Accordingly, for patients who had primary KOA, our study detailedly assessed the potential association of preoperative EA exponent and postoperative acute DVT risk following TKA with routine anticoagulation of LMWH. We found a tight correlation between the lower EA exponent and the increased risk of DVT, especially in female KOA patients. This emerging evidence appeared to supported an increasingly larger role of EA in the etiopathogenesis of DVT, which can be considered as a novel finding.
Actually, VTE is initiated by inflammation and blood stasis which may lead to the generation of thrombi rich in fibrin and erythrocytes. From the perspective of hemorheology, erythrocytes can contribute to VTE under certain conditions mainly by promoting a rise in hematocrit, blood viscosity (BV)), marginate platelets and fibrin deposition, an elevation in EA, a decrease in erythrocyte deformability and/or its self-generated complex effects on blood clot structure and stability[12–14]. It can be indicated that erythrocytes are not only major components of venous thrombi and critical influence factors of VTE risk, but also actively incorporated into VTE pathophysiology. Biologically, EA is commonly manifested by roleaux (linear arrays of stacked cells) or two- and three-dimensional aggregates with blood stasis in a osmotic gradient mechanism, which is thought to be reversible and shear dependent[18, 19]. The aggregates of erythrocytes can potentially increase BV and hydrodynamic resistance of larger vessels exactly as lower extremity veins[15, 19]. Also, the extent of EA is the main determinant of low shear BV which is closely relevant to DVT[15, 19]. Accordingly, the underlying effects exerted by alterations of EA due to qualitative, quantitative, and interactive changes of erythrocytes in the pathogenesis of DVT is of considerable importance[11, 14].
In clinic, it is notable that the results seem to be somewhat inconsistent from the conclusions of the available studies[20–23]. Different confounding factors used for adjustment, testing time points for EA, and study populations can partly be the explanations. It has been expounded that the damage to the vessel wall, blood hypercoagulable state after surgery, and the venous stasis because of long-term bed rest are thought to be the 3 major reasons for the formation of postoperative DVT.
Considering our conclusions, it is tempting to speculate that the prothrombotic effects of erythrocytes in patients with a low EA exponent before surgery may be more prone to be affected by multiple factors during TKA surgery, which in turn lead to a relatively large increase of EA that ultimately have an imperceptible impact on DVT.
In spite of this, systemic hemorheological alterations may be not comparable to those in local areas where minimum disturbances can be more associated with DVT[11
]. To our best knowledge, the exact mechanisms linking EA and DVT await clarification and the results of our study may open new perspectives in this field.
A local hemorheological variation may played a crucial role in DVT formation and confirming the pathogenic significance of locally altered blood rheology in the development of DVT is much-required.
Noteworthily, both OA and obesity have been gradually recognized as lowgrade inflammatory disorders accompanied with an elevation of systemic inflammatory cytokines[25, 26]. Notably, there is mounting physiological evidence for the important role of inflammatory biomarkers in thrombogenesis[27, 28]. KOA is more common in obese people and these abnormally expressed inflammatory mediators in KOA patients may also affect EA in pleiotropic pathways. In this regard, the interactions between inflammatory state and EA have not been unequivocally established, further research is required before regulating EA can become therapeutic alternatives for DVT prophylaxis and treatment.
For the specific population of KOA patients who needed to undergo TKA, we firstly and systematically analyzed the correlation between preoperative EA exponent and post-surgery DVT risk. After adjustment for important confounders and effect modifiers, the findings emphasized the importance of EA in DVT prevention and are of a certain accuracy, which may have great guiding significance for follow-up clinical work. Still, the small sample size of males and the possible uncontrollable factors during TKA surgery may limit our results.