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Therapeutic apheresis

ASFA guidelines overview


Editorial Board Member: Melissa R. George, D.O.
Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.
Muharrem Yunce, M.D.
Mrigender Singh Virk, M.D.

Last author update: 9 February 2023
Last staff update: 9 February 2023

Copyright: 2021-2024, PathologyOutlines.com, Inc.

PubMed Search: ASFA guidelines

Muharrem Yunce, M.D.
Mrigender Singh Virk, M.D.
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Table of Contents
Definition / general | Essential features | Terminology | Diagrams / tables | Case reports | Treatment | Sample assessment & plan | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Yunce M, Virk MS. ASFA guidelines overview. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedicineASFAguidelines.html. Accessed December 4th, 2024.
Definition / general
  • American Society for Apheresis (ASFA) was formed in 1982 with a mission to advance apheresis sciences and set a stage for physicians and allied health care workers to share their knowledge
  • ASFA publishes guidelines to systematically review the available evidence and provides a categorical way to approach the request of apheresis procedures in different diseases
  • ASFA guidelines are updated every few years; other than a few examples, this entry does not detail specifics of particular disease states
Essential features
  • ASFA guidelines organize diseases and their therapies into category and grading systems
  • Category describes the efficacy and priority of apheresis in treatment of a disease
  • Grading describes the quality of evidence to support apheresis treatment of a disease
Terminology
  • ASFA: American Society for Apheresis
  • Apheresis: a modality in which the blood of a person is passed through a device that separates blood into different components, removes 1 constituent and returns the rest, with or without a replacement fluid (J Clin Apher 2013;28:3)
Diagrams / tables

Category definitions for therapeutic apheresis
Category Description
I Apheresis is accepted as first line therapy, either as a primary standalone treatment or in conjunction with treatment modalities
II Apheresis is accepted as second line treatment, either standalone or in conjunction with other treatment modalities
III Apheresis decision should be individualized; the optimum role of apheresis is not established
IV Disorders for which apheresis is ineffective or harmful based on the published data

Grading recommendations and evidence for therapeutic apheresis
Description Methodological quality of supporting evidence Implications
Grade 1A Strong recommendation, high quality evidence Randomized controlled trials without important limitations or overwhelming evidence from observational studies Strong recommendation; can apply to most patients in most circumstances without reservation
Grade 1B Strong recommendation, moderate quality evidence Randomized controlled trials with important limitations (inconsistent results, methodological flaws, indirect or imprecise) or exceptionally strong evidence from observational studies Strong recommendation; can apply to most patients in most circumstances without reservation
Grade 1C Strong recommendation, low quality or very low quality evidence Observational studies or case series Strong recommendation but may change when higher quality evidence becomes available
Grade 2A Weak recommendation, high quality evidence Randomized controlled trials without important limitations or overwhelming evidence from observational studies Weak recommendation; best action may differ depending on circumstances or patients' or societal values
Grade 2B Weak recommendation, moderate quality evidence Randomized controlled trials with important limitations (inconsistent results, methodological flaws, indirect or imprecise) or exceptionally strong evidence from observational studies Weak recommendation; best action may differ depending on circumstances or patients' or societal values
Grade 2C Weak recommendation, low quality or very low quality evidence Observational studies or case series Very weak recommendation; other alternatives may be equally reasonable

Case reports
  • 16 year old girl with systemic lupus erythematosus and thrombocytopenia was ultimately diagnosed with thrombotic thrombocytopenic purpura (Medicine (Baltimore) 2022;101:e28908)
  • 33 year old man with chronic kidney disease, highly HLA sensitized, successfully treated with plasma exchange (Transpl Immunol 2022;74:101656)
  • 66 year old woman with weight loss and loss of appetite was found to have white blood cell (WBC) count of 122K (Oncol Lett 2014;8:1825)
Treatment
  • Plasma exchange (PLEX): plasma is removed from whole blood and replaced with albumin, fresh frozen plasma (FFP), cryo poor FFP or a combination of these fluids
  • Red blood cell exchange (erythrocytapheresis): red cells are removed from whole blood and replaced with donor RBCs
  • Leukocytapheresis: white blood cells are removed from whole blood and no replacement fluid is needed
  • Thrombocytapheresis: platelets are removed from whole blood and no replacement fluid is needed
  • Extracorporeal photopheresis: buffy coat is collected from whole blood, psoralen is added to the buffy coat and cells are photoactivated and returned to the patient (J Clin Apher 2019;34:171)
Sample assessment & plan
  • Case 1: A 35 year old man presented to the emergency department with altered mental status and easy bruising. His significant other reports that he was in his usual state of health until last night when he started to have a headache and was talking incoherently. He was going to the bathroom when he fell and hit his arm, where he had a large bruise. He has no history of solid organ or stem cell transplant.
    • On exam he seems pale, sclera is icteric, large bruise on his right arm. He is febrile and mildly tachycardic.
    • Labs: significant for hemoglobin (Hgb) 7 g/dL, platelet (PLT) 20 x 109/L, lactate dehydrogenase (LDH) of 1,200 IU/L
    • The findings may represent thrombotic thrombocytopenic purpura, since patient has acute unexplained thrombocytopenia, microangiopathic hemolytic anemia, fever and neurological findings. An emergent plasma exchange needs to be carried out.
    • Daily plasmapheresis treatments should occur with fresh frozen plasma as replacement fluid until the platelet count is > 150 x 109/L for 2 - 3 days
    • Each treatment generally exchanges 1 plasma volume
    • Stopping treatment versus tapering is controversial
    • Ancillary treatments, such as rituximab or eculizumab, may be considered after ceasing plasmapheresis
    • Therapeutic monoclonal antibodies may be removed by plasmapheresis and consideration must be given to timing such treatments after rather than concurrent with apheresis

  • Case 2: A 70 year old man with no significant history presented to the emergency with fatigue for the past 2 weeks and an inability to thrive. He has lost 10 pounds in the past 2 weeks. In the emergency department he suddenly becomes hypoxic, requiring high flow nasal cannula O2 support with 20 liters per minute (LPM). He also has sudden onset of altered mental status.
    • His labs are notable for WBC: 200 x 109/L, Hgb of 6.6 gr/dL, PLT of 30 x 109/L
    • These findings of hyperleukocytosis and end organ damage are worrisome for symptomatic hyperleukocytosis. Emergent leukocytapheresis needs to be carried out.
    • The role of leukapheresis in improving long term outcomes in leukemia with hyperleukocytosis is controversial
    • Leukapheresis is generally contraindicated in promyelocytic leukemia
    • Leukapheresis should not delay more definitive chemotherapeutic interventions
    • The primary team should be reminded of the potential for pseudohyperkalemia in hyperleukocytosis
    • Whole blood potassium measurements are preferred over serum potassium for this reason
    • 1.5 to 2 blood volumes are generally processed
    • One procedure can reduce the WBC by 30 - 60%

  • Case 3: A 22 year old man with HgbSS presented to the emergency department with right side facial droop and right side body weakness. Imaging demonstrates left middle cerebral artery stroke and multiple silent strokes.
    • On exam, the patient has right side facial droop, he is not able speak in full sentences and he is not able to move the right side of his body.
    • His labs are notable for Hgb of 10g/dL, hemoglobin S (HgbS) of 50%, WBC and PLT are within normal limits (WNL).
    • Weight: 150 Ib; height: 5'3"
    • The patient shows signs of acute stroke and his HgbS needs to rapidly be reduced to < 30%. He requires red blood cell exchange.
    • The role of ongoing prophylactic red cell exchange in stroke prevention for patients with HbSS is controversial
    • Patients receiving ongoing red cell exchange often experience venous access issues
    • Exact HbS measurement might not be available off hours, so estimation might be necessary
    • Target hematocrit should be 30 + 3% to avoid hyperviscosity
    • End HbS should be < 30%
    • The volume of packed red blood cell units to be exchanged can be calculated based upon starting and end hematocrit, fraction of patient's own cells remaining (FCR) and starting and end HbS levels
Board review style question #1
A 25 year old man with no significant medical history presents to the emergency department, where his significant other describes that he was not himself for the past day and had a fever. He is also looking pale compared to before. Last night, he hit his arm while trying to get to the bathroom, which caused a large area of bluish discoloration.

  • On arrival vitals: temperature of 39.0 °C, heart rate of 110, blood pressure of 110/70, O2 of 95% on radial artery (RA), respiration rate (RR) of 20
  • Labs significant for hemoglobin (7 g/dL), hematocrit (14.2%), platelet count (10 x 109/L), haptoglobin (< 30 mg/dL), lactate dehydrogenase (LDH; 1,885 U/L) and indirect bilirubin (3.2 mg/dL)
  • Peripheral blood smear revealed an abnormally high reticulocyte count (18.7%) and presence of schistocytes

A medicine resident inquires about the evidence for plasma exchange procedure. What does American Society for Apheresis (ASFA) recommend for this patient?

  1. ASFA category I, grade 1A
  2. ASFA category I, grade 1B
  3. ASFA category II, grade 1A
  4. ASFA category II, grade 1B
  5. ASFA category III, grade 2C
Board review style answer #1
A. This indication for plasma exchange (PLEX) carries ASFA category I, grade 1A recommendation. This patient presents with profound thrombocytopenia, hemolytic anemia, fever and neurological changes, which are consistent with thrombotic thrombocytopenic purpura (TTP) until proven otherwise. The most recent 2019 ASFA guidelines recommend PLEX as first line therapy, which would be category I indication with grade 1A recommendation (strong recommendation, high quality of evidence). The categories and grading system are explained in tables 1 and 2.

Comment Here

Reference: ASFA guidelines overview
Board review style question #2
A 65 year old woman with a history of diabetes and hypertension presents to her primary care office with fatigue and difficulty breathing for the past week. As part of workup, her primary care provider orders a CBC and results come back with WBC 150 x 109/L, hemoglobin (Hgb) 7.5 g/dL and platelet (PLT) count of 10 x 109/L. The primary care provider refers her to the emergency department immediately but she wants to stay home. After a couple of days, she becomes increasingly short of breath and is brought in by ambulance with O2 requirement of 10 L.

  • In the emergency department, her WBC went up to 190 x 109/L, Hgb 7.0 g/dL
  • Peripheral smear shows 80% of blasts consistent with acute leukemia
  • Coagulation profile is within normal limits

A hematology oncology fellow who has already looked at the American Society for Apheresis (ASFA) guidelines calls you and states that he found this indication carries a category II, grade 2C recommendation. What does this ASFA recommendation indicate?

  1. Apheresis should be considered as first line standalone therapy with strong recommendation and high quality evidence
  2. Apheresis should be considered as a second line treatment with strong recommendation and high quality evidence
  3. Apheresis should be considered as a second line treatment with strong recommendation and low quality evidence
  4. Apheresis should be considered as a second line treatment with weak recommendation and low quality evidence
  5. Apheresis should not be considered with strong recommendation and high quality evidence
Board review style answer #2
D. Apheresis should be considered as a second line treatment with weak recommendation and low quality evidence. Category II: apheresis procedure is considered as a second line treatment either standalone or in conjunction with other treatment modalities. Grade 2C: weak recommendation with low quality of evidence.

Comment Here

Reference: ASFA guidelines overview
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