Thrombo-Haemorheological Coupling in Haemoglobinopathies: Mechanistic Insights into the Bidirectional Interplay between Coagulation Activation and Erythrocyte Flow Properties
Adenuga Jacob Olaitan *
Department of Haematology and Blood Transfusion Science, Faculty of Medical Laboratory Science, Achievers University, Owo, Ondo State, Nigeria.
Olusegun Taiwo Oke
Department of Haematology and Blood Transfusion Science, Faculty of Medical Laboratory Science, Achievers University, Owo, Ondo State, Nigeria.
Muhibi Musa Abidemi
Department of Haematology and Blood Transfusion Science, Faculty of Medical Laboratory Science, Achievers University, Owo, Ondo State, Nigeria and Department of Medical Laboratory Science, Faculty of Applied Health Sciences, Edo State University, Iyamho, Edo State, Nigeria.
Adesina Beatrice Ebun
Department of Haematology and Blood Transfusion Science, Faculty of Medical Laboratory Science, Achievers University, Owo, Ondo State, Nigeria.
Olatunji Oluwatobi
Department of Chemical Pathology and Immunology, Faculty of Medical Laboratory Science, Achievers University, Owo, Ondo State, Nigeria.
Ajao Oluwadare Amos
Department of Haematology and Blood Transfusion Science, Faculty of Medical Laboratory Science, Achievers University, Owo, Ondo State, Nigeria.
M. B. Ajayi
Department of Microbiology and Parasitology, Faculty of Medical Laboratory Science, Achievers University, Owo, Ondo State, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Hemoglobinopathies (e.g., HbS, HbC, HbF) are the most common single-gene disorders worldwide, especially in sub-Saharan Africa. Beyond affecting red blood cells and oxygen transport, they significantly disrupt blood clotting (hemostasis) and blood flow properties (haemorheology).
This review synthesizes current evidence from molecular biology, cellular hematology, and clinical hemostasis research to construct a mechanistically integrated framework for thrombo-haemorheological coupling in hemoglobinopathies. We examine how hemoglobin structural variants alter erythrocyte membrane phospholipid topology, intracellular viscosity, and cytoskeletal integrity to produce downstream procoagulant signaling, and conversely, how activated coagulation factors, fibrin deposition, and platelet-mediated networks feed back to impair erythrocyte flow properties. Specific genotype-phenotype relationships are examined across HbAA, HbAS, HbSS, HbSC, HbCC, HbAC, and elevated HbF phenotypes. The role of the vascular endothelium, neutrophil extracellular traps (NETs), and the thrombo-inflammatory axis is critically evaluated. We propose the Thrombo-Haemorheological Coupling Axis (THCA) as a framework for future research and therapeutic targeting.
Keywords: Hemoglobinopathy, hemorheology, coagulation cascade, erythrocyte deformability, thrombo-inflammation, sickle cell disease, blood viscosity, hemostasis