Coronary Artery Bypass Grafting and Mitral Valve Replacement in a Patient with a Rare Platelet Disorder known as Glanzma

Introduction

Glanznmann’s Thrombasthenia (GT) is a rare inherited platelet disorder with an autosomal-recessive inheritance pattern affecting the gluycoprotien IIb-IIIa complex. It is this hetero-dimer that is responsible for platelet-platclot binding. Patients with this condition have a notable haemorrhagic tendency often demonstrating epistaxis and gingival bleeding. As of 1990, 177 Cases of GT had been reported worldwide, with 12 of those occurring in the United States. Cardiopulmonary bypass (CBP) activates platelets with resultant structural and biochemical changes. A patient presenting for cardiac surgery requiring CPB obligates the surgical team to prepare for this bleeding disorder. This case report describes the management of a patient with a history of GT who required surgical replacement of his miltral valve and coronary artery revascularization.

Case Description

A 65-year old male presented with a history significant for childhood rheumatic fever, rheumatic heart disease with mitral regurgitation, GT, recurrent GI bleeding with a history of gastric ulcer, treated with laser surgery one year prior, history of epistaxis and gingival bleeding, splenectomy status post three years, type II diabetes mellitus, hypertension and hypercholesterolemia. He complained of increasing fatigue and dyspnea on exertion with fast walking or lifting any items.

The patient was on the following medications pre-operatively: Methyldopa, the diuretic Triamterene HCTZ and the angiotensin II inhibitor Cozaar (losartan potassium) for the treatment of hypertension, and Humulin (Insulin) for the treatment of diabetes. Pre-operative laboratory values were as follows:

Table 1: Patient Lab Values Value Reference Value
Platelet Count 203 130-400
PT 11 10.8-12.8
PTT 26.9 23.0-33.0
Fibrinogen 214.9 200-400

Cardiac catheterization revealed two vessel coronary artery disease and mitral regurgitation. The patient was scheduled for coronary artery bypass surgery and replacement of the mitral valve.

Procedure

In order to conduct a safe cardiopulmonary bypass, minimize complement activation and trauma to the blood components, specifically platelets, two million units of Aprotinin and four mg Dexamethasone were administered in the CPB circuit. The patient had received one unit of single donor platelets prior to cardiac catheterization (six days prior to the day of surgery) and one unit just prior to his transfer to the operating room. He received neither Heparin nor Aspirin prior to the surgery, a precaution to avoid massive bleeding and preserve his clotting factors. The base line ACT was 121.

The CPB circuit consisted of a Cobe hollow fiber membrane oxygenator with a hard shell venous reservoir/cardiotomy Cobe tubing and Sorin BCD Vanguard cardioplegia set. The circuit was primed with 1700 cc of Normsol to which was added 5,000 units of heparin, two million units of aprotinin and 4 mg of dexamethasone.

CPB was established in the routine fashion achieving a flow index of 2.4 liters per minute per meter squared. The operation was carried out at normathermia. The heart was fibrillated, aorta cross-clamped, and myocardial preservation was achieved by administering cold blood cardioplegia in an antegrade and retrograde fashion. Two units of packed red blood cells were given through the bypass circuit to maintain the hemoglobin level above 8mg/dl, The mitral valve was replaced with 27min Carpentier Edwards bioprosthetic heart valve and received two coronary artery bypass grafts: left internal mammary artery (LIMA) to the left anterior descending (LAD), and a saphenous vein graft (SVG) to tile right coronary artery (RCA). During bypass activated clotting times (ACT) were maintained greater than 600 seconds, with 5,000 units of heparin added 90 minutes into the bypass run to elevate the ACT from 550 to 700 seconds. The patient was successfully weaned from cardiopulmonary bypass after 127 minutes. Protamine was administered to reverse heparin and the final ACT was 109 seconds. Post operatively the patient was on Dopamine, Nitroglycerine and Propofol. While surgical bleeding was not significant after the termination of CPB or after the completion of Protamine administration, 2 units of single donor platelets, 2 units of packed red blood cells, 10 units of cryoprecipitate and 4 units of flesh frozen plasma (FFP) were given to prevent anticipated bleeding in light of his GT. The patient was transferred to the surgical intensive care unit in stable condition.

Results

The patient received neither heparin nor aspirin therapy after his surgery and did not require any further blood products thereafter. He was transferred to a step down unit on postoperative day 2, and on postoperative day 3 he was sent to the cardiac step-down unit. On POD #5 an echocardiogram revealed a pericardial effusion, probably due to severe platelet dysfunction, and the patient was transfused with 1 unit of single donor platelets. Although the pleural effusion was significant, a thoracentesis was deemed contraindicated due to his bleeding dyscrasia. The patient was discharged on POD # 11 and was maintained on the following medications: the diuretic Lasix, potassium (K-dur), Humulin insulin, an oral anti-hyperglycemic (Glucophage), the ACE inhibitor Prinivil, beta I blockers Toprol and Lopressor, and Prilosec to inhibit gastric secretions.

Table 2: Patient Bleeding Times Pre-Operative Post-Operative Range
(12/10/98)
(12/26/98)

7.5
> 10.0
3-9

Discussion

The term Thrombasthenia means weak platelets. G1azmann knew that the platelets were weak because clots from such platelets did not shrink or express serum. Congenital platelet function defects are bleeding disorders characterized by prolonged bleeding time in spite of normal platelet counts. There is usually a family history of a bleeding disorder consisting of prolonged bleeding or easy bruising. GT is a condition, which causes mucosal and postoperative bleeding which may be severe. Clinical features include nose bleeds, intra-operative and post- operative bleeding, easy bruising, prolonged bleeding with superficial injuries, abnormal menstrual periods, bleeding gums, and may extend to purpura, thromboembolism, mucocutaneous and post-traumatic hemorrhage.

Laboratory features include a normal platelet count, normal or abnormal PT and PTT, and an abnormal impaired clot retraction and prolonged bleeding time.

GT is classified into 3 different types. Type I shows a severe deficiency of both GPIIb-IIIa complex and alpha-granule storage pool of fibrinogen. Type II shows a moderate deficiency of both and the third type shows a half-normal to normal level of GPIIb-IIIa complex.

Platelet adhesion in GT is normal. The bleeding tendency is due to an impaired platelet haemostatic plug formation. Fibrinogen is required for normal platelet aggregation. GPIIb-IIIa complex functions as a fibrinogen receptor. Thus, this explains the lack of aggregation in response to all physiologic aggregation inducers and the ability to support clot retraction. In order to avoid life threatening bleeding in patients with GT, platelet transfusion is the only treatment, but be should be used carefully because patients may develop platelet-specific alloantibodies directed against platelet antigens that are expressed on GPIIb-IIIa. Those patients may also develop human leukocyte antigen (HLA) antibodies and thus become refractory to subsequent platelet transfusions. All patients with bleeding disorders should avoid taking Aspirin, because it prolongs the bleeding time.

References

Michel R. Leduc, Bernard-Soulier syndrome and Glanzmann’s Thrombasthenia. Cand J MedTech 1995;57:211-214.

Roby L. Rogers, MD, John Lazarchick, MD, Clinical Pathology Rounds: Identifying Glanzmann’s Thrombasthenia. Lab Medicine 1 996;27:579- 581.

Arjuna Weerasinghe, FRCS, Kenneth M. Taylor, MD, The Platelet in Cardiopulmonary Bypass. Ann Thorac Surg 1998;66: 2145-52.