VPB0757 - TREGs-induced Immune Thrombotic Thrombocytopenia in Polycythemia Vera

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Rossella Cacciola, PhD

Head of Haemostasis Unit
Università di Catania
Catania, Sicilia, Italy

Co-Author(s)

VV

Veronica Vecchio

medical student
School of Medicine University of Catania
Catania, Sicilia, Italy
EG

Elio Gentilini Cacciola

resident doctor
Sapienza University of Rome
Rome, Lazio, Italy
EC

Emma Cacciola

Co-Head Haemostasis Unit
Università di Catania
Catania, Sicilia, Italy

Background: T-regulatory cells (Tregs) defined as CD4+, CD25high, CD127low cells prevent autoimmunity. The Ph1-negative myeloproliferative neoplasms (MPNs) show a JAK/STAT-mediated reduction of Tregs.

Aims: We investigated Tregs and platelet and coagulation activation in Polycythemia Vera (PV) and thrombosis.

Methods: We enrolled 60 WHO-defined PV patients (30 men, 30 women; mean age 45±10 years) without cardiovascular risk factors or thrombotic history having poplitea deep vein thrombosis (40/60) and pulmonary embolism (20/60) on lower-limb ultrasonography and computed tomography angiography. 60 healthy age- and sex-matched were controls. All patients were evaluated for Tregs, PF4-dependent antibodies, platelets, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimer (DD). Tregs were measured by flow cytometry, PF4-dependent antibodies by PF4-dependent EIA, platelets by automated analyzer, PT and APTT by coagulometric test, Fib using Clauss method, and DD using ELISA. Complete blood hemostasis was studied by PFA-100 on Collagen/ADP (CT-ADP) and Collagen/Epinephrine (CT-EPI) cartridges and Thromboelastometry method on Clotting Time (CT), Clotting Formation Time (CFT), Maximum Clot Firmness (MCF), and clot lysis at 30 minutes (LY-30).

Results: All patients had low Tregs (1,5±0,5% vs 5±1%) thrombocytopenia (70±5x109/L vs 230±20x109/L), longer PT (30±10 s vs 14±2 s) and PTT (60±10 s vs 30±5 s), lower Fib (90±20 mg/dl vs 180±20 mg/dl), higher DD (650±100 μg/l vs 150±50 μg/l) and shorter C/ADP and C/EPI (C/ADP, n.v. 68-121 s (40±10 s vs 80±20 s) and C/EPI n.v. 84-160 s (35±5 s vs 95±10 s). All patients had shorter CT (INTEM 35±20 s vs 180±20 s, EXTEM 20±10 s vs 52±10 s), shorter CFT (INTEM 15±10 s vs 90±10 s, EXTEM 20±10 s vs 70±30 s), longer MCF (INTEM 130±10 mm vs 60±10 mm, EXTEM 120±10 mm vs 62±10 mm), and lower LY-30 (INTEM 0.9% vs 15%, EXTEM 0.8% vs 15%).

Conclusion(s): These findings shed new light on thrombotic pathogenesis in patients with PV.