Roman M. Sniecienski

Bio: Roman M. Sniecienski is an academic researcher. The author has contributed to research in topics: Thrombin & Cryoprecipitate. The author has an hindex of 1, co-authored 1 publications receiving 213 citations.

Fibrinogen and hemostasis: a primary hemostatic target for the management of acquired bleeding.

Abstract: Fibrinogen plays several key roles in the maintenance of hemostasis. Its cleavage by thrombin and subsequent polymerization to form fibrin strands provides the structural network required for effective clot formation. During cases of acute blood loss, attempts to maintain circulating volume and tissue perfusion often involve the infusion of crystalloids, colloids, and red blood cells. Intravascular volume resuscitation, although vital, frequently results in dilution of the remaining clotting factors and onset of dilutional coagulopathy. In such cases, fibrinogen is the first coagulation factor to decrease to critically low levels. There currently is a lack of awareness among physicians regarding the significance of fibrinogen during acute bleeding and, at many centers, fibrinogen is not monitored routinely during treatment. We reviewed current studies that demonstrate the importance of considering fibrinogen replacement during the treatment of acquired bleeding across clinical settings. If depleted, the supplementation of fibrinogen is key for the rescue and maintenance of hemostatic function; however, the threshold at which such intervention should be triggered is currently poorly defined. Although traditionally performed via administration of fresh frozen plasma or cryoprecipitate, the use of lyophilized fibrinogen (concentrate) is becoming more prevalent in some countries. Recent reports relating to the efficacy of fibrinogen concentrate suggest that it is a viable alternative to traditional hemostatic approaches, which should be considered. The prospective study of fibrinogen supplementation in acquired bleeding is needed to accurately assess the range of clinical settings in which this management strategy is appropriate, the most effective method of supplementation and a comprehensive safety profile of fibrinogen concentrate used for such an approach.

NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases

Abstract: IL-1β production is critically regulated by cytosolic molecular complexes, termed inflammasomes. Different inflammasome complexes have been described to date. While all inflammasomes recognize certain pathogens, it is the distinctive feature of NLRP3 inflammasome to be activated by many and diverse stimuli making NLRP3 the most versatile, and importantly also the most clinically implicated inflammasome. However, NLRP3 activation has remained the most enigmatic. It is not plausible that the intracellular NLRP3 receptor is able to detect all of its many and diverse triggers through direct interactions; instead, it is discussed that NLRP3 is responding to certain generic cellular stress-signals induced by the multitude of molecules that trigger its activation. An ever increasing number of studies link the sensing of cellular stress signals to a direct pathophysiological role of NLRP3 activation in a wide range of autoinflammatory and autoimmune disorders, and thus provide a novel mechanistic rational, on how molecules trigger and support sterile inflammatory diseases. A vast interest has created to unravel how NLRP3 becomes activated, since mechanistic insight is the prerequisite for a knowledge-based development of therapeutic intervention strategies that specifically target the NLRP3 triggered IL-1β production. In this review, we have updated knowledge on NLRP3 inflammasome assembly and activation and on the pyrin domain in NLRP3 that could represent a drug target to treat sterile inflammatory diseases. We have reported mutations in NLRP3 that were found to be associated with certain diseases. In addition, we have reviewed the functional link between NLRP3 inflammasome, the regulator of cellular redox status Trx/TXNIP complex, endoplasmic reticulum stress and the pathogenesis of diseases such as type 2 diabetes. Finally, we have provided data on NLRP3 inflammasome, as a critical regulator involved in the pathogenesis of obesity and cardiovascular diseases.

Trauma-induced coagulopathy.

Abstract: Uncontrolled haemorrhage is a major preventable cause of death in patients with traumatic injury. Trauma-induced coagulopathy (TIC) describes abnormal coagulation processes that are attributable to trauma. In the early hours of TIC development, hypocoagulability is typically present, resulting in bleeding, whereas later TIC is characterized by a hypercoagulable state associated with venous thromboembolism and multiple organ failure. Several pathophysiological mechanisms underlie TIC; tissue injury and shock synergistically provoke endothelial, immune system, platelet and clotting activation, which are accentuated by the 'lethal triad' (coagulopathy, hypothermia and acidosis). Traumatic brain injury also has a distinct role in TIC. Haemostatic abnormalities include fibrinogen depletion, inadequate thrombin generation, impaired platelet function and dysregulated fibrinolysis. Laboratory diagnosis is based on coagulation abnormalities detected by conventional or viscoelastic haemostatic assays; however, it does not always match the clinical condition. Management priorities are stopping blood loss and reversing shock by restoring circulating blood volume, to prevent or reduce the risk of worsening TIC. Various blood products can be used in resuscitation; however, there is no international agreement on the optimal composition of transfusion components. Tranexamic acid is used in pre-hospital settings selectively in the USA and more widely in Europe and other locations. Survivors of TIC experience high rates of morbidity, which affects short-term and long-term quality of life and functional outcome.