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4Ts Score for Heparin-Induced Thrombocytopenia

Calculators  Hematology
4Ts is a clinical scoring system to differentiate patients with heparin induced thrombocytopenia (HIT) from those with other causes for thrombocytopenia.
Thrombocytopenia (Low blood platelet count)
Platelet count loss >50% and platelet nadir >=20 2
Platelet count loss 30–50% or platelet nadir 10-19 1
Platelet count loss<30% or platelet nadir <10 0
Timing of platelets count loss
Clear onset between 5–10 days or platelet loss ≤1 day (prior heparin exposure within 30 days) 2
Consistent with days 5–10 fall, but not clear; onset after day 10 OR fall ≤1 day (prior heparin exposure 30–100 days ago) 1
Platelet count decline <4 days without recent exposure 0
Thrombosis or other abnormality
New thrombosis OR skin necrosis; acute systemic reaction post-IV heparin bolus 2
New thrombosis OR skin necrosis; acute systemic reaction post-IV heparin bolus 1
None 0
Other causes for thrombocytopenia
None apparent 2
Possible 1
Definite 0
Result:

Background

Measured Factor
Pretest clinical score for HIT
Measured Factor Disease
  • Thrombosis
Measured Factor Detail
The calculation of a pretest clinical score for the diagnosis of heparin-induced thrombocytopenia involves factors like thrombocytopenia, timing of platelet count fall, thrombosis or other sequelae, and other causes for thrombocytopenia.
Speciality
Haematologist
Body System
Hematology
Measured Factor Low Impact
  • 4Ts Scores of 1-3 correspond to low probability of heparin induced thrombocytopenia (HIT).
Measured Factor High Impact
  • 4Ts Scores of 4-5, and 6-8 are considered to correspond to a intermediate and high probability of HIT, respectively.

Result Interpretation

Ranges Ranges
  • Critical Low: Less than 3
  • Critical High: More than 3
  • Normal: Less than 3
  • Normal Adult Male: Less than 3
  • Normal Adult Female: Less than 3
  • Normal Pediatric: Less than 3
  • Normal Neonate Female: Less than 3
  • Normal Geriatric Male: Less than 3
  • Normal Geriatric Female: Less than 3
Result Low Conditions
  • Low values indicate least probability of thrombosis.
Result High Conditions
  • Thrombosis
  • Venous thromboembolism
  • Risk of amputation or death
False Positive
  • Analytical interferences associated with the presence of non-specific antibodies in high-performance liquid chromatography serotonin release assay (HPLC-SRA) and immunoassay may lead to false positive results.
Test Limitations
Although the 4Ts score has an advantage in that it eliminates HIT without carrying out an HIT antibody test due to its high negative predictive values, some patients are reported to develop HIT even with a low 4Ts score. Some patients with positivity for anti-PF4/heparin antibodies proven by ELISA have been reported to be negative for platelet activation when tested using a functional assay, indicating that they do not develop clinical HIT. A discrepancy between the 4Ts score and PF4/heparin Ab has been experienced especially in critically ill patients.

Studies

Study Validation 1
Systematic review and meta-analysis to estimate the predictive value of the 4Ts in patients with suspected HIT has been performed in various studies in comparison to reference standards. A low probability 4Ts score appears to be a robust means of excluding HIT and patients with intermediate and high probability scores require further evaluation.
References: 2
Study Validation 2
A study analysed data of patients who underwent the heparin-induced platelet aggregation (HPA) test from 2006 to 2010 and compared diagnostic performance of the novel model HIT expert probability ('HEP'), which has been validated in a population mainly comprising surgical patients first, by 
the previously published model '4Ts' score. Clinical courses of the patients were also reviewed to ensure that HPA test results were accurate. There were 47 suspected HIT patients. The majority was from medical (70.2%) and/or critical  care (61.7%) units. The HEP score did not display better diagnostic performance than the 4Ts score for predicting HIT in our population.
References: 3
Study Validation 3
A retrospective study was conducted on 100 consecutive patients who were tested for HIT during their hospitalization at Hahnemann University Hospital (Philadelphia, PA) in 2009. Of the 100 patients analyzed, 72, 23, and 5 patients had 4T pretest probability scores of low, intermediate, and high, respectively. A positive HIT ELISA (optical density > 1.0 unit) was detected in 0 of 72 patients  (0%) in the low probability group, in 5 of 23 patients (22%) in the intermediate probability group, and in 2 of 5 patients (40%) in the high probability group. Fourteen (19%) of the 72 patients with a low pretest probability of HIT were treated with a direct thrombin inhibitor. Ten (71%) of the 14 patients in the low probability group treated with a direct thrombin inhibitor had a major complication of bleeding requiring blood transfusion support. In this retrospective study, a low 4T score showed 100% correlation with a negative HIT antibody assay. The study recommends incorporating the 4T scoring system into institutional core measures when assessing a patient with suspected HIT, selecting only patients with intermediate to high probability for therapeutic intervention, which may translate into reduced morbidity and lower health care costs.
References: 4
Study Additional 1
The study evaluated the clinical usefulness of the 4Ts score in the diagnosis of HIT in 104 critically ill patients  who were admitted to our intensive care unit and who underwent the antiplatelet factor 4/heparin complex  antibodies (PF4/heparin Ab) test with suspected HIT. The primary endpoint variable was the 4Ts score. The secondary endpoint variables were laboratory data, length of stay, and mortality, compared between the PF4/heparin Ab positive and negative groups. the outcomes of the study indicate discrepancy between the 4Ts score and PF4/heparin Ab. When HIT is suspected in critically ill patients, an immediate HIT antibody test and initiation of therapeutic management of HIT are required regardless of the 4Ts score.
References: 5
Study Additional 2
A study performed on 82 patients from multiple ICU settings who underwent laboratory testing for HIT were classified as low-, intermediate-, or high-risk patients based on retrospectively adjudicated 4Ts scores. These results were compared with platelet-factor 4 enzyme-linked immunosorbent assays (PF4 ELISAs), optical density (OD) values, and serotonin-release assays (SRAs) to assess the utility of the 4Ts score to rule out ICU-related HIT and reduce laboratory and drug expenditures. The study shows  that 4Ts scoring system appears to be an effective tool for predicting HIT in the ICU and could avoid significant drug and laboratory expenditures if implemented prospectively.
References: 6
Study Additional 3
A retrospective study reviewed records from cardiothoracic surgical patients whose serum was tested with both the serotonin release assay (SRA) and the PF4/heparin immunoassay from January 2007 through December 2010. The study assigned a high, intermediate, or low clinical "4Ts" probability score that quantifies thrombocytopenia, timing of platelet decrease, and thrombotic complications in each patient and further compared the clinical score and the PF4/heparin immunoassay against the "gold standard" diagnostic test, the SRA. The results of the study demonstrated that the use of the 4Ts clinical score combined with the PF4/heparin immunoassay for HIT diagnosis increases the sensitivity and specificity of HIT testing compared with the PF4/heparin immunoassay alone. Furthermore, with an intermediate 4Ts score and positive PF4/heparin antibody test, a confirmatory platelet activation assay such as the SRA is necessary.
References: 7

Authors

Lo GK
MD
Juhl D
MD
Professor, Department of immunology and transfusion medicine, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany
Research Interests: Transfusion medicine and haematology
Andreas Greinacher
MD, 1988
Associate member of the drug commission since 2004, Head of the Institute of Immunology and Transfusion Medicine at the University Hospital Greifswald, Germany
Research Interests: Transfusion medicine, hemostaseology
Expert in drug-induced immune reactions, diagnosis and therapy of immune-mediated and congenital thrombocytopenia

References

  1. 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(4):759-65.
  2. 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. 2012,15;120(20):4160-7
  3. Uaprasert N, Chanswangphuwana C, Akkawat B, Rojnuckarin P. Comparison of diagnostic performance of the heparin-induced thrombocytopenia expert probability and the 4Ts score in screening for heparin-induced thrombocytopenia. Blood Coagul Fibrinolysis. 2013 Apr;24(3):261-8.
  4. 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.
  5. Matsumura Y, Nakada TA, Oda S. Relationship between the 4Ts scoring system and the antiplatelet factor 4/heparin antibodies test in critically ill patients. Acute Med Surg. 2013 Dec 26;1(1):37-44.
  6. Pierce W, Mazur J, Greenberg C, Mueller J, Foster J, Lazarchick J. Evaluation of heparin-induced thrombocytopenia (HIT) laboratory testing and the 4Ts scoring system in the intensive care unit. Ann Clin Lab Sci. 2013 ;43(4):429-35.
  7. Demma LJ, Winkler AM, Levy JH. A diagnosis of heparin-induced thrombocytopenia with combined clinical and laboratory methods in cardiothoracic surgical intensive care unit patients. Anesth Analg. 2011 Oct;113(4):697-702.