Blood Collection

• Only 8 out of 100 million eligible blood donors actually donate
• We use a VOLUNTARY donor system

Ø  paid donors associated with higher rick of passing on transmissible diseases

• Blood is a “drug”Þ regulated by the FDA
• How do we select blood donors?

Ø  there is a uniform donor “screening” process

Ø  process ensures safety for both the donor and the recipient

Ø  Process includes

1)     volunteer donors only

2)     general health questions about the donor

3)     medical history of the donor is taken before the donation

4)     physical examination before the donation

5)     lab tests on the donated blood

6)     national donor deferral agency check

7)     providing a method in which the donor can confidentially designate the unit as unsuitable for transfusion after the donation

• Steps to ensure protection of the donor

1)     age limit: usually at least 17 –some rare cases this is ignored)

2)     Reasons for deferral

-        heart or lung disease, pregnancy, major illness or surgery, abnormal bleeding problems

3)     Can only donate EVERY 8 WEEKS.

• Step to ensure protection of the recipient

1)     donor questions to detect at risk donors

-        malaria, AIDS risks behaviors, signs and symptoms of HIV-1 infection, Hx of other infectious diseases, recent vacinnations or immunizations

• Physical examination of the donor

1)     inspect arms for signs of IV drug abuse

2)     generally in good health

3)     weight, temp., BP, and HR within NL

4)     Minimun Hemoglobin – 12.5 g/dL

Testing the Donor Blood after the Donation

• All units – ABO group, Rh type, and the presence of alloantibodies
• Serologic tests done on all donated blood

1)     Syphilis – RPR

2)     HbsAg

3)     Anti-HBc

4)     Anti-HCV

5)     Anti-HTLV-I/II

6)     Anti-HIV-1/2

7)     HIV-1 p24 Ag

8)     HIV and HCV by Nucleic Acid Testing –Further closes the window of opportunity)

• Other things such as CMV can be tested for before transfusion in the cases of certain individuals

Special Donor Categories

Directed Donations –Also known as Designated Donations)

• donations given by someone for direct use in that patient
• usually done because patient or family “hopes” that the blood is “safer”

Ø  data has not proven that directed donor blood is safer than that from anonymous donors.

Ø  If not used, the directed-donor units are “crossed over” into the general supply

• Some instances it is appropriate for directed donations to be used.

1)     patients w/ certain blood group antibodies for which finding compatible blood is difficult

2)     Those that need many transfusions over a period of time –usually children and infants)

Ø  avoids the exposure of the patient to different donors

Autologous Donation

• Donor and recipient are the same
• Safest form of blood transfusion
• Usually occurs when patient has advanced knowledge of the possible need for blood products.
• No age or weight restrictions
• Hg must be at least 11 g/dL
• Can donate as often as every 72 hours
• Blood that is not used is NOT CROSSED OVER
• Give oral iron therapy or erythropoietin
• Special circumstances

1)     Acute Normovolemic Hemodilution

Ø  removal of 1-2 units of whole blood immediately before or after induction of anesthesia

Ø  as the blood is infused, Blood volume is maintained by infusing crystalloid or colloid.

Ø  Done when the expected blood loss is > 1L or 20% or more of the exstimated blood volume

Ø  Advantages

1.     Autologous blood available

2.     Fresh blood available

3.     Reduction in RBC loss during surgery

4.     Better hemodynamics and O₂ availability

2)     Intraoperative Blood Salvage

Ø  blood collected from the operative site or extracorporeal circuits and returned to the patient

Ø  only RBCs are reinfused because the washing removes the plasma and platelets

3)     Postoperative Blood Salvage

Ø  Blood collected from chest tube or drainage from joint spaces

Ø  Usually not washed before transfusion

Ø  Concerns?

1)     quality of RBCs being transfused

2)     some people say that this form of autologous donation is dangerous.

Blood Component Therapy

Blood Component Preparation

• Citrate is used as an anti-coagulant
• Preservatives – phosphate, dextrose, adenine
• The anti-coagulant and preservatives are designed to prolong the shelf-life of the stored bloob

• Blood is usually separated into components by differential centrifugation

1)     RBCs

2)     Fresh Frozen Plasma –FFP)

3)     Platelets –Plts)

4)     Cryoprecipitate –Cryo) – comes from fresh frozen plasma

Concepts of Blood Component Therapy

• a “unit” of any blood component is the amount of that component prepared from a single unit of whole blood.

Ø  normal adult – 8-10 units of whole blood in the body

• a “dose” refers to pooling several units of a particular component together for transfusion to a single patient

Ø  Usually platelets and cryoprecipitate are the only components given as pooled components

1)     Hermann – 6 units/dose

2)     Methodist – 10 units/dose

Whole Blood

• usually consists of 450 mL of blood and 50mL of the anticoagulant/preservative solution –500 ml total)
• Average hematocrit = 38-40%
• Stored in the ice box for 21-35 days –1 month)

Ø  Side note: the WBCs, platelets, and blood factors –Factors 5 and in the stored whole blood are not useful after 48 hours.

• Provides O₂-carrying capacity and volume expansion
• 1^o indication – active bleeding with > 25% blood loss
• One unit of whole blood will raise the Hematocrit by 3-4% or the hemoglobin by 1 g/dL

RBCs –”Packed Cells”, “Red Cells”)

• volume usually 250-350 mL – depends on the type of preservative soln used
• hematocrit ususally 55-65%
• no viable platelets, granulocytes, or coagulation factors
• stored in refrigerator for up to 42 days.
• Used to treat symptomatic, normovolemic anemia.
• 1^o indication – to increase O₂ carrying capacity
• decision to transfuse must be made on the patient’s clinical condition, not the #s!!!
• Hgb > 10 g/dL – usually no need to transfuse
• Hgb< 7 g/dL – usually transfuse especially is anemia is acute
• Most common reason for acute anemia – GI bleeding.
• Will raise the hematocrit 3-4%; Hgb 1 g/dL –same as whole blood)

Certain types of modifications of RBCs

1)     Leukocyte-Reduced RBCs

Ø  Problem with regular RBC transfusions: HLA antigens located on WBCs

Ø  When transfused into patients the patient forms HLA antibodies.

Ø  These HLA antibodies can cause

1)     febrile transfusion reactions

2)     refractoriness to platelet transfusions

3)     vascular rejection of solid organ transplants.

Ø  Indications for use of Leukocyte-Reduced RBCs

1)     decrease risk of HLA alloimmunization –in patients that will be chronically transfused)

2)     decrease the risk of CMV transmission

3)     transfusions of patient with a history of recurrent febrile transfusion reactions

4)     reduce incidence of wound infections in selected surgical patients

2)     Frozen RBCs

Ø  RBCs can be frozen w/ glycerol as a cryoprotective agent

Ø  Can store up to 10 years

Ø  When you need them, you have to dethaw and deglycerolize and then reconstitute them in sterile saline

Ø  Hematocrit 70-80%

Ø  Once thawed, the expiration date is 24 hours.

Ø  Indications for use

1)     long term storage of RBCs

2)     long term storage of autologous blood

Fresh Frozen Plasma

• contains all coagulation factors present in fresh blood
• does not contain RBCs
• Stored frozen for up to 1 year
• Must be thawed prior to use; expiration date is 24 hours from time thawed
• Indications

1)     bleeding patients with multiple coagulation factor deficiencies –liver disease, DIC, or massive transfusion)

2)     replacement of coagulation factors in patient with congenital factor deficiencies

3)     reversal of warfarin

• Contraindications

1)     Should not be used as a volume expander –use albumin, crystalloid, or colloid)

2)     Correction of a mildly prolonged PT or PTT when the patient shows no evidence of bleeding

• Dosage

1)     start with 2-4 units or give 10-20 mL/Kg body weight

2)     will increase the level of coagulation factors by 20%

3)     monitor the patients PT and PTT

4)

Platelet Concentrates

• each bag contains platelets suspended in 50-70 mL of plasma
• SMALL amounts of RBCs are present
• Stored at room temperature with constant agitation for up to 5 days
• Indications for use

1)     bleeding due to thrombocytopenia

2)     Bleeding due to functionally abnormal platelets –congenital or acquired)

3)     Prophylactic use in patients with platelet count < 5-10000 –chemo, tumor invasion of bone marrow, …)

4)     “Transfusion triggers” – 5,000 to 20000

• Contraindications

1)     usually not useful in patients with DIC, ITP, TTP, septicemia, hypersplenism

• Dosage

-        normally in an 70 Kg adult, one platelet concentrate raises the platelet count 5000-10000.

-        Usual dose – 1 unit/10 Kg body weight

Ø  this is where the “pooling” comes in

Ø  once pooled. The expiration date decreases to 4 hrs

• Special Preparation of platelets

Ø  Apheresis platelets –also called single-donor platelets)

• platelets collected from one donor during an aperesis procedure
• usually results in equivalent of 6-8 units
• paid donors
• one unit of apheresis platelets increases the platelet count 30-40000.

Cryoprecipitate

• concentrated preparation of Factor VIII, Factor XIII, von Willebrand factor, and fibrinogen
• suspended in 10-15 mL of plasma
• NO RBCs are present
• Same long term storage as FFP –1 year)
• Thawed prior to use and then kept at room temp for up to 6 hrs.
• Indications

1)     treatment of factor XIII deficiency

2)     use in hemophilia A and von Willebrand’s disease ONLY when virus-inactivated concentrates are not available through the pharmacy

3)     congenital or acquired fibrinogen deficiency

4)     preparation of fibrin glue

• Dosage

1)     depends on level of factor to be replaced

2)     for fibrinogen – 1 unit cryo/10 Kg body weight should raise the fibrinogen level 50 mg/dL

3)     usually “pooled” in 6-10 unit doses

Cryoprecipitate Contains:

1.     Factor VIII

1. Factor XIII
2. Von Willebrand factor
3. Fibrinogen

Administration of Blood

Informed Consent

• must obtain consent prior to transfusion in non-emergent situations
• certain information must be given to patient

1)     explanation of the procedure of blood transfusion

2)     potential benefits of blood transfusion

3)     potential risks

4)     alternatives to transfusion –such as autologous transfusion)

• Patients have the right to refuse transfusion

Accurate identification

• required
• patient’s armband and ID label on blood unit must match exactly

Blood filters

• required for all transfusions
• 1^st generation – 170 microns
• 2^nd generation – 40 microns

Compatible Intravenous Solutions

• ONLY NORMAL SALINE –0.9%) or Normal serum albumin –5%) is acceptable to be given with blood products
• Unacceptable

1)     D₅W – is hypotonic and will cause hemolysis

2)     Ringer’s Lactate – conatins calcium which can bind the citrate anticoagulant; can lead to formation of small blood clots in the infusion line

3)     Medications of any kind

Rate of Transfusion

• depends on patients condition
• maximum time permitted = 4 hours

Component

Transfuse

Do not Transfuse

RBCs

Only to increase O₂ carrying capacity in anemic patients

• for volume expansion only
• in place of a hematinic
• to enhance wound healing
• to improve general well being

Fresh Frozen Plasma

To increase the level of clotting factors in patients with a demonstrated deficiency

• for volume expansion
• nutritional supplement
• prophylactically with massive blood transfusion
• prophylactically following cardiopulmonary bypass

Platelets

To control or prevent bleeding associated with deficiencies in platelet number or function

• to patients with ITP, TTP, or DIC, unless there is a clinically significant life threatening bleeding
• Prophylactically with massive blood transfusion
• Prophylactically following cardiopulmonary bypass

Cryoprecipitate

For treatment of congenital or acquired fibrinogen or Factor XIII deficiency.  Occasionally for hemophilia A and vWD.

• to patients with deficiencies of factors other than Factor VIII, fibrinogen, vWF, or factor XIII.
• Prophylactically with massive blood transfusion

Immunohematology Basics

• Immunohematology = study of Blood Group Antigens and the antibodies directed against those antigens
• Blood group antigens = antigens found on RBCs
• Blood group system antigens = group of related, but distinctly different blood group antigens. Inherited separately from othe blood group system antigens

Ø  Examples = ABO system, Rh system, Kidd system, Duffy system

• Genetics

Ø  blood group antigens are codominant – if gene present, antigen is expressed

• Antibodies can form to almost any of the blood group antigens

Ø  IgG or IgM –IgM’s are insignificant)

Ø  Abs can be formed without a prior antigenic stimulus OR they can form if the individual has been exposed to the antigen through pregnancy or RBC transfusion

• “Clinical Significance” or a red blood cell antibody

Ø  IgMs – work best when cold –<37^o C) – not considered to be clinically significant

Ø  IgG – most of those that form in response to exposure to foreign red cell antigens

-        react optimally at 37^o C and may bind complement

-        clinically significant

The ABO Blood Group System

• Landsteiner groups in 1900
• Three alleles –A,B,O), Four Blood Groups–A,B,O,AB)
• O gene is an “amorph” since it codes for no detectable product
• Inheritance is straightforward

ABO System Phenotypes and Genotypes

Phenotype

• ABO antibodies

Ø  Landsteiner’s rule: If you lack the RBC antigen, you make the antibody to it

Blood Group

A

B

AB

O

Antigen –inherited)

A antigen

B antigen

A & B antigen

No antigen

Antibodies –formed)

Anti-B

Anti-A

No antibodies

Anti-A and Anti-B

• O negative – Universal Blood Donor
• AB negative – Universal Plasma Donor

The Rh Blood Group System

Rh antigens –D antigen)

• Rh + = presence of “D” antigen
• There is a variant of the D antigen that is weaker = weak D antigen
• Approx 85% of individuals are Rh positive
• No allele of the D antigen has been ID’d
• 60-80% of Rh —) individuals will form anti-D antibodies following repeated exposure to RBCs with the D antigen

Rh Antibodies

• not naturally occuring like those of the ABO groups
• only produced when Rh —) person exposed to Rh –+) RBCs –transfusion or pregnancy)
• Almost always IgG

Ø  react optimally at 37^o C

Ø  do not bind complement, so the red cell destruction occurs extravascularly

• result in hemolytic transfusion reactions and hemolytic disease of the newborn.

Other Blood Group Systems

• most less immunogenic than the “D” antigens
• therefore patients are matched for ABO antigens and D antigens
• if the patient is found to have a significant alloantibody, RBCs can be tested for the lack of the corresponding antigen in that blood selected for transfusion

Pretransfusion testing

1)     ABO typing

2)     Rh typing

3)     Antibody screening

4)     Compatibility testing

• typing of the ABO and Rh type uses specific antisera to detect the corresponding antigens

Antihuman Globulin Serum

• used to detect presence of Abs or complement on surface of RBCs
• Direct Antiglobulin Test – detects Abs coating the RBC surface in vivo
• Indirect Antiglobulin Test – detects red cell Abs present in the patient’s serum –in vitro binding of IgG)

Antibody Detection/Antibody Screening

• used to detect red cell antibodies in a patient other than their naturally occuring anti-A or anti-B.
• The patient’s serum is tested against 2-3 reagent RBC samples that contain all major RBC antigens on the RBCs surface. If the patient makes an Ab, it will bind to the corresponding RBC antigen.
• If you find an unexpected antibody, antibody id studies are performed to determine the antibody’s specificity and clinical significance.

Compatibility Testing

• aim – to detect clinicall sig Abs in the patient’s serum which would react with antigens on the donor’s RBCs.
• Includes

1)     Proper ID of the patient

2)     Proper collection of the appropriate samples to be tested

3)     ABO and Rh blood group typing

4)     Performance of antibody screening test

5)     Selection of compatible ABO and Rh donor units

6)     Performance of the crossmatch with the donor units

7)     Transfusion

• The crossmatch

Ø  Patient’s serum is mixed with the donor’s RBCs and observed for agglutination

Ø  Compatible crossmatch DOES NOT guarantee normal survival of transfused RBCs

Ø  FFP, Plts, and Cryo do not require a crossmatch because they don’t contain a significant amount of RBCs

• Selection of the donor unit

Ø  ABO-specific = same blood group

Ø  ABO-compatible = compatibility

Ø  Rh —) = Rh —)

Emergency Transfusions

• you can tolerate up to 15% loss of one’s blood volume usually
• >50% – shock to death
• can use crystalloid or colloid solutions to initially correct blood volume loss

Ø  allow time for ABO and Rh typing –as well as antibody testing)

• In cases where transfusion is to be done prior to completeion of compatibility testing, physician must sign statement of responsibility …
• O negative = universal RBC donor
• Uncrossmatched Group ant type Specific – takes about 5 minutes

Massive Transfusions

• Definition = transfusion approximating or exceeding the patient’s blood volume within a 24 hour period.
• Average blood volume of 70 Kg adult = 10 units of whole blood ~ 5 liters
• Coagulation abnormalities due to massive transfusion

1)     dilution of the patient’s platelets and coagulation factors

2)     treat according to the clinical observation, platelet count, PT, PTT, and fibrinogen level.

• Metabolic side effects of massive transfusion

1)     Most common abnormality = alkalosis –due to citrateÞbicarbonate in the liver)

2)     Acidemia – lactic acidosis due to inadequate blood supply to tissues –NOT from low pH of stored blood)

3)     Hypocalcemia – due to the rapid infusion of citrate; usually rapidly metabolized by the liver and excreted in the kidney –impaired renal or hepatic function)

4)     Hypokalemia – due to the development of metabolic alkalosis from citrate metabolism

• Cold toxicity

Ø  hypothermia and cardiac compromise

Ø  use blood warmers

Transfusion Reactions

Acute Hemolytic Transfusion Reaction

• serious business
• RBCs with antigen–s) that the recipient has an alloantibody to.
• Complement, coagulation , and kinin systems activated
• Can lead to shock, DIC, and acute renal failure
• MOST COMMON CAUSE – CLERICAL ERROR
• Frequency 1:6000-25000 transfusions –Mortality 10%)
• Clinical Signs and Symptoms

Ø  Fever – 48%

Ø  Fever & Chills – 40%

Ø  Chest pain

Ø  Hypotension

Ø  Nausea

Ø  Flushing

Ø  Feeling of impending doom

Ø  Microvascular bleeding

• Results of acute hemolytic transfusion reaction

1)     Ag-Ab complexes activate complement – leads to lysis of the RBCs, release of vasoactive amines

2)     Hypotension due to activation of the sympathetic nervous system

3)     Renal, splanchnic, pulmonary, and cutaneous vessel constriction

4)     Activation of the plasma kinin system

Ø  generation of bradykinin – dilates arterioles –can lead to fall in MAP)

5)     Coagulation system activation

Ø  initiates DIC – leads to uncontrolled bleeding

6)     Renal vasoconstriction and intravascular thrombi – may lead to acute tubular necrosis

• Lab findings

Ø  Anemia, Hemoglobinemia, hemoglobinuria, increased serum bilirubin, increased LDH, decreased haptoglobin

Ø  Positive direct Coomb’s –IgGs on RBCs)

• Treatment

1)     prevention

2)     stop the transsfusion!!

3)     Treat the hypotension

4)     Maintain renal perfusion

5)     If DIC occurs, treat the depleted coagulation factors

Febrile Nonhemolytic Tranfusion Reaction

• characterized by a temperature elevation of 1^o C or more that cannot be explained by the patients clinical condition
• 1% of all transfusions –higher in multiply transfused and multiparous patients)
• usually due to anti-leukocyte Abs

Ø  severity of reaction directly related to the # of leukocytes in the blood component

• more commonly associated with platelet transfusions

Ø  recent evidence show that IL-1, IL-6 and TNF-a accumulate in platelets during storage

• does not occur with transfusion of FFP or cryoprecipitate –do not contain leukocytes)
• Clinical Signs and Symptoms

1)     Fever –chill, cold, discomfort associated)

2)     Headaches, N&V

3)     Rigors

4)     Often begins early in the transfusion

5)     Self-limited

• Treatment

Ø  Stop transfusion

Ø  Give anti-pyretics

• Prevention

Ø  give anti-pyretics

Ø  repeat rxns uncommon

Ø  leukocyte-reduced blood products

Allergic/Anaphylactic Reactions

Allergic Reactions

• caused by IgE antibodies in the patient directed against plasma proteins present in the transfused blood product
• 1-2% of all transfusions
• Clinical Signs and Symptoms

1)     typically localized urticaria anywhere on body

2)     dyspnea & wheezing maybe

• Treatment

Ø  do not have to completely stop transfusion because urticaria is not a sign of hemolytic transfusion reaction.  ONLY ONE YOU DON’T HAVE TO STOP.

Ø  Give antihistamines –diphenhydramine-Benedryl)

• Prevention

Ø  premedicate with antihistamines

Anaphylactic Reactions

• occur in patients who are IgA deficient and hav formed anti-IgA antibodies
• rare, but often fatal, reaction
• Signs & Symptoms

1)     urticaria, flushing, erythema

2)     laryngeal/facial edema

3)     bronchospasm

4)     wheezing, dyspnea

5)     hypotension and shock

• Treatment

Ø  epinephrine, corticosteroids, intubation, aminophylline

• Prevention

Ø  use of washed RBCs and platelets

Ø  use of plasma from other IgA-deficient individuals

Transfusion Related Acute Lung Injury –TRALI)

• results in noncardiogenic pulmonary edema
• rare
• Due to passive infusion of anti-leukocyte antibodies in the donor unit that react with the recipient’s leukocytes

> aggregates of activated leukocytes are trapped in the pulmonary microcirculation, which causes transient changes in vascular permeability.

• Implicated donors are usually multiparous or multiply-transfused
• Clinical Signs & Symptoms

1)     looks like ARDS

2)     fever

3)     Tachypnea, dyspnea

4)     Cyanosis

5)     Hypotension

6)     Chest pain

7)     Blood-tinged sputum

8)     Occurs w/in 4 hours of transfusion

9)     + CXR for acute pulmonary edema

• Treatment

Ø  stop transfusion

Ø  provide respiratory support

• No set standard for prevention

Other Immediate Transfusion Reactions

Circulatory Overload

• iatrogenic transfusion reaction
• at risk: infants, those with compromised cardiac or pulmonary status and/or chronic anemia.

Nonimmune Hemolysis

• Can be caused by:

1)     transfusing hemolyzed RBCs to patient

2)     giving hypotonic solutions or medications with the RBCs –hypotonic saline, D₅W, etc.)

3)     overheating in a blood warmer –microwave is not to be used)

4)     too small of a needle –high gauge)

Bacterial Contamination

• Cryophilic organisms associated with refrigerated blood components – E. coli, Pseudomonas, and Yersinia)
• Components at room temperature – Yersinia, Serratia, & Salmonella
• Signs and Symptoms

1)     chills, N&V

2)     HIGH FEVER

3)     Hypotension

4)     Progresses to DIC and septic shock

• Need high degree of clinical suspicion to diagnose

Delayed Hemolytic Transfusion Reaction

• 1-2 weeks post RBC transfusion
• due to 2^o response of immune system –Antibody production)
• Most patients asymptomatic

Ø  evidence detected upon subsequent Blood Bank testing

• Clinical Signs and Symptoms

1)     anemia and fever –6-8 days following transfusion)

2)     laboratory evidence of hemolysis – decreased hemoglobin, decreased haptoglobin…

• Treatment rarely necessary

Graft-versus-Host Disease

• transfused lymphocytes mount immune response against the HLA antigens present in the recipient
• Patients are usually severely immunocompromised.
• Clinical Signs and Symptoms

1)     4-30 days post-transfusion

2)     fever, diarrhea, elevated LFTs, pancytopenia, skin rash

• Treatment

Ø  usually unsuccessful

Ø  mortality 90%

• Prevention

Ø  use irradiated blood components to prevent lymphocyte proliferation

Ø  irradiate blood for the following groups of patients

1)     congenital immunodeficiency syndromes

2)     bone marrow transplant recipients

3)     infants receiving intrauterine or exchange transfusions

4)     leukemia, lymphoma, or neuroblastoma

Trasfusion-Transmitted Diseases

Hepatitis

• Usually Hep B and Hep C
• For Hep B

Ø  donors tested for HbsAG and Anti-HBc

Ø  risk 1:200,000

• For Hep C

Ø  majority of transfusion-related hepatitis

Ø  donors screened for anti-HCV and elevated ALT levels

Ø  Problem – Anti-HCV seroconversion can be delayed for up to a year following exposure to the virus

Ø  Risk – 1:150000

HIV-1 and HIV-2

• donor screening for anti-HIV 1 began in 1985
• 80-90% of patients with severe hemophilia A are anti-HIV positive 2^o to infusion of Factor VIII concentratres prepared prior to the mid-1980s
• Current risk of HIV-1 transmission with the new Nuclei acid testing – 1:2,000,000
• The risk of getting HIV-2 from blood is also much lower.

HTLV-1 and HTLV-2

• no reported cases of transfusion-transmitted disease.
• Risk 1:2,000,000
• 98% of individuals with the HTLV-1 virus are asymptomatic

Cytomegalovirus

• skipped because of the new leukocyte-reduction of all RBCs.

Odd Funky Diseases

• can only prevent them by goo donor screening
• rare
• include

1)     Malaria –3 cases in Houston from transfusion in last 5 years)

2)     Chagas’ Disease – thatched roofs

3)     Syphilis – Spirochetes do not survive the cold temperatures

4)     Creutzfeldt-Jakob Disease –CJD) – none reported via transfusion –has been reported via human pituitary-derived GH and dura mater transplants.

Hemolytic Disease of the Newborn

Definition

• abnormal destruction of RBCs in the newborn period
• also called erythroblastosis fetalis, hydrops fetalis, and hemolytic disease of the fetus
• Etiology

Ø  most commonly blood group incompatibility between mother and fetus.

Ø  Anti-D in most severe cases

Ø  However, HDN due to ABO incompatibility is more common

Pathophysiology of HDN

• fetal RBCs which contain some antigen –which mother lacks) pass through the placenta to mother and the mother’s immune system recognizes as foreign and produces IgG antibodies against the RBC antigen. The newly synthesized IgG antibodies pass through the placenta and attack the antigens on fetal RBCs.
• Effects of antibody on the fetus

-        fetal anemia

-        anemia leads to increased hematopoiesis in liver, spleen, and bone marrow

-        hydrops fetalis, hepatosplenomegaly, portal HTN, hypoproteinemiz, and massive edema

• The increased bilirubin load is cleared by mom.
• Effects of Antibody on the Newborn

-        anemia, hyperbilirubinemia, and jaundice

-        kernicterus – yellow staining of the basal ganglia, pontine nuclei, and dentate nuclei in the cerebellum

Mechanisms of Maternal Immunization

• IgGs result from previous immunizations to foreign RBC antigens through pregnancy or transfusion
• Rh Immunization and Pregnancy

-        Rh negative mother and Rh positive baby –mom makes anti-D)

-        First pregnancy is usually not affected

-        In 2^nd pregnancy to Rh positive baby, a 2^o response is initiated which results in mass quantities of IgG anti-D being produced

• Other antibodies associated with HDN

Ø  many group O individuals have IgM & IgG anti-A and anti-B, and therefore HDN can occur due to these ABO antibodies.

-        most common type of HDN

-        termed ABO-HDN

-        almost always restricted to Group A or B infants born of Group O mothers

-        can occur in any pregnancy

-        majority are mild and go unnoticed

Ø  other IgG antibodies that can cause HDN

-        anti-C, E, K –Kell), Fy –Duffy) and Jk –Kidd)

-        less common

Management of the Sensitized Pregnancy

• Prenatal studies

Ø  1^st visit studies

1)     ABO group

2)     Rh type

3)     Antibody screen –indirect Coomb’s test)

• Maternal History
• Can test father for D antigen –Rh type)

Ø  if mom has anti-D –does not have D antigen, therefore Rh —)), and dad has Rh —) then fetus must be Rh —) and not at risk for HDN

Ø  if mom has anti-D and dad types as Rh-positive, then fetus may be Rh –+) and therefore at risk for HDN

Ø  If mom does not have anti-D and types as Rh Positive –has D antigen) then fetus is not at risk

Ø  If mom does not have anti-D and types as Rh Negative then she has just not become immunized.

• Maternal Antibody Titers

Ø  clinically significant antibodies id’d in the mother are titered to determine their strength.

Ø  The titer roughly is in direct relation to the severity of RBC destruction in the fetus

Ø  Titer of 16 is considered sginificant and indicates some action should be taken.

• Amniotic Fluid Analysis

Ø  can become discolored due to accumulation of bilirubin pigments

Ø  positive correlation between the quantity of bilirubin in amniotic fluid and the severity of fetal hemolytic disease.

Ø  Use the Liley graph to analyze

-        Bilirubin’s absorption peak on spectrometry is about 450 nm

-        The height of the peak correlates with the conc. of bilirubin in the amniotic fluid

-        Normally – falls steadily between 26 weeks and term

-        Three zones on the Liley graph

1)     Zone I – mild or no disease – no intervention

2)     Zone II – moderate disease – do amniocentesis every 2 weeks…

3)     Zone III – severe, life threatening disease – intrauterine transfusion or delivery required

• Percutaneous Umbilical Cord Blood Sampling –PUBS) or Cordocentesis

Ø  can be performed as early as 16-18 weeks gestation

Ø  use the MCV to determine adult vs. fetal

• Intrauterine transfusion

Ø  may be necessary because of immature lungs

Ø  intraperitoneal route – transfuse into fetal abdomen and they are absorbed via subdiaphragmatic lymphatics; requires several days

Ø  Intravascular route – can use PUBS to assess fetal vasculature; way more difficult

Ø  Fetal risks: perforation of internal structures, bleeding from punctured site

Ø  Maternal risks: premature labor, infection, placental separation

Management and Treatment of Newborn with HDN

• HDN is characterized by early onset of jaundice occuring within the first 24-36 hours of life.

Ø  due primarily to unconjugated bilirubin

Ø  low levels of glucuronyl transferase

Ø  can cause kernicterus

Ø  without treatment, hyperbilirubinemia can reach a peak at 3-5 days.

Ø  At levels > 20 mg/dl, CNS toxicity can result.

Ø  The reason the kernicterus does no occur at birth is due to transplacental passage of bilirubin into the maternal circulation

• Direct Coomb’s test is usually positive
• Anemia at birth rarely seen with ABO-HDN; common in Rh-HDN

Treat with phototherapy or exchange transfusion

Ø  phototherapy

-        usually for LOW levels of hyperbilirubinemia

-        420-475 nm wavewlength light

Ø  exchange transfusion

-        removes antibody-coated RBCs in the infant and replaces them with compatible RBCs

-        correction of anemia

-        removes bilirubin

-        to remove free antibody from the infant’s circulation

-        RESERVED for more severe anemia and hemolysis

Prevention of Rh immunization in Rh —) women

• Rh Immune Globulin –RhIG)

Ø  comercially available high-titered IgG anti-D preparation

Ø  passive administration of RhIG –anti-D) to an Rh —) mother will prevent her from responding to the incompatible Rh –+) fetal RBCs

Ø  RhIG binds to those fetal RBCs –Rh positive) before Mom’s immune system has a chance to get a whack at them.

Ø  One vial of RhIG will protect against 15 mL of Rh–+) fetal red cells –~30 mL of fetal whole blood)

• antepartum administration of RhIG

Ø  If RhIG is administered w/in 72 hours post-delivery the chances of developing anti-D decrease from 8% to 1%.

Ø  RhIG administered at 28 weeks gestation further decreased the risk to 0.1%

Ø  Thus it is recommended that one vial of RhIG be given at 28 weeks to all Rh —) women who have not formed anti-D

• Post partum administration of RhIG

Ø  give it to all Rh—) mothers that deliver Rh–+) infants

Ø  NOT CANDIDATES for RhIG

1)     Rh —) woman with Rh—) infant

2)     Rh –+) women

3)     Rh —) woman who have already made anti-D

When to Give RhIG:

Routine

• At 28 weeks gestation
• Within 72 hours of delivery of an Rh-positive infant

After an invasive prenatal diagnostic procedure

• Chorionic villus sampling
• Amniocentesis
• PUBS

Ectopic Pregnancy

Spontaneous or therapeutic abortion

Antepartum bleeding due to:

• threatened abortion
• suspected placental abruption
• placenta previa

• blunt trauma to the abdomen
• MVA

Detection and Quantitation of Fetomaternal Hemorrhage

• do I need to give more than one vial of RhIG?
• Incidence of hemorrhage of > 15 mL of Fetal RBCs is about 0.3%, so it may be necessary in some women
• Kleihauer-Betke Acid Elution test

Ø  based on principle that RBCs with fetal Hgb are resistant to acid buffer.

Ø  Maternal blood smear is treated with acid and then counterstained

Ø  Maternal RBCs appear as ghosts while fetal RBCs stain bright pink

Ø  % of fetal cells to maternal cells is determines and the volume of fetomaternal hemorrhage is calculated.

Ø  Once you know the volume of FMH, you can easily determine the number of vials to be used.

Tags: Acute Normovolemic Hemodilution, Autologous donation, Blood Component Therapy, coagulation factor deficiencies, Cryoprecipitate, DIC, fibrinogen, Hemolytic Transfusion Reaction, HLA alloimmunization, Immunohematology, leukocytes, liver disease, plasma, syphilis

This entry was posted on Sunday, July 19th, 2009 at 5:00 am and is filed under Pathophysiology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.