Transfusion Medicine

“Blood transfusion is like marriage: it should not be entered upon lightly, unadvisedly or wantonly or more often than is absolutely necessary.” –Robert Beal, past director of International Federation of Red Cross

Transfusions: History 1660s: First experiments in blood transfusion, transfused dog blood to humans. Patient died and experiments were banned. 1818: James Blundell, British OBGYN, inspired after seeing women bleed to death from uterine losses. Successfully did human transfusions. Mortality up to 50% likely due to ABO incompatibility. 1900: Karl Landsteiner discovered ABO blood groups. 1940: Red Cross established to help supply blood products during WWII. Transfusions: History

Blundnell’s gravitator (1818) “On the transfusion of blood by the syringe.” Source: Blood Journal

Blood components & products Whole blood Red blood cells (PRBCs) Fresh frozen plasma (FFP) Cryoprecipitated AHF Platelets Granulocytes Blood components & products

Blood Collection: whole blood

Blood collection: apheresis (“a taking away”)

Red Blood Cells

Red blood cells

Red blood cell transfusion Indications for transfusion Symptomatic anemia Red blood cell exchange Action Increases oxygen carrying capacity by increasing circulating red cell mass Dosing Each unit contains enough Hgb to increase by about 1 g/dL Each unit contains 250 mg of iron Administration Must be ABO compatible ABO/Rh typing, Ab screen, crossmatch Initial portion of each unit transfused slowly to look for reactions, then infusion can be as rapid as tolerated Finish transfusion within 4 hours (do not leave at room temp > 4 hrs) Red blood cell transfusion

Transfusion of Blood Products Collections and Storage of pRBCs Half Life of stores platelets is somewhat shorted than normal expected RBC lifespan (120 days) Lifespan of transfused red cells closer to 50-60 days Thought 2/2 to depletion of 2,3 DPG Stores of ATP are diminished in stored RBCs Transfusion of Blood Products

Blood Groups - ABO First described by Karl Landsteiner in 1900 Won the Nobel Prize in Medicine for his work First successful, “matched” blood transfusion was done by Dr. Reuben Ottenberg at Mt. Sinai Hospital in 1907. Blood Groups - ABO

Carbohydrate antigens in which the alleles are determined by the end moiety Addition of n-acetylgalactomine to the base structure yields blood group A Addition of galactose to the base structure (a galactose moiety) yields blood group B Lack of any additional moieties yields blood group O Blood Groups - ABO

Minor Antigen Groups

Rh Blood Groups RH Blood Group 2nd most important after ABO Consists of 50 antigens D, C, c, E, e are most important RH positive vs negative refers to the presence of absence of the D antigen Part of the routine Type and Screen and Crossmatch antigens that we test for Rh Blood Groups

Most clinically relevant in hemolytic disease of the newborn An Rh negative mother with an Rh positive father can result in an Rh positive child Exposure of fetal cells to mother creates anti- D Abs Use of RhoGAM has reduced the incidence from close to 16% down to less than 1% Given at week 28-30 and again within 72 hrs postoperatively RH Blood Group

Blood Groups Type and Screen Front type: what antigens are on the patient’s RBCs Back type: identify Ab in the patient’s serum A antigen only Type A B antigen only Type B A and B antigen Type AB Neither A or B Type O anti-B Type A anti-A Type B anti-A and anti-B Type O neither anti-A or anti-B Type AB Blood Groups

Screen Look for red cell alloantibodies that may have formed in pregnancy or after prior transfusions If screen is positive, need to identify the Ab

Blood Groups Type and Cross Crossmatching involves actually taking donor red cells and mixing with a portion of the patient’s serum to look for a reaction At least 2 units of PRBCs are crossmatched for the patient and reserved for the patient – these units cannot be used by anyone else Blood Groups

So why are these important in transfusion medicine? Blood Groups - ABO

Complications of RBC transfusion Acute hemolytic transfusion reaction Febrile nonhemolytic transfusion reaction Allergic reaction Anaphylactic reaction Transfusion related acute lung injury (TRALI) TACO Iron overload

Blood Groups - ABO Acute Hemolytic Transfusion Reaction Symptoms Due to ABO incompatibility Usually due to human ID errors (mislabeling) Symptoms Classic Triad: Fevers/Chills, Flank Pain and Red Urine Also dyspnea, chest/back pain, shock If patient is in surgery under anesthesia: red urine, hypotension, DIC Blood Groups - ABO

Treatment: supportive Lab findings: Hemoglobinuria Elevated bilirubin Positive DAT/Direct Coomb’s Treatment: supportive Stop transfusion immediately Notify blood bank to review Send blood sample from patient along with implicated unit Maintain/correct BP Correct coagulopathy, if present Promote and maintain urine flow

Delayed transfusion reaction Occur in patients who are previously alloimmunized Antigens on transfused cells provoke antibody production Usually occurs 2-14 days after transfusion Signs/symptoms: fever, positive DAT, decrease in H&H, elevated LDH and bili Most times this is benign and requires no treatment

Transfusion Febrile nonhemolytic transfusion reaction Fever shortly after transfusion (without infection) Due to cytokines or Abs against WBCs in the transfused blood More likely to occur if alloimmunized during pregnancy or previous transfusion Reduce occurrence by using leukocyte reduced RBCs or platelets Incidence: in less than 1% of LR-RBCs and less than 5% of LR-platelets Transfusion

Anaphylactic reactions Reported in IgA deficient patients who develop Abs to IgA Symptoms: hypotension, tachycardia, N/V, diarrhea, bronchospasm, laryngospasm Use epinephrine, supportive care Reduce incidence: use washed cellular components

TRALI Thought to be caused by WBC Abs in donors or inflammatory molecules in blood product Stimulate an inflammatory response in a “primed” donor Cause injury to alveolar capillary membrane, increased permeability, pulmonary edema Symptoms: acute onset of hypoxia and non- cardiogenic pulmonary edema within 6 hrs of a transfusion Treatment: Aggressive supportive care Reduce occurrence by leukoreducing blood products and preferentially using plasma donated by males.

TACO Circulatory overload leading to pulmonary edema Occurs after transfusing high volumes or at very rapid rates Higher risk in people with underlying cardiopulmonary or renal disease, very young or elderly, and people with chronic anemia who have low red cell mass and high plasma volume Treat: supportive, reduce pulmonary edema

Bacterial sepsis Due to gram negative or positive organisms in the transfused product, often skin contaminants Symptoms: high fever, hypotension, shock during or shortly after transfusion Treat: stop transfusion, give abx and pressors prn. Send blood cxs from patient and culture specimens from container and blood administration set, report to blood bank. Occurs more often with platelets (stored at room temp). Most platelets are routinely tested for bacterial contamination.

Infectious risks Infection transmission Blood products are all tested for: HIV (1 in 1,000,000) HTLV I and II (1 in 2,000,000) Hepatitis B (1 in 200,000) Hepatitis C (1 in 1,000,000) Syphilis (treponema pallidum) West Nile Virus Chagas (trypanosome cruzi) Other risks: CMV, malaria, bacteria, Lyme, Dengue, Babesiosis, Creutzfeld-Jakob Infectious risks

Blood components & products Whole blood Red blood cells (PRBCs) Fresh frozen plasma (FFP) Cryoprecipitated AHF Platelets Granulocytes Blood components & products

Fresh Frozen Plasma Plasma: FFP Contains all plasma proteins including all coagulation factors 10-15 mL/kg raises factors ~25% Ready to use after thawing, must be discarded after 24 hrs or stored as thawed plasma Indications for use Preop or bleeding patients who need replacement of multiple factors (liver disease, DIC) Patients taking warfarin who need transient reversal of warfarin before Vit K would take effect TTP (transfuse or plasma exchange) Patients with plasma protein or factor deficiencies, if no specific factor concentrate or recombinant product is available Fresh Frozen Plasma

Fresh Frozen Plasma FFP precautions One unit is about 250 mL (can be up to 600 mL if apheresis derived). High risk for volume overload. Plasma must be ABO compatible with the patient’s red cells. Average INR of FFP is 1.5. Will not correct INR below this value. Fresh Frozen Plasma

Fresh Frozen Plasma FFP: complications/hazards Infection (bacterial, viral) Allergic reactions Febrile reactions TACO TRALI Fresh Frozen Plasma

Blood components & products Whole blood Red blood cells (PRBCs) Fresh frozen plasma (FFP) Cryoprecipitated AHF Platelets Granulocytes Blood components & products

Cryoprecipitate Cryoprecipitated anti-hemophilic factor That FFP  recover the precipitate Contains: Fibrinogen Factor VIII Factor XIII vWF Fibronectin Each unit contains 80 IU Factor VIII and 150 mg fibrinogen in 5-20 mL plasma Cryoprecipitate

Cryoprecipitate Indications: Control bleeding due to low fibrinogen Treat Factor VIII deficiency when recombinant proteins not available Second line therapy for vWD and hemophilia A ABO compatible preferred Dose: 1 bag per 10 kg of body weight will raise fibrinogen by 50-75 mg/dL Cryoprecipitate

Blood components & products Whole blood Red blood cells (PRBCs) Fresh frozen plasma (FFP) Cryoprecipitated AHF Platelets Granulocytes Blood components & products

Platelet Transfusions Platelets needed for normal hemostasis Platelets are collected from a single donor (separated from whole blood) or pheresed and pooled from different donors (1 unit = 4-6 single donor units) Platelet Transfusions

Platelet Transfusions Indications for transfusion: Thrombocytopenia Dysfunctional platelet bleeding Active platelet related bleeding Prophylactic use for high risk of bleed Hematologic conditions Patients on ECMO or cardiopulmonary bypass Do not use: In HIT, TTP, or ITP, unless patient has significant bleeding Platelet Transfusions

Platelet Transfusions Compatibility testing not routinely necessary Therapeutic dose: 1 unit apheresis platelets 4-6 units of whole blood derived platelets Should raise platelets by 5-10k Transfused platelets have a short lifespan! 3-5 days Platelet Transfusions

Platelet Transfusions Platelet alloimmunization Platelets have HLA and platelet specific antigens on their surface Patients who get transfusions often develop HLA antibodies and may become refractory to platelets Check CBC 10-60 minutes post transfusion  if Abs present, will not see response If poor response is due to splenomegaly, sepsis, fever, or DIC, will usually see early response to transfusion but reduced 24 hr survival Can do tests to look for presence of Ab against platelet antigens Platelet Transfusions

Factor Concentrates Prothrombin Complex Concentrate (PCC) Contains Vitamin K dependent factors (II, VII, IX, X) Used to reverse the effects of Vitamin K antagonists Factor Concentrates

Special scenarios Massive transfusion for severe hemorrhage (trauma) Transfuse RBCs, platelets, plasma in 1:1:1 ratio Need FFP otherwise clotting factors will be diluted and worsen coagulopathy Blood is anticoagulated with sodium citrate and citric acid. In massive transfusion, can get metabolic alkalosis and hypocalcemia from excessive citrate. Hypothermia can develop when transfusing more than 3 units  use a blood warmer. Special scenarios