adverse effects of plasma therapy

8/6/2019 Adverse Effects of Plasma Therapy

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Adverse effects

ofPlasma Therapy


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Adverse Effects of Plasma Usage

VolumeAntibodies

and

other Proteins

CYTOKINESCELLUL

ARCONTE

NT

CONTAMINANTS

ORGANISMS


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It is Important to Diagnosebecause..

How To Manage?

What to do with current Transfusion?

What all investigations to be done?

When and How to give next transfusion?

Does the patient need any special blood

products in future?


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Immediate

Allergic Reactions

Anaphylactic/Anaphylactoid

Febrile Non Hemolytic Transfusion Reactions

Hemolytic Transfusion Reactions

TRALI

TACO

Bacterial Contamination


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Delayed

Transfusion Transmitted Diseases

Transfusion Related Immuno Modulation


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Rare with FFP

RBC ALLOIMMUNISATION

TA-GVHD


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FREQUENCY

Allergic-1 in 33 to 1 in 100

FNHTR-1 in 100

Anaphylactic -1 in 20,000 to 50,000

HTR-1 in 12,000-20,000 TRALI-1 in 5000-10,000

TACO-1 in 150


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Allergic Reactions

Type 1 immediate hypersensitivity reaction

Immediately after transfusion

Atopic individuals more prone

Histamine and leukotriene mediated

MILD

ALLERGIC

SEVERE

systemic

ANAPHYLACTIC


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Mechanism

IgE antibodies in recipient react withproteins in transfused plasma

IgE antibodies in donor Reacts with

proteins in recipient plasma Rarely due to chemicals in bag/tubing


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Treatment

Transfusion temporarily discontinued

IV /oral antihistaminic

Diphenhydramine 25-50mg

PM/CPM Resume within 30 minutes in presence of doctor

Develops generalised urticaria,hypotension,facial/laryngeal edema -discontinue

Adrenaline if needed


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Prevention

Premedication with anti histamine(oral/parenteral) -only for those with >2 episodes of allergic reactions

May be donor induced

Masks some hemolytic symptoms

25-50 mg Pheneramine/diphenhydramine half to 1 hrbefore transfusion

if found ineffective -hydrocortisone 100 mg Remove plasma by washing from other

products(RBC,Platelets)


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Anaphylactic/AnaphylactoidReactions

Rapid

Serious Life Threatening

Transfusion of Few ml is enough

Systemic nature and severitydifferentiates from allergic


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Difference

Anaphylactic

Allergen in plasma reacts with Ig E in recipient

Anaphylactoid Allergen in plasma reacts with non IgE

antibodies in recipient


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Anaphylactoid reaction due to IgAdeficiency

The best documented reason for anaphylactoid reactions

IgA deficient individuals-1 in 700

Reaction frequency lower- 1 in 20,000-50,ooo

Mechanism antibodies against IgA in recipients body Other protein deficiencies

Complement

VwF

Haptoglobin


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URTICARIA

GENERALISED ITCHING

PRURITUS

ANGIOEDEMA

COUGH

HOARSENESS OF VOICE

STRIDOR ,RESPIRATORY OBSTRUCTION

WHEEZING,

CHEST TIGHTNESS

CRAMPS

NAUSEA

VOMITING

DIARRHOEA

HYPOTENSION

TACHYCARDIA

ARRYTHMIA

CARDIAC ARREST

IMMEDIATE

DRAMATIC ONSET

SYSTEMIC&

CUTANEOUS

SYMPTOMS

OTHER CAUSES

SHOULD BE RULED

OUT

INVESTIGATIONS

NOT MUCH,MAINLY CLINICAL

TRYPTASE LEVELS

IgA LEVELS

SKIN

RESPIR

ATORY

ABDOMI

NAL

CARDIAC


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Management

STOP the Transfusion,should not RESTART

Medical emergency

Same for anaphylactic and Anaphylactoid

Adrenaline

.3-.5 ml , 1:1000 s/c or IM

Severe hypotension,laryngel edema/resp.failureIV 1:10000

Oxygen,B agonist &/theophylline

Maintain BP

Trendelenberg

Fluids,

Dopamine

CONSIDER COINCIDENTIAL

OCCURRENCE

MyocardiaI Infarction?PulmonaryEmbolism?

Or something else?


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PREVENTION

Saline washed blood components-RBC&Platelets

Plasma Transfusion -only If unavoidable

Only IgA deficient plasma should be given to IgA deficientindividuals

Screen the family members

WHAT TO DO WITH NON IgA

DEFICIENT RECURRENT SEVERE

ANAPHYLACTICS?


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HYPOTENSIVE REACTIONS IN ACEINHIBITOR USERS

Mimics Anaphylaxis

Metabolism Bradykinin in transfusedplasma/PPF/Albumin -inhibited by ACE

Inhibitor Activation by prekalleikrein activator in

plasma

A/s with large volumes TPE etc

Also seen in Certain leukoreduction filters

Dialysis membranes

Immunoabsorption columns


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Febrile NonHemolytic TransfusionReactions

Increase in body temperature of 1C or more

During or within several hours of transfusion

Unrelated to hemolysis, sepsis, or other known

causes of fever. Frequency 1 in 100


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SIGNS AND SYMPTOMS

Early in transfusion or delayed

Fever

Chills and Rigors

Important d/d bacterial contamination,HTR

RARELY..

HYPOTENSION

TACHYCARDIATACHYPNOEA,DYSPNOEA,CYANSIS AND COUGH

LEUKOPENIA


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MECHANISMS

1.Antibodies in recipient plasma (usually anti HLA)

Acts against transfused HLA carrying cells-Lymphocyte,Granulocyte,platelets.

Cytokine Release 2.Antibodies in donor plasma-Rare

Acts agains recipient cells

Cytokine release

3.Infusion of Cytokines already accumulated in plasmaduring storage.

H/O BLOOD TRANSFUSION

H/O PREGNANCY


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Treatment

Transfusion discontinued

IV line kept patent

Antipyretics Paracetamol

ANTIHISTAMINES Are not of Use-most FNHTRsdoesnt involve histamine release

Restart ?


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BACTERIAL CONTAMINATION

50-250 fold more risk than TTD

Important cause of transfusion morbidity and mortality

Immediate or hours later,depends on the load

Maximum with platelets-PC and PRP(room temperature) 1 in 1000

Staph epidermidis

Bacilleus cereus


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Frozen products

More with cryoprecipitate-cryobath

Pseudomonas cepacia

Pseudomonas aeruginosa

Less with frozen plasma-temperature


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Symptoms

Fever

Chills

Rigor

Tachycardia

Hypotension

Low back pain

SHOCK

DIC

Diagnosis

SEND THE UNIT FOR GRAM STAIN-

MAY NOT PICK UP CULTURE

BLOOD CULTURE OFPATIENT


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Treatment

Delay in diagnosis if symptoms occur hours later

Start IV antibiotics and other supportive treatment


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Prevention Blood bank

Careful donor selection,not even trace evidence of viremiaaccepted

Sterile phlebotomy

Diversion pouch Storage

Look for appearance of blood product-not useful much in plasma

Colour change

hemolysis

After thawing should not be kept outside>4 hrs Should not immerse in water for thawing

Take care when transporting


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Hemolytic Transfusion Reaction

IMMUNE

Donor antibodies

Alternate group

Error

Inventory

Infants

BMT Dangerous O

Irregular hemolysingantibodies in donor

NON IMMUNE

Lysed RBCs transfused


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TREATMENT

Stop and do not restart

PROMPT IDENTIFICATION AND TREATMENT

Send the unit and sample

Liberal fluids Keep urine flow rate 1ml/kg/hr

Furosemide 40-80 mg IV

Low dose dopamine

Antipyretics

No response ? Consult nephro

Watch for DIC

Document


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PREVENTION in case of plasmatransfusion

Careful in alternate groups-plasmareduction for other products

Titration whenever needed esp exchange

Minor cross match Donor selection

Avoid clerical and ID errors


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How to differentiate febrileReactions

FNHTR IHTR BACTERIALCONTAMINATION

FEVER,CHILLS FEVER,CHILLS FEVER,CHILLS

Mild to moderate subside

with antipyretic

All invg.NEGATIVE

ANTI HLA Ab +

Mild to Severe

MAY NOT RESPOND

DCT +

Ab screen positive

Mild to severe

May not respondto antipyretic

Evidence of HemolysisGRAM STAIN

CULTURE +

See the product

Other recipients


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TRALI

Non cardiogenic Pulmonary edema

1 in 5000 to 10,000

5-10% fatal

SIMILAR TO ARDS RDP

WBC

APHERESIS

FFP

CRYO

GRANULO


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TRALI

A /c respiratory insufficiency and sudden deterioration inlung function

Hypoxemia PaO2/FIO2


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Chest tightness

Breathlessness

Dry cough

Tachypnoea

Tachycardia

Hypotension

Widespread creps

on chestauscultation

Nausea

Dizziness

fever -may develop laterRigor -not always

Copious frothy tracheal exudate on

suction

Like lightly whipped egg white

Hall mark of severe TRALI

CHEST X RAY

Nodular ShadowingBAT WING pattern

(ARDS)

Hypoxia

Hypercapnea

Leukopenia

Anti HLA antibody

Normal BNP

PA occlusion Pressure less


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A Different Presentation

Typically with cellular components

Usually within 30 mt

Fever and chills

Transient respiratory dysfunction Pulmonary Edema Not always demonstrated

Hypertension not Hypo

Recovery within 1-2hrs

Anti HNA -2a?


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Mechanism of TRALI

Antibodies in donor react with recipient antigens

HLA class 1 or 11

HNA-neutrophil antigens

Antgens on Monocytes /pulmonarymacrophages/Platelets

Antibodies in Recipient reacts with donor antigens


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COMPLEMENT

Direct lung injury

C3 a C5a Histamine and serotonin

released from basophils&platelets

LEUCO

AGGLUTINATES

Clog the pulmonarycapillary bed

CAPILLARY DAMAGE

AND LEAK

INTERSTITIAL EDEMA

OF LUNG

FLUID IN ALVEOLAR

SPACE

TRALI


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2 HRS 24 HRS

TRALI


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Management

In all A /c pulmonary reactions transfusion should bestopped

TRALI-Should not be restarted even after symptomsabate

Correct hypoxemia

O2 therapy

Ventilatory assistance if necessary

Symptomatic Most patients recover within 2-4 days


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Prevention

Leuco reduced products

No need of special products if donorinduced-may not recur

Donor tracing-hence reporting isimportant

HLA crossmatch/antibody detection


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TACO-Transfusion AssociatedCirculatory Overload

More risk in

Cardiac insuffi ciency,

Renal impairment,

Chronic anemia. Restricted blood volumes-neonates

Elderly

More risk with rapid infusion


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SYMPTOMS AND SIGNS

Dyspnoea

Orthopnoea

Tachypnoea

Tachycardia Hyper tension

Crepitations

Raised JVP

ECG changes


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TREATMENT

Stop the transfusion.

If transfusion is critical use the slowest possiblerate

Sitting position Diuretics-(frusemide 40 mg)

O2 as needed

Severe overload

Phlebotomy ??!! Not prudent in anemia/hypoxemia


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PREVENTION

Rapid transfusion -into a patient who is not activelyhemorrhaging produces no benefit and can causeHarm

Infusion should be at a rate not to exceed 2 to 4mL/kg/hour

Patients at high risk of circulatory overload.

Rate should be lower (1 mL/kg/hour)

Furosemide can be given prophylactically

Aliquoting can be tried

Centrifugation and plasma removal

FEATURE TRALI TACO


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FEATURE TRALI TACO

BODY TEMPERATURE FEVER NO FEVER

BLOOD PRESSURE HYPOTENSION HYPERTENSION

RESPIRATORYSYMPTOMS

A/C DYSPNEA A/C DYSPNOEA

NECK VEINS UNCHANGED DISTENDED

AUSCULTATIONS RALES RALES,S3

CHEST RADIOGRAPHS DIFFUSE B/L

INFILTRATES

DIFFUSE B/L

INFILTRATES

P/A OCCLUSIONPRESSURE

18mm Hg

RESPONSE TO

DIURETICS

MINIMAL SIGNIFICANT

WHITE CELL COUNT TRANSIENTLEUKOPENIA

UNCHANGED

BNP 1200 pg/ml

LEUKOCYTES DONOR LEUKOCYTEANTIBODIES PRESENT

MAY/MAY NOT BEPRESENT


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SPECIAL SITUATIONS

Citrate toxicity

Hypothermia

Inhibitor formation

Air embolism-very rare now


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Transfusion TransmittedDiseases


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HIVHBV

HCV

HTLV

CMV

EBV

HHV-8

HAV

HEV

GBVParvovirus B 19

SEN

Torgue Teno Virus

DENGUE

LCMV

SARS

SFVWNV

COAGULASE NEGATIVESTAPH,S.AUREUS.B.CEREUS

SERRATIA

YERSINIA

ENTEROBACTER

E COLI

PSEUDOMONAS

PRIONS

TREPONEMA

PALLIDUM

BORRELIA

PLASMODIUM

BABESIA

LEISHMANIA

T.CRUZI

RICKETTSIAE


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HBV-1:65000-1 lakh

HCV-1:5 lakh

HIV-1:1,20000

Malaria -5-50/million


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Prevention

Avoid unnecessary transfusion

Use of latest screening technology in bloodbank

Careful donor selection Vaccination if available in risk population


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Transfusion RelatedImmunomodulation

Increased Recurrence of Resected Malignancies

Increased Risk of Postoperative BacterialInfection


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TRIM effects, postulated mediatorsof TRIM, and preventive strategies


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How to manage a TransfusionReaction

Stop the transfusion

Keep IV line open with saline

Try to diagnose the cause

Mild ?allergic/FNHTR R /o identification error

call BB and r/o clerical error

Restart within 30 mts if suspected allergic&

do not re start in case of suspicion manage according to provisional diagnosis


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Reaction Form

Name,IP,Ward,Unit

History of previous transfusions

Time of reception,time of transfusion Amount of transfusion

Reaction occurred at----hrs

Signs and symptoms

Clinical diagnosis of patients original disease Investigations sent

Enclose 3 cc plain and EDTA samples from a differentlimb


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Contra Indications

Absolute

Documented intolerance to plasma or itscomponents

IgA deficiency Relative

Cardiac failure,pulm.oedema


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Inappropriate use of Plasma

Inappropriate

Concerns-

Adverse Effects Conservation

Inability to provide adequate dose to thepatient

Not it l f or

rti l r occasion

Not ing it atiscorr ct or roper


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WHY?


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WHAT TO DO?

WE SHALL SORT OUTTOGETHER!


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BLOOD IS ALSO COSTLY!!!

BLOOD BAG

Screening

Cross matching

Others


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Inappropriate Use of Plasma

Hypovolemia

Hypoproteinemia

Correction of abnormal laboratory parametersin the absence of bleeding

Correction of single coagulation factordeficiency for which factor concentrate isavailable

Nutritional deficiency

Vitamin K deficiency when there is time to

correct with vit.K Wound infection

Treatment of immune deficiency states


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Hypovolemia

Upto 30% blood loss can be managed without blood

Non protein colloids can be used unlesscontraindicated

Even after >30% blood loss,RBC will suffice FFP only in the setting of massive transfusion

Co-Existing Coagulopathy as evidenced byabnormal PT,aPTT


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Hypovolemia-Non Haemorrhagic

First line Crystalloids

Colloids if unresponsive

Specific Need for albumin only if hetastarch,dextran

etc are contraindicated Albumin rapidly decreases even after administration

in septic shock


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C/c Hypoproteinemia

Causes Defective Albumin Production

Malnutrition Mal absorption Liver disease etc

Excessive loss thro excretion Nephrotic syndrome Protein losing enteropathy Cirrhosis

Increased protein catabolism

Thyrotoxicosis Pancreatitis Common in critically ill,c/c diseases Think of Analbuminemia HAS


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How to minimise

Determine the underlying cause and treat

Restrict for A/c complications of c/c hypoalbuminemia,largevolume paracentesis etc

Improve circulating protein levels by dietary means Hypoalbuminemia need not be corrected to completely

normal levels


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Plasma in Albumin Correction

Universally opposed

TTD risk

Difficult to give adequate correction with plasma

Deficit in gX2Xplasma volume inlitres

5x2X2.5=25 g

PV=.07XwtX(1-Hct)

500 ml

albumin5%=25g

1 U SDP=4-6g

SDP

25/6=4.2 UALBUMIN

1U


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Correction of factor Deficiency

Should not use plasma if a factor concentrateavailable

Proper timing can reduce the usage

Exposure to large number of donors needed toprovide adequate dosage

Cost benefit

Difficulty in procuring the donors


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Nutritional & immunodeficiencystates

Oral and parenteral nutritionalsupplements freely available

Immunoglobulins much saferand effective forimmunodeficiency states


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Wound Infection

Earlier studies have shown equivocal results

Slight benefit of correcting the albumin so as toreduce edema and tissue tension

An array of alternate options-Antibiotics

Inadequate dosing

TRIM


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Reconstitution of whole blood

Reconstitution was earlier used

To reduce viscosity

In trauma

Still used in exchange transfusion-plasmais indicated

Not justified in absence of coagulopathy

Rarely used these days

Indications of whole blood itself is rare


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adverse effects of plasma therapy

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