Massive aortic thrombus in a hypercoagulable patient with heparin induced thrombocytopenia: a case report

Abstract

Large ascending aortic thrombus can lead to devastating consequences and requires astute recognition and evaluation, systemic anticoagulation, and urgent surgical intervention. Perioperative and surgical management of a large ascending aortic thrombus is further complicated in patients who develop heparin induced thrombocytopenia (HIT) as the risks of further thrombosis and perioperative bleeding must be carefully navigated. We report the case of a patient who presents with multiple thromboses, including a massive ascending aortic mural thrombus, indicative of an underlying hypercoagulable state, who developed acute HIT after systemic anticoagulation and required urgent cardiac surgery for removal of the aortic thrombus. Following stabilization of acute HIT with argatroban, surgical thrombectomy of the large aortic thrombus and endarterectomy of a penetrating aortic ulcer was successfully performed using bivalirudin anticoagulation for cardiopulmonary bypass without complication. Postoperatively the patient was maintained on argatroban followed by transition to outpatient warfarin without new thromboembolic or bleeding complications.

Introduction

Ascending aortic thrombus is a rare phenomenon associated with significant morbidity and mortality due to myocardial infarction, stroke, acute limb ischemia, and visceral ischemia, thus urgent cardiac surgery is indicated to improve patient outcomes [1, 2]. Cases of large floating and mural aortic thrombi have been reported in the literature [3–5], however there has not yet been a report of management of a mural thrombus in the ascending aorta of a patient with acute preoperative heparin-induced thrombocytopenia (HIT). HIT is a potentially life-threatening immune reaction to heparin in which antibodies to platelet factor four and heparin complexes result in platelet activation, promoting the formation of thrombosis [6]. While heparin is the standard of care for anticoagulation therapy during cardiopulmonary bypass (CPB) [7], patients with sensitivities to heparin require alternative approaches, adding significant complexity to operative management to balance the risks of thrombosis and bleeding.

Bivalirudin, a direct thrombin inhibitor, has been shown to be a safe and effective alternative therapy for anti-coagulation in CPB [8–11], however it lacks a direct reversal agent and is associated with increased risk of early post-operative bleeding [11, 12], necessitating careful and individualized operative planning. Here, we describe the perioperative and surgical management in the unique case of a hypercoagulable patient requiring urgent cardiac surgery for a thrombectomy with endarterectomy of an aortic ulcer that developed preoperative HIT. Utilizing bivalirudin anticoagulation for CPB, we employed a ‘less is more’ operative approach to balance the risks of bleeding and thrombosis in this high-risk patient while mitigating adverse events.

Case report

A 46-year-old male who was undergoing a stroke workup in the emergency department that revealed a right transverse sinus thrombus associated with a small intraparenchymal bleed was incidentally found to have a filling defect in the aorta on computed tomography angiogram (CTA) of the head and neck. Subsequently, CTA thorax revealed a calcification just superior to the level of the sinotubular junction along the anterior wall of the ascending aorta with a large thrombus extending almost the full length of the ascending aorta to the proximal aortic arch (Fig. 1a). In addition to the right transverse sinus and aortic thrombi, multiple other thrombi were identified on imaging including a small thrombus in right ventricle embedded within the papillary muscles, and multiple peripheral deep vein thromboses, suggestive of an underlying hypercoagulable state.

A continuous heparin drip and hypercoagulable workup were initiated. CBC, coagulation studies, genetic testing, rheumatologic, and infectious workup were all within normal limits. Once the patient was cleared from a neurology perspective to undergo systemic anticoagulation with high-dose heparin, cardiac surgery was scheduled however, on hospital day 8, the patient developed severe thrombocytopenia (platelet count 37, reference 150–400 × 10³/μL) (Fig. 2), thus the originally scheduled aortic thrombectomy was postponed due to concerns for HIT. Initial HIT platelet Immunoglobulin G antibody testing was positive, but serotonin release assay (SRA) was negative. Despite negative SRA, there was a high clinical suspicion for HIT, thus heparin was discontinued and argatroban drip was initiated. Repeat SRA resulted positive, confirming the diagnosis. After hematology completed their hypercoagulable/HIT workup, the patient was cleared to undergo systemic anticoagulation with alternative agent bivalirudin for cardiac surgery. Aortic thrombectomy was scheduled for hospital day 28, contingent on maintaining a platelet count ˃100.

On hospital day 28, argatroban was held 6 h prior to surgery. Following median sternotomy, intraoperative systemic anticoagulation was initiated using bivalirudin due to patient’s HIT. After achieving satisfactory anticoagulation as determined by activated clotting time (ACT), the aorta was cannulated, and cardiopulmonary bypass was initiated. The ascending aorta was incised to reveal a massive thrombus (Fig. 1b) attached at a calcific area of a penetrating aortic ulcer that was immediately superior to the right coronary ostium. The thrombus was excised, and endarterectomy of the calcific ulcer was performed with subsequent placement of a bovine pericardial patch, as aortic replacement was unfavorable due to close proximity of the ulcer to the right coronary ostium. The excised thrombus measured 5.6 cm by 2.2 cm by 1.0 cm (Fig. 1c). Bivalirudin was discontinued upon anticipation of termination of bypass to allow for washout. Two packs of platelets, two units of fresh frozen plasma, and one unit of cryoprecipitate was given to address coagulopathy. After hemostasis was obtained, the chest wall was closed, and patient was transferred to the cardiac intensive care unit and extubated on post-operative day (POD) 0. Surgical pathology was consistent with thrombus formation and negative for tumor (Fig. 1d).

Argatroban anticoagulation was reinitiated on POD 1. The patient’s platelet count remained stable and normalized by POD 3 (Fig. 2). On POD 9, argatroban was discontinued after achieving therapeutic International Normalized Ratio on warfarin. Patient was discharged on 6 months of anticoagulation with outpatient follow-up by hematology. At 2 years follow-up, patient’s aorta has remained free of re-development of thrombus.

Discussion

To our knowledge, this is the first report of a case of a patient presenting with a massive ascending aortic mural thrombus who developed HIT after systemic anticoagulation with heparin. Given that HIT is associated with significant morbidity and mortality in cardiovascular patients, primarily due to thrombotic complications [13], this case highlights both the need to evaluate patients who present with large aortic thrombi for HIT and the need to evaluate patients who present with HIT for large aortic thrombi. The very large size of this patient’s thrombus coupled with the development of several different thrombi even prior to the development of HIT indicated that urgent cardiac surgery was needed due to the risk of embolization or occlusion should the thrombus further enlarge. While a combined strategy of preoperative anticoagulation with argatroban and intraoperative bivalirudin is commonly used in patients with HIT undergoing cardiac surgery [12], the large aortic thrombus in the setting of HIT in this case creates a unique challenge of balancing the risks perioperative bleeding versus the technical aspects and complications associated with thrombus resection.

Bivalirudin, a first-line alternative to heparin for CPB [9], lacks a direct reversal agent which creates intraoperative challenges to achieve hemostasis and it has been associated with increased risk of early post-operative bleeding [11, 12]. In this case, there was no significant perioperative bleeding, indicating that appropriate hemostatic control can still be obtained. Here, we carefully timed the discontinuation of bivalirudin therapy prior to the termination of bypass to provide sufficient washout time prior to chest wall closure, as the half-life of bivalirudin is ~20–30 min [12], and judiciously administered of blood products which allowed us to successfully achieve hemostasis, contributing to a positive outcome. Additionally, while not a concern for our patient, bivalirudin must be carefully titrated in patients with preoperative kidney failure or renal replacement to account for its renal elimination to balance the risk of post-operative bleeding with the need for appropriate anticoagulation during cardiac surgery [14, 15].

The large size of the aortic thrombus is also of significance because it poses further bleeding risk, since it often requires more extensive aortic surgery. Multiple suture lines, greater tissue mobilization, involvement of the aortic root leading to longer operative times, and extension into the aortic arch with potential hypothermic circulatory arrest can all exacerbate coagulopathy and would be particularly unfavorable in a patient with already elevated bleeding risk such as with HIT. In our case, given the close proximity of the calcific ulcer to the right coronary ostium, aortic replacement was unfavorable as it would require coronary artery reimplantation resulting in increased CPB time and additional suture lines, increasing bleeding risk in an already highly vulnerable patient. Therefore, endarterectomy with subsequent placement of a bovine pericardial patch was performed as a more conservative operative approach to mitigate the risk of post-operative bleeding. As our patient did not experience any postoperative bleeding or thrombotic complications, perioperative argatroban, and intraoperative bivalirudin anticoagulation combined with this ‘less is more’ operative approach proved to be safe and effective for the management of ascending aortic thrombus in the setting of HIT.

Conclusion

Large ascending aortic thrombi require thorough evaluation and careful anticoagulation management, with subsequent urgent surgical thrombectomy. The development of HIT in these hypercoagulable patients poses a challenge to balance the risks of thrombosis and bleeding, but can be safely managed with perioperative argatroban and intraoperative bivalirudin for cardiopulmonary bypass anticoagulation, along with judicious operative technical strategies.

Acknowledgements

We greatly acknowledge the many people involved in the care of this patient as well as the patient for consenting to the publication of his case.

Conflicts of interest

Authors do not have any conflicts of interest to disclose.

Funding

No funding was utilized for this case report.

References