The question of the safety of direct oral anticoagulants (DOACs), despite their high efficacy in the prevention of thrombotic events in atrial fibrillation (AF), remains relevant due to the risk of developing hemorrhagic events while taking standard doses, which requires a thorough personalized approach. The article presents a clinical case of the development of spontaneous hematomas on the skin of the upper and lower extremities and hemarthrosis of the knee joint while taking 20 mg of rivaroxaban in a 72-year-old patient with AF without impaired renal and hepatic function. Due to the increase in the residual plasma concentration of rivaroxaban, a pharmacogenetic study and the Thrombodynamics (TD) test were performed. A pharmacogenetic study did not reveal significant gene polymorphisms associated with the metabolism of rivaroxaban. However, TD allowed us to confirm the presence of significant hypocoagulation at the peak of the residual blood concentration of the drug in the blood, which could cause recurrent hemorrhagic events in the patient. In addition, the patient is taking amiodarone at a dosage of 200 mg per day, which does not allow us to rule out drug-drug interaction, despite the inconsistency of the literature data.
Thromboembolic syndrome, the frequency of which is 8–15%, is the main danger for a patient with atrial fibrillation (AF). The left atrial appendage is the most common source of thromboembolia in atrial fibrillation. The frequency of detection of left atrial appendage thrombus in AF is 15.2% in the absence of anticoagulant therapy and 1–8% in patients using this group of drugs. The reason for the formation of thrombi in this localization during anticoagulant therapy today it is not reliably known. This article describes a clinical case of a 67-year-old patient with persistent AF and left atrial appendage thrombosis, who was hospitalized to determine further management strategies. A left atrial appendage thrombus lasted for a year despite continuous anticoagulant therapy with various oral anticoagulants at doses consistent with clinical guidelines due to the patient's absolute refusal to take warfarin, vitamin K antagonist. In addition, this article discusses the use of Thrombodynamics, a new global coagulation test, in patients with AF, which revealed a plasma hypercoagulable state with underlying persistent thrombosis in this patient on continuous oral anticoagulant treatment. The Thrombodynamics test is a promising procedure for assessing the coagulation system state and may be promising as a method for measuring the effectiveness of any oral anticoagulant. However, it is impossible to draw any definite conclusions on the basis of single observations; large clinical studies with the potential of long-term case follow-up of patients are needed.
Antirestriction proteins of the ArdB/KlcA family are specific inhibitors of restriction (endonuclease) activity of type-I restriction/modification enzymes. The effect of conserved amino acid residues on the antirestriction activity of the ArdB protein encoded by the transmissible R64 (IncI1) plasmid has been investigated. An analysis of the amino acid sequences of ArdB homologues demonstrated the presence of four groups of conserved residues ((1) R16, E32, and W51; (2) Y46 and G48; (3) S81, D83 and E132, and (4) N77, L(I)140, and D141) on the surface of the protein globule. Amino acid residues of the fourth group showed a unique localization pattern with the terminal residue protruding beyond the globule surface. The replacement of two conserved amino acids (D141 and N77) located in the close vicinity of each other on the globule surface showed that the C-terminal D141 is essential for the antirestriction activity of ArdB. The deletion of this residue, as well as replacement by a hydrophobic threonine residue (D141T), completely abolished the antirestriction activity of ArdB. The synonymous replacement of D141 by a glutamic acid residue (D141E) caused an approximately 30-fold decrease of the antirestriction activity of ArdB, and the point mutation N77A caused an approximately 20-fold decrease in activity. The residues D141 and N77 located on the surface of the protein globule are presumably essential for the formation of a contact between ArdB and a currently unknown factor that modulates the activity of type-I restriction/modification enzymes.
Aim. Syncopal condition in young people are a relatively frequent and poorly understood medical problem. Non-cardiogenic syncope is not sufficiently studied because often they are not raise fears among doctors or patients, and at the same time their causes are associated with many complex medical and diagnostic aspects. The aim of the presented work is to identify the most significant risk factors in the development of non-cardiogenic syncopal conditions, identify triggers and assess the relationship between these factors, the lifestyle and development of syncope.Material and methods. The article presents the results of a descriptive research, including 1031 young people with a history of syncope episodes. The study took into account the presence of chronic diseases which could become a syncope trigger. External triggers (prolonged upright staying, stuffy room, and so on) were also determined.Results. In a multifactor survey of students living in Russia and abroad, the more frequent occurrence of non-cardiogenic syncopal episodes in young girls compared with young men was found. The effect of longterm upright and oxygen corporal were most likely risk factors for syncope.Conclusion. A significant correlation was found between the onset of reflex syncope and the presence of anemia and autonomic dysfunction syndrome. We proved the absence of a correlation between the level of daily load and the frequency of syncope conditions.
The article presents a clinical observation of the left atrial appendage thrombosis in a 51-year-old female patient with a paroxysmal form of nonvalvular atrial fibrillation which occurred despite long-term anticoagulant therapy with apixaban in a full dose (5 mg b.i.d.), and the patient’s management. The patient was admitted with recurrent symptomatic paroxysm for more than 48 hours, because of which, in accordance with the recommendations, transesophageal echocardiography was performed before an emergency rhythm restoration. Thrombus in the left atrial appendage 0.5×1.03 cm in size was detected. It was decided to refrain from the immediate restoration of the rhythm due to the very high risk of thromboembolic complications. In connection with the categorical refusal of the patient from warfarin, it was decided to replace apixaban with another direct oral anticoagulant – dabigatran 150 mg bid for a period of 4 weeks followed by performing a control transesophageal echocardiographic study. As a result, no thrombus was found on control echocardiography. The particularity of this observation is concomitant hypertrophic cardiomyopathy and diabetes mellitus type 1 in this patient.
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