BACKGROUND AND AIMS: It is well known that elevated cholesterol is associated with enhanced platelet aggregation and patients suffering from familial hypercholesterolemia (FH) have a high risk of thrombotic cardiovascular events. Although decreasing cholesterol level is associated with attenuation of platelet hyperactivity, there are currently no data on the effect of convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9ab) on platelet reactivity in FH. The aim of the study was to analyse the impact of different therapies including PCSK9ab on platelet aggregation in FH. METHODS: This study enrolled all 15 patients treated in the University Hospital Hradec Králové for FH. PCSK9ab have been administered in 12 of 15 patients while 8 patients were also undergoing lipid apheresis. Blood samples from all patients including pre- and post-apheresis period were tested for platelet aggregation triggered by 7 inducers, and the effect of 3 clinically used drugs (acetylsalicylic acid, ticagrelor and vorapaxar) was compared as well. RESULTS: Although apheresis decreased the reactivity of platelets in general, platelet responses were not different between non-apheresis patients treated with PCSK9ab and apheresis patients (post-apheresis values) with the exception of ristocetin. However, when compared to age-matched healthy population, FH patients had significantly lower platelet aggregation responses to 4 out of 7 used inducers and higher profit from 2 out of 3 used antiplatelet drugs even after exclusion of FH patients regularly receiving conventional antiplatelet treatment. CONCLUSION: This study showed for the first time the suitability of PCSK9ab treatment for reduction of platelet reactivity in FH patients.

• Klíčová slova
• ADP receptor, Acetylsalicylic acid, Antiplatelet, Dyslipidemia, Ticagrelor, Vorapaxar,
• MeSH
• agregace trombocytů * účinky léků   MeSH
• dospělí MeSH
• hyperlipoproteinemie typ II * krev   terapie   farmakoterapie   MeSH
• inhibitory agregace trombocytů * terapeutické užití   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   farmakologie   MeSH
• PCSK9 inhibitory * MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 * imunologie   MeSH
• senioři MeSH
• separace krevních složek * MeSH
• trombocyty účinky léků   metabolismus   imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inhibitory agregace trombocytů * MeSH
• monoklonální protilátky MeSH
• PCSK9 inhibitory * MeSH
• PCSK9 protein, human MeSH Prohlížeč
• proproteinkonvertasa subtilisin/kexin typu 9 * MeSH

Elevated low-density lipoprotein (LDL) cholesterol levels lead to atherosclerosis and platelet hyperaggregability, both of which are known culprits of arterial thrombosis. Normalization of LDL cholesterol in familial hypercholesterolemia (FH) is not an easy task and frequently requires specific treatment, such as regularly performed lipid apheresis and/or novel drugs such as proprotein convertase subtilisin kexin 9 monoclonal antibodies (PCSK9Ab). Moreover, a high resistance rate to the first-line antiplatelet drug acetylsalicylic acid (ASA) stimulated research of novel antiplatelet drugs. 4-methylcatechol (4-MC), a known metabolite of several dietary flavonoids, may be a suitable candidate. The aim of this study was to analyse the antiplatelet effect of 4-MC in FH patients and to compare its impact on two FH treatment modalities via whole-blood impedance aggregometry. When compared to age-matched, generally healthy controls, the antiplatelet effect of 4-MC against collagen-induced aggregation was higher in FH patients. Apheresis itself improved the effect of 4-MC on platelet aggregation and blood from patients treated with this procedure and pretreated with 4-MC had lower platelet aggregability when compared to those solely treated with PCKS9Ab. Although this study had some inherent limitations, e.g., a low number of patients and possible impact of administered drugs, it confirmed the suitability of 4-MC as a promising antiplatelet agent and also demonstrated the effect of 4-MC in patients with a genetic metabolic disease for the first time.

• Klíčová slova
• 4-methylcathechol, familial hypercholesterolemia, lipid apheresis, platelet,
• MeSH
• hyperlipoproteinemie typ II * farmakoterapie   MeSH
• LDL-cholesterol MeSH
• lidé MeSH
• monoklonální protilátky farmakologie   terapeutické užití   MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 MeSH
• proproteinkonvertasy terapeutické užití   MeSH
• separace krevních složek * metody   MeSH
• subtilisin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 4-methylcatechol MeSH Prohlížeč
• LDL-cholesterol MeSH
• monoklonální protilátky MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 MeSH
• proproteinkonvertasy MeSH
• subtilisin MeSH