An accurate prognosis for aSAH patients is critical in determining the appropriate therapeutic strategy. This study is the first to explore the significance of DAR in predicting the prognosis of patients with aSAH. These results demonstrated that high DAR was associated with aSAH severity and clinical prognosis of patients after adjusting for age, WFNS grade, HH grade, CAR, and DCI. These data suggested that DAR could be potentially used as a predictive tool for aSAH clinical outcomes.
Hypoalbuminemia are common in patients with aSAH and are independently associated with a poor prognosis.Similarly, we had observed a negative correlation between albumin concentration and clinical outcome, which was in consistent with former studies[11, 12]. Hypoproteinemia in patients with aSAH may be caused by systemic inflammation, malnutrition and active catabolic metabolism. Additionally, emerging evidence has suggested that albumin had neuroprotective effects via promotion of neurovascular remodeling and attenuation of brain damage. Preclinical studies had confirmed that intravenously-administered albumin could ameliorate neurological impairment of patients suffering from intracranial hemorrhage. Furthermore, one study suggested that 1.25 g/kg/day albumin treatment might have neuroprotective effects in patients with aSAH. In addition, intravenously administered albumin has been shown to modify cerebral vascular integrity, impact cerebral vasospasm, and even modulate neuroinflammation and microglia functions.Collectively, albumin might be a promising therapeutic candidate for aSAH patients.
D-dimer, as another blood factor, has been widely investigated in many diseases, such as deep vein thrombosis, cerebral hemorrhage, and acute aortic dissection. Elevation of D-dimer indicated an enhanced fibrinolysis activity, which could be used as a biomarker of hypercoagulative state or subsequent fibrinolysis in patients with aSAH. Previous studies have shown that aSAH patients with high D-dimer levels tended to have poor prognosis, which was consistent with the results reported here. Following hemorrhagic stroke, blood vessel integrity is ravaged and an endogenous coagulation system is activated following tissue factor exposure. Free blood can enter the subarachnoid space, further initiating the coagulation process and promoting microthrombosis, which explains the elevation of D-dimer. It has been suggested that microthrombosis is associated with blood brain barrier (BBB) disfunction, neuronal injury, and the occurrence of DCI. Additionally, emerging evidence has focused on thromboinflammation—a hyper-coagulative state promoted by the occurrence of microthrombosis in response to hemorrhagic ictus or disturbed micro-circulation. This could favor the adhesion of migrating immune cells and further exaggerate inflammation, thus disrupting the integrity of the BBB, and leading to an unfavorable clinical prognosis, even without occurrence of vasospasm or DCI.
DAR has been shown as an independent prognostic marker in patients with infection, malignancy, and other disease[6, 7], so it is not surprising that multivariate analysis in this study showed that DAR was an independent predictor of poor prognosis in aSAH patients, better than D-dimer or albumin alone.
Other blood factors have also been assessed in aSAH patients. One characteristic feature of aSAH injury is the destruction of the BBB, and the subendothelial space damaged by neutrophil infiltration plays an important role in the increase of BBB permeability. Disruption of the vessel wall can lead to leakage of plasma and molecules into the extravascular space, thereby exacerbating cerebral edema. In our study, the poor-prognosis aSAH patients had a higher neutrophil count, similar to previous reports. High CRP levels have been shown to correlate with the severity of aSAH, and though the underlying mechanism remains obscure, CRP could be used as a reliable prognostic factor in aSAH patients. Moreover, previous studies have also demonstrated that NLR and CAR had a predictive value for poor prognosis in aSAH[11, 18]. Here, a significant correlation between the predictive value of NLR and CAR on patient outcomes was also observed. In this study, we have proved that the predictive power of DAR ratio was at least comparable, if not better than that of neutrophil/lymphocyte ratio or c-reactive protein/albumin ratio. Taken together, DAR could be used as an independent predictor of poor prognosis in aSAH patients.
While the present study has several limitations. This is a single-center, retrospective study with limited enrolled patients. Additional studies are warranted with a larger patient population. Besides, the follow-up period was a short-term visit, long-term follow-up studies are needed to further evaluate the prognostic potential of DAR.