In this episode of Hospital Medicine Unplugged, we demystify inpatient thrombophilia workups—why not to test now, who (rarely) to test later, and how to time it so results actually matter.

We start with the do-firsts: treat the clot (full-intensity anticoagulation), document provoking factors, and plan follow-up. Thrombophilia status does not change acute management.

Why routine inpatient testing is discouraged:
• Low clinical yield in the hospital; results rarely alter immediate care.
• Distorted labs during acute thrombosis/illness or on anticoagulants → false positives/negatives (protein C/S, antithrombin, antiphospholipid tests).
• Cost + harm: overdiagnosis, unnecessary anxiety, and inappropriate long-term anticoagulation.
• Guidelines agree: ASH 2023 recommends against routine inpatient testing for acute VTE.

Who to actually consider (selectively) and usually as an outpatient:
• Young patients with VTE (<40–50).
• Unprovoked events or recurrent VTE.
• Unusual sites (cerebral/splanchnic/portal).
• Strong family history of early VTE.
• Pregnancy/postpartum or estrogen-associated VTE—only if results would change future management.

Timing that keeps you out of trouble:
• Defer most testing until after the acute phase and off anticoagulation (often around completion of initial therapy, ~3 months).
• APS requires persistent positivity ≥12 weeks apart; avoid testing during intercurrent illness or while anticoagulated if it will confound assays.
• If you must assess hereditary defects early (rare): favor DNA tests (FVL, prothrombin G20210A) over clot-based assays that DOACs/heparin can skew.

What to test (focused—not a fishing expedition):
• Hereditary: factor V Leiden, prothrombin G20210A, antithrombin, protein C, protein S (use functional assays; confirm hereditary deficiency later as needed).
• Acquired: antiphospholipid syndrome panel (lupus anticoagulant, anticardiolipin, anti-β2GP1) with correct timing.
• Do NOT order MTHFR, factor VIII/IX/XI levels, PAI-1, or broad “hypercoagulable panels”—they don’t guide care.

Interpretation pitfalls to dodge:
• Warfarin ↓ protein C/S → false “deficiency.”
• Heparin can affect antithrombin and clot-based tests.
• DOACs interfere with many clot-based assays (APC resistance, LA).
• Acute phase, liver disease, nephrotic syndrome, pregnancy/estrogen can lower natural anticoagulants without heredity.
• Always contextualize with provocation status, family history, and timing.

Consult the pros:
• Hematology input before ordering improves appropriateness, targeting, and counseling—and prevents waste.

A practical hospital bundle that works:

1. Default: no inpatient thrombophilia panel for acute VTE.

2. EHR guardrails: hard-stops or best-practice alerts that route orders to hematology.

3. Document an outpatient plan (who/when/what to test) at discharge.

4. If testing later: specify off-anticoagulation timing, which assays, and how results might change therapy (e.g., indefinite anticoagulation in high-risk defects like antithrombin deficiency or triple-positive APS).

5. Educate patients: results often won’t change today’s treatment; testing aims to inform long-term risk and family planning.

Bottom line: Don’t shotgun thrombophilia tests during admission. Treat the clot, identify provoking factors, and schedule targeted, well-timed outpatient testing—preferably with hematology—so results are reliable, actionable, and worth the poke.