Therapeutic Plasma Exchange – Indications, Contraindications

Therapeutic plasma exchange (TPE) is a procedure employed to “cleanse” the blood of various pathologic entities including antibodies, immune complexes, cellular elements, infectious agents, and toxins. A variety of conditions are responsive to therapy with TPE either as a first-line intervention or adjunct therapy. TPE, or plasmapheresis, consists of the separation of whole blood into its liquid and cellular components via centrifugal or membrane-filter technique followed by reintroduction of albumin and/or donor plasma tp the cellular components and re-infusion. This activity reviews the process of TPE, the evaluation and treatment of conditions responsive to therapeutic plasma exchange, and the role of an interprofessional team performing this interventional therapy.

Therapeutic plasma exchange (TPE) is a procedure in which blood or plasma is separated, removed, and replaced with a colloid solution of either albumin and/or donor plasma so as to accomplish the elimination of a pathologic entity.  Plasma is exchanged in volumes, usually between 1 to 1.5 L to remove dysfunctional cells, autoantibodies, immune complexes, cellular byproducts, parasites/bacteria, and toxins.  There are two different methods for plasma separation – manual and automated.

Plasma exchange is a therapeutic procedure used to treat a variety of diseases through the bulk removal of plasma. To apply this treatment to patients appropriately, it is essential to understand the methods to remove plasma, its effects on normal plasma constituents, the role of replacement fluids in the treatment, and the risks associated with the procedure. To facilitate the appropriate evidence-based use of plasma exchange and to encourage research, the American Society for Apheresis has published guidelines providing practical guidance and information to those responsible for ordering or providing this treatment.

Indications of Therapeutic Plasma Exchange

The American Society for Apheresis guidelines, Eight Edition, published in 2019, includes a periodically updated lengthy list of diseases with indications for TPE alone or along with other therapies.  It serves as a reference for TPE management of diseases, thoroughly detailing rationale, impact, technical issues, therapeutic plan, clinical/laboratory endpoints, and timing/location.  This summary is not nearly as inclusive or comprehensive as that reference, however, below are the most commonly encountered indications.

  • Sickle cell disease is an autosomal recessive group of inherited disorders affecting the production of the beta-globin subunits of hemoglobin.  Under episodes of physical insult (ie: hypo/hyperthermia, dehydration, emotional stress, hypoxia, etc) the red blood cells transform into a rigid sickled shape that does not easily traverse the vasculature. Sickle cells have abnormally short lifespans resulting in anemia in the affected individual. Additionally, patients suffering from sickle cell disease are also predisposed to certain bacterial infections and painful vaso-occlusive events known as sickle cell crisis, stroke, and death in addition to other comorbidities. Therapeutic plasma exchange is indicated for severe anemia and multiorgan failure.  The objective is to decrease vaso-occlusion by lowering the sickle hemoglobin to below 30% and raising the hemoglobin oxygen saturation.  At least one study has demonstrated that TPE has synergistic effects with red cell exchange therapy in patients with multi-organ failure.
  • Neonatal polycythemia is a neonatal condition whereby hematocrit (Hct) measures >65% in an infant born at term. It results from chromosomal anomalies, twin to twin transfusion syndrome, or growth restriction in the womb.  These infants are at risk of hyperviscosity and may develop symptoms of hypoglycemia, cyanosis, and apnea if not quickly managed with intravenous hydration.  Therapeutic plasma exchange is indicated for progressive symptoms refractory to initial treatment.  This must be initiated quickly as Hct peaks a few hours after birth.  In a systematic review and meta-analysis, it was found that crystalloid was as effective as a colloid in managing hematologic state by use of partial exchange transfusion.
  • Neonatal hyperbilirubinemia occurs when a neonatal born >35 weeks has a total bilirubin (TB) >25 mg/dL.  The causes are either physiologic (transient period of mismatched increased red blood cell production and bilirubin metabolism) or pathologic (a number of disease states involving immune-mediated hemolysis).  These infants are at risk for brain injury from bilirubin-induced neurologic dysfunction in which bilirubin crosses the blood-brain barrier and builds up within the tissue.  Phototherapy (PT) with ultraviolet light is the mainstay of therapy, however, TPE is indicated for persistently elevated TB levels despite PT.  Double-volume exchange transfusion will remove about 50% to 75% of TB from pre-exchange value.  Triple-volume exchange removes approximately 95% of TB but is rarely required.  Due to the prohibitive cost of even more advanced therapies such as intrauterine transfusion and immunoglobulin therapy, TPE is the primary alternative to phototherapy in the management of severe hyperbilirubinemia in the developing world.
  • Babesiosis is a disease caused by the parasite Babesia microti. It is carried and transmitted by the deer tick, Ixodes scapularis, and may also result from transmission from infected mother to fetus or infected blood product transfusion.  The parasite infects, replicates within, and destroys red blood cells resulting in hemolytic anemia and flu-like symptoms. The treatment regimen of atovaquone and azithromycin is often used for uncomplicated cases.  Severe cases involving end-organ damage (respiratory distress, sepsis, etc) may benefit from therapeutic plasma exchange – reducing parasite burden, correcting anemia, and removing inflammatory mediators and toxic by-products.
  • Guillain-Barre syndrome (GBS), or acute inflammatory demyelinating polyradiculoneuropathy, is an acute immune-mediated disorder targeting the myelin of the peripheral nervous system.  This is usually incited by antecedent bacterial or viral infections of the gastrointestinal or respiratory tract.  Initially, symptoms are numbness and weakness bilaterally starting in the distal extremities and progressing proximally.  GBS can become life-threatening if innervation of the cardiac and pulmonary systems is involved, or when severe chest wall skeletal muscle weakness develops.  Treatment is supportive measures along with intravenous immunoglobulins and TPE for severe cases.  The acute phase reactant, plasma fibrinogen, is elevated in acute GBS and its level is inversely related to treatment success.  Treatment with TPE is conducted until a continuous 30% decrease in plasma fibrinogen is observed.
  • Myasthenia gravis (MG) is an autoimmune disease characterized by chronic bilateral skeletal muscle weakness, particularly the ocular, oral, and facial muscles. Significant extremity weakness and respiratory muscle paralysis are usually affected only in cases of myasthenic crisis.  MG is caused by antibodies to the acetylcholinesterase (Ach) receptor at the terminal endplate of the neuromuscular junction. The consequence of diminished Ach activity due to inhibited and reduced Ach receptors accounts for the clinical presentation.  Treatment typically involves Ach inhibitors and immunosuppressants.  TPE removal of acetylcholine receptor antibodies is indicated for severe exacerbations involving bulbar dysfunction and/or respiratory compromise.  Treatment goals are short-term improvement in skeletal muscle strength and motor performance (neuromuscular junction transmission) as well as improvement in respiratory function.
  • Heparin-induced thrombocytopenia (HIT) is an anti-platelet antibody-mediated condition resulting in thrombocytopenia and thrombophilia. Heparin bound to the chemokine, platelet factor 4 (PF4), elicits an immune response directed against this structure.  The resulting complex of IgG, PF4, and heparin bind with and further activate platelets causing thrombi and thrombocytopenia. Initial treatment involves discontinuation of heparin.  Therapeutic plasma exchange is indicated in severe or persistent cases to remove such “HIT complexes”. A recent international practice survey revealed cardiovascular surgery followed by HIT-associated thrombosis as the most common reason to prophylactically treat re-exposures in patients requiring heparin.  The fluid replaced was often plasma and the occurrences of treatment were laboratory/clinical response-dependent.
  • Thrombotic thrombocytopenic purpura (TTP) is an autoantibody-mediated condition characterized by thrombophilia and thrombocytopenia. Often idiopathic, TTP’s mortality rate exceeds 90%, untreated. Antibodies crossreact against the ADAMTS13 enzyme, which catalyzes the degradation of von Willebrand factor (vWF).  When ADAMTS13 is inhibited, vWF’s action is unopposed and thrombophilia results.  Symptoms include diffuse ecchymosis and petechiae, jaundice, fever, weakness, headaches, confusion, tachycardia, and tachypnea.  TPE is employed to remove IgG and resupply with functional ADAMTS13. Plasma exchange is more effective than plasma infusion.  TPE is conducted daily until levels of lactate dehydrogenase (which increases in thrombophilic conditions) and platelets normalize.
  • Goodpasture syndrome (GPS) or anti-glomerular basement membrane disease is an idiopathic, autoimmune disease directed against the basement membrane (alpha-3-subunit of type IV collagen) in tissues unique to lungs and kidneys. Symptoms typically consist of chest pain, shortness of breath, hemoptysis, and hematuria. Mortality is high without proper diagnosis and intervention.  Treatment with immunosuppressants and TPE reduces renal and pulmonary injury and provides symptom relief. The anti-GBMs promptly decrease with TPE and immunosuppression, thus serving as an effective marker to guide ongoing therapy.
  • Renal transplant is yet another application of TPE. It is indicated prior to, during, and after transplantation. TPE aids in the desensitization of the immune system and to remove antibodies that damage renal vasculature following transplant and potentially result in rejection.
  • Malaria is a disease caused by several species of the Plasmodium parasite, typically transmitted via the Anopheles mosquito. Once in the bloodstream the parasite infects and destroys liver cells and red blood cells.  Severe flu-like symptoms of fluctuating shivers and sweats, diffuse body pain, and weakness accompanied by jaundice and respiratory distress are the disease hallmarks. Death is not uncommon. Treatment with antimalarial medications (often artemisinin-combination therapy) is typically effective in uncomplicated cases.  Though not endorsed by the World Health Organization or the United States Centers for Disease Control and Prevention, TPE is occasionally used.  One retrospective study found mixed results with TPE in observed physiologic improvements (liver functions and inflammatory markers) but no improvement in parasite burden or disease state.
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Equipment of Therapeutic Plasma Exchange

Intravenous access (needles, catheters, tubing, etc) for two sites on the body, centrifuge (speeds of 2000-2500 rpm), or plasma separation filter (60 to 900 kDa = albumin to IgM), anticoagulant (citrate or heparin), and replacement fluid (albumin or fresh frozen plasma).

Personnel

The individuals necessary for the performance of TPE are the pheresis technician, pathologist, and hematologist beyond the treating physician. Contact and communication between these individuals are vital to the expeditious treatment of each patient.

Preparation

To assure blood product safety, several measures require implementation during product collection, manufacturing, and storage. The World Health Organization has supported a global initiative to improve access to safe and sufficient blood supply. Once collected, the blood is tested for donor blood type and screened for any clinically significant donor antibodies. The collecting facility typically holds the blood until the appropriate preparation and routine screening for potential transfusion-transmitted infections is complete.  When all legal and industry standards have been met and the product is ready for transfusion, then it is “labeled” (i.e. identified as ready for use).

Widespread prioritization of testing for transfusion-transmitted infections has improved blood product safety worldwide. There is a summary of information on countries that responded to questionnaires about their particular policies and guidelines surrounding the testing of donor blood in Figure 2 according to the World Health Organization 2016 Global Status Report on Blood Safety and Availability report. The survey found that the majority of responding countries had policies for testing the most common and clinically relevant transfusion-transmitted infections including HIV, hepatitis C, hepatitis B, and syphilis. Eighteen nations in Latin America reported having a policy for testing all blood donations for Trypanosoma cruzi along with twelve countries implementing selective testing for T cruzi in donors who have traveled to high-risk areas or have defined risk factors. Thirty-seven nations reported having a policy of testing all blood donations for antibody to human T-lymphotropic virus (HTLV-I/II) along with seven countries reporting selective additional testing for new donors.

Following the collection of a blood donation, several procedures can take place during the preparation of blood for transfusion. Leukodepletion is a procedure to reduce the number of white blood cells in a blood product to reduce the risk of febrile reactions, HLA sensitization, and CMV transmission. Bacterial contamination testing of platelets can be performed prior to transfusion to avoid septic transfusion reactions. Plasma fractionation provides the opportunity to derive specific factors concentrates and intravenous immune globulin.  Gamma irradiation of blood products can be performed to reduce the risk of transfusion-associated graft-versus-host disease, which is nearly always fatal. Plasma reduction or washing of blood products limits the amount of plasma within a cellular blood product, which reduces the risk of allergic transfusion reactions or the effects of incompatible ABO antibodies.  Volume reduction can also be used to reduce excess potassium and cytokines which can cause electrolyte imbalance and febrile non-hemolytic transfusion reactions, respectively. Blood typing and screening for donor and recipient alloantibodies as well as compatibility testing are also important aspects of preparation for transfusion.  Screening the donated blood for alloantibodies is essential in the prevention of hemolytic transfusion reactions in recipients.

The new frontier in blood product safety is pathogen reduction (pathogen inactivation) which is a broad term for various methodologies applied to blood products post-collection to reduce the risk of transmission of infectious agents. Many of these technologies confer protection across different classes of infectious agents including viruses, bacteria, and parasites. Another potential benefit is that some of these technologies also inactivate donor white blood cells, which has allowed some to gain approval for the prevention of transfusion-associated graft-versus-host disease (as an alternative to irradiation). Pathogen reduction procedures are currently approved in some countries for platelets and plasma. These novel technologies can increase the shelf life of platelets and decrease the incidence of adverse transfusion reactions and bacterial contamination. These approaches are increasingly common in practice and should help improve blood product safety profiles.

Technique of Therapeutic Plasma Exchange

Centrifugal therapeutic plasma exchange: A continuous flow extracorporeal circuit is formed from the patient to the centrifuge and back to the patient. Citrate (anticoagulant) is added to the blood flow of 10-150 ml/min, while centrifugal forces separate and sieve off plasma from the heavier (white and red cells) of blood.  A replacement fluid (albumin and/or fresh frozen plasma) is recombined with the blood and returned to the patient.

Membrane therapeutic plasma exchange: A continuous flow extracorporeal circuit is formed from the patient to the filter-membrane and back to the patient. Heparin (anticoagulant) is added to the blood flow of 150 ml/min while membrane ultrafiltration properties of pore size and distribution separate and sieve off plasma from the heavier (white and red cells) of blood.  A replacement fluid (albumin and/or fresh frozen plasma) is recombined with the blood and returned to the patient.

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An important aspect of the donation process is the donor screening questionnaire. Donor recruitment represents an essential front-line mechanism for ensuring blood safety. The highest rates of transfusion-transmitted infections are present among donors receiving monetary compensation, and conversely, the lowest rates of infection are among unpaid volunteer donors.   “Replacement” and “family” donors are relied on in some countries, but these are not considered as safe as true altruistic unpaid volunteers.  A great reduction in the risk of transfusion-transmitted HIV, HCV, HBV, and syphilis infections have transpired with the initial donor screening questions and improved testing, including serology and nucleic acid amplification testing. According to the United States, Food and Drug Administration, highly sensitive donor screening questionnaires designed to defer high-risk donors for infection transmission exclude an estimated 90% of potentially infectious donors from blood donation.  Donors that have incentives to donate (such as monetary gain or wanting to help a friend) may not be completely truthful during screening.

Individual blood service organizations may have subtle variations in collection procedures, but the World Health Organization provides guidelines on the proper technique for venipuncture for blood donation.  These standardize the process and are in place to prevent transfusion-transmitted infections. A safe collection is paramount to ensure that blood products remain safe through the collection, storage, and transfusion.

Bacterial contaminants typically come from normal skin flora; therefore, proper antiseptic technique before the collection is required. The recommended procedure by the World Health Organization includes the application of a combination 2% chlorhexidine gluconate and 70% isopropyl alcohol for 30 seconds followed by 30 seconds drying time.  A closed collection system (not open to the air) is used to ensure sterility.   This procedure means that the anticoagulant-containing collection bag has an intrinsically attached tube and needle. The first 15 to 20 mL of blood is collected in a diversion bag so that, in the case of possible skin contamination, the initial blood collected is used for laboratory testing and not transfused. This diverted blood is the most likely to be contaminated by skin flora and the skin plug (created by the needle), therefore removing this from the transfusion reduces contamination risk.  Blood volumes collected vary by the technique used. According to the World Health Organization, generally for whole blood transfusion, 350 milliliters of blood is collected, and for double or triple bags to make packed red cells, fresh frozen plasma, and platelet concentrations, a volume of 450 milliliters is necessary. The volume is selected to prevent donor transfusion-associated anemia and other adverse events.

Blood donations can be separated into four main components (red blood cells, platelets, plasma, and cryoprecipitate) or left as whole blood. Once the blood has undergone processing, it is stored at appropriate temperatures (often +2 C to +6 C).  Platelets and fresh frozen plasma (FFP) require preparation within 8 hours of collection. Platelets are stored at room temperature and with agitation typically for five days unless additional shelf life-extending mechanisms are employed.  Depending on the national regulations, fresh frozen plasma can remain stored at −18 C for one year, −25 C for 36 months, or at −65 C for seven years.   Many countries are moving toward making “plasma” instead of FFP, which gives them up to 24 hours after collection before processing and freezing are required.  The temperature and duration of storage depend on blood service guidelines and storage capabilities of individual institutions. Sterility is maintained during processing and storage steps to avoid contamination. Blood units are unavailable for transfusion until undergoing appropriate testing, including ABO and Rh blood group typing and antibody screening, as well as serologic testing for transfusion-transmitted infections.

Function

Red Blood Cells

The literature strongly supports adhering to a restrictive transfusion strategy (7 g/dL) in hospitalized adult and pediatric intensive care patients who are hemodynamically stable. The evidence is not as compelling for patients with cardiovascular disease, but recommendations are to adhere to a restrictive strategy (hemoglobin 8 gm/dL) for patients with preexisting cardiovascular disease. There is insufficient evidence to make recommendations for patients with the acute coronary syndrome.

RBC transfusion is indicated in actively bleeding patients. The amount should be based on clinical assessment and, if possible, by laboratory tests to guide targeted therapy. However, in patients with upper gastrointestinal bleeding, patients with a restrictive transfusion strategy may have better outcomes.

Plasma

There is minimal guidance for plasma transfusion. However, plasma is a frequently prescribed intervention, often for mild to moderate elevations in prothrombin time or an international normalized ratio (INR). This continues to occur despite numerous studies that failed to show a relationship between these elevations and the risk of bleeding or that INR has any ability to predict bleeding.

The Cochrane Reviews found no evidence to support plasma transfusions in patients who were not coagulopathic undergoing elective cardiac surgery or critically ill patients.

The British Society of Haematology (BSH) published recommendations in 2018 for various patient groups in the absence of major bleeding.

  • There is no evidence to support the prophylactic use of plasma in non-bleeding patients with abnormal standard coagulation tests pre-procedure
  • The impact of commonly used doses to correct clotting results or to reduce the bleeding risk is very limited, especially when the PT ratio or INR is between 1.5 to 1.9.
  • Vitamin K should be administered in patients with prolonged PT that is likely to be due to acquired vitamin K deficiency.

In patients with liver disease, plasma is often transfused to correct a prolonged INR. British Society of Haematology recommends these guidelines:

  • PT and APTT do not reflect the true hemostatic status of patients with advanced liver disease.
  • There is no good evidence to endorse the use of prophylactic plasma for correction of abnormal clotting tests in non-bleeding patients prior to interventions such as elective variceal bleeding.
  • There is no good evidence to support a role for prophylactic plasma to reduce the risk of bleeding from a percutaneous liver biopsy.
  • Prophylactic transfusion of plasma should not be given in low bleeding risk procedures.
  • Do not use plasma for volume replacement.

And for sites that have 4-Factor Prothrombin Concentrates such as K-Centra and Bebulin, this should always be the first therapeutic of choice to reverse warfarin emergently.

Cryoprecipitate

There are little data on the use of cryoprecipitate in non-bleeding patients, and it is often used prophylactically but not based on good quality evidence.

The British Society of Haematology recommends:

  • There is insufficient evidence on which to base a recommendation about the threshold of fibrinogen to transfuse cryoprecipitate, or the optimal dose, in patients with hypofibrinogenemia undergoing procedures.
  • If fibrinogen is <1.0g/L (100 mg/dL) and other factors (i.e., personal/family bleeding history, drug history, bleeding risk associated with planned procedure) indicate a significant bleeding risk before a procedure, a starting dose of two five donor pools of cryoprecipitate [10 individual units] can be considered (but there is no evidence to support this).

Many US sites consider fibrinogen <2.0 g/L (<200 mg/dL) in a bleeding obstetric patient as an indication to transfuse cryoprecipitate.

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Platelets

Common guidelines for platelet transfusions include:

  • Prophylaxis against bleeding—PLT count <10,000 mg/dL
  • Neonate—PLT count <50,000 mg/dL
  • Bedside procedure—PLT count <50,000 mg/dL
  • Kidney or liver biopsy—PLT count <50,000 mg/dL
  • Bronchoscopy without biopsy—PLT count <50,000 mg/dL
  • Bronchoscopy with biopsy—PLT count <75,000 mg/dL
  • Intra-/postoperative bleeding—PLT count <50,000 mg/dL
Clinical bleeding with dysfunctional PLTs
  • PLT count <50,000 mg/dL (medical)
  • PLT count <100,000 mg/dL (surgical
  • Neurosurgery—PLT count <100,000 mg/dL

Cell Salvage

The Association of Anaesthetists guidelines make the following transfusion recommendations: Use cell salvage when it can be expected to reduce the likelihood of allogeneic (donor) red cell transfusion and/or severe postoperative anemia. Collection of blood for potential cell salvage (‘collect only’ mode) should be considered for surgical procedures where blood loss may exceed 500 ml (or > 10% of calculated total blood volume) in adult patients or > 8 mL/kg (> 10% of calculated total blood volume) in children weighing > 10 kg.

Whole Blood

There has been increasing interest in using low titer group O whole blood (LTOWB) in military and civilian trauma, and there is evidence to show that it saves lives.  It has also been used in non-trauma massive hemorrhage cases. LTOWB provides all of the components of blood (RBCs, platelets, and plasma with fibrinogen) and provides a balanced resuscitation addressing oxygen needs and coagulopathy in a single bag of blood. The whole blood has a critical titer of anti-A and anti-B of less than 50 to 200). The transfusion of up to 4 units of whole blood has been shown to be safe.

Complications

There are multiple complications of blood transfusions, including infections, hemolytic reactions, allergic reactions, transfusion-related lung injury (TRALI), transfusion-associated circulatory overload, and electrolyte imbalance.

According to the American Association of Blood Banks (AABB), febrile reactions are the most common, followed by transfusion-associated circulatory overload, allergic reaction, TRALI, hepatitis C viral infection, hepatitis B viral infection, human immunodeficiency virus (HIV) infection, and fatal hemolysis which is extremely rare, only occurring almost 1 in 2 million transfused units of RBC.

Adverse Event And Approximate Risk Per Unit Transfusion Of RBC

  • Febrile reaction: 1:60
  • Transfusion-associated circulatory overload: 1:100
  • Allergic reaction: 1:250
  • TRALI: 1:12,000
  • Hepatitis C infection: 1:1,149,000
  • Human immunodeficiency virus infection: 1:1,467,000
  • Fatal hemolysis: 1:1,972,000

Febrile reactions are the most common transfusion adverse event. Transfusing with leukocyte-reduced blood products, which most blood products in the United States are, may help reduce febrile reactions. If this occurs, the transfusion should be halted, and the patient evaluated, as a hemolytic reaction can initially appear similar and consider performing a hemolytic or infectious workup. The treatment is with acetaminophen and, if needed, diphenhydramine for symptomatic control. After treatment and exclusion of other causes, the transfusion can be resumed at a slower rate.

Transfusion-associated circulatory overload is characterized by respiratory distress secondary to cardiogenic pulmonary edema. This reaction is most common in patients who are already in a fluid overloaded state, such as congestive heart failure or acute renal failure. Diagnosis is based on symptom onset within 6 to 12 hours of receiving a transfusion, clinical evidence of fluid overload, pulmonary edema, elevated brain natriuretic peptide, and response to diuretics.

Preventive efforts, as well as treatment, including limiting the number of transfusions to the lowest amount necessary, transfusing over the slowest possible time, and administering diuretics before or between transfusions.

Allergic reaction, often manifested as urticaria and pruritis, occurs in less than 1% of transfusions. More severe symptoms, such as bronchospasm, wheezing, and anaphylaxis are rare. Allergic reactions may be seen in patients who are IgA deficient as exposure to IgA in donor products can cause a severe anaphylactoid reaction. This can be avoided by washing the plasma from the cells prior to transfusion. Mild symptoms, such as pruritis and urticaria can be treated with antihistamines. More severe symptoms can be treated with bronchodilators, steroids, and epinephrine.

Transfusion-related lung injury (TRALI) is uncommon, occurring in about 1:12,000 transfusion. Patients will develop symptoms within 2 to 4 hours after receiving a transfusion. Patients will develop acute hypoxemic respiratory distress, similar to acute respiratory distress syndrome (ARDS). Patients will have pulmonary edema without evidence of left heart failure, normal CVP. Diagnosis is made based on a history of recent transfusion, chest x-ray with diffuse patchy infiltrates, and the exclusion of other etiologies. While there is a 10% mortality, the remaining 90% will resolve within 96 hours with supportive care only.

Infections are a potential complication. The risk of infections has been decreased due to the screening of potential donors so that hepatitis C and human immunodeficiency virus risk are less than 1 in a million. Bacterial infection can also occur, but does so rarely, about once in every 250,000 units of red cells transfused.

Fatal hemolysis is extremely rare, occurring only in 1 out of nearly 2 million transfusions. It is the result of ABO incompatibility, and the recipient’s antibodies recognize and induce hemolysis in the donor’s transfused cells. Patients will develop an acute onset of fevers and chills, low back pain, flushing, dyspnea as well as becoming tachycardic and going into shock. Treatment is to stop the transfusion, leave the IV in place, intravenous fluids with normal saline, keeping urine output greater than 100 mL/hour, diuretics may also be needed, and cardiorespiratory support as appropriate. A hemolytic workup should also be performed which includes sending the donor blood and tubing as well as post-transfusion labs (see below for list) from the recipient to the blood bank.

  • Retype and crossmatch
  • Direct and indirect Coombs tests
  • Complete blood count (CBC), creatinine, PT, and PTT (draw from the other arm)
  • Peripheral smear
  • Haptoglobin, indirect bilirubin, LDH, plasma free hemoglobin
  • Urinalysis for hemoglobin

Electrolyte abnormalities can also occur, although these are rare, and more likely associated with large volume transfusion.

  • Hypocalcemia can result as citrate, an anticoagulant in blood products binds with calcium.
  • Hyperkalemia can occur from the release of potassium from cells during storage. Higher risk in neonates and patients with renal insufficiency.
  • Hypokalemia can result as a result of alkalinization of the blood as citrate is converted to bicarbonate by the liver in patients with normal hepatic function.

Transfusion Reactions

Transfusion reactions that can occur with the transfusion of blood range from life-threatening reactions to circumstances in which transfusion can continue, once the cause of the reaction is determined (e.g. simple allergic reaction).  The most common reactions include the following:

  • Transfusion-associated circulatory overload (TACO)
  • Transfusion-related acute lung injury (TRALI)
  • Transfusion-associated dyspnea (TAD)
  • Simple allergic reaction
  • Anaphylactic reaction
  • Hypotensive transfusion reaction
  • Febrile non-hemolytic transfusion reaction (FNHTR)
  • Acute hemolytic transfusion reaction (AHTR)
  • Delayed hemolytic transfusion reaction (DHTR)
  • Delayed serologic transfusion reaction (DSTR)
  • Transfusion-associated graft vs. host disease (GVHD)
  • Post-transfusion purpura (PTP)
  • Transfusion-transmitted infection (TTI)

References