Introduction

• Blood can be transfused either as whole blood or as individual blood components.
• Blood is made of plasma, RBCs, WBCs, and platelets.
• Plasma makes up about 55% of whole blood, it’s acellular and contains water, electrolytes, proteins (like clotting factors and albumin), hormones, waste products, and antibodies.
• RBCs comprise 40-45% of the whole blood, and WBCs and platelets comprise the rest.

Whole blood transfusion

Whole blood transfusion carries the risk of volume overload, immune reactions including GVHD, and febrile reactions! In addition, whole blood has a much shorter shelf life, and WBCs and platelets lose function over time. For these reasons, whole blood transfusion is rarely used nowadays! Instead, We transfuse the individual blood components.

Packed RBCs transfusion

• Indications for PRBC transfusion vary depending on the patient’s condition:
  • Stable, nonbleeding, and asymptomatic patients: transfusion is indicated when hemoglobin (Hgb) is below 7 g/dL, multiple clinical trials including the relatively recent MINT trial support this restrictive transfusion strategy even in acute MI.
  • Patients with active bleeding and/or hemodynamic instability: RBC transfusion should continue until bleeding is controlled and hemodynamic stability is achieved, regardless of the hemoglobin level.
• Don’t be misled by the initial hemoglobin level in patients with active bleeding. This value is often falsely elevated due to hemoconcentration and only reflects the level at the time of blood draw. The true hemoglobin is likely much lower!
• In hemodynamically unstable patients, blood can be transfused as quickly as possible, similar to an IV fluid bolus.
• Each PRBC unit is about 300 ml and can be administered over 20–30 minutes, multiple units can be administered simultaneously.
• In cases where volume overload is a concern, an IV loop diuretic may be administered during or immediately after the transfusion.
• In stable patients, the PRBC unit can be transfused over 4 hours in patients at risk of volume overload, and over 2-4 in patients without that risk.
• HD patients may receive the transfusion during HD in nonemergent situations.
• O-negative blood is the fastest option in emergencies requiring packed red blood cells (PRBCs). Immediately order O-negative blood and request a type and crossmatch for the estimated number of units needed. A type and crossmatch differs from a type and screen:
  • Type and Crossmatch: Determines the patient’s ABO and Rh blood type and tests the patient’s blood against specific donor units to ensure compatibility.
  • Type and Screen: Identifies the patient’s ABO and Rh blood type and screens the patient’s serum for any clinically significant antibodies.
  • Use a type and crossmatch when transfusion is highly likely or urgent. A type and screen is appropriate when transfusion is possible but not certain.
• Wait at least 15 minutes after the transfusion is complete before drawing blood to repeat the H/H. This applies to all kinds of transfusion.

Platelet transfusion

• Platelet transfusion is indicated in the following situations:
  • Actively Bleeding Patients if plt count < 100k in CNS bleeding and < 50k for bleeding outside the CNS.
  • Before Major Surgeries if plt count < 100k in CNS surgeries and < 50k in major surgeries outside the CNS.
  • Disseminated Intravascular Coagulation (DIC) when platelet count is less than 10,000/µL to minimize serious bleeding risk.
• Avoid platelet transfusion in conditions characterized by platelet destruction, such as Immune Thrombocytopenic Purpura (ITP), Thrombotic Thrombocytopenic Purpura (TTP), Hemolytic Uremic Syndrome (HUS), and HELLP syndrome, transfused platelets are often rapidly destroyed, providing limited benefit. However, in cases of significant or life-threatening bleeding, platelet transfusions may be considered to help control hemorrhage.
•  Platelets are either obtained from a single donor by a process known as apheresis, or from Whole blood (WBD) pooled рlatеlеts (Multiple donors).
• A single donor unit roughly equals 6 to 8 random donor platelet units and is expected to raise the platelet counts by 30000/microL.

• Unlike PRBCs, platelets ABO compatibility is preferred but not necessary, ABO incompatible platelets can be used with minimal risk. However major compatible platelet transfusions are associated with higher count increments.
• RhD-negative girls or women of childbearing age must receive prophylaxis with Rh immune globulin (RhIg) if they receive platelets obtained from RhD-positive donors.

Plasma Transfusion

• Fresh frozen plasma (FFP) is indicated in INR reversal and plasma exchange.
• INR reversal is indicated in:
  • Wаrfariո-associated life-threatening bleeding
  • Before emergent or urgent procedures.

• For warfarin-associated life-threatening bleeding:
  • 4-factor Prothrombin Complex Concentrate (4-factor PCC), which contains factors II, VII, IX, and X, is the first-line reversal solution.
  • 3-factor PCC and factor 7 combination can be used if 4-factor PCC isn’t available. 3-factor PCC lacks factor 7.
  • FFP is used when PCC solutions are not available.
• FFP has a greater impact on INR at higher INR levels; as INR approaches normal, each unit’s effect diminishes. This means it takes less FFP amount to reduce the INR from 6 to 5 than from 4 to 5.
•  Each unit of FFP is 200-300 ml. Effective hemostasis generally requires coagulation factors at 25–30% of normal levels and fibrinogen levels of at least 75–100 mg/dL. To achieve this, about one-quarter to one-third of a patient’s plasma volume may need to be replaced. Adult plasma volume is approximately 40 mL/kg.

•  Each unit of FFP can be transfused roughly over 30-60 minutes, A slower rate or a loop diuretic can be considered if volume overload is a concern.
• In most cases, the goal is to bring INR to ≤ 1.5.
• Check the INR level 15-30 minutes after completion of the infusion and repeat the infusion until INR is ≤ 1.5; if it’s elevated, we can repeat the dose.
• The effect of fresh frozen plasma (FFP) typically lasts 6–8 hours. Keep this in mind when using FFP to reverse INR before a procedure.

Cryoprecipitate

• FFP isn’t rich in fibrinogen but can be processed in multiple ways to produce cryoprecipitate.
• Cryoprecipitate is rich in fibrinogen, Factor VIII, von Willebrand factor, and Factor XIII.
• Cryo is usually given in pools, each pool is made of 5 units or packs, and each unit is 10 to 20 mL only, which means it doesn’t carry the risk of volume overload. Each pool is typically transfused over 30 minutes.
• Cryoprecipitate is used in DIC patients who have:
  • Serious bleeԁiոg.
  • At high risk for blеeԁiոg (eg, after surgery).
  • Require invasive procedures.
• If the plasma fibriոоgen level is <100 mg/dL, we administer cryoprecipitate to increase it to >100 mg/dL.
• If the plasma fibriոоgen level is >100 mg/dL and the PТ or аPΤТ remains significantly elevated, we administer FFΡ.

• 1 unit of cryoprecipitate per 10 kg of body weight is often sufficient to raise fibrinogen by approximately 50-70 mg/dL. For a 70-kg patient with a fibrinogen level of 50 mg/dl, we will need 7 units or packs of cryo to raise the fibrinogen level to > 100 mg/dl.
• Repeat labs 30-60 minutes after all the transfusions are finished. If fibrinogen is > 100 mg/dl and the PТ or аPΤТ remains significantly elevated, we administer FFΡ.

Massive transfusion

• Massive transfusion is defined as the transfusion of 10 or more units of whole blood (WB) or packed red blood cells (PRBCs) within 24 hours, 3 or more units of PRBCs in one hour, or 4 or more blood components within 30 minutes.

• Massive transfusion may lead to dilutional coagulopathy, hypocalcemia due to citrate toxicity, hyperkalemia, and hypothermia. To address these risks, massive transfusion protocols have been developed.
• In massive transfusion, we aim to follow a 1:1:1 ratio—one unit of PRBCs, one unit of platelets, and one unit of plasma.
• Cryoprecipitate should be given if the fibrinogen level falls below 100 mg/dL, and hypocalcemia should be managed with calcium supplementation.

Transfusion reactions

• Remember that the PRBC and platelet units contain some WBC and some plasma, plasma units are acellular, and they don’t contain cells!
• Transfusion reactions may occur with any blood product and are categorized into immune and nonimmune reactions.
• Immune reactions include the hemolytic reaction, febrile Non-Hemolytic Reactions, allergic reactions, TRALI, and GVHD.

Hemolytic reactions

• Although rare today, it can still occur due to procedural errors from a major ABO incompatibility, leading to the recipient’s antibodies attacking transfused red blood cells.
• Strict ABO compatibility is required for RBC and FFP transfusions, while for platelets transfusion, ABO compatibility is preferred to reduce the risk of minor reactions or platelet refractoriness, but it is not absolutely necessary.
• Hemolytic reactions are characterized by the development of fever, chills, back or chest pain, flank pain, or pink/red urine or serum during transfusion or within 24 hours afterward.
• Stop the transfusion immediately, perform a transfusion reaction panel, and monitor the patient closely.
• The development of disseminated intravascular coagulation (DIC) and acute kidney injury (AKI) supports the diagnosis of AHTR. If confirmed, treatment is primarily supportive, and the patient should be monitored in the ICU.

Febrile Non-Hemolytic Reactions

• They are caused by reactions to donor white blood cells or cytokines present in the transfused product.
• They are characterized by an isolated fever above 38°C or 100.4℉, chills, or rigors during a transfusion or within 4 hours afterward.
• Primarily occurs with RBC and platelet transfusions and is rare with plasma transfusions, as plasma is acellular.
• To reduce the risk of febrile reactions, RBCs and platelets can undergo leukocyte reduction, resulting in leukocyte-depleted RBCs or platelets.
• Stop the transfusion immediately and perform a transfusion reaction panel.
• Acetaminophen can be administered to reduce fever.
• If the transfusion reaction panel is negative and the fever resolves, the transfusion can be resumed with a new unit.
• Consider using leukocyte-depleted units if available, and discard the unit that led to the reaction.
• It’s worth noting that there is no strong evidence to support premedication with acetaminophen or antihistamines.

Allergic Reactions

• This happens due to hypersensitivity to proteins in donor plasma.
• Common with platelets and FFP transfusions due to plasma proteins but less with PRBCs transfusion.
• It is characterized by the development of pruritus, hives, urticaria, or localized angioedema—without wheezing, shortness of breath, systemic angioedema, or hemodynamic instability.
• This reaction may occur during, at the end of, or shortly after a transfusion.
• Stop the transfusion immediately and administer diphenhydramine, which usually resolves symptoms quickly. If symptoms persist, a second dose of diphenhydramine may be given.
• To reduce the risk of allergic reactions, the platelets and RBC can be washed from the plasma, so-called washed RBCs or platelets.
• Once symptoms have subsided, the transfusion may be resumed with the same unit, as the remainder can be used safely, unlike with other types of transfusion reactions.

Anaphylactic reactions

• Typically occurs within seconds to minutes of starting the transfusion with rapid onset of shock, hypotension, angioedema, respiratory distress, and/or wheezing.
• Immediately stop the transfusion and administer epinephrine along with antihistamines and other supportive treatments as needed.
• Evaluate these patients for IgA deficiency, as IgA-deficient individuals may have antibodies that can trigger severe reactions.
• For future transfusions, consider using IgA-deficient blood products or washed red blood cells to minimize the risk of recurrence.
• Premedication with antihistamines and corticosteroids may also be considered, though its effectiveness varies.

TRALI (Transfusion-related acute lung injury)

• It may happen due to donor antibodies reacting with recipient leukocytes, causing inflammation and capillary leak in the lungs.
• It’s more likely to happen with plasma-containing products (FFP, platelets, and to some extent cryo) due to the risk of donor antibodies against recipient leukocytes.
• TACO (Transfusion-associated circulatory overload) is a nonimmune reaction caused by fluid overload from the transfusion, resulting in pulmonary edema.
• Both TRALI and TACO can present with similar symptoms, including shortness of breath, hypoxia, and bilateral infiltrates on a chest X-ray. However, TRALI tends to cause more severe hypoxia and respiratory distress.
• Stop transfusion, administer IV loop diuretics, and provide supplemental oxygen to correct hypoxia, patients likely will require noninvasive positive pressure ventilation or mechanical ventilation. If it’s TACO, the patient responds quickly to diuretics, while TRALI does not and requires supportive care similar to acute respiratory distress syndrome (ARDS).
• An individual with previous TRALI can receive blood products from other donors without restrictions but should not receive any remaining untransfused portion of the implicated product or any other products from the implicated donor.

Graft versus host disease (GVHD)

GVHD transfusion reaction is rare and happens in immunocompromised patients when the donor lymphocyte identifies the recipient’s tissues as foreign and attacks them. To reduce this risk, PRBC or platelets can be irradiated to destroy the donor WBC including lymphocytes before transfusion to immunocompromised patients.

To wrap up:

• Leukocyte-reduced RBC/platelets are used to reduce the risk of febrile nonhemolytic transfusion reactions.
• Washed RBC/platelets are used to reduce the risk of allergic reactions.
• Irradiated RBC/platelets are used in immunocompromised patients to reduce the risk of GVHD.