Case Report

Severe Acute Thrombocytopenia After Treatment with Tirofiban: A Case Series Approach

Register or Login to View PDF Permissions
Permissions× For commercial reprint enquiries please contact Springer Healthcare:

For permissions and non-commercial reprint enquiries, please visit to start a request.

For author reprints, please email
Information image
Average (ratings)
No ratings
Your rating


Glycoprotein IIb/IIIa inhibitors are an adjuvant therapy for the treatment of patients with acute coronary syndromes. The main adverse reactions are bleeding and thrombocytopenia in 1–2% of cases. A 66-year-old woman arrived at the emergency department with ST-elevation MI. The catheterisation lab was busy, so she received thrombolytic therapy. Coronary angiography revealed a 90% stenosis in the middle segment of the left anterior descending artery and Thrombolysis in MI 2 flow. Subsequent percutaneous coronary intervention showed abundant thrombus and a coronary dissection and it was necessary to insert five drug-eluting stents. Non-fractionated heparin and a tirofiban infusion were used. After the percutaneous coronary intervention, she developed severe thrombocytopenia, haematuria and gingivorrhagia, for which infusion of tirofiban was suspended. In follow-up, no major bleeding or subsequent haemorrhagic complications were identified. It is crucial to distinguish between heparin-induced thrombocytopenia and thrombocytopenia caused by other drugs. A high level of suspicion should be employed in these cases.

Disclosure:The authors have no conflicts of interest to declare.



Published online:

Informed Consent:

Written informed consent was obtained from all individuals included in the study.

Ethics Approval Statement:

This document was reviewed by the local bioethics committee and was approved.

Correspondence Details:Gian-Manuel Jiménez-Rodríguez, Interventional Cardiology Department, National Institute of Cardiology Ignacio Chávez, Juan Badiano No 1, 7 Col Sección XVI, Tlalpan, Mexico City 14080, Mexico. E:

Open Access:

This work is open access under the CC-BY-NC 4.0 License which allows users to copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.

Glycoprotein IIb/IIIa inhibitors (GPI) are an adjuvant therapy for the treatment of patients with acute coronary syndromes before, during and after percutaneous coronary intervention (PCI).1 The main adverse reactions are bleeding and thrombocytopenia in 1–2% of cases, the latter being a rare presentation but with potential catastrophic consequences. Although the pathogenesis of this phenomenon is not well established, it has been proposed that the main mechanism involved is the appearance of antibodies which react with the platelets coated with the IIb/IIIa antagonist and cause their destruction.1 Unlike other types of drug-induced thrombocytopenia, this complication can occur within hours of the patient’s first exposure to the drug.2

Tirofiban is a non-peptide molecule that reversibly inhibits fibrinogen-dependent platelet aggregation, with thrombocytopenia <100 × 103/mm3 occurring in 1.1–1.9% and severe thrombocytopenia (-50 × 103/mm3 platelets) in 0.2–0.5%.3

We report on a case of severe thrombocytopenia 6 hours after administration of tirofiban in a patient who underwent PCI in the context of acute coronary syndrome.

Case Report

A 66-year-old woman with a body weight of 90 kg and a history of smoking and hypertension arrived at the emergency department with an acute MI with ST-segment elevation (STEMI). The catheterisation lab was busy so she received thrombolytic therapy with tenecteplase 40 mg with ECG criteria of successful reperfusion at 90 minutes. Subsequently, a PCI via right radial access showed a left anterior descending artery (LAD) with a long lesion in the middle segment and a sub-occlusive site with thrombolysis in MI (TIMI) 2 distal flow. During the procedure, loss of distal flow was observed secondary to dissection and abundant thrombus, so it was necessary to insert five drug-eluting stents (Supplementary Materials Videos 1,2,3,4 and 5). Non-fractionated heparin IV 15,000 IU (divided into three doses of 5,000 IU throughout the procedure) was administered with activated coagulation time (ACT) during the procedure of 280 seconds and a final ACT of 240 seconds, and an infusion of tirofiban IV 12.5 mg in 250 ml of physiological saline at 18 ml/h for abundant load of thrombus without bolus. The total duration of the coronary intervention was 70 minutes.

Evolution of Platelets Over Time

Article image

Peripheral Blood Smear with Ethylenediaminetetraacetic Acid

Article image

When she was admitted to hospital, the patient had a normal blood count with a platelet count of 323 × 103/mm3 – a normal range is defined as 150–400 × 103/mm3 – and preserved renal function. Six hours after the PCI, she developed severe thrombocytopenia with a platelet count of 21 × 103/mm3 corroborated by two samples, accompanied by mild haematuria and gingivorrhagia, so the infusion of tirofiban was suspended and 2.5 mg of fondaparinux every 24 hours was continued. Hospital follow-up was maintained and the absence of major bleeding or subsequent haemorrhagic complications was confirmed.

Serial platelet count determinations were performed with the last count being 278 × 103/mm3 (Figure 1). Pseudothrombocytopenia was ruled out (Figure 2). An immunological test of heparin-dependent antibodies specific for platelet factor 4 (heparin-induced thrombocytopenia (HIT)-Ab was negative and ruled out HIT and a manual platelet count corroborated the presumptive diagnosis of thrombocytopenia secondary to use of tirofiban. She was discharged with no symptoms 4 days after the PCI.

Literature Search

We used PubMed to search for case reports related to tirofiban-induced thrombocytopenia. Nine case reports were found from January 2017 to September 2022; those studies that reported the use of tirofiban, dose, secondary events and number of platelets were included in our discussion with no language restriction (Table 1). Paediatric patients were excluded.


The use of tirofiban as an adjuvant in the treatment of acute MI has been shown to be associated with decreased rates of morbidity, mortality and re-infarction within 30 days after the intervention.4 In the current European Society of Cardiology guidelines, GPI should be considered as a bailout treatment if there is evidence of no reflow or a thrombotic complication (class IIa); the American College of Cardiology/American Heart Association recommends the use of GPI in acute coronary syndrome for patients with large thrombus burden, no reflow, or slow flow (class IIa).5–7 This patient had a high thrombotic burden and multiple overlapping stents, which are fundamental risk factors for thrombosis, so treatment with tirofiban was administered as an adjuvant therapy at the recommended infusion dose of 0.15 µg/kg/min.1,2 The vast majority of the cases reported using recommended doses between 0.1–0.15 µg/kg/min of tirofiban, mentioning mild-to-severe clinical manifestation of bleeding, from mild events, such as gingivorrhagia, petechiae and ecchymosis, up to serious events, such as bleeding from the upper digestive tract, as reported by Teke et al., rectal bleeding according to Ibrahim et al., pulmonary haemorrhage as described by Nettersheim et al., or even haemorrhagic shock secondary to haematemesis, showing that the clinical manifestations of thrombocytopenia can have a wide spectrum.8–10

Summary of Published Case Reports Found on PubMed Involving Tirofiban-induced Thrombocytopenia, January 2017–September 2022

Article image

Work-up of Thrombocytopenia after Catheterisation Lab Procedure

Article image

Others recommend the use of GPI in ACS when the patient is allergic or cannot tolerate P2Y12 inhibitors or in patients who are undergoing PCI that have received P2Y12 inhibitors but at higher risk for thrombus formation and in those who are allergic to aspirin.11

In the general setting, most of the cases with platelet counts <20 × 103/mm3 on admission may be due to bone marrow failure, severe coagulopathy or immune-mediated platelet consumption, but it is important to remember that thrombocytopenia is a possible complication of treatment with GPI during PCI.12 One study reported thrombocytopenia with a platelet count of less than 100 × 103/mm3 in 0.5% of those treated with tirofiban.13

There are multiple definitions of thrombocytopenia, with most studies defining mild thrombocytopenia as having a platelet count 90–100 × 103/mm3, severe thrombocytopenia <50 × 103/mm3, and profound thrombocytopenia <20 × 103/mm3.12 The antiaggregant effects of tirofiban are reversed a few hours after the end of the infusion.4 In our case, severe thrombocytopenia was demonstrated 6 hours after initiation of the tirofiban infusion at the aforementioned dose, which began to subside once the infusion was discontinued.

In practice, the diagnosis of drug-induced immune thrombocytopenia (DITP) is difficult, suspected mainly by clinical criteria and by laboratory tests that demonstrate the presence of drug-dependent platelet antibodies, these being the only methods that can demonstrate the diagnosis.14

To help establish the likelihood that a particular drug was the cause of thrombocytopenia, several clinical scoring systems have been developed. In 1982, Hackett et al. proposed the following criteria15:

  • Thrombocytopenia developed while the patient was taking the drug, resolved once the drug was discontinued and did not recur while the patient was off the drug;
  • Exclusion of other causes of thrombocytopenia;
  • Thrombocytopenia that recurs after drug readministration; and
  • In vitro test for drug-dependent platelet antibodies.16

In patients treated with multiple drugs, including heparin, it is important to differentiate HIT from other DITPs. Heparin-induced thrombocytopenia is a DITP that is usually secondary to heparin-dependent antibodies specific for platelet factor. Laboratory tests available to diagnose HIT include the identification of antibodies directed against platelet factor 4/heparin complexes, which were performed in this clinical case.14 Diagnosis of DITP requires routine platelet counts before and within 26 hours after initiation of treatment and every 8 hours until stopping, especially for patients receiving a GPI, allowing early diagnosis and the prevention of complications.3 In our case, platelet counts were documented with serial tests, which allowed us to make a reliable diagnosis.

Some patients who develop thrombocytopenia are asymptomatic or have only scattered petechial haemorrhages. Others experience bleeding at catheterisation sites, gastrointestinal or urinary bleeding, or haematoma formation. In those severe cases, platelet transfusion may be ineffective in the first hours after stopping GPI, so fibrinogen supplementation with cryoprecipitate or fresh frozen plasma might be considered.3

In the case of this patient, the bleeding event that led to the suspicion of thrombocytopenia was gingivorrhagia and haematuria. Supportive measures in case of profound thrombocytopenia may include IV immunoglobulins and corticosteroids.17 In Figure 3 we propose a work-up algorithm for thrombocytopenia after a catheterisation lab procedure based on the most common causes related to the standard medication.18


Early identification of thrombocytopenia events secondary to tirofiban can prevent the onset of serious bleeding complications. It is essential to rule out the rest of the potential causes of thrombocytopenia and discontinue the drug. Platelet levels quickly reach normal levels after withdrawal from the drug. The thrombotic and haemorrhagic risk must be weighed in all patients who have PCI with the intention of preventing complications.

Click here to view Supplementary Materials Videos 1,2,3,4 and 5

Clinical Perspective

  • The pathogenesis of tirofiban-related thrombocytopenia is not well established.
  • Most of the patients who receive tirofiban also receive heparin, so it is important to identify which of those is causing thrombocytopenia and terminate its use promptly.
  • Since tirofiban-related thrombocytopenia can appear very early after the drug’s infusion begins, it is essential to monitor the patient’s platelet count carefully in the first 624 hours.
  • Even in cases with profound thrombocytopenia, the risk of severe haemorrhage is low when it is recognised promptly.


  1. Rahman N, Jafary FH. Vanishing platelets: rapid and extreme tirofiban-induced thrombocytopenia after percutaneous coronary intervention for acute myocardial infarction. Tex Heart Inst J 2010;37:109–12.
  2. George JN, Aster RH. Drug-induced thrombocytopenia: pathogenesis, evaluation, and management. Hematology Am Soc Hematol Educ Program 2009;2009:153–8.
    Crossref | PubMed
  3. Aster RH, Curtis BR, Bougie DW, et al. Thrombocytopenia associated with the use of GPIIb/IIIa inhibitors: position paper of the ISTH working group on thrombocytopenia and GPIIb/IIIa inhibitors. J Thromb Haemost 2006;4:678–9.
    Crossref | PubMed
  4. Valgimigli M, Biondi-Zoccai G, Tebaldi M, et al. Tirofiban as adjunctive therapy for acute coronary syndromes and percutaneous coronary intervention: a meta-analysis of randomized trials. Eur Heart J 2010;31:35–49.
    Crossref | PubMed
  5. Ibanez B, James S, Agewall S, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2018;39:119–77.
    Crossref | PubMed
  6. Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Rev Esp Cardiol (Engl Ed) 2021;74:544.
    Crossref | PubMed
  7. Writing Committee Members. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2022;79:e21–129.
    Crossref | PubMed
  8. Teke HÜ, Teke D. Profound thrombocytopenia related with tirofiban: will it be enough to only stop medicine? Platelets 2013;24:335–7.
    Crossref | PubMed
  9. Ibrahim T, El Karak F, Araji A, El Rassy E. Tirofiban-induced thrombocytopenia occurring with Crohn’s disease. Case Rep Cardiol 2016;2016:4605139.
    Crossref | PubMed
  10. Nettersheim FS, Hohmann C, Pfister R, Michels G. Severe tirofiban-induced thrombocytopenia and thrombotic microangiopathy after percutaneous coronary intervention. Dtsch Med Wochenschr 2019;144:109–13. [In German]
    Crossref | PubMed
  11. Tummala R, Rai MP. Glycoprotein IIb/IIIa Inhibitors. In: StatPearls. Treasure Island, FL: StatPearls Publishing, 2022. (accessed 9 March 2023).
  12. Dasgupta H, Blankenship JC, Wood GC, et al. Thrombocytopenia complicating treatment with intravenous glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis. Am Heart J 2000;140:206–11.
    Crossref | PubMed
  13. Merlini PA, Rossi M, Menozzi A, et al. Thrombocytopenia caused by abciximab or tirofiban and its association with clinical outcome in patients undergoing coronary stenting. Circulation 2004;109:2203–6.
    Crossref | PubMed
  14. Vayne C, Guéry EA, Rollin J, et al. Pathophysiology and diagnosis of drug-induced immune thrombocytopenia. J Clin Med 2020;9:2212.
    Crossref | PubMed
  15. Hackett T, Kelton JG, Powers P. Drug-induced platelet destruction. Semin Thromb Hemost 1982;8:116–37.
    Crossref | PubMed
  16. Arnold DM, Nazi I, Warkentin TE, et al. Approach to the diagnosis and management of drug-induced immune thrombocytopenia. Transfus Med Rev 2013;27:137­–45.
    Crossref | PubMed
  17. Tempelhof MW, Benzuly KH, Fintel D, Krichavsky MZ. Eptifibatide-induced thrombocytopenia: with thrombosis and disseminated intravascular coagulation immediately after left main coronary artery percutaneous coronary angioplasty. Tex Heart Inst J 2012;39:86–91.
  18. Tempelhof MW, Rao SV. Thrombocytopenia in PCI Patients. Cardiac Interventions Today January/February 2008. (accessed 25 January 2023).
  19. Christen JR, Soubrier C, Martinez E, et al. Long-lasting thrombocytopenia induced by glycoprotein IIb/IIIa inhibitor. Rev Med Interne 2017;38:769–73. [In French]
    Crossref | PubMed
  20. Meghrajani V, Sabharwal N, Namana V, et al. A case of hyperacute severe thrombocytopenia occurring less than 24 hours after intravenous tirofiban infusion. Case Rep Hematol 2018;2018:4357981.
    Crossref | PubMed
  21. Liu YY, Dong QT, Guo YL, et al. Tirofiban-induced severe thrombocytopenia. Am J Ther 2019;26:e659–61.
    Crossref | PubMed
  22. Patti R, Sinha A, Rodriguez D, et al. Severe thrombocytopenia due to intravenous tirofiban therapy. Am J Ther 2019;26:e534–7.
    Crossref | PubMed
  23. Rawala MS, Ahmed AS, Posina K, Sundaram V. Tirofiban induced thrombocytopenia: a rare but severe adverse effect. J Community Hosp Intern Med Perspect 2020;10:171–3.
    Crossref | PubMed
  24. Wang S, Sawalha K, Khan A. An unusual case of drug-induced thrombocytopenia. J Investig Med High Impact Case Rep 2020;8:2324709620947891.
    Crossref | PubMed
  25. Abdeladim S, Elharras M, Elouarradi A, et al. Thrombocytopenia induced by glycoprotein (GP) IIb-IIIa antagonists: about two cases. Pan Afr Med J 2021;38:9.
    Crossref | PubMed
  26. Gulati A, Tiwari A, Shetty V, et al. Tirofiban: a rare cause of thrombocytopenia in a patient undergoing percutaneous coronary intervention. Cureus 2021;13:e18217.
    Crossref | PubMed