Transfusions Transfusions are always based on clinical grounds.

. Treat the patient, not the lab value; there is no such thing as a trigger value for transfusion. Different blood components have different indications: Whole blood: Used only for rapid, massive blood loss or exchange transfusions (poisoning, TTP). Packed RBCs: Used instead of whole blood when the patient needs a transfusion. Washed RBCs: Free of traces of plasma, WBCs, and platelets; good for IgA deficiency and allergic or previously sensitized patients. Platelets: Given for symptomatic thrombocytopenia (usually <10,000/L). Granulocytes: Rarely used for neutropenia with sepsis caused by chemotherapy (colony-stimulating factors such as filgrastim preferred). Fresh-frozen plasma: Contains all clotting factors; used for bleeding diathesis when one cannot wait for vitamin K to take effect (DIC, severe warfarin poisoning) or when vitamin K will not work (liver failure). Cryoprecipitate: Contains fibrinogen and factor VIII; used in von Willebrand disease and DIC. The most common cause of a hemolytic blood transfusion reaction is lab error. Type O negative blood can be used when you cannot wait for blood typing or the blood bank does not have the patient's type. If a transfusion reaction occurs, the first step is to stop the transfusion! ABO mismatch can cause fever, hemolysis, DIC, and flank pain within 1 hour of transfusion. Patients with associated oliguria should be treated with IV fluids and diuresis (mannitol or furosemide). Massive transfusions can lead to bleeding diathesis from thrombocytopenia (look for oozing from puncture or IV sites) and citrate (calcium chelator). Hyperkalemia can also develop. Types of transfusion reactions: Allergic reaction (urticaria, edema, dizziness, dyspnea, wheezing, anaphylaxis) from reaction to a (usually unknown) component in donor serum Febrile reaction (chills, fever, headache, back pain) from antibodies to WBCs Hemolytic reaction (anxiety or discomfort, dyspnea, chest pain, shock, jaundice) from antibodies to RBCs; usually occurs 2 to 10 days after transfusion

Disseminated Intravascular Coagulation

DIC is most commonly caused by pregnancy and obstetric complications (50%), malignancy (30%), sepsis, and trauma (especially head trauma, prostate surgery, and snake bites). DIC usually manifests as bleeding diathesis. Look for the classic oozing or bleeding from puncture or IV sites, but patients might have thrombotic tendencies. Lab results reveal prolonged prothrombin time (PT), partial thromboplastin time (PTT), and bleeding time; positive D dimer and increased

fibrin degradation products; thrombocytopenia; and decreases in fibrin and clotting factors (including factor VIII, which is normal in hepatic necrosis). Treat the underlying cause (evacuate uterus; give antibiotics). Patients might need transfusions, fresh-frozen plasma, or (rarely) heparin (only in the presence of thrombosis).

Coagulopathies
The lupus anticoagulant can cause a prolonged PTT, but the patient has a tendency toward thrombosis. Look for associated lupus symptoms, positive Venereal Disease Research Laboratory or rapid plasma reagin test result for syphilis, or a history of miscarriages. Factor V Leiden; prothrombin G20210A gene mutation; hyperhomocysteinemia; elevated factor VIII level; and deficiencies in protein C, protein S, or antithrombin III can also cause an increased tendency toward thrombosis. Other causes of increased tendency toward thrombosis include antiphospholipid syndrome (lupus anticoagulant and anticardiolipin antibody), pregnancy, cancer, and estrogen-containing medications. Patients are treated with anticoagulant therapy to prevent deep venous thrombosis, pulmonary embolism, and other complications. Clotting tests: Use PT for extrinsic system (prolonged by warfarin), PTT for intrinsic system (prolonged by heparin but not affected by low-molecular-weight heparins), and bleeding time for platelet function. Causes of thrombocytopenia include: Alcohol Autoimmune disease Deficiencies (vitamin B 12 or folate) DIC Hemolytic uremic syndrome Heparin (treat by first stopping heparin) Human immunodeficiency virus (HIV) infection Idiopathic thrombocytopenic purpura

Medications (especially quinidine and sulfa drugs) Pancytopenia of any cause Splenic sequestration TTP Bleeding from thrombocytopenia is in the form of petechiae, nosebleeds, and easy bruising. Microcytic Normocytic Macrocytic Normal to Elevated Reticulocyte Index Hemoglobinopathy Acute blood loss None; all forms have a low RI Thalassemia Hemolytic (multiple causes) Medications (antibody causing) Low Reticulocyte Index Anemia of chronic disease (some) Anemia of chronic disease (some) Iron deficiency Aplastic anemia Lead poisoning Sideroblastic Cancer, dysplasia (e.g., myelophthisic anemia) anemia Endocrine failure (thyroid, pituitary) Renal failure Clues to the presence of hemolytic anemia: Elevated lactate dehydrogenase (LDH) Elevated bilirubin (unconjugated as well as conjugated if the liver is working) Jaundice Low or absent haptoglobin (with intravascular hemolysis) Positive urobilinogen, bilirubin, or hemoglobin in the urine Only conjugated bilirubin appears in the urine, and hemoglobin appears only when haptoglobin has been saturated, as in brisk intravascular hemolysis. Vitamin B 12 deficiency Cirrhosis, liver disease Folate deficiency Medications (methotrexate, phenytoin)

Classic Findings of Anemia on Peripheral Smear Smear Finding Acanthocytes, spur cells Basophilic stippling Bite cells Echinocytes, burr cells Heinz bodies Howell-Jolly bodies Hypersegmented neutrophils Iron inclusions in RBCs of bone marrow Parasites inside RBCs Polychromasia Rouleaux formation Schistocytes, helmet cells, fragmented RBCs Sickled cells Spherocytes, elliptocytes Target cells Teardrop-shaped RBCs Usual Cause Abetalipoproteinemia Lead poisoning G6PD deficiency and other hemolytic anemias Uremia G6PD deficiency and -thalassemia Asplenia, splenic dysfunction Folate or vitamin B 12 deficiency Sideroblastic anemia Malaria, babesiosis Reticulocytosis (consider hemolysis) Multiple myeloma Intravascular hemolysis Sickle cell anemia Hereditary spherocytosis or elliptocytosis Thalassemia, liver disease Myelofibrosis

Disease DIC

PT High

PTT High

BT High

Platelet Count Low

Hemophilia A or Normal High B Heparin ITP TTP Liver failure Scurvy von Willebrand disease Warfarin Normal High Normal Normal

Normal Normal Normal High

RBC Other Count Normal or Appropriate history, low factor VIII level low X-linked recessive; A = low factor VIII, B = Normal low factor IX Watch for thrombocytopenia and thrombosis

Watch for preceding URI Hemolysis, CNS symptoms; treat with Normal Normal High Low Low plasmapheresis; do not give platelets Normal or Normal or Normal or Jaundice, normal factor VIII level; do not give High Normal high low low vitamin K (ineffective) Fingernail and gum hemorrhages, bone Normal Normal Normal Normal Normal hemorrhages Normal High High Normal High Normal Normal Normal Autosomal dominant (look for family history) Vitamin K antagonist (factors II, VII, IX, and X)

Normal or Normal low Low Normal

Normal Normal

Transfusion compatibility testing is based on agglutination. The direct antibody (or Coombs) test assesses the presence of immunoglobulin or complement bound to RBCs.

The indirect antibody test uses a multistep process to screen for a specific antigen, alloantibody, or crossmatch reaction. Antibody identification involves a complex procedure where 11 or more reagent cells are tested against patient plasma.

A crossmatch order asks the laboratory to reserve a particular RBC unit for a particular patient. IV. Transfusion Medicine A. Blood Products 1. Blood products are available to treat volume depletion, ischemia, coagulation, and immune deficiency. 2. Several basic blood products are derived from whole blood donations; these may be used individually or in combination as part of component therapy. 3. Component therapy administers only the fraction required to correct the patients immediate deficiency (eg, RBCs for anemia; platelets for thrombocytopenia; plasma for coagulopathies; granulocytes for immunosuppression.) 4. RBCs are available as leukoreduced RBCs, packed RBCs, or whole blood for symptomatic patients with deficient oxygen capacity. a. Hemoglobin <6 g/dL usually requires transfusion. b. Hematocrit can be misleading, especially in the setting of acute blood loss; the decision to transfuse should weigh all pertinent clinical findings and not rely solely on a single hemoglobin measurement. c. Each unit is approximately 300 mL. d. The standard dose is 2 units for adults or 10 mL/kg in pediatric patients. e. The expected response to each unit is an increase of 1 g/dL hemoglobin and three points of hematocrit. 5. Platelets are available as either platelet units (drawn from a single donor), or platelet concentrates (pooled from whole blood). a. Counts less than 10,000/mcL require prophylactic transfusion. b. Greater than 50,000/mcL is required for surgery. c. A platelet target of 100,000/mcL is appropriate for neurosurgery and during massive transfusion. d. Platelets are frequently ineffective in patients with idiopathic thrombocytopenic purpura and are contraindicated in patients with TTP. e. The standard adult dose is 1 unit or 10 mL/kg in pediatric patients, and the expected response is a platelet count increase of 30,000 60,000/mcL. 6. Plasma is available as fresh frozen plasma (FFP) or thawed plasma. a. Plasma products should be administered to increase the level of clotting factors in patients with a demonstrated deficiency. 1. If the PT and PTT are less than 1.5 times normal, FFP is rarely needed. 2. Compared with FFP, thawed plasma has reduced concentrations of labile plasma factors such as factors VII and VIII, but the two products are used interchangeably.

b. Plasma should not be used for volume expansion or when virally inactivated factors concentrates are available to treat specific factor deficiencies. c. The standard dose is 23 units in adults or 15 mL/kg in pediatric patients; however, a dose of 46 units or 20 mL/kg is often required for full correction. 7. Cryoprecipitate is a concentrated solution of factor VII (the antihemophilic factor), fibrinogen, and fibronectin produced from plasma frozen to 70C then thawed to 4C. a. These products are used to correct hypofibrinogenemia. b. Therapy with cryoprecipitate is most effective when the serum fibrinogen level is less than 80 mg/dL. c. The standard dose is 10 units for adults or 1 unit/10 kg in pediatric patients. d. The expected response is an increase in fibrinogen of about 50 mg for every 10 units. 8. Factor concentrates are derived from fractionation of human or animal plasma and recombinant factor concentrates. a. Factor VIII concentrate has replaced cryoprecipitate as the treatment of choice for hemophilia A, but neutralizing antibodies develop in some patients rendering them refractory. b. Recombinant factor VIIa is licensed for use in hemophilia A patients resistant to factor VIII concentrates, and it is also used for emergent reversal of warfarin-induced hemorrhage. c. Factor IX concentrates may be used to treat hemophilia B and severe von Willebrand disease. 9. Granulocyte concentrates are collected by apheresis in about 200-300 mL containing an average of 5 109 granulocytes. a. The product must be infused within 24 hours of collection. b. Granulocytes cannot be leuko-reduced. To make them CMV-virus safe, the unit must be from a donor who is CMV negative. c. These products are indicated for short-term support of leukopenic patients with life-threatening fungal or bacterial infections that have not responded to antibiotics. B. Compatibility Testing 1. Pretransfusion processing is used to ensure the safety and compatibility of blood products. a. Potential donors are excluded on the basis of risk factors, including infectious disease status (HIV, hepatitis, or malaria), history of injection drug use, or recent transfusion. b. The risk of malaria and Creutzfeldt-Jakob disease is considered with the travel history. c. Each unit of donated whole blood for allogeneic transfusion is screened for the following: 1. Hepatitis B core antibody (anti-HBc) 2. Hepatitis B surface antigen (HBsAg) 3. Hepatitis C virus antibody (anti-HCV) 4. HIV-1 and HIV-2 nucleic acid and antibodies 5. Human T-cell virus (HTLV-1 and HTLV-2) antibodies

6. West Nile virus 7. Infection with Treponema pallidum 2. Leukoreduction is the filtration of white blood cells to decrease the quantity of white cells by 99.9%. a. It reduces the risk that the recipient will raise antibodies to the donated blood, a process known as alloimmunization, and this makes febrile transfusion reactions less likely. b. The process also reduces the potential for CMV transmission, since CMV infects only white cells. c. Irradiation lowers the mitotic index of donor T-lymphocytes and is considered for patients who are either immunocompromised (secondary to hereditary conditions, HIV, chemotherapy, or stem cell transplantation) or enrolled in directed-donation program. d. Despite these procedures, small but quantifiable risks of disease transmission remain (Table 187). 3. Compatibility testing helps ensure both transfusion safety and maximal survival of transfused cells. a. Safety begins with the patient blood sample in the correct type tube (usually purple) and properly labeled with the patients name and medical record number; blood samples that do not meet these criteria must be rejected and recollected. b. Pretransfusion testing involves determining the recipients blood type and the presence of any recipient antibodies that may cause hemolysis. c. Typing includes ABO and Rh expression. d. The process takes approximately 1 hour. C. Blood Groups 1. More than 630 distinct antigens are expressed on the surface of RBCs; however, only a few cause significant problems. 2. ABO antigens were among the earliest characterized and are the most familiar to healthcare professionals. a. The A and B codominant genes code for glycoproteins, the A and B antigens, which are added to an H precursor. b. Patients homozygous for the O gene produce neither the A nor the B antigen, only the H precursor. c. Anti-A or anti-B antibodies are produced to the ABO antigen not expressed by the host. d. When blood products are required emergently, type O RBCs and type AB plasma may be given with the least concern for transfusion reaction (Table 188). 3. The Rh (Rhesus) antigens are a large class of more than 50 related antigens, including D, C, c, E, and e. a. Rh-positive individuals produce the D antigen b. Rh-negative individuals do not produce the antigen and do not produce antibodies to D unless exposed to it through pregnancy or another form of transfusion. c. These Rh antibodies may induce hemolytic reactions. 4. In addition to the Rh system, other clinically significant antigens include Kell, Kidd, and Duffy and are listed with their associated antibodies in Table 189. D. Complications

1. Reactions to transfused products must be recognized. 2. Potential complications may be characterized by timing (acute or chronic) and temperature (febrile or afebrile). 3. Adverse transfusion reactions are common. a. Fever (increase of 1C) occurs in 1:200 transfusions. b. Allergic reaction occurs in 1:300 transfusions. c. Fatal hemolytic reaction is rare (1:250,000) d. Recipients must understand risks and benefits to give informed consent prior to transfusion. e. When there are signs or symptoms of a transfusion reaction, the transfusion must be stopped immediately. 4. In addition to obtaining vital signs and performing a brief physical examination, a posttransfusion blood specimen is evaluated for hemoglobinemia, antibody coating, and confirmatory typing. 5. Febrile nonhemolytic reactions are the most common complication of either platelet or RBC transfusion, and are caused by recipient antibodies against donor leukocytes. a. Fever, chills (rigors), and dyspnea occur 16 hours after transfusion, and these are usually self-limited. b. Patients may be premedicated with acetaminophen. c. The use of leukoreduced cellular products also reduces the incidence of this type of reaction. d. No hemolysis is detected during routine workup. 6. Transfusion-related acute lung injury is currently the most common cause of fatal transfusion reactions. a. It is due to donor anti-HLA or anti-neutrophil antibodies that incite host neutrophil activation and subsequent adherence to pulmonary epithelium. b. Similar to acute respiratory distress syndrome, symptoms include fever and shortness of breath with signs of oxygen desaturation and noncardiogenic pulmonary edema pattern on chest radiograph, all arising within 16 hours after infusion. 7. Acute hemolytic transfusion reactions may be fatal. a. These usually involve a type O patient receiving a non-O RBC unit due to an administrative error (patient misidentification, mislabeled specimens, etc). b. Early-onset fever, hypotension, wheezing, burning, or impending sense of doom are part of the clinical picture, and subsequent DIC may lead to later bleeding. c. The transfusion must be stopped immediately. d. Prevention requires meticulous attention to patient identification during phlebotomy (sampling for pretransfusion testing) and infusion. 8. Allergic reactions to various donor proteins are the second most common type of adverse event overall. a. A range of allergic reactions is possible from mild urticaria and pruritus to severe anaphylaxis with respiratory difficulty. b. The symptoms of mild allergic reactions usually begin at the very onset of transfusion. c. Anaphylactic reactions are potentially life-threatening.

d. The cause may lie with either the donor or the recipient. 1. Donor anaphylatoxins (such as C3a and C5a) or IgE antibodies can respond to recipient antigens. 2. Conversely, recipient antibodies may arise against donor plasma antigens, especially among recipients with an underlying selective IgA deficiency. e. In mild cases, an antihistamine is helpful both in the immediate management and prophylaxis of future episodes; severe anaphylaxis, however, mandates more extensive supportive care and avoidance of plasma-containing products. 9. Transfusion-associated circulatory overload (TACO) results from poorly compensated volume expansion by transfused products. a. It is more prevalent among infants, the elderly, and patients with impaired cardiac function (eg, congestive heart failure); therefore, these patients are less tolerant of volume status changes and may experience dyspnea, orthopnea, and edema. b. Signs and symptoms include shortness of breath, wheezing, and oxygen desaturation. 1. These occur after significant volume has been infused. 2. Cardiogenic pulmonary edema is seen on chest radiograph. c. Treatment includes stopping the transfusion and placing the patient in an upright position as well as administering oxygen, diuretics, and cardiac medication. d. TACO may be prevented with a combination of slower infusion rate (1 mL/kg/h), volume-reduced products, and diuretics before, during, or after infusion. 10. Chronic (or delayed) reactions may occur long after transfusion, between 24 hours and 3 months later. a. Delayed hemolytic transfusion reactions may not be reliably associated with fever; however, they are distinguished from acute hemolytic reactions by the location of hemolysis. 1. Acute hemolytic reactions occur intravascularly, producing gross hemoglobinemia and hemoglobinuria. 2. Delayed hemolytic reactions are a form of extravascular hemolysis resulting in decreased circulating erythrocytes with increased bilirubin. b. They are most often caused by IgG antibodies that are raised in response to a previous transfusion or pregnancy. 1. These antibodies may then fall to such low levels as to be undetected on subsequent antibody screens. 2. Another dose of a blood product containing the originally offending antigen induces an anamnestic response that marks the donor RBCs for engulfment by macrophages (extravascular hemolysis). c. Many common antigens have been implicated, including members of the Rh, Kell, Kidd, Duffy, and MNSs systems. 11. Transfusion-associated graft-versus-host disease (TA-GVHD) results from donor T-lymphocytes engrafting within an immunocompromised recipient and attacking host tissue.

a. These patients have rash, diarrhea, liver abnormalities, and pancytopenia. b. The prognosis is grim; most cases are fatal. c. TA-GVHD does not respond to drugs used to control GVHD in transplant recipients. d. This complication, however, may be prevented with the use of irradiated (not simply leukodepleted) blood products as described abov e. Table 189. Red blood cell antigens and antibodies. Antigen Antibody Frequency and Significance D Anti-D Extremely common Most frequent cause of hemolytic disease of newborn Kell Anti-K Common; 10% of blood incompatible May cause newborn hemolytic disease Kidd Anti-Jka or Anti Dangerous (killer Kidd) Jkb Causes acute hemolytic transfusion reaction Duffy Anti-Fya or Anti Anti-Fya most common Fyb

Quantitative Platelet Disorders Drug-induced thrombocytopenia Bone marrow failure Hypersplenism Disseminated intravascular coagulation Idiopathic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Hemolytic uremic syndrome Viral infections

Qualitative Platelet Disorders Uremia von Willebrand disease Bernard-Soulier syndrome Glanzmann thrombasthenia Myeloproliferative disorders Drugs and dietary supplements Postcardiac bypass platelet dysfunction