Predictive value of preoperative platelet count and D-dimer levels for spinal cord injury following acute type A aortic dissection

doi:10.21203/rs.3.rs-2822183/v1

Background

This study aims to identify the risk factors contributing to spinal cord injury (SCI) following a type A acute aortic dissection (TA-AAD).

Methods

This retrospective study was conducted at a single center and involved 481 patients who received frozen elephant trunk stent implantation for TA-AAD and underwent total arch replacement with the deep hypothermic circulatory arrest at Fuwai Hospital between September 2016 and April 2020.

Results

The resulting data of the multivariate logistic regression analysis demonstrated that preoperative platelet count (odds ratio [OR] 0.774) and D-dimer levels (OR 2.247) held potential as independent predictors for postoperative SCI in patients diagnosed with TA-AAD.

Conclusion

The study results indicated that preoperative platelet count and D-dimer levels are independent risk factors for postoperative SCI in individuals with TA-AAD. This finding holds significance regarding clinical implications for prognosis and therapeutic responses in TA-AAD.

spinal cord injury，acute type A aortic dissection，platelet ，D-dimer

Type A acute aortic dissection (TA-AAD) is a clinically fatal acute and critical condition with a pre-hospital mortality rate of 49%. This condition is considered as one of the most urgent surgical procedures in cardiovascular surgery [1, 2, 3, 4]. The effects of the dissection can extend to multiple organs in the body, including the spinal cord, where ischemia and postoperative spinal cord injury (SCI) occur as important complications with an incidence of 3.5–20% [5]. These complications may have negative implications for the prognosis of patients and their quality of life following surgery. However, in recent years, with the widespread use of total arch replacement (TAR) with frozen elephant trunk (FET) technique, the mortality rate of TA-AAD has been gradually decreasing. Nonetheless, SCI remains a serious postoperative complication. Therefore, it may be potentially beneficial to reduce the incidence of SCI by identifying the individuals at high risk for postoperative SCI early in the preoperative period and thus intervening more aggressively in their treatment.

Patient population

Patients with Stanford TA-AAD admitted to the Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing (China) from September 2016 to April 2020 were retrospectively analyzed based on the electronic medical records and laboratory tests. The patients were excluded if the they did not undergo TAR (ascending aorta replacement alone or partial aortic arch replacement), deep hypothermic circulatory arrest (DHCA) (e.g., hybrid total aorta replacement), or chronic type A aortic arch dissection.

Study design

This retrospectively designed study analyzed patients diagnosed with TA-AAD who underwent TAR with DHCA using the FET technique. The preoperative parameters, intraoperative details, and postoperative outcomes of these individuals were the main focus of the research. This single-center study was approved by the Ethics Committee of the Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China). The provision of informed written consent by each participant or their caregivers was necessary for inclusion. The diagnostic criterion for TA-AAD was the examination using enhanced computed tomography (CT). In addition, the research investigated the incidence of postoperative SCI in individuals with TA-AAD and assessed the risk factors associated with this complication.

Surgical procedures

Standard anesthetic management and endotracheal intubation were used during surgery. Cardiopulmonary bypass (CPB) was applied in the process of surgery through right axillary artery cannulation. Intraoperatively, DHCA was applied, and the unilateral or bilateral cerebral perfusion was selectively performed. Four-branch prosthetic vessels were used to perform TAR, with the right innominate brachiocephalic trunk, left common carotid artery, and left subclavian artery re-anastomosed to the branches of the prosthetic vessels, respectively. The FET stent was implanted in the descending aorta during the surgery.

SCI was diagnosed using the American Spinal Injury Association (ASIA; https://asia-spinalinjury.org/) criteria into 5 grades, of which Grade A represented a complete injury. Grade B referred to an incomplete injury, with sensory function present below the nerve plane but without any motor function. Grade C represented an incomplete injury, with more than half of the motor function preserved below the nerve plane and a key muscle strength lower than Level 3. Grade D also referred to an incomplete injury, with more than half of the motor function retained below the nerve plane. The incomplete impairment indicated by Grade D meant that more than half of the motor function was preserved below the nerve plane, and key muscle strength was greater than or equal to Level 3. Grade E was assigned if both motor and sensory function was normal. Whereas, Grade A reflected the most severe SCI, i.e., paraplegia, in ASIA classification, while the spinal cord at Grade E was normal.

Statistical analysis

The data distribution was examined through the Kolmogorov-Smirnov test. The format of mean ± standard deviation (SD) was utilized for continuous data in case of a normal distribution, whereas the median value and interquartile range were utilized for non-normally distributed data. Counts and percentages were utilized for categorical variables. The Chi-square test or Fisher exact test were used to analyze categorical data, while one-way analysis of variance or Wilcoxon rank sum test was utilized for assessing the comparison of continuous variables. The logistic regression model was employed for the determination of the univariate and multivariate predictors of postoperative SCI. SPSS 26 (SPSS, IBM Corp. Armonk, USA) was employed for the analysis of the data, with p less than 0.05 representing statistical significance.

Baseline characteristics

Overall, 774 individuals with TA-AAD were enrolled through the electronic information system for inpatient physicians. Among them, 293 were excluded as their surgical procedure did not meet the inclusion criteria. Specifically, this included 226 cases of partial aortic arch replacements without DHCA, 45 of hybrid total aortic arch procedures, and 22 of chronic type A aortic arch dissections. Ultimately, 481 TA-AAD cases were screened out with a mean age of 47.2 ± 16.4 years (29-75 years). Of these, 425 were men and 56 were women. The final 39 patients developed SCI postoperatively, with an incidence of 8.1%. Among these, 21 were paraplegic and 18 had incomplete SCI. The preoperative baseline parameters of the two groups are shown in Table 1. Regarding baseline information and preoperative indicators, the two groups lacked any notable statistical variance in age, body mass index (BMI), time from onset to surgery, preoperative complications, preoperative ultrasound, preoperative leukocytes and hemoglobin, and the number of intercostal vessels involved. However, they varied significantly in terms of gender, preoperative platelets, preoperative D-dimer, and Adamkiewicz artery involvement.

Table 1 Preoperative baseline characteristics of patients with TA-AAD

Baseline characteristics	Normal group (n = 442)	SCI group (n = 39)	P
Demographic information
Age	46.9 ± 17.2	50.7 ± 17.9	0.084
Gender (male)	396 (89.5%)	29 (74.3%)	0.009
BMI	24.9 ± 3.2	26.7 ± 4.1	0.612
Onset to surgery time (h)	45[21,124]	42[19,140]	0.194
Medical history
Hypertension	407 (92.0%)	36 (92.3%)	0.795
Diabetes	11 (2.4%)	2 (5.1%)	0.645
Cerebrovascular disease	21 (4.7%)	3 (7.6%)	0.670
Smoking history	224 (50.6%)	23 (58.9%)	0.408
COPD	2 (0.4%)	0	> 0.999
Preoperative situation
Lactic acid (mmol/L)	1.9 ± 0.7	2.1 ± 0.9	0.091
PaO₂/FiO₂	265 ± 82	249 ± 76	0.163
D-dimer (μg/mL)	1.1[0.4,2.9]	2.7[0.8,3.4]	0.004
Leukocytes (10^9/L)	12.7 ± 2.4	11.6 ± 3.5	0.071
Hemoglobin (g/L)	134 ± 21	131 ± 25	0.647
Platelets (10^9/L)	179 ± 28	144 ± 21	< 0.001
Blood creatinine (μmol/L)	87.5 ± 29.4	90.6 ± 30.4	0.117
Troponin I	0.02[0.00,0.06]	0.02[0.00,0.08]	0.911
Aortic root diameter (mm)	42.1 ± 8.4	42.9 ± 10.2	0.379
Ascending aorta diameter (mm)	45.8 ± 7.6	46.7 ± 8.1	0.317
Left ventricular ejection fraction (%)	62.5 ± 6.4	63.8 ± 5.8	0.453
Adamkiewicz artery involvement	89 (20.1%)	16 (41.0%)	0.004
Number of intercostal vessels involved	3 [0.6]	4 [0,7]	0.847

Note: TA-AAD, type A acute aortic dissection; SCI, spinal cord injury; BMI, body mass index; COPD, chronic obstructive pulmonary disease;

The intraoperative conditions of the groups are presented in Table 2. No statistical variance was indicated between the groups concerning surgery duration, intraoperative CPB duration, aortic block duration, and DHCA duration, and intraoperative nasopharyngeal temperature. However, intraoperative blood loss and cerebrospinal fluid pressure exhibited considerably higher values in the SCI group in contrast to the control group.

Table 2 Intraoperative characteristics of patients with TA-AAD

Features	Normal group (n = 442)	SCI group (n = 39)	P
Surgery duration (h)	8.7 ± 1.9	9.2 ± 2.2	0.068
CPB duration (min)	174 ± 52	180 ± 57	0.059
Aortic block duration (min)	139 ± 46	144 ± 57	0.228
DHCA duration (min)	21 ± 4.7	22 ± 5.4	0.314
Nasopharyngeal temperature (℃)	24.7 ± 2.9	24.2 ± 4.5	0.773
Intraoperative blood loss (mL)	1071 ± 446	1453 ± 579	0.035
Intraoperative cerebrospinal fluid pressure (mmHg)	14.7 ± 5.4	19.5 ± 7.6	0.015

Note: TA-AAD, type A acute aortic dissection; SCI, spinal cord injury; CPB, cardiopulmonary bypass; DHCA, deep hypothermic circulatory arrest.

Postoperative conditions in both groups are shown in Table 3, with in-hospital mortality slightly increased in the SCI group than in the normal group (12.8% vs. 2.9%). Postoperative outcomes such as intensive care unit (ICU) stay, renal replacement, low cardiac output and gastrointestinal complications were notably increased in the SCI group in contrast to the normal group.

Table 3 Postoperative outcomes of both groups

Outcomes	Normal group (n = 442)	Paraplegic group (n = 39)	P
In-hospital death in 30 days	13 (2.9%)	5 (12.8%)	0.007
ICU stay (days)	5 [3,11]	9 [6.17]	0.001
Postoperative renal replacement therapy	26 (5.8%)	11 (28.2%)	<0.001
Re-thoracotomy	4 (0.9%)	0	0.746
Postoperative low cardiac output	5 (1.1%)	6 (15.3%)	<0.001
Postoperative gastrointestinal complications	14 (3.1%)	5 (12.8%)	0.011

Note: ICU, intensive care unit.

In the univariate logistic regression analysis, preoperative, intraoperative, and postoperative factors were analyzed, and multivariate logistic regression analysis was undertaken on parameters with P < 0.1. Using the backward-stepwise regression method, factors with P ≥ 0.1 were removed from the regression model in each step. After correction for confounding factors, the results are shown in Table 4. Preoperative platelet count (odds ratio [OR] = 0.774, 95% confidence interval [CI] 0.416-0.895, P = 0.007) and D-dimer levels (OR = 2.247, 95% CI 1.756-4.226, P = 0.016) were determined as independent risk factors for SCI after TA-AAD. Other factors left in the multivariate logistic regression model were gender (OR = 3.117, P = 0.004), intraoperative cerebrospinal fluid pressure (OR = 1.816, P = 0.029), and postoperative low cardiac output (OR = 2.149, P = 0.017).

Table 4. Risk factors in multivariate logistic regression analysis of postoperative paraplegia in patients with TA-AAD

Factor	OR	95% CI	P
Gender	3.117	1.592 - 8.063	0.004
Preoperative platelet count	0.774	0.416 - 0.895	0.007
Preoperative D-dimer levels	2.247	1.756 - 4.226	0.016
Intraoperative cerebrospinal fluid pressure	1.816	1.469 - 3.274	0.029
Postoperative low cardiac output	2.149	1.736 - 5.075	0.017

Note: TA-AAD, type A acute aortic dissection; OR, odds ratio; CI, confidence interval

The present research revealed that the decline in preoperative platelet and the elevation in D-dimer levels held promise as independent risk factors for postoperative SCI. Despite advances in surgical techniques, TA-AAD continues to present significant surgical challenges. However, as TAR using the FET technique gains increasing popularity, the rate of mortality and re-thoracotomy for TA-AAD is gradually decreasing. SCI and paraplegia are serious complications that affect the prognosis of patients, not only increasing their mortality but also affecting their quality of life in the long term. The incidence reported in the literature related to SCI varies widely, with incidence rates ranging from 3.5–20% [ 5 ].

Prior research has primarily focused on intraoperative surgical procedures and intraoperative spinal cord protection strategies, such as the reconstruction of the intercostal vessels and Adamkiewicz artery. Some studies suggest that the intraoperative circulatory arrest with a core body temperature ≥ 28°C and a duration > 40 min as well as the inadequate cerebral protection may function as risk factors for postoperative SCI. It remains a matter of debate whether FET technique leads to inadequate spinal cord blood supply and thus increases the risk of SCI. Chakos et al. [6] have reported an increased incidence of SCI with the FET technique compared to conventional aortic arch repair (CAR) using a soft elephant trunk (FET: 3.8% vs. CAR: 1.4%, P < 0.01). However, this finding was not supported by the study of Ling et al. [7]. They argued that the FET stent did not elevate the risk of postoperative paraplegia, and that the "cutoff" sign after descending aortic surgery may be an important cause of early postoperative paraplegia. Some studies have proposed that excessive coverage of the intercostal artery by the FET stent with its distal anchorage area below Th10 may act as a risk factor for SCI [8–9]. However, other studies could not substantiate this concept [10]. According to the study of Hori et al. [11], higher creatinine levels and significant perfusion of the spinal cord by the false lumen may be risk factors contributing to postoperative SCI.

The spinal circulation is a longitudinal, continuous, and flexible system [12, 13], so the input of any single segmental artery along its length is not critical. The spinal cord circulation is fragile in the first few days after extensive segmental artery embolization and disruption of the balance of the spinal cord blood supply due to hypovolemia, hyperthermia, and high venous pressure should be avoided. Once the anterior spinal artery proliferates and new vessels are generated and converted into large arteries, the spinal cord blood supply will return to normal. Therefore, rapid thrombosis of the preoperative false lumen leading to reduced spinal arterial blood supply may be a pivotal risk factor for postoperative SCI.

Notably, preoperative platelet count decline and preoperative D-dimer level elevation were risk factors for postoperative SCI in this study. The mechanism may be related to the massive platelet depletion due to preoperative pseudoluminal thrombosis of the dissection. The persistent decline in platelets often suggests exacerbation of dissection in patients. A study by Liu et al. [14] has suggested that postoperative platelet count decline in aortic dissection was associated with 3-year mortality.

The D-dimer level is an indicator of coagulation in the body. It has been established that D-dimer is a by-product of cross-linked fibrin degradation in humans. It is significant in the anticoagulation system of the body and performs a critical role in maintaining the permeability of the vascular walls and normal blood flow. Furthermore, D-dimer plays a crucial role in both coagulation and fibrinolysis, and is commonly used as a serum marker to reflect these processes in patients. As reported previously, D-dimer reflects the fibrinolytic process of coagulation and its level is linked to the size of the thrombus formed and the contact area of thrombus with blood [15]. Wang et al. [16] also demonstrated that D-dimer levels were considerably elevated in individuals with type A aortic dissection after massive thrombosis of the false lumen than in type B dissection, and that individuals who died had obviously higher D-dimer levels than surviving patients.

Limitations

This research is limited in some aspects. The data were retrieved from a single center with a relatively small size for this retrospective study, which may have introduced selection bias. Additionally, the impact of factors such as the personal experience of surgeons and the treatment philosophy of different medical institutions on the results were not taken into consideration. Hence, prospective studies are still needed to validate these results.

This research indicates that preoperative platelet count decrease and D-dimer level increase are two independent risk factors for postoperative SCI in TAAAD patients undergoing TAR using the FET technique. Therefore, these patients should be actively managed with appropriate preventive measures to reduce the risk of developing postoperative SCI.

Conflicts of interest statement: The authors have no conflicts of interest to declare.

Source of Funding: This work has no source of funding.

Ethical Approval

The study was approved by the ethics committee of research setting Hospital (Ethical approval number: 2021-1557). Written informed consent from all patients for this study was waived.

Competing interests

Consent was obtained from the patients or their relatives

Authors' contributions

Conception and design: Fengbo Pei, Jinhua Wei, Zujun Chen;

Provision of study materials or patients: Fengbo Pei, Jinhua Wei,

Collection and assembly of data: Fengbo Pei, Jinhua Wei, Yao Yao1, Hui Wu,

Data analysis and interpretation: Fengbo Pei, Jinhua Wei,

Manuscript writing: Fengbo Pei, Jinhua Wei, Zujun Chen

Final approval of manuscript: All authors.

Competing interests

The authors declare that they have no competing interests

Availability of data and materials

Additional data are available by request through emailing Chen Zujun

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No competing interests reported.

Predictive value of preoperative platelet count and D-dimer levels for spinal cord injury following acute type A aortic dissection

Status:

Journal Publication

Version 1

Abstract

Background

Methods

Patient population

Study design

Surgical procedures

Statistical analysis

Results

Discussion

Limitations

Conclusion

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1