Pulmonary Artery Endarterectomy with Deep Hypothermic Circulatory Arrest in a Patient with a Congenital Antithrombin III Deficiency

Dear Editor, Congenital AT III deficiency is a rare condition (prevalence ranging from 0.02% to 0.2%) that is associated with a high risk of venous thrombotic events.[1] Cardiovascular surgery with cardiopulmonary bypass (CPB) in the context of AT III deficiency may necessitate preoperative AT III supplementation to achieve optimal heparinization.[2,3] Management of AT III deficiency during conventional cardiac or thoracic aortic surgery has already been described, but data in patients undergoing pulmonary artery endarterectomy (PAE) are scarce.[2,3] CPB during PAE is different from conventional one as it includes a longer duration, a large variation of the patient’s blood temperature over alternating periods of cooling then rewarming, and one or more periods of circulatory arrest. We report the anesthesia and CPB management of a patient with a type 1 congenital AT III deficiency who underwent PAE surgery. Written informed consent was obtained from the patient. The patient was a 45-year-old man (weight 72 kg, height 170 cm) with a medical history of pulmonary embolism related to congenital AT III deficiency. Preoperative right heart catheter values, blood cell count, prothrombin time, fibrinogen, and serum AT III concentration are presented in Table 1. Surgery was conducted according to our local protocol with a description available in the supplemental material.Table 1: Patient characteristics, preoperative data, and intraoperative dataPreoperative serum AT III activity level was 36% (normal range 80-120%). A single dose of AT III (AclotineTM) 3500 IU (50 IU/kg) was administered intravenously following chest opening and then a single dose of 22,000 IU (300 IU/kg) of unfractionated heparin (UFH) was administered. The activated clotting time (ACT) 2 min in was 650, allowing the safe insertion of aortic and vena cava cannulas. ACT was monitored every 20 min and remained above 450 s during the whole surgery without any needs for UFH. CPB duration, aortic cross clamp time, and cumulated circulatory arrest time were 239, 60, and 30 min, respectively. The patient was weaned from CPB without difficulties and circulating heparin was antagonized by protamine 22,000 IU of Protamine (1:1 ratio). Intraoperative fluids balance, transfusion requirement, cell saver administration, and urine output are presented in Table 1. AT III activity level was monitored four times during the surgery: five minutes after the injection of AT III, at the temperature of 18°C before circulatory arrest, during the rewarming period at 25°C (bladder temperature), and at the end of the surgery after chest closure. Intraoperative AT III activity is presented in Figure 1.Figure 1: Perioperative AT III and anti-Xa activity. The intraoperative and postoperative values of AT III (blue curve) and anti-Xa activity (orange curve). The left vertical axis corresponds to the level of AT III activity in percentage, and the right vertical axis corresponds to the anti-Xa activity in IU/ml. The times of each AT III supplementation are also displayedThe postoperative course was uneventful. Anticoagulation therapy with unfractionated heparin was initiated 6 h after surgery. AT III activity levels were monitored on a daily basis and supplementation was administered on three occasions when it dropped below 50% [Figure 1]. No bleeding or embolic events were reported during the in-hospital stay. At 3-month follow-up, the patient reported significant clinical improvement. Previous studies have already described CPB management of ATIII deficiency during conventional open surgery and aortic thoracic surgery.[2-4] Nishimura et al.[4] recommended to achieve preoperative and postoperative AT III activity above 120% and 80%, respectively. They reported no adverse events during the postoperative period in their cohort.[4] Ando et al.[5] also described the case of two patients with AT III deficiency who underwent PAE; however, the management of anticoagulation during and after CPB was not reported. CPB during PAE has a prolonged duration related to the induction of deep hypothermia followed by rewarming, and one or more circulatory arrests. CPB per se and heparin administration increase the consumption of AT III. A high rate of AT III consumption was expected but interestingly, after an initial drop following CPB initiation, the AT III activity remained stable during the whole surgery [see Figure 1]. The drop was lower than previously reported whereas the CPB duration was much longer.[3,4] Possibly, AT III consumption could be slowed by deep hypothermia although this should be confirmed by further observation. A single injection of AT III (50 IU/kg) allowed for an AT III activity above 80% to be reached quickly within 10 min. ACT levels were constantly above 450 s throughout CPB, whereas AT III activity ranged between 55% and 60%. The postoperative period is also critical because the risk of thromboembolic events must be weighed against the risk of bleeding. Patients undergoing PAE are by definition, at higher risk of thrombotic events with potentially life-threatening outcomes. Postoperative hypoxemia and residual hypertension are common, and recurrence of acute pulmonary embolism could have devastating consequences. Thus, anticoagulation therapy must be quickly resumed postoperatively. In the present case, an AT III activity threshold activity below 50-60% was targeted to trigger supplementation. It allowed for optimal anticoagulation (UFH anti-Xa activity ranging from 0.3 to 0.6 IU/ml) without excessively increasing intravenous heparin needs and limiting excessive AT III supplementation. This could be of clinical relevance as a recent meta-analysis raises concerns about a significantly increased risk of acute kidney injuries and in-hospital mortality after cardiac surgery in patients supplemented with AT III.[6] Declaration of Patient Consent Written consent was obtained from the patient before writing this case report. Data availability statement The dataset used and/or analyzed during the current study is available from the corresponding authors on reasonable request. Financial support and sponsorship Support was provided solely from institutional and/or departmental sources. Competing interest None of the authors has any conflicts of interest to disclose.