Podcast Summary: Episode 132 - VTE Series: Approach to Hypercoagulable/Thrombophilia Testing

Released on April 2, 2025, by Rouleaux University Medical Center, "The Fellow on Call: The Heme/Onc Podcast" delves into the complexities of hematology and oncology with a focus on practical management approaches. In Episode 132, the hosts continue their Venous Thromboembolism (VTE) series by exploring hypercoagulable and thrombophilia testing alongside the discussion of anticoagulant reversal agents.

1. Introduction

The episode kicks off with the hosts, Ronak, Vivek, and Dan, setting the stage for an in-depth discussion on VTE management, specifically hypercoagulable testing and anticoagulant reversal agents.

• Ronak [00:24]: "Today we're moving on to discussions about hypercoagulable testing and also reversal agents for our commonly used anticoagulants."

2. Case Presentation

Dan introduces a clinical case to anchor the discussion:

• Dan [03:04]: "Last episode, we were talking about our 58-year-old guy with a DVT and PE in the setting of pancreatic cancer... discussing the utility of running additional tests to determine underlying prothrombotic conditions."

3. When to Order Hypercoagulable Testing

Vivek elaborates on the appropriate timing and necessity of hypercoagulable testing:

• Vivek [03:37]: "The overwhelming majority of the time when we're asked about running testing... the answer is, let's just sit tight. Not yet."

Key Points:

• Testing during the acute phase or while on anticoagulants is often inaccurate.
• Most results do not alter immediate management, typically leading to a standard anticoagulation regimen.

4. High-Risk and Low-Risk Thrombophilias

The hosts differentiate between high-risk and low-risk hereditary thrombophilias.

• Ronak [22:29]: "Factor V Leiden and the prothrombin gene mutation are both very common in the heterozygous state and are considered low-risk mutations."

4.1 High-Risk Conditions

• Antithrombin Deficiency:

  • Dan [19:24]: "Antithrombin 3 deficiency is the highest risk condition... requires antithrombin replacement for maximal anticoagulation effectiveness."

• Protein C and Protein S Deficiency:

  • Dan [19:24]: "Production is vitamin K dependent and can be falsely low on warfarin... increases the risk for warfarin skin necrosis."

4.2 Low-Risk Conditions

• Factor V Leiden and Prothrombin Gene Mutation:
  • Ronak [22:29]: "These are low-risk and have fewer implications for therapy unless in homozygous or compound heterozygous states."

5. Acquired Thrombophilias

Ronak expands on non-hereditary causes of hypercoagulability:

• Ronak [24:03]:
  • JAK2V617F Mutation: Associated with myeloproliferative neoplasms (MPN).
  • Paroxysmal Nocturnal Hemoglobinuria (PNH): Detected via flow cytometry.
  • Inflammatory Conditions: Such as Inflammatory Bowel Disease (IBD) and Nephrotic Syndrome.
  • Malignancy-Associated Hypercoagulability: Particularly in cancers like pancreatic cancer.

6. Conditions and Tests Not Recommended

Dan emphasizes certain tests that lack clinical utility:

• Dan [25:18]:
  • Tests to Avoid: PAI1, MTHFR mutation, homocysteine levels, elevated factor VIII.
  • Rationale: Lack of high-quality evidence linking these tests to meaningful clinical outcomes. For example, elevated homocysteine levels have not proven to affect recurrence rates when treated.

7. Cancer Screening in Unprovoked VTE

Vivek addresses the common query about cancer screening in patients with unprovoked thrombotic events:

• Vivek [27:02]: "We shouldn't be fishing for or over-proceduralizing our patients with PET scans or full-body CT scans without other symptoms."

Key Points:

• Recommended Approach: Age-appropriate cancer screenings (e.g., colonoscopy, mammography) rather than extensive, symptomless screenings.
• Rationale: Low yield in finding occult malignancies without other clinical indications.

8. Clinical Implications and Shared Decision-Making

The hosts stress the importance of individualized patient discussions:

• Vivek [09:04]: "We can start labeling patients with extra diagnoses, leading to unnecessary anxiety."
• Dan [15:23]: "Most patients with hypercoagulable tests don’t have test results that change management, so excessive testing can lead to confusion and unwarranted treatments."

9. Recap and Takeaways

Dan summarizes the key points, reinforcing the appropriate use of hypercoagulable testing:

• Dan [28:27]: "Most of the time when you're asked about hypercoagulable testing, it's not the appropriate time to do it... focus on high-risk underlying conditions that require beyond anticoagulation management."

Final Takeaways:

• **Avoid testing during acute VTE or while on anticoagulants unless it will change management.
• **Focus testing on unusual clot locations, strong family histories, and young patients.
• **Exclude low-yield tests to prevent unnecessary anxiety and medical interventions.
• **Adhere to standard cancer screening protocols without overreaching in asymptomatic patients.

10. Conclusion

Ronak wraps up the episode by highlighting the practical aspects of applying these insights in clinical settings:

• Ronak [30:52]: "Ask how the test will impact management. It's critical to provide that insight to your patient because from the patient's lens, more testing feels better, but that's not always the case."

The hosts tease upcoming episodes focusing on anticoagulant reversal agents and antiphospholipid antibody syndrome, encouraging listeners to stay tuned.

Notable Quotes:

• Vivek [03:37]: "Not yet. Because it's not going to change management."
• Ronak [22:29]: "Factor V Leiden and the prothrombin gene mutation... are considered low-risk mutations."
• Dan [25:18]: "We don't see a role for [PAI1, MTHFR, etc.] in clinical practice."
• Vivek [27:02]: "We shouldn't be fishing for... full-body CT scans on these patients."

Closing Remarks:

This episode serves as a comprehensive guide for healthcare professionals navigating the challenges of hypercoagulable and thrombophilia testing in VTE patients. By emphasizing evidence-based practices and the importance of tailored patient discussions, the hosts provide valuable insights that align with contemporary clinical standards.