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Ann Thorac Surg 1995;60:1159-1160
© 1995 The Society of Thoracic Surgeons
Department of Cardiovascular Surgery, Hôpital Broussais, 96 Rue Didot, 75674 Paris Cedex 14, France
To the Editor:
We read with interest the article entitled ``Heparin-Induced Thrombocytopenia and Heart Operation: Management With Tedelparin'' [1]. It is certainly interesting to successfully treat this serious complication, particularly in the setting of patients who have previously undergone open heart operation and require repeat cardiopulmonary bypass with reexposure to heparin. Unfortunately, few effective and manageable alternatives to heparin exist for patients in this situation. Org 10172 (heparanoid), iloprost, prostacyclin, low-molecular-weight heparin (LMWH), and ancrod are alternative drugs to heparin that are short-acting enough to be used routinely in clinical practice.
We recently published 5 cases of early thrombus formation after open heart operation; 4 of these patients had development of major intracardiac thrombosis and 1 had vascular thrombosis [2]. The diagnosis of heparin-induced thrombocytopenia and thrombosis (HITT) was confirmed in 4 patients by positive in vitro platelet aggregation studies performed with an aggregometer. The incidence of HITT after open heart operations between January 1990 and January 1993 was found to be 0.097% in our institution. One of the 5 patients died of an extensive thrombus involving the aortic bioprosthesis and both coronary ostia. Three of the 4 surviving patients underwent thrombectomy requiring a second heparinization for cardiopulmonary bypass. These patients were successfully managed by the use of preoperative aspirin (325 mg twice a day) before the reoperation.
Aspirin acts against aggregation by inhibiting cyclooxygenase and thromboxane production that is stimulated with the heparin antiplatelet antibody. In a study of 16 patients with HITT, Makhoul and associates [3] showed that aspirin was able to totally inhibit platelet aggregation in vitro in 9 patients and significantly reduced it in the remaining 7. Although they considered aspirin as a not completely reliable inhibitory agent, and despite the presence of a heparin-dependent platelet-aggregating factor, they successfully managed 2 patients with aspirin and dipyridamole administered before full reheparinization for cardiopulmonary bypass and continued throughout the perioperative period [4]. Our 3 patients who required redo open heart operations confirmed the clinical usefulness of aspirin to inhibit heparin-induced platelet aggregation by reverting positive platelet aggregation tests to negative and achieving subsequent successful reexposure to heparin. We believe that the simultaneous use of dipyridamole can contribute to the effects of aspirin by inhibiting the cyclic adenosine monophosphate-phosphodiesterase thromboxane and increasing prostacyclin production.
As is mentioned by Altès and associates, LMWHs might be used successfully in HITT; however, repeat platelet aggregation studies are mandatory during their use. In their study, Makhoul and associates [3] concluded that some forms of LMWH could cause platelet aggregation without differing significantly in reaction times and maximal aggregation degree from the other heparin molecules. Although the immunogenic region inducing heparin-antiplatelet antibody is contained in different types of LMWH, the risk of HITT seems to be variable. Predicting the in vivo effect of LMWHs with in vitro platelet aggregation tests as was recommended by Altès and associates seems to be a reasonable approach in the management of this devastating complication that still retains some unknown aspects. We believe that thrombosis may not be caused only by the activation of circulating platelets, but also by the endothelial cells. Another key element of our observation is the fact that HITT can manifest itself either in intracardiac cavities that had previously been explored through incisions or in arteries that had been catheterized for coronary arteriography. Although it is very difficult to know exactly whether various cardiac incisions or preoperative arterial or venous catheterizations could sensitize susceptible patients to HITT, we believe that the fact that heparin-dependent platelet antibody can cross-react with the endothelial cells should be taken into consideration [5]. The immune mechanism involving the expression on endothelial cells of the antigen that is common to several heparin types cannot be predicted with the in vitro platelet aggregation studies performed to choose the most appropriate LMWH preparation. Thrombotic events that are observed despite negative results of platelet aggregation tests using different fractions of LMWH should cause one to suspect HITT. Although many other factors can contribute to early thrombus formation in heart cavities or vessels, the choice of aspirin as associated to an antivitamin K drug as substitutive anticoagulant treatment in HITT may reduce the sensitivity of the endothelial cells to recreate thrombus at the sites of previous incisions or catheterizations. This might also be explained by the suppression of endothelial thromboxane production and increase of prostacyclin formation.
In conclusion, we would like to recommend the routine use of aspirin in all patients who present positive platelet aggregation or serotonin tests for the above-mentioned effect of aspirin. We believe that the prompt recognition of HITT is mandatory to prevent the consequences of this potentially fatal condition. Therefore the period of postoperative heparinization should be as short as possible, and antivitamin K anticoagulation should be started on postoperative day 1 with subsequent daily platelet counts.
References
Departament d'Hematologia, Unitat d'Hemostasia i Trombosi, Hospital de Sant Pau, Avda. SAM Claret, 167, 08025, Barcelona, Spain
Reply To the Editor:
We thank Kalangos and associates for their comments regarding our case report concerning a patient who suffered heparin-induced thrombocytopenia during heart operation, and who was successfully managed with tedelparin [1]. Their experience, recently reported, enriches our knowledge about this matter. Nevertheless, we wish to briefly comment on their observations.
Deficiency in the number and function of platelets has been suggested as an important cause of bleeding after open heart operation. During extracorporeal perfusion in the presence of heparin, the number of circulating platelets decreases 40% to 60% [2], and in 2 hours these platelets become 100-fold less sensitive to epinephrine as an agonist for aggregation [3]. No correlation has been found between aspirin ingestion and operative blood loss after cardiopulmonary bypass [4], but aspirin exacerbates the platelet damage and the bleeding time after bypass. Moreover, the effect of aspirin on platelets is not quantifiable by any laboratory method, and treatment of hemorrhagic diathesis can be difficult in this setting. We agree that a benefit can probably be obtained by using aspirin in patients with heparin-induced thrombocytopenia, but this will increase the hemorrhagic risk of the patient. The low frequency of heparin-induced thrombocytopenia does not allow the performance of controlled, randomized studies.
In our work, we predicted the in vivo effect of LMWH tedelparin with in vitro platelet aggregation tests, but we do not think, as Kalangos and associates state, that repeat platelet aggregation studies are mandatory during its use. These tests are very difficult to interpret after extracorporeal perfusion, because platelet aggregation is very impaired in this setting. Moreover, repeated platelet counts are a more rapid, accurate, and useful method to monitor the effect of LMWH on platelets.
Finally we absolutely agree with Kalangos and associates that antivitamin K anticoagulation should be started as soon as possible after operation.
References
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