BLOOD TRANSFUSION

Ranjita Pallavi, MDInternal MedicinePGY 3

Introduction

1988: “ No single criterion should be used as an indication for red cell component therapy and that multiple factors related to the patient's clinical status and oxygen delivery needs should be considered”

National Institutes of Health Consensus Conference on Perioperative Red Blood Cell Transfusions

Guidelines for red cell transfusions and volume replacement in adults

Uptodate 2010

Red Cell Transfusion

Treatment of symptomatic anemia • Prophylaxis in life-threatening anemia • Restoration of oxygen-carrying capacity in case of

hemorrhage • RBC are also indicated for exchange transfusion w Sickle cell disease w Severe parasitic infection (malaria, babesiosis) w Severe methemoglobinemia w Severe hyperbilirubinemia of newborn

Red Cell Transfusion RBC transfusion is not routinely indicated for pharmacologically treatable

anemia such as:

• Iron deficiency anemia

• Vitamin B12 or folate deficiency anemia

Dosage and administration

• One unit of RBC will raise the hemoglobin of an average-size adult

by ~1g/dL (or raise HCT ~3%)

• ABO group of RBC products must be compatible with ABO group

of recipient

• RBC product must be serologically compatible with the recipient

(see Pretransfusion Testing). Exceptions can be made in

emergencies (see Emergency Release of Blood Products).

• Rate of transfusion

w Transfuse slowly for first 15 minutes

w Complete transfusion within 4 hours (per FDA)

Red Cell Transfusion

AABB Guideline Update

AABB Guideline makes three recommendations: Adhering to a restrictive transfusion strategy (7 to 8 g/dL)

in hospitalized, stable patients; Adhering to a restrictive strategy in hospitalized patients

with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less; and

Considering symptoms as well as hemoglobin concentration during transfusion decisions.

Transfusable Blood Components

Choice of component 

Whole blood: use for patients who have bled acutely and massively after receiving approximately five to seven units of red cells plus crystalloids

Red cell preparations containing minimal plasma: use for Chronic anemia since volume replacement is not required

Choice of component 

Irradiated blood products

- inactivates lymphocytes

- immunocompromised bone marrow or organ transplant recipients

Washed RBC’s

- removes about 99% of plasma proteins, electrolytes and antibodies

- plasma proteins may cause serious anaphylactic reactions

Leukoreduced products:

- filtered blood

- usually for chronically transfused patients

- potential transplant recipients

- patients with previous transfusion reactions

Choice of component 

Autologous blood- an individual may donate his or her own blood to be stored and used for transfusion at a future date - considered acceptable by some

Jehovah's Witnesses if the blood does not leave the bedside for processing

- damages cells to some degree, and less than 10 to 15 liters is recommended

Platelets Thrombocytopenia or dysfunction of platelets in the

presence of bleeding Prophylactic : plt.counts below 10,000-20,000 Prophylactic preoperative : plt.counts below 50,000 Microvascular bleeding in surgical patient with platelets

< 50,000 Neuro/ ocular surgery > 75,000 Massive transfusion with microvascular

bleeding with platelets < 100,000 Qualitative dysfunction with microvascular bleeding

(may be > 100,000)

Fresh Frozen Plasma Initial therapeutic dose : 10-15 ml/kg Isolated factor deficiencies Reverse warfarin therapy Correction of coagulopathy associated with liver disease Used in patients who have received massive blood

transfusion with microvascular bleeding Complications (PATCH) : Platelets – dec, Potassium –

inc., ARDS, Acidosis, Temp dec., Citrate intoxication, Hepatitis

Antithrombin III deficiency TTP ( Thrombotic thrombocytopenic purpura ) Do not use for volume

Cryoprecipitate

10 ml: fibrinogen (150-250 mg), VIII (80-145 U), fibronectin, XIII

1U/ 10kg fibrinogen 50 mg/dL (usually a 6- pack)

Hypofibrinogenemia (congenital or acquired)

Microvascular bleeding with massive BT (fibrinogen < 80-100mg/dL)

Bleeding patients with vWD (or unresponsive to DDAVP)

Pre – Transfusion

Does the patient need the transfusion? Does the patient want the transfusion?

- Consent How many units to Cross? Massive Transfusion Protocol activation

Pre-transfusion

- Obtain Informed consent, risks and benefits of procedure, witness

- Type and Screen, crossmatch

- Inform Blood bank for product availability

- Fill up Blood Requisition Form

- Escort for pick-up of form, blood product if available

- IV access, at least 18 gauge to allow adequate flow, standard filter

- observe for 5-10 minutes initially for adverse side effects and then at regular intervals thereafter

Blood Pickup Requisition Slip

Pre-transfusion

- “Type and Screen” on order review, Now STAT or via phlebotomy

- Order Label, Pink top EDTA tube, Green ID band, Biohazard bag

- Countersign Label and Green ID band with your initials

- Put sticker label to green ID band then attach green ID band to patient’s arm (cross check with patient’s admission ID band-name and MR #)

- Place sticker from green ID band at Pink top tube

- Put pink top tube in the biohazard bag with excess green ID band and send it to blood bank/escort pick-up (don’t send by “shoot”/pneumatic tube)

Transfusion Orders:

Blood Bank Practices

1) Crossmatching (50 min)

2) Confirms ABO and Rh typing

3) Detects antibodies to the other blood group systems

4) Detects antibodies in low titers or those that do not agglutinate easily

Type and screen vs Type and crossmatch

T&S -determines ABO and Rh status and the presence of most commonly encountered antibodies – risk of adverse rxn is 1:1000

-takes about 5 mins T&C -determines ABO and Rh status as well as

adverse rxn to even low incidence antigens – risk of rxn is 1:10,000

-takes about 45 mins

TRANSFUSION REACTIONS

Adverse effects from transfusion

Volume overload: Administration of blood products greater than the normal blood volume of patient in a 24-hr period

Hypothermia: caused by chilled blood, cause cardiac dysrhythmias, use blood warming device

Citrate intoxication: in massive transfusions, Tx. Stop transfusion, if symptomatic give calcium. ( common in hepatopathy)

Hyperkalemia:occurs in stored RBC or irradiated products, also in pt. already hyperkalemic, avoid by using new blood

Infectious Risks

Types of Reactions

Immune mediated transfusion reactions Febrile non hemolytic tranx rxns Immune mediated hemolysis

---Acute and delayed hemolytic reactions Anaphylactic transfusion rxns Urticarial transfusion rxns Post-transfusion purpura GVHD TRALI (pulm leuko-agglutinin reactions)

Types of Reactions

Non immune mediated transfusion reactions Physical reactions: thermal i.e. heat or cold induced Infectious; Hepatitis B/C, malaria, HIV, CMV, Chagas

dx, CJ Virus, West Nile virus Chemical; citrate toxicity, hypo/hyperkalemia, iron

overload Acute hypotensive reaction: mediated by bradykinins

and occurs in patients with faulty bradykinin metabolism on ACE I

Osmotic injury Congenital and acquired hemolytic anemia

Immunologic rxnsclassic blood tranx rxns are usually immunologic and occur 2/2 to interactions of inherited/ acquired Ab with foreign Ag from transfused blood

Incidence of rxns SHOT trial (serious hazards of tranx)

-most common cause is tranx of non-matched blood mostly 2/2 to clerical error

-2x more common in infants than adults

-more common in pxts with hematological and oncological conditions

Case scenario 1

A 35-year-old woman was hospitalized for anemia 2/2 sickle cell disease, she is receiving 2 units of PRBC. After her 1st unit of blood she developed a temp of 38.3 °C (101.0°F). She has no other symptoms.

On exam she appears anxious but her vital signs are stable with Bp 120/70mmHg, HR 80bpm 18cpm Pox 98% 0n RA

She has no skin rash and her urine color is amber

What are your differential diagnosis and how would you manage this pxt?

Febrile non hemolytic tranx rxns

Most common, usually benign without sequelae Concerning because initial presentation is similar to more adverse

rxns. i.e. fever, chills +/- mild dyspnea. 15% will have a rxn in the future with subsequent tranx

Etiology1. Class 1 HLA ab directed against contaminating wbc in red cell

conc. Although these are not always found2. 2/2 to cytokines IL-1, 6,8 and Tnf alpha generated in stored

blood/products.3. Determining factor is age of blood products

ManagementDiscontinue tranx, rule out hemolysis i.e. check labels, repeat type and

cross, coombs testAntipyretics +/- meperidine for chills and rigors

Prevention • Leukoreduction: evidence is scarce but few studies have shown a

decrease in number of reactions.

• Although tylenol and antihistamine premedication is widely used there are no evidence to support that their use actually prevents rxn.

Case scenario 2 A 35-year-old woman was hospitalized for anemia 2/2 sickle cell disease,

she is receiving 2 units of PRBC. Her 1st unit of blood was transfused without events but 5minutes into her 2nd unit, She complains of new flank pain and fever.

On exam she appears very anxious, diaphoretic and in acute distress, she is febrile to 38.8C with Bp 100/60mmHg, HR 101 bpm, 18cpm, Pox 98% 0n RA

She has no skin rash but is oozing out of IV sites and her urine color is now reddish brown.

Labs: elevated Bun/creat, increased PTT, PT and decreased HCT.

What is the diagnosis and how would you manage this patient?

Acute hemolytic rxns

Medical emergency Occurs due to rapid transfused RBC destruction by

preformed recipients Abs Mostly 2/2 to ABO incompatibility-typically type O

receiving non O blood. May occur with other blood types

IgM mediated complement fixation leading to rapid intra vascular hemolysis

Most common causes are clerical or procedural errors Complications includes DIC, shock, ARF 2/2 to ATN

Clinical presentation Classic presenting triad of Fever, flank pain and reddish brown urine from

hemoglobinuria is rarely seen DIC may be presenting mode

Labs Direct Coombs +, Pink plasma, Lactate, FDP in DIC

Management1. Stop transfusion, alert blood bank to start search for clerical error since

another patient may be at risk 2. R/o tranx rxn i.e. check labels, repeat type and cross with unit, check urine for

hemoglobin 3. Supportive care; ABC +/-pressors4. cardiac monitoring because of risk of hyperkalemia5. Infuse NS to maintain BP and promote diuresis, avoid LR and dextrose because

calcium in LR will promote clotting in IV line and dextrose will increase hemolysis. Maintain urine output >100-200ml/hour

6. With DIC early heparinization 10u/kg/hr may be beneficial

Delayed hemolytic transfusion rxns

Generally occurs within 2-10 days of tranxUsually due to senescent Ab response on re-exposure to a foreign red cell Ag History of previous pregnancy, transfusion or transplantUsually extra vascular and is less severe than acuteOther Abs often Rh and Kidd

Clinical presentationFalling HCT, low grade fever, slight increase in indirect bili, spherocytes on blood smear

DiagnosisNew +DAT and new Ab test when new blood is ordered

Txt None in the absence of rapid hemolysisAvoid offending Ag in future tranx

Anaphylactic reactions-life threatening emergency-Occurs within a few seconds to minutes following tranx-Characterized by rapid onset of anaphylaxis -Can occur with all blood products but generally seen with serum albumin, plasma protein fractions or coagulation factors

Incidence 1 in 20-50 thousand

MechanismPresence of class specific IgG and anti IgA abs in pxts who are IgA def -Selective IgA def is fairly common, occurring in 1/300-500 people but majority of them do not develop Abs -Ahaptoglobinemia with antihaptoglobin Abs is similar and occur primarily in East Asian

TreatmentAs in all cases of anaphylaxis: stop tranx, epi 0.3ml of 1.1000 soln IMConsider IV epinephrine dripABC +/- pressor support

ANAPHYLACTIC REACTIONS 

PreventionEstablish diagnosis: usually after the factUse IgA def products for all further tranx (extra washed red cells or platelets)

Urticarial reactions-Allergenic products in blood products activates IgE in recipient leading to histamine release from mast cells and basophils-Only rxn in which tranx can be resumed-Give benadryl 25-50mg IV/PO if urticaria is extensive

Case scenario 3

30 year old kidney transplant recipient on chronic Immunosupressive therapy admitted for anemia and received 2 units of non irradiated PRBC from his sister 3 days ago develops skin bullae, diarrhea and abdominal cramps

VS: notable for low grade fever of 37.9C otherwise normal PE: Jaundice, swollen skin with multiple bulla

Labs; new thrombocytopenia, elevated LFT, increased bilirubin.

What is your diagnosis?

Very rare (0.1-1%) complication seen in Immuno-compromised individuals esp in solid tumor cancer pxts on chemo, but can occur with acute/chronic leukemia, lymphomas, new borne with erythroblastosis fetalis and transplant pxts

Different from transplant GVHD by it’s effect on bone marrow (BM aplasia)

It occurs in immuno-compromised recipients of blood products from donors with identical HLA haplotypes. They are heterozygous for a HLA haplotype for which the donor is homozygous .e.g. genetically identical relatives

HLA ag are shared by donor and recipient, thus donor lymphocyte are engrafted by recipient because they are the only Ag seen by the host.

On the flip side the donor lymphocytes view the recipient’s tissues as foreign leading to immunologic activation and GVHD.

Bone marrow aplasia is the primary cause of death

Transfusion associated GVHD

Clinical presentation

Skin: Swollen, erythroderma and bullae formation- most common

GI: Diarrhea and abdominal cramps

Liver: Elevated LFT and Hyperbilirubinemia

Heme: Bone marrow aplasia, persistent thrombocytopenia

Skin manifestation of GVHD Generalized swelling, erythroderma and bullous formation

Non Irradiated whole blood PRBC Platelets Granulocytes Fresh non frozen plasma

It has not been seen with frozen deglycerolized RBC, FFP or Cryoprecipitate

Treatment

Poor response to standard immunosuppressive therapies,

Thalidomide has been tried with variable success.

Prevention

Key since response to treatment is poor

Gamma irradiation and leuko-reduction of products

Avoid blood products from genetically identical donors

Implicated products

Case scenario 4 A 35-year-old woman was hospitalized for thrombotic thrombocytopenic

purpura for which she underwent therapeutic plasma exchange with fresh frozen plasma. After 7 days of treatment, she had improved sufficiently to allow for weaning from daily transfusions; however, at the conclusion of plasma exchange, she developed a cough and a temperature of 38.3 °C (101.0 °F), with progression of respiratory symptoms to severe dyspnea, with some wheezing.

On physical examination, the blood pressure is 120/80 mm Hg. There is no rash or hives. She is tachycardic and cyanotic on cardiopulmonary examination. Oxygen saturation is 80% on room air, and a blood gas study shows an arterial PO2 of 55 mm Hg. A chest radiograph reveals diffuse opacifications of both lungs and a normal-sized heart and no pleural effusion.

Which of the following is the most likely cause for this patient's reaction?

1. Pulmonary embolism 2. Antileukocyte antibodies 3. Allergy to donor plasma proteins 4. Circulatory overload

Transfusion related acute lung injury

New acute lung injury occurring during or within 6 hour of blood product tranx

All blood products have been implicated May progress to ARDs Immune mediated non cardiogenic pulm edema

Risk factors No definite risk factors but prolonged storage of blood

products, massive tranx, cytokine txt, multiparity, thrombocytopenia and active infections have been implicated in a number of studies.

Pathogenesis -Abs against HLA -2 hit hypothesis: 1st hit is an underlying pulm pathology that leads to localization of

neutrophils in the pulm vasculature 2nd hit is the transfusion of blood products containing sensitized

neutrophils Ab leading to release of vasoactive Cytokine and pulm edema

Leading cause of transfusion related fatalities in the USA 1 case for every 1000-2400 units transfused 6-9% mortality rate

Epidemiology

Clinical presentation

Acute onset of respiratory distress (hypoxemia) during or shortly after blood tranx. On the average within 1-2 hours post tranx

Fever, tachycardia, tachypnea, +/-hypotension In intubated pxts; elevated peak airway pressures, pink frothy airway

secretion CXR bilateral patchy alveolar infiltrates, normal cardiac picture Labs; eosinophilia and transient drop in neutrophils, Leuko-agglutinin

testing

DiagnosisClinical presentation and CXR findings-Labs; granulocyte/ leuko-agglutinating abs, decline in C3 or C5 levels

12-36 hours after onset of symptoms followed by rise 4-7 days later

(a) Bilateral patchy alveolar infiltrate in TRALI (b) Complete resolution

a b

Criteria for the diagnosis of TRALI• No acute lung injury immediately before transfusion• New acute lung injury: 1. acute onset lung injury, 2. no circulatory overload or PA pressures <18mmHg, 3. bilateral pulm infiltrate on Cxr, 4. Hypoxemia:Pa02/FiO2 <300, or sat <90% on RA.• Onset within 6 hours after transfusion • No temporal relation to an alternate risk factor for acute lung injury

Popovsky TP et al TRALI; definition and review. Crit care Med 2005

Ddx includes Acute fluid overload: ↑ JVP, ↑SBP and widened pulse pressure

during dyspneic episode, ↑ pulm vascular markings on CXR Hemolytic transfusion rxns IgA mediated anaphylaxis in IgA def patients

Management -Mostly supportive with abrupt resolution in symptoms within a few days-A majority of patients may require mechanical ventilation-Diuretics play no role in management since it is microvascular damage and not due to volume. It has been shown to actually worsen TRALI

PrognosisIncreased risk of recurrence if they receive products from the implicated donor but no risk from other donors

POSTTRANSFUSION PURPURA 

occurs primarily in women sensitized by pregnancy

severe degrees of thrombocytopenia, often lasting days to weeks, develop about 5 to 10 days following transfusion of a platelet-containing product such as red cells, platelets, whole blood

Usually self limited, but high mortality if severe thrombocytopenia

preferred therapy is IVIG in high doses (400 to 500 mg/kg per day, usually for five days); alternatively, 1.0 g/kg per day for two days can be given for severe thrombocytopenia. Plasmapheresis is also a option

usually takes about four days for the platelet count to exceed 100,000/microL

Blood Infusion Record

Transfusion Reactions:

Transfusion Reactions:

Transfusion Reactions:

Transfusion Reactions:

Transfusion Reactions:

Approach to patients who are unwilling or unable to receive RBC transfusions

reduce blood loss by phlebotomy and obtain necessary testing in pediatric tubes

EPO is often of benefit

Most cases, concurrent use of oral or parenteral iron is also recommended with increase of 1-2 g/dl over approx a week

Finally:

Important numbers:

Blood bank Ext. - 6891/92/93

Patient Escort Ext. - 6500

Phlebotomy Ext. - 6201

Phlebotomy Pager - 6790, 6791,6792

STAT Lab Ext. - 6775

“Blood is still the best possible thing to have in our veins” - Woody Allen

Blood transfusion is a lot like marriage. It should not be entered upon lightly, unadvisedly or wantonly, or more often than is absolutely necessary” - Beal