Eur J Cardiothorac Surg 2000;18:353-356
© 2000 Elsevier Science NL
Are patients with Werlhof's disease at increased risk for bleeding complications when undergoing cardiac surgery?
Stefan Christiansena,
Jürgen Rötkera,
Norbert Roedera,
Ulli R. Jahnb,
Jörg Stypmannc,
Hans H. Schelda,
Christof Schmida
a Klinik und Poliklinik für Thorax-, Herz- und Gefäßchirurgie, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany
b Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany
c Klinik und Poliklinik für Kardiologie und Angiologie, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany
Received 20 October 1999;
received in revised form 10 January 2000;
accepted 18 January 2000.
Corresponding author. Tel.: +49-251-834-7401; fax: +49-251-834-8316
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Abstract
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Background: It is generally assumed, that patients with Werlhof's disease (WD) are at increased risk for bleeding complications when undergoing cardiac surgery with extracorporeal circulation. Therefore we performed this case control study to estimate the real risk for bleeding complications of these patients. Methods: Between 05/95 and 07/98, ten patients with WD (eight males, two females) underwent cardiac surgery employing extracorporeal circulation (WD-group). Five of these patients with platelet counts below 80/nl were treated by immunoglobulins preoperatively. Each patient with WD was matched to five patients without WD (no-WD-group) using diagnosis, age, gender, ejection fraction, number of distal anastomosis and body-mass-index as matching criteria. Results: Mean number of platelet counts were significant lower in the WD-group than in the no-WD-group despite a significant increase of platelet counts after immunoglobulin treatment (54/nl
112/nl, P=0.018). On the day before, directly after and on the first day after surgery they were 141/nl vs. 215/nl (P=0.012), 75/nl vs. 147/nl (P=0.001) and 93/nl vs. 136/nl (P=0.009). Accordingly, patients of the WD-group received significantly more platelet concentrates than patients of the no-WD-group (mean number of platelet concentrates: 2.3 versus 0.7, P=0.007). Total drainage loss via the mediastinal chest tubes was almost identical (1197 ml in the no-WD-group and 1140 ml in the WD-group). One patient of each group suffered from a bleeding complication requiring reexploration. Three patients of the no-WD-group (6%) and one patient of the WD-group (10%) expired postoperatively unrelated to WD. Conclusions: Patients with WD may possibly undergo cardiac surgery without a markedly enhanced risk for bleeding complications despite a more than usual transfusion requirement and significantly lower platelet counts perioperatively.
Key Words: Werlhof's disease • Cardiac surgery • Bleeding complications
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1. Introduction
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It is generally assumed, that patients suffering from Werlhof's disease (WD) and undergoing surgical interventions, are at increased risk for postoperative bleeding complications. This is especially true for cardiac operations employing extracorporeal circulation due to necessity of full heparinization and destructive effects of extracorporeal circulation on all blood components. Because of the rare combination of WD and coronary artery disease there are only few reports with small numbers of patients in the Anglo-American literature [1–8], so that the real risk for bleeding complications remains unclear until now. We therefore performed this case control study comparing patients with and without WD to estimate the risk for bleeding complications.
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2. Materials and methods
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Between May 1995 and July 1998, ten patients (eight males, two females) with WD (WD-group) were referred to our institution for cardiac surgery with extracorporeal circulation (ten of 4533 patients, 0.22%). Five patients without WD were matched to each patient with WD using diagnosis, age, gender, ejection fraction, number of distal anastomosis and body-mass-index as matching criteria (no-WD-group). For qualitative data correspondence was requested, for quantitative data deviations up to 10% were accepted. The matching criteria are presented in Table 1.
The preoperative parameters noted included severity and treatment of WD, NYHA classification and urgency of surgical intervention. Furthermore, cross-clamp time, duration of extracorporeal circulation and surgery as well as stay in the intensive care unit were evaluated. With regard to the perioperative risk we analyzed extent of blood loss and transfusion requirements as well as mortality and morbidity.
Anticoagulation for extracorporeal circulation was done by heparin (400 U/kg, activated coagulation time >400 s) in all patients. Heparin effects were reversed by a reduced dose of protamine (0.3 ml/kg), because it is well-known, that this management leads to less blood loss and higher platelet counts postoperatively [9].
The diagnosis of WD was made, when chronic thrombocytopenia with normal bone marrow morphology (two patients presented an increased megacaryocytopoieses), lack of splenomegaly and absence of other causes of secondary thrombocytopenia existed. Eight of the WD patients were asymptomatic and not treated medically. Two patients had undergone splenectomy due to a spontaneous bleeding tendency prior to admission, but it was successful in only one patient. The other patient received cyclosporine and corticosteroids, but this treatment also failed. Five patients with platelet counts <80/nl were treated by immunoglobulins (0.4 g/kg per day for 4–5 days) preoperatively, the other five patients with platelet counts >80/nl did not receive a special treatment.
Statistical analysis was done by Fisher's exact-test for qualitative data and the Mann–Whitney test for quantitative data. Paired comparisons were calculated by the Wilcoxon test. A P-value <0.05 was considered significant.
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3. Results
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Statistical analysis did not reveal any differences between both groups regarding the matching criteria (Table 1).
Significant differences were found in the mean number of transfusion requirements for packed red blood cells and platelet concentrates as well as in the mean number of platelet counts on the day before, directly after and on the first day after surgery. On the second and third day after surgery the differences between both groups regarding the platelet counts were not longer significant. The transfusion requirements are presented in Table 2 and the perioperative course of platelet counts in Fig. 1
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Fig. 1. Perioperative course of platelet counts. With transfusion of platelet concentrates and infusion of 60 g immunoglobulins in one patient on the first postoperative day mean platelet counts did not fall below 75/nl in patients of the WD-group postoperatively (data are given as mean and range). no-WD-group, - - - -; WD-group, — #P=0.012;  P=0.001; *P=0.009.
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All patients underwent coronary artery bypass grafting electively. Duration of surgery and extracorporeal circulation as well as cross-clamp-time and blood loss are depicted in Table 2. One patient of the WD-group had also a high-grade stenosis of the left internal carotid artery, which had led to a prolonged reversible ischemic neurologic deficit 2 months before cardiac surgery. Therefore he had to undergo endarterectomy of the left internal carotid artery simultaneously with coronary artery bypass grafting. Furthermore, an intraaortic balloon pump was implanted preoperatively because of a severe left ventricular dysfunction. The pump was removed on the second postoperative day without complications.
The duration of artificial ventilation and time in intensive care were 17.6 h (9–50 h) and 4.0 days (2–7 days), respectively, in the WD-group and 12.0 h (4–26 h) and 4.2 h (1–23 h) in the no-WD-group.
One reexploration in a patient of the no-WD-group had to be performed for a pericardial tamponade, which was caused by a diffuse bleeding tendency. Also one bleeding complication occurred in the WD-group: it was caused by a bleeding branch of the left internal thoracic artery. One patient in each group expired due to intractable cardiac arrhythmias: two other patients of the no-WD-group died because of multiorgan failure and pneumonia secondary to artificial ventilation.
Further postoperative complications occurred in nine patients of the no-WD-group. Two patients had to be reintubated for respiratory insufficiency; after several days they were weaned successfully from mechanical ventilation. Four patients required postoperative implantation of an intraaortic balloon pump for hemodynamic stabilization. All patients were weaned from the intraaortic balloon pump successfully, but one patient had to undergo a fasciotomy due to a compartment syndrome. Wound healing disturbances were managed conservatively in two patients and required operative revision in one patient.
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4. Comment
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Our current study demonstrates, that platelet counts of WD patients are significantly lower in the perioperative course (Fig. 1) despite preoperative treatment with immunoglobulins as described above. Therefore, the number of transfused blood products (Table 2), especially platelet concentrates, exceeds the usual requirement.
According to previous reports [4,5,8], lower platelet counts beside the deleterious effects of extracorporeal circulation on platelets, necessity of full anticoagulation and impaired function of circulating platelets were suggested to be responsible for an increased risk of postoperative bleeding complications, reexplorations and transfusion of blood products. Because conservative therapy of WD, consisting of corticosteroids and/or immunosuppressive treatment, was rarely successful with regard to normalization of platelet counts and regression of symptoms, several strategies were described to reduce the risk of WD patients for postoperative bleeding complications:
Splenectomy was proposed as simultaneous procedure or prior to cardiac surgery [4,5]. Drawbacks of the combined procedure are the increased operative risk and the fact, that it takes several days to normalize platelet counts. Therefore, the patient does not benefit from the additional procedure, that is splenectomy, in the early postoperative course, in which the risk for bleeding complications is the greatest. Therefore, the staged procedure was introduced, but this management leads to an additional operative intervention, which also carries the risk for bleeding complications, and delay of cardiac surgery.
Preoperative immunoglobulin treatment may be a better therapeutic modality [6,10,11]. It leads to a temporary increase of platelet counts, which can easily be controlled by analyzing platelet counts, allows optimal timing of surgical interventions and continues in the direct postoperative course [12,13]. In our recent report we could demonstrate this effect of immunoglobulin treatment clearly in patients with platelet counts below 80/nl: mean platelet counts increased from 54/nl 5 days preoperatively to 112/nl on the day before operation (P=0.018) and did not fall below 60/nl postoperatively [11]. Patients with platelet counts above 80/nl were not treated by immunoglobulins without suffering from an increased risk for postoperative bleeding complications [11]. The exact mode of immunoglobulin action is still unclear; several possibilities are discussed: impairment of thrombocyte phagocytosis by the reticuloendothelial system, neutralization of autoantibodies, inhibition of the autoantibody synthesis or impairment of interaction between thrombocytes and activated complement factors [12,14].
Administration of blood products, especially platelet concentrates in WD patients, represents a well-known step to enhance platelet counts. The crucial question is, when and why transfusion of blood products in WD patients is indicated. According to Salmenperä et al. [15], platelet counts fall progressively during extracorporeal circulation and remain half baseline until the fourth postoperative day. Furthermore, beside activation of platelets by contact with foreign surfaces of the extracorporeal circulation, dysfunction of platelets, which is caused by alterations of the platelet membrane by shear stress, surface adherence, and turbulent flow, is common. Despite platelet activation a prolonged bleeding time after cardiac surgery due to platelet dysfunction is well-known and the most likely cause for a non-surgical bleeding complication [15]. Therefore, appropriate treatment of WD patients with low platelet counts starts already preoperatively. As described above, in WD patients with platelet counts below 80/ml we administer immunoglobulins to enhance platelet counts.
Intraoperative administration of blood products was not necessary in our WD patients. Postoperatively, transfusion of blood products follows the usual guidelines in cases of excessive bleeding [15]. In patients with no obvious bleeding tendency, platelet concentrates are transfused empirically, if platelet counts fall below 60/nl. This threshold is supported by Simon et al. [16], who reported, that prophylactic administration of platelet concentrates neither reduces chest tube blood loss and transfusion requirements nor improves clinical outcome in patients with mild thrombocytopenia (platelet count of 58/nl). Packed red blood cells are transfused in elderly patients (age above 65 years), if the hemoglobin is less than 10 g/dl; in younger, stable patients the transfusion threshold is a hemoglobin below 8 g/dl [17].
The early application of blood products in WD patients (especially transfusion of platelet concentrates in patients without obvious bleeding tendency and platelet counts below 60/nl) may be the reason for the fact, that we could not demonstrate any significant differences in total drainage loss between both groups of our study. Of course, the major limitation of our study is the small number of WD patients, so that we possibly failed to demonstrate the expected differences in blood loss or an increased risk for postoperative bleeding complications. But our study clearly shows, that perioperative platelet counts are significantly lower and transfusion requirements are significantly increased in WD patients.
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5. Conclusion
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Patients with WD may possibly undergo cardiac surgery without a markedly enhanced risk for bleeding complications despite a more than usual transfusion requirement and significantly lower platelet counts perioperatively.
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Abstract
1. Introduction
