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CARDIOVASCULAR ANESTHESIA

Perioperative Management of a Heterozygous Carrier of Glanzmann’s Thrombasthenia Submitted to Coronary Artery Bypass Grafting With Cardiopulmonary Bypass

Valter Casati, MD^*, Armando D’Angelo, MD, Luciano Barbato, MD, Edoardo Rossi, MD, Maria Antonietta Grasso, MD^*, Salvatore Spagnolo, MD, and Ezio Panzeri, MD

From the *Division of Cardiovascular Anesthesia and Intensive Care, Policlinico di Monza, Monza, Italy; Coagulation Service and Thrombosis Research Unit, Ospedale San Raffaele, Milano, Italy; Division of Cardiac Surgery, Policlinico di Monza, Monza, Italy; Division of Hematology, Ospedale Sacco, Milano, Italy.

Address correspondence and reprint requests to Valter Casati, MD, Division of Cardiovascular Anesthesia and Intensive Care, Policlinico di Monza, via Amati 111, Monza (20052), Italy. Address e-mail to valter.casati{at}policlinicodimonza.it.

	Abstract

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Glanzmann’s thrombasthenia is a congenital hemorrhagic disorder transmitted as an autosomal recessive trait and characterized by altered production and/or assembly of the platelet membrane glycoprotein IIb/IIIa receptor. We describe the perioperative management of a heterozygous carrier of Glanzmann’s thrombasthenia submitted to cardiac surgery with cardiopulmonary bypass and the case was complicated by early excessive postoperative bleeding.

	Introduction

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Glanzmann’s thrombasthenia is a congenital severe hemorrhagic disorder transmitted as an autosomal recessive trait and characterized by altered production and/or assembly of the platelet membrane glycoprotein (Gp) IIb/IIIa receptor (CD41) for fibrinogen (1). The severity of hemorrhagic manifestations is inversely related to the amount of functional platelet receptor expressed. Glanzmann’s thrombasthenia is classified as type I (<5% of the normal GpIIb/IIIa receptor levels) or type II (10%–20% receptor levels). Heterozygous carriers of Glanzmann’s thrombasthenia have approximately 50% platelet receptor levels (2) and rarely suffer spontaneous bleeding. Cardiac surgery with cardiopulmonary bypass (CPB) induces a significant impairment of platelet aggregation (3), exposing patients with congenital platelet defects to a substantial bleeding risk (4); whether this is also the case for heterozygous carriers of Glanzmann’s thrombasthenia is not known.

We describe the perioperative management of a heterozygous carrier of Glanzmann’s thrombasthenia submitted to coronary artery bypass grafting with CPB, and which was complicated by early excessive postoperative bleeding.

	CASE REPORT

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A 73-yr-old patient was referred to our center for coronary artery surgery. He was the father of a female patient with diagnosed type I Glanzmann’s thrombasthenia, and carriership of the disease (47% of the normal GpIIb/IIIa receptor levels) was confirmed by quantitative flow cytometry using an antihuman CD-41 monoclonal antibody (BD Biosciences; San Diego, CA).

His medical history included arterial hypertension, treated since the age of 59 yr with angiotensin-converting enzyme inhibitors, carvedilol, furosemide, and nitrates; a cerebral ischemic attack causing temporary aphasia at the age of 62 yr; a first anterior myocardial infarction at the age of 72 yr, treated in another hospital with primary percutaneous transluminal angioplasty of the left anterior descending coronary artery (LAD) and complicated by coronary dissection requiring stent implantation with successful recanalization. Eight months later, the patient experienced a second anterior myocardial infarction, and he was admitted to the same hospital. Coronary angiography showed intrastent re-stenosis, and critical stenosis of a diagonal branch of the LAD and of the right coronary artery. Because of unsuccessful percutaneous transluminal angioplasty attempts on the diagonal branch of the LAD, the patient was treated with fibrinolytic therapy. Abciximab infusion was started at a standard dosage, and the patient experienced early diffuse bleeding. Abciximab infusion was stopped, but he required transfusion of allogeneic packed red blood cells and platelet concentrates.

Two months later, he was referred to our center for surgical coronary revascularization. After the induction of anesthesia with propofol, fentanyl, and pancuronium bromide, tranexamic acid was administered as a bolus dose of 1 g in 20 min, followed by a continuous infusion of 400 mg/h (5). Acute normovolemic hemodilution was performed as previously described (6). Autologous blood (1.35 L) was withdrawn through a large-bore catheter (8F) placed into the internal jugular vein and collected into 3 sterile 450-mL bags containing citrate phosphate dextrose. The amount of blood was calculated on the basis of the preoperative hematocrit (44.3%), the estimated circulating blood volume (70 mL/kg body weight), the prime of CPB (1250 mL), the estimated volume of cardioplegic solution (500 mL), and a hematocrit target value of 22% during CPB (7). Each unit of blood was labeled with the patient’s data and kept under agitation at room temperature in the operating room, using a blood mixer and balance system until reinfusion. No colloids were administered, and isovolemia was maintained by the infusion of crystalloid solutions at a 1.5:1 volume ratio, monitoring systemic arterial blood pressure, central venous pressure, and heart rate. ST segment analysis of lead II and V₅ of the electrocardiogram were continuously monitored for potential signs of ischemia.

The patient was operated on through a full median sternotomy. At direct exploration of the coronary vessels, the surgeon did not consider it possible to perform off-pump coronary artery bypass (OPCAB) grafting because of the intra-myocardial positioning of the LAD. Before aortic cannulation, on the basis of a celite-activated clotting time of 156 s, 300 IU/kg of porcine mucous heparin was administered. The circuit for normothermic CPB included a roller pump, warranting a nonpulsatile blood flow, and a hollow fiber membrane oxygenator. The priming solution of the circuit consisted of lactated Ringer’s solution (1000 mL), 18% mannitol (250 mL), and heparin (5000 IU). The activated clotting time, measured at 20-min intervals during CPB, ranged from 894 to 625 s, with no additional heparin boluses. After the start of CPB, 500 mg of tranexamic acid was additionally administered. Aortic clamp-time and total CPB-time were 42 and 63 min, respectively. During surgery, shed blood collected in a cardiotomy and blood remaining in the CPB circuit was processed and washed, eliminating heparin residues, through a cell salvage system, and reinfused at the end of CPB. The reinfusion of autologous blood was started after heparin reversal with protamine (300 mg), and completed during the first 2 h postoperatively in the intensive care unit (ICU). Tranexamic acid infusion was stopped before transferring the patient to the ICU. He experienced early excessive blood loss through the thoracic drainage tubes after the arrival in the ICU (200 mL and 300 mL in the first and second postoperative hours). The administration of tranexamic acid was re-started as an IV bolus of 1 g followed by continuous infusion of 2 mg/kg body weight/h (8). The shed blood was collected through an autotransfusion system, and reinfused during the first 6 h postoperatively (a total of 850 mL). Bleeding progressively diminished in the following hours, and the total blood loss during the first 24 h postoperatively was 1150 mL. Tranexamic acid infusion was stopped after 24 h, and the drainage tubes were removed on the second postoperative day.

The patient did not require allogeneic transfusions nor did he experience additional complications. Hematocrit values were 37.5%, 32.8%, and 30.2% on the first, second, and third postoperative days, respectively. He was discharged from the cardiac surgical unit on postoperative day 7 with a hematocrit value of 30.9%. Because of a diagnosis of moderate hyperhomocysteinemia (fasting total homocysteine = 24.3 µmol/L) obtained before surgery, multivitamin treatment was administered later.

	DISCUSSION

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This is the first report describing the management of a known heterozygous carrier of Glanzmann’s thrombasthenia undergoing coronary surgery with CPB. It is now recognized that even patients with type 1 Glanzmann’s disease are not protected from atherosclerosis (9,10); our patient had a severe history of thrombosis in association with hypertension and moderate hyperhomocysteinemia (11). Although free from spontaneous bleeding, he had previously suffered severe bleeding requiring transfusion of allogeneic blood products on challenge with abciximab at a dosage inadvertently not corrected for the reduced levels of the platelet Gp IIb/IIIa receptor levels (47%). CPB leads to impaired primary hemostasis through platelet dysfunction associated with selective -granule release (3). In addition, it requires large doses of heparin, it activates fibrinolysis, and it should possibly be avoided in this type of patient. However, the anatomical condition of the LAD excluded the OPCAB approach in this patient. Believing our patient to be at increased bleeding risk, we applied a comprehensive blood conservation strategy aimed at reducing the need for allogeneic transfusions (12).

Antifibrinolytic drugs are widely used in cardiac surgery (13), and they are usually administered to control bleeding in patients with type 1 Glanzmann’s disease (2). Aprotinin, extracted from bovine lung, exerts protective effects on GpIIb/IIIa platelet receptors (14), but because of the emergence of bovine spongiform encephalopathy in 1997, this antifibrinolytic drug is no longer available in Italy. For its proven efficacy in reducing perioperative bleeding, tranexamic acid is routinely administered at our institution as an alternative to aprotinin in both CPB and OPCAB heart surgery patients (5,15). In addition to quenching fibrinolysis, tranexamic acid also prevents plasmin-dependent platelet activation during CPB, thus preserving platelet function (16). The relatively short half-life of the drug (approximately 80 minutes), interruption of tranexamic acid administration before transferal to the ICU, and the consequent progressive reduction of its plasma concentrations may have played a role in the excessive bleeding observed in our patient during the first 2 hours postoperatively (500 mL). Restoration of therapeutic plasma concentrations of the drug was associated with a marked reduction in bleeding, which amounted to a total of 1150 mL during the first 24 postoperative hours.

Use of tranexamic acid probably would have been insufficient to avoid transfusion of allogeneic blood products in our patients if additional blood-sparing strategies had not been implemented. Even though still debated (17), acute normovolemic hemodilution has been reported effective in reducing perioperative allogeneic transfusions in major surgery with expected significant bleeding (18). Most of the blood loss occurs during surgery or in the first postoperative hours, and hemodilution leads to less intraoperative net loss of red blood cells. In addition, autologous whole blood contains quiescent platelets that improve hemostasis after open-heart operations (19). In our patient, reinfusion of autologous blood during the first 2 postoperative hours led to an obvious increase in hematocrit levels and avoided the administration of large volumes of crystalloid and colloid solutions to maintain adequate volemia.

Finally, the use of the intraoperative cell salvage system and the postoperative autotransfusion of the shed mediastinal drainage blood also contributed to avoiding transfusions in our patient (20).

In conclusion, although we cannot prove that the disease state and the interventions were strictly related to the clinical course and outcome of our patient, the successful management of this case suggests that proper application of a comprehensive blood-sparing protocol may control excessive bleeding and avoid the requirement for allogeneic transfusions in patients with minor congenital platelet defects submitted to CPB heart surgery.

	Footnotes

 
Accepted for publication April 17, 2006.

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