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Transfusion Reactions

Jul 16, 2007 Hemato-oncology 林建廷. Transfusion Reactions. First Blood Transfusions. Harvey Discovered Circulation of Blood. 1628. Wilkins & Lower Transfusions from dog to dog. 1665-’66. 1667. Jean-Baptiste Denis Performed first recorded blood transfusions from animals to humans.

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Transfusion Reactions

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  1. Jul 16, 2007 Hemato-oncology 林建廷 TransfusionReactions

  2. First Blood Transfusions Harvey Discovered Circulation of Blood 1628 Wilkins & Lower Transfusions from dog to dog 1665-’66 1667 Jean-Baptiste Denis Performed first recorded blood transfusions from animals to humans

  3. 19th Century Transfusions James Blundell, Obstetrician 1818 First transfusion of human to human

  4. 20th Century Transfusions 1901 Karl Landsteiner Discovers A, B, O Blood Groups

  5. 20th Century Transfusions 1902 AB Group discovered Importance of crossmatching blood between donor & recipient 1907 Sodium Citrate proposed as anticoagulant 1914 1936 First Blood Bank: Barcelona, Spanish Civil War Levine & Landsteiner, Rh blood Group System 1940

  6. WBC • Neutrophil: cytokine, intracellular pathogen (CMV) • Lymphocyte: alloimmunization, t-GVHD, (EBV) • RBC (malaria) • PLT (bacteria contamination) • Plasma and protein • Coagulation factors • Cytokine Contents in Blood Products

  7. 血液在儲存中的變化? 2,3-DPG 任何一種保存液均是針對RBC的 --CPDA1 --CPD-SAGM K, phospholipid Cytokine 採集 10 20 35 42

  8. 新鮮血比較好？ 概念：--RBC的存活率接近正常--2-3-DPG接近正常--鉀的含量不高。 一般認為CPD-A1保存7天之內的血符合這三個條件。 儘量不輸當天採集的血液：1：HBsAg；HCV；HIV；HTLV-1； ALT檢測；2：梅毒螺旋體在4°C保存3天可滅活。

  9. Risk of Transfusion 輸血中的輸血反應 Iron overload 開始 30分 1小時 1.5小時 Alloimmunization PTP 過敏反應 急性血管內溶血 FNHTR HBV/HCV/HIV Fluid Overload TRALI TA-GVHD 血製品污染

  10. 致命性輸血反應 Fever Acute hemolysis Bacteria污染 過敏反應(Anaphylaxis) TRALI TA-GVHD Dyspnea

  11. Acute hemolysis 突然出現chills、fever、dyspnea、chest pain、tea-color urine。重者出現血壓下降、DIC。 臨床

  12. 機轉 ABO mismatch的RBC transfusion，如A型RBC輸入O型患者體內。 抗原與抗體反應，RBC破裂-Hemoglobinemia及Hemoglobinuria,急性腎小管壞死,血壓下降 。 ABO mismatch只要10 ml以上就可能發生嚴重的intravascular hemolysis，可能會致死

  13. 原因? 工作人員失誤...

  14. Accident waiting to happen? Reported incidents 1/600,000 fatalities 1/30,000 ABO incompatible transfusions 1/12,000 incorrect units administered Near-Miss Events ???????? Kaplan & Battles 2001

  15. 處理 Stop transfusion Keep intravascular volume Diuretics、 監測血壓及呼吸 Steroid 留取血液檢體送血庫

  16. Risk 最高???? Platelet—1/6000 血液製品的細菌污染 輸血中突然出現chills、fever、腹痛、肌痛、腎衰甚至敗血性休克、DIC、 臨床

  17. 原因 細菌可以通過靜脈穿刺過程中進入血袋（前提是消毒不嚴格） 血液成分製備過程中發生. Donor在捐血時處於菌血症期. 唯一須室溫保存的製品??? 預防?

  18. 過敏性輸血反應—Urticaria/ RashAnaphylaxis 頭痛、面部潮紅、蕁麻疹、itching、rash、呼吸困難，嘔吐腹瀉，重者出現支氣管痙攣及喉頭水腫, angioedema。 臨床

  19. 機轉 IgE-mediated、受血者針對血品中血漿蛋白成分發生的抗原-抗體反應。 組織肥大細胞(mast cell)及嗜鹼細胞(basophil)釋放histamine引起呼吸及消化道平滑肌收縮及血管擴張。 在血小板濃縮液中組胺濃度較高。

  20. 預防 • Vena • Steroid • Washed RBC • Filter????

  21. Febrile non-hemolytic transfusion reaction (FNHTR) 發熱性非溶血性輸血反應 輸血中或輸血後(可達數小時)在排除其它因素影響下體溫升高1℃以上 RBC輸注的1-3%，血小板輸注的30% 多數輕微& self-limited(8-10h)

  22. 原因 • 血液儲存中WBC產生的cytokine（IL-1β, IL-6, and TNF-α ),尤其是: • 血小板 • 儲存越久者

  23. 處理 • D/D acute hemolysis, bacteria contamination • Acetaminophen • Steroid • 如出現過發熱性輸血反應（FNHTR）,再次輸血導致fever機會是1/8,建議應用去除WBC血液成分。 • --Filter--減白PLT, 減白RBC--Washed RBC

  24. Transfusion-related acute lung injury (TRALI) 輸血相關性急性肺損傷 輸血相關性死亡的第三位 發生頻率：1/1000to 1/4500

  25. 臨床 • 在輸血開始後1-6小時發生，從輕度的呼吸困難到非心源性肺水腫(non-cardiogenic lung edema) • 寒戰、發熱、呼吸困難及血壓下 • Almost all blood products can cause TRALI: WB-PLT > FFP > pRBC

  26. “TRALI” • ALI (AECC, 1992) • Acute onset • Hypoxemia (PaO2/FiO2≦300 or SpO2<90% on room air) • Bilateral infiltrates on CXR • No evidence of LA hypertension (ie. Circulatory overload, wedge< 18 mm-Hg) • No preexisting ALI before transfusion • During or ＜6 hrs of transfusion (most common 1-2 hr) • No alternative risk factor for ALI • “Possible TRALI” • ALI • No preexisting ALI before transfusion • During or ＜6 hrs of transfusion • Alternative risk factor for ALI Diagnostic Criteria of TRALI

  27. 機轉 • 血液製品中anti-HLA I/II or anti-neutrophil Ab • 對抗受血者WBC，使活化的WBC產生黏附分子(CD11/CD18)並黏附與肺內皮細胞，間質滲出，neutrophil釋放cytokine/ enzyme，毛細血管permeability增加 ，肺水腫

  28. NEJM 2000;341:1334-1349

  29. 處理 Stop transfusion O2(Intubate if necessary) 。 Steroid?? Diuretic?? 供者HLA或中性粒細胞特異性抗體檢測

  30. Severity: mild ~ severe • 100% required O2 support • 72% required mechanical ventilation • 5-10% mortality (40% for ARDS) • Severity not correlate with volume infused (only 10-15 cc plasma is enough) TRALI Course Transfusion. 1985;25:573-577.

  31. Resolution rapidly • 80% pts resolved within 96 hrs • 20% pts required longer support＞ 7 days • Survivors: • No long-term sequelae TRALI Course

  32. 預防 • Filter?? • Washed RBC • PLT & FFP & IVIG 怎麼辦?? • 新鮮的製品較佳 • 此Donor不宜繼續為donor…

  33. 負荷過量Fluid overload 發生頻率：1/100-1/700輸血

  34. 臨床 • 輸血過程中出現dyspnea、tachycardia及saturation decrease，尤其在老年人及poor RFT易發生。 • 除非有active bleeding，儘量不要快速輸血。

  35. 處理 預防 LMNO --Lasix --Morphine --NTG --O2

  36. 使血品中的lymphocyte inactivation；但granulocyte中的CMV仍然存在。 • 正常情形下: 血品中的lymphocyte會被recipient的防衛系統給消滅。 • Immunocompromised pts: 可能有一部分血品的lymphocyte可以在recipient中存活, 反過來對抗recipient的組織(t-GVHD), 嚴重時會致死，且致死率頗高 • 何時該電血? • Immunocompromised pt • 近親輸血 • 哪些血液製品要電血? • RBC & PLT (FFP, cryopricipitate不必) 電血的目的及使用

  37. Filter目的? • 濾掉WBC (granulocytes、lymphocytes)，但未被濾掉的lymphocyte仍具活性（較少t-GVHD） • 將在granulocytes中的CMV過濾掉 • 濾掉WBC，減少cytokine，減少FNHTR （已釋出在血品中的cytokine則無法拿掉） • 何時該用Filter? • 降低FNHTR • 減少將來產生抗體產生的機會 • 需要濾掉granulocyte 中的CMV時ex. Post-BMT patient怕CMV infection or CMV disease Filter的目的及使用

  38. 何謂『減白血小板』? • 因在儲存前已拿掉WBC，故被釋放到血品中的cytokine已盡可能減少 • 何時該用『減白血小板』? • 何謂『washed RBC』? • 將血品中的plasma完全以N/S來取代，所以無法提供RBC足夠的energy，故RBC的儲存時間很短（＜24 hrs），需特別訂製。特點是幾乎將全部的WBC及cytokine移除。 • 何時該用『washed RBC』? 特殊血液製品

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