Melana Yuzefpolskaya, MD
People with hematologic disorders undergoing heart transplantation have an increased risk of severe primary graft dysfunction (PGD), postoperative infections, and acute cellular rejection, but the same survival benefit as patients without these conditions, shows a new study in Clinical Transplantation. Led by Melana Yuzefpolskaya, MD, a cardiologist at NewYork-Presbyterian/
“From our clinical and observational experience, we had an inclination that these patients may do worse than patients without pre-existing hematologic disorders,” says Dr. Yuzefpolskaya. “That was the impetus to look at our institution’s data and see whether that holds true.”
“We wanted to prove that these patients may represent a higher-risk population. And by higher risk we mean, do hematologic disorders impact survival afterheart transplantation?” she continues. “And do they impact the rates of PGD, infection, length of hospital stay, blood product requirements, and rejection that may occur after transplant? We wanted to characterize these patients better.”
From our clinical and observational experience, we had an inclination that these patients may do worse than patients without pre-existing hematologic disorders. That was the impetus to look at our institution’s data and see whether that holds true.
— Dr. Melana Yuzefpolskaya
Analyzing Past Cases
Dr. Yuzefpolskaya and the other study authors reviewed the medical records of heart transplant patients who had a heart transplant at Columbia University Irving Medical Center between 2010 to 2019. A board-certified hematologist identified those with hematologic disorders, which included heparin-induced thrombocytopenia (HIT), possible immune thrombocytopenia purpura, possible antiphospholipid antibody syndrome, thrombocytosis, antithrombin III deficiency, Factor V Leiden, polycythemia vera, and other relevant diagnoses. A total of 490 transplant patients were included in the study and of these, 29 (5.9%) had pre-existing hematologic disorders.
The analysis showed that having a hematologic disorder did not impact survival. “Patients with pre-existing hematologic disorders had a comparable 3-year survival to those with no bleeding or clotting disorders,” says Dr. Yuzefpolskaya.
However, the rates of PGD—meaning the transplanted heart didn’t immediately function to its full capacity—and the concomitant need for mechanical circulatory support (MCS) with extracorporeal membrane oxygenation (ECMO) was significantly higher. Heart transplant patients with primary bleeding or clotting disorders had a three-fold higher rate of severe PGD and postoperative temporary MCS.
Having a hematologic disorder also conferred a three-times greater risk for postoperative infection and two-times the risk for acute cellular rejection. Additionally, patients with bleeding and clotting problems spent more time in the hospital after heart transplant (31 days versus 26 days for patients with no hematologic disorders).
There were no differences between the two groups in the need for red blood cell or platelet transfusions during the procedure and no statistically significant differences in the development of cardiac allograft vasculopathy or donor-specific antibodies within the three years following the transplant.
Emerging Theories
While answering some questions, the study begs new ones, such as how hematologic conditions lead to higher rates of PGD and the need for ECMO post-transplant. Possible explanations rest on the pro-inflammatory effects of coagulation.
Digital illustration of a human heart
“It is possible that bleeding and clotting disorders contribute to enhanced inflammatory response and immune dysregulation in the immediate postoperative period, thereby leading to early graft failure,” Dr. Yuzefpolskaya says. The inflammatory response could also contribute to vasoplegia that increases the risk for postoperative PGD and MCS.
Understanding how hematologic conditions raise postoperative infection risk is another line of inquiry. “Here, the interplay between coagulation and the innate immune system could explain increased susceptibility to infection in those with disorders of bleeding or clotting,” Dr. Yuzefpolskaya suggests. “Alternatively, higher rates of temporary MCS use postoperatively would also expose those with hematologic disorders to infectious complications.”
The wide swath of hematologic diagnoses represented in the study limited researchers’ ability to delineate the mechanisms for these effects. However, bleeding and clotting disorders occur infrequently among transplant recipients, necessitating their inclusion.
Future Steps
More research is needed to provide mechanistic explanations for the findings of the study and advance treatments. “It would be beneficial to have a multicenter study, where we can share data, and create a robust cohort of patients. These retrospective analysis can provide a platform for developing management algorithms for these higher risk patients and test them prospectively, in an effort to improve complications rates observed,” says Dr. Yuzefpolskaya.
Patients with hematologic disorders derive the same survival benefits from heart transplant and bleeding and clotting problems should never be viewed as a contraindication. “We should be on high alert that some complications may occur at higher rates among these patients and perhaps tailor their management accordingly.”
— Dr. Melana Yuzefpolskaya
In the meantime, the study may already make a difference in heart transplantation in patients with bleeding and clotting problems. Dr. Yuzefpolskaya believes the findings call for a multidisciplinary approach, with hematologists, intensive care specialists, heart failure specialists, and cardiothoracic surgeons all weighing in on protocols.
“Patients with hematologic disorders derive the same survival benefits from heart transplantation and pre-existing bleeding and clotting disorders should never be viewed as a contraindication,” Dr. Yuzefpolskaya says. “We should be on high alert that some complications may occur at higher rates among these patients and perhaps tailor their management accordingly.”
