To the best of our knowledge, this is the first study to explore the association of coagulation parameters and HT in non-AF patients; and to explore the effect of coagulation parameters on long-term outcomes after HT in non-AF patients. Our present study showed that three coagulation parameters including low PLT, low MPV, and high FIB were significant and dependent risk factors with HT in non-AF patients, instead of AF patients. Furthermore, we found that MPV and FIB levels were independently and significantly associated with unfavorable long-term functional outcomes in non-AF HT patients.
Consistent with many studies, we identified that AF was a reliable risk factor of HT, and the incidence of HT among AF patients was higher than non-AF patients [7, 8, 22, 23]. Considering the complex interaction between AF and HT , we did a subgroup analysis of our patients to explore the association between coagulation functions and HT. Interestingly, we found none of the coagulation parameters was associated with HT among AF patients. This may be that most AF patients received anticoagulant therapy before AIS which may influence coagulation parameters.
However, our study suggested that PLT, MPV, and FIB were associated with HT significantly in the non-AF patients. PLT is a key factor in the coagulation process. According to clinical guidelines from the American Heart Association/American Stroke Association published in 2018, low PLT levels (< 100,000 counts/µl) would increase the risk of HT  and do not recommend these patients to receive reperfusion therapies. Several studies also pointed out that PLT was associated with the occurrence of HT [8, 26]. Furthermore, a previous study identified that lower coated-platelets counts increased the likelihood of early HT in patients with non-lacunar ischemic stroke . Platelet-endothelial interactions could maintain the structural integrity of blood vessels when stroke occours . The patients with low PLT levels are weak in maintaining the blood vessels’ integrity and are more likely to develop HT after AIS. Salas-Perdomo et al. found in the experiment that using an anti-platelet serum in mice would lead to larger intraparenchymal hematomas after stroke , thus stressed the vital hemostatic function of platelets in AIS. This may because that platelets can physically cover the damaged vascular endothelium or release protective factors to protect the endothelial barrier function. These all indicated the importance of PLT in HT.
MPV describes the sizes of PLT, which is a marker of PLT activity and influences bleeding [30, 31]. In our study, MPV among HT patients was lower than non-HT. Besides, logistic regression analysis showed low MPV was a risk factor of HT. Early study found that larger PLT had more granules and would produce more vascular activity as well as pre-clotting factors, which may raise the hemostatic efficiency [31, 32]. A retrospective study suggested that baseline MPV was associated with unfavorable stroke outcomes but its relationship with HT was still uncertain .
Previous studies briefly mentioned the relationship between FIB and HT [26, 34, 35]. And we found that higher FIB may be associated with a higher incidence of HT among AIS patients, which is congruent with some reports[34, 35]. However, Wang et al. found that FIB < 1.50 g/L was a risk factor for HT . We hypothesize that high levels of FIB may be associated with HT by participating in the inflammatory process. When HT occurs, endothelial dysfunction of capillaries would further lead to abnormal blood-brain barrier permeability within the infarcted area . The dysfunction of blood-brain barrier in the infarcted area was proved to be the main casue of HT. Meanwhile, a review proposed that FIB was a ligand of cell surface receptors and this could promote the intercellular adhesion between inflammatory cells and endothelial . In another study, an anti-inflammatory thrombolytic drug called SMTP-7 could decrease the incidence of HT, which suggested the relationship between HT and inflammation . Thus, the relationship between FIB and HT remains unknown and this needs to be further investigated.
In our study, we found that coagulation functions were associated with unfavorable long-term outcomes in non-AF HT patients. Its exact mechanism remains unknown; however, the mechanism by which coagulation function is related to unfavorable outcomes in intracerebral hemorrhage (ICH) is unclear. Unfavorable outcomes after hemorrhage were reported to be conducted by the inflammatory effects of intraparenchymal blood .Recently, Krenzlin H et al. found that the activated cerebral thrombin system was related to poor outcome after ICH in mice. They suspected that the activated cerebral thrombin system may contribute to secondary brain damage. Meanwhile, a previous study suggested that coagulation function may influence neurovascular injury and neuroprotection.
Our study has some limitations. First, this was a single-center and retrospective study, so it is necessary to conduct multi-center, prospective studies to establish causality and provide long-term prognostic information. Second, our study did not discuss the association between different subtypes of HT (hemorrhagic infarction or parenchymal hematoma) and coagulation functions. In the further study, we could explore the association between the severity of HT and coagulation functions. Third, owing to the infarction size were not documented, the associations between infarction size and HT was not described in detail.