I. How to Use

When to Use

  • Consider using the 4Ts scoring system to stratify patients’ risk for HIT in patients with thrombocytopenia who are currently or were recently on heparin-derived agents.

  • Patients with low probability for HIT do not need further testing for HIT.

  • Patients with intermediate or high probability for HIT should switch from heparin to a non-heparin anticoagulant while working up for HIT.

Pearls / Pitfalls

The 4Ts Score is a tool developed to help clinicians rule out heparin-induced thrombocytopenia (HIT) in patients who develop thrombocytopenia in a clinical setting. It helps differentiate who should receive HIT diagnostic testing.

  • The initial study included patients being evaluated for thrombocytopenia or suspected HIT in two clinical settings: inpatients at Hamilton General Hospital (HGH) in Canada and various clinicians in a variety of healthcare settings in Germany and Austria.

  • The study prospectively applied previously developed scoring systems using various clinical features of HIT.

  • The proposed scoring system consisted of four items, each scored as 0, 1, or 2 points.

  • The study used ≤3 points to define the low probability group (≤5%) for HIT, 4-5 points for the intermediate group, and 6-8 points for the high group.

  • Gold standard for diagnosis of HIT was either:

    • A platelet serotonin release assay (SRA) with ≥ 50% serotonin release and a positive PF4/polyanion-enzyme immunossay (EIA) (not a cutoff of > 0.40 OD), OR

    • A positive heparin-induced platelet activation (HIPA) test in at least 3 of 4 donor platelets.

  • Other causes of thrombocytopenia could include sepsis, recent cardiopulmonary bypass, medications, acute pulmonary embolism, end-stage renal disease, cirrhosis, or indwelling arterial devices.

Points to keep in mind

  • Scoring system criteria for HIT was slightly different between the 2 main sites.

  • The study used different testing algorithms to diagnose HIT, depending on the site.

  • One of the four components of their scoring system (“other causes for thrombocytopenia”) is subjective.

  • The 2 sites had statistically significant differences in HIT incidence for both the intermediate and high probability groups.

  • There is moderate interobserver variability in 4Ts score calculation.

  • Concerns exist regarding the 4Ts score application in daily practice given the low prevalence of HIT and reproduced sensitivity scores of 80-90%.

A subsequent review and meta-analysis of the 4Ts scoring system for HIT found that patients in the low-risk group had a negative predictive value of 0.998, irrespective of type of clinician, prevalence of HIT, or patient population.

Why to Use

Consider using the 4Ts scoring system to determine which patients with thrombocytopenia should receive additional diagnostic testing for HIT and in the interim should switch from a heparin-derived anticoagulant to a non-heparin anticoagulant.

II. Next Steps

Advice

The 4Ts score should not be the sole basis for care, and clinicians should use judgment and full clinical evaluation to guide management.

Management

  • Low Probability (score 0-3): HIT is extremely unlikely.

    • Do not order HIT antibody testing or functional assay.

    • Evaluate for other causes of thrombocytopenia and consult hematology if needed.

    • Continue or restart heparin if indicated.

  • Intermediate Probability (score 4-5): HIT is possible.

    • Discontinue heparin-derived anticoagulant and substitute with non-heparin anticoagulant.

    • Order HIT antibody (ELISA) only. Based on result, determine if functional assay (e.g., serotonin release assay) is needed to diagnose HIT.

    • Assess for thrombosis if HIT is diagnosed

    • Consider hematology consult.

  • High Probability (score 6-8): HIT is likely.

    • Discontinue heparin-derived anticoagulant and substitute with non-heparin anticoagulant.

    • Order HIT antibody testing (ELISA) only. Based on result, determine if functional assay (e.g., serotonin release assay) is needed to diagnose HIT.

    • Assess for thrombosis if HIT is diagnosed.

    • Consider hematology consult.

Critical Actions

Consider using the HEP score in conjunction with the 4Ts scoring system as an alternative evaluation tool prior to time-consuming antibody testing for HIT or empiric substitution of heparin for another anticoagulant. The HIT Expert Probability (HEP) score was developed based on expert opinion of 26 HIT experts and had better interobserver agreement than the 4Ts score.

Consider further laboratory evaluation for HIT or switching to a non-heparin derived anticoagulant in those patients that are above the screening threshold for HIT based on their 4Ts score.

III. Evidence

Evidence Appraisal

In 2018, the American Society of Hematology (ASH) guidelines on venous thromboembolism management and HIT most strongly recommended the use of the 4Ts score rather than clinical gestalt for estimating the probability of HIT. They also strongly recommended only ordering laboratory follow-up testing if HIT probability was intermediate or high based on moderate certainty of evidence.

Formula

Category 2 points 1 point 0 points
Thrombocytopenia Platelet count fall >50% AND platelet nadir ≥20 × 109 L−1 Platelet count fall 30%–50% OR platelet nadir 10–19 × 109 L−1 Platelet count fall <30% OR platelet nadir <10 × 109 L−1
Timing of platelet count fall Clear onset between days 5 and 10 OR platelet fall ≤1 day (prior heparin exposure within 30 days) Consistent with days 5–10 fall, but not clear (e.g. missing platelet counts) OR onset after day 10 OR fall ≤1 day (prior heparin exposure 30–100 days ago) Platelet count fall <4 days without recent heparin exposure
Thrombosis or other sequelae New thrombosis (confirmed) OR skin necrosis at heparin injection sites OR acute systemic reaction after intravenous heparin bolus Progressive or recurrent thrombosis or nonnecrotizing (erythematous) skin lesions or suspected thrombosis (not proven) None
Other causes for thrombocytopenia None apparent Possible Definite

Facts & Figures

  • ≤3 points: low probability for HIT (≤5% PPV in original study, <1% PPV in meta-analysis).

  • 4-5 points: intermediate probability (~11% PPV in original study, ~14% PPV in meta-analysis).

  • 6-8 points: high probability (~34% PPV in original study, ~64% PPV in meta-analysis).

Literature

Original/Primary

Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 2006;4:759–65.

Validation

Vatanparast R, Lantz S, Ward K, Crilley PA, Styler M. Evaluation of a pretest scoring system (4Ts) for the diagnosis of heparin-induced thrombocytopenia in a university hospital setting. Postgrad Med. 2012;124(6):36-42.

Other References (including meta-analyses, CPGs, and impact analyses)

Cuker A, Gimotty PA, Crowther MA, Warkentin TE. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood. 2012; 120(20):4160-7.

Cuker A, Arepally GM, Chong BH, Cines DB, Greinacher A, Gruel Y, Linkins LA, Rodner SB, Selleng S, Warkentin TE, Wex A, Mustafa RA, Morgan RL, Santesso N. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018;2(22):3360-3392.

Linkins LA, Bates SM, Lee AYY, Heddle NM, Wang G, Warkentin TE. Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study. Blood. 2015;126(5):597-603.

Larsen EL, Nilius H, Studt JD, Tsakiris DA, Greinacher A, Mendez A, Schmidt A, Wuillemin WA, Gerber B, Vishnu P, Graf L, Kremer Hovinga JA, Goetze JP, Bakchoul T, Nagler M. Accuracy of Diagnosing Heparin-Induced Thrombocytopenia. JAMA Netw Open. 2024;7(3):e243786.

Nagler M, Fabbro T, Wuillemin WA. Prospective evaluation of the interobserver reliability of the 4Ts score in patients with suspected heparin-induced thrombocytopenia. J Thromb Haemost. 2012;10(1):151-2.

Nagler M, Angelillo-Scherrer A. Diagnostic value of the 4Ts score for heparin-induced thrombocytopenia in the critically ill. J Crit Care. 2014;29(6):1126-7.

Cuker A, Arebpally G, Crowther MA, Rice L, Datko F, Hook K, Propert KJ, Kuter DJ, Ortel TL, Konkle BA, Cines DB. The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion. J Thromb Haemost. 2010;8(12):2642-50.