Association Of Coagulation Factor Ⅷ And Von Willebrand Factor On Postoperative Recurrence In Patients With Chronic Subdural Hemotoma And A Nomogram Model Construction

Objective: Coagulation factor Ⅷ(CFⅧ)is the core enzyme factor in the body’s endogenous coagulation pathway.It plays an important role in the coagulation cascade.Thus,the decrease in the activity and expression of CFⅧ factors was associated with the increasing risk of intracranial hemorrhage.Meanwhile,CFⅧ and von Willebrand factor(v WF)circulate as a complex in plasma and have a major role in the hemostatic system.VWF has a dual role in hemostasis.It promotes platelet adhesion by anchoring the platelets to the subendothelial matrix of damaged vessels and it protects FⅧ from proteolytic degradation.Moreover,VWF is an acute phase protein that has multiple roles in vascular inflammation and is massively secreted from Weibel-Palade bodies upon endothelial cell activation.Activated FⅧ on the other hand,together with coagulation factor IX forms the tenase complex,an essential feature of the propagation phase of coagulation on the surface of activated platelets.Therefore,if the expression of VWF and CFⅧ are insufficient or the activation are reduced,it can lead to a series of hidden bleeding events,such as intra-articular bleeding,spontaneous intracranial hemorrhage,etc.This study aimed to investigate the association of CFⅧ and v WF on the recurrence in patients with chronic subdural hematoma(CSDH).And then set up a prediction Nomogram model combined with CFⅧ,v WF levels and other risk factors for CSDH recurrence,so as to provide a scientific basis for developing targeted strategies for the prevention and control of the risk of CSDH recurrence.Methods: CSDH patients who were treated in the Department of Neurosurgery of Jiangsu North Jiangsu People’s Hospital from September 2017 to September 2019 were prospectively collected.All cases were treated by novel YL-1 hollow needle aspiration drainage system.The patients were divided into two groups with or without recurrence,according to whether postoperative recurrence occurred or not.The χ2 and Fisher exact tests were used in univariate analysis to access the relationships between the predictors and recurrence initially.Subsequently,predictors with P < 0.05 were included in multivariate logistic regression analysis.Multivariate analysis were used to analyze the correlation between CFⅧ,v WF and recurrence,and identify the risk factors influencing recurrence.P values,odds ratios and 95% confidence intervals(CIs)were used to describe all the risk factors of recurrence in this study.Then,each factor was scored by Nomogram method to construct the prediction model.Receiver operating characteristic curve(ROC)was drawn to assess the predictive value of CFⅧ,v WF and Nomogram model in the occurrence of CSDH recurrence.Furthermore,the predictive ability of the nomogram model was internally validated using the Bootstrap method by calculating the C-index and drawing the calibration plot.Results: Ultimately,a total of 152 CSDH patients who met the inclusion and exclusion criteria were included in our study.Among the 152 patients,91 were male and 61 were female.The average age was 63.61 ± 13.01 years,ranged from 35 to 86 years.The total rate of recurrence after initial surgery for CSDH was 15.13%(23/152)during the following 3 months.Univariate analysis showed that there was a statistically significant difference in the age,degree of brain atrophy,hematoma density,hematoma volume,midline shift and postoperative subdural gas accumulation in patients with recurrence and non-recurrence(P<0.05).Plasma level of CFⅧ and v WF in CSDH patients who developed recurrence were significantly lower than those without recurrence(P<0.05).Other clinical characteristics were not significantly different between the two groups,such as gender,smoking,drinking,head trauma events,hypertension,diabetes,coronary heart disease,other intracranial lesions,clinical symptoms,preoperative condition [GCS(Glasgow Coma Scale)score],hematoma side comparison,etc(p > 0.05).ROC curve analysis showed that CFⅧ and v WF have certain predictive value for the occurrence of CSDH recurrence,and the optimal cut-off value were 80.5%,86.5% respectively.Their predictive sensitivity,specificity,and area under the curve(AUC)were 53.5%,82.6%,and 0.670(95%CI: 0.569~0.770,P=0.010),and 76.0%,65.2%,0.737(95%CI: 0.643~0.832,P<0.001)respectively.According to whether the levels of the two factors were reduced(CFⅧ<80.5%,VWF<86.5%),Patients with acute ischemic stroke were divided into 4 groups: both FⅧ and VWF within normal range(FⅧ-/VWF-);reduced FⅧ,but normal VWF(CFⅧ↓/v WF-);FⅧ within normal range,but reduced VWF(CFⅧ-/VWF↓);and reduction of both FⅧ and VWF(CFⅧ↓/VWF↓).The CFⅧ/v WF complex abnormal includes CFⅧ↓/v WF-,CFⅧ CFⅧ-/VWF↓,and CFⅧ↓/VWF↓,Subgroup analysis showed that the CFⅧ/v WF complex abnormal group had a higher probability of recurrence than the normal group(25.86% vs.8.51%),and the difference was statistically significant(P = 0.004).The multivariate logistic regression analysis showed that heterogeneous hematoma(OR=7.553,95%CI: 2.251~25.343,P=0.001),hematoma volume ≥130ml(OR=3.430,95%CI: 1.103~10.666,P=0.033),postoperative subdural air collection width ≥10mm(OR=4.485,95%CI: 1.106~18.193,P=0.036)and FⅧ/v WF dysfunction(OR=3.860,95%CI: 1.258~11.849,P=0.018)are independent risk factors for postoperative recurrence.These risk factors were incorporated into the Nomogram.The consistency index of the model was good(C-index=0.834,P<0.01).ROC curve analysis showed that the model combining the CFⅧ/v WF and other prognostic factors(AUC=0.868,95%CI: 0.782~0.954,P<0.001)showed more favorable predictive ability than the model without the CFⅧ/v WF(AUC=0.803,95%CI: 0.698~0.907,P<0.001).In the calibration graph,the standard curve properly fitted with the predicting calibration curve.The predicted value of postoperative recurrence obtained was in good agreement with the observed value.Conclusion: CFⅧ and v WF are closely correlated with the postoperative recurrence in patients with CSDH.Plasma level of CFⅧ and v WF in CSDH patients who developed recurrence were significantly lower than those without recurrence(P<0.05).FⅧ/v WF dysfunction(CFⅧ<80.5% and/or v WF<86.5%)is an independent risk factor of affecting the recurrence with CSDH after surgical treatment and it had some values to predict recurrence.A nomogram combining the heterogeneous hematoma,hematoma volume,postoperative subdural air collection width and FⅧ/v WF dysfunction could more accurately predict the recurrence of CSDH,and it was helpful to improve the early identification and screening ability of those high-risk patients.This model is noninvasive,rapid,and low cost,it is easy to promote and has wide application prospects in clinical practice of CSDH management to improve the prognosis in this population.