Transfusion Medicine

Mar 3, 2018

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

ระหวางรอทหอผปวยขอใดหามเกบในตเยนเดดขาด

1.Whole blood

2.Pack red cell

3.Fresh frozen plasma

4.Platelet concentrate

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

ช 60 ป ถายด าแดง 1 วน

• 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

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

ช 55 ป sepsis/pneumonia at ICU

• โรคเดม : DM,HTN,DLP

•BP 130/70, P 90, R 18

•On ventilator, FiO2 0.4

•O2 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

Keep Hb 7-9

Keep Hb 10-12

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%

(Preop: Hct 34%)

Rx anemia

1. PRC

2. PFB

3. Erythropoietin

4. No transfusion

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

ญ 29 ป เหนอย 2 สปดาห เดนไมไหว 2 วน

• BP 100/60, P 125, R 20

• Pale, dyspnea, dry lip, mild

jaundice, systolic ejection

murmur at Lt.2nd parasternal area gr.II

• Hb 3 g/dL, Hct 10%, MCV

125, DCT 4+; spherocyte 2+

• Na 140, K 4, Cl 96, HCO3 18

• G/M PRC: no compatible blood

Steroid IV, O2

Other Rx?

1. PRC

2. EPO

3. Rituximab

4. Wait and see

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

ช 25 ป หนาวสนมากหลงไดรบเลอด

•HbH with CS dis ไดรบเลอดเฉพาะชวง

มไขไมสบาย มอาการ

หนาวสนมากทกคร ง

บางคร งมแนนหนาอก

หายใจล าบาก ความ

ดนต า

Best choice of rbc

1. PRC

2. LPB

3. Irradiated rbc

4. Washed rbc

5. Prestorage filtered

rbc

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

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

Red Blood Cell Components

Component Character Indications

Washed rbc plasma

depleted, use within 24 hr

↓severe allergic reactions,

↓anaphylaxis in IgA def

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

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

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.

ญ ๒๒ ป จ าเขยวทขา ๑ สปดาห

• มจดเลอดออก และจ าเขยวทขาสองขาง ประจ าเดอนปกต ไมกนยาใด ไมมไข

• 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

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

ABO group selection for PLT 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

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 ม PLT 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

ช 16 ป ปวดบวมขอเขาซาย มา 2 ชวโมง

• เปนโรค 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. NovosevenR

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

ช 16 ป Hemophilia A ปวดทองมา 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

• No factor VIII inhibitor

Proper Rx

1. Cryo 25 bags

2. Cryo 15 bags

3. Cryo 10 bags

4. NovosevenR

5. DDAVP

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

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

ช 66 ป STEMI ปวดหวอาเจยน หลงฉดยา Streptokinase

• เปนโรค STEMI & CHF ไดรบ streptokinase ตอมา 3 ชม. ปวดหวอาเจยนพง

• 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

5. 1+3+4

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

FNHTR AHTR Allergic

reaction

Microbial TACO TRALI

Fever +,chill +,chill + +

Itch, 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

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)

• 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

• 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 after transfusion hemolysis of donor rbc (Hbnot 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

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