Aetna Plasmapheresis Coverage Update

Medically Necessary Indications — Therapeutic Apheresis

Aetna considers plasmapheresis (PP), plasma exchange (PE), or therapeutic apheresis medically necessary when ALL/ANY logic below is met for the specified indications.

ANY of the following

Acute humoral rejection of renal transplant
- Acute humoral (antibody-mediated) rejection of a renal transplant
Severe neurologic MS exacerbation refractory to steroids
- Acute, severe neurological deficits caused by multiple sclerosis with poor response to high-dose glucocorticoids
ANCA-associated vasculitis refractory
- Anti-neutrophil cytoplasmic antibody-associated vasculitis (Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome) unresponsive to conventional therapy
Babesiosis with high-risk features (RBC exchange)
- Babesiosis with high-grade parasitemia (>= 10%), severe anemia (Hgb <= 10 g/dL), or hepatic, pulmonary, or renal compromise requiring red blood cell exchange
Catastrophic antiphospholipid syndrome
- Catastrophic antiphospholipid syndrome with widespread thromboembolic disease and visceral damage
CIDP severe refractory
- Chronic inflammatory demyelinating polyneuropathy (CIDP) with severe or life‑threatening symptoms who have failed conventional therapy
  Diagnosis should be documented by progressive/relapsing course >= 2 months with characteristic neurophysiological abnormalities
Essential thrombocythemia with extreme thrombocytosis
- Essential thrombocythemia when platelet count > 1,000,000/mm3 (platelet pheresis)
Goodpasture’s syndrome / Anti-GBM glomerulonephritis
- Glomerulonephritis associated with anti-glomerular basement membrane antibodies with advancing renal failure or pulmonary hemorrhage
HELLP postpartum worsening
- HELLP syndrome if thrombocytopenia, hemolysis, or renal failure continues to worsen 48–72 hours postpartum
Hemolytic uremic syndrome or TTP
- Hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP) — treatment with plasma exchange
Hyperglobulinemia / hyperviscosity syndromes
- Hyperglobulinemias (including multiple myeloma, cryoglobulinemia, hyperviscosity syndromes)
Hypertriglyceridemia‑induced acute pancreatitis (TPE) — ALL must be met
- Serum triglyceride level > 1,000 mg/dL> 1000 mg/dL
- Lipase > 3 times the upper limit of normal
- Worrisome clinical features: hypocalcemia, lactic acidosis, signs of worsening systemic inflammation or organ dysfunction and/or multi‑organ failure
Last‑resort severe neuroinflammatory or autoimmune conditions
- Acute disseminated encephalomyelitis, life‑threatening rheumatoid vasculitis, or life‑threatening SLE when conventional therapy has failed
Leukapheresis for leukostasis
- Leukemia with white blood cell count > 100,000/µL for acute debulking (leukapheresis)
Myasthenia gravis indications
- Impending respiratory crisis or acute need for short‑term rapid improvement of strength (e.g., pre‑surgery)
- Requires chronic intermittent treatment because of failure to respond to all other treatments
Neuromyelitis optica refractory to steroids
- Neuromyelitis optica spectrum disorder refractory to glucocorticoids
Paraproteinemic demyelinating neuropathies (IgG/IgA)
- Paraproteinemic demyelinating neuropathies associated with IgG or IgA MGUS (excluding multiple myeloma)
Pemphigus vulgaris refractory
- Pemphigus vulgaris resistant to standard therapy (dapsone, corticosteroids, immunosuppressants)
Pruritus from cholestatic liver disease, last‑resort
- Pruritus from cholestatic liver disease (plasma perfusion/charcoal filters) after failure of bile acid resins, rifampin, ursodeoxycholic acid, and opioid antagonists
Recurrent FSGS in transplant
- Recurrence of focal and segmental glomerulosclerosis in the kidney allograft
Refsum's disease
- Refsum's disease
ABO/positive cross‑match transplant desensitization
- Renal transplant from live donor with ABO incompatibility or positive cross‑match when a suitable non‑reactive donor is unavailable
- Solid organ transplant from donor with positive cross‑match when a suitable non‑reactive donor is unavailable
Scleroderma or polymyositis unresponsive
- Scleroderma or polymyositis unresponsive to conventional therapy
Severe Guillain‑Barré syndrome
- Severe (grades 3–5) Guillain‑Barré syndrome; initiate PE within 2 weeks of onset for ambulant individuals and within 4 weeks for non‑ambulant individuals
Homozygous/heterozygous familial hypercholesterolemia LDL apheresis
- Homozygous familial hypercholesterolemia refractory to diet and maximum drug therapy with LDL‑C > 500 mg/dL
- Heterozygous familial hypercholesterolemia refractory to diet and maximum drug therapy with LDL‑C > 300 mg/dL, or LDL‑C > 200 mg/dL with documented coronary artery disease
Sickle cell disease therapeutic cytapheresis
- Sickle cell disease when therapeutic cytapheresis criteria met (therapeutic red cell exchange)
TTP / microangiopathic hemolytic anemia
- Thrombotic thrombocytopenic purpura (TTP) or microangiopathic hemolytic anemia — treatment
Transverse myelitis steroid‑refractory
- Transverse myelitis when corticosteroid treatment has failed
Waldenstrom’s macroglobulinemia prophylactic on rituximab/ofatumumab
- Waldenstrom's macroglobulinemia: prophylactic plasmapheresis when IgM >= 5000 mg/dL in patients receiving rituximab or ofatumumab to avoid IgM flare

title':'Medically Necessary Indications'

Coverage Criteria — Medically Necessary and Not Medically Necessary Indications

Use of plasmapheresis/PE/therapeutic apheresis is considered experimental, investigational or not medically necessary when used for indications not listed as medically necessary, including but not limited to the following:

ANY of the following

Acute pancreatitis related to hyperlipidemia (routine plasmapheresis without meeting HTG‑AP severe criteria)
Alzheimer's disease
Amyotrophic lateral sclerosis
Anti‑MAG neuropathy
Autoimmune inner ear disease

Coding — CPT, HCPCS, and ICD-10 Guidance

Covered CPT / HCPCS / Related CodesmixedCovered

36514	Therapeutic apheresis: for plasma pheresis
36511	Therapeutic apheresis: for white blood cells (leukapheresis)
36512	Therapeutic apheresis: for red blood cells (therapeutic cytopheresis)
0342T	Therapeutic apheresis with selective HDL delipidation and plasma reinfusion
83690	Lipase
84478	Triglycerides
93015-93018	Cardiovascular stress test
J2323	Natalizumab, 1 mg
J7500	Azathioprine, oral, 50 mg
J7501	Azathioprine, parenteral, 100 mg

1–10 of 13

1/2

Selected ICD-10 codes covered if selection criteria are metICD-10Covered

A81.2	Progressive multifocal leukoencephalopathy [natalizumab-associated]
B60.0	Babesiosis
C88.0	Waldenström macroglobulinemia
C90.0 - C90.02	Multiple myeloma
D47.2	Monoclonal gammopathy [MGUS]
D47.3	Essential (hemorrhagic) thrombocythemia
G35	Multiple sclerosis [acute, severe neurological deficits with poor response to glucocorticoids]
G61.0	Guillain-Barre syndrome
G61.81	Chronic inflammatory demyelinating polyneuritis [CIDP]
G70.00 - G70.01	Myasthenia gravis

1–10 of 11

1/2

ICD-10 codes not covered for indications listed in the CPBICD-10Not Covered

A40.0 - A41.9	Streptococcal and other sepsis
G30.0 - G30.9	Alzheimer's disease
G12.21	Amyotrophic lateral sclerosis
K85.00 - K85.92	Acute pancreatitis [related to hyperlipidemia]
K51.00 - K51.919	Ulcerative colitis

inv-31: Serum triglyceride level (key threshold used in coding/criteria)

Serum triglyceride levelgreater than 1,000 mg/dL

ContextUsed as a primary threshold for considering apheresis in hypertriglyceridemia-induced acute pancreatitis

MonitoringTriglyceride levels should be monitored every cycle of plasmapheresis (continue until target achieved)

inv-32: Lipase threshold (used in HTG-induced pancreatitis criteria)

Lipase thresholdgreater than 3 times the upper limit of normal

Combined criteriaLipase >3× ULN is required alongside TG >1000 mg/dL for HTG-induced pancreatitis apheresis consideration

Source guidanceReferenced in UpToDate and policy criteria for HTG-induced acute pancreatitis

inv-33: IgM level prompting consideration of plasmapheresis before rituximab in Waldenstrom's

IgM levelgreater than or equal to 5000 mg/dL

IndicationPlasmapheresis prior to or in the context of rituximab/ofatumumab to avoid IgM flare in Waldenstrom's with IgM ≥5000 mg/dL

Guideline sourceNCCN recommendation referenced in policy

inv-34: LDL levels for LDL apheresis thresholds (homozygous/heterozygous CAD modifiers)

LDL threshold — homozygous FHgreater than 500 mg/dL

LDL threshold — heterozygous FHgreater than 300 mg/dL (or >200 mg/dL with documented coronary artery disease)

Prior therapy requirementMaximum tolerated combination drug therapy (6-month trial) required before LDL apheresis

inv-35: WBC count threshold for leukapheresis in hyperleukocytosis

WBC count thresholdgreater than 100,000/µL

IndicationLeukapheresis for acute debulking/hyperleukocytosis/leukostasis to rapidly reduce WBC prior to chemotherapy

Clinical contextHyper-leukocytosis defined as WBC >100,000/µL and may cause leukostasis, TLS, DIC

inv-36: Babesiosis high-grade parasitemia threshold

High-grade parasitemiagreater than or equal to 10%

IndicationRed cell exchange is appropriate for babesiosis with parasitemia ≥10%

Treatment goalTarget ~90% reduction in parasitemia with exchange transfusion per UpToDate guidance

inv-37: Severe anemia threshold in babesiosis (Hb ≤ 10 g/dL)

Severe anemia thresholdhemoglobin less than or equal to 10 g/dL

IndicationSevere anemia (Hgb ≤10 g/dL) is an indication for red cell exchange in babesiosis

Management noteExchange transfusion should be managed in consultation with hematology and pheresis experts

inv-38: Babesiosis parasitemia threshold reiterated (>=10%)

Parasitemia threshold (reiterated)>=10 percent

PurposeThreshold used to prompt consideration of red cell exchange to clear infected RBCs and remove inflammatory mediators

Target reductionAim for ~90% reduction in parasitemia

inv-39: Hemoglobin threshold for exchange in babesiosis (<=10 g/dL)

Hemoglobin threshold for exchange<=10 g/dL

Clinical useHgb ≤10 g/dL in babesiosis supports consideration of red cell exchange transfusion

Volume planningEstimated allogeneic RBC volume to achieve target reduction ≈2.5× recipient RBC volume

inv-40: Triglyceride threshold for considering TPE in HTG-induced pancreatitis (>1000 mg/dL)

Triglyceride threshold for TPE consideration> 1000 mg/dL

Combined requirementRequire TG >1000 mg/dL plus lipase >3× ULN and worrisome clinical features to consider TPE

GuidanceUpToDate suggests TPE (Grade 2C) in such patients and to continue until TG <500 mg/dL

inv-41: IgM level prompting plasmapheresis pre-rituximab (IgM ≥ 5000 mg/dL)

IgM level prompting plasmapheresis pre-rituximabIgM ≥ 5000 mg/dL

PurposePerformed before or in context of rituximab/ofatumumab to avoid IgM flare and symptomatic hyperviscosity

Guideline sourceNCCN Waldenstrom's guidance referenced in policy

inv-42: Triglyceride level relevant to DFPP (>1000 mg/dL)

Triglyceride level for DFPPgreater than 1000 mg/dL

IndicationDFPP used in severe hypertriglyceridemia to rapidly reduce triglyceride levels (pilot studies used TG >1000 mg/dL)

Treatment objectiveAim to reduce TG to normal (<1.7 mmol/L ≈150 mg/dL) per DFPP pilot protocol

inv-43: Triglyceride threshold for HTG-induced pancreatitis (>1000 mg/dL) — duplicate threshold entry for emphasis

Repeated TG threshold for HTG-induced pancreatitis> 1000 mg/dL

Policy emphasisUsed consistently across policy and UpToDate as the defining severe HTG threshold prompting consideration of plasmapheresis/DFPP

Clinical noteConsider only when accompanied by elevated lipase and worrisome systemic features

inv-44: TPE target triglyceride level to continue plasmapheresis (<500 mg/dL)

TPE target triglyceride level< 500 mg/dL (5.6 mmol/L)

MonitoringTriglyceride levels should be monitored each cycle of plasmapheresis and TPE continued until TG <500 mg/dL

Guidance basisUpToDate recommendation cited in policy

Provider Actions — Prior Authorization, Documentation, and Step Therapy

Prior Authorization

Prior Authorization Required for Guideline‑Supported Indications

Prior authorization is required for plasmapheresis/plasma exchange (PP/PE/TPE) when the request is for guideline-supported indications (e.g., symptomatic Waldenström macroglobulinemia with hyperviscosity, TTP, severe Guillain–Barré syndrome, antibody‑mediated renal transplant rejection) and when selection criteria in the policy apply. Requests should reference the applicable ICD‑10/CPT codes and demonstrate that policy clinical criteria have been met.

Submit documentation of diagnosis, prior therapies, and clinical parameters relevant to the indication
Include targeted plasma volume planned and replacement fluid choice when available

Prior Authorization

Preoperative Justification Required for PLEX in HIT

For members with heparin‑induced thrombocytopenia (HIT) who require urgent cardiovascular surgery, preoperative justification is required when plasma exchange is proposed as part of the perioperative anticoagulation strategy. Document the HIT phase (acute, subacute A, subacute B, or remote), rationale for not delaying surgery, prior functional and immunoassay results, and the planned intraoperative anticoagulation approach per ASH guidance.

If proposing preoperative PE to allow intraoperative heparin, include timing and number of planned exchanges and anticoagulation plan (e.g., heparin after PE, bivalirudin alternative)
Document consultation with cardiovascular surgery and hematology

Prior Authorization

Prior Authorization and Documentation Requirements for HTG‑Induced Pancreatitis

Prior authorization is required for plasmapheresis in hypertriglyceridemia‑induced acute pancreatitis (HTG‑AP). Requests must document baseline serum triglyceride level, lipase elevation, and the presence of worrisome clinical features that may justify TPE over conventional therapy.

Provide initial TG level (mg/dL) and lipase (>3× ULN)
List worrisome features present (e.g., hypocalcemia, lactic acidosis, worsening systemic inflammation, organ dysfunction, multi‑organ failure)
Document conventional treatments tried or considered (e.g., insulin infusion for diabetics, heparin, aggressive IV fluids, bowel rest) and rationale for escalation to TPE

Denial Risk

TPE for Snakebite‑Associated TMA — Evidence and Coverage Risk

Therapeutic plasma exchange (TPE) for snakebite‑associated thrombotic microangiopathy (TMA) is not supported by available evidence. Systematic review data do not demonstrate benefit of TPE for dialysis‑dependent AKI in snakebite‑associated TMA; requests for TPE in this setting carry a high risk of noncoverage and require strong justification.

If TPE is requested, include detailed justification, prior anti‑venom therapy, timing relative to envenoming, renal status, and consultation notes from toxinology/hematology

Note

Systematic Review Evidence — HTG‑AP: No Clear Superiority of Plasmapheresis

A systematic review of plasmapheresis for hypertriglyceridemia‑induced acute pancreatitis found no superiority over conventional treatment for patient‑centered outcomes and reported higher costs. When ordering TPE for HTG‑AP, document evidence that conventional care was inadequate or that the patient meets guideline‑recommended severity criteria.

Attach relevant study or guideline excerpts if used to support the clinical plan
If relying on limited evidence or pilot studies, describe why TPE is being chosen for this specific patient

Note

Administrative Note — No Other Administrative Rules Stated

Administrative: no additional administrative prior‑authorization exceptions or alternative step therapy rules are stated within these referenced chunks beyond the specific prior authorization and documentation requirements noted above.

Coverage determinations remain subject to member‑specific benefits and contract terms
Clinical Policy Bulletins assist in administration of benefits and are not contracts

Documentation Required

PE Session Parameters and Procedural Documentation

When ordering a PE/TPE session, document procedure parameters and treatment intent: the estimated plasma volume to be exchanged (typically 1.0–1.5 × estimated plasma volume at approximately 40 mL/kg), planned anticoagulation method (e.g., citrate), and replacement fluid (e.g., albumin versus plasma) as well as monitoring and complication‑management plans.

Record estimated plasma volume target and rationale
Specify anticoagulation strategy and replacement fluid selection
Indicate number of sessions planned and criteria for stopping or repeating therapy

Documentation Required

MOG Antibody Testing and Clinical Documentation for PE

For suspected or confirmed MOG‑antibody disease (MOG‑AD) being considered for PE, document that MOG‑IgG testing was performed using a validated live cell‑based assay and that clinical and MRI features are consistent with MOG‑AD. Also document prior high‑dose steroid therapy and the clinical response; PE is generally considered a second‑line option after steroid resistance (commonly 3–5 cycles).

Attach MOG‑IgG assay result with test methodology and laboratory reference range
Document steroid regimen given and objective measures of nonresponse prior to PE
Include MRI findings and clinical phenotype (e.g., optic neuritis, transverse myelitis) correlating with MOG‑AD

Documentation Required

Documentation Requirements — HTG‑Induced Acute Pancreatitis

For HTG‑induced acute pancreatitis, document baseline triglycerides and lipase, details of conventional management attempted, and the presence of severity/worrisome features per guideline (TG >1000 mg/dL plus lipase >3× ULN and features such as hypocalcemia, lactic acidosis, worsening inflammation or organ dysfunction). Triglyceride levels should be monitored each cycle and TPE continued until TG <500 mg/dL when used.

Provide serial TG levels pre‑ and post‑procedure and target TG goal (<500 mg/dL)
Document why conventional measures (insulin, heparin, fluids) are insufficient or contraindicated

Step Therapy

Step Therapy and Documentation for LDL Apheresis

LDL apheresis requires step therapy documentation: prior to apheresis, providers must document a 6‑month trial of diet plus maximum tolerated combination drug therapy (agents from at least two separate classes of hypolipidemic drugs). Include lipid results over the 6‑month period and documentation of intolerance or failure of medications when applicable.

Attach 6 months of lipid panels and medication history
Document maximum tolerated doses and reasons for not using additional agents

Step Therapy

Hypertriglyceridemia — Stepwise Treatment Approach and Documentation

Approach to hypertriglyceridemia management follows a stepwise pathway: TPE is reserved for severe HTG (TG >1000 mg/dL, often >2000 mg/dL) with clinical factors increasing risk for or indicating severe AP. Conservative measures (diet, control of secondary factors, insulin for diabetics, heparin in select cases) should be considered and documented before TPE except when immediate TPE is clinically indicated.

Document secondary factors (uncontrolled diabetes, medications, pregnancy, alcohol) and steps taken to address them
If TG thresholds and worrisome features are present, describe urgency and planned TPE regimen

Prior Authorization

PLEX After Steroids in MOG‑AD and Demyelinating Presentations

For MOG‑AD and other neuroinflammatory conditions, PE is typically used as second‑line therapy after inadequate response to high‑dose IV corticosteroids; document steroid doses, duration, objective response measures, and rationale for escalation to PE.

Include dates and dosing of steroid therapy and neurological status before and after steroids
Note number of steroid cycles attempted and timing of PE initiation (commonly after steroid failure)

Documentation Required

Conservative/Conventional Treatments Should Be Documented Before TPE

Conservative and conventional treatments should be considered and documented prior to approving plasmapheresis for many indications where evidence is limited. Provide records showing which standard treatments were considered or attempted and why they were inadequate or contraindicated for the member.

List specific conventional therapies tried, dates, doses, and objective responses
If bypassing conventional care, state clear clinical justification and supporting specialty consultation notes

Regimen	Details / Prerequisites
LDL apheresis	Frequency typically averages about once every 2 weeks to achieve an intrapheresis LDL‑C ≤120 mg/dL; requires prior 6‑month trial of diet plus maximum tolerated combination drug therapy (trial of drugs from at least 2 separate classes).

Regimen	Details / Monitoring
Daily leukapheresis (example)	Examples include daily leukapheresis for 3 consecutive days as an initial cytoreductive measure; instrument settings should be adapted based on the differential blood count and physiologic response (document WBC, clinical status); used prior to or in conjunction with chemotherapy for symptomatic hyperleukocytosis/leukostasis.

Background and Context

Plasmapheresis, plasma exchange, and therapeutic apheresis are procedures that separate and remove plasma components to eliminate pathogenic circulating substances or to rapidly modify blood composition. In plasma exchange (PE) the patient’s plasma is discarded and replaced with a substitute fluid, whereas plasmapheresis (PP) refers to separation of plasma that may be manipulated and returned. These therapies are used to treat toxin‑ or antibody‑mediated disorders, manage hyperviscosity syndromes, perform cytoreduction (eg, leukapheresis), and rapidly lower lipid or immunoglobulin burdens in selected acute settings.

inv-74: Definition — plasmapheresis (plasma separated by centrifugation or membrane filtration)

Plasmapheresis — definitionA procedure in which plasma is separated from the blood either by centrifugation or membrane filtration and can be manipulated

Process descriptionBlood is pumped into a cell separator where red cells, white cells, and plasma are separated; plasma can be discarded or treated and returned

Terminology notePP/PE often used interchangeably in the policy though they denote different procedures

inv-75: Definition — plasma exchange (plasma discarded and replaced)

Plasma exchange — definitionProcedure where separated plasma is discarded and substituted with replacement fluid

Replacement fluidsReplacement may include albumin or plasma (eg, FFP) depending on indication

DistinctionPE denotes discarding plasma versus plasmapheresis which may manipulate and return plasma fractions

inv-76: Plasmapheresis (PP) — definition entry (duplicate definitional content across chunks)

Plasmapheresis (PP) definitionProcedure in which plasma is separated from blood by centrifugation or membrane filtration; plasma can be manipulated

SynonymsAlso referred to as therapeutic plasmapheresis or platepheresis in some contexts

Clinical useUsed to remove toxic circulating elements or pathogenic antibodies in various indications

inv-77: Plasma exchange (PE) — definition entry (duplicate definitional content across chunks)

Plasma exchange (PE) definitionProcedure in which separated plasma is discarded and replaced with a substitution fluid

Interchangeable usePolicy notes PP and PE are often used interchangeably though they are distinct technically

Typical replacementColloid solutions such as albumin or donor plasma used depending on indication

inv-78: Apheresis definition — process of passing blood through device to separate components

Apheresis definitionProcess of passing blood through a medical device to separate components and returning the remaining components to the body

Technique variantsIncludes plasmapheresis, filtration-based methods, therapeutic plasma exchange (TPE), and double filtration plasmapheresis (DFPP)

Clinical purposeUsed to remove specific circulating components (eg, lipoproteins, antibodies, cells) based on indication

inv-79: PE session parameters — treatment goal: exchange 1–1.5 × plasma volume (40 ml/kg estimation)

PE session treatment goalExchange between 1 and 1.5 times the patient's plasma volume (estimated at 40 ml/kg)

AnticoagulationCitrate commonly used to anticoagulate during PE sessions

DocumentationEstimate of plasma volume targeted should be documented to support medical necessity

inv-80: Hyper-leukocytosis / leukostasis definition and clinical intent for leukapheresis

Hyper-leukocytosis / leukostasis definitionOften defined as WBC >100,000/µL and may cause leukostasis, tumor lysis syndrome, and DIC

Clinical intentPrimary objective is rapid cytoreduction (eg, leukapheresis and/or hydroxyurea) to reduce morbidity and mortality

DocumentationPhysiologic measures (respiratory status, SpO2) and WBC/differential should be recorded when performing leukapheresis

inv-81: MOG-AD definition — disease description and distinguishing features

MOG-AD definitionAn acquired CNS demyelinating disorder identified by MOG-IgG cell-based assays presenting with optic neuritis, transverse myelitis, ADEM, or brainstem encephalitis

Clinical featuresDistinct from MS and AQP4-positive NMO; median age onset in 4th decade; residual disability common

Treatment contextPE commonly used as second-line after steroid resistance (regimen varying 3–5 cycles) with observational benefit reported

inv-82: MOG-AD — duplicate definitional content for emphasis/clarity

MOG-AD (emphasis)MOG antibody disease is a distinct CNS demyelinating disorder; validated cell-based MOG-IgG assays recommended to avoid misdiagnosis

Evidence gapRandomized trials lacking; observational series inform use of steroids and plasma exchange

Recovery rateObservational series report ~40% complete or nearly complete recovery in optic neuritis/myelitis cases after PE

inv-83: DFPP definition — double filtration plasmapheresis technique used in severe HTG

DFPP definitionDouble filtration plasmapheresis — a filtration-based plasmapheresis technique used to remove lipoprotein-rich plasma fraction to rapidly reduce triglyceride levels

Use caseUsed in severe hypertriglyceridemia (eg, TG >1000 mg/dL) to rapidly lower serum triglycerides

Pilot dataSmall pilot (n=7) reported mean TG reduction ~58% after one DFPP session

inv-84: DFPP — duplicate definition entry (remove duplication in content phase if needed)

DFPP (duplicate)DFPP removes lipoprotein-rich plasma fraction to rapidly reduce serum triglycerides; used in sHTG pilot studies

Technique detailsBlood flow 100–120 ml/min; plasma separation 800–1000 ml/hour; anticoagulation LMWH in pilot protocol

Treatment objectiveDecrease TG to normal (<1.7 mmol/L) per study protocol

inv-85: HTG-induced pancreatitis definition — TG >1000 mg/dL with lipase >3× ULN

HTG-induced pancreatitis definitionAcute pancreatitis occurring with serum triglyceride level >1000 mg/dL and lipase >3× upper limit of normal

Associated featuresWorrisome features include hypocalcemia, lactic acidosis, worsening systemic inflammation or organ dysfunction

RecommendationUpToDate suggests plasmapheresis/TPE for such patients (Grade 2C) and continuing until TG <500 mg/dL

Definitions — Key Terms and Thresholds

inv-74: Plasmapheresis definition (chunk reference repeated for definitions section)

Plasmapheresis — definition (repeat)Procedure in which plasma is separated from the blood either by centrifugation or membrane filtration and can be manipulated

Clinical notePlasma may be returned, discarded, or treated depending on the technique used

TerminologyPolicy uses PP/PE as combined descriptors though technical distinctions exist

inv-75: Plasma exchange definition

Plasma exchange — definition (repeat)Procedure in which separated plasma is discarded and replaced with a substitution fluid

Use casesUsed when removal of pathogenic plasma components is required and replacement is necessary (eg, TTP)

Replacement optionsAlbumin or donor plasma depending on indication and bleeding risk

inv-78: Apheresis general definition

Apheresis general definitionProcess of passing blood through a device to separate components and return the remainder to the patient

IncludesPlasmapheresis, filtration-based apheresis, TPE, DFPP, cell-specific apheresis (leukapheresis, erythrocytapheresis)

PurposeRemove toxic circulating elements (eg, autoantibodies, lipoproteins, cells) depending on indication

inv-80: Hyper-leukocytosis / leukostasis definition (WBC >100,000/µL)

Hyper-leukocytosis definitionWBC >100,000/µL

Clinical significanceCan cause leukostasis and related complications; warrants rapid cytoreduction measures such as leukapheresis

DocumentationRecord physiologic parameters and differential to support leukapheresis use

inv-81: MOG-AD definition (disease-specific)

MOG-AD definition (concise)An acquired CNS demyelinating disorder identified by MOG-IgG cell-based assays with presentations including optic neuritis and transverse myelitis

Diagnostic noteUse validated cell-based MOG-IgG assays to avoid misdiagnosis; MRI and clinical features help differentiate from MS/NMO

Therapeutic rolePE commonly used as second-line after steroid resistance (3–5 cycles) with observational benefit

inv-83: DFPP definition (technique-focused)

DFPP definition (concise)Double filtration plasmapheresis: filtration technique to remove lipoprotein-rich plasma fraction to rapidly lower triglycerides

Typical applicationUsed in severe hypertriglyceridemia-induced pancreatitis to rapidly reduce serum TG

Pilot evidenceSmall pilot studies report substantial TG reductions after one session

inv-85: HTG-induced pancreatitis definition and thresholds (TG >1000 mg/dL, lipase >3× ULN)

HTG-induced pancreatitis thresholdsSerum triglycerides >1000 mg/dL plus lipase >3× ULN

Clinical qualifiersPresence of hypocalcemia, lactic acidosis, worsening systemic inflammation or organ dysfunction increases consideration for TPE

Treatment targetContinue plasmapheresis/TPE until triglyceride levels are <500 mg/dL

OpenPayer

Plasmapheresis / Plasma Exchange / Therapeutic Apheresis

Coverage Criteria — Medically Necessary and Not Medically Necessary Indications

Coding — CPT, HCPCS, and ICD-10 Guidance

Provider Actions — Prior Authorization, Documentation, and Step Therapy

Covered Regimens — Typical Treatment Frequencies and Protocols

Line of Therapy — Initial and Salvage Use

Background and Context

Definitions — Key Terms and Thresholds

Revision History

References and Evidence Summaries