ModifiedPremera BluecrossPolicy N/A

Pharmacotherapy of Thrombocytopenia (Pharmacy / Medical Policy - 5.01.566)

Coverage and medical necessity criteria for pharmacologic treatments of thrombocytopenia (including ITP, severe aplastic anemia, hepatitis C–associated thrombocytopenia, chemotherapy‑induced thrombocytopenia, and prophylaxis for procedures) and which drugs require prior approval. Affects providers prescribing or requesting coverage for listed agents.

Policy Summary

PayerPremera Bluecross

PolicyPharmacotherapy of Thrombocytopenia (5.01.566)

Policy CodePolicy N/A

Change TypeMultiple additions and revisions (new agents, pediatric expansion, updated limits)

Effective DateJun 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with medical records documenting diagnosis, prior therapies, platelet counts, and required baseline monitoring to request up to a 12-month approval when medical necessity criteria are met.

SourceLink

POLICY UPDATE CHANGES

Revised criteria after insufficient response to corticosteroids to require the individual has had an insufficient response to an immune globulin (IVIg), rituximab, or splenectomy.

Added coverage criteria for Alvaiz (eltrombopag choline).

Added coverage criteria for Adzynma (ADAMTS13, recombinant-krhn) for treatment of certain individuals with congenital thrombotic thrombocytopenic purpura (cTTP).

Added coverage criteria for Doptelet Sprinkle (avatrombopag) oral granules for pediatric patients 1 year to <6 years and expanded tablet indication to pediatric patients 6 years and older.

Added coverage criteria for WinRho SDF for treatment of ITP in Rho(D) positive, nonsplenectomized children and adults and for suppression of Rh isoimmunization in certain pregnancies.

Updated initial authorization and re-authorization length of approval to 12 months unless noted otherwise for specific drugs under the medical necessity criteria.

Updated quantity limits for Alvaiz (eltrombopag choline), generic eltrombopag olamine, and Promacta (eltrombopag olamine) to add specific per 30 day limits (Alvaiz limited to 60 tablets per 30 days).

multipledrugs listed with criteria

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60 / 30dAlvaiz qty limit

60 / 30dDoptelet Sprinkle limit

Black Boxeltrombopag warning

Coverage and Medical Necessity Criteria

Safety and monitoring conditions

ALL of the following

Development and progression of hematologic malignancies have been observed with eltrombopag and romiplostim; these agents should not be used to treat thrombocytopenia other than ITP.
Source: safety section
Eltrombopag carries a boxed warning for hepatotoxicity.
Monitor liver tests per prescribing information
Measure ALT, AST, and bilirubin prior to initiation of eltrombopag, every two weeks during dose titration, and monthly after a stable dose has been established.
If abnormal, repeat within 3–5 days; if confirmed, monitor weekly until resolution
Discontinue eltrombopag if ALT ≥ 3 times baseline and progressive, persistent ≥ 4 weeks, or accompanied by increased direct bilirubin, clinical symptoms of liver injury, or evidence of hepatic decompensation.
Follow prescribing information
Cataracts have developed or worsened in some individuals treated with eltrombopag; perform ocular examination prior to initiation and monitor for signs/symptoms of cataracts during treatment.
Pre-clinical and clinical observations
Romiplostim (IV) has not been associated with hepatotoxicity in trials, likely due to lack of first-pass metabolism; monitor patients according to product labeling and clinical judgment.
Safety distinction between agents
For all thrombopoietic agents, monitor platelet counts regularly to assess response and adjust dose to avoid excessive thrombocytosis and thrombotic risk (per product-specific dosing guidance).
Operational: ensure documentation of platelet goals and changes
Document baseline relevant labs and follow-up monitoring in the medical record to support ongoing therapy and prior authorization re-authorization (e.g., liver tests, platelet counts, ocular exam results when eltrombopag is used).
Documentation requirement for continuation reviews

Billing and Coding

HCPCS codes referencedHCPCS

J2792	Injection, Rho D immune globulin, intravenous, human, solvent detergent, 100 IU.
J2802	Injection, romiplostim (Nplate), 1 microgram.
J7171	Injection, adamts13, recombinant-krhn, (Adzynma) 10 iu

Historical HCPCS (terminated)HCPCS

C9167

HCPCS code (terminated)

Current HCPCS additionsHCPCS

J7171

HCPCS code added to policy

HCPCS additionsHCPCS

J2792

HCPCS code added related to WinRho SDF

HCPCS code updatesHCPCS

J2796	HCPCS code (termed and replaced)
J2802	HCPCS replacement code

Platelet count thresholds used across criteria

Severe thrombocytopenia thresholdPlatelet count <30,000/µL

Low platelet with increased bleeding riskPlatelet count <50,000/µL with increased risk for bleeding

Procedure prophylaxis thresholdPlatelet count <50,000/µL for chronic liver disease procedural prophylaxis

Chemotherapy-induced thrombocytopenia thresholdPlatelet count <100,000/µL for chemotherapy‑induced thrombocytopenia (romiplostim criteria)

Pediatric ITP thresholdsSame numeric thresholds applied for pediatric ITP criteria (as specified per agent age limits)

Prior Authorization, Documentation, and Monitoring

Prior Authorization

Prior Authorization Required

Prior authorization is required for medications covered under this policy. Initial approvals and re-authorizations will generally be issued for up to 12 months unless a specific drug criterion states otherwise. Coverage determinations are subject to member benefit plan limits and the member's specific pharmacy or medical benefit terms.

Prior authorization required; typical approval length: up to 12 months
Approvals follow FDA prescribing information and any drug-specific duration limits
Coverage is controlled by the member's benefit plan

Prior Authorization

Benefit Channel / Prior Authorization

Some agents in this policy are managed through the pharmacy benefit while others are managed through the medical benefit. Verify the benefit channel before submitting authorization requests to ensure the correct prior authorization pathway is used.

Managed through pharmacy benefit: Alvaiz (eltrombopag choline), Doptelet (avatrombopag) and Doptelet Sprinkle, generic eltrombopag, Mulpleta (lusutrombopag), Promacta (eltrombopag olamine), Tavalisse (fostamatinib)

Step Therapy Requirements and Sequences

Requirement	Details
Prior inadequate response to corticosteroids, IVIG, rituximab, or splenectomy
Must have tried and had inadequate response or intolerance to listed prior therapies before approving many thrombopoietic agents (policy requires insufficient response to corticosteroids and to IVIG, rituximab, or splenectomy per guideline-based criteria).

Requirement	Details
Prior inadequate response to eltrombopag or romiplostim
Tavalisse (fostamatinib) requires the individual to have had an insufficient response to eltrombopag or Nplate (romiplostim) before approval.

Requirement	Details
Second-line therapy prerequisites
Revised criteria require insufficient response to corticosteroids and to IVIG, rituximab, or splenectomy prior to certain second-line approvals (policy reflects ASH guidance).

Change	Effect on coverage
Removal of prior-try requirement for avatrombopag (Doptelet)
Step therapy that previously required an insufficient response to eltrombopag (Promacta) or romiplostim (Nplate) for Doptelet was removed from the policy; Doptelet criteria no longer mandate prior trial of those agents.

Dosage and Quantity Limits

Alvaiz (eltrombopag choline) — 60 tablets per 30 days

Standard monthly quantity60 tablets per 30 days

Associated dose limitsDose limits apply per indication (e.g., 54 mg/day for chronic ITP; 108 mg/day for severe aplastic anemia)

Applied in prior authorizationQuantity limit included in Alvaiz medical necessity criteria and prior auth requirements

Eltrombopag (generic/Promacta) — age/strength-specific quantity limits vary by strength

Quantity limits vary by strength12.5 mg and 25 mg: 30 tablets per 30 days; 50 mg and 75 mg: 60 tablets per 30 days

Dose caps by indicationDose limited to 150 mg/day for severe aplastic anemia (adult/pediatric ≥2 yrs) and other dose limits per indication

Benefit Channel and Site-of-Service Guidance

Note

Rituximab site‑of‑service review (infusion center/office/hospital outpatient)

Rituximab products may be subject to site‑of‑service review for administration (infusion center, office, or hospital outpatient); see policy 5.01.556 for non‑oncologic uses.

Billing Rule

Pharmacy‑managed agents require pharmacy prior authorization

Certain agents are managed under the pharmacy benefit (oral agents and some injectables such as Alvaiz, Doptelet, Doptelet Sprinkle, generic eltrombopag, Mulpleta, Promacta, Tavalisse) and require prior authorization through pharmacy channels.

Billing Rule

Medical‑benefit agents require medical prior authorization and site‑appropriate administration

Continuation and Re-authorization

Continuation / Re-authorization

Re-authorization may be granted when the following are met

Re-authorization: May be approved up to 12 months if drug-specific conditions are met, the individual demonstrates clinical benefit (e.g., platelet count meets goal), and no clinically significant bleeds have occurred while on therapy.

Long-term/continuation evidence

Long-term extension data and continuation considerations

Eltrombopag long-term response: EXTEND trial: ~50% had continuous response >4 weeks, 35% >10 weeks, 24% >6 months; at one year ~7% still showed response; 48% could discontinue or reduce concomitant ITP meds per manufacturer's dossier.

Interpret cautiously; extension/post-hoc data

Romiplostim long-term response:

Clinical Background

Thrombocytopenia is defined by a reduced platelet count that increases bleeding risk. Chronic immune thrombocytopenia (ITP) is an immune-mediated disorder in which autoantibodies and immune processes accelerate platelet destruction and may impair production. Management is guided by platelet count, bleeding symptoms, and underlying cause and can include corticosteroids, intravenous immunoglobulin (IVIg), anti-D/Rho(D) immune globulin, thrombopoietic agents, anti-CD20 therapy (rituximab), ADAMTS13 replacement for congenital TTP, and other targeted agents. This policy describes which pharmacologic treatments require prior authorization and the clinical thresholds and monitoring requirements that support medical necessity determinations.

Definition — Chronic immune thrombocytopenia (ITP) summary

Definition summaryChronic immune thrombocytopenia (ITP) is an immune-based thrombocytopenia where the immune system attacks and destroys platelets, causing low platelet counts and increased bleeding risk.

Affected populationsOccurs in both adults and children; treatment depends on age, symptoms, and platelet levels

Clinical implicationsManagement includes thrombopoietic agents, immunoglobulins, ADAMTS13 replacement, kinase inhibitors, and anti-CD20 agents as appropriate

Policy Summary

PayerPremera Bluecross

PolicyPharmacotherapy of Thrombocytopenia (5.01.566)

Policy CodePolicy N/A

Change TypeMultiple additions and revisions (new agents, pediatric expansion, updated limits)

Effective DateJun 1, 2026

Next Review DateN/A

SourceLink

On This Page

Alvaiz quantity limit (per 30 days)

Alvaiz quantity limit (per 30 days)60 tablets per 30 days

Dose limits referencedDose limits for Alvaiz described separately (e.g., 54 mg/day for chronic ITP; 108 mg/day for severe aplastic anemia)

Prior authorization noteQuantity limit applied within prior authorization approvals (up to 12 months when criteria met)

Doptelet Sprinkle quantity limit (per 30 days)

Doptelet Sprinkle quantity limit (per 30 days)Does not exceed 60 oral granule capsules in 30 days

Per-course dosing for pediatricsDose limited to 20 mg per day for ages 1 to <6 years; quantity cap applied monthly as noted

Prior authorization contextQuantity limit enforced in prior authorization approvals and history reflects update effective Feb 6, 2026

Managed through both pharmacy and medical benefit: Nplate (romiplostim)

Billing Rule

Authorization Duration and Quantity Limits

Quantity and dosing limits and duration of authorization follow the policy coverage criteria and the product's FDA prescribing information. Initial authorization and re-authorization lengths are generally 12 months unless otherwise noted. Specific quantity limits (for example, Alvaiz limited to 60 tablets per 30 days) are enforced as listed in the drug criteria.

Alvaiz (eltrombopag choline): dose limit 108 mg/day; quantity limit 60 tablets per 30 days
Promacta (eltrombopag olamine) and generic eltrombopag: quantity limits per 30 days as specified in criteria
Nplate (romiplostim): dose limited to 10 mcg/kg weekly for ITP
Initial and re-authorization lengths: up to 12 months unless otherwise specified

Denial Risk

Denial Triggers (General)

Coverage may be denied for common, preventable reasons. Ensure submitted records demonstrate required prior treatments, appropriate baseline and ongoing monitoring, dosing within policy limits, and that the requested drug is managed under the correct benefit channel.

Missing or incomplete medical records documenting diagnosis, prior therapies, or monitoring
Failure to document required step therapy or prior treatment trials where applicable
Requests for doses or quantities exceeding policy or FDA limits
Lack of required baseline testing (e.g., peripheral blood smear, CBC, liver tests) prior to initiation

Documentation Required

Baseline and Ongoing Monitoring

Baseline evaluations and ongoing monitoring must be performed as specified for each agent. Failure to obtain required baseline or follow-up monitoring may affect coverage or lead to denial of continued therapy.

Obtain baseline peripheral blood smear and CBCs prior to initiating eltrombopag or romiplostim
CBC monitoring monthly after initiation; if therapy is stopped, obtain weekly CBCs for at least two weeks to monitor for rebound thrombocytopenia
For eltrombopag: obtain ALT, AST, and bilirubin prior to initiation, every two weeks during dose titration, and monthly after stable dosing; repeat abnormal tests within 3–5 days and monitor weekly if confirmed
Perform ocular examinations prior to initiating eltrombopag and monitor for cataract symptoms during treatment

Documentation Required

Required Documentation and Duration

Medical records submitted for prior authorization must document that medical necessity criteria are met. Include office visit notes with diagnosis, relevant history, physical exam, and complete medication history. Attach laboratory test results and any relevant imaging or specialist consultations supporting the request.

Office visit notes documenting diagnosis, history, physical exam, and medication history
Results of required baseline tests (CBC, peripheral smear, liver tests, ADAMTS13 when applicable)
Documentation of prior therapies tried and reason for failure or intolerance (e.g., corticosteroids, IVIG, rituximab, splenectomy, generic eltrombopag when required)
For genetic diagnoses (e.g., cTTP): molecular genetic testing and ADAMTS13 activity results

Step Therapy

Step Therapy / Required Prior Treatments

Step therapy and prior treatment requirements are enforced where specified. Many agents require documented inadequate response or intolerance to first-line therapies (corticosteroids, IVIG), and in some cases to second-line agents (eltrombopag, romiplostim, rituximab, or splenectomy) before approval of alternative agents.

For chronic ITP: requirement of insufficient response to corticosteroids, immunoglobulins (IVIG), rituximab, or splenectomy prior to some second-line agents
Some agents require prior inadequate response or intolerance to generic eltrombopag before approving brand eltrombopag formulations
Per 2023 update: the step therapy requirement that mandated prior failure of Promacta (eltrombopag) or Nplate (romiplostim) was removed for Doptelet (avatrombopag)
Selection and sequencing of second-line therapy should align with ASH guidance and consider patient-specific factors

Step Therapy

Step Therapy and Sequence

When sequencing second-line therapies, follow guideline-aligned ordering and document why a chosen agent is appropriate for the patient. Consider rituximab as a second-line option for chronic adult ITP or for patients unresponsive to or relapsing after first-line therapy; consider TPO-receptor agonists per ASH guidance and policy criteria.

Use clinical judgment to select second-line therapy based on bleeding risk, activity level, side-effect profile, and patient preference
Document prior therapies and reasons for discontinuation or failure to support sequencing decisions
Ensure requests for second-line agents meet the policy's 'insufficient response' definitions

Applied to generic and PromactaStrength-specific per-30-day limits apply to generic eltrombopag olamine and Promacta

Doptelet (avatrombopag) - procedure course — fifteen 20 mg tablets

Procedure course quantityFifteen 20 mg tablets (one course per procedure)

IndicationFor prophylaxis in individuals with chronic liver disease scheduled for invasive procedure with platelet count <50,000/µL

TimingAdministered when procedure scheduled within 14 days

Mulpleta (lusutrombopag) — seven 3 mg tablets

Procedure course quantitySeven 3 mg tablets (one course per procedure)

IndicationFor prophylaxis in chronic liver disease patients with platelet count <50,000/µL undergoing invasive procedure

Dose capDose limited to 75 mg per day per prescribing criteria (Mulpleta dosing guidance)

WinRho SDF (Rho[D] Immune Globulin) — 300 IU per kg (60 mcg/kg)

WinRho dosing (weight-based)300 IU per kg (60 mcg/kg) per dose

IndicationsTreatment of ITP in Rho(D)-positive, nonsplenectomized individuals and Rh isoimmunization suppression per listed obstetric indications

Prior auth contextDose limit specified within medical necessity criteria and applied at authorization

Adzynma (ADAMTS13) — 40 IU/kg

Adzynma prophylactic dose40 IU/kg once weekly (prophylactic)

IndicationFor congenital thrombotic thrombocytopenic purpura (cTTP) with ADAMTS13 activity <10% and confirmed molecular testing

Use conditionsUsed when inadequate response or contraindication to plasma transfusion therapy or allergy to plasma products

eltrombopag — age-specific dosage and quantity limits updated

Age-specific updatesEltrombopag dosage and quantity limits include age-specific guidance (updated 2017 and applied in criteria)

Pediatric dosing considerationsPromacta and generic eltrombopag include pediatric dosing and per-strength quantity caps (e.g., pediatric ≥2 yrs for certain indications)

Applied across product listingsAge-specific dosage/quantity limits reflected in eltrombopag, Promacta, and Alvaiz criteria

Alvaiz (eltrombopag choline) — quantity limit summary (60)

Summary monthly quantity60 tablets per 30 days (Alvaiz) — applied as the policy quantity limit

Related dose limitsDose limits also specified (e.g., 54 mg/day for chronic ITP; 108 mg/day for severe aplastic anemia)

Effective updateQuantity limit added in 2026 update and included in prior authorization rules

Doptelet Sprinkle (avatrombopag) oral granules — quantity limit summary (60)

Oral granules monthly capDoes not exceed 60 oral granule capsules in 30 days

Pediatric indicationDoptelet Sprinkle indicated for ages 1 year to <6 years with persistent or chronic ITP; monthly cap applied

History of changeQuantity limit update recorded in policy history and effective Feb 6, 2026 (provider notification noted)

Products administered as biologics or plasma‑derived therapies (e.g., Adzynma, WinRho SDF) are managed through the medical benefit and require medical‑benefit prior authorization and administration in applicable sites of care.

Note

Historical: IV therapy site‑of‑service review applicable to age ≥13

Historical site‑of‑service language noted IV therapy review applicable to age 13 and older for some therapies; confirm current site‑of‑service rules per policy history and local coverage policies.

Open-label extension reported platelet responses of 30% after first dose and 51% after third dose; responders had response during 67% of weeks enrolled; long-term data limited.

Reported as percentages without raw numbers

Re-authorization duration

Re-authorization approvals are generally for the following duration unless specified otherwise

Re-authorization duration: Re-authorization approvals generally up to 12 months unless otherwise specified for a particular drug.12 months

Definition — Chronic ITP platelet threshold definition

Policy platelet threshold (IWG reference)International Working Group update sets platelet count threshold as less than 100,000/µL for IWG nomenclature context

Policy operational thresholdsPolicy uses thresholds such as <30,000/µL or <50,000/µL (with increased bleeding risk) for treatment decision criteria

Indication-specific thresholdsHigher threshold (<100,000/µL) used for chemotherapy‑induced thrombocytopenia criteria (romiplostim)

Definition — standardized term usage for chronic ITP in policy

Standardized term usageThe policy standardizes terminology to 'chronic immune thrombocytopenia (ITP)', replacing older terms such as chronic immune (idiopathic) thrombocytopenia and immune thrombocytopenia purpura.

Documented updatesChange implemented in 2019 update and consistently used in subsequent revisions

Applies across criteria sets'Chronic immune thrombocytopenia (ITP)' used throughout drug-specific and monitoring criteria in the policy