ModifiedUnitedHealthcarePolicy CS004OH.C

Therapeutic apheresis (plasmapheresis/photopheresis/other apheresis procedures) — Ohio

Defines UnitedHealthcare's Ohio-specific medical policy for therapeutic apheresis procedures, listing covered indications, unproven/not medically necessary uses, documentation expectations, and applicable billing codes under Ohio Administrative Code 5160-101.

Policy Summary

PayerUnitedHealthcare

PolicyTherapeutic apheresis (plasmapheresis/photopheresis/other apheresis procedures) — Ohio

Policy CodePolicy CS004OH.C

Change TypeRevised exclusion languageadded documentation guidanceupdated references

Effective DateJan 1, 2026

Next Review Date

Key ActionObtain and submit complete, legible medical records supporting medical necessity (history, exam, diagnostic results) with prior authorization requests.

SourceLink

POLICY UPDATE CHANGES

Replaced language indicating therapeutic apheresis is unproven and not medically necessary for treating the [listed] conditions/diagnoses with language that it is unproven and not medically necessary for treating any other conditions/diagnoses not listed in the policy as proven and medically necessary.

Added Medical Records Documentation Used for Reviews language describing that medical records may be required, must support medical necessity, and may include history, exam, and diagnostic test results.

Updated Supporting Information sections (Clinical Evidence, FDA, and References) to reflect current information and archived previous policy version CS004OH.B.

01/01/2026Policy revision date

OhioGeographic applicability

0342T,36511-36516,36522

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Example CPT / procedure codes cited

~20Distinct disease indications discussed

mostly insufficient evidenceCoverage stance across indications

Coverage Criteria for Therapeutic Apheresis

inv-01: Medically necessary (proven) indications

Therapeutic apheresis is proven and medically necessary for the following when clinically indicated:

Covered indications list: Acute inflammatory demyelinating polyneuropathy (primary treatment); Acute liver failure requiring high‑volume therapeutic plasma exchange (TPE‑HV); Anti‑glomerular basement membrane disease (dialysis‑independent and diffuse alveolar hemorrhage presentations); Chronic acquired demyelinating polyneuropathies (IgG/IgA/IgM related; anti‑myelin‑associated glycoprotein); Chronic inflammatory demyelinating polyneuropathy; Cryoglobulinemia (second‑line therapy); Cutaneous T‑cell lymphoma (erythrodermic mycosis fungoides; Sézary syndrome); Erythrocytosis, polycythemia vera; Idiopathic dilated cardiomyopathy (NYHA II–IV) via immunoadsorption; Familial hypercholesterolemia (homozygotes – lipoprotein apheresis; heterozygotes – lipoprotein apheresis second‑line; all patients via TPE as specified); Focal segmental glomerulosclerosis recurrent in transplanted kidney (second‑line therapy); Graft‑versus‑host disease (acute; chronic second‑line); Hereditary hemochromatosis; Severe hypertriglyceridemic pancreatitis

Full list and clinical context in policy chunk 2

inv-02: Unproven / Not medically necessary indications

Therapeutic apheresis is considered unproven and not medically necessary for the following conditions unless otherwise addressed in the policy as proven:

Not medically necessary / Unproven list: Extensive indications including but not limited to: acute disseminated encephalomyelitis (ADEM); acute liver failure and acute fatty liver of pregnancy (unless meeting proven high‑volume TPE criteria); acute toxins/venoms/poisons; age‑related macular degeneration (dry); Alzheimer's disease (mild or moderate); systemic dialysis‑related amyloidosis; ANCA‑associated rapidly progressive glomerulonephritis dialysis‑independent (MPA/GPA) when not meeting proven criteria; anti‑GBM disease dialysis‑dependent without diffuse alveolar hemorrhage; many dermatologic, rheumatologic, neurologic, infectious, and hematologic conditions listed in policy chunks 5–7 (e.g., pemphigus vulgaris, post‑transfusion purpura, immune thrombocytopenia refractory, stiff‑person syndrome, toxic epidermal necrolysis, Kawasaki disease, chronic multiple sclerosis, long‑term myasthenia gravis therapy, neuromyelitis optica spectrum disorders maintenance, myeloma cast nephropathy as standalone therapy), and other conditions enumerated in the policy exclusions.

See policy chunks 5–7 for full enumerations and context; use may be considered investigational or not medically necessary absent stronger evidence or guideline support.

inv-03: Transplantation / desensitization considerations

Transplantation and desensitization contexts have distinct evidence and operational considerations; when used, document timing and adjunctive therapies:

Desensitization and transplant-related use: Plasmapheresis or immunoadsorption used with adjuncts (e.g., low‑dose IVIG, rituximab) can reduce HLA antibody levels and has been associated with improved outcomes in selected live‑donor desensitization series (e.g., Montgomery et al. n=211), but antibody reductions are often not durable unless transplantation occurs within days after last treatment. Small observational studies and meta‑analyses of prophylactic plasmapheresis for prevention of recurrent FSGS after transplant have not demonstrated consistent benefit; evidence is limited by heterogeneity and small samples.

Document antibody MFI, timing of transplant relative to last apheresis, number of sessions, and concurrent immunomodulatory therapy; see chunks 18,19,21.

inv-04: Evidence summaries by indication

Summaries of clinical evidence for selected indications — presented as 'When considered':

Desensitization for HLA‑sensitized kidney transplant: When considered for HLA‑sensitized patients, plasmapheresis or immunoadsorption combined with IVIG and prompt transplantation can reduce HLA antibodies and was associated with improved survival in a large live‑donor series (Montgomery et al., n=211); prospective trials needed to validate broader applicability.

Durable antibody reduction generally requires transplantation within days after last treatment (chunks 21,18).

Familial hypercholesterolemia (hoFH) and lipoprotein apheresis: When considered in children with hoFH on medication, lipoprotein apheresis reduced LDL‑C substantially; more frequent sessions (weekly or twice weekly) produced greater LDL‑C lowering and some patients reached mean LDL‑C <3.5 mmol/L.

Registry data (n=50) with limited generalizability (chunk 23).

Hypertriglyceridemic pancreatitis: When considered for severe HTG‑induced acute pancreatitis, plasmapheresis lowers serum triglycerides more rapidly within 24 hours than conventional therapy but has not demonstrated improved prognosis or mortality in pooled observational data.

inv-05: Coverage considerations by indication

Coverage considerations based on available evidence in the cited studies:

Myeloma cast nephropathy (light chain cast nephropathy): Plasmapheresis has not been shown to provide survival or renal recovery benefit independent of chemotherapy based on a systematic review of 56 articles; therefore plasmapheresis alone should be supported only when combined with appropriate chemotherapy and clear rationale is documented.

Gupta et al., 2010 systematic review (chunk 36)

NMOSD acute optic neuritis: PLEX is used as second‑line/adjunctive therapy; quantitative synthesis of observational studies did not show statistically significant visual acuity improvements—consider PLEX when first‑line therapies fail and document prior therapy and expected goals.

Naphattalung et al., 2023 (chunk 37)

Pediatric ABO‑incompatible heart transplantation: ABO‑PE and ABO‑IA demonstrate comparable survival and rejection outcomes in retrospective series; ABO‑IA may reduce transfusion volume and permit older recipients in some centers—coverage can be considered when indication, method, and outcomes are documented.

Issitt et al., 2021 (chunk 38)

inv-06: ANCA-associated vasculitis (MPA/GPA) — evidence

Evidence summary for ANCA-associated vasculitis (MPA/GPA):

ANCA-associated vasculitis (MPA/GPA): Randomized trials comparing plasma exchange (PE) versus no PE showed no association with mortality, complete remission, or adverse events, though PE was associated with reduced early end‑stage renal disease incidence at 3 months in some analyses; no RCT data exist for EGPA.RCT evidence: 4 trials vs no PE (n=827) and 1 RCT vs pulse steroid (n=137)

Further investigation required before broad clinical recommendations (chunks 54–55).

inv-07: Alzheimer's disease — evidence

Evidence summary for Alzheimer's disease (mild or moderate):

Alzheimer's disease (mild or moderate): Overall evidence quality is insufficient to support routine apheresis for Alzheimer's disease. One randomized trial (AMBAR analyses) suggests plasma exchange with albumin replacement (PE‑Alb) can alter peripheral and CSF inflammatory mediators and was associated with positive clinical outcomes in that trial subset, but findings require reproduction and further study.AMBAR biomarker subset n=142

Limited sample size and need for replication (chunks 56–58).

inv-08: FSGS — evidence

Focal segmental glomerulosclerosis (FSGS):

FSGS (steroid‑resistant or native kidney): There is insufficient quality evidence to support therapeutic plasma exchange for steroid‑resistant FSGS in native kidneys or the routine use of lipoprotein apheresis in FSGS; small Japanese studies suggest possible delay to ESRD but generalizability is limited.

Additional long‑term and generalizable studies needed (chunk 59).

inv-09: Idiopathic inflammatory myopathies — evidence

Idiopathic inflammatory myopathies — evidence summaries:

Necrotizing autoimmune myopathy (NAM): Retrospective case series report CK reductions and clinical responses to TPE, particularly in patients with HMGCR or SRP antibodies refractory to immunosuppression; evidence is limited by small, retrospective designs and requires controlled trials.median 7.5 TPE procedures in case series

Kruse et al., 2022 (chunk 61).

PM/DM‑associated interstitial lung disease (acute, refractory): Retrospective series suggest some patients (61.1% in one study) improved after ≥4 rounds of TPE; subcutaneous/mediastinal emphysema and high ferritin predicted poor response; controlled data lacking.study n=18

Ning et al., 2019 (chunk 62).

inv-10: ITP — evidence

Immune thrombocytopenia (ITP):

Chronic refractory ITP: Evidence is insufficient to support routine apheresis for ITP; small multicenter retrospective series (n=17) reported partial or complete platelet responses after TPE in some patients, but prospective randomized studies are needed.n=17 in cited retrospective series

Basturk et al., 2021 (chunk 63).

inv-11: Other indications — evidence

Other indications — summarized evidence statements:

Pemphigus vulgaris: One RCT (n=40) evaluating plasma exchange was inconclusive; overall evidence inadequate to determine efficacy and further RCTs are needed.systematic review n=11 studies, 404 participants

Martin et al., 2011 (chunk 64).

Post‑transfusion purpura (PTP): Evidence limited to case reports; TPE may have contributed to remission in single‑patient reports but insufficient for general recommendations.single‑patient report

Porretti et al., 1992 (chunks 65–66).

Sepsis with multiorgan failure: Systematic reviews and meta‑analyses suggest adjunct TPE may reduce short‑term mortality in critically ill septic patients, but heterogeneity and small trials limit certainty and larger RCTs are required.

inv-12: Guideline-based covered indications (selected)

Selected guideline‑based indications and conditional recommendations where coverage aligns with specialty society guidance:

Guillain‑Barré syndrome (GBS): TPE is recommended to hasten recovery in adults with GBS, especially non‑ambulatory within 4 weeks of onset or ambulatory within 2 weeks, per AAN practice parameter; combination with IVIG is not beneficial.time_window <= 4 weeks non‑ambulatory or <=2 weeks ambulatory

AAN practice parameter (chunk 76).

Sickle cell disease (SCD): Automated red cell exchange (RCE) is an option for acute stroke, severe acute chest syndrome, and for chronic transfusion programs; transfusion type and goals follow ASH/ASH guidelines and individualized clinical factors.acute neurologic deficit -> prompt transfusion within 2 hours as indicated

ASH guidance (chunk 79) and evidence summarized in chunks 45–46.

LDL apheresis:

inv-13: General Exclusion / Not Medically Necessary for Unlisted Indications

Policy-level exclusion for unlisted indications:

Not medically necessary for unlisted indications: Therapeutic apheresis, including plasma exchange (plasmapheresis) or photopheresis, is unproven and not medically necessary for treating or managing any conditions/diagnoses not specifically listed in the policy as proven and medically necessary.

Revised language effective 01/01/2026 (policy history chunk 100).

Due to insufficient evidence of efficacy, therapeutic apheresis procedures — including plasma exchange (plasmapheresis) and extracorporeal photopheresis — are designated unproven and not medically necessary for a broad set of conditions not supported by adequate data. The policy lists many specific diagnoses (for example, acute disseminated encephalomyelitis, Alzheimer’s disease, acute liver failure requiring TPE, and numerous neurologic, dermatologic, rheumatologic, infectious, and hematologic disorders) as examples where apheresis is considered investigational or not medically necessary; see the policy exclusions for the full enumerations.

Systematic review evidence cited for multiple myeloma with acute renal injury (myeloma cast nephropathy) indicates that extracorporeal removal of serum free light chains (sFLCs) by plasmapheresis did not demonstrate a survival benefit independent of appropriate chemotherapy. Therefore, plasmapheresis for sFLC removal should not be expected to provide standalone survival advantage apart from effective antimyeloma systemic therapy.

Available studies and systematic reviews do not support plasmapheresis as an effective standalone therapy for myeloma cast nephropathy. The evidence emphasizes that any extracorporeal sFLC reduction is most meaningful when performed in conjunction with prompt, appropriate chemotherapy; prophylactic or isolated plasmapheresis without concurrent antimyeloma treatment lacks supportive high‑quality data and may be denied absent clear documentation of concurrent therapy and rationale.

The randomized trials and pooled analyses assessing plasma exchange in ANCA‑associated vasculitis focused on microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) and did not include eosinophilic granulomatosis with polyangiitis (EGPA). As a result, there are no RCT data in these cited analyses that support or quantify benefit of plasma exchange for EGPA, and evidence for EGPA remains unestablished.

The policy aligns with guidance that apheresis indications classified by ASFA as Category IV — or other uses where guideline panels explicitly state evidence is insufficient — should be considered unsupported. Category IV denotes disorders for which published evidence suggests apheresis is ineffective or potentially harmful; institutional review and IRB oversight are appropriate if such treatments are undertaken, and routine coverage is not supported without high‑quality evidence.

UnitedHealthcare’s policy language specifies that therapeutic apheresis, including plasmapheresis or photopheresis, is unproven and not medically necessary for treating or managing any conditions or diagnoses that are not explicitly listed in the policy as proven and medically necessary. This revised exclusion replaces prior wording that referenced only the previously listed conditions and clarifies that unlisted indications are considered not medically necessary absent specific policy exception.

The policy provides numerous examples of conditions for which apheresis is considered not medically necessary or unproven. Examples include, but are not limited to: acute disseminated encephalomyelitis (ADEM); acute liver failure requiring TPE; Alzheimer’s disease (mild or moderate); myeloma cast nephropathy; idiopathic inflammatory myopathies; immune thrombocytopenia (refractory ITP); pemphigus vulgaris; toxic epidermal necrolysis; and various transplant‑related and vasculitic contexts not otherwise specified in the proven indications. Refer to the policy exclusion lists for the comprehensive set of specific diagnoses.

For prevention of recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation, the aggregate data do not demonstrate a clear benefit for prophylactic plasmapheresis. Systematic reviews and single‑center retrospective studies reported no significant reduction in recurrence with prophylactic plasmapheresis or with rituximab ± plasmapheresis; therefore, routine prophylactic use in deceased‑donor recipients is not supported by current evidence and is considered not medically necessary absent compelling case‑specific justification.

In neuromyelitis optica spectrum disorder (NMOSD/NMO) presenting with acute optic neuritis, the available observational studies of plasma exchange (PLEX) as second‑line or adjunctive therapy did not demonstrate consistent, statistically significant improvements in visual acuity at evaluated post‑treatment time points. Consequently, PLEX is not established as a proven therapy for visual recovery; use should be considered second‑line with documentation of prior therapies and expected clinical goals.

Across many indications summarized in the policy, the evidence quality is insufficient to support routine apheresis. Examples called out include Alzheimer’s disease, focal segmental glomerulosclerosis (FSGS), idiopathic inflammatory myopathies, immune thrombocytopenia (ITP), pemphigus vulgaris, post‑transfusion purpura, stiff‑person syndrome, toxic epidermal necrolysis, and Kawasaki disease. For these conditions, studies are often retrospective, small, or heterogeneous, and the policy characterizes apheresis as investigational or not medically necessary unless higher‑quality supportive data are provided.

Specialty society positions are referenced to contextualize coverage decisions: the American Academy of Neurology (AAN) notes insufficient evidence to support or refute plasmapheresis for several neurologic indications (including myasthenia gravis, PANDAS, and Sydenham chorea), while the American Society for Apheresis (ASFA) framework categorizes uses into I–IV with Category IV denoting indications where apheresis appears ineffective or harmful. These guideline statements inform the policy’s cautious stance and expectations for prior authorization and supporting documentation when apheresis is requested for such indications.

In summary, therapeutic apheresis therapies (including plasmapheresis, immunoadsorption, and photopheresis) are considered unproven and not medically necessary for indications that lack sufficient high‑quality evidence or are not specifically listed as proven and medically necessary in this policy. Requests for apheresis for unlisted or investigational indications will generally be denied unless robust supporting clinical documentation and compelling, peer‑reviewed evidence are provided to support use in the specific clinical context.

Procedure and Billing Codes

Applicable procedure CPT/HCPCS codes referencedCPT

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.

Applicable procedure CPT/HCPCS codes referenced (grouped duplicate)CPT

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.

High-Volume Plasma Exchange (HVP) — key parameters

HVP exchange volumeExchange equal to 15% of ideal body weight (representing ~8–12 L)

Removal ratePlasma removed at 1–2 L per hour during HVP

Replacement fluidEquivalent volume plasma used for replacement during HVP

HLA antibody MFI thresholds (desensitization studies)

Reported HLA antibody MFI thresholdAntibody specificities with MFI > 2000 were analyzed in desensitization study cohorts

Strongly positive MFIStrongly positive antibodies defined as MFI > 10,000 with larger absolute reductions observed after multiple sessions

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Ohio prior authorization/medical necessity evaluation

This Medical Policy only applies to the state of Ohio. Requests for apheresis/plasmapheresis, therapeutic plasma exchange (TPE), leukapheresis, LDL apheresis, immunoadsorption, or extracorporeal photopheresis that are not clearly within proven indications should be evaluated for medical necessity and prior authorization per Ohio Administrative Code 5160-101 and any applicable federal/contractual requirements.

Prior authorization (PA) is recommended for multi-session apheresis courses (studies commonly report mean 3–4 sessions) and for repeated/serial procedures.
PA should reference InterQual® as the primary medical/surgical criteria; when InterQual® is not applicable, use applicable UnitedHealthcare medical policies, coverage determination guidelines, or utilization review guidelines as approved by the Ohio Department for Medicaid Services.
Documentation insufficiency may trigger denial — lack of legible, complete medical record support (history, exam, diagnostic tests, prior therapies, and procedural details) can result in denial per federal/state/contract terms.

Prior Authorization

Prior authorization for multi-session apheresis and guideline-limited indications

Background and Clinical Context

Therapeutic apheresis encompasses several distinct extracorporeal procedures performed to remove pathogenic plasma components or cellular elements. Common modalities include plasmapheresis (plasma exchange), immunoadsorption, and extracorporeal photopheresis, as well as lipoprotein apheresis and cellular apheresis procedures; these therapies are typically delivered in outpatient settings over several hours and differ by mechanism, indication, and evidence base.

Definitions and Key Terms

Plasma Exchange (Plasmapheresis) — definition and process

DefinitionPlasma exchange (plasmapheresis) is a procedure that separates and removes plasma from blood cells and replaces the plasma with a solution prior to reinfusion into the patient.

Setting and durationUsually performed in an outpatient facility and typically requires several hours; in some situations may be performed daily for at least 1 week.

Procedure typesIncludes membrane or centrifugation-based separation; replacement fluids may be plasma, albumin, or crystalloid/colloid as clinically indicated.

High-Volume Plasma Exchange (HVP) — exchange volume definition

HVP definitionHigh‑Volume Plasma Exchange (HVP) is defined as an exchange of 15% of ideal body weight (representing ~8–12 L)

Flow rate

Policy Revision History

2026-01-01policy_revisionLatest

Replaced prior wording that limited 'unproven and not medically necessary' status to 'the [listed] conditions/diagnoses' with broader language stating therapeutic apheresis (including plasma exchange/plasmapheresis and photopheresis) is unproven and not medically necessary for treating or managing any other conditions/diagnoses not listed in the policy as proven and medically necessary.

2026-01-01documentation_addition

Added 'Medical Records Documentation Used for Reviews' language clarifying that benefit coverage is determined by federal, state, or contractual requirements, that medical records may be required to assess clinical criteria but do not guarantee coverage, and specifying types of documentation expected (history, exam, pertinent diagnostic tests) and availability upon request.

Policy Summary

PayerUnitedHealthcare

PolicyTherapeutic apheresis (plasmapheresis/photopheresis/other apheresis procedures) — Ohio

Policy CodePolicy CS004OH.C

Change TypeRevised exclusion languageadded documentation guidanceupdated references

Effective DateJan 1, 2026

Next Review Date

Key ActionObtain and submit complete, legible medical records supporting medical necessity (history, exam, diagnostic results) with prior authorization requests.

SourceLink

On This Page

Meta‑analysis showed greater 24‑hour TG reduction but no improved clinical outcomes (chunk 25).

Dilated cardiomyopathy and immunoadsorption: When considered for idiopathic dilated cardiomyopathy (NYHA II–IV), meta‑analysis of small studies reported improved LVEF, reduced LVEDD, and symptom severity with immunoadsorption, but larger trials are needed to confirm safety and long‑term benefit.

Meta‑analysis of 12 studies, limitations include heterogeneity (chunk 27).

Inflammatory bowel disease (ulcerative colitis) and GMA/cytapheresis: When considered as adjunctive therapy in UC, granulocyte/monocyte adsorptive apheresis has shown induction and maintenance of remission in trials and observational studies, though benefit compared with modern biologics is unclear.

Observational studies with limited comparative data (chunk 31).

Myasthenia gravis (acute): When considered for acute MG exacerbations, plasmapheresis is associated with higher odds of short‑term symptom improvement versus IVIG in meta‑analysis, although severity score changes were similar between treatments and complication profiles differ.

Meta‑analysis of IVIG vs plasmapheresis (chunk 33).

Myeloma cast nephropathy (adjunctive): When considered as an adjunct to chemotherapy in MM with AKI, plasmapheresis can reduce free light chains and, in some series, reduce dialysis dependence; systematic reviews do not support benefit independent of chemotherapy, and randomized evidence is limited.

Observational studies show FLC reduction; systematic review found no independent survival benefit (chunks 35,36).

NMOSD acute optic neuritis: When considered for acute optic neuritis in NMOSD/NMO as second‑line therapy, observational data (five studies, 48 participants) did not show statistically significant visual acuity improvements at pooled time points; consider PLEX after failure of first‑line therapy with clear documentation of goals.

Quantitative synthesis limited and inconclusive (chunk 37).

PANDAS/PANS: Evidence is limited and low quality; occasional reported improvements after TPE exist but rigorous comparative data lacking—approve only with documentation of prior therapies and clear clinical rationale, and consider investigational absent stronger evidence.

Sigra et al., 2018 and series in chunk 41

Refractory rheumatoid arthritis (selected): Leukocytapheresis and specific immunoadsorption have shown ACR responses in subsets of refractory RA patients in single‑arm and randomized trials; consider coverage for selected refractory cases with documented prior DMARD/biologic failure and treatment matching studied protocols.

Kitagaichi and RCT data summarized in chunk 42

Sickle cell disease — ACS and chronic transfusion: Red cell exchange (RCE) is reported safe and effective for acute chest syndrome and for chronic transfusion programs; consider RCE for ACS with respiratory distress and for chronic programs with individualized AE risk assessment; document indications and transfusion goals.

Velasquez 2009; Wade 2022; chunk 45,46

ANCA‑associated vasculitis (MPA/GPA): Meta‑analyses and RCTs do not show consistent reductions in mortality or overall ESRD with PLEX, though early treatment phases showed reduced ESRD incidence at 3 months in some analyses; use PLEX selectively (e.g., rapidly progressive renal failure) with documentation of expected benefit and counseling about uncertain mortality benefit.

Bellos 2021 and Yamada 2021 meta‑analyses (chunks 53–55)

meta‑analysis RR 0.59

Kuklin et al., 2024 (chunk 67).

Stiff‑person syndrome (anti‑GAD65): Retrospective series (n=10) report variable responses; TPE may be used for acute exacerbations or chronic maintenance in refractory cases but evidence is insufficient.single‑center retrospective n=10

Albahra et al., 2019 (chunk 68).

Sydenham's chorea: Small RCT (n=18) showed clinical improvement across groups; differences not statistically significant—evidence inconclusive.RCT n=18

Garvey, 2005 summary (chunk 69).

Toxic epidermal necrolysis (TEN)/SJS: Observational studies and meta‑analyses with heterogeneous designs report mixed findings; evidence quality is low and benefits of plasmapheresis are not definitively established.meta‑analysis 96 studies, 3248 patients

Han et al., Zimmerman et al. (chunks 70–72).

Kawasaki disease (IVIG‑refractory): Retrospective data suggest fewer coronary artery lesions with plasma exchange versus additional IVIG in selected high‑risk, IVIG‑refractory children, but studies are limited and RCTs are needed.p < 0.0012 for CAL difference in one retrospective series

Mori et al., 2004 (chunk 73).

Consider LDL apheresis for homozygous familial hypercholesterolemia and in exceptional heterozygous FH with progressive symptomatic heart disease despite maximal tolerated lipid‑modifying therapy per NICE/EAS guidance; generally after maximized medical therapy has been tried.

maximized medical therapy tried

NICE recommendations (chunk 85, and registry evidence chunk 23).

Extracorporeal photopheresis (ECP): FDA‑cleared ECP device indication is limited to palliative treatment of CTCL skin manifestations; other guideline uses exist but approvals vary by indication.FDA indication specific to CTCL

NICE/NCCN and device indications summarized in chunks 84–85.

Leukapheresis in hematologic malignancy: Leukapheresis is not recommended routinely for APL leukocytosis but can be considered in life‑threatening leukostasis unresponsive to other modalities per NCCN guidance.life‑threatening leukostasis unresponsive to other modalities

NCCN guidance (chunk 84).

Clinical implicationDurable antibody reduction generally requires transplantation within days after the last plasmapheresis/immunoadsorption session

Lipoprotein apheresis — LDL‑C outcomes in pediatric series

Patient populationRegistry of 50 children with homozygous or compound heterozygous familial hypercholesterolemia on medication plus lipoprotein apheresis

Treatment frequency linked to better LDL-CWeekly or twice-weekly apheresis produced greater LDL‑C lowering (most effective schedules)

LDL‑C target achievement17% (7 of 50) of children reached mean LDL‑C < 3.5 mmol/L; all 7 were treated weekly (n=4) or twice weekly (n=3)

Triglyceride reduction at 24 hours — comparative outcomes

TG reduction with plasmapheresis (24 h)Mean triglyceride decrease 24 h after plasmapheresis: 70.4% ± 15.1%

TG reduction with medical therapy (24 h)Mean triglyceride decrease 24 h with medical therapy: 59.7% ± 17.3%

Statistical noteDifference in 24‑hour TG reduction between groups was statistically significant (p = 0.032) though clinical outcome benefit remains uncertain

Prior authorization is recommended for apheresis/TPE requests for indications supported mainly by small, heterogeneous, or second-line evidence, or when guidelines limit use to exceptional circumstances.

Examples where PA is typically required: indications with insufficient quality evidence (Alzheimer's disease, idiopathic inflammatory myopathies, ITP, pemphigus vulgaris, Kawasaki disease, sepsis with MOD, FSGS in native kidney, etc.).
PA is also recommended before LDL apheresis for heterozygous FH in exceptional circumstances (NICE guidance: try lipid-modifying therapy first, especially in patients <16 years).
When apheresis is requested as sole therapy for conditions where benefit is unclear (e.g., myeloma cast nephropathy without concurrent chemotherapy), PA is expected.

Prior Authorization

ABO-incompatible pediatric heart transplant — method and outcomes

Requests for ABO-incompatible pediatric heart transplantation procedures that use antibody-reduction methods should include the method and outcome expectations. Both intraoperative anti-A/B immunoadsorption (ABO-IA) and plasma-exchange-facilitated (ABO-PE) approaches have been reported with equivalent early survival and similar rejection and isohemagglutinin titer outcomes in pediatric cohorts.

Include the specific antibody-reduction method requested (ABO-IA versus ABO-PE), number/timing of sessions, and expected timing of transplant relative to antibody reduction (transplant typically performed within days of last plasmapheresis to maintain antibody suppression).
Provide prior and post-procedure isohemagglutinin titers, transfusion volumes, rejection history, and graft survival follow-up when available.

Documentation Required

Required medical record documentation and denial risk for insufficiency

Documentation must fully support medical necessity. Benefit's applicability is governed by federal, state (OAC), or contractual requirements and applicable laws; medical records may be requested to assess criteria but do not guarantee coverage.

Required elements: relevant medical history, focused physical exam findings, diagnostic test results (labs, antibody titers, imaging), prior and concurrent therapies (including dates and responses), and procedural details (route, replacement fluid, number and timing of exchanges).
Operational notes or procedure records should be legible and available on request.
Insufficient or missing documentation may result in denial or request for additional information.

Prior Authorization

Clinical outcome uncertainty and implications for prior authorization

Clinical scenarios with uncertain or limited outcome benefit are likely to require PA and careful documentation; provide specific supportive clinical data when seeking coverage.

HTG-induced acute pancreatitis: provide rationale that TPE is expected to change clinical prognosis in the individual case; studies show early TG reduction but no proven improvement in clinical outcomes.
Myeloma cast nephropathy: plasmapheresis may reduce free light chains but evidence does not support benefit independent of chemotherapy; when requested as sole therapy, expect PA scrutiny and possible denial.
Alzheimer's disease and other indications with insufficient evidence: expect denials or require enrollee to meet strict criteria and provide evidence of trial enrollment or rationale for exceptional use.
For NMOSD/optic neuritis, document prior treatments (steroids, immunotherapies) and clinical trajectory that justifies TPE as second-line therapy.

Documentation Required

Suggested supporting clinical documentation

Suggested supporting clinical documentation to include with PA requests to facilitate timely review and minimize denial risk.

History and indication, including diagnosis date and severity measures (e.g., CK trends for myopathies, TG levels and pancreatitis severity scores, platelet counts for ITP).
Prior and concurrent therapies with dates and objective response (including trials of conventional therapies where applicable).
Antibody titers or relevant serologies (e.g., isohemagglutinin titers for ABO-incompatible transplant; myositis or NMOSD antibodies).
Planned apheresis regimen: number of sessions, frequency/timing relative to transplant or other therapies, replacement fluid, and expected clinical endpoints.
For specialty guideline-limited indications (e.g., leukapheresis for life-threatening leukostasis), provide documentation that alternative measures were attempted and were ineffective or contraindicated.

Step Therapy

PA for guideline-limited indications and requirement to try conventional therapies

When published guidelines or high-quality evidence limit routine use (e.g., NCCN, NICE), PA should ensure guideline-consistent care and that conventional therapies were tried before apheresis.

Example: NICE recommends lipid-modifying drug therapy before LDL apheresis in patients under 16 and reserves LDL apheresis for exceptional circumstances in heterozygous FH — PA should document trials of maximal tolerated lipid-lowering therapy.
NCCN: leukapheresis not routine in APL; consider only for life-threatening leukostasis unresponsive to other measures — document attempts at other modalities.

Prior Authorization

Prior authorization and criteria source

Coverage determinations should reference the controlling federal/state/contractual requirements and use InterQual® as the primary source for medical necessity criteria; when InterQual® lacks applicable criteria, use UnitedHealthcare-approved policies or review guidelines.

Operational reviewers should document which criteria set (InterQual®, UHC policy, or state/contractual rule) was applied and include that citation in decision rationale.
For Ohio Medicaid or contract-specific mandates, the OAC 5160-101 requirements govern coverage determinations.

Plasma removed at a rate of 1–2 L per hour during HVP

ReplacementReplacement performed with plasma in equivalent volume during the HVP procedure

Immunoadsorption (IA) — definition

DefinitionImmunoadsorption (IA) is a procedure in which separated plasma is passed through a device that specifically binds and removes immunoglobulins (e.g., Staphylococcal protein A columns).

MechanismDevice-based selective removal of antibodies or immunoglobulin classes while returning processed plasma components to the patient.

Clinical useUsed in desensitization protocols and antibody‑mediated diseases where targeted immunoglobulin removal is desired; efficacy depends on number of sessions and adjunctive therapies.

Extracorporeal Photopheresis (ECP)/Photopheresis — definition

DefinitionExtracorporeal photopheresis (ECP) involves separating the buffy coat or blood, treating it extracorporeally with a photoactive compound (e.g., psoralens) and ultraviolet A light, then reinfusing the treated product to the patient.

Typical indicationUsed for indications such as cutaneous T‑cell lymphoma (CTCL) and other immune‑mediated disorders per guideline/device approvals.

Procedure logisticsPerformed over several hours, usually in outpatient settings; treated cellular components are returned during the same procedure.

Desensitization (transplant) — definition and durability note

DefinitionDesensitization in transplant context refers to use of plasmapheresis or immunoadsorption combined with adjuncts (e.g., IVIG) to reduce HLA antibodies prior to transplantation.

Durability noteDurable antibody reduction generally requires transplantation within several days after the last plasmapheresis/immunoadsorption session.

Treatment intensityMultiple sessions (often several) are usually required; antibody removal magnitude depends on initial MFI and number of procedures.

Lipoprotein apheresis (LA) — definition and frequency considerations

DefinitionLipoprotein apheresis (LA) is a procedure to selectively remove LDL‑C and lipoprotein(a) from the blood, returning remaining components to the patient.

Frequency effectFrequency and duration of sessions (e.g., weekly or twice weekly) influence the magnitude of LDL‑C reduction and the likelihood of reaching target LDL‑C levels.

Use in hoFHUsed in homozygous familial hypercholesterolemia and selected severe heterozygous cases as adjunct to maximal medical therapy.

ABO‑PE — definition (ABO‑incompatible heart transplantation)

DefinitionABO‑PE: plasma exchange protocols used to facilitate ABO‑incompatible heart transplantation by reducing isohemagglutinin titers pre‑ or intra‑operatively.

Clinical contextRetrospective pediatric series compare ABO‑PE to intraoperative immunoadsorption with similar survival and rejection outcomes; method details and transfusion volumes are relevant for authorization decisions.

Documentation needsProviders should document indication, method (ABO‑PE vs ABO‑IA), age, transfusion volumes, and outcomes when used for pediatric ABO‑incompatible transplants.

ABO‑IA — definition (intraoperative immunoadsorption for ABO‑incompatible transplant)

DefinitionABO‑IA: intraoperative anti‑A/B immunoadsorption technique used as an alternative to plasma exchange for ABO‑incompatible heart transplantation.

Comparative findingIn retrospective series, ABO‑IA was associated with lower transfused blood volume and allowed older recipients in one center, with no difference in early graft survival compared with ABO‑PE.

Procedure noteABO‑IA is performed intraoperatively and selectively removes isohemagglutinins via immunoadsorption columns rather than large‑volume plasma exchange.

ANCA‑associated vasculitis (AAV) — definition and evidence note

DefinitionANCA‑associated vasculitis (AAV) is a group of small‑vessel vasculitides that includes microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA); eosinophilic granulomatosis with polyangiitis (EGPA) was not evaluated in the cited RCTs.

Evidence summaryRandomized trials comparing plasma exchange vs no plasma exchange showed no association with mortality or complete remission, though some analyses showed reduced early ESRD at 3 months.

Coverage implicationConsider PLEX selectively (e.g., rapidly progressive renal failure) with documentation given mixed trial results and lack of data for EGPA.

Necrotizing autoimmune myopathy (NAM) — definition and antibody associations

DefinitionNecrotizing autoimmune myopathy (NAM) is an autoimmune myopathy subtype often associated with antibodies such as HMGCR and SRP and may be refractory to standard immunosuppression.

Treatment responseSmall retrospective series report CK reductions and clinical responses after TPE, particularly among patients with HMGCR or SRP antibodies who failed immunosuppression.

Evidence limitationData are limited to small, single‑center retrospective cohorts; randomized trials are needed to validate effectiveness.

ASFA categories — definitions and implications

Category IApheresis accepted as first‑line therapy (primary standalone or with other treatments).

Category IIApheresis accepted as second‑line therapy (standalone or with other treatments).

Category IIIOptimum role not established — individualized decision making required.

Category IVEvidence suggests apheresis is ineffective or harmful; IRB approval desirable if treatment undertaken.

InterQual — definition and use in coverage decisions

DefinitionInterQual is the primary medical/surgical criteria system used by UnitedHealthcare for coverage determinations.

ApplicationIf InterQual lacks applicable criteria, UnitedHealthcare may use other UnitedHealthcare Medical Policies, Coverage Determination Guidelines, or Utilization Review Guidelines approved by Ohio Medicaid.

Governance noteCoverage decisions must reference federal, state (OAC), or contractual requirements which govern in case of conflict with this policy.

2026-01-01supporting_info_update

Updated Supporting Information sections (Clinical Evidence, FDA, and References) to reflect current information and archived previous policy version CS004OH.B.