ABSTRACT
Glioblastomas are among the most malignant tumors which, despite aggressive treatment, currently have an abysmal prognosis. These lesions are known to cause local and systemic perturbations in the coagulation system, leading to neo-angiogenesis and a high risk of venous thromboembolism. Indeed, there have been multiple proposals of the coagulation system being a possible target for future treatment of these patients. However, non-selective anticoagulant therapy has proven suboptimal and leads to a significant increase of intracranial hemorrhage. Thus, recognizing factors which lead to hyper-coagulation is considered paramount. Hyperglycemia is a well-known pro-thrombotic factor, a fact which has received little attention in neuro-oncology so-far. We previously hypothesized that patients with brain tumors could be highly susceptible to iatrogenic glycemia dysregulation. Here, we analyzed the connection between glycated hemoglobin (HbA1c) and the routine coagulation markers (D-dimers, prothrombin time (PT) and activated partial thromboplastin time (aPTT)) in patients with de novo intracranial glioblastomas. Included in this study were 74 patients, operated on in three hospitals, Clinical Hospital Dubrava, Zagreb, Croatia; University Hospital Center Split, Split, Croatia and University Hospital de la Princesa, Madrid, Spain. We found a significant inverse correlation between HbA1c and aPTT (ρ=-0.379; P=0.0009). We also found a significant inverse correlation between Ki67 immunoreactivity and aPTT (ρ=-0.211; P=0.0082). No connection was found between HbA1c and D-dimers or PT. Our results suggest that hyperglycemic patients, with a more proliferative glioblastoma, could in fact have their coagulation profile significantly disrupted, primarily through the intrinsic coagulation pathway. Such findings could have great clinical importance. Further research in this area could help elucidate the vicious connection between glioblastomas and coagulation, and help combat the deadly disease.
ABSTRACT
Meningiomas are among the most common primary tumors of the central nervous system. Previous research into the meningioma histological appearance, genetic markers, transcriptome and epigenetic landscape has revealed that benign meningiomas significantly differ in their glucose metabolism compared to aggressive lesions. However, a correlation between the systemic glucose metabolism and the metabolism of the tumor hasn't yet been found. We hypothesized that chronic levels of glycaemia (approximated with glycated hemoglobin (HbA1c)) are different in patients with aggressive and benign meningiomas. The study encompassed 71 patients with de novo intracranial meningiomas, operated on in three European hospitals, two in Croatia and one in Spain. Our results show that patients with WHO grade 2 meningiomas had significantly higher HbA1c values compared to patients with grade 1 lesions (P = 0.0290). We also found a significant number of patients (19/71; 26.7%) being hyperglycemic, harboring all the risks that such a condition entails. Finally, we found a significant correlation between our patients' age and their preoperative HbA1c levels (P = 0.0008, ρ(rho) = 0.388), suggesting that older meningioma patients are at a higher risk of having their glycaemia severely dysregulated. These findings are especially important considering the current routine and wide-spread use of corticosteroids as anti-edematous treatment. Further research in this area could lead to better understanding of meningiomas and have immediate clinical impact.
