Defines UnitedHealthcare Idaho coverage policy for therapeutic apheresis procedures (including plasma exchange, photopheresis, LDL apheresis, immunoadsorption, and related procedures) and lists covered and not-medically-necessary indications; applies to Idaho plans including Idaho Medicaid Plus.
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Evidence supports selective use of apheresis-based desensitization in specific transplant contexts when objective antibody metrics are used to guide therapy.
Kidney transplant desensitization evidence: Plasmapheresis combined with low-dose IVIG (and other desensitization protocols such as protein A immunoadsorption) has been reported to convert positive T- and/or B-cell cytotoxic crossmatches to negative and enable deceased- and live-donor renal transplantation in highly sensitized patients; antibody titer/strength (e.g., high-titer donor-specific antibodies) influences AMR risk and outcomes.HLA class I PRA >50% described in cohort
Observational cohorts and series report conversion to negative crossmatch and variable rejection rates; desensitization often used with transplantation within days of treatment to maintain antibody suppression.
Pre-transplant antibody reduction therapies: Pretransplant plasmapheresis and/or immunoadsorption can reduce panel reactive antibodies (PRA) and has been associated with lower graft rejection and loss compared with sensitized patients not receiving these procedures in observational studies.Some patients achieved negative PRA after PP/IA
Evidence from multiple single-center and registry reports; prospective trials limited.
Pediatric ABO-incompatible heart transplant support: Perioperative plasma exchange and intraoperative anti-A/B immunoadsorption reduce isohemagglutinin titers and have enabled successful ABO-incompatible pediatric heart transplantation with comparable survival and rejection rates to ABO-compatible transplants; intraoperative immunoadsorption was associated with lower blood product utilization in one single-center series.Comparative cohorts described (ABO-IA vs ABO-PE)
Data from Issitt et al. and Dipschand et al. support these approaches in infants and young children when documented titer reduction is achieved.
inv-04: Non-transplant apheresis evidence
Selected non-transplant apheresis indications reported in the literature show variable biochemical effects and low-certainty clinical outcome evidence.
Lipoprotein apheresis in hoFH and refractory angina: Lipoprotein apheresis produces substantial LDL-C reductions in children with homozygous familial hypercholesterolemia and may improve myocardial perfusion reserve in small trials for refractory angina with elevated Lp(a); evidence is primarily registry and small randomized trial data.Treatment frequency up to twice weekly associated with lower LDL-C
Registry data (Luirink et al.) and small RCTs inform benefit; generalizability limited.
Plasmapheresis in hypertriglyceridemic pancreatitis: Plasmapheresis lowers serum triglyceride levels within 24 hours compared with conventional treatment but does not clearly improve prognosis; higher observed in-hospital mortality in plasmapheresis groups may reflect confounding by severity.Triglyceride reduction at 24 hours
Systematic reviews (Yan et al.) show biochemical benefit but uncertain clinical outcome improvement.
ABO-incompatible pediatric heart transplant evidence: Single-center series and cohort studies report equivalent survival and comparable rejection outcomes between ABO-incompatible and ABO-compatible infant heart transplantation when perioperative plasma exchange or intraoperative immunoadsorption protocols are used; procedures reduce isohemagglutinin titers (for example, reductions from as high as 1:32 to 0-1:16 reported) and can enable transplantation in older pediatric recipients in some series, with reduced blood product utilization noted with immunoadsorption in one cohort.Reported isohemagglutinin titer reductions in series
Evidence derives from Issitt et al. (2012, 2021) and Dipschand et al. (2010); centers document exchange volumes and titer monitoring as part of evaluations.
inv-06: SCD transfusion and exchange — evidence summary
Red cell exchange and transfusion strategies in sickle cell disease (SCD)
RCE efficacy and safety: Retrospective and prospective series report that red cell exchange (RCE) can reduce respiratory distress in acute chest syndrome and is generally safe in pediatric and adult programs, though adverse events occur (e.g., 19.7% AE rate reported in a pediatric chronic RCE review); automated RCE may be more efficient but meta-analyses show variable HbS and ferritin benefits compared with manual exchange.AE rate reported 19.7% in pediatric chronic RCE series
Wade et al. and Velasquez et al. provide safety and efficacy observational data; randomized evidence limited.
Stroke prophylaxis evidence: Observational cohort data suggest exchange transfusion at time of first stroke presentation reduces risk of a second stroke compared with simple transfusion (retrospective cohort showing ~5-fold greater RR with simple transfusion), supporting exchange modalities for secondary prevention; ASH guidelines recommend TCD screening and regular transfusion to maintain HbS <30% and hemoglobin ≥9 g/dL in children with abnormal TCDs.Maintain HbS <30% and hemoglobin >=9.0 g/dL for children with abnormal TCD
Hulbert et al. and ASH guidance inform these recommendations; trial-level evidence is limited and mostly observational.
inv-07: Apheresis in autoimmune, nephrologic, and myopathy indications
Therapeutic apheresis in autoimmune, nephrologic, and myopathy indications
ANCA-associated vasculitis: Systematic reviews and RCT meta-analyses in ANCA-associated vasculitis show plasma exchange is not associated with mortality or clinical remission benefit overall but may reduce incidence of end-stage renal disease in the early treatment phase (e.g., lower ESRD at 3 months in some pooled comparisons); RCT evidence for EGPA is lacking.ESRD reduction observed at 3 months in pooled comparison
Yamada et al. synthesize RCT data with mixed outcomes and highlight need for further research.
FSGS and idiopathic inflammatory myopathies: There is insufficient high-quality evidence to support routine use of therapeutic plasma exchange or LDL apheresis for steroid-resistant FSGS in the native kidney and insufficient evidence for idiopathic inflammatory myopathies, though small case series report potential benefit in select antibody-positive necrotizing autoimmune myopathy cases.
ECRI and small series (Kruse et al., Ning et al.) document limited and heterogeneous data.
inv-08: Indications with insufficient evidence (not routinely supported)
Indications with insufficient evidence (not routinely supported)
Insufficient evidence indications: The following conditions are identified as having insufficient quality evidence to support routine apheresis use: idiopathic inflammatory myopathies (including necrotizing autoimmune myopathy except select antibody-positive cases), immune thrombocytopenia (ITP), pemphigus vulgaris, post-transfusion purpura (PTP), stiff-person syndrome, Sydenham's chorea, toxic epidermal necrolysis (TEN), Kawasaki disease vasculitis, sepsis with multiorgan failure, and other disorders listed in the policy. Requests for these indications require strong, case-specific justification and documentation of failure of standard therapies.
Evidence largely from retrospective series, small trials, or case reports; ASFA/other guideline categorizations vary and further RCTs are needed.
inv-09: Indications with some guideline or meta-analytic support
Indications with some guideline or meta-analytic support
Supportive indications: Adjunct therapeutic plasma exchange in select critically ill adults with sepsis and multiorgan dysfunction has been associated with reduced short-term mortality in pooled small trials (meta-analysis); red blood cell exchange is recommended by ASFA/ASH as an option for acute stroke, severe acute chest syndrome, and for primary or secondary stroke prophylaxis in sickle cell disease, with automated exchange preferred for chronic transfusion programs due to efficiency and reduced iron accumulation.
Kuklin et al. meta-analysis for sepsis and ASFA/ASH guidelines for SCD inform these statements; larger trials needed for sepsis.
inv-10: SCD: Acute and prophylactic red blood cell exchange criteria
Covered when ALL of the following are met for SCD-related apheresis/exchange
SCD acute/secondary stroke indications: RBC exchange (automated or manual) is indicated for patients with acute ischemic stroke, severe acute chest syndrome, multiorgan failure, and as therapy for primary or secondary stroke prophylaxis in patients meeting guideline criteria.
ASFA and ASH guidance support these indications; selection of modality depends on clinical scenario and resources.
Pediatric TCD screening and transfusion: For children (ages 2–16) with HbSS or HbS β0 thalassemia and abnormal Transcranial Doppler (TCD) velocities, annual TCD screening and regular blood transfusions (typically every ~3–4 weeks) are recommended to maintain HbS <30% and hemoglobin ≥9.0 g/dL to reduce stroke risk.HbS <30%; hemoglobin >= 9.0 g/dL
Strong ASH recommendation in settings where regular transfusion and chelation are feasible.
Acute neurologic deficits in SCD: For acute neurologic deficits (including TIA) in children or adults with SCD, prompt blood transfusion within 2 hours is recommended; the choice among simple transfusion, modified exchange, or apheresis depends on patient factors and local resources. If exchange cannot be arranged within 2 hours and hemoglobin ≤8.5 g/dL, simple transfusion may be given while arranging exchange.
inv-11: LDL apheresis: FH criteria
Covered when ALL of the following are met for LDL apheresis
Homozygous FH: LDL (lipoprotein) apheresis should be considered for adults and children/young people with homozygous familial hypercholesterolemia depending on response to lipid-modifying therapy and presence of coronary artery disease; frequency and duration individualized based on LDL-C control and clinical course.
NICE and EAS consensus recommend consideration of LA in hoFH; registry data support LDL-C reductions with frequent treatments.
Heterozygous FH exceptional cases: LDL apheresis may be considered for heterozygous familial hypercholesterolemia in exceptional circumstances (progressive symptomatic heart disease not responding to maximal tolerated lipid-modifying therapy and optimal medical/surgical care).Failure of maximal tolerated therapy
NICE guidance frames heterozygous FH apheresis as exceptional rather than routine.
inv-12: Plasmapheresis and leukapheresis: guideline-based indications
Covered when clinically indicated based on guideline-recommended uses
Symptomatic hyperviscosity: Plasmapheresis is indicated as adjunctive therapy for symptomatic hyperviscosity syndromes (for example, multiple myeloma with hyperviscosity).Symptomatic hyperviscosity
NCCN guidelines support plasmapheresis for symptomatic hyperviscosity and removal of free light chains in select myeloma kidney presentations.
Neurologic autoimmune disorders: Plasma exchange is used for acute attacks of neuromyelitis optica and similar disorders where guidelines recommend corticosteroids plus plasma exchange for relapses or steroid-refractory presentations.Acute relapse refractory/intolerant to steroids or per guideline
NINDS/NMO guidance and evidence syntheses support PLEX as second-line therapy for severe relapses.
Leukapheresis in leukostasis:
Therapeutic apheresis, as defined in this policy, is a set of extracorporeal procedures for removal or modification of blood components and does not include stem cell collection or harvesting for use in bone marrow/stem cell transplantation. The distinction is important for coding and prior authorization because stem cell collection is a separate transplant-related service rather than apheresis for therapeutic removal or replacement of pathogenic blood elements.
A 2010 systematic review (Gupta et al.) evaluating extracorporeal removal of serum free light chains in multiple myeloma with acute renal injury did not demonstrate a benefit of plasmapheresis independent of chemotherapy. This finding is cited to justify that plasmapheresis alone is not supported as a routine, stand-alone therapy for cast nephropathy in multiple myeloma.
The policy states there is insufficient quality evidence to support therapeutic plasma exchange (TPE) for steroid-resistant focal segmental glomerulosclerosis (FSGS) in the native kidney and similarly limited evidence for LDL apheresis in FSGS. Likewise, for idiopathic inflammatory myopathies the document concludes evidence is inadequate to endorse routine apheresis use, and available reports are primarily small, retrospective series or case reports.
The policy identifies multiple conditions for which the evidence base is weak or inconsistent; these include idiopathic inflammatory myopathies, immune thrombocytopenia (refractory ITP), pemphigus vulgaris, post-transfusion purpura (PTP), stiff-person syndrome, Sydenham's chorea, toxic epidermal necrolysis (TEN), and Kawasaki disease. For these indications the policy characterizes apheresis as having insufficient quality evidence to support routine use and therefore not routinely medically necessary absent compelling, case-specific documentation.
Guidance from professional bodies is summarized: the European Atherosclerosis Society (EAS) supports consideration of lipoprotein apheresis for very high Lp(a) or in select familial hypercholesterolemia cases after maximal medical therapy, and NICE recommends that Extracorporeal Photopheresis (ECP) not be used outside research for Crohn's disease. These guidance statements inform the policy's conservative stance on LDL apheresis and ECP in those contexts.
The policy lists numerous diagnoses and clinical scenarios as unproven or not medically necessary for therapeutic apheresis, including but not limited to acute disseminated encephalomyelitis (ADEM), many ANCA-associated rapidly progressive glomerulonephritis presentations, certain acute liver failure indications, Alzheimer’s disease, chronic multiple sclerosis/myasthenia gravis long-term uses, Sepsis with multiorgan failure, and many dermatologic and neurologic disorders. Providers should refer to the policy detail for the full enumerated list when preparing authorization requests.
For focal segmental glomerulosclerosis (FSGS) and idiopathic inflammatory myopathies, the policy emphasizes that available studies are small, heterogeneous, or of limited quality and therefore do not provide sufficient evidence to support routine use of apheresis (TPE or LDL apheresis). While isolated case series suggest possible benefit in select antibody-positive necrotizing myopathies, these data are considered inadequate to change the overall coverage position without stronger prospective evidence.
Requests for apheresis for the conditions identified as having insufficient evidence are treated as not routinely medically necessary. Authorization for these indications requires strong, case-specific justification and documentation of prior guideline-recommended therapies and objective clinical data supporting the proposed use; lack of such documentation increases the likelihood of denial.
The policy notes that routine leukapheresis is not recommended for hyperleukocytosis in acute promyelocytic leukemia (APL) per NCCN guidance; leukapheresis may be considered only in select life‑threatening leukostasis cases that are unresponsive to other modalities, and with appropriate clinical justification.
Applicable Procedure and Diagnosis Codes
Applicable procedure codes (examples)CPT | HCPCS
0342T
Therapeutic apheresis with selective HDL delipidation and plasma reinfusion.
36511
Therapeutic apheresis; for white blood cells.
36512
Therapeutic apheresis; for red blood cells.
36513
Therapeutic apheresis; for platelets.
36514
Therapeutic apheresis; for plasma pheresis.
36516
Therapeutic apheresis; with extracorporeal immunoadsorption, selective adsorption or selective filtration and plasma reinfusion.
36522
Photopheresis, extracorporeal
S2120
Low density lipoprotein (LDL) apheresis using heparin-induced extracorporeal LDL precipitation
HVP definitionHigh-Volume Plasma Exchange (HVP) defined as exchange of 15% of ideal body weight (~8–12 L) with plasma replacement; removal rate ~1–2 L/hour
Typical volume rangeApproximately 8–12 liters per HVP session (equivalent to 15% ideal body weight)
Procedure tempoPlasma removed at about 1–2 L per hour during HVP sessions
Clinical uses notedUsed in settings requiring large plasma clearance (e.g., selected acute liver failure, hyperviscosity syndromes) per policy descriptions
inv-24: HLA antibody MFI
Examples of MFI thresholdsStudies in desensitization report HLA antibody mean fluorescence intensity (MFI) examples such as >2,000 and >10,000 to characterize antibody strength
Provider Actions, Authorization, and Documentation
Prior Authorization
Prior Authorization Required
Prior authorization is required for the therapeutic apheresis procedures identified by the applicable CPT/HCPCS codes in this policy. Providers should submit a prior authorization request that includes the clinical indication, prior therapies attempted and responses, planned procedural details (type of apheresis, number of exchanges/sessions, replacement fluid), and transfusion goals when relevant. UnitedHealthcare may use clinical decision tools (e.g., InterQual) to assist in review and reserves the right to modify authorization requirements per applicable federal, state, or contractual benefit terms.
Include diagnosis, relevant lab values, and prior treatments tried and failed
Specify planned replacement fluid (e.g., albumin, donor plasma) and number of exchanges/sessions
Document transfusion goals (e.g., target HbS%, target hemoglobin) for sickle cell or exchange transfusion requests
Attach recent medical records; lack of documentation may result in denial
Prior Authorization
Authorization: Apheresis-Based Desensitization for Transplant
Authorization for apheresis-based desensitization (e.g., plasmapheresis with IVIG or intraoperative immunoadsorption) intended to enable transplantation must document the sensitization status (PRA or donor-specific antibody titers), the planned desensitization protocol (number and timing of plasmapheresis/IA procedures and IVIG dosing), and expected transplant timing. Note that some patients may remain with a persistent positive crossmatch despite desensitization; authorization reviewers will consider antibody titers and realistic likelihood of achieving transplant.
Candidate Criteria for Transplant and Specialized Apheresis
inv-60: Kidney transplant desensitization
Kidney transplant desensitization — Desensitization and transplant-related apheresis indications discussed
Kidney transplant desensitization and prophylaxis: Desensitization strategies referenced include protein A immunoadsorption, plasmapheresis plus low-dose IVIG, and other protocols demonstrating HLA antibody MFI reduction and enabling transplantation; plasmapheresis is used for desensitization, treatment of antibody-mediated rejection, and for recurrent FSGS post-transplant in select cases.
Observational series (Montgomery et al., Yuan et al., Chen et al., Campise et al.) provide evidence of conversion to negative crossmatch and variable graft outcomes; detailed antibody and MFI data inform evaluation.
inv-61: Kidney transplant candidate scenarios
Kidney transplant candidate situations where apheresis/desensitization has been applied
Highly sensitized kidney transplant candidates: Candidates with high PRA or positive T-/B-cell cytotoxic crossmatch have undergone plasmapheresis plus low-dose IVIG to convert crossmatch to negative and receive deceased- or live-donor renal transplants; higher donor-specific antibody titers are associated with increased AMR risk after desensitization.
Evaluation and Monitoring Requirements
Documentation Required
Report HLA antibody MFI, crossmatch status, and response for kidney desensitization
For kidney transplant desensitization authorization and evaluation, document HLA antibody strength (MFI levels), crossmatch status, and prior response to desensitization (number of sessions and antibody reductions).
Provide pre‑ and post‑treatment MFI values and the number of PA/IA or plasmapheresis sessions performed.
Report whether crossmatch converted from positive to negative and the timing of transplantation relative to last treatment.
Documentation Required
Document pre‑ and post‑procedure crossmatch and isohemagglutinin titers
Include pre‑ and post‑procedure crossmatch results and isohemagglutinin titers as key metrics to assess response to desensitization and readiness for transplantation.
Document titer reductions and timing of measurements relative to exchanges or immunoadsorption.
Center and Operational Requirements
Note
Follow related transplant policy references and center standards
Related transplant policies and transplant‑specific apheresis indications are listed in the policy; providers should follow transplant center standards and plan requirements when requesting transplant‑related apheresis.
See related policy references for heart, kidney, liver, lung, and HSCT transplant apheresis indications.
Documentation Required
Document center capability and experience for pediatric ABO‑incompatible procedures
Operational capability for specialized intraoperative circuits and pediatric extracorporeal techniques is implied for centers performing pediatric ABO‑incompatible heart transplantation; document center experience and capability when requesting authorization.
Describe center experience with intraoperative immunoadsorption or large‑volume perioperative plasma exchange protocols as applicable.
Listed therapeutic usesPlasmapheresis (therapeutic plasma exchange) and immunoadsorption are described as treatments for antibody-mediated rejection and for recurrent disease post-transplant (e.g., recurrent FSGS)
Modalities includedPolicy lists plasmapheresis (TPE/PE) and immunoadsorption (IA/PA-IA) among transplant-related apheresis therapies
Common clinical roleUsed as adjunctive therapy combined with immunosuppression/IVIG for desensitization, AMR management, and recurrent disease after transplant
inv-77: Monitoring of isohemagglutinin titers and rejection surveillance
Post-transplant monitoring parameterIsohemagglutinin titers should be measured pre- and post-procedure to assess response to ABO desensitization and for surveillance after transplant
Definitions and Key Terms
inv-50: High-Volume Plasma Exchange (HVP)
HVP definition (concise)High-Volume Plasma Exchange: exchange of 15% ideal body weight (~8–12 L) with plasma replacement; removal rate ~1–2 L/hr
Plasma exchange (general)Plasma exchange (plasmapheresis) separates and removes plasma from blood cells and replaces it with solution prior to reinfusion
RBC exchange noteRed Blood Cell (RBC) Exchange described as removal of patient RBCs and replacement with donor RBCs and colloid solution
inv-51: Immunoadsorption (IA)
Definition of ImmunoadsorptionImmunoadsorption (IA): separated plasma is passed through a device that specifically binds and removes immunoglobulins (e.g., protein A columns)
Typical useIA is used to selectively remove pathogenic antibodies as part of desensitization or AMR management
Contraindications and Patient Safety Considerations
Within the document excerpts provided there are no explicit absolute contraindications to therapeutic apheresis listed; the policy instead refers to standard procedural considerations and indicates that usual contraindications and patient‑specific risks should be applied in clinical decision making.
In a reported highly sensitized kidney transplant cohort (Yuan et al.), persistent positive crossmatch after desensitization prevented transplantation for some patients. The policy highlights that ongoing positive crossmatch or very high donor‑specific antibody burden may preclude proceeding to transplant despite desensitization efforts.
Patient-specific factors associated with higher adverse event rates during red cell exchange (RCE) are described and include baseline hematocrit ≥30%, pre‑procedure systolic blood pressure below the 50th percentile, severe central nervous system vasculopathy, and certain non‑SCA genotypes. These factors warrant individualized risk assessment prior to RCE.
No transplant‑specific absolute or relative contraindications to apheresis procedures are detailed in the cited sections; the policy instead emphasizes individualized assessment and alignment with transplant center practice and safety considerations.
Evaluation, Monitoring, and Lab Surveillance
Note
Evaluate HLA antibody MFI, crossmatch, and response for kidney desensitization
For kidney transplant desensitization, evaluate and report HLA antibody MFI, crossmatch status, and prior response to desensitization when requesting authorization or documenting candidate suitability.
Provide MFI thresholds and session response data used by cited studies (examples include baseline MFI values and percent reduction after serial PA‑IA sessions).
Documentation Required
Report crossmatch results and isohemagglutinin titers pre‑ and post‑procedure
Include pre‑ and post‑procedure crossmatch results and isohemagglutinin titers in documentation to assess response to desensitization and readiness for transplant.
Report whether crossmatch converted to negative and the timing of transplant relative to last desensitization treatment.
Note
Background and Evidence Summary
Therapeutic apheresis is an umbrella term that includes a range of extracorporeal procedures: plasmapheresis/plasma exchange (TPE), extracorporeal photopheresis (ECP), lipoprotein/LDL apheresis, immunoadsorption, and cellular procedures such as red blood cell exchange (RCE), platelet or leukocyte apheresis. These procedures separate blood components, remove pathogenic plasma constituents or cellular elements, and return remaining components to the patient; some techniques (e.g., ECP) involve treatment of the buffy coat with a photoactive agent and UVA light before reinfusion.
Transplant-related evidence mapping (duplicate): Observational and single-center series describe desensitization protocols (plasmapheresis + IVIG, protein A immunoadsorption) that reduce HLA/isohemagglutinin antibody levels and in many cases enable transplantation; antibody strength, crossmatch status, and timing relative to transplantation influence outcomes.
See Yuan et al., Montgomery et al., Issitt et al., Meng et al. for cohort details.
Policy Revision History
2025-06-01New Medical PolicyLatest
Policy created and published as a new UnitedHealthcare medical policy for therapeutic apheresis (CS004ID.A) effective 2025-06-01.
Immunoadsorption in dilated cardiomyopathy: Meta-analyses suggest immunoadsorption can improve LVEF and NYHA class in idiopathic dilated cardiomyopathy, though heterogeneity and limited safety data warrant further RCTs.Improved LVEF and LVEDD reported
Bian et al. meta-analysis shows physiologic and symptomatic improvement but limited trial size and heterogeneity.
Granulocyte/monocyte apheresis in ulcerative colitis: GMA/LCAP may induce and maintain remission in ulcerative colitis as adjunctive therapy; evidence is heterogeneous and of low-to-moderate certainty compared with conventional therapy and unclear relative to modern biologics.Variable remission rates reported
Systematic reviews and RCTs summarized (Kiss et al., Domènech, Eberhardson) with low certainty conclusions.
Plasmapheresis in multiple myeloma cast nephropathy: Adjunctive plasmapheresis can reduce free light chains and dialysis dependence in some observational studies and meta-analyses, but systematic reviews do not consistently show survival benefit independent of chemotherapy.Reduced 6-month dialysis-dependent ratio in some analyses
Mixed findings across retrospective series and small RCTs; generally adjunctive to chemotherapy.
PLEX for NMOSD optic neuritis: Observational data support use of plasma exchange as a second-line therapy for acute optic neuritis in NMOSD with variable visual recovery; evidence remains inconclusive and limited by small, retrospective studies.Variable time to visual recovery reported
Systematic review (Naphattalung et al.) highlights limited and heterogeneous evidence.
Deliver transfusion within 2 hours; Hb threshold <= 8.5 g/dL for simple transfusion option
ASH guidance specifies urgency and modality flexibility.
Leukapheresis is not routinely recommended for acute promyelocytic leukemia but may be considered with caution for life-threatening leukostasis unresponsive to other modalities.
Life-threatening leukostasis not responsive to other therapy
NCCN AML guidance advises caution and selective use.
Strongly positive antibodiesMFI >10,000 described as 'strongly positive' with greater clearance challenges and differential removal by IA/PA-IA
Lower-positive antibodiesMFI >2,000 used in reporting cohorts and to track pre/post treatment reductions
Treatment response contextPA-IA and plasmapheresis studies report percent MFI reductions across sessions and note class-specific differences (class I vs II) in clearance
Prior authorization CPT/HCPCS codesCPT | HCPCS
0342T
Therapeutic apheresis with selective HDL delipidation and plasma reinfusion.
36511
Therapeutic apheresis; for white blood cells.
36512
Therapeutic apheresis; for red blood cells.
36513
Therapeutic apheresis; for platelets.
36514
Therapeutic apheresis; for plasma pheresis.
36516
Therapeutic apheresis; with extracorporeal immunoadsorption, selective adsorption or selective filtration and plasma reinfusion.
36522
Photopheresis, extracorporeal
S2120
Low density lipoprotein (LDL) apheresis using heparin-induced extracorporeal LDL precipitation
Provide baseline and most recent PRA or donor-specific antibody titers and crossmatch results
Describe prior desensitization or immunomodulatory therapies tried (e.g., rituximab, bortezomib)
Include intraoperative/perioperative plan if applicable (e.g., intraoperative immunoadsorption versus pre-op plasma exchange)
Documentation Required
Documentation for ABO-Incompatible Heart Transplant Cases
Prior authorization requests for ABO-incompatible pediatric heart transplantation using plasma exchange or intraoperative immunoadsorption should include procedural and laboratory documentation demonstrating the perioperative isohemagglutinin management plan. Required documentation may be requested to assess appropriateness and must include pre- and post-procedure isohemagglutinin titers, intraoperative exchange volumes, and transfusion/transfusion-product utilization.
Pre-procedure isohemagglutinin titers (A/B) and most recent values
Post-procedure maximum isohemagglutinin titers (anticipated or measured)
Intraoperative details if immunoadsorption is planned
Prior Authorization
Prior Authorization Recommended for Sepsis and Sickle Cell Indications
For requests involving sepsis with multiorgan dysfunction or sickle cell disease indications (including RBC exchange), prior authorization is recommended. Requests should clearly document severity, prior standard-of-care management, and the rationale for adjunctive apheresis or exchange transfusion.
Sepsis: document organ dysfunction, timing and details of standard sepsis management, and justification for adjunctive TPE
Sickle cell disease: document indication (e.g., acute stroke, severe ACS), transfusion goals (target HbS% and hemoglobin), and whether automated RCE is preferred
Include relevant imaging/lab data (e.g., neurologic findings, TCD results, hemoglobin/HbS%)
Denial Risk
Medical Records Requirement and Documentation-Driven Denials
Medical records and supporting documentation may be required to determine whether the member meets coverage criteria. Lack of adequate documentation to demonstrate that clinical criteria or prior-therapy requirements are met can lead to a documentation-driven denial of the authorization request.
Submit recent medical records, clinic notes, operative reports, and laboratory values supporting the indication
If prior therapies are required by the policy (e.g., lipid therapy before LDL apheresis, immunosuppressive trials before second-line TPE), document dates, durations, and responses
Failure to provide requested records in a timely manner may result in denial
Documentation Required
Required Clinical and Procedural Documentation
Authorization requests must include the clinical justification summary and procedural plan: indication, urgency, prior therapies and their outcomes, number and frequency of planned exchanges/sessions, replacement fluid type, and transfusion goals. For chronic or maintenance apheresis (e.g., LDL apheresis, chronic RCE), document prior medical therapy optimization and monitoring plans.
Clinical indication and urgency, including target clinical or laboratory goals (e.g., target HbS% for SCD, LDL targets or symptoms for LDL apheresis)
Prior therapies attempted and documented failure or intolerance (dates and specifics required)
Planned number of sessions and interval (initial course and maintenance schedule if applicable)
For LDL apheresis in children, document lipid-lowering drug therapy trial per NICE/EAS guidance before apheresis when applicable
Note
FDA Approval Informational
Descriptive and regulatory information about FDA approvals for devices used in therapeutic apheresis is provided for informational purposes only. FDA device clearance or approval does not, by itself, determine coverage.
Devices are regulated as Class II or III depending on technology (centrifugation vs filtration)
Therakos CELLEX/UVAR XTS ECP system has FDA PMA approval for palliative treatment of cutaneous T-cell lymphoma skin manifestations only
Coverage decisions are governed by federal, state, and contractual benefit requirements, not solely by FDA status
Step Therapy
Second-Line Therapy Expectations
When apheresis is being requested as a second-line therapy (policy-specified), prior authorization must include documentation that first-line therapies were attempted and inadequate or contraindicated. Examples include cryoglobulinemia, recurrent FSGS after transplant, certain graft-versus-host disease presentations, and familial heterozygous FH when specified as second-line.
List first-line therapies tried, duration, and objective response
Explain why apheresis is required now (e.g., refractory disease, rapid progression, transplant-related need)
Documentation Required
Apheresis as Adjunctive Therapy
Apheresis or plasma exchange used as adjunctive therapy to other systemic treatments (for example, plasmapheresis combined with chemotherapy in myeloma cast nephropathy) should be justified with evidence of intended additive benefit and documentation of concurrent or planned therapies.
Document the concurrent primary therapy (e.g., chemotherapy agents and schedule) and clinical rationale for adjunctive apheresis
Provide outcomes measures to be used to assess benefit (e.g., free light chain reduction, renal recovery)
Step Therapy
Lipid Therapy Before LDL Apheresis
For LDL apheresis candidates, document trials of lipid-modifying drug therapy prior to authorization when applicable (especially in patients under 16 years) and include evidence of inadequate response or intolerance to maximal medical therapy per guidance from NICE and EAS.
Provide lipid panel trends, prior drug trials (agents, doses, durations), and objective evidence of progressive cardiovascular disease if heterozygous FH is being considered for exceptional LDL apheresis
For familial homozygous FH, document diagnosis and prior therapy attempts
HLA class I PRA >50% documented in cohort
Yuan et al. and Meng et al. describe cohorts where PP/IA led to negative crossmatches in many patients and improved access to transplantation, though AMR risk correlates with antibody strength.
Infant/child ABO-incompatible heart transplant candidates: Infants and young children have been transplanted across ABO incompatibility using perioperative plasma exchange or intraoperative immunoadsorption to reduce isohemagglutinin titers; studies report comparable survival and rejection outcomes to ABO-compatible recipients and document exchange protocols and titer responses as part of candidate assessment.Age ranges reported in series include infants up to 8 years in some cohorts; isohemagglutinin titer reductions documented
Issitt et al. and Dipschand et al. provide single-center series supporting candidate selection with documented titer reduction protocols.
Pediatric heart transplant candidate considerations when ABO incompatibility is present
Candidate suitability for ABO-incompatible transplant: Infants and young children may be candidates for ABO-incompatible heart transplantation when perioperative plasma exchange or intraoperative immunoadsorption protocols reduce donor-specific isohemagglutinin titers; reported cohorts show survival and complication rates comparable to ABO-compatible transplants, and documentation of exchange protocols and titer monitoring is important for clinical review.Age ranges in reported series: neonates/infants to young children (e.g., 3–44 months; cohorts ≤14 months noted)
Centers should document exchange volumes, number of exchanges, and pre/post titers when evaluating candidates.
Note
Provide baseline labs, titers, and AE risk factors before procedures
Pre‑procedure documentation should include the indication, baseline hemoglobin/hematocrit, and isohemagglutinin titers for ABO‑incompatible transplant cases, plus prior transfusion history and AE risk assessment.
For chronic RCE candidates, document transfusion goals, baseline labs, and any factors increasing AE risk (e.g., baseline Hct ≥30%).
Documentation Required
Document transfusion goals, TCD screening, and imaging for SCD chronic transfusion evaluation
For SCD patients considered for chronic transfusion or exchange, document transfusion goals, TCD screening results in children where applicable, and relevant imaging or neurologic risk stratification when planning initiation or cessation of transfusion therapy.
Include TCD velocities, target HbS percentage, transfusion interval, and MRI/MRA findings if used for risk stratification.
Include details on extracorporeal circuit adaptation (e.g., adult reservoir/pediatric oxygenator use) and prior institutional outcomes if available.
Note
Follow-up outcomes
Studies report multi-year follow-up of rejection incidence and survival comparable to ABO-compatible recipients in pediatric series
Documentation for authorizationPre/post titers and crossmatch results are reported as key metrics for evaluating desensitization efficacy
inv-78: Monitoring and laboratory surveillance
Required lab surveillancePost-transplant monitoring should include isohemagglutinin titers plus routine graft surveillance (e.g., creatinine, biopsy/cardiac monitoring as indicated)
No excess complications reportedAuthors report no excess graft vasculopathy or malignancy versus ABO-compatible controls in cited pediatric cohorts
Use in clinical reviewIsohemagglutinin trends and procedural details (exchange volumes, number of exchanges) are used to evaluate ongoing management
inv-79: plasmapheresis/immunoadsorption for desensitization or treatment of recurrent disease
Adjunctive transplant therapyPlasmapheresis and immunoadsorption are used as adjunctive therapies for desensitization to reduce donor-specific antibodies and for treatment of recurrent disease post-transplant (e.g., recurrent FSGS)
Combined regimensDesensitization protocols commonly combine plasmapheresis/IA with low-dose IVIG and additional immunosuppression rather than as standalone therapy
Evidence basisObservational studies and single-center series support use for enabling transplantation in sensitized patients, though randomized data are limited
Relation to plasma reinfusionSome IA systems allow selective adsorption with return of remaining plasma components
ECP processExtracorporeal Photopheresis (ECP): buffy coat is separated, treated with a photoactive compound (e.g., psoralens/UVADEX), exposed to UVA, then reinfused during same procedure
Device/regulatory noteFDA has approved the Therakos CELLEX/UVAR XTS photopheresis systems for palliative treatment of CTCL skin manifestations; UVADEX is the photoactive drug referenced
Indications contextECP is device-based and used in select immune-mediated conditions per policy references and device labeling
inv-53: Desensitization
Desensitization definition and examplesDesensitization: pre- or intraoperative procedures (plasmapheresis, immunoadsorption) often combined with low-dose IVIG to remove donor-specific antibodies or isohemagglutinins to enable transplantation
Common modalitiesExamples include plasmapheresis (TPE), protein A immunoadsorption (PA-IA), and IVIG adjuncts
Clinical aimGoal is reduction or removal of pathogenic antibodies to allow transplantation or reduce AMR risk
inv-54: Lipoprotein apheresis (LA)
Lipoprotein apheresis definitionLipoprotein apheresis (LA): selective removal of low-density lipoproteins and lipoprotein(a) from blood with return of remaining components
Techniques mentionedLA methods include charge-based (dextran sulfate), size-based (double-membrane filtration), precipitation (HELP), and immunoadsorption against ApoB-100
Clinical use exampleUsed in homozygous familial hypercholesterolemia and refractory cases per registry and guideline statements
inv-55: Plasma exchange (TPE)
Plasma exchange (TPE) definitionPlasma Exchange (Plasmapheresis/TPE): machine separates and removes plasma from blood cells and replaces plasma with solution prior to reinfusion
Indications summaryTPE used for antibody-mediated diseases, hyperviscosity, select autoimmune disorders, and transplant-related indications per policy
Replacement fluidsReplacement typically with plasma or albumin as specified in procedural documentation
inv-56: Red cell exchange (RCE/XC)
Red cell exchange (RCE/XC) definitionRed Cell Exchange: patient blood passed through device to remove patient red blood cells and replace with donor RBCs and colloid solution
Automated vs manualAutomated RCE is more efficient than manual exchange and can limit transfusional iron accumulation; used for acute and chronic SCD indications
Safety considerationsProcedure-specific AE risks identified (e.g., higher AE rates with baseline Hct ≥30% and certain patient factors); individual risk assessment recommended
inv-57: ASFA categorization and grades
ASFA categoriesCategory I: first-line accepted; Category II: second-line accepted; Category III: role not established (individualize); Category IV: ineffective/harmful (IRB approval desirable)
Recommendation gradesGrades: 1A (strong, high-quality) through 2C (weak, low-quality) used to augment ASFA categories for clinical decision-making
PurposeCategories and grades classify strength of recommendation and quality of evidence for therapeutic apheresis indications
inv-58: Automated RCE / Red cell exchange
Automated RCE definitionAutomated red blood cell exchange: apheresis procedure that removes sickled RBCs and replaces them with donor RBCs using automated equipment
Efficiency advantageAutomated exchange is more efficient than manual methods and reduces transfusional iron accumulation for chronic therapy
Clinical preferenceASFA/ASH statements favor automated RCE for chronic transfusions and many severe SCD complications
inv-59: Extracorporeal photopheresis (ECP)
ECP device and drugExtracorporeal photopheresis (ECP) uses device-based separation of buffy coat, treatment with a photoactive drug (UVADEX/methoxsalen), UVA exposure, then reinfusion
FDA PMA statusTherakos CELLEX/UVAR XTS systems have FDA premarket approval for palliative treatment of CTCL skin manifestations; UVADEX has orphan drug listings for several transplant/immune contexts
Procedure characteristicsECP is performed in specialized centers and is device- and drug-dependent per labeling and policy references