ГЕПАРИНИНДУЦИРОВАННАЯ ТРОМБОЦИТОПЕНИЯ (ОБЗОР)

Heparin-induced thrombocytopenia (HIT) is a serious and potentially life-threatening side effect of heparinotherapy. It is an antibody-mediated process that causes platelet activation, increases the procoagulant characteristics of the blood and, as a result, endangering limbs and life-threatening thrombosis. Venous thrombosis is more common than arterial thrombosis, especially deep vein thrombosis of the lower limbs and pulmonary artery thrombosis. Mortality from complications of heparinotherapy occurs with a frequency of 20–30 % of cases. Diagnosis of HIT is difficult. Such basic symptoms as thrombocytopenia and thrombosis are extremely non-specific and may be present in cancer patients and patients with cardiosurgical pathologies without the impact of heparin. Women are twice as likely to have HIT as men. This review describes pathogenesis, clinical features, modern diagnostic methods, risk factors for the emergence of this formidable complication of heparinotherapy, gives an overview of the most frequent use of drugs for the treatment of HIT, and gives modern clinical recommendations for different groups of patients.Гепарининдуцированная тромбоцитопения (ГИТ) является серьезным и потенциально опасным для жизни побочным эффектом проводимой гепаринотерапии. Это опосредованный антителами процесс, приводящий к активации тромбоцитов, повышению прокоагулянтных характеристик крови и, как результат, угрожающему конечностям и опасному для жизни тромбозу. Венозные тромбозы при этом случаются чаще, чем артериальные, особенно распространены тромбозы глубоких вен нижних конечностей и тромбоэмболии легочной артерии. Смертность от осложнений гепаринотерапии происходит с частотой 20–30% случаев. Диагностика ГИТ затруднена. Такие основные симптомы, как тромбоцитопения и тромбообразование, крайне неспецифичны и могут присутствовать у онкологических больных и больных с кардиохирургическими патологиями без воздействия гепарина. У женщин вероятность развития ГИТ в 2 раза выше, чем у мужчин. В данном обзоре описываются патогенез, клинические особенности, современные методы диагностики, факторы риска для возникновения этого грозного осложнения гепаринотерапии, приведен обзор наиболее частых в применении препаратов для лечения ГИТ, даны современные клинические рекомендации для разных групп пациентов

Фибронектин: структура, функции, клиническая значимость (обзор)

Plasma fibronectin is a high molecular weight adhesive glycoprotein. There are two types of fibronectin: plasma (soluble) and cellular derived (insoluble). Electron microscopy revealed two types of structural organization of fibronectin: compact and expanded. In solution, fibronectin has a compact conformation, and after binding to certain substrates (collagen, fibrin, heparin), it is expanded. Plasma fibronectin is one of the main opsonins of blood plasma in relation to the “targets” of phagocytosis of a predominantly non-bacterial nature, as well as to some types of bacteria. For the treatment of septic processes, as well as respiratory distress syndrome of adults with severe fibronectin deficiency, plasma cryoprecipitate is used – a donor plasma preparation containing a large amount of plasma fibronectin (more than 2 mg/ml). It was proposed to replenish the level of fibronectin in patients with sepsis and other conditions that cause plasma fibronectin deficiency with the help of donor freshly frozen plasma. Transfusion of large volumes of freshly frozen plasma (up to 1000–1500 ml) to patients effectively eliminates the deficiency of plasma fibronectin. The concentration of plasma fibronectin in the blood significantly decreases after the addition of severe infectious processes to hematological diseases, as well as acute DIC syndrome. Extracorporeal methods of blood purification – selective plasmapheresis – have been developed to correct immunocomplex and fibronectin-complex pathology. Two variants of selective plasmapheresis have been proposed: the method of heparinocryoprecipitation of plasma proteins and the method of heparinocryofractionation. In 1987, a plasma heparin precipitate was proposed as a source of fibronectin for the treatment of patients with trophic skin lesions. In 1992, a new method was proposed for obtaining blood preparations with a high concentration of plasma fibronectin from patients themselves (heparin cryofractionation). Autofibronectin preparations obtained by such methods are effective in the local treatment of trophic ulcers in 90–93% of cases. The proposed drugs are safe against infection of patients with infectious diseases transmitted through the blood.Плазменный фибронектин (ФН) является высокомолекулярным адгезивным гликопротеином. Существует два типа ФН: плазменный (растворимый) и клеточный (нерастворимый). Методом электронной микроскопии обнаружено два типа структурной организации ФН: компактная и развернутая. В растворе ФН имеет компактную конформацию, а после связывания с определенными субстратами (коллагеном, фибрином, гепарином) – развернутую. Плазменный ФН является одним из основных опсонинов плазмы крови по отношению к мишеням фагоцитоза преимущественно небактериальной природы, а также к некоторым видам бактерий. Для лечения септических процессов, а также респираторного дистресс-синдрома взрослых, протекающих с выраженным дефицитом ФН, используют плазменный криопреципитат – препарат донорской плазмы, в котором содержится большое количество плазменного ФН (более 2 мг/мл). Было предложено восполнять уровень ФН у пациентов с сепсисом и другими состояниями, вызывающими дефицит плазменного ФН, при помощи донорской свежезамороженной плазмы. Переливание пациентам больших объемов свежезамороженной плазмы (до 1000–1500 мл) эффективно нивелирует дефицит плазменного ФН. Концентрация плазменного ФН в крови достоверно снижается после присоединения к гематологическим заболеваниям тяжелых инфекционных процессов, а также острого ДВС-синдрома (диссеминированное внутрисосудистое свертывание). Для коррекции иммунокомплексной и фибронектинокомплексной патологии разработаны экстракорпоральные методы очистки крови – селективные плазмаферезы. Было предложено два варианта селективного плазмафереза: метод гепаринокриопреципитации плазменных белков и способ гепаринокриофракционирования. В 1987 г. в качестве источника ФН для лечения больных с трофическими поражениями кожи был предложен препарат плазменного гепаринового преципитата. В 1992 г. предложен новый способ получения – от самих же пациентов препаратов крови с высокой концентрацией плазменного ФН (гепаринокриофракционирование). Полученные таким способом препараты аутофибронектина эффективны при местном лечении трофических язв в 90–93% случаев. Предлагаемые препараты безопасны в отношении заражения больных инфекционными заболеваниями, передающимися через кровь

Аpplication of plasma proteins cryoheparinoprecipitation method in the treatment of patients with cryoglobulinemia

Introduction. The term “cryoglobulinemia” is currently used to identify immunoglobulins in vitro in the blood serum that precipitate at temperatures below 37 °C; in vivo they form immune complexes that can be deposited in small vessels and activate the complement system with the development of leukocytoclastic vasculitis. Cryoglobulinemia may develop in various lymphoproliferative, autoimmune and infectious diseases. Aim of study. To develop the technique of plasma proteins cryofraction (selective plasmapheresis with the use of heparin as a stimulant of fibronectin opsonic activity and purified autoplasma to compensate for the removed volume), to evaluate the effectiveness and tolerability of the developed technique in the treatment of patients with cryoglobulinemia. Materials and methods. 159 patients were treated (120 women and 39 men aged 21 to 83 years). Research results. Heparinocryofraction technique is a highly effective method of extracorporeal blood purification, which allows to selectively remove from the patients’ plasma such pathological components as cryoglobulins (up to 100% of the initial content), adhesive proteins (up to 84% of the initial content), fibronectin and immune complexes (up to 7% of the initial content). It is possible to reduce significantly and reliably the level of cryoglobulins, circulating immune complexes, non-specific markers of inflammation, daily proteinuria, as well as to normalize the initially reduced concentration of complement components and hemoglobin in the blood of patients with cryoglobulinemia before and after the procedure of cryofractionation. Purified by the proposed method autoplasma is a solution of albumin and normal immunoglobulins, which allows to use it for plasma substitution during a course of cryofractionation procedures, on average 7 procedures with an interval of 1–2 days. Conclusion. The technique of cryofractionation using heparin and purified autoplasma can and should be widely used in the complex treatment of patients with cryoglobulinemia. Carrying out 6–-7 sessions of plasma cryofractionation allows to remove cryoglobulins from plasma effectively and selectively. Application of purified autoplasma allows to avoid using of blood preparations in plasmapheresis. The proposed method allows to significantly improve the efficiency and tolerance of medication therapy and increase the duration of disease remission

Cell-binding microarray application in diagnosis of hairy cell leukemia

We describe an application of a cell-binding microarray – to parallel study of morphology, tartrate-resistant acid phosphatase activity and detection of surface markers on peripheral blood lymphocytes of 90  atients with suspected hairy cell leukemia (HCL). We have formulated the microarray-based diagnostic criteria for hairy cell leukemia, hairy cell leukemia variant (HCLv) and splenic marginal zone lymphoma (SMZL). According to these criteria we have suggested the presence of HCL for 55 patients, HCLv – for 7 patients and SMZL – for 10 patients from the studied cohort. These diagnoses were confirmed by standard diagnostic methods in all cases. These results show that the cellbinding microarray can be used in differential diagnosis of HCL, while the high sensitivity of the microarray permits to detect the leukemic cells in spite of leukopenia and low hairy cell content

Visible light regulates neurite outgrowth of nerve cells

The neurite outgrowth of PC12 cells on collagen-coated glass plates under light emitting diode (LED) irradiation at several wavelengths (i.e., 455, 470, 525, 600, 630, 880 and 945 nm) was investigated. No neurite outgrowth was observed during cultivation under irradiation from the lamp of an inverted light microscope through filters (yielding mixed light at ca. 525 nm and more than 800 nm), whereas neurite outgrowth was observed during cultivation in the dark. When these cells were irradiated with monochromatic LED light, neurite outgrowth was slightly, but not completely, suppressed at 455, 525, 600, 630, 880 and 945 nm, as was observed in the case of mixed light. Long connected neuronal outgrowths (e.g., 3 mm length) were observed with LED light at 470 nm and 1.8 mW/cm2 intensity. No such outgrowths were observed at other LED light wavelengths (i.e., 455, 525, 600, 630, 880 and 945 nm). Irradiation at 470 nm may have caused specific responses to transductional signals in these cells that led to the connection of neuronal outgrowths between cells. Not only suppressed neurite outgrowth but also long connected neurite outgrowths were observed when PC12 cells were cultured under several different wavelengths of light