Clin Med Transfusion Medicine PDF

Transfusion Medicine Clinical Medicine Hematology Erin Kunz, MHS, PA-C Blood donor criteria Potential blood donors are screened for eligibility prior to donation Screening includes a history and limited physical exam to include Age, weight, medical conditions, travel history, medication use There...

Transfusion Medicine Clinical Medicine Hematology Erin Kunz, MHS, PA-C Blood donor criteria Potential blood donors are screened for eligibility prior to donation Screening includes a history and limited physical exam to include Age, weight, medical conditions, travel history, medication use There are some temporary as well as permanent contraindications to blood donation Basic eligibility requirements Donor must be healthy or chronic medical conditions well controlled At least 17 years of age in most states Weigh at least 110lbs Blood donor criteria Medications: Most medications are OK Medications that are not allowed prior to donation include Known teratogens like Accutane/ finasteride and chemotherapeutics Coumadin/heparin Certain live vaccines Antiplatelet drugs may donate red cells but not platelets Blood donor criteria Medical conditions Bleeding or clotting disorders - never Acute illness with fever Hypotension - minimum BP 80/50 Cancer – depending on type (lymphoma/leukemia in lifetime not eligible) Hgb minimum 12.5g/dl Cannot donate if you have received blood in the last 12 months or in since 1980 in UK or since 1977 in Africa - never IV drug use – never Piercings – fine if sterile procedure – wait 12 months if unsure Tattoos – 12 month wait in most states STDs - 12 month wait after treatment for syphilis or gonorrhea HIV or Hepatitis C – never Blood donor criteria Travel Donors must wait 12 months after traveling to area where malaria is found 3 years after living in an area where malaria is found 12 months after travel to Iraq Concerns for Leishmanaisis People who were born in or lived in certain countries in West Africa are not eligible due to HIV type O strain Some terms to know in transfusion medicine Alloimmunization = the production of antibodies directed against the blood group antigens of another individual Alloantibodies = the antibodies produced against another individual’s blood group antigens How do you develop antibodies against RBC antigens? May result from “natural” exposure Antibodies that occur via natural stimuli are usually produced by a T cell-independent response (thus generating no memory) and are IgM isotype Autoantibodies (antibodies against autologous blood group antigens) arise spontaneously or as the result of infection These antibodies are often clinically insignificant due to their low affinity for antigen at body temperature However, IgM antibodies can activate the complement cascade and result in hemolysis More about antibodies Antibodies that arise due to allogeneic exposure (such as transfusion or pregnancy) are usually IgG IgG antibodies commonly bind to antigens and may hemolyze RBCs Unlike IgM antibodies, IgG antibodies can cross the placenta and bind fetal RBCs bearing the corresponding antigen, resulting in hemolytic disease of the newborn ABO Most common clinically relevant blood group antigen systems Rheus (Rh) Kell Duffy Kidd ABO antigens and antibodies ABO First blood group antigen system recognized in 1900 Most important blood group of transfusion medicine Blood types are designated as: A B AB O ABO antigens and antibodies ABO antigens are carbohydrates attached to a precursor backbone and are found on the RBC membrane H substance is the immediate precursor on which the A and B antigens are added The genes that determine the A and B phenotypes are found on chromosome 9p and are expressed in Mendelian codominant manner ABO antigens and antibodies This system is important because essentially all humans produce antibodies to the ABH carbohydrate antigen that they lack Naturally occurring anti-A and anti-B antibodies are termed isoagglutinins ABO antigens and antibodies Type A individuals have A antigen and produce anti-B antibodies Type B individuals have B antigen and produce anti-A antibodies Type AB individuals have A and B antigen and do not produce anti-A or anti-B antibodies Type O individuals have neither A nor B antigen and produce both anti-A and anti-B antibodies ABO antigens and antibodies ABO antigens and antibodies There are rare individuals that lack the H gene and cannot form H substance These individuals are homozygous for the silent h allele (hh) and have the Bombay phenotype (Oh) They produce antibodies to H substance (which is present on all A, B and O cells except for those of hh phenotype) as well as to both A and B antigens and are therefore compatible only with other hh donors In most people A and B antigens are secreted by the cells and are present in the circulation The Rh system Rhesus (Rh) The Rh system is the second most important blood group system in pre-transfusion testing (behind ABO) The Rh System Rhesus (Rh) Rh antigens are found on RBC membrane protein >40 different antigens in the Rh system have been described, five determinants account for the vast majority of phenotypes The presence of the D antigen confers Rh “positivity” while persons lacking the D antigen are Rh “negative” The D antigen is a potent alloantigen About 15% of individuals lack this antigen (are Rh negative) Exposure of these Rh-negative people to even small amounts of Rh-positive cells, either by transfusion or pregnancy can result in the production of anti-D alloantibody Other blood group systems Kell Kell protein is very large (720 amino acids) and its secondary structure contains many different antigenic epitopes Immunogenicity is third behind ABO and Rh systems Duffy Antigens are codominant alleles, Fya and Fyb that also serve as receptors for Plasmodium vivax More than 70% of persons in malaria-endemic areas lack these antigens, probably from selective influences of the infection on the population Kidd Jka and Jkb may elicit antibodies transiently A delayed hemolytic transfusion reaction that occurs with blood tested as compatible is often related to delayed appearance of anti- Jka More than 100 blood group systems are recognized, composed of more than 500 antigens. The presence or absence of certain antigens has been associated with various diseases and anomalies; antigens can also act as receptors for infectious agents. Some clinical advice and tidbits If you’re planning to test a patient for factor deficiency, coagulopathy, anti-platelet antibody, etc - test before you transfuse A person’s blood type can change after bone marrow transplant. Immunohematology tests Blood type Done to determine ABO and Rh Antihuman globulin (Coombs’) serum test Direct antiglobulin (DAT) Indirect antiglobulin test (antibody screening test) Type & Screen Crossmatch HLA testing Antihuman globulin serum test Otherwise known as the Coombs’ test Coombs’ reagent is a rabbit IgM antibody raised against human IgG or human complement There are two types of Coombs’ test DAT = direct antiglobulin test (direct Coombs’) Indirect antiglobulin test (indirect Coombs’) Antihuman globulin serum test DAT = direct antiglobulin test (direct Coombs’) Mix the patient’s RBC with the Coombs reagent and look for agglutination which indicates antibody on the RBC surface Used in the diagnosis of hemolytic anemia Antihuman globulin serum test Indirect antiglobulin test (indirect Coombs’) Sometimes also called the “antibody test” How the test is done: Mix the patient’s serum with a panel of type O red blood cells and incubate Add Coombs’ reagent Agglutination indicates the presence of free antibody on the patient’s serum Used to detect in-vitro antibody-antigen reactions Can detect very low concentrations of antibodies present in a patient's plasma/serum prior to a blood transfusion When the indirect Coombs’ test is used to test a sample of the patient’s blood against a potential donor’s blood this is a called a match cross- Then what is a type & screen? Type & Screen Combination of blood type and the indirect Coombs’ test This gives you three pieces of information ABO Rh a positive or negative antibody screen Though there are many antigen systems present on the RBC only ABO and Rh are specifically tested prior to all transfusions Order this when you need to know a blood type and any major antibodies Often used upon hospital admission in case blood will be needed, preoperatively and as part of prenatal testing Health systems usually have strict guidelines about type & screens and blood transfusions And what is a crossmatch? I need 4 units typed and crossed. STAT! Crossmatch Also known as the type & cross Ordered when there is a high probability that the patient will require a PRBC transfusion Blood selected for cross-matching must be ABO compatible and lack antigens for which the patient has alloantibodies Non-reactive cross-matching confirms the absence of any major incompatibility and reserves that unit for the patient HLA = human leukocyte antigen And what about HLA? HLA test detects antigens (genetic markers) on white blood cells. There are four types of human leukocyte antigens: HLA-A, HLA-B, HLA-C, and HLA-D. HLA testing Why would you test for HLA type? HLA testing is used to provide evidence of tissue compatibility typing of tissue recipients and donors HLA testing is not routinely done with RBC transfusions Many of the alloantibodies that cause platelet destruction are directed at HLA antigens, so patients requiring long periods of platelet transfusions should be monitored to document adequate responses to transfusions so that the most appropriate product can be used. Alloimmunized patients may benefit from HLA-matched platelets. Universal donor/Universal recipient ABO/Rh compatibility for transfusion Remember the isoagglutinins? The naturally occurring anti-A and anti-B antibodies Type A patients have anti-B antibodies Type B patients have anti-A antibodies Type AB patients have neither Type O patients have both anti-A and anti-B antibodies Here’s where you get the terms universal donor/universal recipient Persons with type AB are universal recipients because they do not have antibodies against any ABO phenotype Persons with type O blood can donate to essentially all recipients and are called universal donors because their cells are not recognized by any ABO isoagglutinins Donors and Recipients www.redcrossblood.org Fresh whole blood Packed red blood cells Leukocyte-poor blood What products are available to transfuse? Frozen packed red blood cells Autologous packed red blood cells Platelets Granulocytes Plasma components • Fresh frozen plasma • Cryoprecipitate Think before you transfuse… Weigh the risks and benefits of transfusion Remember that blood products are a limited resource Discuss with the patient and their family and obtain consent Transfusion: Red Cells Red cells should be given in cases of anemia when oxygenation is decreasing secondary to level of anemia The decision to give RBCs should be based on the clinical situation and not an arbitrary lab value Important to look at the entire clinical picture i.e. signs of hemodilution as the cause of anemia Transfusion: Red Cells There are multiple forms of red cells that can be transfused Fresh whole blood Packed red blood cells Leukocyte-poor blood Frozen packed red blood cells Autologous packed red blood cells Transfusion: Red Cells Fresh whole blood Contains red cells, plasma and fresh platelets Fresh whole blood is never absolutely necessary since all components are available separately Indications: Cardiac surgery Massive hemorrhage When more than 10 units is required in a 24 hour period Transfusion: Red Cells Packed red blood cells Often denoted as PRBCs The most commonly used component to raise the hematocrit Each unit is about 300ml which has about 200ml of red blood cells One unit will usually raise the hematocrit by ~4% Indications: Anemia Transfusion: Red Cells Leukocyte-poor blood red blood cells Patients with severe leukoagglutinin reactions to packed red blood cells may require depletion of white blood cells and platelets from transfused units Removing the WBC can be done by centrifuge or by washing Expensive to prepare and leads to loss of some red cells Yet, most RBC products are now leukoreduced in-line during acquisition and are thus prospectively leukocyte poor Transfusion: Red Cells Frozen packed red blood cells Fresh RBCs can be packed and stored for up to 3 years Frozen blood should be used sparingly Usually, it’s used to maintain a supply of rare blood types Occasionally used for patients with leukoagglutinin reactions or anaphylactic reactions to plasma proteins Frozen blood has essentially all white blood cells and plasma components removed Transfusion: Red Cells Autologous packed red blood cells Patient’s own blood donated prior to elective surgery Can be donated up to 35 days prior to planned use before freezing is necessary Not always recommended as this can lead to anemia prior to surgery Not without risk: Still have the risk of allergic type transfusion reactions and bacterial contamination Transfusion: Platelets Platelets Usually given as pools prepared from 5-8 random donors or as single donor apheresed units Used in the treatment of thrombocytopenia due to decreased platelet production Can be used in immune thrombocytopenia as well when active bleeding is present The transfused platelets will be used quickly though, as are exposed to the same pathophysiologic forces as the patient’s own platelets Transfusion: Platelets Platelets cont. Platelets can be given When platelet counts fall below 80K and the patient is bleeding As prophylaxis prior to surgery in patients with the intent to raise the platelet count to at least 50K Remember spontaneous bleeding can occur when platelets are extremely low Life threatening spontaneous bleeds at less than 5K Usually, prophylactic platelets are given at levels less than 10K. Don’t give platelets in the case of TTP or HUS Transfusion: Granulocytes Granulocytes Seldom indicated and now nearly obsolete because of myeloid growth factors (G-CSF) that speed neutrophil recovery after myelosuppressive chemotherapy Filgrastim, pegfilgrastim Transfusion: Granulocytes Granulocytes, cont. Rare use in the patient with profound neutropenia (<100/mcl) who has gramnegative sepsis, progressive soft tissue infection or invasive fungal infection despite optimal antibiotics Donor cells usually contain lymphocytes capable of producing GVHD in HLAincompatible hosts whose immunocompetence may be impaired Irradiation of the granulocyte products will prevent lymphocyte proliferation and thus prevent GVHD without functional harm to the granulocytes or platelets in the unit Transfusion: Plasma Plasma components Fresh frozen plasma Available in units of approximately 200ml. FFP contains normal levels of all coagulation factors Used to correct coagulation factor deficiencies and to treat TTP or HUS Cryoprecipitate Made from FFP by cooling the plasma to 4ºC and collecting the precipitate One unit of cryo has a volume of 20ml and contains approximately 250mg of fibrinogen and 80-100units of factor VIII and vWF Used to supplement fibrinogen in acute DIC Let’s break here… Potential adverse effects of transfusion Transfusion reactions result from two mechanisms Immune-mediated reactions Nonimmunemediated reactions Immune-mediated transfusion reactions Acute hemolytic transfusion reaction Delayed hemolytic transfusion reaction Febrile nonhemolytic transfusion reaction Allergic reaction Anaphylactic reaction Graft-versus-Host Disease Transfusion-Related Acute Lung Injury Post-transfusion pupura Alloimmunization Immune-mediated transfusion reactions Acute hemolytic transfusion reactions Immune mediated hemolysis occurs when the recipient has preformed antibodies that lyse donor RBCs ABO isoagglutinins are responsible for the majority of these reactions, although alloantibodies directed against other RBC antigens like Rh, Kell and Duffy may result in hemolysis Clinical presentation: Hypotension, tachypnea, tachycardia, fever, chills, decreased hemoglobin and hemoglobinuria, chest and/or flank pain, discomfort at the infusion site, renal dysfunction Immune-mediated transfusion reactions Acute hemolytic transfusion reactions cont. Treatment: Monitor vital signs closely during transfusions If suspected STOP TRANSFUSION immediately Send post transfusion blood sample and un-transfused blood back to blood bank for analysis Measure serum haptoglobin, LDH and indirect bilirubin Give IV fluids and ensure diuresis Check coags (PT, PTT), fibrinogen and platelet count – looking for DIC Immune-mediated transfusion reactions Acute hemolytic transfusion reactions cont. Errors at the patient’s bedside such as mislabeling the sample or transfusing the wrong patient are responsible for the majority of these reactions Immune-mediated transfusion reactions Delayed hemolytic and serologic transfusion reactions DHTR (delayed hemolytic transfusion reactions) are not completely preventable Reactions occur in patients who have been previously sensitized to RBC alloantigens yet have a negative alloantibody screen due to low antibody levels When the patient is transfused with antigen-positive blood an amnestic response results in the early production of alloantibody that binds donor RBCs Immune-mediated transfusion reactions Delayed hemolytic and serologic transfusion reactions The alloantibody is detectable 1-2 weeks following the transfusion and the post-transfusion DAT may become positive due to circulating RBCs coated with antibody or complement The transfused, alloantibody-coated RBCs are cleared by the RES system These reactions are detected most commonly in the blood bank when a subsequent patient sample reveals a positive alloantibody screen or a new alloantibody in a recently transfused patient No specific therapy is usually required, although additional RBC transfusions may be necessary Immune-mediated transfusion reactions Febrile non-hemolytic transfusion reaction The most frequent reaction associated with cellular blood components is fever Chills and rigors and a greater than or equal to 1ºC rise in temperature Likely caused by the leukocytes and HLA antigens in the blood Use of leukocyte reduced blood products may prevent this Premedication with acetaminophen is common before transfusions to prevent this Immune-mediated transfusion reactions Allergic reactions Urticarial reactions are related to plasma proteins Mild reactions can be treated symptomatically by temporarily stopping the transfusion and administering antihistamines diphenhydramine 50mg orally or IM Transfusion can be completed after the signs and symptoms resolve Patients with a history of allergic transfusion reaction should be pre-medicated with antihistamine Often this is part of a standing order prior to transfusion with diphenhydramine 25mg PO Immune-mediated transfusion reactions Anaphylactic reactions Severe reaction that presents after transfusion of only a few mL of blood component Signs and symptoms include: Difficulty breathing, coughing, nausea, vomiting, hypotension, bronchospasm, loss of consciousness, respiratory arrest, shock Treatment includes: STOPPING THE TRANSFUSION Maintain IV access Administer epinephrine Give IV steroids in severe cases Immune-mediated transfusion reactions Graft-Versus-Host Disease GVHD is a frequent complication of allogeneic stem cell transplantation lymphocytes from the donor attack and cannot be eliminated by an immunodeficient host With transfusions this is when donor T lymphocytes recognize host HLA antigens as foreign and mount an immune response Signs and symptoms include: fever, cutaneous eruption, diarrhea, LFT abnormalities, marrow aplasia and pancytopenia Transfusion associated GVHD is highly resistant to treatment with immunosuppressive therapy, clinical manifestations appear 8-10 days after transfusion and death 3-4 weeks post-transfusion GVHD can be prevented by irradiation of cellular components before transfusion to atrisk patients Population at risk includes fetuses receiving intrauterine transfusions, lymphoma patients, immunocompromised patients, recipients of donor units know to be from a blood relative and marrow transplant patients Directed donations from family members should be discouraged as often families share HLA antigens Immune-mediated transfusion reactions Transfusion-Related Acute Lung Injury TRALI is an uncommon reaction from the transfusion of donor plasma that contains high-titer anti-HLA antibodies that bind recipient leukocytes Leukocytes aggregate in the pulmonary vasculature and release mediators that increase capillary permeability Clinical presentation: Respiratory compromise with dyspnea, tachypnea, hypoxia, signs of non-cardiogenic pulmonary edema, including bilateral interstitial infiltrates on CXR Treatment is supportive Patients usually recover without sequelae Immune-mediated transfusion reactions Post-transfusion purpura Thrombocytopenia 7-10 days after platelet transfusion with purpura Occurs predominantly in women Platelet specific antibodies are found in the recipient's serum Delayed thrombocytopenia is due to the production of antibodies that react to both donor and recipient platelets Additional platelet transfusions can worsen the TCP and should be avoided Treatment is with IVIG Immune-mediated transfusion reactions Alloimmunization A recipient may become alloimmunized to a number of antigens Detected during pretransfusion testing presence of multiple antibodies may create delays in finding antigen-negative crossmatch compatible products for transfusion Women of childbearing age who are sensitized to certain RBC antigens (i.e., D, c, E, Kell or Duffy) are at risk for bearing a fetus with hemolytic disease of the newborn To prevent alloimmunization use leukoreduced units and limit transfusions Potential adverse effects of transfusion Transfusion reactions result from two mechanisms Immune-mediated reactions Nonimmunemediated reactions Nonimmune-mediated transfusion reactions Fluid overload Blood components are excellent volume expanders and transfusion may quickly lead to volume overload Monitoring the rate and volume of the transfusion and using a diuretic can minimize this problem Often patients with delicate fluid balance problems (CHF) you give IV furosemide after PRBCs Nonimmunemediated transfusion reactions Hypothermia Refrigerated blood (4ºC) or frozen (-18ºC) blood components can result in hypothermia when rapidly infused. Cardiac arrhythmias can result from exposing the sinoatrial node to cold fluid Use of an in-line warmer can prevent this complication Nonimmune-mediated transfusion reactions Electrolyte abnormalities RBC leakage during storage increases the concentration of potassium in the unit Neonates and patients in renal failure are at risk for hyperkalemia. Preventative measures such as using fresh or washed RBCs are warranted for neonatal transfusions because this complication can be fatal Citrate is used as an anti-coagulant in the unit because it chelates calcium and inhibits the coagulation cascade Hypocalcemia can happen from multiple rapid transfusions Signs and symptoms include: • Circumoral numbness, tingling of the fingers and toes Nonimmunemediated transfusion reactions Iron overload Each unit of PRBCs contains 200-250mg of iron Over time multiple transfusions can cause build up of iron leading to cardiac, liver and endocrine problems Nonimmunemediated transfusion reactions Hypotension Transient hypotension may be noted in transfused patients who take ACE inhibitors Blood products contain bradykinin that is normally degraded by ACE, patients on ACE inhibitors may have increased bradykinin levels that cause hypotension Typically resolves without intervention Nonimmune-mediated transfusion reactions Immunosuppression Transfusion can increase the risk of infection This is demonstrated by poorer outcomes in cancer patients May be good for renal transplant patients as multiply transfused recipients are less likely to reject the graft Thought to be mediated by transfused leukocytes Since the majority of the blood supply now is leukocyte depleted and immunosuppression continues to happen there is more research to be done Nonimmune-mediated transfusion reactions Infectious complications Viral Testing for HIV and HCV began in 1985 West Nile virus testing began in 2003 CMV, Syphilis, HTLV, Parvovirus B-19 also tested Risk of HCV is now about 1 in 2 million units transfused Infection may be asymptomatic or lead to chronic active HCV, cirrhosis and liver failure Risk of HIV is 1 in 2 million units transfused Risk of Hepatitis B is 1 in 63,000 units vaccination for Hep B is widely available and can be given to patients who will require long-term transfusion therapy Risk of HTLV is 1 in 641,000 units transfused CMV risk can be reduced by leukocyte-depleted components Parvovirus B-19 causative agent of erythema infectiosum (fifth disease in children) Nonimmune-mediated transfusion reactions Infectious complications Bacterial contamination Most bacteria do not grow well at cold temps so PRBCs and FFP are not common sources of bacterial contamination Platelet concentrates however, are stored at room temp and are more likely to contain skin contaminates such as gram+ organisms including coag-neg staph estimated 1 in 1000-2000 units of platelets is contaminated risk of death due to transfusion-associated sepsis is 1 in 17,000 for single unit platelets derived from whole blood donation and 1 in 61,000 for apheresis product Signs/symptoms: fevers and chills, can progress to septic shock and DIC may happen within minutes of initiating the transfusion or after several hours Treatment: stop the transfusion, give broad-spectrum antibiotics, culture the patient and send the unit for culture as well Others (like parasites) Malaria, babesiosis, Chagas disease, Lyme disease, variant Creutzfeldt-Jakob disease (Mad cow disease) Rh hemolytic disease of the newborn Alloantibodies in the mother (from previous transfusion or pregnancy) are usually IgG and can cross the placenta during pregnancy These antibodies may attack the fetal RBCs bearing the corresponding antigen resulting in hemolytic disease of the newborn In severe cases fetal tissues become swollen and can be fatal - hydops fetalis Since the 1970s routine prenatal care includes screening of all expectant mothers to find those whose pregnancy might be at risk There have been dramatic decreases in the incidence of Rh hemolytic disease Rh hemolytic disease of the newborn The major cause is usually incompatibility of the Rh blood group between mother and fetus Most commonly the D antigen of the Rh system If mother is Rh D- and becomes pregnant with a Rh D+ fetus, the mother’s immune response to the fetal D antigen is to form antibodies against it Sensitization usually occurs during the first pregnancy It only takes a small amount of blood In subsequent pregnancies the mother is now sensitized Rh hemolytic disease of the newborn Expectant mothers are screened first with blood type (ABO and Rh) If mother is Rh – then do indirect Coombs to see if she has been sensitized This finds anti-RhD antibodies before the fetal RBCs have been attacked Treatment: Decrease risk of future sensitization by giving all mothers anti-D Ig which “mops up” any fetal RBCs that may have leaked into the maternal circulation reducing the risk of first-time exposure to D antigen Treat with Rho(D) Immune Globulin treatment "RhoGAM" Schedule Mothers receive the first injection of anti-D Ig around 28 weeks which is about the time that fetal RBCs start to express the D antigen another dose at 34 weeks final dose after delivery Rh hemolytic disease of the newborn There is no routine prophylaxis for HDN caused by incompatibility of other blood groups What happens if the mother has already been sensitized and the fetal blood type is Rh D+? Pregnancy is carefully monitored for signs of HDN with regular ultrasounds and anti-D in the mother’s serum If fetal blood tests confirm fetal anemia, then a blood transfusion can be done in utero to replace the lysed fetal RBCs Blood transfusions may be needed in the newborn period Questions? If you have questions later… E-mail me, Erin Kunz at [email protected]