Admission pH as a risk factor for preoperative deep vein thrombosis in elderly hip fracture patients: a retrospective cohort study

We observed a linear correlation between serum pH and preoperative DVT in elderly patients with hip fracture. pH is a risk factor for DVT development; however, the relationship is curvilinear. pH 7.39 is the inflection point in the curve, and pH is highly associated with DVT at pH < 7.39 (OR 19.47; 95% CI 1.45–260.91; ask= 0.0249). Patients with lower pH values ​​had a lower chance of DVT before surgery, and for every 0.1 unit change in pH value, the risk of DVT increased by 18.47 times. Although pH >7.39, pH was not associated with DVT (OR 1.26; 95% CI 0.85–1.86; ask= 0.2561), the probability of DVT does not change with pH, ​​and the highest risk of thrombosis is reached.According to the comparison between logistic regression and PSM results, logistic regression is more accurate.¹⁹ In the research. In fact, the results of logistic regression and PSM results in this study have the same inflection point.

The recognized pathogenesis of lower extremity DVT is based on the three main elements of DVT formation proposed by Virchow in 1856: slow blood flow, intimate injury, and blood hypercoagulability.^twenty.Although most hip fractures in the elderly are caused by low-energy injuries, the proportion of high-energy injuries is relatively low^{twenty one}

Hip joint injury has a more significant impact on the systemic condition of elderly patients, especially hemodynamic instability and homeostasis imbalance, which are more likely to stimulate the exogenous coagulation mechanism and increase the risk of DVT.^{twenty two}.

The formation of DVT is a complex and dynamic physiological process. The susceptibility to DVT thromboembolism is related to its metabolites.^{twenty three}.The most common metabolites potentially associated with DVT are carnitine, glucose, phenylalanine, 3-hydroxybutyrate, lactate, tryptophan, and some monounsaturated and polyunsaturated fatty acids¹⁴. Studies have shown that lactate levels can affect coagulation or platelet aggregation of all of these metabolites.Most elderly patients often have occult blood loss after hip fracture^{twenty four}. Acute blood loss results in reduced cardiac output, tachycardia, hypotension, organ hypoperfusion, and interference with aerobic metabolism, while increased anaerobic metabolism results in lactic acid production and metabolic acidosis. In addition, an increase or decrease in pH can also lead to disturbances in the internal environment.Due to the reduction or obstruction of blood supply, a hypoxic microenvironment is formed at the fracture site, and anaerobic enzymes are enhanced, leading to the accumulation of lactic acid, thereby forming an acidic microenvironment with a low pH value at the fracture site.^25.26. Elevated lactate levels are thought to be related to enhanced erythrocyte glycolysis within the thrombus. A study by Maekawa et al.²⁷ Lactate was found to be the most abundant metabolite in blood clots, with levels at least five times higher than those in venous blood. As Crowell et al. Studies have shown that lactic acid stimulates whole blood coagulation and hinders platelet aggregation to a certain extent.As pH decreases, lactate infusion is significantly associated with shortened whole blood clotting times in vitro and in vivo²⁸

. In addition, acid-base imbalance can damage vascular endothelium. Damaged endothelial cells can release tissue factors, activate the blood barrier system, reduce fibrinolytic activity, and enhance platelet adhesion and aggregation.The potential impact of an acidic environment at low pH on cell function is critical²⁹. The decrease in blood pH can lead to an increase in the enzyme activity of coagulation factors, a decrease in the anticoagulant activity of heparin, and an increase in platelet aggregation, leading to blood hypercoagulation and ultimately DVT. Therefore, we speculate that the correlation between pH value and DVT is that local lactic acid accumulation in trauma caused by blood loss changes the pH value of the internal environment and affects the normal metabolic environment through various pathways, leading to the formation of DVT. However, this hypothesis should be tested in future research.

In the current study, we performed univariate analyzes to derive a more reliable relationship between admission pH and DVT and to identify confounding factors for DVT development. Gender, fracture classification, multiple injuries, operative time, dementia, gastritis, and activated partial thromboplastin time were identified as confounding factors. Multivariate logistic regression was performed after further adjusting for confounding variables, and the results were found to be statistically significant when pH was used as a continuous variable, but not in the trend test. Use curve fitting to infer a curvilinear relationship between pH and DVT. The pH value of 7.39 was found to be the inflection point of the curve.

This study is the first to examine the relationship between admission pH and DVT development. A curvilinear relationship between these two factors was found for the first time.Regarding other blood data (D-dimer, fibrinogen, activated partial thromboplastin time, prothrombin time, thrombin time, albumin, hemoglobin, total cholesterol, triglycerides), the meta-analysis reported that these parameters did not Significant differences³⁰

. This highlights the importance of pH as a predictor of DVT.

This study has several limitations. First, this retrospective study examined the relationship between admission pH and DVT development. However, this study was unable to determine a cause-and-effect relationship between these two factors. Second, our study population came from the largest trauma center in northwest China. Due to reasons such as region, race, and living habits, there may be certain biases in the selection of the research population. These results cannot be generalized to the entire population. All these shortcomings need to be further confirmed in future studies.

In conclusion, pH is nonlinearly related to preoperative DVT in elderly hip fracture patients and may be considered a predictor of DVT risk.