Characterizing Thrombotic Risk in TEMPI Syndrome: A Retrospective Case Series

Introduction: TEMPI Syndrome was first described in 2011 as a rare syndrome that typically presents with five core clinical characteristics specified by its acronym: telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. Since its first description, cases have been reported with additional clinical features including other cutaneous findings, serous cavity effusions, and vascular events, including thrombosis and hemorrhage. The suggested diagnostic criteria include three major criteria that appear in all patients with TEMPI syndrome (telangiectasias, elevated erythropoietin (EPO) level and erythrocytosis, and monoclonal gammopathy) and two minor criteria that are not always present (perinephric fluid collections and intrapulmonary shunting). The possibility of an “other criterion” of venous thromboembolism (VTE) has been suggested, but there has been limited research to understand its true incidence.

Several characteristics of TEMPI Syndrome are associated with VTE in other clinical contexts. There is an increased risk of VTE in disorders of erythrocytosis such as Polycythemia Vera, Chuvash Polycythemia, secondary erythrocytosis, and idiopathic erythrocytosis. In addition, monoclonal gammopathy (MG), both of undetermined significance (MGUS) and of clinical significance (MGCS), has a statistically significant association with VTE.

Methods: To understand the incidence of VTE in TEMPI Syndrome, we reviewed the literature for all published cases of TEMPI Syndrome. The authors of each publication were contacted to provide clinical data including age, sex, TEMPI characteristics, type and timing of thrombosis if present, treatment of TEMPI, and whether the patient was undergoing phlebotomy.

Results: We identified 42 patients with TEMPI Syndrome reported in the literature. Detailed clinical data on VTE was obtained for 14 patients. The three major clinical criteria were present in all 14 patients. Of the 14 patients, nine experienced at least one VTE event. For the 9 patients with VTE, the median age was 53 (36-67) and 56% were female. For the 5 patients without VTE, the median age was 56 (range 40-75) and 60% were female. Most patients had IgG Kappa MG which is the most common form of MG found in TEMPI Syndrome. However, one patient with VTE and two patients without VTE had IgA Lambda MG, while another patient with VTE had IgM Lambda MG. EPO levels varied; patients with VTE had EPO levels from 73.5 to >5000 mU/mL and patients without VTE had levels from 433 to 5728 mu/mL. The hematocrit ranged from 55-64% in patients with VTE and 51-59% in patients without VTE. Of the patients with VTE, the type included lower extremity DVT + pulmonary embolism (PE) (2), jugular venous thrombosis (2), upper extremity DVT alone (1), lower extremity DVT alone (1), cerebral venous sinus thrombosis (2), Superior Vena Cava thrombus (1), and cardiac apex thrombus (1). There were no arterial clotting events in any of the 14 patients.

Conclusion: The prevalence of VTE in patients with TEMPI Syndrome is high, with at least 21.4% of known patients developing VTE during their clinical course. VTE in TEMPI Syndrome can occur as a PE, DVT, or atypical site thrombosis, but the small sample size limits analysis of specific risk factors. Details on thrombotic events are lacking in the literature and further attempts to obtain these data are underway. Clinicians should be aware of the risk of VTE in patients with TEMPI, particularly in unusual locations, and further research on the impact of treatments such as phlebotomy and myeloma-directed therapies is underway to distinguish pathophysiology

Strobl:Pfizer: Consultancy; Janssen: Honoraria. Elli:BMS: Membership on an entity's Board of Directors or advisory committees; ABBVIE: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Sykes:Clear Creek Bio: Consultancy, Current equity holder in private company. O'Connell:Sobi: Membership on an entity's Board of Directors or advisory committees.