1. Chronic neutrophilic leukemia (CNL) 2. Chronic eosinophilic leukemia/ hypereosinophilic syndrome (HES) 3. Chronic MPD, unclassifiable (MPDu) 4. MDS/MPD Chronic myelomonocytic leukemia (CMMoL); atypical CML (acml); juvenile MMoL; MDS/MPD, unclassifiable WHO 2008 : 2001 년과달라진점 만성골수증식성질환 (CMPD) 에서골수증식성종양 (MPN) 으로명칭변경 Mast cell disease를편입 CMPD에속하던 hypereosinophilic syndrome을 MPN에서분리하여 myeloid neoplasm with PDGFRA, PDGFRB, FGFR1 rearrangement로분류 글리벡적용가능 JAK2 변이를주진단기준으로추가
JAK2 V617F Mutation Campbell BJ. NEJM 2006:355;2452 JAK2 변이율 (N=266) KMPNWP 60% 85% 33% 80% Bang SM. Thromb Haemost 2009:101;547
ET 진단 Tip 반응성고혈소판증배제 : 철결핍성빈혈, 염증및고형암, PV, MF, CML and MDS JAK2 변이검사를시행 : homozygote (ET 는 <1%) 면 PV와 MF 를반드시감별 변이양성이면혈소판이 45만이상에서진단 변이음성이면혈소판이 60만이상, 한달간지속되면진단 Campbell BJ. NEJM 2006:355;2452 혈전발생위험도 * Hypertension, hypercholesterolemia, diabetes, smoking ET 치료원칙