Ann Thorac Surg 2000;69:61-64
© 2000 The Society of Thoracic Surgeons
Original Articles
Preoperative immunoglobulin treatment in patients with Werlhof’s disease undergoing cardiac operation
Stefan Christiansen, MDa,
Christof Schmid, MDa,
Klaus Redmanna,
Ulli R. Jahn, MDb,
Jörg Stypmann, MDc,
Hans H. Scheld, MDa,
Dieter Hammel, MDa
a Department of Cardiothoracic Surgery, Westphalian Wilhelms-University, Münster, Münster, Germany
b Department of Anesthesiology and Operative Intensive Care Medicine, Westphalian Wilhelms-University, Münster, Münster, Germany
c Department of Cardiology and Angiology, Westphalian Wilhelms-University, Münster, Münster, Germany
Address reprint requests to Dr Christiansen, Department of Cardiothoracic Surgery, Westphalian Wilhelms-University, Münster, Albert-Schweitzer-Str 33, 48149 Münster, Germany
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Abstract
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Background. Patients with Werlhof’s disease and undergoing a cardiac surgical procedure with cardiopulmonary bypass are at increased risk for bleeding complications. We report the usefulness of preoperative immunoglobulin treatment in selected patients.
Methods. Between May 1995 and July 1998, 10 patients with Werlhof’s disease underwent a cardiac surgical procedure with cardiopulmonary bypass in our department. Five patients with mean platelet counts of less than 80 x 109/L received immunoglobulin therapy preoperatively (group 1). The other 5 patients with mean platelet counts higher than 80 x 109/L were not so treated (group 2).
Results. In group 1, mean platelet count increased from 54 x 109/L 5 days before operation to 112 x 109/L after immunoglobulin treatment (p = 0.018) and did not fall to less than 60 x 109/L postoperatively. Patients in group 1 received 16 units of packed red blood cells and 5 units of platelet concentrate. Patients in group 2 required 24 units of packed red blood cells, 5 units of platelet concentrate, and 23 units of fresh frozen plasma. Only 1 patient (group 2) had a surgical bleeding complication that required reexploration. Mean drainage loss was 1,100 mL in group 1 and 1,210 mL in group 2.
Conclusions. Our data demonstrate that immunoglobulin treatment of patients with Werlhof’s disease and mean platelet counts of less than 80 x 109/L significantly augments platelet counts preoperatively. It may be useful in selected patients.
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Introduction
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Patients with Werlhof’s disease (WD) who have to undergo a surgical intervention are at increased risk for bleeding complications. This is especially true for cardiac operations with cardiopulmonary bypass because of the necessity for full heparinization and the destructive effects of cardiopulmonary bypass on all blood components. As the combination of WD and coronary artery disease is rare, there are but few reports [1–8] in the English-language literature that focus on the perioperative anticoagulation management of these patients. We report here our experience with the usefulness of preoperative immunoglobulin (IG) treatment of selected cardiosurgical patients with WD.
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Material and methods
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Between May 1995 and July 1998, 10 patients with WD (10/4,533 patients, 0.22%) were referred to our institution for a cardiac operation with cardiopulmonary bypass. The 8 men and 2 women ranged from 40 to 75 years old, and all had coronary artery disease. Five patients with platelet counts lower than 80 x 109/L were treated preoperatively with IG (Venimmun, Centeon Pharma, Marburg, Germany) (0.4 g · kg-1 · day-1 for 4 to 5 days) (group 1). The other 5 patients had platelet counts greater than 80 x 109/L and did not receive special treatment with respect to WD (group 2). Prior to this admission, 1 patient in each group had undergone splenectomy because of a tendency to bleed spontaneously.
The preoperative variables noted included severity and treatment of WD, age, sex, concomitant diseases, risk factors, New York Heart Association classification, and urgency of surgical intervention. Aortic cross-clamp time, duration of cardiopulmonary bypass, duration of the operation, and length of stay in the intensive care unit and normal ward were evaluated. The effects of IG therapy with respect to platelet counts, postoperative blood loss and transfusion requirements, and postoperative mortality and morbidity were assessed.
Statistical analysis was done using the 
2 test for qualitative data and the Wilcoxon test for quantitative data as appropriate. Differences between groups were analyzed by the Student t test. A p value of less than 0.05 was considered significant.
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Results
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Chronic thrombocytopenia with normal bone marrow morphology (2 patients had increased megakaryocytopois), lack of splenomegaly, and absence of other causes of secondary thrombocytopenia led to the diagnosis of WD in all patients. Eight of the patients were asymptomatic and were not treated medically. One patient in group 1 received cyclosporine and corticosteroids because platelet counts did not normalize after splenectomy, and he repeatedly experienced extensive hematoma formation. However, medical treatment failed to improve symptoms or to increase platelet counts. In contrast, 1 patient in group 2 was in complete remission 18 months after splenectomy.
Age, sex, risk factors, and associated diseases are presented in Table 1. All patients had coronary artery disease. One patient in group 1 also had a high-grade stenosis of the left internal carotid artery, which had led to a prolonged reversible ischemic neurologic deficit 2 months before the cardiac operation. All patients were in New York Heart Association class III preoperatively, and all operative procedures were elective.
The most important operative data are presented in Table 2. One patient in group 1 required preoperative implantation of an intraaortic balloon pump because of severe left ventricular dysfunction (ejection fraction, 0.31) and endarterectomy of the left internal carotid artery because of a high-grade stenosis. The intraaortic balloon pump was removed on the second postoperative day without complications. The left internal thoracic artery was used as a graft to the left anterior descending coronary artery in all patients. Vein grafts were used as sequential grafts to shorten the duration of the surgical procedures.
Mean duration of artificial ventilation, mean time in intensive care and mean duration of hospitalization were 12 hours (range, 9 to 15 hours), 3.2 days (range, 2 to 5 days), and 8.5 days (range, 3 to 13 days), respectively, in group 1 and 27 hours (range, 10 to 50 hours), 5.3 days (range, 2 to 7 days), and 11.9 days (range, 4 to 15 days), respectively, in group 2. Seven patients had an uneventful postoperative course, and 3 experienced complications. One patient in group 1 sustained intractable cardiac arrhythmias on the fifth postoperative day and died. One patient in group 2 required reexploration on the first postoperative day for hemothorax on the left side, which was caused by a bleeding branch of the left internal thoracic artery. This patient received most of the blood products in group 2. After successful hemostasis, the patient had an uneventful postoperative course. Another patient in group 2 with impaired renal function preoperatively (creatinine value, 3.5 mg/dL) underwent hemodialysis on the third and fifth postoperative days. After this treatment, renal function recovered, and the creatinine value returned to the preoperative level.
The preoperative and postoperative course of platelet counts for both groups is shown in Figure 1. The mean platelet count in group 1 rose from 54 x 109/L (range, 40 to 60 x 109/L) 5 days before operation to 112 x 109/L (range, 88 to 170 x 109/L) after IG treatment on the day before operation. The mean platelet counts on the day of operation and on the first, second, third, and fourth days postoperatively were as follows: 60 x 109/L (range, 31 to 100 x 109/L); 84 x 109/L (range, 43 to 138 x 109/L); 102 x 109/L (range, 47 to 180 x 109/L); 134 x 109/L (range, 50 to 249 x 109/L); and 133 x 109/L (range, 69 to 241 x 109/L), respectively. In group 2, the mean platelet count was 190 x 109/L (range, 95 to 380 x 109/L) on the day before operation. The mean counts on the day of operation and postoperative days 1 through 4 were as follows: 102 x 109/L (range, 53 to 200 x 109/L). 108 x 109/L (range, 65 to 173 x 109/L); 90 x 109/L (range, 57 to 150 x 109/L), 106 x 109/L (range, 82 to 151 x 109/L); and 109 x 109/L (range, 74 to 157 x 109/L). With transfusion of platelet concentrate and infusion of IG, 60 g, in 1 patient on the first postoperative day, mean platelet counts did not fall to less than 60 x 109/L in group 1 postoperatively.
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Fig 1. Perioperative course of mean platelet counts for the two patient groups (nL = x 109/L; - = days before operation; 0 = day of operation; + = days after operation.)
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Transfused blood products, use of IG, and blood loss are shown in Table 3. One patient in group 2, who had a bleeding complication, received the most blood products (19 units of packed red blood cells, 23 units of fresh frozen plasma, and 4 units of platelet concentrate); the remaining 4 patients in this group received a total of only, 5 units of packed red blood cells and 1 unit of platelet concentrate.
Mean follow-up for the 9 surviving patients was 14 months (range, 1 to 36 months). No late complications occurred.
Statistical analysis failed to demonstrate any significant differences between groups. There were no significant differences with respect to transfused blood products when the patient with the surgical bleeding complication was excluded from consideration. Only the increase in preoperative platelet counts in group 1 demonstrated significant differences, that is, when platelet counts 5 days before operation were compared with those on the day before operation (mean counts, 54 x 109/L versus 112 x 109/L, p = 0.018).
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Comment
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Previously, it has been reported that patients who have WD and undergo cardiac operation are at increased risk for postoperative bleeding complications and that reexploration or transfusions of blood products are not unusual [4, 5, 8]. The increased complication rate was attributed to thrombocytopenia and impaired function of circulating thrombocytes as well as both the deleterious effects of cardiopulmonary bypass on platelets and the necessity for full anticoagulation. However, it is currently impossible to comment on the real risk of bleeding complications in patients with WD because reports on large patient populations are lacking. Our study cannot give clear-cut estimates on the perioperative risk for this special patient cohort, but it does provide useful information for the clinician.
Conservative therapy for WD, consisting of corticosteroids, immunosuppressive treatment, or both, is rarely successful in regard to normalization of platelet counts and regression of symptoms. Therefore, some authors suggest splenectomy, which can be performed simultaneously with or prior to the cardiac operation [4, 5]. The combined procedure, that is, splenectomy and cardiac operation, is associated with an increased operative risk. Moreover, as it takes several days for platelet counts to normalize after splenectomy, a staged procedure is preferred.
Preoperative IG treatment may be a better therapeutic modality. It leads to a temporary increase in platelet counts, which can easily be controlled by analyzing them, allows optimal timing of surgical interventions, and continues into the postoperative course [9, 10]. Our data demonstrated a significant effect of preoperative IG treatment (p = 0.018): mean platelet counts increased from 54 x 109/L (range, 40 to 60 x 109/L) 5 days preoperatively to 112 x 109/L (range, 88 to 170 x 109/L) on the day before operation and did not fall to less than 60 x 109/L postoperatively in group 1 patients. The exact mode of IG action is still unclear; possibilities include impairment of thrombocyte phagocytosis by the reticuloendothelial system, neutralization of autoantibodies, inhibition of autoantibody synthesis, and impairment of interaction between thrombocytes and activated complement factors [9, 11].
Side effects of IG treatment include headache, facial flushing, light-headedness, chills, fever, nausea, diaphoresis, hypotension, and anaphylactic shock. This occurrence is rare (< 1%) and can be relieved for the most part by stopping the drug infusion or avoided by a very slow infusion [6]. As life-threatening situations can occur, IG therapy has to be restricted to patients who absolutely require this treatment.
In conclusion, our limited data demonstrate that preoperative IG treatment of patients with WD and platelet counts lower than 80 x 109/L significantly augments platelet counts and that this effect lasts postoperatively. It is our strategy to use IG therapy preoperatively for these patients only; those with platelet counts higher than 80 x 109/L are not so treated. Despite this special treatment strategy, the transfusion requirement in patients with WD is still higher than average.
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Accepted for publication June 1, 1999.
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Are patients with Werlhof's disease at increased risk for bleeding complications when undergoing cardiac surgery?
Eur. J. Cardiothorac. Surg.,
September 1, 2000;
18(3):
353 - 356.
[Abstract]
[Full Text]
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Abstract
Introduction
