Plasmapheresis is a therapeutic intervention that involves extracorporeal removal, return, or exchange of blood plasma or components. The underlying mechanism of this procedure is accomplished by either centrifugation or filtration using semipermeable membranes. This activity reviews plasmapheresis as a therapeutic intervention that involves extracorporeal removal, return, or exchange of blood plasma or components. This intervention results in a filtered plasma product that can be used for the treatment of numerous diseases. It also highlights the interprofessional team strategies for improving care coordination and communication to advance plasmapheresis and improve outcomes.
Plasmapheresis is a therapeutic intervention that involves extracorporeal removal, return, or exchange of blood plasma or components.[rx][rx] The underlying mechanism of this procedure is accomplished by either centrifugation or filtration using semipermeable membranes. While centrifugation is based on the principle of separation using different specific gravities of various blood components, membrane plasma separation filters blood components based on their particle size.[rx][rx]
The preferred method of plasmapheresis in most centers worldwide is by automated centrifuge-based technology.[rx] However, in certain hospitals and patients on hemodialysis, plasmapheresis is done using membrane plasma separation.[rx] In plasmapheresis using centrifugation, filtered plasma is discarded, and RBCs and replacement fluid (donor plasma or colloids) are returned. Membrane plasma separation allows selective removal of undesired macromolecules; hence, filtered, processed plasma is returned to the patient, eliminating the need for replacement fluids.
Indications 0f Plasmapheresis
Therapeutic plasmapheresis is used for numerous diseases. The conditions involve the presence of a toxic substance in plasma (e.g., immunoglobulin), which can be filtered. The disorders where therapeutic plasmapheresis can be done are grouped into four categories by the Apheresis Applications Committee of the American Society for Apheresis (ASFA). Category 1 includes disorders where plasmapheresis can be done as a first-line treatment, category 2 includes disorders where plasmapheresis can be done as a second-line treatment in addition to the existing standard of care, category 3 includes disorders in which the evidence of the benefit of plasmapheresis is minimal, and therapy must be individualized, and category 4 includes disorders in which the evidence suggests that plasmapheresis is either ineffective or harmful, however, may be considered after approval from the institute ethics committee.[rx]
The alphabetical list of various indications for plasmapheresis, along with their ASFA category, is as follows.
Category 1
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Acute inflammatory demyelinating polyradiculoneuropathy/Guillain-Barre syndrome
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ANCA-associated rapidly progressive glomerulonephritis (dialysis-dependent or associated with diffuse alveolar hemorrhage)
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Anti-glomerular basement membrane disease-Goodpasture syndrome (dialysis independent or associated with diffuse alveolar hemorrhage)
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Chronic inflammatory demyelinating polyradiculoneuropathy
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Focal segmental glomerulosclerosis (recurrent in the transplanted kidney)
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Hyperviscosity in monoclonal gammopathies
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Liver transplantation: Desensitization
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Myasthenia gravis
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N-methyl D-aspartate receptor antibody encephalitis
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Paraproteinemic demyelinating neuropathies/chronic acquired demyelinating polyneuropathies (IgA/IgG/IgM mediated)
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Progressive multifocal leukoencephalopathy associated with natalizumab
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Renal transplantation: Desensitization and antibody-mediated rejection
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Thrombotic microangiopathy (Factor H autoantibodies and ticlopidine)
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Thrombotic thrombocytopenic purpura
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Wilson disease (fulminant)
Category 2
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Acute disseminated encephalomyelitis
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Cardiac transplantation: Desensitization
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Catastrophic antiphospholipid syndrome
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Cryoglobulinemia; symptomatic/severe
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Dilated cardiomyopathy, idiopathic (NYHA 2-4)
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Hashimoto encephalopathy: Corticosteroid responsive encephalopathy associated with autoimmune thyroiditis
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Hematopoietic stem cell transplantation, ABO-incompatible
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Lambert-Eaton myasthenic syndrome
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Multiple sclerosis
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Myeloma cast nephropathy
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Neuromyelitis Optica spectrum disorders
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Overdose, envenomation, and poisoning, such as mushroom
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Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)
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Phytanic acid storage disease (Refsum disease)
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Systemic lupus erythematosus (severe)
Category 3
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Acute liver failure
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ANCA-associated rapidly progressive glomerulonephritis (dialysis independent)
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Anti-glomerular basement membrane disease, Goodpasture syndrome (dialysis-dependent, no DAH)
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Aplastic anemia, pure red cell aplasia
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Autoimmune hemolytic anemia
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Burn shock resuscitation
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Cardiac neonatal lupus
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Cardiac transplantation: Antibody-mediated rejection
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Chronic focal encephalitis (Rasmussen encephalitis)
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Complex regional pain syndrome; chronic
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Erythropoietic porphyria, liver disease
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Hemolysis liver enzymes low platelet (HELLP) syndrome (postpartum)
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Hematopoietic stem cell transplantation, HLA desensitization
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Hemophagocytic lymphohistiocytosis; hemophagocytic syndrome; macrophage activating syndrome
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Henoch-Schonlein purpura
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Heparin-induced thrombocytopenia and thrombosis
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Hypertriglyceridemic pancreatitis
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Immune thrombocytopenia; refractory
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IgA nephropathy; crescentic
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Lung transplantation: Desensitization and antibody-mediated rejection
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Paraneoplastic neurological syndromes
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Pemphigus Vulgaris; severe
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Pruritus due to hepatobiliary diseases
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Scleroderma (systemic sclerosis)
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Sepsis with multiorgan failure
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Stiff-person syndrome
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Thrombotic microangiopathy (complement factor gene mutations, MCP mutations, clopidogrel, and calcineurin inhibitors)
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Thyroid storm
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Toxic epidermal necrolysis (refractory)
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Vasculitis
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Voltage-gated potassium channel antibodies
Category 4
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Amyloidosis, systemic
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Dermatomyositis/polymyositis
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HELLP syndrome (antepartum)
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Lupus nephritis
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Thrombotic microangiopathy (gemcitabine and quinine)
Contraindications of Plasmapheresis
The contraindications for therapeutic plasmapheresis are as follows:[rx]
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Non-availability of central line access or large bore peripheral lines
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Hemodynamic instability or septicemia
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Known allergy to fresh frozen plasma or replacement colloid/albumin
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Known allergy to heparin
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Hypocalcemia (restricts the use of citrate as an anticoagulant during the procedure); relative contraindication
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Angiotensin-converting enzyme (ACE) inhibitor used in last 24 hours; relative contraindication
Equipment
Venous access for this procedure is either by a central venous catheter or large bore peripheral lines. There are multiple manufacturers of centrifuge-based plasmapheresis machines.
Another technique of performing plasmapheresis is by using semipermeable membrane filters with a standard hemodialysis machine. However, for this technique, central venous access is mandatory due to the need for higher blood flow rates of 100 mL/min to 150 mL/min. There are two membrane-based technologies that are currently available; hollow fiber and parallel plate. Hollow fiber dialyzers are cylindrical shell-like structures, consisting of multiple polysulfone capillary fibers.
Parallel plate dialyzers consist of layered membranes, with ridges and grooves which facilitate filtration. Both these dialyzers allow plasma filtration based on particle size and pressure gradients. Hollow fiber dialyzers are more gentle as opposed to parallel plate dialyzers and are preferred for pediatric patients, whereas hollow fiber dialyzers use less blood volume, and hence require a reduced dose of citrate or heparin for anticoagulation.
The major advantage of membrane-based plasmapheresis over centrifuge-based technology is that the removed processed plasma by ultrafiltration can be returned to the patient eliminating the need for replacement fluids or colloids.[rx]
Personnel
Plasmapheresis was traditionally performed in blood banks by centrifuge-based techniques. However, therapeutic plasmapheresis procedures are routinely performed by critical care specialists in the intensive care unit, nephrologists, and dialysis-technicians after specialized skill-based training.
Preparation
No specific patient preparation is needed for this procedure. However, while inserting a central line, a local anesthetic may be needed. For this purpose, 2% lidocaine injection is used routinely. In pediatric patients, sedation with opioids and benzodiazepines may be considered for pain and anxiety control.
The patient is positioned supine for plasmapheresis; however, the position, especially of the neck, maybe altered according to the location of central venous access to maintain adequate blood flow throughout the procedure.
A close watch on patient vitals is recommended throughout the procedure to assess for volume depletion, hypocalcemia, and complications of fresh frozen plasma transfusion.
Technique
The steps for performing plasmapheresis using centrifuge-based equipment are as follows:[rx]
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Initially, a waste of around 3-5 mL of blood from the central venous catheter is discarded.
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After drawing baseline samples for complete hemogram, calcium, and fibrinogen, it is flushed with 5-10 mL of heparinized saline.
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The double lumen catheter is now connected to the machine tubing to start the priming procedure.
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The machine calculates the total body volume (TVB), and the effective plasma volume (which equals TVB × (1 – hematocrit)) of the patient based on the operator’s entered height and weight.
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The replacement product to be used and its desired volume (40 – 60 mL/kg) is decided by the clinician, and entered into the machine, based on which it calculates the centrifuge speed.
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The separated plasma is discarded by the machine, and the RBCs are returned back to the patient along with the replacement fluid.
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Finally, post-procedure, tubings are connected to heparinized saline, and reinfusion is initiated.
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Post-plasmapheresis blood for fibrinogen and calcium is sent again, and lumens of central venous catheters are flushed.
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.[rx][rx][rx]
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
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Febrile reaction: 1:60
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Transfusion-associated circulatory overload: 1:100
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Allergic reaction: 1:250
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TRALI: 1:12,000
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Hepatitis C infection: 1:1,149,000
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Human immunodeficiency virus infection: 1:1,467,000
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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.
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Retype and crossmatch
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Direct and indirect Coombs tests
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Complete blood count (CBC), creatinine, PT, and PTT (draw from the other arm)
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Peripheral smear
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Haptoglobin, indirect bilirubin, LDH, plasma free hemoglobin
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Urinalysis for hemoglobin
Electrolyte abnormalities can also occur, although these are rare, and more likely associated with large volume transfusion.
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Hypocalcemia can result as citrate, an anticoagulant in blood products binds with calcium.
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Hyperkalemia can occur from the release of potassium from cells during storage. Higher risk in neonates and patients with renal insufficiency.
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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:[rx]
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Transfusion-associated circulatory overload (TACO)
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Transfusion-related acute lung injury (TRALI)
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Transfusion-associated dyspnea (TAD)
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Simple allergic reaction
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Anaphylactic reaction
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Hypotensive transfusion reaction
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Febrile non-hemolytic transfusion reaction (FNHTR)
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Acute hemolytic transfusion reaction (AHTR)
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Delayed hemolytic transfusion reaction (DHTR)
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Delayed serologic transfusion reaction (DSTR)
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Transfusion-associated graft vs. host disease (GVHD)
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Post-transfusion purpura (PTP)
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Transfusion-transmitted infection (TTI)
References
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