수혈요법의 실제 경희의대 종양혈액내과 조 경 삼

학습목표 헌혈과 수혈의 과정을 이해하여 수혈이 필요한 환자의 처치를 적절하게 실시한다. 헌혈의 기준을 설명한다. 성분수혈의 종류와 적응증을 설명한다. 수혈과정에 필요한 검사와 그 의의를 설명한다 수혈의 부작용을 설명한다. 수혈 부작용의 치료를 설명한다. 수혈 부작용의 예방책을 설명한다.

Blood Group Antigens and Antibodies Alloantibodies; Autoantibodies ABO antigens and antibodies H substance (O); Oh(Bombay phenotype: hh) N-acetylgalactosamine (A) Galactose (B) Isoagglutinins: naturally occurring anti-A, anti-B Rh system E/e, D, C/c

HTR : hemolytic transfusion reaction HDN : hemolytic disease of newborn

RD : random donor, SDAP : single donor apheresis platelet CCI : corrected count increment : (increased platelet count/ transfused platelet count X 1011)X Body surface area

Pretransfusion testing Type : forward (RBC); reverse (serum) Alloantibody screening : to O RBC Cross maching : donor RBC with patient serum

BLOOD Biologic agent Limited supply Significant side effects

Blood transfusion Donor : genetic differences Blood banking Blood compatibility tests Component therapy Apheresis therapy Transfusion reactions

Blood donation (헌혈) 1954: 국립혈액원 1958: 적십자혈액원 1975: 매혈금지법 1954: 국립혈액원 1958: 적십자혈액원 1975: 매혈금지법 1981: 485,814 (남 63%, 30세 미만: 95%) 1988: 999,444 (남 89%, 30세 미만: 89%) 1995: 2,007,691 (남 85%, 30세 미만: 86%) 1998: 2,529,302 (남 79%, 30세 미만: 86%) 총인구수의 5% (26% 군인, 44% 학생)

헌혈기준(1) - 채혈금지(1999.5 개정) 전염병예방법 제2조 제1항 규정에 의한 전염병 환자(간염 및 크로이츠펠트-야콥병 환자 포함) 체중: 남<50 kg, 여<45kg 구강체온 >37.5oC Systolic BP <90 or >180 mmHg Diastolic BP >100 mmHg 맥박: <50, >100/분 임신, 분만 후 6개월 이내 외과수술 후 6개월이내

헌혈기준(2) - 채혈금지(1999.5 개정) 수혈 후 1년 이내 광견병 예방접종 후 1년 이내 콜레라, 장티푸스, 렙토스피라증 예방접종 후 24시간 이내 말라리아 경력자 (3년 전에 치유된 자는 제외) 호흡기질환, 심장병, 당뇨병, 경련, 알콜중독자, 마약중독자, 또는 혈액관련질환자 심신상실자 문진 결과 헌혈불가로 판정된 자 기타 의사의 진단으로 부적절한자

헌혈기준(3) - 채혈금지(1999.5 개정) 320 mL 전혈 400 mL 전혈 <16, >65 <16, >65 혈액비중 <1.053, Hb <12.5 g/dL, Hct < 38.0% 전혈 채혈 2개월 이내, 성분 채혈 14일 이내 과거 1년 이내에 전혈 채혈 횟수가 5회 이상인 자 400 mL 전혈 <17, >65, 체중 < 50 kg 혈액비중 <1.053, Hb <12.5 g/dL 전혈 채혈 2개월이내, 성분채혈 14일 이내

헌혈기준(4) - 채혈금지(1999.5 개정) 500 mL 혈장 성분 채혈 400 mL 혈소판 성분 채혈 <17, >65 혈액비중 <1.052, Hb < 12.0 g/dL 전혈 채혈 2개월이내, 성분 채혈 14일 이내 400 mL 혈소판 성분 채혈 <17, >60 혈청담백 < 6.1 g/dL 혈소판 < 15만/mm3 전혈 채혈 2개월 이내, 혈소판 성분채혈 72시간 이내

헌 혈 자진 헌혈 (volunteer donation) 지정 헌혈 (directed donation) 헌 혈 자진 헌혈 (volunteer donation) 지정 헌혈 (directed donation) 자가 헌혈 (autologous donation)

헌혈자 반응 2%, vasovagal reaction 창백, 발한, 탈력감, 현기증, 오심 저혈압, 구토, 졸도, 발작 저칼슘혈증 : 감각이상, 비충혈, 재채기, 홍조 헤파린 : 오한, 비출혈, 출혈, 두드러기, 아나필락시성 쇽 Ethylene oxide : 알레르기성 반응

Alternatives to Donor Blood Autologous blood transfusion Preoperative autologous deposit Preoperative dilution Intraoperative salvage Postoperative salvage Directed donor program Legal, emotional, economic, GVH Indication Contraindication

지정 헌혈(directed donation) 유사한 감염성질환 표지자 양성률 시간적, 경제적 부담 이식편대숙주병(GVHD) 발생 가능성 혈액 관리에 추가의 노력 Contraindication 임신가능 연령 : 남편 골수이식환자 : 친족 신생아용혈성질환 : 부

헌혈 혈액 검사 ABO, Rh(D) HBsAg anti-HCV anti-HIV ALT VDRL 기타 : HTLV-I/II, HIV p24, anti-HBc

Blood Banking Anticoagulants Preservation of cell viability Preservation of cell function

RBC storage lesions Nucleotide depletion Membrane ATP -- ADP -- AMP -/- IMP -- hypoxanthine exogenous adenine and inorganic phosphate Membrane discocyte - ecchynocyte transformation loss of lipids, and small amount of protein, alteration in structural proteins 2,3-DPG(diphosphoglycerate) depletion

Preservation of Blood Anticoagulants Preservative solutions Citrate Heparin Preservative solutions Trisodium citrate : 1 wk ACD (acid citrate dextrose) : 3 wk CPD (citrate phosphate dextrose) : 3 wk CPDA-1 (CPD + adenine) : 5 wk (1991. 3.)

항응고보존액 ACD-B CPDA-1 Sodium citrate 13.2 g 26.3 g Citric acid 4.8 g 3.27 g Dextrose 14.7 g 31.9 g Sodium biphosphate 2.51 g Adenine 0.275 g Blood 100ml 25 mL 14 mL

혈액의 보존 농축적혈구 1-6 oC 35일 세척적혈구 1-6 oC 24시간 신선액상혈장 1-6 oC 12시간

혈액성분제제 농축적혈구 농축혈소판 신선동결혈장 동결침전제제 알부민 면역글로불린 혈액응고인자 (VIII, IX-prothrombin complex) Antithrombin III

혈액성분제제의 제조 전혈 농축적혈구 혈소판풍부혈장 신선액상혈장 신선동결혈장 백혈구제거적혈구, 감마선조사적혈구, 세척적혈구, 동결적혈구 혈소판풍부혈장 농축혈소판 신선액상혈장 신선동결혈장 동결침전제제, 동결혈장 --- 알부민, 면역글로블린 혈액응고인자제제

혈액성분제제의 특성 전혈 : 456 mL (400 + 56) 365 mL (320 + 45) 농축적혈구 : 250 mL (Hct 70%) 혈소판풍부혈장 : 200 mL (5.5 X 1010) 혈소판농축액 : 50 mL (5.0 X 1010) 성분채집혈소판: 200 – 250 mL (>3 X 1011) 신선동결혈장 : 160 mL

Blood Substitutes Perfluorocarbons : Fluosol-DA, Oxygent High oxygen binding Pulmonary toxicity Complement activation RES blocking Chemically modified Hb Partial polymerization: Hemopure Pyridoxal-5-phosphate: PolyHeme

Pretransfusion tests ABO and Rh typing Antibody screening test Antibody identification test Cross matching

Antibody Screening Test Expected Ab : regular Ab Unexpected Ab : irregular Ab Korean : 0.6% (37oC 반응: 0.2%) Lea, P1, Leb, I, E, M, D, P, IH, N, C, e, i, H, Lua, Jka , Jkb 37oC 식염수법 -- 알부민법, -- 항글로불린법 저이온강도식염수법 -- 37oC 식염수법 -- 항글로불린법

Crossmatching Major : 환자의 혈청과 수혈할 적혈구 Minor : 환자의 적혈구와 수혈할 혈청 실온식염수법 저이온강도식염수법 알부민법 항글로불린법 효소법

Problems in Crossmatcing Pseudoaggutination Increased ESR Dysproteinemia Dextran, hydroxyethyl starch Autoagglutination Cold agglutinin Warm reacting autoantibody Polyagglutination Radioisotope crossmatching

Administration of Blood Identification of recipient and donor at bedside Appropriate set with filter: standard : 170 um microaggregate blood filter : 20 - 40 um Aseptic technique First 15 min. Within 4 hr

Blood warming Adult : > 50 mL/kg/hr 소아 : >15 mL/kg/hr 영아의 교환수혈 한냉응집소를 가진 환자 Central catheter를 통한 빠른 수혈

Red cell transfusion Whole blood Red blood cells (packed RBC) Red cell suspension : SAG-M, AS-1,2,3 Leukocyte-depleted RBC (filter) Washed RBC Frozen-thawed-deglycerolized RBC Irradiated RBC

RBC Therapy Indications Whole blood massive bleeding, exchange transfusion Packed RBC anemia Leukocyte-poor prior febrile reaction Washed RBC prior urticarial reaction IgA deficiency PNH (complement) Frozen RBC rare blood type autologous donation disaster

Transfusion guidelines in chronic anemia Stable patient with Hb > 6 - 7 g/dL : no absolute indication for transfusion Unexplained lassitude, malaise, tachycardia, dyspnea with Hb < 9-10 g/dL : consider transfusion Cardiopulmonary disease, fever, surgery : maintain Hb level at 10 g/dL If management protracted (years) : monitor for evidence of iron overload

Sign and Symptom of Blood Loss Volume lost mL % Clinical sign 500 10 None; occasional vasovagal reaction 1000 20 Possibly a slight postural drop in BP Tachycardia with exercise 1500 30 Neck vein flat Postural hypotension 2000 40 Drop in CVP, cardiac output, BP Air hunger, rapid thready pulse, Cold clummy skin 2500 50 Lactic acidosis, severe shock, death

Volume Replacement Crystaloid : saline, Ringer’s lactate Colloid : hydroxyethyl starch, dextran (40, 70) Albumin FFP Plasma

Transfusion in Surgical Patients Optimal hemoglobin concentration Duration of anemia Possibility of blood loss Maximal surgical blood order schedule (MSBOS) Type and screen: ABO, RhD, antibody screening test

Platelet transfusion Platelet rich plasma Platelet concentrate: random donor Apheresis platelet: single donor HLA matched donor Refractoriness

Guidelines for platelet transfusion Platelet < 10,000 - 20,000/mm3 : spontaneous bleeding prophylactic Platelet < 50,000/mm3 with bleeding or minor surgery : platelet transfusion Major surgery : platelet > 80,000/ mm3 Refractoriness : HLA matched donor

Leukocyte transfusion Granulocyte transfusion Hematopoietic growth factor Lymphocyte transfusion LAK cell DLI

Fresh Frozen Plasma (FFP) 160 mL (400 mL + 56 mL CPDA-1) Fibrinogen : 230 - 240 mg/dL Factor V : 119 U/dL Factor VII : 89 - 94 U/dL Factor VIII : 49 - 94 U/dL Factor IX : 84 - 125 U/dL Other factors : 100 U/dL Antithrombin, albumin, protein C, S

Indication for FFP Factor deficiency Rapid reversal of warfarin effect Vitamin K deficiency DIC TTP Antithrombin III, Protein S, C C1 esterase inhibitor deficiency Massive transfusion, liver disease, cardiopulmonary bypass surgery

Cryoprecipitates 60 mL Factor VIII : 96 U Fibrinogen : 372 mg Factor XIII : 20 - 30 % of FFP vWF : 40 - 70 % of FFP Fibronectin

Plasma protein products Albumin Immune globulin, hyperimmune globulin Factor VIII concentrates Factor IX concentrates (prothrombin complex) Fibrin sealants Alpha A1 -proteinase inhibitor Antithrombin III C1-esterase inhibitor Protein C and activated protein C

Factor VIII concentrate Intermediate purity, high purity F VIII(U) = 40 x BW(kg) x {wanted F VIII conc.(%) - patient F VIII conc.(%)}/100 250, 500, 1000 U/BT : 10, 20, 30 ml 8 - 12 hr

Intravenous Immunoglobulin Hypogammaglobulinemia CMV infection in BMT Autoimmune disease (ITP) Adverse reaction First dose effect Flushing, chest tightness, chills, fever, nausea, vomiting, diarrhea, dizziness, wheezing, diaphoresis, hypotension

Hyperimmune globulin RhoGam, WinRho : anti-D Hepatitis B Varicella-zoster virus CMV Other infectious agents

Apheresis Plasma apheresis Leukapheresis Platelet apheresis Peripheral stem cell collection

Transfusion reactions(1) Immunologic transfusion reactions Major (acute) hemolytic reactions Delayed transfusion reactions Febrile nonhemolytic reactions Allergic reactions Noncardiogenic pulmonary edema GVHD Posttransfusion purpura Alloimmunization Immunosuppressive effect

Major Hemolytic Transfusion Reaction ABO incompatibility : clerical error Jka, K, Fya, Rh system Chills and fever within first 30 min, low back pain, chest pain, restlessness, dyspnea, pain at the site of transfusion Tachycardia, hypotension, tachypnea, oliguria, hemoglobiuria, DIC

Management of MHR Stop transfusion immediately but do not remove the IV route Hydration and maintain BP and urine output greater than 100 mL/hr Sample for retyping and cross matching Observe the plasma and urine color DIC study Treatment for renal failure

Transfusion associated GVHD Immunocompromized patients : BMT, acute leukemia, malignant lymphoma etc. Blood donor is homozygous for one of the HLA haplotype of recipient Rash, diarrhea, liver failure, pancytopenia 1,500 cGy irradiation to all blood products

Transfusion reactions(2) Nonimmunologic transfusion reactions Volume overload Hypothermia Hypocalcemia Hyperkalemia Air embolism Coagulation factor deficiency Iron overload : 200-250 mg/U Hypotensive reaction : ACE inhibitor : bradykinin

Transfusion reactions(3) Transfusion-transmitted infections Hepatitis A, B, C, G HIV, HTLV-I CMV, EBV, Parvovirus B-19 Parasitic: malaria, Chaga’s disease, toxoplasma, babesiosis Bacterial: syphilis, Yersinia, Pseudomonas, coagulase negative Staphylococcus, Streptpcoccus, Serratia, Salmonella, E. coli, brucellosis, Lyme disease