Clot Club: Hypercoagulation During Sickle Cell Disease
Posted: May 25, 2021
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Clot Club: Hypercoagulation During Sickle Cell Disease
Sickle cell disease (SCD) is an inherited hemoglobin disease that disrupts the ability of red blood cells (RBCs) to deliver oxygen throughout the body. RBCs are normally round and flexible, which allows them to flow easily through the vasculature. However, in SCD, RBCs are crescent-shaped due to the expression of an atypical sickle hemoglobin variant (HbS). The abnormal shape of sickle RBCs can cause them to clump together and block blood flow and promote thrombosis. Due to the hypercoagulable state of SCD, thrombotic complications can drive ischemic stroke, venous thromboembolism, severe pain episodes, and organ damage.
Coagulation factors are key initiators in the pathogenesis of SCD. Interestingly, the coagulation system can be activated and elevated in individuals with SCD, even in the absence of vascular occlusions.
Coagulation Markers in Research
It is suggested that aberrant coagulation and platelet overactivation contribute to the pathogenesis of SCD. Further research and clinical trials are needed to explore the mechanisms driving abnormal coagulation in SCD and to identify effective therapies to treat it.
| Coagulation Factors | Components | Function | Biomarkers and Methods of Evaluation | Activity in Sickle Cell Disease |
| Extrinsic Pathway | Tissue factor (TF) FVII | Primary pathway to initiate coagulation following vascular endothelial injury | Prothrombin time (PT) | Increased TF expression |
| Intrinsic Pathway | Prekallikrein HMWK, FXII, FXI |
Activated by exposed collagen in the subendothelium and functions to initiate clot formation | Activated partial thromboplastin time (aPTT) | Decreased Prekallikrein, FXII, and HMWK plasma levels Increased levels of procoagulant microparticles |
| Common Pathway | FV, FVIII, FIX, FX thrombin FXIII fibrin |
Catalysts in the final steps of coagulation to cleave fibrinogen and form blood clots | Thrombin Generation Assays (TGA), TAT, PAP, F1.2, D-dimers, Fibrinogen | Increased thrombin levels |
| Fibrinolysis | Plasmin | Enzymatic degradation of fibrin in blood clots | uPA, tPA, PAI-1, D-dimers | Increased fibrinolytic activity |
| Platelet Activation | Collagen Fibrinogen, vWF ADAMTS-13 |
Platelets activate and aggregate to form a platelet plug | vWF, ADAMTS-13 | Increased platelet numbers, platelet activation, and platelet aggregation |
| Complement System | C3a C5a |
Activated by the coagulation system and contributes to thrombus formation | C3a and C5a | Increased C3a and C5a expression |
| Anticoagulant Proteins | Protein C Protein S |
Negative feedback to regulate coagulation and inflammation | Protein C Protein S |
Decreased Protein C and Protein S levels |
Automated Measurement of Primary and Secondary Hemostasis Markers
| Instrument | Fully Automated Coagulation Analyzer | Clot Growth & Fibrinolysis Dynamics | Primary Hemostasis and Platelet Function Testing | |
| Ceveron® 100 Series | Thrombodynamics | T-TAS® 01 | Atlas PST | |
Ceveron® series, Thrombodynamics®, and Atlas® PST are for research use only. Not for use in diagnostic procedures.
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