HIT – 4T Score

The 4T score was first proposed by Warkentin and Greinacher in 2006 as a means to differentiate patients with HIT from those with other reasons for thrombocytopenia. In their paper, they made the following observations:

  • There are several potential explanations for thrombocytopenia in a patient receiving heparin besides HIT.
  • Although there are sensitive assays available to detect pathogenic HIT antibodies, major limitations remain:
    • Test results are not always available in a timely fashion.
    • Tests often detect non-pathogenic antibodies, causing diagnostic uncertainty.
  • Decision to stop heparin, or to substitute heparin with an alternative anticoagulant, can be problematic:
    • Simply stopping heparin in a patient with HIT is frequently complicated by thrombosis.
    • Conversely, substituting heparin with an alternative anticoagulant, such as lepirudin or argatroban, in a patient who does not have HIT is expensive and could be associated with major bleeding.

They then went on to write:

Based on these considerations, it could be useful to have a clinical scoring system that has a high-negative or -positive
predictive value (or, ideally, both) for diagnosis of HIT. Here, we provide evidence that a clinical scoring system yielding a low score has high-negative predictive value in assessing patients with suspected HIT.

A systematic review and meta-analysis on the predictive value of the 4T scoring system for HIT was published in 2012:

  • Based on thirteen studies, collectively involving 3068 patients
  • The negative predictive value of a low probability 4Ts score was 0.998 (95% CI, 0.970-1.000) and remained high irrespective of:
    • The party responsible for scoring
    • The prevalence of HIT
    • The composition of the study population
  • The positive predictive value of an intermediate and high probability 4Ts score was 0.14 (0.09-0.22) and 0.64 (0.40-0.82), respectively.
  • A low probability 4Ts score appears to be a robust means of excluding HIT. Patients with intermediate and high probability scores require further evaluation.

What are the T’s in the 4T score?

Let’s take a closer look at the 4T score:

Parameter2 points1 point0 pointsComments
Thrombo-
cytopenia
Platelet count fall > 50% AND platelet nadir ≥ 20 × 109 L−1Platelet count fall 30%–50% OR platelet nadir 10–19 × 109 L−1Platelet count fall < 30% OR platelet nadir < 10 × 109 L−1Fall from highest platelet count that immediately precedes the putative HIT-related platelet count fall. 95% of cases of HIT are reported to develop in temporal association with heparin therapy; typically > 50% platelet count fall, but not to levels < 20 × 10 9 /L; only a few patients show 30%-50% platelet count fall; typical nadir is 40-80 × 109/L, with median of 55 × 109/L.
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 exposureDay 5 to 10 for initial platelet count fall with day 0 representing first heparin exposure; earlier fall if patient exposed to heparin with previous 30 days. Days are rounded off. For example, day 4.3 would count as day 4.
Thrombosis or other sequelae

New thrombosis (confirmed) OR skin necrosis at heparin injection sites OR acute systemic reaction after intravenous heparin bolusProgressive or recurrent thrombosis or non-necrotizing (erythematous) skin lesions or suspected thrombosis (not provenNone
Other causes for thrombocytopeniaNone apparentPossibleDefinite

Scoring 0, 1, or 2 points for each of 4 categories, maximum possible score = 8:

  • Low score 0-3 points
  • Intermediate score 4-5 points
  • High score 6-8 points

Low 4Ts score may rule out HIT but high 4Ts score may not be sufficient to diagnose HIT.

The 4T score is used to estimate the pretest probability of having heparin-induced thrombocytopenia (HIT). The following table shows the negative and positive predictive values of the 4T score for diagnosis of HIT:

NPV, negative predictive value; PPV, positive predictive value

As shown below, the results of the 4T score determine the course of action with regard to further investigation (immunoassay) and management (continue or stop heparin). If heparin is stopped, an alternative non-heparin anticoagulant must be started.