Acute heparin-induced thrombocytopenia (HIT) without thrombocytopenia post aortocoronary bypass grafting

Abstract

Heparin-induced thrombocytopenia (HIT) after cardiac surgery is a clinical condition associated with increased incidence of thromboembolic events and mortality. HIT without thrombocytopenia is a rare clinical entity poorly reported in the literature, especially after cardiac surgery. In this case report, we present the case of a post aortocoronary bypass grafting patient who presented with HIT in the absence of thrombocytopenia.

Introduction

Heparin-induced thrombocytopenia (HIT) is not a rare condition after cardiac surgery as its incidence ranges from 0.7 to 2% [1], but its consequences are devastating with mortality ranging from 21.8 to 45% and thromboembolic complications reaching 70% [2, 3]. Although HIT presents with thrombotic events along with thrombocytopenia, there are a couple of published cases reporting HIT in the absence of thrombocytopenia [4, 5].

In the following paragraphs, the case of a man after cardiac surgery with HIT without thrombocytopenia is presented.

Case report

A 53-year-old patient was admitted to our department diagnosed with left main (80%) and 3-vessel coronary artery disease. His medical background consisted of hypertension and dyslipidemia. He underwent coronary artery bypass grafting (CABG) on pump with 4 grafts (left internal mammary to the left anterior descending, right internal mammary to the right coronary artery, radial artery free graft to the first oblique marginal and saphenous vein graft to first diagonal). The operation and the postoperative course were uneventful until the 6^th postoperative day. Anti-platelet treatment and anticoagulant treatment were initiated the 1^st postoperative day (daily administration of aspirin 100 mg and enoxaparin sodium 4000 IU).

He presented with angina and ST segment elevation in II, III, AVF on the electrocardiograph (ECG). Despite drug administration (nitroglycerin, opioids), the symptoms were persistent and heart ultrasound confirmed pathologic movement of the inferior wall and the apex of the left ventricle. He underwent urgent coronary angiography which revealed complete absence of perfusion of the epiaortic grafts (radial graft and saphenous vein graft), well-functioning left mammary graft, and occlusion of the right coronary artery with a thrombus proximally to anastomosis which was close to crux (initial right coronary stenosis was 70% proximal and 90% in the middle of the right coronary artery) (Fig. 1). It should be mentioned that the diameter of the vessel at the point of anastomosis was approximately 2 mm and the anastomosis was performed without technical difficulties. The coronary flow was restored with placement of two drug-eluting stents in the right coronary artery proximally to right internal mammary artery anastomosis without its coverage. Additionally, one stent was placed in the left circumflex. Heparinization and catheter manipulation resulted in the removal of thrombus at the anastomosis of the right internal mammary. Abnormalities on ECG resolved and hemodynamic status was stabilized. After a few minutes while the patient was still at the cath lab, he developed intense pain and bradycardia. In addition to this, complete atrioventricular block was present. Urgent coronary angiography showed that the stent on the right coronary was completely thrombosed. The thrombus was removed and sinus rhythm was restored. Right internal mammary graft was patent and sufficient perfusion was provided to the posterior descending artery (Fig. 2). After this event, the patient was administered continuous infusion of cangrelor 4 μg/kg/min, while aspirin 325 mg and unfractioned heparin 10,000 IU were administered before the stent placement.

Fig. 1.

A Initial coronary angiography during ST elevation. On the left, the first mid of the right coronary artery is patent and then is totally occluded on antegrade perfusion. B A thin catheter is forwarded to the posterior descending artery. The right internal mammary is still patent (presence of contrast) with perfusion of the posterior descending artery but the flow is obstructed proximally to anastomosis (green arrow)

Fig. 2.

A Depiction of the right mammary artery on antegrade perfusion from the right subclavian artery. B The course of the right mammary artery is indicated by contrast presence. C Two stents are placed in the right coronary artery and the pedicled right internal mammary is patent (orange arrow)

The patient remained hemodynamically stable and 48 h after the myocardial infarction, he was transferred to the cardiac surgery department from intensive care unit. Hyperacute thrombosis of the stent grew suspicions regarding the cause of this event. Computed tomography of pulmonary angiogram (CTPA), ultrasound of arterial and venous system of legs, coronavirus disease 2019 (COVID-19) polymerase chain reaction (PCR) test, and laboratory tests were performed. More specifically, laboratory tests aimed to investigate any possible cause of this hypercoagulable state and included investigation of factors affecting coagulant system as antithrombin III, protein C, and S deficiency. All examination was negative except from anti-heparin antibody. Although the platelet (PLT) count was within normal values, the anti-heparin antibody PF4 was positive (1.427 optical density, positive laboratory value more than 0.227) and PLT serotonin release assay confirmed the diagnosis. PLT count was preoperatively 227 × 10³, the first postoperative day 274 × 10³ and gradually increased to 379 × 10³ at the time of diagnosis and more than 600 × 10³ at the day of discharge. The anti-platelet therapy administered after the cangrelor discontinuation in second day after percutaneous coronary intervention (PCI) was aspirin 325 mg s:1 × 1, ticagrelor 90 mg s:1 × 2, and fondaparinux 5 mg s:1 × 1 according to consultation of a hematologist. Repeat coronary angiography revealed satisfactory results, while deep vein thrombosis was excluded by ultrasound of the legs and pulmonary embolism by computed tomography of the pulmonary artery. The fifth day after the myocardial infarction, he was discharged in very good clinical condition and heart ultrasound was satisfactory (ejection fraction of the left ventricle 55% and normal myocardial movement). The treatment administered at discharge was aspirin 325 mg s:1 × 1, ticagrelor 90 mg s:1 × 2, and fondaparinux 5 mg s:1 × 2. Despite the fact that fondaparinux is related to rare cases of HIT, hematologists supported that its administration was necessary. Repeated laboratory tests 1 month after discharge found that anti-heparin antibody examination was still present, while PLT count was within normal 1 week after discharge and during 3 months of follow-up. Anti-heparin antibody was negative after the second month from discharge.

Discussion

On literature search, we found two cases of HIT without accompanying thrombocytopenia. We investigated on PubMed and Cochrane Library search engines using the following key words: HIT, cardiac surgery, CABG, HIT without thrombocytopenia. One of the patients developed HIT without thrombocytopenia after CABG, and presented with pulmonary embolism [5]. The other patient developed HIT after mitral valve replacement and presented with a thombosed mitral bioprosthesis requiring urgent reintervention [6]. Similarly, in our case, urgent intervention was required. Moreover, such a high hypercoagulable state was developed that the stent was thrombosed after few minutes from placement. Additionally, both venous and arterial grafts were thrombosed, despite the fact that after CABG, the occlusion rate for saphenous vein grafts, but not arterial conduits, is significantly increased in HIT patients compared with non-HIT controls [7].

Usually, after cardiac surgery and cardiopulmonary bypass implementation, PLT count decreases as a consequence of hemodilution or consumption [3]. In cases that thrombocytopenia (defined as less than 150 × 10³ platelets or less than 50% of the preoperative value) is present for more than 5–10 days after cardiac surgery and thromboembolic event occurs, HIT should be investigated with anti-heparin antibody PF4. Moreover, PLT count often surpasses the preoperative values usually between the 5^th and 7^th postoperative days and reaches peak in about the 14^th day after cardiac surgery and this fact should be kept in mind [8]. Additionally, when the clinical suspicion is high, repeated laboratory tests are indicated, at least three times, for HIT detection as the incidence of false positive results is elevated [2]. In this case, serious thrombotic events (graft thrombosis) occurred without the presence of thrombocytopenia. One assumption is that the platelets were not consumed at the time of the event, but the overall course showed that platelets were normal or elevated and followed the expected variation after cardiac surgery. Additionally, the typical progressive increase in PLT count was not observed after heparin discontinuation as it is usually observed in HIT. Although the PLT count course in our case could be related to reactive thrombocytosis after CABG, the identification of anti-heparin antibody is also indicative of the diagnosis of HIT without thrombocytopenia [9]. Enzyme-linked immunosorbent assay (ELISA) for HIT detection is a sensitive method (more than 90%), but its specificity is still uncertain in post cardiac surgery patients according to some authors. It should be mentioned that the possibility of false positive result is possible, but in our case, antibody PF4 were detected in multiple consecutive blood tests [10].

This case report indicates that HIT must be included in the differential diagnosis when thromboembolic events are present regardless of the detection of thrombocytopenia.

Conclusions

HIT after cardiac surgery is associated with poor outcomes; therefore, early diagnosis and treatment is of great importance. In our case, HIT occurred without thrombocytopenia, and thus we recommend investigating for HIT in cases of unexplained thromboembolic events even in the absence of thrombocytopenia.

Funding

None.

Data Availability

Data available on request due to privacy/ethical restrictions.

Declarations

Bioethics statement

All human rights and animal rights were preserved according to the Declaration of Helsinki and local legislation. Personal data were preserved according to the law. N/A IRB approval, consent statement, and clinical trial registration.

Conflict of interest

None declared.