Another Example of Devastating Complication of Heparin-Induced Thrombocytopenia Post-Cardiac Surgery

We describe a patient who developed catastrophic consequences of heparin-induced thrombocytopenia (HIT) post cardiac surgery, for which she required reoperation using CPB. We also illustrate the impact of intraoperative transesophageal echocardiography (TEE) in the surgical management of this patient.


Summary
In 2004, a 51-year-old woman underwent coronary artery bypass grafting surgery complicated by heparin-induced thrombocytopenia with thrombosis 9 days post operatively.Because this patient was already anticoagulated with danaparoid, the decision was made to use this anticoagulant during cardiopulmonary bypass for extraction of thrombi from both atria and pulmonary arteries.Clots were observed in the surgical field despite recommended dosing.Post-operatively, this patient exhibited excessive bleeding requiring massive transfusion and suffered from a stroke.Failure of danaparoid anticoagulation in our patient reinforces the need for an alternative anticoagulant.

Case Presentation
In 2004, a 51-year-old woman developed crescendo angina for which she was treated with unfractioned heparin (UFH).She underwent uncomplicated coronary artery bypass grafting (CABG) surgery.She was re-admitted nine days after her CABG with dyspnea and hypoxemia, where she was started on UFH for a suspected pulmonary embolus (PE).A complete blood count revealed a hemoglobin of 90 g/L and a platelet count of 42 000/l.Transthoracic echocardiogram (TTE) illustrated a large RA (right atrium) thrombus measuring 6 × 2 cm floating in and out of the right ventricle (RV) as seen in Fig-ure 1.A spiral CT of the chest revealed massive emboli in the right and left pulmonary arteries.A clinical diagnosis of heparin-induced thrombocytopenia with thrombosis (HITT) was made.All heparin containing substances were discontinued, and the patient was anticoagulated with danaparoid (2250 U bolus, followed by 400 U/hr) the patient was then referred to cardiac surgery for removal of a right atrial thrombus and pulmonary embolectomy.Because the patient was already anticoagulated with danaparoid, the decision was made to use this anticoagulant during cardiopulmonary bypass (CPB).Therefore a bolus of danaparoid 3000 u was administered before CPB and the infusion was continued until separation from CPB. Arrangements were made with the hematologist and the laboratory to get urgent anti-Xa levels intra-operatively, in order to appropriately adjust the danaparoid levels.An additional bolus of danaparoid 1500 U was administered because visible clots were observed in the surgical field during CPB.Aprotinin was given in the hopes of minimizing post-operative bleeding as previously described in patients receiving danaparoid during cardiac surgery, though its efficacy is unproven in this setting [1].

Method
Intra-operative TEE was performed, and showed a left atrial (LA) thrombus, in addition to the RA thrombus

Discussion
The largest study reported results of 47 patients with HIT given danaparoid for cardiac surgery [1].In two patients, surgery was abandoned because significant clots were observed in the operative field or the CPB circuit.In another 16 patients, further danaparoid doses had to be given because of clots in the field.Severe bleeding was observed in 22% of patients (requiring > 20 u of blood products) and 38% of patients required re-exploration for excessive post-operative bleeding.At 6 week follow-up, 77% of patients were still alive.As a result of both persistent thrombosis despite "appropriate" dosage, and increased bleeding, lack of reliable assay for intra-operative use and its long t 1/2 , danaparoid is a poor option for patients with HIT II undergoing CPB.Al-though danaparoid is still available in Canada and continental Europe, it has been removed form the US market in April 2002.
There are also several reports of Bivalirudin successful use for CPB in patients with HIT II [2,3,4].Bivalirudin's short t 1/2 , significant organ independent elimination, and possibly its titratibility to the ACT, makes result in it a being an extremely better option for treatment of patients with HIT II undergoing CPB.
Our patient had already been started on danaparoid by the intensivist as soon as the suspicion of HIT II was entertained.Given its long t 1/2 , and the complexity of dosing another anticoagulant with danaparoid already on board, we decided to continue the use of danaparoid for CPB.
The patient underwent pulmonary embolectomy, and removal of RA, RV and LA thrombus.The intraoperative TEE can confirm pre-operative findings while ensuring that there are no new thrombi.Post cardiopulmonary bypass, the intraoperative TEE can also be used to confirm that there are no residual thrombi.

Results
Two days after her surgery, the patient developed dense left hemiparesis.This complication may have occurred as an embolic phenomenon from an intra-cardiac thrombus.Cross reactivity of danaproid with HIT antibodies may have also occurred, resulting in arterial thrombosis.Lastly, there have been speculations with regards to the danger of using aprotinin in patients with HIT II considering their degree of thrombogenicity.[1] This case report illustrates yet another example that danaparoid is a sub-optimal choice for anticoagulation in patients with HIT II whereby clots were observed in the surgical field despite recommended dosing.In addition, the patient exhibited excessive bleeding requiring massive transfusion, and suffered from a stroke post-opera-tively.Failure of danaparoid anticoagulation in our patient reinforces the need for an alternative anticoagulant and the establishment of a multidisciplinary, hospital-based protocol in patients with HIT II requiring urgent surgery.In our opinion, the use of bivalirudin represents the best non-heparin anticoagulant currently available for patients with HIT that require anticoagulant for both off-pump [5] and on-pump cardiac surgical cases.The use of intraoperative TEE is also recommended both to facilitate the hemodynamic management of these patients and to ensure that there are no new thrombi or residual thrombi at the end of surgery.

Figure 1 .
Figure 1.Transgastric right ventricular inflow view.Note arrows indicating thrombi in both the right atrium (RA) and right ventricle (RV)