Blood Bank Flashcards
In 2012, the AABB’s Clinical Transfusion Medicine Committee issued 3 clinical practice guidelines regarding RBC transfusion. That are they?
- Adhere to a restrictive transfusion strategy (7 to 8 g/dL as a transfusion trigger) for hospitalized, stable patients. 2. Adhere to a restrictive transfusion strategy in hospitalized patients with preexisting cardiovascular disease and consider transfusion for patients with symptoms or with a hemoglobin level of 8 g/dL or less. 3. Transfusion decisions should be influenced by symptoms as well as hemoglobin concentration. There was high-quality evidence for recommendation #1 and moderate-quality evidence for recommendation #2.
What is contained in prothrombin complex concentrate and in activated prothrombin complex concentrate?
PCC contains vitamin K-dependent clotting factors (factors II, VII, IX, and X) (mostly unactivated forms) and proteins C and S. aPCC has higher amounts of the activated forms (factors VIIa and Xa). To prevent activation, most PCC contain heparin.
Are prothrombin complex concentrates approved for hemophilia B?
Neither PCC nor aPCC are approved for hemophilia B (factor IX deficiency) because recombinant or purified factor IX products are available. PCC is approved for congenital prothrombin or factor X deficiencies, and is used off-label for urgent reversal of warfarin over-anticoagulation. aPCC is approved for acute bleeds in hemophilia A or B and in patients with clotting factor inhibitors.
Prothrombin complex concentrates are produced by…
PCC are produced by ion-exchange chromatography from the cryoprecipitate supernatant of large plasma pools after removal of antithrombin and factor XI. Different processing techniques involving ion exchangers enable the production of either three-factor (i.e., factors II, IX and X) or four-factor (i.e., factors II, VII, IX and X) concentrates with a final overall clotting factor concentration approximately 25 times higher than in normal plasma. To prevent activation of these factors, most PCC contain heparin. PCC may also contain the natural coagulation inhibitors protein C and protein S. The PCC are standardised according to their factor IX content. All PCC undergo at least one step of viral reduction or elimination (solvent detergent treatment, nanofiltration, etc.).
Dabigatran (Pradaxa) is an alternative to warfarin FDA approved 10/2010 for patients with atrial fibrillation. Currently there is no reversal medication available. If there is bleeding, the recommendation is ___. If there is severe bleeding or CNS bleeding, the recommendation is ___.
If there is bleeding, the recommendation is to give plasma. If there is severe bleeding or CNS bleeding, the recommendation is to give plasma and Novo-7.
At UTMCK, all factor concentrates are stored in and dispensed from the pharmacy. The only non-blood product in our blood bank is ___.
At UTMCK, all factor concentrates are stored in and dispensed from the pharmacy. The only non-blood product in our blood bank is Rh IG.
3-factor PCCs and 4-factor PCCs.
All prothrombin complex concentrates contain factors II, VII, IX, but some products contain no or very little FVII. PCCs with normal amounts of VII are known as 4-factor PCCs while the products without VII are 3-factor PCCs. In the United States, two 3-factor PCCs are available (Bebulin VH, Profilnine, Profilnine SD), and one 4-factor PCC is available (Proplex T).
FFP vs. PCC for emergency anticoagulation reversal for warfarin.
FFP contains normal levels of all the coagulation factors while PCCs contain factors II, IX and X with variable amounts of factor VII in a concentrated form. PCCs are virally inactivated and can be given in a small volume without the need to thaw the product first. FFP however, has to be thawed before use, must be blood group specific and because it needs to be given at a dose of at least 10–15 mL/kg, it risks precipitating volume overload in the recipients who are often frail and elderly. Some guidelines recommend PCCs over FFP because of their more rapid administration and complete INR correction.
In UTMCK massive transfusion protocol, how many units of RBCs are in each cooler?
4 units RBCs per cooler. After 3 coolers, there is no need to crossmatch additional units, since 8-10 units RBCs is considered complete blood volume replacement.
All platelet units at UTMCK are (whole blood derived/apheresis derived).
All platelet units at UTMCK are apheresis derived.
For platelet apheresis donation, single dose aspirin or piroxicam use is a __ day deferral, daily aspirin or piroxicam use is a __ day deferral, and clopidogrel and ticlopidine use is a __ day deferral.
For platelet apheresis donation, single dose aspirin or piroxicam use is a 2 day deferral, daily aspirin or piroxicam use is a 14 day deferral, and clopidogrel and ticlopidine use is a 14 day deferral.
Patients undergoing cardiopulmonary bypass may have platelet dysfunction due to ___.
Patients undergoing cardiopulmonary bypass may have platelet dysfunction due to activation of platelets during the procedure. Because of this pump effect, post-bypass platelet transfusion is based upon clinical findings rather than platelet counts.
What two conditions are absolute contraindications for platelet transfusion, and what condition is a strong relative contraindication?
Absolute contraindications: TTP and HIT. Immune thrombocytopenia (idiopathic thrombocytopenic purpura and post-transfusion purpura) are strong relative contraindications; Do not transfuse unless severe thrombocytopenia with life-threatening bleeding; Large numbers of units may be needed due to rapid immune destruction.
Can platelets be transfused with an IV pump?
The use of an IV pump is contraindicated for transfusion in most circumstances because the platelets could become activated, depending upon the pump type and FDA clearances. At UTMCK, since only some of our pumps are FDA approved for platelet transfusion and it could cause confusion, nursing policy is that IV pumps are not to be used for platelet transfusion.
What is the #1 cause of transfusion-related deaths?
TRALI.
Are FFP, FP24, and 5-day cold plasma considered equivalent blood products?
Generally yes, except that FP24 and 5-day cold plasma should not be used for replacement of Factor V or Factor VIII. However, selective Factor V deficiency is rare, occuring in ~1/million and the general population and is not associated with a bleeding tendency; also, Factor VIII concentrate is an available product, and cryoprecipitate can be used if factor concentrate is unavailable. So FFP, FP24, and 5-day cold plasma are basically equivalent blood products.
At UTMCK, we use FP24 or 5-day cold plasma instead of FFP for all uses except for ___.
At UTMCK, we use FP24 or 5-day cold plasma instead of FFP for all uses except for the NICU, for preparation of red cells for exchange transfusion, and for therapeutic apheresis.
Place the following blood types in decreasing order of amount of H antigen: A1, A2, A1B, A2B, B, O.
O»A2>B>A2B>A1>A1B.
What lectin is used to distinguish A1 from A2 RBCs?
Dolichos biflorus lectin is used to distinguish A1 from A2, as it will agglutinate A1 but not A2 RBCs.
In ABO blood types, there are at least __ different A subgroup alleles and ___ B subgroup alleles, as well as __ different O alleles.
In ABO blood types, there are at least 41 different A subgroup alleles and 18 B subgroup alleles, as well as 61 different O alleles. This heterogeneity makes ABO typing with DNA technologies complicated. In addition, the same genotype gives rise to different phenotypes even within families, which further adds to the complexity.
The Rh system has at least (#) antigens, most notably (5).
The Rh system has at least 45 antigens, most notably C, c, E, and e antigens, which are carried on the RhCE protein encoded by the RHCE gene, and the D antigen on the RhD protein encoded by the RHD gene. The RHCE and RHD genes are 96% homologous and are adjacent to one another on chromosome 1.
What are the Rh null and Rh mod phenotypes?
The Rh antigens are carried on hydrophobic 12-pass transmembrane proteins. The RhAG protein does not carry Rh antigens, but is important for bringing the RhD and RhCE proteins to the membrane. Lack of RhAG results in the absence of Rh antigen expression (Rh null phenotype) or marked reduction of Rh antigen expression (Rh mod phenotype).
What are the regular and amorph types of Rh-null?
Rh-null RBCs lack expression of Rh antigens, are stomatocytic and spherocytic, and affected individuals have variable degrees of anemia. The regulator type is caused by mutations in the RHAG gene so they have no Rh or RhAG proteins, and the amorph type is caused by mutations in the RHCE gene on a deleted RHD background so they have no Rh proteins and reduced RhAG proteins.
Anti-D, anti-c, anti-C, anti-e, and anti-E Rh antibodies. Which cause severe HDFN and which cause no or mild HDFN?
Anti-D and anti-c can cause severe HDFN, while anti-C, anti-e, and anti-E usually cause no or mild HDFN.
In blood donor deferral durations for history of recent vaccination, some live attenuated viral and bacterial vaccines are a 2 week deferral, while others are a 4 week deferral. What vaccines fall into these 2 categories?
2 week deferral: Measles (rubeola), mumps, polio (Sabin/oral), typhoid (oral), yellow fever. 4 week deferral: German measles (rubella), chickenpox (Varicella zoster).
What are donation intervals for whole blood, 2-unit RBC, infrequent plasmapheresis, and plasma-, platelet-, or leukapheresis?
> or =56 days after whole blood donation. > or=112 days after 2-unit RBC donation. > or=28 days after infrequent plasmapheresis. > or =2 days after plasma-, platelet-, or leukapheresis.
Blood donation is deferred if a patient is currently pregnant or has been pregnant within the last __ weeks.
Blood donation is deferred if a patient is currently pregnant or has been pregnant within the last 6 weeks.
For testing blood donors, list the infectious diseases that fall into each of the following 3 categories: Tests are available but may not detect early-stage or window-period infections. Tests are available but not used in all donor centers. No licensed laboratory tests are available for blood donor screening.
Tests are available but may not detect early-stage or window-period infections: Chagas disease. Hepatitis (HBV, HCV). HIV-1,-2. HTLV, types I and II. West Nile Virus. Tests are available but not used in all donor centers: HIV group O. No licensed laboratory tests are available for blood donor screening: Babesiosis. CJD. Variant CJD. Malaria.
What is Evans syndrome?
Evans syndrome is an autoimmune disease in which an individual’s antibodies attack their own RBCs and platelets. Both of these events may occur simultaneously or one may follow on from the other. Its overall pathology resembles a combination of autoimmune hemolytic anemia and ITP. The diagnosis is made upon blood tests to confirm not only hemolytic anemia and idiopathic thrombocytopenic purpura, but also a positive DAT and an absence of any known underlying etiology. Other antibodies may occur directed against neutrophils and lymphocytes, and “immunopancytopenia” has been suggested as a better term for this syndrome. Initial treatment is with glucocorticoid corticosteroids or IVIg, a procedure that is also used in ITP cases. Although the majority of cases initially respond well to treatment, relapses are not uncommon and immunosuppressive drugs are subsequently used. Splenectomy is effective in some cases, but relapses are not uncommon. The only prospect for a permanent cure is allogeneic HSCT.
What are the compositions of the RBC additive solutions CPD, CPDA-1, and AS-1, and the outdates for products with these additive solutions?
CPD: citrate, sodium phosphate, dextrose; 21 days. CPDA-1: citrate, sodium phosphate, dextrose, adenine; 35 days. AS-1: dextrose, sodium phosphate, adenine, mannitol, sodium chloride; 42 days.
Random donor platelets must contain as least ___ of platelets, while pheresis platelets must contain at least ___ platelets.
Random donor platelets must contain as least 5x10^10 of platelets, while pheresis platelets must contain at least 3x10^11 platelets.
Irradiated RBCs, for the prevention of GVHD, are good for __ days post-irradiation, or the original outdate, whichever comes first.
Irradiated RBCs, for the prevention of GVHD, are good for 28 days post-irradiation, or the original outdate, whichever comes first.
When plasma is separated from platelet concentrate, it must be placed into an __ C or colder freezer within __ hours of blood collection to make FFP. It expires in __ years. After thawing it expires in __ hours.
When plasma is separated from platelet concentrate, it must be placed into an -18 C or colder freezer within 8 hours of blood collection to make FFP. It expires in 1 year. After thawing it expires in 24 hours.
The degree of leukoreduction depends on the goal. If meant to prevent febrile reactions, the unit must contain <__ WBCs.
The degree of leukoreduction depends on the goal. If meant to prevent febrile reactions, the unit must contain <5x10^6 WBCs.
What are 4 definitions of “massive transfusion?”
Transfusion of an amount of blood equal to the patient’s blood volume in 24 hours. Transfusion of 10+ units of blood in 24 hours. Transfusion of 50% of blood volume in 3 hours. Transfusion to replace blood loss of over 150 mL/min.
What RBCs can you give if… 1. Blood is needed now (30 min.
- Uncrossmatched group O neg. May start out with O pos if male or older female during emergencies. 2. Uncrossmatched ABO group and Rh type specific. 3. Crossmatched ABO group and Rh type specific. *Use all possible means to give D-negative blood to childbearing age and younger females. *When D-negative blood is used, be prepared to switch to D-positive blood if massive use depletes inventory.
The half-life of RhIG is ___.
The half-life of RhIG is ~25 days. However, it can be detected for as long as 6 months.
Platelet refractoriness is the inability to respond to platelet transfusion with a significant qualitative increase in platelet count. Are immune or nonimmune causes more frequent?
Nonimmune causes outweigh immune causes. Nonimmune causes include: fever, splenomegaly, DIC, bleeding (?), drugs (such as amphotericin). Immune causes include anti-HLA and/or anti-platelet antibodies.
Pink-top blood collection tubes are used in immunohematology for ABO grouping, Rh typing, and antibody screening. These tubes have a special cross-match label for information required by ___.
Pink tubes are used in immunohematology for ABO grouping, Rh typing, and antibody screening. These tubes have a special cross-match label for information required by the American Association of Blood Banks (AABB) and approved by the U.S. Food and Drug Administration (FDA) for blood bank collections.
Leukocyte reduction of blood components reduces the risk of what 3 things?
Leukocyte reduction of blood components reduces alloimmunization to human leukocyte antigens, cytomegalovirus transmission, and febrile reactions.
Failure to respond to platelet transfusion may be due to what 3 general categories of causes? Give examples within each category as well.
Failure to respond to platelet transfusion may be due to immune causes (human leukocyte antigens or platelet-specific antibodies), nonimmune clinical causes (bleeding, splenomegaly, disseminated intravascular coagulation, medications), or product-specific causes (ABO incompatibility, age of component).
Plasma transfusion is generally indicated for what conditions/situations?
Plasma transfusion is generally indicated for coagulation factor deficiency, disseminated intravascular coagulation, dilutional coagulopathy, urgent warfarin reversal, and thrombotic thrombocytopenic purpura.
Blood centers and transfusion services (collectively known as ___) are regulated by ___.
Blood centers and transfusion services (collectively known as blood establishments) are regulated by the FDA. All blood establishments must be registered with the FDA, and blood centers that manufacture blood components must be licensed. Criteria for the acceptability of blood donors, performance of pretransfusion testing, manufacture of blood components, donor infectious disease testing, and evaluation and reporting of adverse events associated with transfusion are all defined by the FDA. Blood establishments are subject to periodic unannounced inspections by the FDA.
There are rare circumstances under which directed donation may be desirable. What circumstances?
These include rare blood group compatibility requirements and limitations of donor exposure for patients with long-term expected transfusion requirements such as aplastic anemia. In cases of neonatal alloimmune thrombocytopenia, collection of maternal platelets may be the best way of providing compatible antigen-negative platelets. In the past, donor-specific transfusion was utilized in kidney transplantation. However, with current immunosuppressive regimens, the value of donor-specific transfusion in prolonging renal graft survival is questionable.
What are vital signs requirements for allogeneic blood donation?
BP less than or equal to 180/100. Pulse 50-100 bpm without pathologic irregularities; <50 acceptable is an otherwise healthy athlete. Temp less than or equal to 37.5 C.
What infectious disease risks are an indefinite deferral from allogeneic blood donation?
Viral hepatitis after 11th birthday. Positive test for hepatitis B surface antigen. Repeat reactive test for anti-HBc on more than one occasion. Clinical or laboratory evidence of HCV, HTLV, or HIV infection by current FDA regulations. Previous donation associated with hepatitis, HIV, or HTLV transmission. Behavioral risk factors for HIV infection according to current FDA guidance. History of babesiosis or Chagas’ disease. Stigma of parenteral drug use. Injection of nonprescription drugs. Risk of vCJD according to current FDA guidelines.
What infectious disease risks are a 12-month deferral from allogeneic blood donation?
Mucous membrane exposure to blood. Nonsterile skin or needle penetration. Sexual contact with an individual with a confirmed positive test for hepatitis B surface antigen. Sexual contact with an individual with viral hepatitis. Sexual contact with an individual with HIV infection or at higher risk for HIV infection. Incarceration in a correctional institution for longer than 72 consecutive hours. History of syphilis or gonorrhea.
The maximum allowable storage time for RBCs is defined by ___.
The maximum allowable storage time for RBCs is defined by the requirement for recovery of 70% of transfused cells 24 hours after transfusion.
Plasma may be stored in the liquid state at __–__° C, or it may be frozen for extended preservation. In the liquid state at refrigerator temperatures, there is loss of labile clotting factors, particularly factor __ and factor __. Fresh frozen plasma (FFP) is separated from the RBCs and is placed at __ C within __ hours of collection. Plasma frozen within 24 hours after phlebotomy (FP24) is manufactured similarly to FFP but may not be frozen for up to 24 hours after collection. Frozen plasma may be stored for up to 1 year at __ C or lower. Before transfusion, both FFP and FP24 are thawed at __ C and must be transfused within __ hours. Thawed plasma not used within 24 hours may be relabeled as “Thawed Plasma.” Thawed plasma can be kept at refrigerator temperatures for up to __ days, while adequate levels of factors __ and __ are maintained.
Plasma may be stored in the liquid state at 1°–6° C, or it may be frozen for extended preservation. In the liquid state at refrigerator temperatures, there is loss of labile clotting factors, particularly factor VIII and factor V. Fresh frozen plasma (FFP) is separated from the RBCs and is placed at −18° C within 8 hours of collection. Plasma frozen within 24 hours after phlebotomy (FP24) is manufactured similarly to FFP but may not be frozen for up to 24 hours after collection. Frozen plasma may be stored for up to 1 year at −18° C or lower. Before transfusion, both FFP and FP24 are thawed at 37° C and must be transfused within 24 hours. Thawed plasma not used within 24 hours may be relabeled as “Thawed Plasma.” Thawed plasma can be kept at refrigerator temperatures for up to 5 days, while adequate levels of factors V and VIII are maintained.
Do granulocyte units for transfusion need to be ABO compatible with the recipient?
Yes. Granulocyte units contain a substantial number of RBCs and must be ABO compatible with the recipient.
Why is prestorage leukocyte reduction favored over poststorage leukocyte reduction?
Both methods are effective for removing leukocytes. However, prestorage leukocyte reduction has the advantage of preventing accumulation of leukocyte-derived biological response modifiers, particularly cytokines, which may cause adverse reactions. In addition, filtration at the time of manufacture allows for better process control.
To be considered leukocyte reduced, blood components must be prepared by a method known to reduce the total number of residual leukocytes to fewer than ___ per unit for RBC and fewer than ___ for whole blood–derived PC.
To be considered leukocyte reduced, blood components must be prepared by a method known to reduce the total number of residual leukocytes to fewer than 5 × 106 per unit for RBC and fewer than 8.3 × 105 for whole blood–derived PC.
Why is irradiation not equivalent to leukocyte reduction?
Irradiation causes chromosomal damage, which prevents replication of transfused lymphocytes in the recipient. However, irradiated cells are immunogenic. Thus, irradiation is not equivalent to leukocyte reduction.
What is the minimum radiation dose for preparation of irradiated blood components?
The minimum dose is 25 Gy delivered to the center of the blood container and no less than 15 Gy to the periphery.
Red blood cells can be stored in the frozen state after addition of a cryoprotective agent, such as glycerol. Frozen RBCs can be stored in mechanical freezers or liquid nitrogen for up to ___. Frozen units are thawed rapidly at __ C, then the cryoprotective agent must be removed by progressive addition of washing solutions with decreasing osmolality. After deglycerolization, red cells can be stored for up to ___ at __–__ C if processed by an open method, or up to ___ if processed by a closed method. The main use of frozen RBCs is to ___.
Red blood cells can be stored in the frozen state after addition of a cryoprotective agent, such as glycerol. Frozen RBCs can be stored in mechanical freezers or liquid nitrogen for up to 10 years. Frozen units are thawed rapidly at 37 C, then the cryoprotective agent must be removed by progressive addition of washing solutions with decreasing osmolality. After deglycerolization, red cells can be stored for up to 1 day at 1–6 C if processed by an open method, or up to 14 days if processed by a closed method. The main use of frozen RBCs is to maintain an inventory of rare antigen-negative units.
2010 blood donor infectious disease testing required entities.
Hep B surface antigen (EIA). Hep B core antibody (EIA). Hep C virus antibody (EIA). HIV-1 and HIV-2 antibodies (EIA) (combined HIV p24 antigen, HIV-1 antibodies, and HIV-2 antibodies acceptable). HTLV-I and HTLV-II antibodies (EIA). Trypanosoma cruzi antibodies (EIA). Serologic test for syphilis. Hep C RNA (NAT). HIV RNA (NAT). West Nile virus DNA (NAT).
What are medications that are cause for deferral of allogeneic blood donation, and what are the deferral periods?
Finasteride, isotretinoin—defer 1 month after last dose. Dutasteride—defer 6 months after last dose. Acitretin—defer 3 years after last dose. Etretinate—defer indefinitely. Bovine insulin manufactured in the United Kingdom—defer indefinitely. Ingestion of medications that irreversibly inhibit platelet function (aspirin) within 36 hours of donation precludes use of donor as sole source of platelets.
In what situations is directed donation contraindicated?
Donation of any plasma-containing blood component from a mother to her child is particularly problematic because the formation of human leukocyte antigens (HLA) antibodies to fetal antigens is common in pregnancy, and transfusion of such antibodies can precipitate transfusion-related acute lung injury (see later). Transfusions from close relatives should be avoided in recipients of hematopoietic progenitor cell transplants because of the risk of immunization to HLA and other histocompatibility antigens, which may endanger graft survival.
What is a computer cross-match?
An alternative to a major cross-match performed between recipient serum or plasma and donor RBCs for ensurance of ABO compatibility is the so-called computer cross-match. This is applicable when at least two determinations of the recipient’s ABO group have been made, at least one on a current sample, and there are no unexpected antibodies. A validated computer system can then ensure that issued blood complements are ABO compatible.
What are desirable rates of infusion for blood products?
The desirable rate of administration depends on the patient’s blood volume, cardiac status, and hemodynamic state. Except for urgent resuscitation, the transfusion should be started slowly (approximately 2 mL/minute for the first 15 minutes). The patient should be carefully observed for the first 15 minutes of infusion because severe reactions such as hemolysis, anaphylaxis, or sepsis may manifest after a small volume has entered the circulation. Subsequently, the administration rate may be increased. In general, it is desirable to complete a red cell transfusion within 2 hours and a platelet or plasma transfusion within 30–60 minutes. Any transfusion should be completed within 4 hours of initiation. Patients at risk of volume overload may require slower administration. If the total administration time exceeds 4 hours, smaller-volume blood components should be provided. When high flow rates are required, such as in some resuscitation or surgical situations, a pressure infusion device may be used. When such devices are used, care must be taken to avoid mechanical hemolysis or air embolism.
In general, it is desirable to complete a red cell transfusion within __ hours and a platelet or plasma transfusion within __ -__ minutes. Any transfusion should be completed within __ hours of initiation.
In general, it is desirable to complete a red cell transfusion within 2 hours and a platelet or plasma transfusion within 30–60 minutes. Any transfusion should be completed within 4 hours of initiation.
List general guidelines for red cell transfusion.
Symptomatic anemia in a euvolemic patient. Acute blood loss of >15% of estimated blood volume. Preoperative Hb 500 mL. Hb <60%.
List general guidelines for platelet transfusion.
In bleeding associated with platelet dysfunction, or thrombocytopenic bleeding associated with coagulopathy, there is no single transfusion threshold, and therapy must be guided by the patient’s clinical condition. Otherwise, transfusion thresholds in the case of thrombocytopenia due to decreased production are as follows: Stable patient - platelet count <100,000/µL.
Platelet transfusion in ITP is (not/relatively/absolutely) contraindicated.
The platelet transfusion is relatively contraindicated in immune thrombocytopenic purpura. In this setting, posttransfusion platelet survival is extremely brief, and platelet transfusion is indicated only if there is severe hemorrhage.
Transfusion of one apheresis platelet unit, or an equivalent pool of whole blood–derived platelet concentrates, can typically be expected to raise the platelet count of an adult by ___–___/µL.
Transfusion of one apheresis platelet unit, or an equivalent pool of whole blood–derived platelet concentrates, can typically be expected to raise the platelet count of an adult by 20,000–40,000/µL.
A platelet corrected count increment of >___ at 1 hour or >___ at 24 hours generally indicates a successful transfusion.
A CCI >7500 at 1 hour or a CCI >4500 at 24 hours generally indicates a successful transfusion.
What is the formula for the platelet corrected count increment?
In assessing platelet transfusion effectiveness, it is useful to take into account dose and body size by calculating the CCI. CCI = (Platelet count increment x Body surface area in m^2) / Number of platelets transfused (x10^11).
How can obtaining a platelet count within 1 hour of completing a platelet transfusion be helpful in distinguishing immune from nonimmune causes of platelet refractoriness?
Typically, immune refractoriness will result in an inadequate platelet increment when measured at 1 hour. Typically, nonimmune refractoriness will manifest as an adequate CCI at 1 hour but shortened survival time, so that the platelet count by 24 hours may be back to baseline.
List the guidelines for plasma transfusion.
Coagulation factor deficiency, factor concentrate unavailable. Dilutional coagulopathy. Hemorrhage in liver disease. DIC. Coumadin reversal. TTP. Acute trauma resuscitation.
Standard coagulation tests such as PT and APTT are commonly used to assess the need for plasma transfusion; however, these tests are poorly predictive of bleeding risk. In general, if the PT and APTT are less than ___ times the midpoint of the reference range, no benefit will be obtained from plasma transfusion. If the INR is used, in general, no benefit will be derived from plasma transfusion if it is less than ___, although for nervous system and retinal hemorrhage, plasma may be reasonably used unless the INR is less than ___.
Standard coagulation tests such as PT and APTT are commonly used to assess the need for plasma transfusion; however, these tests are poorly predictive of bleeding risk. In general, if the PT and APTT are less than 1.5 times the midpoint of the reference range, no benefit will be obtained from plasma transfusion. If the INR is used, in general, no benefit will be derived from plasma transfusion if it is less than 1.5, although for nervous system and retinal hemorrhage, plasma may be reasonably used unless the INR is less than 1.3.
For maximal hemostatic effect, when should plasma be transfused in relation to the time of the invasive procedure? For a bleeding patient, how often may plasma transfusion have to be repeated to maintain adequate coagulation factor levels? In general, what dose of plasma per kilogram is needed to achieve hemostasis?
For maximal hemostatic effect, plasma should be transfused immediately before an invasive procedure is performed. For the bleeding patient, plasma transfusion may have to be repeated every 3–4 hours to maintain adequate coagulation factor levels. In general, a dose of 10–20 mL per kilogram is necessary to achieve a hemostatic effect.
List the guidelines for cryoprecipitate transfusion.
Factor VIII deficiency, factor concentrate unavailable. von Willebrand disease, factor concentrate unavailable. Hypofibrinogenemia. Factor XIII deficiency. Uremic bleeding (DDAVP preferred). Topical fibrin sealant (commercial product preferred).
Exchange transfusion of the neonate for hyperbilirubinemia is usually indicated if the total bilirubin is greater than ___ mg/dL.
Exchange transfusion of the neonate for hyperbilirubinemia is usually indicated if the total bilirubin is greater than 25 mg/dL. A two-blood volume exchange is typically used, which can be expected to reduce the total bilirubin by 25% and the fetal red cell mass by about 70%.
List the guidelines for neonatal transfusion of RBCs, plasma, and platelets.
For RBC transfusion: Hct 35% or mechanical ventilation with MAP >6 cm H2O. Hct <100,000/µL in unstable premature infant.
Patients with deficiency of ___ or ___ can develop antibodies against them and have anaphylactic transfusion reactions.
Patients with deficiency of IgA or haptoglobin can develop antibodies against them and have anaphylactic transfusion reactions.
Acute hemolytic transfusion reactions, by definition, present within ___ of transfusion.
Acute hemolytic transfusion reactions, by definition, present within 24 hours of transfusion, while delayed hemolytic transfusion reactions occur at least 24 hours after transfusion of the offending unit. The time from transfusion to diagnosis of a DHTR is variable. Most patients present within the first 2 weeks after receiving the transfusion. However, clinical DHTR may be recognized more than 6 weeks later.
How long after transfusion do delayed hemolytic transfusion reactions occur?
Delayed hemolytic transfusion reactions occur at least 24 hours after transfusion of the offending unit. The time from transfusion to diagnosis of a DHTR is variable. Most patients present within the first 2 weeks after receiving the transfusion. However, clinical DHTR may be recognized more than 6 weeks later.
What is the most common general cause of delayed hemolytic transfusion reactions?
Almost all DHTRs are due to an anamnestic response to a red cell antigen to which the patient has previously made an antibody, the concentration of which was too low to detect in pretransfusion testing. Rarely, a DHTR may be due to primary alloimmunization to a red cell antigen.
Intravascular hemolysis is more common in (acute/delayed) hemolytic transfusion reactions.
Intravascular hemolysis is much more common in acute hemolytic reactions than is extravascular hemolysis. In delayed hemolytic reactions, hemolysis is typically extravascular, but intravascular hemolysis may occur also.
What are FDA approved methods for detection of bacterial contamination of platelets?
AABB standards require that blood banks and transfusion services have methods to detect and limit bacterial contamination of platelets. FDA approved methods include culture, measurement of oxygen consumption, and rapid qualitative immunoassay. Measurements of pH or glucose and inspection for “swirling” have been used as indicators of contamination but are not sufficiently sensitive to meet current AABB standards.
List the absolute indications and probable indications for irradiation of blood components for prevention of TA-GVHD.
Absolute indications: Congenital cellular immunodeficiency. Hematopoietic progenitor cell transplantation. Hodgkin lymphoma. Granulocyte transfusions. Intrauterine transfusions (IUTs). Transfusion to neonates who have received IUT. Transfusions from biological relatives. Chemotherapy with purine analogs (fludarabine). Probable indications: Low-birthweight infants (<1200 g). Hematologic malignancies other than Hodgkin lymphoma. HLA-matched platelet concentrates. High-dose chemotherapy, radiation therapy, and/or aggressive immunotherapy.
List the controversial indications and situations where irradiation is not indicated.
Controversial indications: Solid organ transplantation. Large-volume or exchange transfusion of infants who did not receive IUT. Aplastic anemia. Absolute lymphopenia (Absolute lymphocyte count <500/mL). Situations where irradiation is not indicated: HIV infection. Hemophilia. Small-volume transfusion of term infants who did not receive IUT. Elderly patients. Typical dose immunosuppressive therapy (other than purine analogs). Immunocompetent surgical patients. Pregnancy. Red cell membrane, metabolic, or hemoglobin disorders (e.g., thalassemia, SCD).
True or false. Humoral immunodeficiencies are a risk factor for TA-GVHD.
False. Patients with with marked cellular immunodeficiencies are at risk of TA-GVHD. These include congenital cellular immunodeficiencies (DiGeorge syndrome, severe combined immunodeficiency syndrome), immaturity of the immune system (intrauterine transfusions, very-low-birthweight infants), disease-associated immunodeficiencies (Hodgkin lymphoma), and therapy-associated cellular immunodeficiencies (hematopoietic progenitor cell transplantation, fludarabine treatment). Humoral immunodeficiencies, such as common variable immunodeficiency (CVID), are not a risk factor for GVHD.
True or false. HIV infection is a risk factor for TA-GVHD.
False. HIV infection, although it may cause marked T cell dysfunction, does not increase the risk of TA-GVHD.
In what situation may a patient with normal immunity be at risk for TA-GVHD?
Patients with normal immunity may be at risk of TA-GVHD if the recipient is homozygous for an HLA haplotype and the donor is heterozygous but shares one haplotype. In this case, recipient lymphocytes are unable to recognize transfused lymphocytes as foreign, but transfused cells see recipient cells as foreign. This is most likely to occur with donations from close (first- or second-degree) relatives but may also occur owing to chance, particularly in populations that are relatively homogeneous.
How long after transfusion does TA-GVHD usually manifest? What are characteristic physical findings? Mortality?
TA-GVHD typically manifests 2–50 days after transfusion. Characteristic findings include rash, diarrhea, fever, liver dysfunction, and pancytopenia. Mortality is greater than 90%, with most patients dying of infection.
What is thought to be the cause of transfusion-associated hypotension?
The cause of transfusion-associated hypotension has not been established definitively. However, the condition is most likely due to the release of bradykinin through activation of the contact pathway of coagulation. Some reactions have been associated with angiotensin-converting enzyme (ACE) inhibitor drugs in the recipient and/or the use of leukocyte reduction filters. ACE is the major enzyme that breaks down bradykinin in the circulation. Some filters, particularly those with a net-negative surface charge, appear to cause activation of kallikrein and cleavage of high molecular weight kininogen, which results in the release of bradykinin. However, there is variability because not all such filtered units show activation.
What measures can be taken to prevent transfusion-associated circulatory overload in at-risk pateints?
Blood should be transfused slowly. Although a transfusion usually should be completed within 4 hours, the duration may be extended if medically indicated. If longer than 6 hours is required, however, alternative strategies should be considered. Small volumes can be transfused with adequate time between transfusions to allow for diuresis. To avoid additional donor exposures, a unit can be split using sterile technique and a portion retained in the blood bank for later transfusion. Units can also be concentrated by plasma removal. A diuretic can be administered before or during the transfusion.
What are the 2010 risk estimates for per-unit risk of transfusion-associated infectious disease transmission for: HIV, HBV, HCV, HTLV-I/II, and West Nile virus?
HIV - 1:1,467,000. HBV - 1:280,000-1:357,000. HCV - 1:1,149,000. HTLV-I/II - 1:641,000-1:1,900,000. West Nile virus - ~1:7,000,000.
Approximately __% of blood donors are CMV seropositive, although the estimated risk of transmission by a seropositive transfusion is about __%.
Approximately 50% of blood donors are CMV seropositive, although the estimated risk of transmission by a seropositive transfusion is about 1%.
List the top 12 most immunogenic clinically important blood group antigens and their relative potencies (approximate percentage of persons negative for a specific antigen who, if transfused with one unit of corresponding antigen-positive blood, would develop antibodies to that specific antigen).
D - 0.70. K - 0.10. C - 0.041. E - 0.0338. k - 0.030. e - 0.0112. Fya - 0.0046. C - 0.0022. Jka - 0.0014. S - 0.0008. Jkb - 0.0006. s - 0.0006.
What are the top 3 most immunogenic clinically important blood group antigens and their relative potencies (approximate percentage of persons negative for a specific antigen who, if transfused with one unit of corresponding antigen-positive blood, would develop antibodies to that specific antigen).
D - 0.70. K - 0.10. C - 0.041.
True or false. All Ig classes (M, G, A, D, and E) can have kappa or lambda light chains.
True.
What are the valencies (Ag binding) for the 5 Ig classes?
IgG: 2. IgM: 5 (valency of 10 can be seen with very small haptens). IgA: 2-4. IgD: 1. IgE: 1.
True or false. Babesia species are capable of surviving in refrigerated red blood cells.
True.
Intravascular RBC hemolysis is usually caused by antibodies directed against the ABO antigens. In what other rare situations can there be intravascular hemolysis?
Rarely, other IgM blood group antibodies, as well as some complement-fixing IgG antibodies (e.g., anti-Kidd antibodies), can induce intravascular hemolysis.
Which Ig class causes the majority of extravascular hemolysis?
IgG antibodies cause the majority of extravascular hemolysis via the RE system, which removes complement-coated RBCs.
What are the steps in the complement pathway that occur in extravascular hemolysis?
IgG antibodies cause the majority of extravascular hemolysis via the RE system. When IgG antibodies bind RBCs and activate complement, complement regulatory proteins generally stop the activation process at the C3/C4 level. RBC-bound C3b is degraded to iC3b, which is enzymatically inactive, by factor I and factor H. iC3b is further degraded to C3c and C3dg by factor I and CR1, a cofactor and C3b/C4b receptor. Initially, C3b/iC3b-coated RBCs are rapidly sequestered in the liver by monocytes and macrophages, which have receptors for C3b. A portion of the RBCs sequestered in the liver are immobilized and destroyed by phagocytosis with a half-life of about 2 minutes. Within 15–20 minutes, however, destruction slows, and many of the cells escape extravascular destruction through the action of the complement regulatory protein, factor I, as previously described. C3dg, the iC3b fragment produced by factor I cleavage, remains attached to RBCs but has no enzymatic or opsonic properties. As a result, sequestered C3dg-coated RBCs are released back into the circulation and survive normally. In the circulation, C3dg is cleaved, leaving C3d attached to the RBC membrane.
Clinically significant blood group antibodies are typically of what Ig type?
The majority of clinically significant blood group antibodies are IgG or IgM, although occasionally an IgA antibody is encountered.
More than __ erythrocyte antigens have been reported in the literature and have been organized into __ blood group systems by the International Society of Blood Transfusion (ISBT).
More than 700 erythrocyte antigens have been reported in the literature and have been organized into 30 blood group systems by the International Society of Blood Transfusion (ISBT).
What are the frequencies in the US population of blood groups O, A, B, and AB among Caucasians, Blacks, Native Americans, and Asians?
Group O: 45%, 49%, 79%, 40%. Group A: 40%, 27%, 16%, 28%. Group B: 11%, 20%, 4%, 27%. Group AB: 4%, 4%, <1%, 5%.
Compare the two blood group A subtypes, A1 and A2, for the following: reaction with diluted anti-A, reaction with Dolichos biflorus lectin, presence of anti-A1 in serum, N-acetyl-galactosaminyltransferase activity, and number of antigen sites.
Reaction with diluted anti-A: ++++; ++. Reaction with Dolichos biflorus (anti-A1) lectin: ++++; 0. Presence of anti-A1 in serum: No; 1-8%. N-acetyl-galactosaminyltransferase activity: Normal activity, optimal at pH 6; Decreased activity, optimal at pH 7. Number of antigen sites: A1 adult - 1,000,000; A2 adult - 250,000; A1 newborn - 310,000; A2 newborn - 140,000.
Briefly describe cis-AB, B[A], and acquired B blood phenotypes.
Anomalous ABO expression can be inherited (cis-AB, B[A]) or acquired (acquired B). In the cis-AB phenotype, A and B antigens are synthesized by the same enzyme and are inherited as a single, autosomal dominant allele. Likewise, the B(A) phenotype, an autosomal dominant phenotype characterized by trace A antigen expression on group B RBCs, is due to synthesis of A antigen by the B-gene enzyme. The acquired B phenotype, on the other hand, is an acquired enzymatic modification of group A1 red cells in vivo. The acquired B phenotype usually occurs in the setting of bacterial infection or cancer and reflects enzymatic deacetylation of group A antigen to form a B-like antigen on RBCs. The cis-AB, B(A), and acquired B phenotypes are usually detected because of discrepancies in ABO typing.
On what chromosome is the ABO gene locus and what does it encode for?
The ABO gene locus is located on chromosome 9q34 and encodes the A and B glycosyltransferases The gene is large, spanning 18kb, and contains seven exons, although exons 6 and 7 encode the majority of the active enzyme. The product of the ABO gene is a 41-kD, 353 amino acid type II transmembrane glycoprotein.
Blood groups A and B. How similar are the A gene glycosyltransferase and the B gene glycosyltransferase, and how similar are the product antigens?
Comparison of A and B enzymes shows nearly 98% identity, differing by four key amino acids at residues 176, 235, 266, and 268. Biochemically, the A and B antigens are very similar, differing only by the presence of an N-acetyl group.
ABO antibodies are weak or absent in the sera of newborns until ___ months of age. Adult levels of ABO antibodies are reached by ___ years of age and decrease only slightly with advancing age.
ABO antibodies are weak or absent in the sera of newborns until 3–6 months of age. Adult levels of ABO antibodies are reached by 5–10 years of age and decrease only slightly with advancing age.
What are 2 non-antibody and 2 general categories of antibody causes of TRALI?
Bioactive lipids and CD40L are 2 non-antibody causes of TRALI. Bioactive lipids such as lysophosphatylcholine accumulate during the storage of cellular blood products and can prime neutrophils. CD40L levels increase in stored platelets and can prime neutrophils. HLA class I and II antibodies and HNA (Human Neutrophil Antigens) antibodies are also causes.
List the blood groups A1, A2, A1B, A2B, B, and O in decreasing order of reactivity with anti-H.
O > A2 > B > A2B > A1 > A1B.
M and N antigens are fairly evenly distributed in both blacks and Caucasians, with approximately 25% of donors homozygous for M or N antigen. In contrast, the S antigen is nearly twice as frequent in (blacks/Caucasians).
M and N antigens are fairly evenly distributed in both blacks and Caucasians, with approximately 25% of donors homozygous for M or N antigen. In contrast, the S antigen is nearly twice as frequent in Caucasians (57%) as in black people (30%). In a minority (
What are the 3 major null phenotypes present in the MNS blood group system?
Three major null phenotypes are present in the MNSs system: U−, Mk, and En (a−). The U− phenotype is the most common and is observed exclusively in blacks. In S−s−U− individuals, complete loss or a recombination of glycophorin B occurs, leading to altered expression of S/s and U antigens. The MkMk phenotype lacks all MNSs antigens, including En(a), as the result of recombination and deletion of glycophorins A and B (GYPA and GYPB). The En (a−) phenotype is the result of recombination between glycophorin A and B genes to form a Lepore-type A-B hybrid (exons A1-B2-B5) lacking most of glycophorin A (GYPA).
Biochemistry of the MNS blood group system.
The M/N antigens reside on GYPA (CD235A), a major RBC membrane glycoprotein. In the membrane, GYPA is present as a dimer, usually in association with Band 3, the erythrocyte anion exchanger. Structurally, GYPA is a 31-kD, 131 amino acid, type 1 glycoprotein composed of a large, 72 amino acid extracellular domain, a transmembrane domain, and a short cytoplasmic tail. The M and N antigens reside on the extreme amino-terminus of GYPA. The S/s and U antigens reside on GYPB, a related RBC glycoprotein. GYPB (CD235B) is a 20-kD, 72 amino acid glycoprotein composed of a large, extracellular N-terminal domain containing 11 O-linked glycans. Although GYPB shares considerable homology with GYPA at the amino-terminus, GYPB is smaller, lacking both an N-glycan and a cytoplasmic tail. The S/s epitope is located at amino acid 29.
MNS blood group system. Are antibodies against M and N naturally occuring? Ig isotype? detected at room temp/body temp? show dosage? affected by enzyme treatment? clinical significance?
Antibodies against M and N antigens are naturally occurring antibodies of IgM isotype, usually detected as room temperature saline agglutinins. Anti-M and anti-N may show dosage, reacting more weakly with heterozygous (M/N) cells than with homozygous (M/M or N/N) cells. Because the M and N antigens reside on GYPA, the reactivity of anti-M and anti-N is destroyed by pretreatment of RBCs with proteolytic enzymes or neuraminidase. Some examples of anti-M and anti-N can be enhanced by acidification of serum to pH 6.5, use of an albumin diluent, or preincubation of RBCs in a glucose-containing solution. In general, anti-M and anti-N are clinically insignificant antibodies and only rarely cause hemolytic transfusion reactions or HDFN.
MNS blood group system. Are antibodies against M, N, S, s, and U naturally occuring? Ig isotype? detected at room temp/body temp? show dosage? affected by enzyme treatment? clinical significance?
Antibodies against M and N antigens are naturally occurring antibodies of IgM isotype, usually detected as room temperature saline agglutinins. Anti-M and anti-N may show dosage, reacting more weakly with heterozygous (M/N) cells than with homozygous (M/M or N/N) cells. Because the M and N antigens reside on GYPA, the reactivity of anti-M and anti-N is destroyed by pretreatment of RBCs with proteolytic enzymes or neuraminidase. Some examples of anti-M and anti-N can be enhanced by acidification of serum to pH 6.5, use of an albumin diluent, or preincubation of RBCs in a glucose-containing solution. In general, anti-M and anti-N are clinically insignificant antibodies and only rarely cause hemolytic transfusion reactions or HDFN. Unlike anti-M and anti-N, antibodies against S, s, and U antigens are always clinically significant. All are antibodies of IgG isotype, reactive at 37° C, arising from immune stimulation. Some examples of anti-S and anti-s show dosage. Enzymatic modification of RBCs with proteases, but not neuraminidase, can decrease the reactivity of some anti-S and anti-s. The reactivity of anti-U is resistant to proteolytic digestion. Anti-S, -s, and -U are causes of hemolytic transfusion reactions and HDFN.
MNS blood group system. Are antibodies against S, s, and U naturally occuring? Ig isotype? detected at room temp/body temp? show dosage? affected by enzyme treatment? clinical significance?
Unlike anti-M and anti-N, antibodies against S, s, and U antigens are always clinically significant. All are antibodies of IgG isotype, reactive at 37° C, arising from immune stimulation. Some examples of anti-S and anti-s show dosage. Enzymatic modification of RBCs with proteases, but not neuraminidase, can decrease the reactivity of some anti-S and anti-s. The reactivity of anti-U is resistant to proteolytic digestion. Anti-S, -s, and -U are causes of hemolytic transfusion reactions and HDFN.
MNS blood group system. Which is more common - anti-M or anti-N?
Clinically, anti-M is a commonly encountered antibody in the blood bank. In contrast, anti-N is distinctly uncommon, despite the fact that 25% of patients are negative for N antigen (M homozygous). The rarity of anti-N is due to the presence of ‘N’ antigen on GYPB. When observed, anti-N is usually an autoantibody, reacting with both N and ‘N’ antigens.
What is anti-Nf?
An autoantibody to N antigen in the NMS blood group system. An autoanti-N (anti-Nf) was reported in hemodialysis patients in the past, caused by the use of formaldehyde to sterilize membranes. Formaldehyde reacted with the terminal leucine on N and ‘N’ antigens, creating a neoantigen.
MNS blood group system. Generally, anti-M and anti-N are clinically insignificant antibodies. What phenotype is the exception?
In general, anti-M and anti-N are clinically insignificant antibodies and only rarely cause hemolytic transfusion reactions or HDFN. In contrast, potent hemolytic alloanti-N is observed in patients lacking GYPB (M+N−S−s− phenotype). In these patients, severe hemolytic transfusion reactions and HDFN can occur after transfusion of N+ RBCs.
What antigens does the P blood group system consist of?
P1 (renamed P1PK by the ISBT), and two members of the GLOB collection, P^k and P. Similar to the Lewis system, the P blood group antigens are glycosphingolipids.
True or false. Expression of the P1 antigen in the P blood group system can be lost with in vitro storage.
True.
The P blood group system antigens are: P1 (renamed P1PK by the ISBT), and two members of the GLOB collection, P^k and P. On what cell types are these antigens located?
RBCs are particularly rich in P antigen, which makes up nearly 6% of the total RBC lipid. Pk and P antigens are also expressed on nonerythroid cells, including lymphocytes, platelets, plasma, kidney, lung, heart, endothelium, placenta, uroepithelium, fibroblasts, and synovium. Pk and P antigens are high-frequency antigens on most donor RBCs (>99.9%). In contrast, the P1 antigen is uniquely expressed on RBCs. ~79% of Caucasian and 94% of black donors express P1 on their RBCs.
The P1 and P2 phenotypes in the P blood group system account for >99% of donors. P1 phenotype expresses P^k, P, and P1 RBC antigens. P2 phenotype expresses P^k and P RBC antigens. What are the null and weak P phenotypes?
There are 3 null phenotypes: P1^k (expresses P1, and increased P^k RBC antigens); P2^k (expresses increased P^k RBC antigen); p (no RBC antigens). There are 2 weak phenotypes: Variant P^k (expresses increased P^k and decreased P RBC antigens); Weak P (expresses decreased P^k and decreased P RBC antigens).
P blood group system. Null phenotypes p and P^k (P1^k and P2^k), because they lack P antigen, they are resistant to what microorganism?
Parvovirus B19.
Clinically, the most common antibody observed in the P blood group system is anti-P1, which is detected in one quarter to two thirds of P2 donors. What Ig type? At what temperature does it react? Antibody reactivity can be eliminated by addition of what?
Anti-P1 is a naturally occurring antibody of IgM isotype and is often detected as a weak, room temperature agglutinin. Rare examples of anti-P1 are reactive at 37° C or show in vitro hemolysis. Because P1 expression varies in strength between individuals, anti-P1 may not react with all P1-positive cells tested. Anti-P1 can bind complement and may be detected in the IAT if polyspecific AHG is used. Antibody reactivity can be eliminated by prewarming sera or by adding soluble P1 substance from hydatid cyst fluid, earthworms, and bird eggs. Anti-P1 titers are often elevated in patients with hydatid cyst disease or fascioliasis (liver fluke), and in bird fanciers. Some examples of anti-P1 have I blood group specificity (anti-IP1).
In the P blood group system, is anti-P1 clinically significant?
In general, anti-P1 is not clinically significant, and its presence rarely requires transfusion of antigen-negative blood. The exception is seen in patients with an anti-P1 showing in vitro hemolysis. Because of the risk of immediate and delayed hemolytic transfusion reactions, these patients should receive P1-negative (P2), crossmatch compatible units. Anti-P1 is not a cause of HDFN.
In the P blood group system, what is auto-anti-P?
An autoantibody with anti-P specificity is seen in patients with paroxysmal cold hemoglobinuria, a clinical syndrome that may occur in children following viral infection. In PCH, autoanti-P is an IgG, biphasic hemolysin capable of binding RBCs at colder temperatures, followed by intravascular hemolysis at body temperature. This characteristic can be demonstrated in vitro in the Donath-Landsteiner test.
In the P blood group system, what is alloanti-PP1Pk?
Anti-PP1Pk (historically known as anti-Tja) is a separable mixture of anti-P, anti-P1, and anti-Pk in the sera of p individuals. These antibodies are naturally occurring and may be IgM only or IgM plus IgG (IgG3). Because anti-PP1Pk antibodies are potent hemolysins, patients can be transfused only with p RBCs.
An autoantibody with anti-___ specificity is seen in patients with paroxysmal cold hemoglobinuria, a clinical syndrome that may occur in children following viral infection.
An autoantibody with anti-P specificity is seen in patients with paroxysmal cold hemoglobinuria, a clinical syndrome that may occur in children following viral infection.
Several P blood group antigens are receptors for microbial pathogens. Give examples.
The P blood group antigen is the receptor for parvovirus B19. Pk can bind HIV and may confer resistance to HIV infection. The P1 and Pk antigens are receptors for shiga toxins, produced by Shigella dysenteriae and enterohemorrhagic Escherichia coli (EHEC) strains. In addition to gastroenteritis, EHEC infection is the most common cause of community-acquired hemolytic-uremic syndrome, probably reflecting toxin binding to Pk antigen on glomerular vascular endothelium and platelets. P, Pk, and LKE blood group antigens on uroepithelium are cell receptors for P-fimbriae, a bacterial adhesin and colonization factor expressed on uropathogenic E. coli strains. The Pk antigen also serves as a receptor for Streptococcus suis and Pseudomonas aeruginosa.
What 3 integral membrane proteins does the Rh complex consist of? Biochemistry of these 3 proteins?
Rh complex consists of three integral membrane proteins: RhD, RhCE, and Rh-associated glycoprotein (RhAg). RhD and RhCE are highly homologous proteins, differing by approximately 30 amino acids. Both are 30-kD, 416 amino acid multipass proteins containing 12 transmembrane domains, six extracellular loops, and a cytoplasmic amino- and carboxy-terminus. RhAg is a 45–70-kD multipass glycoprotein, evolutionarily related to RhD and RhCcEe glycoproteins. RhAg is a 409 amino acid glycoprotein with 12 transmembrane domains and a single, large N-linked carbohydrate side chain on the first extracellular loop.
The genes for RhD (RHD) and RhCE (RHCE) proteins span 65kb on chromosome ___ and share nearly 92% sequence identity. The two genes are separated by only 30kb and have opposite orientations, facing each other at their 3′ ends. The RHAG gene (RHAG) resides on chromosome ___ and shares 36% homology with the RHD and RHCE genes.
The genes for RhD (RHD) and RhCE (RHCE) proteins span 65kb on chromosome 1p34-36.1 and share nearly 92% sequence identity. The two genes are separated by only 30kb and have opposite orientations, facing each other at their 3′ ends. The RHAG gene (RHAG) resides on chromosome 6p11.1 and shares 36% homology with the RHD and RHCE genes.
On what chromosomes are these genes: RHD, RHCE, and RHAG.
RHD and RHCE are on chromosome 1. RHAG is on chromosome 6.
Approximately __% of D-positive individuals type as weak D (historically known as Du), characterized by weak or absent RBC agglutination by anti-D during routine serologic testing. In weak D individuals, the D antigen usually requires enhancement with AHG owing to a quantitative decrease in RhD protein. In these individuals, the number of RhD molecules is decreased __–__-fold, ranging from __–__ molecules per red cell.
Approximately 1% of D-positive individuals type as weak D (historically known as Du), characterized by weak or absent RBC agglutination by anti-D during routine serologic testing. In weak D individuals, the D antigen usually requires enhancement with AHG owing to a quantitative decrease in RhD protein. In these individuals, the number of RhD molecules is decreased 40–100-fold, ranging from 66–5200 molecules per red cell.
A weak D phenotype can occur with many partial D phenotypes, such as ___.
A weak D phenotype can occur with many partial D phenotypes, Ce in trans with suppression of RHD, in the Rhmod phenotype, and via autosomal recessive inheritance of two weak RHD alleles. The latter accounts for the majority of weak D phenotypes present in the general population.
What are partial D antigens?
Partial D antigens are RHD proteins with missing D epitopes. Although they type as D-positive, persons with partial D antigens can make alloanti-D antibodies reactive with allogeneic, but not autologous, RBCs. The alloanti-D produced by these individuals recognizes D-specific epitopes missing on their own RBCs. Partial D can result from missense mutations or from genetic recombination of RHD and RHCE genes.
What is the genetic basis of the Rh-negative phenotype for different racial groups?
Rh-negative (D−) occurs in approximately 15% of white donors, almost always in association with a ce/ce or rr phenotype. In most Caucasian people, D− reflects a deletion of the entire RHD gene. In blacks, D− can result from gene deletion or from inheritance of an RHD pseudogene. Nearly 60% of D-negative black people inherit a mutant RHD allele (RHψD) containing a 37–bp internal duplication, frameshift, and premature stop codon. RHD genes containing nonsense mutations and nucleotide deletions have also been reported in some D-negative Japanese and Caucasian donors.
What is the Rh null phenotype?
Extremely rare (<1 in 6 million). Rhnull erythrocytes lack all Rh antigens as a result of an apparent absence of RhD and RhCE proteins. In addition, Rhnull erythrocytes lack the high-frequency antigens Fy5 and LW and may have markedly decreased expression of S/s and U antigens. The absence of these non-Rh antigens reflects the complex topologic association of Duffy, LW, and GYPB proteins with Rh proteins on RBC membranes. Rhnull cells have structural and physiologic abnormalities, showing increased osmotic fragility and a shortened circulating half-life, often accompanied by a mild hemolytic anemia (Rh deficiency syndrome). Because Rhnull individuals can become sensitized to multiple Rh antigens, including high-frequency antigens, transfusion support can be quite difficult.
Rhnull erythrocytes lack all Rh antigens as a result of an apparent absence of RhD and RhCE proteins. In addition, Rhnull erythrocytes lack the high-frequency antigens Fy5 and LW and may have markedly decreased expression of S/s and U antigens. Why?
Rhnull erythrocytes lack all Rh antigens as a result of an apparent absence of RhD and RhCE proteins. In addition, Rhnull erythrocytes lack the high-frequency antigens Fy5 and LW and may have markedly decreased expression of S/s and U antigens. The absence of these non-Rh antigens reflects the complex topologic association of Duffy, LW, and GYPB proteins with Rh proteins on RBC membranes.
What are the Rh null amorph type and Rh null regulator type?
The Rhnull phenotype can arise from two distinct genetic backgrounds—regulator and amorph. The Rhnull-amorph type is the result of nonsense mutations in the RHCE gene in D-negative people. Because of the absence of RhD and RhCE proteins, Rhnull-amorph RBCs have reduced (but not absent) expression of RhAg protein. The Rhnull regulator type arises from mutations in RHAG.
What is the Rh mod phenotype?
Whereas Rhnull RBCs lack all Rh antigens as a result of an apparent absence of RhD and RhCE proteins, Rhmod RBCs have markedly decreased Rh and RhAg expression, detectable only by careful adsorption and elution studies. Similar to Rhnull individuals, persons with Rhmod may have laboratory evidence of Rh deficiency syndrome with a mild hemolytic anemia. Mutations in RHAG are also observed in the Rhmod phenotype.
In general, antibodies against Rh antigens are the result of immune stimulation by transfusion or pregnancy. Exceptions include ___.
In general, antibodies against Rh antigens are the result of immune stimulation by transfusion or pregnancy. Exceptions include some examples of anti-Cw and anti-E, which can be naturally occurring.
For transfusion in patients that are alloimmunized to Rh, RBC units should be negative for the Rh antigen of interest and crossmatch compatible with the recipient’s serum through the AHG phase of testing. One possible exception (where there may be a DHTR due to development of an antibody) may be ___.
For transfusion in patients that are alloimmunized to Rh, RBC units should be negative for the Rh antigen of interest and crossmatch compatible with the recipient’s serum through the AHG phase of testing. One possible exception may be R1R1 (DCe/DCe) patients who have developed anti-E alloantibodies. Because these patients are at increased risk of delayed hemolytic transfusion reactions because of the subsequent development of anti-c, many blood bankers advocate transfusing only R1R1 units to R1R1 patients.
Administration of one vial of Rh immune globulin is recommended for every __ mL whole blood or __ mL packed RBCs transfused. Rh immune globulin should be given within __ hours of exposure to prevent active immunization.
Administration of one vial of Rh immune globulin is recommended for every 30 mL whole blood or 15 mL packed RBCs transfused. Rh immune globulin should be given within 72 hours of exposure to prevent active immunization.
What can cause additional reactivity on forward typing of blood?
Acquired antigens (acquired B phenotype). Transplantation. Out-of-group transfusion. Autoagglutinins. Unwashed red cells (plasma proteins; antibody in patient’s serum to reagent constituent).
What can cause lack of expected reactivity on forward typing of blood?
Malignancy. Transplantation/transfusion (including intrauterine fetal transfusion). Neonates. Excessive soluble blood group substances.
What can cause a mixed field appearance on forward typing of blood?
Chimera (transplantation chimera; genetic chimera (twin); transfusion chimera). Fetomaternal hemorrhage. Some subgroups of A (e.g. A3 and Aend).
What are the 5 most immunogenic Rh antigens?
D is the most immunogenic Rh antigen, followed by c, E, C, and e.
How can malignancies cause lack of expected reactivity on forward typing of blood?
Some cancers, especially of GI tract, ovary, and leukemias, produce A and B-like soluble substances which react with antibodies during testing, neutralizing them. This can be corrected by thoroughly washing, then retesting.
What can cause additional reactivity on reverse typing of blood?
Extra antibodies. Transfusion (plasma components not type-specific to patient; IV Ig/albumin). Transplantation. Subgroup of a major blood type (especially subgroup of A (i.e. A2). Rouleaux (multiple myeloma; chronic inflammatory disorders).
What can cause lack of expected reactivity on reverse typing of blood?
Neonates. Elderly. Severe immunosuppression. Transplantation. Hypogammaglobulinemia. Subgroup of a major blood type.
How many antigens does the Lutheran blood group system contain? One what type of cells/tissues are Lutheran antigens expressed?
The Lutheran (Lu) blood group system contains 19 antigens including four pairs of allelic antigens and 11 high-incidence antigens. Lutheran is a minor constituent of RBC membranes, averaging only 2000–5000 molecules per cell, and can vary in strength between and within individuals. Lutheran antigens are ubiquitously expressed on several human tissues.
What are the null phenotypes of the Lutheran blood group system?
A Lu(a−b−) phenotype can occur in three settings with distinct patterns of inheritance: autosomal recessive, autosomal dominant (In[Lu]), and X-linked recessive. All are very rare.
Are the Lutheran blood group system antibodies clinically significant?
In general, Lutheran antibodies are not clinically significant and are only rarely associated with HDFN and hemolytic transfusion reactions.
What is the most common Lutheran blood group system alloantibody?
Anti-Lua is the most common Lutheran alloantibody encountered in the blood bank and is often an IgM, room temperature agglutinin. Because not all RBCs express detectable Lu antigens, anti-Lua can display mixed field agglutination. Antibodies against Lub and other Lutheran antigens are most often of IgG isotype, reacting best in the IAT. Reactivity of anti-Lua, Lub, and other Lutheran antibodies can be inhibited by pretreatment of RBCs with chymotrypsin, trypsin, 2-aminoethylisothiouronium bromide (AET), and dithiothreitol (DTT).
What are the frequencies in the US white and black populations for the Lutheran blood group system phenotypes Lu (a+b-), Lu (a+b+), and Lu (a-b+)?
Both white and black populations have the same frequencies: Lu (a+b-) 0.1%, Lu (a+b+) 6%, and Lu (a-b+) 94%.
How many antigens are in the Kell blood group system? On what cells/tissues is the Kell antigen expressed?
The Kell blood group system currently consists of 46 high- and low-frequency antigens. The Kell antigen is found on RBCs, erythroid and megakaryocyte progenitors, skeletal muscle, and testis. RBCs express approximately 2000–6000 copies of Kell protein per cell.
