Transfusion Medicine. Mar 3, 2018

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1 Transfusion Medicine Mar 3, 2018

2 Objective ร จ ก blood product ใช blood product อย างเหมาะสม Management of complication

3 Donor WB WB = Whole blood PRC = Pack Red Cell PRC PRP PRP = Platelet-rich plasma FFP = Fresh frozen plasma PC = Platelet concentrate FFP PC CRP = Cryo-removed plasma, CRP 1-6 o C Cryo FFP with cryo.-removed Cryo. = Cryoprecipitate (Fibrinogen, FVIII, FXIII, vwf)

4 Donor WB WBC filter Prestorage-filtered blood products PRC FFP PRP PC LPB Leukocyte Poor Blood CRP 1-6 o C Cryo

5 ระหว างรอท หอผ ป วย ข อใดห ามเก บในต เย นเด ดขาด 1.Whole blood 2.Pack red cell 3.Fresh frozen plasma 4.Platelet concentrate

6 Blood Component PLT dysfunction, Coagulation factor decay Vol (ml) Storage Shelf life WB o c 35 d [CPDA-1] PRC o c 21[ACD,CPD], 35, 42 d [AS-1,-3,-5] FFP <-18 o c 1 yr PLT conc o c 5 days Cryo <-18 o c 1 yr

7 Plasma derivatives: FFP, Cryo. No medications added Return to blood bank if not use within 30 min Most adverse transfusion reactions occur in the first 15 min. Time of transfusion not exceed 4 hr Rate in adult (good cardiac condition) : ml/hr NOT for: volume expansion, protein (alb, glob) nutrient

8 ช 60 ป ถ ายดาแดง 1 ว น Cirrhosis Child C, DM, HT BP 80/60, P 115, R 18 Pale, PR marron stool, NG frank blood continuously Hb 8.1 g/dl, Hct 24.3% NSS was loaded, Blood transfusion? 1. PRC 2. WB 3. PFB 4. No transfusion

9 Liberal strategy : Keep Hb >9 g/dl Restrictive strategy : Keep Hb >7 g/dl

10 Exclude : massive exsanguinating bleeding, acute coronary syndrome, symptomatic peripheral vasculopathy, stroke, TIA, recent trauma or surgery, lower GI bleed

11 Survival Keep Hb>7 Keep Hb>9 Days

12

13 ช 55 ป sepsis/pneumonia at ICU โรคเด ม : DM,HTN,DLP BP 130/70, P 90, R 18 On ventilator, FiO O 2 sat 96% Euvolemia, No bleeding Hb 8, Hct 24% (3 mo ago: Hct 39%) Rx anemia 1. PRC 2. LPB 3. Erythropoietin 4. No transfusion

14 Keep Hb Keep Hb 7-9

15 ญ 70 ป Hip Fracture Surgery U/D: HTN, DLP, coronary artery disease 2 years Postop Day 2 BP 130/70, P 90, R 16 No anemic symptom, No bleeding Hb 8.5, Hct 26% Rx anemia 1. PRC 2. PFB 3. Erythropoietin 4. No transfusion (Preop: Hct 34%)

16 No difference: 60-day death rate, walk ability CAD, CHF, stroke, DVT Patients with cardiovascular disease or CVS risk >50 years Compare : Hb >10 vs. >8 g/dl or anemic symptom

17 RBC Transfusion in Hemodynamically Stable Patients: CPG from AABB, NICE In adult and pediatric ICU patients (pt), transfusion (Tf) should be considered at Hb <7 g/dl [recommendation] In postop surgical pt, Tf should be considered at Hb <8 g/dl or for symptoms (chest pain, orthostatic hypotension or tachycardia unresponsive to fluid resuscitation, or CHF) [recommendation] Not address preop. Tf because of expected operative blood loss Ann Intern Med 2012;157:49-58 NICE guideline. 18 Nov 2015

18 RBC Transfusion in Hemodynamically Stable Patients: CPG from AABB, NICE Hospitalized, stable patients (pt): Hb 7-8 g/dl (recommendation) Hospitalized pt with preexisting cardiovascular dis. and considering transfusion for pt with symptom or Hb <8 g/dl (suggestion) Ann Intern Med 2012;157:49-58 Ann Intern Med 2012;157:49-58 NICE guideline. 18 Nov 2015

19 ญ 29 ป เหน อย 2 ส ปดาห เด นไม ไหว 2 ว น BP 100/60, P 125, R 20 Pale, dyspnea, dry lip, mild jaundice, systolic ejection murmur at Lt.2 nd parasternal area gr.ii Hb 3 g/dl, Hct 10%, MCV 125, DCT 4+; spherocyte 2+ Na 140, K 4, Cl 96, HCO 3 18 G/M PRC: no compatible blood Steroid IV, O 2 Other Rx? 1. PRC 2. EPO 3. Rituximab 4. Wait and see

20 RBC Transfusion Symptomatic & supportive Rx for anemia. Anemia RBC transfusion Use only if no definitive Rx or significant symptomatic anemia not able to wait for effects of definitive Rx

21 ช 25 ป หนาวส นมากหล งได ร บเล อด HbH with CS dis ได ร บเล อดเฉพาะช วง ม ไข ไม สบาย ม อาการ หนาวส นมากท กคร ง บางคร งม แน นหน าอก หายใจลาบาก ความ ด นต า Best choice of rbc 1. PRC 2. LPB 3. Irradiated rbc 4. Washed rbc 5. Prestorage filtered rbc

22 Red Blood Cell Components Component Character Indications PRC Leukocytereduced rbc Lower vol; higher Hct Good flow in AS-1 Red cell deficit febrile reaction, CMV, EBV, alloimmunization (prestorage filter ด กว าแต แพง กว า LPB) Washed rbc plasma depleted, use within 24 hr severe allergic reactions, anaphylaxis in IgA def

23 ญ 60 ป CLL Rx: RFC regimen (rituximab, fludarabine, cyclophosphamide) x 4 cycles last 3 weeks ago Hb 6 g/dl, Hct 18%, Wbc 2,500, PLT 55,000, DCT negative Proper choice of rbc 1. PRC 2. PFB 3. Irradiated rbc 4. Washed rbc 5. Frozen rbc

24 Red Blood Cell Components Component Character Washed rbc plasma depleted, use within 24 hr Frozen rbc [glycerol] Irradiated rbc Long-term storage [10 + y] ; plasma & wbc depletion Gy, expired 28 d after irradiation Indications severe allergic reactions, anaphylaxis in IgA def Rare donor unit storage; autologous storage for postponed surgery TA-GVHD : neonate, cong. immunodef, ATG, donor =1 o relative, stem cell transplant, fludarabine

25 RBC Antigen & Plasma Antibody Anti-A Anti-B O Blood group O Blood group B A A Blood group A Blood group AB Anti-B Anti-A B B AB AB

26 ญ 60 ป TTP, Blood gr.ab, Rh-ve Plasmaphereis is planned. FFP choice is limited. Proper choice? 1. FFP gr AB, Rh+ve 2. FFP gr A, Rh-ve 3. FFP gr B, Rh-ve 4. Choice 1.+ Rh immune globulin 5. FFP gr A, Rh-ve, +irradiated

27 RBC Antigen & Plasma Antibody D Rh+ Rh- No Anti-D Blood group Rh+ve No Anti-D Blood group Rh-ve Rh system: Only RBC-containing components (WB, PRC, PC, SDPs) need to be matched for the D-antigen.

28 ญ ๒๒ ป จ าเข ยวท ขา ๑ ส ปดาห ม จ ดเล อดออก และจ าเข ยวท ขาสองข าง ประจาเด อนปกต ไม ก นยาใด ไม ม ไข BP 100/60, P 70, R 14 Not pale, petechiae & ecchymoses at legs, others unremarkable Hb 13, Hct 39%, wbc ปกต, Plt 2,000 [0-1/OF, giant plt] Coagulogram normal Initial Rx 1. PLT conc [PC] 2. PC + steroid 3. Steroid 4. Steroid + IVIg 5. Steroid + IVIg + PLT conc

29 Platelet Products WB donations Platelet concentrates Apheresis Single donor platelets (SDPs)

30 Platelet Products Platelet conc Single Donor PLT Platelets 5.5x x10 11 One adult dose 6 donors 1 donor cost less more Indications Prophylactic, therapeutic PLT alloantibody [crossmatched plt], neonatal alloimmune thrombocytopenia

31 Therapeutic Platelet Transfusion Low platelet Platelet transfusion Symptomatic & supportive Rx NOT definitive Rx (อย าล มแก สาเหต เกล ดเล อดต า และเหต เล อดออก อ นๆ เช น varice, arterial bleed) Consider in actively bleeding with PLT. <50,000/uL or PLT. dysfunction Contraindication: TTP, HIT (heparin-induced thrombocytopenia)

32 PLT Transfusion: CPG from AABB Hospitalized adult patients with therapyinduced hypoproliferative thrombocytopenia PLT <10,000 (strong recommendation; moderate-quality evidence) Elective central venous catheter placement PLT <20,000 (weak; low-quality) Elective diagnostic lumbar puncture PLT <50,000 (weak; very-low-quality) Ann Interrn Med 2015;162:205-13

33 PLT Transfusion: CPG from AABB Major elective nonneuraxial surgery PLT <50,000 (weak; very-low-quality) PLT transfusion for cardiopulmonary bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of PLT dysfunction (weak; very-low-quality) ICH in patient receiving antiplatelet therapy : cannot recommend for or against PLT transfusion (uncertain; very-low-quality) Ann Interrn Med 2015;162:205-13

34 ABO group selection for PLT transfusion ABO of Recipient O A B AB ABO of Donor (in order of preference) O, A, B, AB A, AB (O after plasma removal and resuspension in additive solutions or negative for high-titer anti-a/a,b) B, AB (O after plasma removal and resuspension in additive solutions or negative for high-titer anti-a/a,b) AB (A, B, O after plasma removal and resuspension in additive solutions or negative for high-titer anti-a/a,b) Blood Transfus 2009;7:132-50

35 PLT Refractoriness Non-immune Fever Sepsis Drug eg,amphotericin Active bleeding Splenomegaly DIC Venoocclusive dis Immune Anti-HLA antibodies Anti-HPA antibodies ABO mismatch Autoantibodies Drug eg, heparin PLT alloantibody+ve Cross-matched PLT

36 1-hr Corrected Count Increment CCI = BSA x PLT count increment x Number of PLT transfused ต วอย าง: BSA = 2 PLT count 10,000 40,000/microL PLT conc 9 bags CCI= 2 x 30,000 x x 5.5 x = 12,121 Plt x m 2 /microl - PLT conc 1 bag ม PLT 5.5x SDP ม PLT 3x10 11

37 PLT Refractoriness Corrected Count Increment (CCI) at 1 hr <7,500 (5,000-10,000) or at hr <4,500 If 1-hr CCI is good, but plt count falls back to baseline by hr likely nonimmune cause If 1-hr CCI is poor x 2 times likely immune cause test for PLT Ab

38 ช 16 ป ปวดบวมข อเข าซ าย มา 2 ช วโมง เป นโรค hemophilia A และม blood group AB not pale, swelling+warm+ tenderness at Lt. knee joint Best Rx 1. FFP gr AB 2. CRP gr AB 3. Cryoprecipitate gr O 4. PCC 5. Novoseven R

39 Hemophilia A Factor VIII concentrates Cryoprecipitate FFP DDAVP vwd DDAVP F VIII concentrates บางย ห อ Cryoprecipitate FFP Hemophilia B Prothrombin complex concentrate (PCC) FFP Cryo. Removed Plasma F IX concentrates

40 ช 16 ป Hemophilia A ปวดท องมา 3 ชม. BW 50 kg Right lower quadrant pain and tenderness, cannot extend right hip due to pain, numbness at right upper thigh Hb 11 g/dl Proper Rx 1. Cryo 25 bags 2. Cryo 15 bags 3. Cryo 10 bags 4. Novoseven R 5. DDAVP No factor VIII inhibitor

41 Rx of Bleeding episodes in Hemophilia Site Initial Level (%) Rx Length Joint days Muscle days Hematuria days Retroperitoneal days GI d Neck d Intracranial d

42 Hemophilia A with hemarthrosis 60 kg. Raise F VIII to 40 % 1 u/kg raise 2% F VIII half life = 12 hr Raise 40% -> 20 u/kg = 20x60 = 1200 u Cryo. 12 bags ( cont. 6 bags q 12 hr)

43 Hemophilia B with hemarthrosis 60 kg. Raise F IX to 40 % 1 u/kg raise 1% F IX half life = 24 hr Raise 40% -> 40 u/kg = 40x60 = 2400 u FFP 2400 ml. ( cont ml. q 24 hr)

44 FFP Contain all soluble coagulation factors, albumin, hormones, vitamins After thawing, the activities of clotting factors decrease esp. labile factors (V,VIII)

45 FFP: Indications Multiple acquired coagulation factor deficiency eg, Liver disease, Massive transfusion, DIC (Rx bleed, Before procedure) Rapid reversal of warfarin effect Plasma infusion or exchange for TTP Congenital coagulation defect C1-esterase inhibitor deficiency acute episodes & prophylaxis of angioedema

46 FFP: Not Indicated Immunodeficiency Burns, Wound healing Reconstitution of packed rbc Volume expansion Source of nutrients Bleeding from Heparin/LMWH (consider protamine), fondaparinux

47 DIC Rx cause Bleeding FFP, PLT concentrate Cryoprecipitate raise fibrinogen > 100 mg/dl : 1 bag/5 kg BW raise fibrinogen 100 mg/dl Thrombosis heparin : purpura fulminans, acral/dermal ischemia, retained dead fetus syndrome, giant hemangioma, aortic aneurysm without rupture

48 ช 66 ป STEMI ปวดห วอาเจ ยน หล งฉ ดยา Streptokinase เป นโรค STEMI & CHF ได ร บ streptokinase ต อมา 3 ชม. ปวดห ว อาเจ ยนพ ง BP 170/90, P 90, R 15 Alert, Rt.hemiparesis CBC ปกต CT Brain left parietal hematoma Best Rx 1. FFP 2. Cryoprecipitate 3. Vitamin K i.v. 4. Tranexamic acid

49 Cryoprecipitate: Indications Fibrinogen Hypofibrinogenemia (cong./acq. eg. DIC, snake bite) Massive transfusion with bleeding A component of fibrin glue Reversal of thrombolytic therapy with bleeding Factor VIII Hemophilia A vwf von Willebrand disease Uremic bleeding F XIII deficiency All ABO group acceptable

50 Cryoprecipitate: Misuses Replacement therapy in patients with normal fibrinogen level Reversal of warfarin therapy Rx of bleeding without evidence of hypofibrinogenemia Rx of hepatic coagulopathy Underuse in massive transfusion with dilutional coagulopathy and bleeding

51 General Management of Transfusion Reactions Stop transfusion Keep IV line open with NSS Supportive care: CVS, RS, Renal Symptomatic therapy Blood product labelling Patient identification Contact blood bank laboratory for additional testing Lancet 2016;388:2825

52 Signs & Symptoms of Acute Transfusion Reactions Sign/Symptom Fever Itching, Rash, Urticaria, Wheeze, facial edema SpO 2 <90% Dyspnea, Respiratory distress, Cyanosis Cancer Control 2015;22:16 Possible Dx FNHTR AHTR TRALI Microbial contamination Allergic reaction TACO TRALI AHTR Allergic reaction Microbial contamination TACO TRALI Sign/Symptom Hypertension, Tachycardia Hypotension Pain at IV infusion site, Abdominal/ chest/flank pain Possible Dx TACO AHTR Allergic reaction Microbial contamination TRALI AHTR Allergic reaction FNHTR, febrile nonhemolytic transfusion reaction; AHTR, acute HTR;, TACO, transfusion-associated circulatory overload; TRALI, transfusion-related acute lung injury

53 FNHTR AHTR Allergic reaction Microbial TACO TRALI Fever +,chill +,chill + + Itch, Rash, Urticaria, Wheeze, facial edema SpO 2 <90% + + Dyspnea, Resp. distress, Cyanosis Hypertension, Tachycardia Transient Hypotension Pain at IV infusion site, Abdominal/ chest/flank pain Other Dx by exclusion + + Dark urine, DIC, ARF FNHTR, febrile nonhemolytic transfusion reaction; AHTR, acute HTR; TACO, transfusionassociated circulatory overload; TRALI, transfusion-related acute lung injury

54 Febrile Non-Hemolytic Transfusion Reaction (FNHTR) Dx by exclusion Rx: Antipyretic drug, pethidine Stop transfusion + antipyretic not improve or Temp >2 o C or clinical signs of new bacterial infection consider septic cause improve, no other symptom continue transfusion Prevention: leukocyte reduction Premed with antipyretics does not decrease rate of reactions in most patients Lancet 2016;388:2825

55 Allergic & Anaphylactic Transfusion Reaction Occur within 4 h Most frequently assoc.with PLT transfusion Mild (cutaneous only) H1 antihistamine resolved restart transfusion if symptoms recur, stop transfusion Anaphylactic IM epinephrine; H1 / H2 antihistamine, bronchodilator, hydrocortisone IV Lancet 2016;388:2825

56 Delayed Hemolytic Transfusion Reaction Risk: Hx of rbc alloab (through pregnancy or transfusion exposure) Ab titre decreases to levels undetectable by routine Ab detection testing Second rbc exposure with relevant Ag anamnestic immune response 24 h to 28 days after transfusion hemolysis of donor rbc (Hb not increase, TB, DCT+ve) Dark urine or jaundice (45-50%), fever, chest/abd./back pain, dyspnea, chills, hypertension Lancet 2016;388:2825

57 Acute Hypotensive Transfusion Reaction Abrupt BP drop >30 mmhg within 15 min of transfusion and resolving quickly (within 10 min) after stopping transfusion Activation of intrinsic contact coagulation pathway bradykinin (vasodilator, intestinal smooth muscle contraction) facial flushing, BP drop, abdominal pain Risk: ACEI, bedside leukocyte reduction filter, apheresis, PLT transfusion Rx: stop transfusion, not restart same unit Lancet 2016;388:2825

58 Onset after transfusion TRALI Within 6 h TACO Within 4-6 h Body temp May increase No change BP Hypotension Systolic BP Pulse +/- Tachycardia Clinical exam Rales Leg edema, JVP, S3 Fluid balance +/- Positive Hypoxemia Always Common LVEF or normal CXR Bilateral infiltrates Bilateral infiltrates, cardiomegaly Response to diuretic Minimal Significant

59 Pulmonary edema fluid/plasma protein ratio TRALI TACO >0.75 (exudate) <0.65 (transudate) BNP <250 pg/ml >1200 pg/ml or pre- /post-transfusion BNP ratio >1.5 CVP Normal/unchanged Increased Pulmonary artery occlusion pressure WBC count WBC antibodies <18 mmhg >18 mmhg May show transient leukopenia Cognate donor WBC antibodies support Dx Unchanged Donor WBC antibodies may or may not be present

60 Crit Care Med 2006;34:S109

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