Our study demonstrated that early hematoma enlargement in patients with intracerebral hemorrhage was significantly associated with poor outcomes and mortality in the short and medium-term after discharge from the hospital. Irregular shape, as a marker of NCCT, can not only well predict the risk of early hematoma enlargement, but also serve as an independent predictor of patients' functional prognosis. The present study explored the factors related to the formation of the irregular shape, indicating for the first time that the elevated plasma D-dimer expression level on admission was significantly correlated with the appearance of the irregular shape of the hematoma, and was probably the cause of its formation.
As a serious disability of the nervous system disease, spontaneous intracerebral hemorrhage (ICH) is attracting more and more researchers' attention on how to predict the occurrence of its adverse outcomes quickly and accurately, and then help clinicians to carry out graded management of patients. Hematoma growth is an independent predictor of poor outcomes and mortality after intracerebral hemorrhage4, and about 1/3 of patients will have sustained bleeding after ICH13. In recently performed clinical experiments, significant progress has been made in predicting hematoma expansion. For example, in patients with intracerebral hemorrhage, serum calcium and magnesium levels at the time of hospital admission were associated with hematoma expansion independently and inversely14,15;Patients with hyperglycemia will mediate the development of hematoma expansion through the inhibition of platelet aggregation by plasma kallikrein 16. In the aspect of imaging, the computed tomography angiography (CTA) spot sign is a well-established imaging marker that can independently predict hematoma expansion in patients with ICH 7. However, due to the complex operation of CTA, it is not routinely performed in the emergency setting, and the patient's condition cannot be judged in time. In cases where CTA was not available, researchers have gradually explored the predictive value of NCCT markers, including blend sign, irregular shape, island sign, for intracerebral hemorrhage expansion, and the results showed equally good predictive performance9,17. Qi et al., in a retrospective analysis of 252 patients with intracerebral hemorrhage, showed that the island sign was an independent predictor of hematoma enlargement and poor outcomes in patients with ICH 18. In the study conducted by Zhang et al,1111 patients with spontaneous intracerebral hemorrhage(ICH)were recruited, and it was found that blend sign could help doctors to grade the management of patients with intracerebral hemorrhage in admission19. In a previous study, Moratti et al established a scoring system to predict instability of the hematoma based on three indicators: presence or absence of the mixed sign, time to the appearance of the mixed sign, and reduction in the density of the hematoma at presentation20. But these studies did not directly use the irregular shape of hematoma to evaluate the prognosis of patients and did not explore the cause of NCCT imaging hallmarks.
The reason for the formation of this imaging hallmark of irregular shape was not investigated intensively in numerous previous studies. The cause of the irregular shape is not clear. Thrombin activation and coagulation disorders are the main influencing factors of hematoma expansion21,22. The massive release of thrombin, which induces inflammatory reactions in the perivascular tissues and then damages the blood-brain barrier(BBB), may lead to early hematoma expansion23,24. However, the association between plasma D-dimer and early hematoma enlargement is not clear. Plasma D-dimer is a fibrin degradation product released from the plasmin degradation of fibrin monomers25, and its expression reflects the level of activation of the systemic coagulation response. Acute brain injury caused by hematoma formation is closely related to coagulation activation, whereas an increase in D-dimer, the end product of coagulation, reflects the activation level of systemic coagulation response26. Plasma D-dimer has been shown to have a good performance in the prediction of poor outcome and mortality in patients with spontaneous ICH 10,27,28. In the retrospective analysis, we demonstrated the predictive efficacy of irregular shapes for hematoma expansion in intracerebral hemorrhage and can be used as an independent predictor to predict the functional outcome of patients. In addition, this study also pioneered the independent inclusion of plasma D-dimer in the prediction of irregularity signs and showed a significant statistical difference. However, in this study, there was no significant statistical association between the level of plasma D-dimer on admission and hematoma expansion, which might be related to the sample size and systematic error. We also analyzed the predictive value of plasma D-dimer in the functional outcome and mortality of patients in this sample, and the results showed that plasma D-dimer was significantly correlated with the prognosis of patients. In our present, the irregular shape is a strong predictor of the outcome situation judgment in intracerebral hemorrhage patients. In survival analysis, patients with irregular shapes had a significantly shorter overall survival (OS) than patients without irregular shapes.
Our study also has certain limitations. First of all, the formation mechanism of irregular shape is not precise, and no study has shown whether D-dimer plays an essential role in hematoma expansion, and the specific mechanism of action has not been explored. Second, all the patients included in this study were admitted to our center's emergency department, and the sample size was small. Patients were generally more severe at the time of admission, which may produce biases regarding patient selection, data collection, and analysis. Third, some patients were admitted to the hospital after a long period of referral, and the disease will develop further during this period of referral, which has a particular influence on the results of various examinations. Fourth, other non-contrast CT markers also have excellent performance in predicting hematoma expansion and poor outcomes. Different markers should be included in predictive studies to enhance functional outcomes' prediction efficiency in patients with ICH。