The abnormalities in blood coagulation in patients with diabetes can lead to a prothrombotic state and requirement for the administration of direct anticoagulants. However, no comparative studies have been conducted on the effects of different direct anticoagulants. A head-to-head investigation of the impact of anticoagulants in 50 patients of type 1 diabetes mellitus (DMT1) was performed, and the data were compared to 50 generally healthy individuals. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured in plasma treated with vehicle, heparin, or four direct anticoagulants at 1 μM. In addition to common biochemical parameters, novel inflammatory markers (neopterin, kynurenine/tryptophan ratio) and major vitamin K forms were measured. Heparin and dabigatran treatments resulted in prolonged coagulation in DMT1 patients compared to healthy individuals in both tests (both p < 0.001). The same phenomenon was observed for rivaroxaban and apixaban-treated samples in PT (p < 0.001). Interestingly, healthy volunteers had higher total vitamin K levels than DMT1. Further analysis suggested that observed coagulation differences were not caused by differences in glycemia but were rather associated with an unexpected, better lipid profile of our DMT1 group. There were also correlations between prolongation of coagulation brought about by the most active anticoagulants and inflammatory markers, and hence inflammatory state probably also contributed to the differences, as well as the mentioned differences in vitamin K levels. Conclusively, this paper suggests the suitability for controlling the effects of direct anticoagulants in DMT1 patients.

• MeSH
• Anticoagulants * pharmacology   therapeutic use   MeSH
• Dabigatran pharmacology   MeSH
• Diabetes Mellitus, Type 1 * blood   drug therapy   MeSH
• Adult MeSH
• Blood Coagulation drug effects   MeSH
• Heparin pharmacology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Partial Thromboplastin Time MeSH
• Prothrombin Time MeSH
• Rivaroxaban pharmacology   MeSH
• Case-Control Studies MeSH
• Vitamin K * blood   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anticoagulants * MeSH
• Dabigatran MeSH
• Heparin MeSH
• Rivaroxaban MeSH
• Vitamin K * MeSH

Familial hypercholesterolemia (FH) is a relatively rare genetic disease associated with high serum cholesterol levels but also with abnormalities in blood coagulation. Novel pharmacotherapeutic approaches in FH including proprotein convertase subtilisin/kexin type 9 antibodies (PCSK9Ab) are very efficient in decreasing cholesterol levels but their impact on coagulation in FH is not yet established. Therefore, we hypothesized that these novel antidyslipidemic drugs can positively impact blood coagulation due to their more potent effect on cholesterol. A total of 15 healthy volunteers and all 15 available patients with severe FH treated at the University Hospital Hradec Králové were enrolled, coagulation was assessed by mechanic coagulometer, and the impact of four clinically used direct anticoagulants was analyzed ex vivo. FH patients were treated effectively as their total cholesterol was 4.11 ± 1.57 mM and LDL cholesterol was 2.44 ± 1.46 mM, which were even lower values than detected in our generally healthy controls. Twelve from the 15 FH patients were finally analyzed as 3 were treated with anticoagulants. Coagulation in FH patients was prolonged more extensively by dabigatran and rivaroxaban, when compared to healthy controls. Treatment with PCSK9Ab or lipid apheresis did not seem to have a significant effect on coagulation. The latter procedure however significantly decreased serum levels of one vitamin K form, MK4. Shorter coagulation time was associated with higher levels of LDL, non-HDL, and total cholesterol. Current treatment of FH seems to improve the effects of direct anticoagulants beyond known effects on LDL cholesterol levels.

• Keywords
• Direct anticoagulants, Familial hypercholesterolemia, Proprotein convertase subtilisin/kexin type 9, Vitamin K,
• MeSH
• Anticholesteremic Agents therapeutic use   MeSH
• Anticoagulants * therapeutic use   pharmacology   MeSH
• Cholesterol blood   MeSH
• Dabigatran therapeutic use   pharmacology   MeSH
• Adult MeSH
• Blood Coagulation * drug effects   MeSH
• Hyperlipoproteinemia Type II * blood   drug therapy   MeSH
• Hypolipidemic Agents * therapeutic use   pharmacology   MeSH
• Cholesterol, LDL blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• PCSK9 Inhibitors MeSH
• Rivaroxaban therapeutic use   pharmacology   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anticholesteremic Agents MeSH
• Anticoagulants * MeSH
• Cholesterol MeSH
• Dabigatran MeSH
• Hypolipidemic Agents * MeSH
• Cholesterol, LDL MeSH
• PCSK9 Inhibitors MeSH
• PCSK9 protein, human MeSH Browser
• Proprotein Convertase 9 MeSH
• Rivaroxaban MeSH