Procoagulant activity in patients with sickle cell trait

Area of Science:

• Hematology
• Thrombosis Research
• Genetics

Background:

• Sickle cell trait (STr) is typically asymptomatic.
• However, STr patients face risks of hypercoagulability, venous thromboembolism, and exertional exercise syndrome.
• The underlying causes of these adverse events remain unclear.

Purpose of the Study:

• To investigate procoagulant activity in monozygotic twins with STr.
• To assess thrombotic risk by evaluating in-vivo and ex-vivo thrombin generation.
• To examine the role of red blood cell (RBC)-derived microparticles and rheology.

Main Methods:

• Assessed in-vivo thrombin generation markers: prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complexes (TAT).
• Measured D-dimer as a fibrinolytic activity marker.
• Utilized ex-vivo thrombin generation test (TGT), flow cytometry for microparticles, and assessed RBC deformability, viscosity, and aggregation.

Main Results:

• Patient 2 showed markedly elevated TAT and F1 + 2, indicating a prothrombotic state; Patient 1 had normal levels.
• Both patients exhibited elevated D-dimer and similar elevations in TGT peak thrombin and endogenous thrombin potential (ETP).
• Both patients had elevated RBC-derived microparticles, while RBC rheology was normal.

Conclusions:

• Sickle cell trait may present with distinct levels of hypercoagulability.
• One twin demonstrated a prothrombotic state, suggesting differential thrombotic risk.
• Measuring these coagulation differences could stratify STr patients into high and low-risk groups for complications.