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Heparin-Induced Thrombocytopenia Differential Diagnoses

  • Author: Sancar Eke, MD, FASN; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
 
Updated: Oct 17, 2015
 
 

Diagnostic Considerations4Ts scoreHIT expert probability scoreOther problems to be considered

Diagnosis of heparin-induced thrombocytopenia (HIT) can be challenging, and both underdiagnosis and overdiagnosis pose potential dangers. Failure to diagnose HIT increases the risk of thrombosis, amputation, or death, while misdiagnosis can result in major hemorrhage (in thrombocytopenic patients treated with alternative anticoagulants) or thrombosis (if heparin treatment is suspended unnecessarily).[33] Consequently, pretest scoring systems have been devised to guide diagnosis of HIT.

The 4Ts is a pretest clinical scoring system for HIT that is widely used in clinical practice.[33] See the Table below. The title refers to four characteristics of HIT:

  • Thrombocytopenia
  • Timing of thrombocytopenia relative to heparin exposure
  • Thrombosis or other sequelae of HIT
  • Likelihood of other (oTher) causes of thrombocytopenia

Table. 4Ts score[31, 34] (Open Table in a new window)

Feature Score
2 points 1 point 0 points
Thrombocytopenia >50% fall



and



platelet nadir 20-100 × 109/L



30%-50% fall



or



platelet nadir 10-19× 109/L



>30% fall



or



platelet nadir < 10× 109/L



Timing of platelet count fall Clear onset on day 5-10, or =1 d if heparin exposure within past 30 d Consistent with day 5-10 fall, but not clear (eg, missing platelet counts); onset after day 10; or fall = 1 day if heparin exposure 30-100 days ago Platelet count fall =4 d without recent heparin exposure
Thrombosis or other sequelae New thrombosis (confirmed); skin necrosis; acute systemic reaction after IV UHF bolus Progressive or recurrent thrombosis; erythematous skin lesions; thrombosis suspected but not proven None
Other causes of thrombocytopenia None apparent Possible Definite

Total scores and corresponding probability of HIT are as follows:

  • 0-3: Low probability
  • 4-5: Intermediate probability
  • 6-8: High probability

A systematic review and meta-analysis by Cuker and colleagues found that a low-probability 4Ts score was a robust means of excluding HIT, with a negative predictive value of 0.998 (95% confidence interval [CI], 0.970-1.000). These researchers proposed that in patients with a low-probability 4Ts score, it may be possible to exclude HIT without further laboratory testing and continue heparin.[33]

Cuker and colleagues reported that the positive predictive value of an intermediate 4Ts score was 0.14 (95% CI, 0.09-0.22) and that of a high-probability score was 0.64 (95% CI, 0.40-0.82).[33] In other studies, the 4Ts model has demonstrated a positive predictive value of 9%–17%.[35]

Furthermore, a retrospective study in surgical intensive care unit patients by Berry and colleagues found that 8.6 % of patients with low-probability 4Ts scores were positive for HIT on laboratory testing, and 57% of patients with high-probability scores of 6-8 were HIT negative. These researchers concluded that testing or treatment for HIT should not depend on the 4Ts score alone.[36]

The HIT expert probability score (HEP) is a more detailed system developed to improve on the diagnostic utility of the 4Ts score. Testing in a validation cohort showed that the HEP model was 100% sensitive and 60% specific for determining the presence of HIT, and demonstrated better correlation with serologic HIT testing and better interobserver agreement than the 4Ts score. Nevertheless, the researchers cautioned that prospective multicenter validation is warranted.[35]

Other conditions that may be considered in the differential diagnosis of HIT include the following:

  • Septicemia with disseminated intravascular coagulation (DIC)
  • Liver disease with hypersplenism
  • Other medications
  • Immune Thrombocytopenia (ITP)
  • Other thrombocytopenic disorders (eg, posttransfusion purpura)
  • Hemodilution (eg, following massive blood transfusions)

Medications known to cause thrombocytopenia include the following:

  • Platelet glycoprotein (gp) IIb/IIIa inhibitors (eg, abciximab,eptifibatide, tirofiban)
  • Quinine
  • Quinidine
  • Sulfonamides (sulfa drugs)
  • Sulfalike drugs
  • Chlorothiazide
  • Chloroquine
  • Rifampicin
  • Gold salts

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Sancar Eke, MD, FASN Physician in Nephrology and Hypertension, Washington

Sancar Eke, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology, American Society of Transplantation, American Society of Diagnostic and Interventional Nephrology

Disclosure: Nothing to disclose.

Coauthor(s)

Sarah K May, MD Consulting Staff, Department of Hematology-Oncology, Caritas Carney Hospital, Commonwealth Hematology-Oncology PC

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Srikanth Nagalla, MBBS, MS, FACP Director, Clinical Hematology, Cardeza Foundation for Hematologic Research; Assistant Professor of Medicine, Division of Hematology, Associate Program Director, Hematology/Medical Oncology Fellowship, Assistant Program Director, Internal Medicine Residency, Jefferson Medical College of Thomas Jefferson University

Srikanth Nagalla, MBBS, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Nothing to disclose.

Additional Contributors

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

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Ultrasonographic image of a deep vein thrombosis (DVT).
Sequential images demonstrate treatment of iliofemoral deep venous thrombosis due to May-Thurner (Cockett) syndrome. Far left: View of the entire pelvis demonstrates iliac occlusion. Middle left: After 12 hours of catheter-directed thrombolysis, an obstruction at the left common iliac vein is evident. Middle right: After 24 hours of thrombolysis, a bandlike obstruction is seen; this is the impression made by the overlying right common iliac artery. Far left: After stent placement, image shows wide patency and rapid flow through the previously obstructed region. Note that the patient is in the prone position in all views. (Right and left are reversed.)
Ventilation-perfusion scan. Left image: Posterior view of normal findings on ventilation-perfusion scan. Right image: Posterior view of a perfusion scan that reveals a perfusion defect in the left upper quadrant. The defect in the middle of the image is due to the position of the heart.
Helical computed tomography scan of the pulmonary arteries. A filling defect in the right pulmonary artery is present, consistent with a pulmonary embolism.
Table. 4Ts score [31, 34]
Feature Score
2 points 1 point 0 points
Thrombocytopenia >50% fall



and



platelet nadir 20-100 × 109/L



30%-50% fall



or



platelet nadir 10-19× 109/L



>30% fall



or



platelet nadir < 10× 109/L



Timing of platelet count fall Clear onset on day 5-10, or =1 d if heparin exposure within past 30 d Consistent with day 5-10 fall, but not clear (eg, missing platelet counts); onset after day 10; or fall = 1 day if heparin exposure 30-100 days ago Platelet count fall =4 d without recent heparin exposure
Thrombosis or other sequelae New thrombosis (confirmed); skin necrosis; acute systemic reaction after IV UHF bolus Progressive or recurrent thrombosis; erythematous skin lesions; thrombosis suspected but not proven None
Other causes of thrombocytopenia None apparent Possible Definite
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