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Transfusion Medicine
Mar 17, 2019
ยงยง ชนธรรมมตร
Objective
• รจก blood product
• ใช blood product อยางเหมาะสม
• Management of complication
WB
PRC PRP
FFP PC
CRP Cryo
WB = Whole blood
PRC = Pack Red Cell
PRP = Platelet-rich plasma
FFP = Fresh frozen plasma
PC = Platelet concentrate
CRP = Cryo-removed plasma,
FFP with cryo.-removed
Cryo. = Cryoprecipitate
1-6oC
(Fibrinogen, FVIII, FXIII, vWF)
Donor
WB
PRC PRP
FFP PC
CRP Cryo
WBC filter
1-6oC
Prestorage-filtered
blood products
≠ LPB
Leukocyte
Poor
Blood
Donor
Blood ComponentVol (ml) Storage Shelf life
WB 500 1-6oc 35 d [CPDA-1]
PRC 180-200 1-6oc 21[ACD,CPD], 35, 42 d [AS-1,-3,-5]
FFP 200-280 <-18oc 1 yr
PLT conc 50 20-24oc 5 days
Cryo. 10-15 <-18oc 1 yr
PLT dysfunction,
Coagulation factor decay
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) : 200 - 300 mL/hr
• NOT for: volume expansion, protein (alb, glob) nutrient
Liberal strategy : Keep Hb >9 g/dL
Restrictive strategy : Keep Hb >7 g/dL
Exclude : massive exsanguinating bleeding,
acute coronary syndrome, symptomatic
peripheral vasculopathy, stroke, TIA, recent
trauma or surgery, lower GI bleed
Survival
Days
Keep Hb>7
Keep Hb>9
Keep Hb 7-9
Keep Hb 10-12
Patients with cardiovascular disease or CVS risk
>50 years
Compare : Hb >10 vs. >8 g/dL or anemic symptom
No difference:
60-day death rate, walk ability
CAD, CHF, stroke, DVT
RBC Transfusion in Hemodynamically Stable Patients: CPG from AABB, NICE
• In adult and pediatric ICU patients (pt), transfusion (Tf) should be considered at Hb <7g/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
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;157:49-58Ann Intern Med 2012;157:49-58
NICE guideline. 18 Nov 2015
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
Red Blood Cell Components
Component Character Indications
PRC Lower vol; higher Hct
Red cell deficit
Leukocyte-reduced rbc
Good flow in AS-1
↓febrile reaction, ↓CMV,
↓EBV, ↓alloimmunization (prestorage filter ดกวาแต แพงกวา LPB)
Washed rbc plasma
depleted, use within 24 hr
↓severe allergic reactions,
↓anaphylaxis in IgA def,
Post-transfusion purpura
Red Blood Cell Components
Component Character Indications
Washed rbc plasma
depleted, use within 24 hr
↓severe allergic reactions,
↓anaphylaxis in IgA def,
Post-transfusion purpura
Frozen rbc
[glycerol]Long-term
storage [10+y]
; plasma & wbc depletion
Rare donor unit storage;
autologous storage for postponed surgery
Irradiated rbc
25-30 Gy,
expired 28 d
after irradiation
↓TA-GVHD : neonate,
cong. immunodef, ATG,
donor =1o relative, stem
cell transplant, fludarabine
RBC Antigen & Plasma Antibody
O A
B AB
A
B AB
Anti-A
Anti-BAnti-B
Anti-A
Blood group O
Blood group ABBlood group B
Blood group A
ABO Group Selection for RBC Transfusion
ABO Group Selection for Plasma Component Transfusion
ABO Group Selection for Platelet Transfusion
ABO of
Recipient
ABO of Donor (in order of preference)
O O, A, B, AB
A A, AB (O after plasma removal and
resuspension in additive solutions or
negative for high-titer anti-A/A,B)
B B, AB (O after plasma removal and
resuspension in additive solutions or
negative for high-titer anti-A/A,B)
AB 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
RBC Antigen & Plasma Antibody
Rh+ Rh-
D
No Anti-D No Anti-D
Blood group Rh+ve Blood group Rh-ve
Rh system: Only RBC-containing components
(WB, PRC, PC, SDPs) need to be matched for the D-antigen.
Platelet Products
• WB donations Platelet concentrates
• Apheresis Single donor platelets (SDPs)
Platelet Products
Platelet conc Single Donor PLT
Platelets 5.5x1010 3x1011
One adult dose 6 donors 1 donor
cost less more
Indications Prophylactic, therapeutic
PLT alloantibody
[crossmatched plt] ,
neonatal alloimmunethrombocytopenia
Therapeutic Platelet Transfusion
• Low platelet ≠ Platelet transfusion
• Symptomatic & supportive Rx
• NOT definitive Rx (อยาลมแกสาเหตเกลดเลอดต า และเหตเลอดออกอนๆ เชน varice, arterial bleed)
• Consider in actively bleeding with PLT. <50,000/uL
or PLT. dysfunction
• Contraindication: TTP, HIT (heparin-induced
thrombocytopenia)
PLT Transfusion: CPG from AABB
• Hospitalized adult patients with therapy-induced 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
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
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
1-hr Corrected Count Increment
- PLT conc 1 bag มPLT 5.5x1010
- SDP ม PLT 3x1011
BSA x PLT count increment x 1011
Number of PLT transfusedCCI =
ตวอยาง: BSA = 2
PLT count 10,000 40,000/microL
PLT conc 9 bags
CCI= 2 x 30,000 x 1011
9 x 5.5 x 1010
= 12,121 Plt x m2/microL
PLT Refractoriness
• Corrected Count Increment (CCI)
at 1 hr <7,500 (5,000-10,000) or
at 18-24 hr <4,500
• If 1-hr CCI is good, but plt count falls back
to baseline by 18-24 hr likely
nonimmune cause
• If 1-hr CCI is poor x 2 times likely
immune cause test for PLT Ab
Hemophilia A
• Factor VIII concentrates
• Cryoprecipitate
• FFP
• DDAVP
Hemophilia B
• Prothrombin complex
concentrate (PCC)
• FFP
• Cryo. Removed Plasma• F IX concentrates
vWD
• DDAVP• F VIII concentrates บางยหอ• Cryoprecipitate• FFP
Rx of Bleeding episodes in Hemophilia
Site Initial Level (%) Rx Length
Joint 40 1-2 days
Muscle 40 2-3 days
Hematuria 50 3-5 days
Retroperitoneal 80-100 5 days
GI 80-100 7-14 d
Neck 80-100 7-14 d
Intracranial 80-100 14-21 d
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)
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. 1200 ml. q 24 hr)
FFP
•Contain all soluble coagulation
factors, albumin, hormones,
vitamins
•After thawing, the activities of
clotting factors decrease esp.
labile factors (V,VIII)
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
FFP: Not Indicated
• Immunodeficiency
• Burns, Wound healing
• Reconstitution of packed rbc
• Volume expansion
• Source of nutrients
• Bleeding from Heparin/LMWH (consider protamine), fondaparinux
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
All ABO group acceptable
deficiency
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
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
Signs & Symptoms of Acute Transfusion Reactions
Sign/Symptom Possible Dx
Fever FNHTR
AHTR
TRALI
Microbial contamination
Itching, Rash,
Urticaria, Wheeze,
facial edema
Allergic reaction
SpO2 <90% TACO
TRALI
Dyspnea,
Respiratory
distress, Cyanosis
AHTR
Allergic reaction
Microbial contamination
TACO
TRALI
Sign/Symptom Possible Dx
Hypertension,
Tachycardia
TACO
Hypotension AHTR
Allergic reaction
Microbial
contamination
TRALI
Pain at IV
infusion site,
Abdominal/
chest/flank pain
AHTR
Allergic reaction
Cancer Control 2015;22:16
FNHTR, febrile nonhemolytic transfusion
reaction; AHTR, acute HTR;, TACO,
transfusion-associated circulatory
overload; TRALI, transfusion-related
acute lung injury
Acute transfu-
sion reactions
FNHTR AHTR Allergic
reaction
Microbial TACO TRALI
Fever +,chill +,chill +,chill +
Itching, Rash,
Urticaria, Wheeze,
facial edema
+
SpO2 <90% + +
Dyspnea, Resp.
distress, Cyanosis+ + + + +
Hypertension,
Tachycardia
Tran-
sient+
Hypotension + + + +
Pain at IV infusion
site, Abdominal/
chest/flank pain
+ +
Other Dx by
exclusionDark urine,
DIC, ARF
PLT conc
> RBC
FNHTR, febrile nonhemolytic transfusion reaction; AHTR, acute HTR; TACO, transfusion-
associated circulatory overload; TRALI, transfusion-related acute lung injury
Febrile Non-Hemolytic Transfusion Reaction (FNHTR)
• Rise in Temp. > 1oC
• Dx by exclusion
• Rx: Antipyretic drug, pethidine
• Stop transfusion + antipyretic • not improve or Temp↑ >2oC or clinical signs of new
bacterial infection consider septic cause
• improve, no other symptom continue transfusion
• Prevention: leukocyte reduction before storage
• Premed with antipyretics does not decrease rate of reactions in most patients
Lancet 2016;388:2825
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
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 (มก 3-7 d) 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
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
• DDx: AHTR, microbial contamination, anaphylactic, TRALI
Lancet 2016;388:2825
TRALI TACO
Onset after
transfusion
Within 6 h 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
TRALI TACO
Pulmonary edema
fluid/plasma
protein ratio
>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
<18 mmHg >18 mmHg
WBC count May show transient
leukopenia
Unchanged
WBC antibodies Cognate donor
WBC antibodies
support Dx
Donor WBC
antibodies may or
may not be present
Crit Care Med 2006;34:S109