*3.3. Multivariate Analysis between Admission Hematocrit Level and Preoperative DVT*

We used three models (Table 3) to correlate hematocrit levels and preoperative DVT. When the hematocrit level was a continuous variable, linear regression was observed. The fully adjusted model showed a preoperative decrease in the risk of DVT of 3% (OR = 0.97, 95% CI: 0.95–0.99, *p* = 0.0019) when hematocrit levels increased by 1% after controlling for confounders. When hematocrit levels were used as a categorical variable, we found statistically significant differences in the hematocrit level groups of the three models (*p* < 0.05). Compared with the hematocrit Q1 group, the hematocrit Q5 group could decrease the risk of preoperative DVT by 31% (OR = 0.69, 95% CI: 0.50–0.97, *p* = 0.0304). However, there were no statistically significant differences among the Q2–Q4 hematocrit groups and the Q1 group. In addition, the *p* for the trend showed *p* < 0.05 in the three models. This instability indicates a nonlinear correlation.

**Table 3.** Multivariate results by logistic regression (N = 1840).


Data in table: OR (95% CI)**,** *p*-value. Outcome variable: preoperative DVT. Exposure variable: hematocrit level at admission. Minimally-adjusted model: adjust for sex. Fully-adjusted model: adjust for sex, dementia, and multiple injuries.

#### *3.4. Curve Fitting and Analysis of Threshold Effect*

As shown in Figure 3, after adjusting for confounders, we fit a curve to explain the association between Hct levels at admission and preoperative DVT. We compared two fitting models to explain this association (Table 4). Interestingly, an inflection point was observed. Admission hematocrit levels of >33.5 vol% were associated with preoperative DVT (OR = 0.94, 95% CI: 0.91–0.97, *p* = 0.0006). At admission hematocrit levels of <33.5 vol%, there was no statistically significant correlation between preoperative DVT and admission hematocrit levels (OR = 0.94, 95% CI: 0.91–0.97, *p* = 0.0006).

**Figure 3.** Curve fitting between admission hematocrit levels and preoperative DVT. Adjusted for sex, dementia, and multiple injuries.



Adjusted for sex, dementia, and multiple injuries.

#### **4. Discussion**

Our study shows that the level of hematocrit at admission is a strong predictor of preoperative DVT in older adults with hip fractures. Specifically, hematocrit levels at admission were nonlinearly associated with preoperative DVT. A hematocrit level of 33.5 vol% was the inflection point in the saturation effect. When the hematocrit level was <33.5 vol%, the hematocrit level at admission was not a potential risk factor for preoperative DVT (OR = 1.00), and the severity of low hematocrit was not associated with preoperative DVT. When the hematocrit level was >33.5 vol%, for each unit increase in hematocrit, the risk of preoperative DVT decreased by 6% (OR = 0.94). Therefore, a hematocrit level of 33.5 vol% is a useful indicator to predict preoperative DVT in older patients with hip fractures. In clinical practice, these findings can be used to identify high-risk patients who may benefit from specialized care.

Older adults with hip fractures are prone to DVT events due to advanced age, comorbidities (hypertension, heart disease, peripheral vascular disease, cerebrovascular disease), or risk factors (trauma, surgery, limb immobilization), further aggravating their poor prognosis. According to previous studies, the incidence of preoperative DVT in patients with hip fracture is 8–34.9%, and the incidence of DVT in patients with delayed surgery can even reach 62% [9,23,24]. A meta-analysis of 2022 analyzed 9823 patients and found that the incidence of preoperative DVT in elderly patients with hip fractures was 16.6%. Age, sex, BMI, low hemoglobin level, time from injury to admission, time from injury to surgery, type of hip fracture, CHD, dementia, pulmonary disease, kidney disease, smoking, fibrinogen, C-reactive protein, and albumin were considered independent risk factors for DVT [25].

Patients with polycythemia vera have been shown to be associated with an increased risk of DVT [26]. A Mendelian randomization study showed that a polygenic risk score for hemoglobin concentration was positively associated with venous thromboembolism risk in the general population [27]. Therefore, the hypothesis that detection of Hct levels has a predictive effect on the occurrence of DVT in elderly hip fractures has strong biological plausibility. The relationship between hematocrit levels and DVT incidence has previously been studied. A prospective study in Norway evaluating 26,108 adults showed that subjects with a hematocrit in the upper 20th percentile had a 1.5-fold higher risk of total DVT compared with subjects with a hematocrit in the lowest 40th percentile [19]. A case–control trial by Vayá et al. found that the proportion of subjects with a hematocrit greater than 45% was significantly higher in patients with DVT than in healthy controls [28]. A population-based cohort study from Denmark found a U-shaped association between Hct and VTE, but the association was not statistically significant [29]. A 2020 study showed that high levels of hematocrit and hemoglobin are associated with an increased long-term risk of VTE [18]. However, in a population-based longitudinal investigation of the etiology of thromboembolism, no significant association was reported between the hematocrit and the incidence of VTE [30]. An earlier case–control study also found no independent relationship between Hct and VTE [31]. Based on the above controversy, it remains to be further investigated whether hematocrit is the real cause of DVT or an innocent interloper, that is, whether the relationship between the two is causal or whether the relationship is confounded by other confounding factors [32].

Previous studies have been based on the general population. Results based on the general population are generally considered to have limited significance for specific populations. To our knowledge, this is the first study to investigate the relationship between hematocrit levels at admission and preoperative DVT in geriatric hip fractures. The prevalence of preoperative DVT in these patients is high (32%). We believe that previous studies may have underestimated the incidence of DVT. It is possible that the symptoms of hip fracture can mask the clinical signs and symptoms of DVT [33]. In this study, we established an association using curve fitting and found a saturation point and, therefore, a meaningful prediction point. Our study showed that hematocrit levels <33.5 vol% were not associated with preoperative DVT, whereas hematocrit levels at admission of >33.5 vol% were associated with preoperative DVT. Furthermore, according to the current anemia criteria, our study supports that anemia is a risk factor for developing DVT, and higher levels of HCT are associated with a lower risk of DVT.

To avoid the impact of COVID-19 on patient admission [34] and for a more accurate assessment of the relationship between hematocrit levels at admission and preoperative DVT, we performed linear regression on the adjusted model and comprehensively considered the variables that needed to be adjusted. Factors with *p* < 0.1 in the univariate analysis and factors included in previous studies were considered. Specifically, we used a sensitivity analysis of the trend test in the linear model. In addition, we considered the association of the curve and found a clinical saturation effect and an inflection point. Curve fitting was more suitable than linear fitting to explain the association between admission hematocrit levels and preoperative DVT.

Despite the large sample size and the many methods used to explain the relationship between variables and preoperative DVT, this study had several limitations. First, as with every other multivariate analysis, we were unable to include all confounding factors. Therefore, the residual confounding factors remained. Second, due to the limitations of the retrospective study design, we could not assess the progression of Hct levels over time. Third, our study was a single center study; all samples were from the same hospital, and hematocrit levels were strongly associated with region and ethnicity [35]. Therefore, these results should be interpreted with caution and the inference points for other ethnicities should be redefined.

In conclusion, hematocrit levels at admission were nonlinearly associated with preoperative DVT, and the hematocrit level at admission was a risk indicator of preoperative DVT. However, the severity of low hematocrit was not associated with preoperative DVT when the hematocrit was <33.5 vol%.

**Author Contributions:** According to the definition given by the International Committee of Medical Journal Editors (ICMJE), the authors listed above qualify for authorship based on making one or more substantial contributions to the intellectual content of the following: Conception and design of the study, B.-F.Z., Y.-M.Z., D.-Y.L., D.-X.L., T.Y. and K.-Y.Z.; analysis of the data, B.-F.Z. and D.-Y.L.; writing of the manuscript, D.-Y.L. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by the Foundation of the Xi'an Municipal Health Commission (Grant Number: 2021ms09).

**Institutional Review Board Statement:** The study was conducted according to the Declaration of Helsinki guidelines and was approved by the Ethics Committee of Honghui Hospital, Xi'an Jiaotong University (protocol code: 202201009 and date of approval: 28 January 2022).

**Informed Consent Statement:** This study was registered on the website of the Chinese Clinical Trial Registry (ChiCTR: ChiCTR2200057323). Informed consent was obtained from all subjects involved in the study.

**Data Availability Statement:** Data were obtained from the Xi'an Honghui Hospital. According to relevant regulations, the data could not be shared but can be requested from the corresponding author.

**Conflicts of Interest:** The authors declare they have no conflict of interest.

**Consent to Publish:** The work described has not been published before (except in an abstract or as part of a published lecture, review, or thesis); it is not under consideration for publication elsewhere; and its publication has been approved by all co-authors.

## **Abbreviations**


#### **References**


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