Transfusion Medicine

GENERAL PRINCIPLES

Transfusion is a therapy for several hematologic and hemostatic aberrations but its benefits must be weighed carefully against its risks as blood products are a limited resource with potentially life­threatening side effects.

TREATMENT

• pRBCs. RBC transfusion is indicated to increase the oxygen-carrying capacity of blood in anemic or bleeding patients.

î Current practice guidelines use the following Hgb thresholds³²:

#9632; Hemodynamically stable adult inpatients, including critically ill patients: #8804;7 g/dL.

#9632; Patients undergoing orthopedic surgery, cardiac surgery, or those with preexisting cardiovascular disease: #8804;8 g/dL.

#9632; Patients with acute coronary syndrome, severe thrombocytopenia, or chronic transfusion­dependent anemia: not established (consider 8-10 g/dL).

° One unit of pRBCs increases the Hgb level by approximately 1 g/dL or Hct by 3% in an average 70 kg adult.

î In the absence of cerebrovascular or cardiovascular injury, transfusions should be avoided for easily treatable anemias such as from iron or vitamin B₁₂ deficiencies.

• Fresh frozen plasma (FFP): Plasma transfusion is indicated to replace coagulation factors to treat bleeding patients, or as bleeding prophylaxis for certain invasive procedures.

î Common indications include the following:

#9632; Acquired coagulopathy in the setting of major bleeding.

#9632; Warfarin overdose with major bleeding. However, four-factor (II, VII, IX, X) prothrombin complex concentrates are generally preferred over FFP.

#9632; Factor deficiencies for which specific factor concentrates are unavailable.

î The usual dose of FFP is 10-20 mL/kg. One unit of FFP contains approximately 250 mL of plasma and 250 units of factor activity for each factor.

î FFP should not be used as a volume expander.

î FFP has been used in patients undergoing high-risk surgery (e.g., neurosurgery) with international normalized ratio (INR) gt;1.5. However, there is no evidence supporting this practice. FFP is typically ineffective for decreasing mildly elevated INR values.

• Platelets: Platelet transfusion is indicated to prevent or treat bleeding in thrombocytopenic patients or patients with dysfunctional platelets (e.g., due to aspirin).

î Current practice guidelines use the following platelet count thresholds³³:

#9632; Nonbleeding, stable inpatients: #8804;10 ? 10⁹#8725;L.

#9632; Nonbleeding, stable outpatients: #8804;20 ? 10⁹#8725;L.

#9632; Central venous catheter placement: #8804;20 ? 10⁹#8725;L.

#9632; Major surgery or lumbar puncture: #8804;50 ? 10⁹#8725;L.

#9632; High-risk surgery (e.g., neurosurgery) or life-threatening bleeding: not established (consider 50­100 ? 10⁹#8725;L).

o Pooled platelets from multiple donors were historically used. However, most platelet products in the US today are from single donors collected by platelet apheresis.

î Platelets have a short shelf life (lt;5 days) and are stored at room temperature; they should not be placed on ice or refrigerated, which can cause platelet activation.

° One unit of single-donor platelets increases the platelet count by 30-50 ? 10⁹#8725;L in an average 70 kg patient, but this response may be blunted in patients with platelet refractoriness.

î Platelet refractoriness (poor platelet count increment after transfusion) may be due to immunologic causes (anti-ABO, anti-HLA, or antiplatelet antibodies) or nonimmunologic causes (e.g., sepsis, DIC, fever, active bleeding, splenic sequestration, certain drugs).

• Cryoprecipitate

î Cryoprecipitate contains the cold-precipitated portion of plasma enriched in the following factors:

#9632; Fibrinogen

#9632; von Willebrand factor (vWF)

#9632; Factor VIII

#9632; Factor XIII

î Cryoprecipitate was used historically to replace vWF and factor VIII; however, specific replacement of these factors is now preferred. The main indication for cryoprecipitate today is to replace fibrinogen in patients with hypofibrinogenemia or DIC.

î One unit increases fibrinogen concentration by approximately 7-8 mg#8725;dL. Doses are typically

ordered in pools of 5 or 10 units.

SPECIAL CONSIDERATIONS

• Pretransfusiontesting

î The type and screen procedure tests the recipient’s RBCs for the A, B, and D (Rh) antigens and also screens the recipient’s serum for antibodies against other RBC antigens.

î The crossmatch tests the recipient’s serum for antibodies against antigens on a specific donor’s RBCs and is performed for each unit of blood that is dispensed for a patient. If a patient has no history of RBC antibodies, the serologic crossmatch may be replaced by an instantaneous computer crossmatch. Plasma and platelets do not require a crossmatch.

• Modifications of blood products

î Leukoreduction is performed by the use of filters to eliminate WBC contamination before storage or at the bedside. It is indicated for all patients to reduce the risk of the following transfusion complications:

#9632; Nonhemolytic febrile transfusion reactions

#9632; Transfusion-transmitted CMV infection

#9632; Formation of HLA alloantibodies

î CMV-seronegative blood products may be indicated for immunocompromised patients who are CMV-seronegative to reduce the risk of CMV transmission. However, prestorage leukoreduced products are considered equivalently “CMV-reduced risk” and can be used in place of CMV- seronegative products.

o Irradiation eliminates immunologically competent lymphocytes to prevent transfusion-associated graft-versus-host disease and is indicated for certain immunocompromised patients, SCT recipients, and patients who receive directed donations from HLA-matched donors or relatives.

î Washing of pRBCs is rarely indicated but should be considered for patients in whom plasma proteins may cause a serious reaction (e.g., recipients with IgA deficiency or a history of anaphylactic reactions).

î Pathogen reduction uses UV light to inactivate replicating pathogens such as bacteria and most viruses, as well as donor leukocytes, replacing CMV reduced risk blood and irradiation. It is currently only approved for platelets and plasma and is not in widespread use.

• Blood administration

° Patient and blood product identification procedures must be carefully followed to avoid any transfusion-related errors including ABO-incompatible transfusion.

° The IV catheter should be at least 18 gauge to allow adequate flow.

î All blood products should be administered through a 170- to 260-#956;m “standard” filter to prevent infusion of macroaggregates, fibrin, and debris.

î No fluids other than saline may be infused into the same line during transfusion.

î Patients should be observed with vital signs for the first 10-15 minutes of each transfusion for adverse effects and at regular intervals thereafter.

î RBC infusion is typically administered over 1-2 hours, with a maximum of 4 hours.

• Emergency transfusion may be considered in situations in which massive blood loss has resulted in cardiovascular compromise.

î Before the patient’s ABO type can be confirmed, “emergency release” blood may be used, consisting of uncrossmatched group O pRBCs and group AB or A plasma.

î If massive transfusion (replacement of #8805;10 units of pRBCs in lt;24 hours) is indicated, hemostatic components (plasma, platelets, and cryoprecipitate) should be included to correct the loss and dilution of hemostatic factors.

COMPLICATIONS

• Transfusion-Iransmittedinfections

î Donors and blood products are screened for HIV-1/2, human T-lymphotropic virus 1/2, hepatitis B, hepatitis C, West Nile virus, Zika virus, COVID-19, syphilis, Trypanosoma cruzi (Chagas), and bacteremia (platelets only).

î Viral transmission may occur when donors are in the “window period” (i.e., undetectable to testing).

#9632; The risk of hepatitis B transmission is approximately 1 in 1,000,000; other tested viruses have a transmission risk of lt;1 in 1,000,000.

#9632; CMV transmission risk may be reduced in immunocompromised patients by the use of CMV- seronegative or prestorage leukoreduced products, as well as pathogen reduction.

o Bacterial transmission may occur from either a donor infection or a contaminant at the time of collection or processing.

#9632; Platelet transfusions are more likely than RBCs to have bacterial contamination because they are stored at room temperature. This risk may be mitigated by pathogen reduction.

#9632; The most common organisms identified are Yersinia enterocolitica in RBCs and Staphylococcus spp. in platelets.

° Blood donors are also screened for COVID-19 antibodies. However, as of 2021, this screen is only used to identify eligibility of a blood donation for convalescent plasma and is not used to prevent the release of a blood product for the purpose of transfusion-transmitted infection prevention.

• Noninfectious hazards of transfusion

î Acute hemolytic transfusion reactions are usually caused by preformed antibodies in the recipient and are characterized by intravascular hemolysis of the transfused RBCs soon after the administration of ABO-incompatible blood.

#9632; Fever, chills, back pain, chest pain, nausea, vomiting, anxiety, and hypotension may develop.

#9632; If a hemolytic transfusion reaction is suspected, the transfusion should be stopped immediately and all IV tubing should be replaced. Samples of the patient's blood should be delivered to the blood bank along with the remainder of the suspected unit for repeat of the crossmatch. Direct and indirect Coombs tests should be performed, and the plasma and freshly voided urine should be examined for free Hgb.

#9632; Management includes preservation of intravascular volume and protection of renal function. Urine output should be maintained at #8805;100 mL/h with the use of IV fluids and diuretics or mannitol, if necessary. The excretion of free Hgb can be aided by alkalinization of the urine. Sodium bicarbonate can be added to IV fluids to increase the urinary pH to #8805;7.5.

î Delayed hemolytic transfusion reactions typically occur 3-10 days after transfusion and are caused by either a primary or an anamnestic antibody response to specific RBC anti gens on donor RBCs.

#9632; Hgb and Hct levels may fall.

#9632; The DAT is usually positive, depending on when the follow-up testing is conducted.

#9632; Reactions may at times be severe; these cases should be treated similarly to acute hemolytic reactions.

î Nonhemolytic febrile transfusion reactions are characterized by fevers and chills.

#9632; Cytokines released from white cells are thought to be the cause.

#9632; Treatment and future prophylaxis may include acetaminophen and prestorage leukoreduced blood products.

î Allergic reactions are characterized by urticaria and, in severe cases, bronchospasm and hypotension.

#9632; The reactions are due to plasma proteins that elicit an IgE-mediated response. The reaction may be specific to the plasma proteins of a particular donor and therefore may occur infrequently or never again.

#9632; Treatment and future prophylaxis may include antihistamines such as diphenhydramine or corticosteroids.

#9632; Anaphylactic reactions may require the addition of corticosteroids and washed or plasma- reduced products. Additionally, check serum immunoglobulins because patients with IgA deficiency who receive IgA-containing blood products may experience anaphylaxis with small exposure to donor plasma.

î Transfusion-associated circulatory overload (TACO) is a relatively common yet underrecognized complication of blood transfusion. Vblume overload with pulmonary edema and signs of CHF may be seen when patients with cardiovascular compromise are transfused. The clinical and radiographic features may be difficult to distinguish from that of transfusion-related acute lung injury (TRALI). Slowing the rate of transfusion and judicious use of diuretics help prevent this complication, as well as avoidance of unnecessary transfusion.

î TRALI is indistinguishable from acute respiratory distress syndrome and occurs within 6 hours of a transfusion.

#9632; Symptoms include dyspnea, hypoxemia, and possibly fever.

#9632; New or worsening pulmonary edema is typically seen on CXR, as with TACO, but without evidence of volume overload.

#9632; Anti-HLA or antineutrophil antibodies in the donor's serum directed against the recipient's WBCs are thought to cause the disorder.

#9632; On recognition, transfusions must be stopped and the blood bank notified so that other products from the donor(s) in question may be quarantined.

#9632; Hypoxemia resolves rapidly, typically in about 24 hours, but ventilatory assistance may be required during that time.

#9632; Despite clinical or radiographic findings that suggest pulmonary edema, data indicate that diuretics have no role and may be detrimental.³⁴

î Transfusion-associated graft-versus-host disease is a rare but serious complication usually seen in immunocompromised patients (and immunocompetent patients receiving blood from a relative) and is thought to result from the infusion of immunocompetent donor T lymphocytes.

#9632; Symptoms include rash, elevated liver function tests, and severe pancytopenia.

#9632; Mortality is gt;80%.

#9632; Irradiation or pathogen reduction of blood products for at-risk patients prevents this disease.

î Posttransfusion purpura is a rare syndrome of severe thrombocytopenia and purpura or bleeding that starts 7-10 days after exposure to blood products. This disorder is described in Chapter 20, Disorders of Hemostasis and Thrombosis, in the “Platelet Disorders” section.