Introduction. Eculizumab inhibits the terminal steps of complement activation and is the standard treatment for paroxysmal nocturnal hemoglobinuria (PNH). Unstable complement inhibition causes “breakthrough” intravascular hemolysis and a suboptimal response to eculizumab therapy in some patients with PNH.

Aim: to evaluate the stability of complement inhibition in eculizumab treatment by testing the kinetic parameters of complement activation.

Materials and methods. The study included 12 PNH patients receiving long-term eculizumab therapy (median 54 months, range 4–66 months). The median age was 35 years (from 22 to 68 years), 92 % of patients were female. The median PNH clone size was 96  % of the granulocytes. The control group consisted of 12 healthy donors (age 25–60 years, women 75 %). Complement activation was evaluated immediately prior to the next eculizumab infusion, and then again after 5 and 10 days. Kinetic parameters (induction period, hemolysis rate, T50-the time required to achieve 50  % hemolysis) were recorded separately for the total complement activity and an alternative activation pathway using rabbit red blood cells (rRBC).

Results. The parameters of complement activation directly before the next eculizumab administration corresponded to a marked inhibition of the overall activity of the system. The induction period was extended by 7 times compared to the control (median 180 vs 25 seconds, p < 0.0001), and the hemolysis rate was 28 times less (median 1.6 vs 45.1 × 106 rRBC/min, p < 0.0001). The T50 value exceeded the control value by 20 times (median 690 vs 35 seconds, p < 0.0001). The parameters of the alternative complement activation pathway were reduced by 2–3 times compared to the control. In one case, repeated tests revealed insuffi cient complement inhibition, which was associated with pharmacokinetic “breakthrough” hemolysis. The degree of further complement inhibition and the tendency to restore activity varied signifi cantly during dynamic testing on days 5 and 10 after eculizumab infusion.

Conclusion. The results of this study demonstrate individual differences in the residual activity of complement in PNH patients receiving long-term eculizumab therapy. Testing of complement activity is necessary with a suboptimal response to eculizumab therapy and when considering therapy correction. Kinetic registration of residual complement-dependent lysis of rabbit red blood cells demonstrates a higher sensitivity than the traditional CH50 study.

Conflict of interest: the authors declare no conflict of interest.

Financial disclosure: the study had no sponsorship.

Background. Combined injuries involving brain damage represent the most severe and life-threatening conditions in hemophilia patients. These injuries are characterised by specific situational and behavioural circumstances indicating the presence of victim behaviour in such patients.

Aim. To analyse the influence of victim behaviour in hemophilia patients on the formation of combined neurosurgical trauma and the choice of neurosurgical and traumatological treatment approaches.

Materials and methods. Twenty five patients (20 patients with hemophilia A and 5 patients with hemophilia B) were included in the study. The patients suffered the following injuries: craniocerebral injuries — 68 (100.0 %); bone fractures — 18 (26.6 %); hematomas of the soft tissues of the face, upper and lower extremities, as well as bruised, lacerated wounds — 50 (73.4 %).

Results. The following types of victim behaviour were identified in the hemophilia patients: paranoid — 7 (28.0 %), dependent — 8 (32.0 %), dissociative — 6 (24.0 %) and antisocial — 4 (16.0 %). The patients underwent hemostatic therapy with coagulation factor VIII or IX concentrates and surgical (neurosurgical and/or traumatological) treatment of the injuries associated with victim behaviour. In 51 (75.0 %) cases there was delayed medical care, which was the reason for the complicated course of the post-traumatic period. It was revealed that the best treatment results in patients with severe injuries, including craniocerebral traumas, were achieved in cases where medical assistance was provided in the first three hours after injury. As a result of the treatment, the majority of the patients demonstrated regression of the clinical manifestations of the injury.

Conclusions. The proposed tactics for the diagnosis and neurosurgical/traumatological treatment of hemophilia patients with signs of victim behaviour, in whom combined brain injuries are detected, includes a comprehensive assessment of medical history data, clinical and laboratory examination, as well as determination of diagnostic criteria for the choice of patient-specific surgical techniques. It is proposed to use the number of patients’ return visits related to their victim behaviour as a quantitative assessment of the degree of victimization.

Conflict of interest: the authors declare no conflict of interest.

Introduction. The majority of drugs used for targeted antitumor therapy are associated with dermatological toxicities. Dermatological adverse events significantly affect patient quality of life and can require the modification of treatment regimens with Bcr-Abl tyrosine kinase inhibitors.

Aim. to analyze specific skin adverse events of Bcr-Abl tyrosine kinase inhibitors in accordance with their activity against the main and additional protein kinase targets.

Main Findings. This article presents data on dermatological adverse events, possible mechanisms for their development, as well as a clinical picture and treatment of the most significant skin adverse events requiring the modification of therapy with Bcr-Abl tyrosine kinase inhibitors. A comparison of clinical and histological data of skin adverse reactions and the dermatological nosologies, which they imitate, is presented. Further investigation into the mechanisms of development of specific dermatological adverse events is of interest to both hematologists an dermatologists. This will contribute to a better understanding of the effect Bcr-Abl tyrosine kinase inhibitors have on skin structures and control of dermatological adverse events, as well as assist in the development of supportive oncodermatology.

Conflict of interest: the authors declare no conflict of interest.

Financial disclosure: the study had no sponsorship.

Introduction. Rodenticides are pesticides used in the control of rodents. In Russia, only anticoagulant rodenticides are allowed to be used.

Aim: describe a case of mass poisoning with anticoagulant rodenticides.

Main findings. An observation is given of poisoning with anticoagulant rodenticides in 80 people due to the consumption of sunflower oil produced from seeds that have been treated with rodenticides. The victims had a pronounced hemorrhagic syndrome: all had ecchymosis, 79 % had macrohematuria, 1 had uterine bleeding, 3 had intra-abdominal hemorrhages, 16 had nosebleeds, 2 had gastrointestinal bleeding, and 2 had intracerebral hemorrhages. The international normalized ratio (INR) was not definable in 56 patients, while the remaining patients had a median INR of 3.9 (fluctuations from 1.29 to 16.2). Activated partial thromboplastin time (APTT) was not definable in 7 patients; the remaining patients had the median APTT of 65 seconds. Three of the victims died of hemorrhagic syndrome. This article analyzes the conducted therapy. In life-threatening hemorrhagic syndrome induced by rodenticide poisoning or warfarin overdose the drugs of choice are prothrombin complex concentrates and recombinant activated clotting factor VII, but not fresh frozen plasma and vicasol. For long-term therapy, vitamin K1 should be used.

Conflict of interest: the authors declare no conflict of interest.

Introduction. Heavy-chain diseases (HCDs) are rare B-cell lymphoproliferative diseases that do not have a classical clinical picture. A characteristic feature of this disease is the secretion of fragmented heavy chains of various immunoglobulin isotypes. Currently, there are four known variants of this disease: μ, γ, α, and δ.

Aim. To describe the clinical observation of μ-HCD, hidden under the mask of systemic amyloidosis, and the associated diffi culties of primary diagnosis.

Main Findings. A rare clinical case of μ-HCD in combination with systemic amyloidosis (light chain amyloidosis-AL), transthyretin amyloidosis (transthyretin amyloidosis-ATTR), and non-amyloid deposits in a 64-year-old patient is presented. The severity of the condition was due to the clinical picture of chronic heart failure, polyneuropathy. Upon examination, Waldenstrom’s macroglobulinemia was diagnosed while a diagnosis of amyloidosis was not established. Immuno-chemotherapy was performed under the RB program (rituximab and bendamustine). The effect of the therapy was minimal and short-term. The patient’s condition progressively worsened, and the patient died due to acute cardiovascular failure. The main diagnosis was revised in favor of μ-HCD. The autopsy revealed widespread amyloid and non-amyloid lesions of organs and tissues.

 Conflict of interest: the authors declare no conflict of interest

Financial disclosure: the study had no sponsorship

Introduction. At the initiative of the Russian Hematology Society, the research group for the study of idiopathic aplastic anemia has developed clinical recommendations for the diagnosis and treatment of idiopathic aplastic anemia.

Aim: to standardize diagnostic and therapeutic approaches for the treatment of acquired aplastic anemia in Russia.

Methods. The methodological approaches used are based on the principles of evidence-based medicine, based on the recommendations of the Russian council of experts on the diagnosis and treatment of patients with idiopathic aplastic anemia, Russian and international experience in managing patients, and the recommendations of the European group for the study of aplastic anemia.

Results. A new revised and updated version of the national clinical guidelines is presented.

Conclusion. These recommendations are intended for doctors of various specialties, health administrators, and medical school students.

Conflict of interest: the authors declare no conflict of interest.

Financial disclosure: this study did not have sponsorship.