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Left ventricle thrombus (LVT) remains an important and potentially devastating complication of acute myocardial infarction (MI). Advances in timely reperfusion and neurohormonal therapies have reduced its incidence, yet LVT increases the risk of systemic embolization, cerebrovascular events, and disability.[1] Despite these risks, there is a scarcity of randomized clinical trials to guide the management of LVT; therefore, current strategies are mainly informed by expert consensus and observational data with inherent limitations for treatment decisions.

The 2022 American Heart Association (AHA) scientific statement on LVT management offers practical recommendations on diagnosis, management, and treatment in diverse clinical settings.[2] It highlights the importance of anticoagulation for at least 3 months, and shared equipoise for the use of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA), although subsequent clinical trials and their pooled analyses showed the viability of DOAC therapy.[3] Repeat imaging is of importance, as it helps guide the decision and type of anticoagulation. In clinical scenarios where there is a persistence in LVT, a trial of an alternative anticoagulant or continued anticoagulation may be reasonable. However, there is very limited knowledge of additional tests that may inform such decisions. The routine testing for inherited thrombophilia is not included in the current guidelines, nor is it mentioned in the 2022 AHA statement[2] for patients with LVT after MI. In addition, testing in arterial thrombosis, in particular LVT, has not historically been considered high yield,[4] although data are weak and lacking.

In this issue of Thrombosis and Haemostasis, the study by Mroz et al[5] addresses a clinical gap in our understanding of LVT; whether inherited thrombophilia influences thrombus resolution and may help inform us about the type or duration of treatment. The authors studied a cohort of 148 consecutive patients with acute MI and LVT referred for further evaluation. The study showed that nearly one-quarter had at least one form of inherited thrombophilia positivity, including Factor V Leiden (52.9%), prothrombin G20210A variant (26.5%), protein C deficiency (8.8%), and protein S deficiency (11.8%). Carriers of thrombophilia demonstrated significantly higher rates of persistent LVT after 3 and 6 months of oral anticoagulation compared to noncarriers (73.5% vs 43.9% at 3 months, 58.5% vs 21.1% at 6 months), associations that persisted after multivariate regressions.[5] Although not powered for statistical significance, there was a higher number of patients on DOAC than warfarin at first diagnosis of persistent LVT (81.8% vs 18.2%, respectively).[5]

These findings add much-needed information in clinical scenarios for persistent LVT. Thrombophilia is a largely overlooked risk modifier or determinant for therapy intensification. The present study by Mroz et al,[5] suggests that a subgroup of patients, those with inherited hypercoagulable abnormalities, may be predisposed to refractory thrombi or thrombi that are less likely to resolve with conventional therapies (duration and dosage) of anticoagulation.

Thus, this study raises further management considerations. Should thrombophilia testing be encouraged in patients with persistent LVT after a course of anticoagulation? Should targeted testing be completed in patients with persistent thrombi after appropriate treatment? If thrombophilia testing is positive, would it alter the choice of anticoagulation and treatment duration?

While the study powerfully poses these questions and may help guide clinicians in equivocal scenarios to consider the merits of treatment alternatives, the findings should be interpreted in the right context. First, this was not a designed comparative effectiveness study. Accordingly, it does not directly guide treatment choices. Second, the small sample size and wide confidence intervals limit the strength of inferences. Third, recognizing the race and ethnic implications in thrombophilia test results, replication in more diverse cohorts will improve the external validity. Finally, testing for nongenetic thrombophilia, including antiphospholipid antibodies, may merit consideration in the right context.[6]

There is an increasing drive toward precision medicine. In venous thrombosis events, although routine testing is not recommended,[7] testing for inherited thrombophilia may result in an alteration in duration of treatment and risk counseling. Whether a similar paradigm should be considered for persistent LVT remains to be established. The current study supports the hypothesis that the presence of an inherited hypercoagulable state may influence thrombus behavior beyond the initial insult,[5] as an acute MI event, challenging the notion of a fixed one-size-fits-all treatment duration.

It is important to recognize the lack of high-level randomized evidence in LVT management. Prospective trials comparing anticoagulant strategies such as extended duration, treatment intensification, or DOAC vs VKA, in patients with persistent LVT or by thrombophilia subtype ([Fig. 1]; [Table 1]) could provide further answers and refine current recommendations. Until such data becomes available, incorporating thrombophilia testing into clinical decision-making should be approached with caution.

Fig. 1 Inherited thrombophilia: laboratory testing and findings. Testing should not be completed in the acute setting. Assays may interact with anticoagulants and should be held or removed based on local lab guidance. APC, activated protein C; aPTT, activated partial thromboplastin time; FVIII, factor VIII; dRVVT, dilute Russell's venom time; PCR, polymerase chain reaction. (Created in BioRender. Ujueta F [2026] https://BioRender.com/2e48r4x). Table 1 Inherited thrombophilia: laboratory testing and findings

Thrombophilia type

Gene/defect

Initial laboratory test(s)

Confirmatory test

Arterial thrombotic risk

Factor V Leiden (FVL)

F5 gene mutation (Arg506Gln) → APC resistance

APC resistance assay

PCR-based genetic testing for FVL mutation

No clear independent association; minimal, if any, increased risk

Prothrombin G20210A mutation

F2 gene mutation → increased prothrombin levels

Prothrombin activity

PCR-based genetic testing

No consistent association

Antithrombin deficiency

SERPINC1 mutation

Antithrombin activity assay

Antigen assay (to distinguish type I vs II)

Limited evidence for independent risk

Protein C deficiency

PROC mutation

Protein C activity assay

Antigen assay (type I vs II)

Possible risk in selected families

Protein S deficiency

PROS1 mutation

Free protein S antigen ± activity

Repeat testing of anticoagulation

Weak association

Dysfibrinogenemia (rare)

Fibrinogen gene variants

Functional fibrinogen assay

Genetic testing

Case reports, minimal evidence

Elevated factor VIII (familial tendency)

Multifactorial

Factor VIII activity level

Repeat testing after 3 mo

Minimal evidence, no clear causal association

Antiphospholipid antibodies

Acquired autoimmune disorder

Lupus anticoagulant testing (dRVVT, aPTT-based assays); anticardiolipin IgG/IgM; anti-β2 glycoprotein I IgG/IgM

Persistent positivity ≥ 12 wk + clinical criteria

Strong association, especially in triple-positive antibodies

Publication History

Received: 03 March 2026

Accepted: 04 March 2026

Article published online:
16 March 2026

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