Tirofiban-induced hyper-acute severe thrombocytopenia and anemia: the first known report in a Native American / American Indian from the capital of The Cherokee Nation, with a brief review of the literature by Prashant Kaushik in Journal of Clinical Case Reports Medical Images and Health Sciences

 Tirofiban-induced hyper-acute severe thrombocytopenia and anemia: the first known report in a Native American / American Indian from the capital of The Cherokee Nation, with a brief review of the literature by Prashant Kaushik in Journal of Clinical Case Reports Medical Images and Health Sciences

Abstract

 Glycoprotein IIb/IIIa inhibitors are critical post-percutaneous coronary artery interventions for preventing thrombus formation. While oral agents are often first-line, there is a significant delay in achieving platelet inactivation as firstpass metabolism is required to obtain an active metabolite. Intravenous antiplatelet medications such as glycoprotein IIb/IIIa inhibitors have a niche role in providing platelet inactivation from the time of infusion. Typically, most patients undergo tirofiban infusion without difficulty; however, some cases have been linked to varying degrees of thrombocytopenia, which can develop immediately post-infusion or several days later. Though a mechanism for tirofiban-induced thrombocytopenia has been postulated, it has not been proven. Here, we present the first case of acute severe tirofiban-induced thrombocytopenia and anemia in a Native American / American Indian from the capital of the Cherokee Nation.

Case Report

 The patient is a 69-year-old Native American / American Indian male with a previous medical history significant for coronary artery disease status post four drug-eluting stents who presented to the outpatient cardiology clinic for cardiac clearance for an upcoming elective cholecystectomy. The patient had routine labs performed pre-procedure, which were significant for a hemoglobin of 14.2g/dL, hematocrit of 46%, RBCs 5.53x106, and 247x10^9/L platelets (see figures 1a and 1b). The following day, the patient underwent a left heart catheterization and was found to have disease involving the left main and right circumflex coronary arteries. Given the patient's upcoming cholecystectomy, balloon angioplasty was performed alone instead of placing drug-eluting stents to avoid the twelve-month course of dual antiplatelet therapy, which would have delayed his surgery. The patient developed acute ST-segment elevation and hypotension during the procedure, which resolved postangioplasty. Tirofiban was then initiated at 0.15 mcg/kg/ min to prevent post-intervention re-thrombosis formation. Laboratory studies approximately two hours after initiating tirofiban revealed a hemoglobin of 13.0g/dL, a hematocrit of 42.0%, an RBC count of 5.07x106, and a platelet count of 1.0x10^9/L notably without clumping (see figures 2a and 2b). Given the severity and timing of the thrombocytopenia, tirofiban was immediately discontinued, and the platelet count was repeated three hours later. At that time, the patient's platelets were undetectable, and their hemoglobin and platelet counts continued to be monitored without significant improvement. Overnight, the patient developed epistaxis, requiring the transfusion of four units of apheresis platelets as their platelet count remained less than 20x10^9/L. The patient's hemoglobin remained above 7.0 g/dL, and no packed red blood cells were transfused. On subsequent laboratory evaluation, no significant improvement in either anemia or thrombocytopenia wasWith the initial platelet decline, a peripheral smear was obtained to classify the thrombocytopenia further and rule out pseudo-thrombocytopenia due to clumping. There was no morphologic evidence of any form of hemolysis (microangiopathic or otherwise) nor any evidence on peripheral blood smear of any underlying primary bone marrow disorder. At the time of discharge, approximately forty-eight hours post initial tirofiban infusion, the patient's hemoglobin had still not recovered to pre-transfusion levels, and the platelet count had only increased to 61x10^9/L. On outpatient labs seven days after discharge, the patient's platelet count had returned to pre-tirofiban levels at 321x10^9/L, and his hemoglobin was within normal limits.

Introduction

 Inhibition of post-procedure thrombus formation remains crucial in percutaneous coronary intervention (PCI) management of coronary artery disease. Often, intravenous antiplatelet medications are used initially as they bypass first-pass metabolism, allowing for inactivation from the time of infusion and thus decreasing the risk of postPCI thrombosis formation while bridging to oral therapy. Historically, intravenous glycoprotein IIb/IIIa inhibitors such as tirofiban, eptifibatide, and abciximab were used. While these medications are effective, they are occasionally associated with inducing cases of thrombocytopenia and, less commonly, anemia. While newer intravenous medications such as the P2Y12 inhibitor cangrelor exist, they are more expensive and often not carried locally, particularly in rural smaller health-care systems. This leaves clinicians with little option but to use medications such as tirofiban post-PCI procedures.tirofiban. Severe thrombocytopenia is estimated to only occur in 0.2 to 1.2% of patients treated with tirofiban [1], with the classification of acute severe thrombocytopenia occurring even less frequently. The etiology of acute severe thrombocytopenia from tirofiban remains obscured. In the setting of thrombocytopenia occurring with the first known exposure to glycoprotein IIb/IIIa inhibitors, it has been postulated to be from naturally occurring drug-dependent antibodies [2]. When thrombocytopenia occurs after a previous dose of glycoprotein IIb/IIIa medications, it could be from post-exposure antibody formation associated with delayed onset thrombocytopenia [3], [4]. Other causes of thrombocytopenia must be ruled out, including but not limited to heparin-induced thrombocytopenia, disseminated intravascular coagulation, and microvascular hemolysis.

Discussion

 Acute severe glycoprotein IIb/IIIa inhibitor-induced thrombocytopenia is a rare but well-known side-effect of The severity and speed to the nadir of the platelets can vary from within a few minutes to several days after tirofiban initiation. There are currently five subclasses of thrombocytopenia that classify the severity and time to nadir [2]. The first is acute severe thrombocytopenia, defined as reaching a nadir of platelets of less than 10x109/L within the first twelve hours after initial exposure to the medication. The second is acute thrombocytopenia, with the onset of thrombocytopenia occurring within the first twelve hours post-exposure. The third class is delayed thrombocytopenia, occurring five to seven days post-exposure. The final two types include anaphylaxis after the first or second exposure to the drug and pseudothrombocytopenia, i.e., clumping or satelliting. While several documented cases of thrombocytopenia exist, to our knowledge, only eight confirmed cases of acute severe thrombocytopenia have been reported, and only four of those have occurred without prior GPIIb/IIIa inhibitor use. Thrombocytopenia is the most observed glycoprotein IIb/IIIa inhibitor hematological cell line abnormality [5- 10]. Less frequently, anemia can occur with and without thrombocytopenia [5] [6]. In this situation, our patient developed a decline in hemoglobin by approximately two grams per deciliter between pre-procedure labs and twenty-four hours post-tirofiban induction. It is unknown how much of that decline was secondary to the epistaxis versus directly from the tirofiban. However, clinically, the epistaxis was not significant enough to produce a two-gram per deciliter decrease in his hemoglobin. It was inferred that the hemoglobin decrease was directly related to initiating tirofiban as it had already dropped by approximately 1.2 grams at the first lab check post-initiation and before developing epistaxis. Use of the Naranjo adverse drug reaction (ADR) probability scale yielded a score of seven, suggesting that the likelihood of thrombocytopenia as an adverse drug reaction was probable [11]. A previously described calculator proposed by Yi et al. estimates the risk of developing tirofiban-induced thrombocytopenia [12]. Using their scoring system, clinicians can estimate the risk of developing perioperative thrombocytopenia between 0.51% and 17.1%, based on how many risk factors apply. Given our patient was over the age of 65 and had the comorbidities of diabetes mellitus and chronic kidney disease, he scored five points out ofthe eight points possible, placing him at moderate risk. Unfortunately, tirofiban was the only option available, and the risk of developing thrombocytopenia was still perceived as less than the risk of acute re-thrombosis.

Conclusion

 Despite the addition of new intravenous P2Y12 inhibitors, they remain cost-prohibitive in smaller rural health-caresystems. Since immediate post-PCI thrombus formation prevention remains critical, glycoprotein IIb/IIIa inhibitors are still used to induce platelet dysfunction. While cases of acute severe thrombocytopenia have been documented with life-threatening complications, the presence of acute severe thrombocytopenia can occur without them. To the best of our knowledge, this is the first such observation of acute severe thrombocytopenia in a Native American / American Indian. Providers who utilize glycoprotein IIb/IIIa inhibitors must continue to be aware of this association and follow the recommended laboratory evaluation schedule to ensure the earliest detection of thrombocytopenia or anemia, thus allowing for therapy modification to provide the best possible patient outcomes. Additionally, providers should adopt the Yi et al. scoring system to further risk stratify their patients before administering tirofiban.  

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