CurrentAetnaPolicy 0780

ADAMTS13 Assay for Thrombotic Thrombocytopenic Purpura (TTP)

This Clinical Policy Bulletin describes Aetna's coverage stance for ADAMTS13 assay testing in the evaluation and management of thrombotic thrombocytopenic purpura (TTP) and lists indications considered experimental/investigational.

Policy Summary

PayerAetna

PolicyADAMTS13 Assay for Thrombotic Thrombocytopenic Purpura (TTP)

Policy CodePolicy 0780

Change TypeNo material change

Effective Date04/24/2009

Next Review Date10/26/2023

Key ActionOrder CPT 85397 only when the policy's selection criteria for ADAMTS13 testing in TTP are met.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

1Covered CPT (if criteria met)

40+Experimental indications

17Clinical study summaries

04/24/2009Policy effective

10/26/2023Last review

Coverage Criteria for ADAMTS13 Assay

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inv-01: Medical necessity — ADAMTS13 assay for prognosis in TTP

Covered when ALL of the following are met

Medical necessity: Aetna considers the ADAMTS13 assay medically necessary for assessing prognosis in persons with thrombotic thrombocytopenic purpura (TTP).

From policy's Medical Necessity section

inv-02: Experimental and investigational indications

The following uses are considered experimental and investigational (insufficient evidence of clinical utility):

Experimental/Investigational uses: ADAMTS13 assay for the enumerated indications (items 1–42 in the policy) including but not limited to: biomarker roles after subarachnoid hemorrhage, COVID-19 disease severity and micro-thrombosis risk, early detection of hepatocellular carcinoma, monitoring progression of acute myocardial infarction, treatment response and prediction in HCC, risk assessment for endometriosis, diabetic retinopathy diagnosis/monitoring, sepsis-associated TMA monitoring, diagnosis of cholangitis, AML diagnosis, acute pancreatitis, arterial thrombosis, cerebral infarction, disseminated intravascular coagulation, IBD activity evaluation, HUS, perioperative assessment in type 1 VWD, ischemic complications of malignant hypertension, liver disease monitoring, pregnancy in COVID-19, post-kidney transplant renal monitoring, obstructive sleep apnea progression, prediction of AKI in COVID-19, PCI and AF outcome prediction, post-operative drainage after CABG, HCC development prediction, HBV HBeAg seroconversion prediction, recurrence and relapse predictions in multiple contexts, pre-eclampsia, melanoma prognosis, TBI prognosis, intracranial aneurysm risk, thrombosis risk in pediatric congenital heart disease, plus additional listed uses; and (separately) ADAMTS13 mutation testing for non-cirrhotic portal hypertension; and use of the VWF:Ag/ADAMTS13 activity ratio as a prognostic biomarker in acute-on-chronic liver failure.

Full enumerated list appears in document chunks 4-5

ADAMTS13 mutation testing for the diagnosis of non-cirrhotic portal hypertension is explicitly listed in the policy as experimental/investigational because of insufficient evidence to support clinical utility. The policy also identifies ICD-10 code K76.6 (portal hypertension) as an example of an associated diagnosis that is not covered for that indication.

Although individual studies report altered ADAMTS13 activity in patients with acute myelogenous leukemia (AML), the policy notes that the NCCN guideline on Acute Myeloid Leukemia (Version 1.2015) does not mention ADAMTS13 as a management tool. This omission supports the policy position that routine ADAMTS13 testing for AML management lacks guideline endorsement and therefore is not supported for routine clinical use.

Background literature summarized in the policy presents multiple observational and small cohort studies reporting associations between ADAMTS13 activity, VWF antigen, and various disease states (for example AML and TMA after pancreatitis). These background sections describe assay methods (FRETS-VWF73 and ELISA) and numeric findings but do not themselves establish medical necessity criteria or definitive coverage decisions; rather, the document treats these findings as preliminary and generally calls for further validation.

The policy notes that UpToDate reviews on von Willebrand disease (including perioperative management and treatment of major bleeding/major surgery) do not reference ADAMTS13 assay as a management tool. This absence is cited to indicate lack of evidence-based guidance supporting routine ADAMTS13 testing in the perioperative care of patients with Type 1 VWD.

Across multiple cited studies the authors repeatedly note methodological limitations that constrain clinical interpretation: many investigations are small and single-center, designs are often cross-sectional or observational, control groups may be limited or absent, and timing of specimen collection varies. These limitations are highlighted throughout the background summaries and are used by the policy authors to justify cautious interpretation and the need for larger, well‑designed confirmatory studies.

The excerpted background material does not list formal policy exclusions beyond the experimental/investigational items, but it does note potential confounding factors that could affect biomarker interpretation (for example, occasional venous thromboembolism such as portal thrombosis may influence the VWF:Ag/ADAMTS13:AC ratio). These possible confounders underscore the difficulty of applying ratio thresholds without careful clinical context.

The policy classifies the numerous indications enumerated under the Experimental and Investigational heading as lacking sufficient evidence of clinical utility. Consequently, all of those listed investigational uses are considered not medically necessary for coverage purposes until robust evidence demonstrates clinical benefit.

Evidence summaries in the policy describe studies in AML showing lower ADAMTS13 activity and higher VWF antigen in newly diagnosed patients and partial normalization after treatment, but the policy emphasizes that guideline sources (NCCN) do not endorse ADAMTS13 testing for AML management. Thus, while biologic associations are reported, guideline absence limits translation into routine clinical testing.

Within the provided excerpt there are no standalone statements framed as explicit 'not medically necessary' declarations beyond the experimental/investigational list; background case reports and study summaries describe clinical scenarios and outcomes but do not themselves create separate coverage determinations in this section.

The policy and cited reviews conclude that the routine clinical value of ADAMTS13, VWF, and their ratio as prognostic biomarkers remains unclear. Proteomic and other novel analytic approaches (including ADAMTS13) have not yet translated into standard clinical practice, and the authors call for further validation before these measures are adopted broadly for routine prognostication or management decisions.

Covered and Research Indications

inv-61: Assessing prognosis in persons with thrombotic thrombocytopenia (TTP)

Covered indication: Assessing prognosis in persons with thrombotic thrombocytopenic purpura (TTP).

Policy explicitly states ADAMTS13 assay is medically necessary for this indication.

inv-62: Evaluation of suspected thrombotic microangiopathy/TTP

Case report evidence: Evaluation of suspected thrombotic microangiopathy/TTP where ADAMTS13 activity measurement supported diagnosis and management (case report: ADAMTS13 activity 55% without anti-ADAMTS13 IgG; therapeutic plasma exchange was effective).

From case report summarized in chunk 36

inv-63: Assessment of ADAMTS13/VWF profiles in DIC and cerebral infarction research contexts to aid diagnosis/prognosis

Research contexts: Assessment of ADAMTS13, VWF and related measures (including VWF pro-peptide) in disseminated intravascular coagulation (DIC) and in cerebral infarction research to aid diagnosis and prognosis; altered ADAMTS13/VWF profiles and ratios have been reported as potentially informative for DIC prognosis and associated with cerebral infarction risk.

From chunks 22 and 28 summarizing observational studies

inv-64: Risk stratification for thrombotic events in systemic lupus erythematosus when combined with other laboratory parameters

SLE risk stratification: Use of ADAMTS13 activity, in combination with other laboratory parameters (VWF:Ag, multimeric structure, VCAM-1, antiphospholipid antibodies), to risk-stratify thrombotic events in systemic lupus erythematosus (SLE).ADAMTS13 activity categories >60%, 60–40%, <40% noted in study

From Martin-Rodriguez et al (2015) summarized in chunk 32

inv-65: Investigational/research uses and associations in diverse conditions (pancreatitis, SAH, NCIPH, IBD, stroke, cancer, TBI, HCC, AMI)

Investigational/research associations: Investigational or research uses and observed associations of ADAMTS13 and VWF in diverse conditions including: TMA following acute pancreatitis, subarachnoid hemorrhage, non-cirrhotic portal hypertension contexts, inflammatory bowel disease, stroke, various cancers, traumatic brain injury, hepatocellular carcinoma, acute myocardial infarction, and others. These uses are described in the literature but lack sufficient evidence for routine clinical utility.

Summarized from multiple background study chunks (36,55,56,66,69)

inv-66: Research and investigational biomarker use to assess disease severity, micro-thrombosis risk, treatment response, and outcomes (COVID-19, HCC, chronic hepatitis B, AMI)

Research biomarker use: Use of ADAMTS13 (activity and antigen), VWF:Ag, and their ratio as investigational biomarkers to assess disease severity, risk of micro-thrombosis, treatment response, and outcomes in conditions such as COVID-19 (severity, AKI), hepatocellular carcinoma (HAIC response and VEGF associations), chronic hepatitis B (HBeAg seroconversion prediction during entecavir therapy), and acute myocardial infarction progression. Evidence is preliminary and authors call for larger confirmatory studies.Study-specific thresholds reported in literature (e.g., VWF:Ag/ADAMTS13:AC >2.7 in HCC HAIC response; longitudinal timepoints in HBV study).

From chunks 66,56,69,55,72

inv-67: Assessment of ADAMTS13 activity and VWF:Ag where TMA or imbalance is suspected (diagnostic evaluation in TTP, prognostic research in COVID-19 and ACLF)

Diagnostic/prognostic assessment: Assessment of ADAMTS13 activity and VWF:Ag where a thrombotic microangiopathy or imbalance is suspected — including diagnostic evaluation in the TTP context and prognostic research in COVID-19 and acute-on-chronic liver failure (ACLF). Such assessments have been associated with AKI and severe COVID-19 outcomes and with ACLF prognosis in observational studies but require further validation.

From chunks 72 and 90

inv-68: Monitoring VWF/ADAMTS13 axis in pregnant women with COVID-19 for potential association with preterm delivery (observational evidence)

Pregnancy COVID-19 monitoring (observational): Monitoring the VWF/ADAMTS13 axis in pregnant women with COVID-19 has been associated with preterm delivery in an observational study; authors suggest monitoring might inform management but note limitations and call for further study.

From Grandone et al (2022) summarized in chunk 78

inv-69: Assessment of ADAMTS13 activity and VWF antigen in suspected TMA and prognostication in liver disease/ACLF; referenced ELISA methods and prognostic associations

ACLF prognostication: Assessment of ADAMTS13 activity and VWF antigen (measured by ELISA) and calculation of the VWF:Ag/ADAMTS13:AC ratio have been used in studies of suspected thrombotic microangiopathies and post-ACLF prognostication; higher VWF:Ag/ADAMTS13:AC (>9) was associated with lower cumulative survival in a post-ACLF cohort, but study limitations were noted.VWF:Ag/ADAMTS13:AC > 9 associated with lower survival

From chunks 90 and 91

Coding and Code Lists

Covered CPT Codes (if selection criteria met)CPTCovered

85397

Coagulation and fibrinolysis, functional activity, not otherwise specified (eg, ADAMTS-13), each analyte.

Other CPT codes referenced in CPBCPT

38204	Allogeneic hematopoietic stem cell transplantation.
38205	Allogeneic hematopoietic stem cell transplantation (range listed).
38208	Allogeneic hematopoietic stem cell transplantation (range listed).
38215	Allogeneic hematopoietic stem cell transplantation (range listed).
38240	Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor.
96413	Chemotherapy administration, intravenous infusion technique; up to 1 hour, single or initial substance/drug.
96415	Chemotherapy administration, intravenous infusion technique; each additional hour (List separately in addition to code for primary procedure).
96416	Chemotherapy administration, intravenous infusion technique; initiation of prolonged chemotherapy infusion (more than 8 hours), requiring use of a portable or implantable pump.
96417	Chemotherapy administration, intravenous infusion technique; each additional sequential infusion (different substance/drug), up to 1 hour (List separately in addition to code for primary procedure).

ICD-10 codes referenced as covered or not coveredICD-10

M31.10	Thrombotic microangiopathy, unspecified.
M31.11	Hematopoietic stem cell transplantation-associated thrombotic microangiopathy [HSCT-TMA].
M31.19	Other thrombotic microangiopathy.
A41.9	Sepsis, unspecified.
B18.0	Chronic viral hepatitis B with delta-agent.
B18.1	Chronic viral hepatitis B without delta-agent.
C18.0	Malignant neoplasm of colon.
C20	Malignant neoplasm of rectum.
C22.0	Liver cell carcinoma.
C43.0	Malignant melanoma of skin.

1–10 of 43

1/5

ICD-10 codes explicitly not covered for some indicationsICD-10Not Covered

K76.6

Portal hypertension (listed as ICD-10 not covered for CPB indications).

ADAMTS13 mutation testingmixedExperimental

ADAMTS13 mutation testing

No specific CPT code listed.

Covered CPT CodesCPT

No codes listed

ADAMTS13 activity level — severe vs moderate/mild

Severe deficiencyUndetectable ADAMTS13 activity — associated with inherited TTP and higher relapse risk

Moderate/mild deficiencyADAMTS13 activity approximately 10–40% of normal plasma value

Clinical implicationUndetectable activity with anti‑ADAMTS13 antibodies predicts higher likelihood of recurrent TTP episodes

High post‑operative drainage definition

High post‑operative drainage (CABG study)>= 1,000 ml within recorded post‑operative drainage measurement period

Associated predictorsPre‑operative low VWF:RCo and low fibrinogen were independent predictors; high ADAMTS13:Ag in highest quartile increased risk

Study contextDefined in Mazur et al (2014) in patients undergoing elective on‑pump CABG (n = 232)

ADAMTS13 activity categories (>60%, 60–40%, <40%)

ADAMTS13 > 60%Category representing relatively preserved activity (>60%)

ADAMTS13 60–40%Intermediate activity category (60% to 40%) associated with variable thrombotic risk

ADAMTS13 < 40%Low activity category (<40%) including levels associated with increased thrombotic events and TTP risk

VWF:Ag/ADAMTS13:AC ratio threshold (HAIC response)

VWF:Ag/ADAMTS13:AC > 2.7Associated with higher VEGF levels and worse response to hepatic arterial infusion chemotherapy (HAIC) in HCC patients

VWF:Ag/ADAMTS13:AC ≤ 2.7Lower ratio associated with lower VEGF and better HAIC response

Measurement methodADAMTS13 activity and VWF:Ag determined by ELISA in the referenced HCC study

VWF:Ag/ADAMTS13:AC ratio (>9) and survival in post‑ACLF

VWF:Ag/ADAMTS13:AC > 9Associated with significantly lower cumulative survival in post‑ACLF patients (HR 10.72 vs ≤9)

VWF:Ag/ADAMTS13:AC ≤ 9Lower ratio associated with higher cumulative survival in the post‑ACLF group

Study contextSingle‑center ACLF prognostic study (n = 101) measuring ADAMTS13:AC and VWF:Ag by ELISA

VWF:Ag/ADAMTS13:AC ratio — risk stratification (≤9 vs >9)

High‑risk thresholdVWF:Ag/ADAMTS13:AC > 9 — associated with lower survival in cirrhosis patients after ACLF

Lower‑risk groupingVWF:Ag/ADAMTS13:AC ≤ 9 — associated with comparatively better prognosis

LimitationsAuthors note single‑center design, small sample size, and potential confounding from VTE (e.g., portal thrombosis)

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization and Coding Requirements

Prior authorization: CPT 85397 (ADAMTS13 activity assay) is subject to prior authorization and is covered only when the policy selection/medical-necessity criteria are met. Claims should document the clinical indication that aligns with allowed ICD-10 codes (e.g., M31.10, M31.11, M31.19) and any selection criteria used to justify testing.

Affected code: CPT 85397 — Coagulation and fibrinolysis, functional activity (eg, ADAMTS-13)
Covered ICD-10 examples when criteria met: M31.10, M31.11, M31.19
Not-covered/Excluded ICD-10 examples called out: A41.9 and select infectious/hepatic codes (see policy)

Note

Authorization and Step-Therapy Notes

No explicit operational prior-authorization triggers, denial triggers, or step-therapy sequencing are stated in the background excerpts beyond the statement that coverage for CPT 85397 is conditioned on meeting selection criteria. The document does not specify automated authorization/denial rules or step-therapy requirements for ADAMTS13 testing.

No step therapy required or described for ADAMTS13 testing
No explicit prior-authorization process steps or denial criteria detailed in these chunks
Policy history and administrative dates present but do not define authorization triggers

Documentation Required

Documentation and Study Limitations

Documentation: Providers should include method and timing details and relevant baseline data when submitting claims or authorization requests. Study reports reference assay methods (eg, FRETS-VWF73, ELISA), index vs pre-/post- measurements, and baseline serum creatinine (SCr) when applicable; limited sample sizes and lack of baseline data were noted as study limitations.

Document assay method if available (eg, ELISA, FRETS-VWF73)
Include timing of specimen relative to clinical presentation and any pre- or post-treatment measurements
Provide baseline renal function (SCr) when AKI is a consideration — absence of pre-COVID SCr was a noted study limitation
Reference pertinent clinical study details as supportive documentation (eg, ADAMTS13 activity, VWF:Ag, VWF:Ag/ADAMTS13:AC ratio)

Billing Rule

Coverage Conditions and Limitations

Coverage scope and limitations: Coverage is specified for TTP-related indications when selection criteria are met; numerous other indications are considered experimental/investigational (eg, use as biomarker in COVID-19 for AKI prediction, various oncologic, hepatic, obstetric, and neurologic indications). UpToDate and NCCN guideline omissions for certain contexts were noted and may affect coverage scrutiny.

ADAMTS13 assay considered medically necessary for assessing prognosis in TTP
Multiple other indications are listed as experimental/investigational in the policy (see policy body)
Guideline absence: NCCN (AML) and UpToDate (VWD perioperative management) do not reference ADAMTS13 for some uses

Ordering and Provider Requirements

Note

Ordering requirements — no provider restrictions stated

No specific ordering-provider restrictions (such as specialist-only) are stated in the CPB; practitioners may order ADAMTS13 testing consistent with the policy's clinical indications.

Note

Ordering requirements — no explicit provider restriction; specialists included in studies

Background study excerpts include testing ordered in specialist contexts, but the policy does not impose explicit ordering-provider limitations.

Note

Ordering requirements — no clinician restrictions stated

The policy excerpts do not specify which clinicians may or may not order ADAMTS13 testing; no ordering clinician restrictions are provided.

Note

Ordering requirements — no provider restriction; genotyping discussed as risk tool only

Although ADAMTS13 genotyping is discussed as a potential pre-transplant risk assessment, the CPB does not require genotyping by specific providers nor limit ordering to particular specialties.

Note

Ordering requirements — no explicit ordering-provider restrictions described

Across the background summaries, there are no explicit statements restricting who may order ADAMTS13 testing; the document does not mandate specialist-only ordering.

Note

Ordering requirements — no restrictions specified in these chunks

The CPB and supporting excerpts do not impose ordering-provider restrictions; order ADAMTS13 testing when clinically indicated per the policy's covered indications.

Testing Frequency and Monitoring

ADAMTS13 assay (CPT 85397)

Test name/CPTADAMTS13 functional activity assay — CPT 85397

DescriptionCoagulation and fibrinolysis, functional activity, not otherwise specified (eg, ADAMTS‑13), each analyte

Coverage conditionListed as covered if selection criteria in the policy are met

Testing frequency limits — summary

Explicit frequency limitsNo explicit testing frequency limits or repeat‑intervals are provided in the cited sections

Study scheduling examplesSome studies reported measurements at specific timepoints (see other items), but policy does not set routine frequency limits

Implication for orderingFrequency should be guided by clinical indication and study protocols rather than a policy‑specified interval

Serial measurement schedule reported in Guo et al.

Longitudinal measurement schedule (Guo et al.)ADAMTS13 activity (ADAMTS13:AC) and VWF:Ag measured at baseline, 3, 12, 24, 36, and 60 months during 5‑year entecavir treatment

Clinical contextStudy of HBeAg‑positive chronic hepatitis B patients on entecavir (n = 114) assessing prediction of HBeAg seroconversion

Use caseDemonstrates longitudinal monitoring protocol used in research, not a mandated clinical frequency in the policy

Serial timing reported in AMI study

AMI serial measurementsADAMTS13, VWF, fibrinogen, and CRP were measured at admission, 3–4 days post‑AMI, and at 3‑month follow‑up

Study contextAl‑Masri et al. serial biomarker study in 80 AMI patients compared with 36 controls

ImplicationExample of short‑interval and medium‑term serial testing used in research settings

Studies — frequency limits not specified

Frequency limits in studiesNo study‑derived frequency limits or repeat testing intervals are specified as policy requirements

Documentation noteStudies vary in timing and often call for further research; policy does not impose standard repeat intervals

Provider guidanceOrder timing should be documented with clinical rationale when used serially for research or prognostication

Not Covered / Experimental Uses

Aetna lists an extensive set of biomarker, diagnostic, predictive, and monitoring uses for the ADAMTS13 assay and states these uses are not covered because they are considered experimental or investigational. The policy therefore does not cover ADAMTS13 testing for the enumerated items (items 1–42 and additional specified uses) outside of the managed, evidence‑based indications described elsewhere in the policy.

ADAMTS13 mutation testing specifically for non‑cirrhotic portal hypertension is identified as experimental/investigational and not covered for that indication. The policy lists ICD‑10 code K76.6 (portal hypertension) in relation to this exclusion.

The policy indicates that, despite reports of altered ADAMTS13 in AML, the National Comprehensive Cancer Network guideline for AML does not include ADAMTS13 testing as a management tool. As a result, routine ADAMTS13 testing for AML management is not supported by guideline-based practice and is not considered an established covered use.

The policy notes that UpToDate reviews on von Willebrand disease do not mention ADAMTS13 assay as part of perioperative management. This absence supports the policy’s view that ADAMTS13 testing does not have an established clinical role in VWD perioperative care.

The policy observes that VWF multimer analysis is technically demanding, time‑consuming, and not widely available in routine laboratories; method standardization is limited and results may be variable. For these practical and methodological reasons, multimer testing is not presented as a routine clinical test in the policy background.

Within the provided background excerpts there are no additional explicit 'not covered' test names or indications beyond those enumerated in the policy’s experimental/investigational and not covered sections; much of the remaining content summarizes study findings rather than listing new coverage exclusions.

Several background sections present evidence summaries and case reports but do not include formal not‑covered statements; those sections are presented as supporting clinical context rather than discrete coverage policy language.

Definitions and Key Terms

ADAMTS13 — definition and function

Definition — ADAMTS13A Disintegrin‑like And Metalloprotease with ThromboSpondin type 1 motif; a metalloproteinase that cleaves multimeric von Willebrand factor to limit platelet thrombogenesis

Physiologic roleRegulates size of VWF multimers and thus modulates platelet adhesion and thrombotic potential

Clinical relevanceSevere deficiency is implicated in thrombotic thrombocytopenic purpura (TTP); moderate reductions occur in other thrombotic/coagulopathic states

Thrombotic thrombocytopenic purpura (TTP)

TTP definitionThrombotic thrombocytopenic purpura (TTP): a thrombotic microangiopathy frequently associated with severe ADAMTS13 deficiency

Diagnostic nuanceADAMTS13 testing is not always required to diagnose TTP in the acute phase; clinical and laboratory heterogeneity exists

Prognostic useUndetectable ADAMTS13 activity and presence of anti‑ADAMTS13 antibodies predict higher relapse risk

ADAMTS13 activity — assay methods and interpretation

Assay methodsADAMTS13 activity commonly measured by functional assays such as FRETS‑VWF73 or other activity assays; ELISA used in several studies

InterpretationReduced activity correlates with thrombotic risk but is not entirely specific to TTP (can be reduced in DIC, sepsis, liver disease, post‑operative states)

ReportingActivity is reported as % of normal plasma or IU/dL depending on assay calibration

VWF:Ag — definition and role

VWF:Ag definitionVon Willebrand factor antigen measured by immunoassay; reflects circulating VWF protein levels

Clinical roleUsed alongside ADAMTS13 to assess hemostatic balance and risk of micro‑thrombosis

PathophysiologyElevated VWF with reduced ADAMTS13 activity increases propensity for platelet‑rich microthrombi formation

ADAMTS13 / VWF ratio — definition and applications

Ratio definitionThe ADAMTS13/VWF or VWF:Ag/ADAMTS13:AC ratio compares VWF protein level to ADAMTS13 activity as a biomarker of hemostatic imbalance

Use casesReported as a prognostic biomarker in COVID‑19, HCC (HAIC response), ACLF prognosis, and AKI risk in COVID studies

Measurement noteRatio calculations depend on assay units and methods; study thresholds are study‑specific

VWF:Ag/ADAMTS13:AC ratio — definition and reported correlations

VWF:Ag/ADAMTS13:AC ratio definitionThe ratio of von Willebrand factor antigen to ADAMTS13 activity, used as a prognostic biomarker in multiple studies

Reported correlationsHigher ratios associated with greater tumor angiogenesis/VEGF and worse chemotherapy response (HCC), and with worse survival in ACLF

Assay methods citedStudies measured ADAMTS13:AC and VWF:Ag by ELISA for ratio calculation

ADAMTS13:AC — activity measurement

ADAMTS13:AC termADAMTS13 activity measurement (ADAMTS13:AC) — used in longitudinal monitoring and prognostic studies

Methods reportedADAMTS13:AC measured by activity assays or ELISA in referenced longitudinal studies

Clinical examplesUsed in 5‑year entecavir study for CHB and in ACLF prognostic analyses

ADAMTS13 activity (ADAMTS13:AC) — ELISA measurement

ELISA measurementSeveral referenced studies measured ADAMTS13 activity (ADAMTS13:AC) by ELISA

Research useELISA‑based activity measures used for prognostic correlations in liver disease and HCC studies

Reporting caveatAssay method should be documented as it affects comparability across studies

VWF:Ag and VWF:Ag/ADAMTS13:AC ratio — measurement and prognostic use

VWF:Ag and ratio useVWF:Ag measured by ELISA and the VWF:Ag/ADAMTS13:AC ratio used as a prognostic biomarker in HCC, AMI, and other contexts

Temporal changesStudies report elevated VWF:Ag during acute events (AMI, COVID‑19) with variable recovery over follow‑up

Combined interpretationBoth absolute VWF:Ag and the ratio to ADAMTS13 activity inform on prothrombotic state rather than either alone

ADAMTS13 — metalloproteinase description

Metalloproteinase descriptionADAMTS13 is a metalloproteinase that specifically cleaves multimeric von Willebrand factor

Physiologic consequenceCleavage reduces pro‑thrombotic ultra‑large VWF multimers and limits platelet aggregation

Pathologic result of deficiencyDeficiency predisposes to microvascular platelet aggregation as seen in TTP

VWF:Ag/ADAMTS13:AC — ratio definition and prognostic use

Ratio termVWF:Ag/ADAMTS13:AC — ratio of von Willebrand factor antigen to ADAMTS13 activity used as a prognostic biomarker

Clinical correlationsHigher ratio associated with disease severity, worse treatment response (HCC), and poorer survival (ACLF)

Study dependenceThresholds and prognostic cutoffs are study‑specific and should be interpreted in that context

OpenPayer

ADAMTS13 Assay for Thrombotic Thrombocytopenic Purpura (TTP)

Coverage Criteria for ADAMTS13 Assay

Covered and Research Indications

Coding and Code Lists

Provider Actions, Prior Authorization, and Documentation

Ordering and Provider Requirements

Testing Frequency and Monitoring

Not Covered / Experimental Uses

Definitions and Key Terms

Background and Evidence Summary

Policy Revision History