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.

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.

ADAMTS13 is a metalloprotease that cleaves multimeric von Willebrand factor; deficiency is implicated in thrombotic thrombocytopenic purpura (TTP). The policy frames this biology as the rationale for the one established, evidence‑based covered use: ADAMTS13 assay for assessing prognosis in persons with TTP, while other proposed biomarker and diagnostic roles remain investigational.

The policy includes background literature summaries that describe associations of ADAMTS13 and VWF measurements with a variety of clinical conditions. These background sections provide context for the coverage decisions but do not independently create new coverage rules; they are cited to explain why many uses remain investigational.