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