Beyond the Thrombophilia Panel: Real-World Overuse, Limited Interpretability, and Poor Guideline Concordance in a Hematology Referral Cohort

Background: Hereditary thrombophilia testing is frequently performed outside guideline-supported indications, generating low-value results and diagnostic uncertainty. We evaluated the spectrum, laboratory validity, and appropriateness of thrombophilia testing in patients referred to hematology. Methods: This single-center retrospective cohort included 131 adults referred between September 2021 and November 2022 with a completed six-variant hereditary thrombophilia panel. Demographic, clinical, thrombotic, and laboratory data were reviewed, and testing appropriateness was assessed against the 2011 Turkish Society of Hematology guideline. Results: Ischemic stroke (25.2%), pulmonary embolism (21.4%), and recurrent pregnancy loss (16.0%) were the leading indications. Of 120 evaluable requests, only seven (5.8%) met guideline-supported criteria, and 42 (32.0%) were ordered during acute thrombosis. Factor V Leiden was associated with pulmonary embolism (48.6% vs. 22.1%, p = 0.003) and deep vein thrombosis (28.6% vs. 9.5%, p = 0.003), whereas ischemic stroke was less frequent among carriers (11.4% vs. 33.7%, p = 0.017). PAI-1, MTHFR c.1298A>C, and prothrombin G20210A showed no consistent associations. Of six low protein C results, only two were confirmed; none of eight low protein S results remained valid after timing and confirmation criteria were applied. Lupus anticoagulant was positive in 18 patients, yet only six underwent appropriately timed repeat testing, establishing four new antiphospholipid syndrome diagnoses. Conclusions: Most thrombophilia panels were ordered inappropriately, and test timing frequently compromised interpretability. Clinically meaningful information arose mainly from factor V Leiden and properly confirmed acquired thrombophilia testing. Targeted, indication-driven testing with strict attention to timing and confirmation should replace indiscriminate panel use.