輸血後疑似TRALI案例報告 台中榮民總醫院病理檢驗部 血庫 謝獻旭

Case Presentation (1) MER case Chief complaint Present illness Admission Date 99/03/19 Age 54 year(s) old Female Chief complaint Acute onset of persistent Gum bleeding for 4-5 days Present illness Increased episodes of common cold in recent months Fatique, weakness, sorethroat, and poor appetite developed she noted that she has ecchymosis easily after trauma.(搥背後會有瘀青) for weeks In recent one week, sudden onset of persistent gum bleeding was noted Past history Hypertension under regular medication HBV carrier

Lab. Data (1) CBC: Other’s DIC profiles (+) leukocytosis(WBC=15100/cumm), anemia(Hb=7.7 g/dl), and thrombocytopenia(plt=10000/cumm) DC：Blast: 2%, promyelocyte: 69%, myelocyte: 4%, meta.: 1%, band: 2%, segment: 8%, lymphocyte: 13%, monocyte: 1% Other’s DIC profiles (+) Prothrombin time : ( C: 10.3 SEC P: 15.7 SEC) INR: 1.51 R (0.85-1.15); APTT : ( C: 27.4 SEC P: 27.9 SEC) (24.3-32.7) D-Dimer : 5507 ug/L D.D.U ( < 324 ug/L D.D.U) Fibrinogen < 100

Lab. Data (2) CRP: 12.16 mg/dL ( < 0.3 mg/dL) LDH: 970 U/l (120-240) BM aspiration & biopsy: acute promyelocytic leukemia Flow cytometry: CD33(+); HLDR (-) Meta-phase cytogenetic data: t(15;17)

Hospital Course Diagnosis: Acute promyelocytic leukemia (FAB classification: M3) Initial treatment: All-trans-retinoid acid (ATRA)(dose :45mg/m2 /day) Blood transfusion: 2 Unit packed RBC 8 Units FFP + 1 unit Plateletpheresis After blood transfusion she suffered from acute onset of dyspnea hypoxia and hypotension Transfer to ICU

CXR Before Transfusion After Transfusion Chest X ray looks like ARDS(Acute Respiratory Distress Syndrome )

TRALI Definition New ALI： Acute onset Hypoxia O2sat≦90％ on room air Bilateral infiltrates on frontal chest radiograph No evidence of atrial hypertension Onset of symptoms within 6 hours of transfusion No preexisting ALI before transfusion

TRALI:What are the triggers?

Leukocyte Antigens Implicated in TRALI Leukoagglutinins HLA antibodies Neutrophil-specific antibodies Human Neutrophil Antigens HNA-1 (1a, 1b, 1c) HNA-2 HNA-3 (3a,2009) HNA-4 (2009) HNA-5 (2009) Human Leukocyte Antigens HLA Class I HLA Class II

Bioactive Lipids Accumulate during the storage of cellular blood products (lysophosphatidylcholine, L-PC) Prime neutrophils: primed neutrophils have a greater response to activating agents Enhance neutrophil-mediated lung injury in animal models Prospective and retrospective studies have found greater levels of bioactive lipids in TRALI implicated units or post-transfusion sera from TRALI patients than controls Silliman et al. Transfusion. 1997;37:719-26 Silliman et al. Blood. 2003;101:454-62

Levels increase in stored platelets Primes neutrophils Soluble CD40L Released by platelets Levels increase in stored platelets Primes neutrophils Inhibition of CD40-CD40L system reduces acute lung injury in animal models A case-control study found higher sCD40L levels in TRALI-implicated units than in control units Khan et al. Blood. 2006;108:2455-62

Clinical Management Stop the transfusion Respiratory Support Supplemental oxygen Mechanical ventilation Pressor agents Rule out of other causes of respiratory distress No evidence of role for diuretics or steroid

TRALI: Clinical Course Symptoms generally resolve in 24 to 48 hours Symptoms may resolve before diagnosis is made Mortality 10% to 50% Moore SB. Critical Care Medicine 2006; 34: S114-117 Rana R et al. Transfusion 2006;46:1478-1483

Patient Factors TRALI is more common in Surgery patients Patients with hematological malignancies and cardiac disease Moore. Crit Care Med 2006; 34: S114-S117 Silliman et al. Blood 2003; 101:454-462

TRALI:Most Frequently Implicated Blood Product Red Blood Cells Fresh Frozen Plasma Platelet Concentrates Apheresis Platelets

SHOT Annual Report 2009

SHOT Annual Report 2009

There is no diagnostic test for TRALI and it is easily confused with other causes of acute lung injury, circulatory overload or infection

TRALI (Transfusion-Related Acute Lung Injury ) TACO (Transfusion-Associated Circulatory Overload )

TACO (Transfusion-Associated Circulatory Overload ) 在短時間內輸血量超過病人生理之耐受量 易發生於： 慢性貧血而血液體積正常者 老年者 心臟功能不佳者 Acute respiratory distress Acute or worsening pulmonary edema Evidence of positive fluid balance. Tachycardia Increased blood pressure

TRALI (Transfusion-Related Acute Lung Injury ) TACO (Transfusion-Associated Circulatory Overload ) ATRA syndrome

臨床發現以all-trans-retinoic acid (簡稱ATRA) 治療APL可達高緩解率，並可減少出血性併發症。 All-trans-retinoid acid (ATRA) 臨床發現以all-trans-retinoic acid (簡稱ATRA) 治療APL可達高緩解率，並可減少出血性併發症。 2 doses of ATRA 2 doses of ATRA 2 doses of ATRA

ATRA syndrome is an unpredictable but frequent complication of the use of ATRA to treat APL. Prominent respiratory distress with concurrent symptoms that are often less immediately appreciable, may lead to the misdiagnosis JASON P. et al Psychosomatics 2006 47:450-451

Diagnosis of ATRA syndrome association of at least three of the following signs weight gain fever respiratory distress lung infiltrates pleural or pericardial effusion hypotension renal failure S de Botton et al Leukemia (2003) 17, 339–342.

CXR (after steroid treatment) 99/03/22 99/03/23 99/03/26

TRALI (Transfusion-Related Acute Lung Injury ) TACO (Transfusion-Associated Circulatory Overload ) ATRA syndrome Atypical pneumonia

Discussion TRALI => Steroid +通報捐血中心 TACO => Diuretics + ICU ATRA syndrome => Steroid + DC drug Atypical pneumonia=> Antibiotics

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