An Improbable Aortic Surgery in the Setting of Giant Platelet Disorder

A 28-year-old woman with Epstein syndrome and profound thrombocytopenia (platelet count of 6,000/μL at presentation) developed severe aortic regurgitation and an aortic root aneurysm with type A dissection. She also had end-stage renal disease for which she was receiving hemodialysis, and her history was notable for spontaneous subdural hematoma a year earlier.

In addition to the aortic findings, imaging at her current presentation revealed a pseudoaneurysm of the right subclavian artery. Her calculated panel-reactive antibody (cPRA) was 87%, which signaled a high degree of platelet transfusion refractoriness due to HLA alloimmunization.

Management: Is aortic surgery possible?

Epstein syndrome is an expression of MYH9-related thrombocytopenia, a rare genetic disorder characterized by giant platelets and thrombocytopenia. Defects in the MYH9 gene lead to premature release of platelets from bone marrow.

The patient had undergone prior surgeries under coverage of platelet transfusions, with variable success and signs of increasing immune refractoriness due to antibodies. Moreover, her chronic kidney disease, with anuria, conferred significant risk of volume overload and transfusion-associated circulatory overload (TACO) if platelet transfusions were pursued without a clear target that properly balanced benefit and risk. The patient’s uremic environment further compromised her platelet function.

These considerations prompted the Cleveland Clinic cardiothoracic surgery team to consult extensively with multidisciplinary colleagues from hematology, transfusion medicine, cardiothoracic anesthesiology and nephrology to explore the feasibility of aortic surgery as well as preoperative and perioperative management to control bleeding in view of the patient’s severe bleeding risk.

Optimization for surgery

Discussions among this multidisciplinary team resulted in establishing 40,000/μL as a realistic target perioperative platelet count. The team began to optimize the patient for surgery with a detailed plan that included weekly administration of the bone marrow stimulant romiplostim.

Initial increases in the platelet count were erratic, but dose escalation eventually achieved the 40,000/μL target preoperatively. Adjunctive HLA-matched platelets were given preoperatively with dialysis.

An uneventful repair

Cannulation was obtained high in the aorta to prevent circulatory arrest, and the patient’s temperature was allowed to drift (to 34 °C) without active cooling.

A successful Bentall procedure was completed with replacement of the aortic valve, aortic root and ascending aorta with composite graft including a Carpentier-Edwards pericardial valve #27. No significant postoperative bleeding issues were encountered, and intraoperative bleeding was controlled with aminocaproic acid, desmopressin and unmatched platelets, in addition to fresh frozen plasma and cryoprecipitate. HLA-matched platelets were given postoperatively to treat any visible bleeding and to maintain the perioperative target count.

The patient was discharged home within a week of the operation.

Discussion

This case represents the first known report of aortic surgery in a patient with MYH9 mutation.

“We wanted to operate because of the patient’s young age and strong indication for surgery, but the bleeding risk was daunting,” says Cleveland Clinic cardiothoracic surgeon Gosta Pettersson, MD, PhD. “That is why the degree of multidisciplinary collaboration in this case was absolutely essential to the surgery’s success.”

Central to that collaboration was hematology expertise. “Platelets in patients with MYH9-related disorder are so large that they can be miscounted as red blood cells using an automated count [see Figure],” explains Anne Neff, MD, of Cleveland Clinic’s Department of Hematology and Oncology. “So we used specialized methodology with fluorescein dye to count the platelets more accurately, which was crucial to determining the safest time at which to attempt surgery in this patient.”

Figure. Patient peripheral smear showing large platelets among red blood cells (RBCs). Note that the platelets are equal in size to RBCs, which can easily lead to miscounting of platelets during an automated count.

“Success in this case was clearly attributable to multidisciplinary development of a comprehensive, consistent and clearly communicated plan encompassing the preoperative, intraoperative and postoperative periods,” adds Suzanne Bakdash, MD, MPH, a transfusion medicine physician in Cleveland Clinic’s Department of Laboratory Medicine. She notes that the plan called for intra- and postoperative platelet transfusion to be guided by bleeding and thromboelastography rather than by platelet count, with close monitoring of volume status and optimization of all other hemostatic parameters.

“Open heart surgery had previously been deemed prohibitive for this patient at other centers,” notes Anand R. Mehta, MD, lead cardiothoracic anesthesiologist on the case. “Her case illustrates that once someone becomes a Cleveland Clinic patient, we will draw on our colleagues’ expertise as broadly as necessary to make treatment possible for the patient and deliver the best outcome achievable.”

“This complex case required extraordinary expertise and seamless collaboration,” adds Cleveland Clinic Chair of Thoracic and Cardiovascular Surgery A. Marc Gillinov, MD. “As a result of these efforts, this 28-year-old woman received a successful operation and returned home to her family.”