C1-inhibitor in patients with severe sepsis and septic shock: Beneficial effect on renal dysfunction

Caliezi, Christoph; Zeerleder, Sacha; Redondo, Maurice; Regli, Bruno; Rothen, H. U.; Zürcher-Zenklusen, Regula; Rieben, Robert; Devay, Jan; Hack, C. E.; Lämmle, Bernhard; Wuillemin, Walter A.

doi:10.1097/00003246-200208000-00008

Cited by 92 publications

(73 citation statements)

References 27 publications

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“…C1-INH was effective in a randomized, double-blind clinical study in septic intensive care unit patients. Whereas the renal dysfunction was reduced, the mortality rate remained unchanged in both groups (140). The only clinical application for C1 inhibitor so far is for C1 inhibitor deficiency leading to hereditary angioedema (141).…”

Section: Immunomodulation Of Complementmentioning

confidence: 92%

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Ehrnthaller

Ignatius

Gebhard

et al. 2010

Mol Med

185

154

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The complement system was discovered a century ago as a potent defense cascade of innate immunity. After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established. Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells. However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences. Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others. The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade. In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically. In the case of uncontrolled complement activation, "friendly fire" is generated, resulting in the destruction of healthy host tissue. Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained. In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects.

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Section: Immunomodulation Of Complementmentioning

confidence: 92%

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Ehrnthaller

Ignatius

Gebhard

et al. 2010

Mol Med

185

154

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“…We recruited 68 patients with thrombocytopenia (platelet count, Ͻ140 ϫ 10 9 /L), including 17 patients from a previous study 18 with severe sepsis or septic shock with or without DIC; 16 patients with heparin-induced thrombocytopenia type 2 (HIT) studied between 1995 and 2001 (all with a high clinical probability of HIT and the diagnosis confirmed by a high titer of antiheparin-platelet factor 4 antibodies; L. Alberio, et al, manuscript submitted); and 35 patients, prospectively enrolled from July 2001 to December 2001, with thrombocytopenic states with the following causes: ITP (n ϭ 10), idiopathic osteomyelofibrosis (n ϭ 3), myelodysplastic syndrome (MDS; n ϭ 4), acute leukemia (n ϭ 6), severe aplastic anemia (n ϭ 2), and miscellaneous (n ϭ 10) ( Table 1). In none of the 68 patients with thrombocytopenia had TTP or HUS been considered as an alternative diagnostic possibility.…”

Section: Study Design Patientsmentioning

confidence: 99%

Von Willebrand factor–cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura

Bianchi

Robles

Alberio

et al. 2002

Blood

297

231

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A severe deficiency in von Willebrand factor-cleaving protease (ADAMTS13) activity (< 5% that in normal plasma) has been observed in most patients with a diagnosis of thrombotic thrombocytopenic purpura (TTP) but not in those with a diagnosis of hemolytic uremic syndrome. However, ADAMTS13 deficiency has been claimed not to be specific for TTP, since it was observed in various thrombocytopenic and other conditions. We studied 68 patients with thrombocytopenia due to severe sepsis or septic shock (n ‫؍‬ 17), heparin-induced thrombocytopenia (n ‫؍‬ 16), idiopathic thrombocytopenic purpura (n ‫؍‬ 10), or other hematologic (n ‫؍‬ 15) or miscellaneous conditions (n ‫؍‬ 10). Twelve of the 68 patients had subnormal levels of ADAMTS13 activity (< 30%), but none had less than 10%. Thus, the study showed that AD-AMTS13 activity is decreased in a substantial proportion of patients with thrombocytopenia of various causes. A severe deficiency of ADAMTS13 (< 5%), identified in more than 120 patients during 1996 to 2001 in our laboratory, is specific for a thrombotic microangiopathy commonly labeled TTP. (Blood. 2002;100:710-713)

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“…Closely interconnected with the immunologic and endothelial system, recent data have indicated a contributing role of the coagulation system in the development of microcirculatory dysfunction and multiple organ failure in patients with sepsis [1][2][3]. Accordingly, anticoagulatory and anti-inflammatory therapies could reduce the severity of organ failure [4][5][6] and improve mortality in patients with sepsis and a high risk of death [7].…”

Section: Introductionmentioning

confidence: 99%

Uncovering Hypercoagulability in Sepsis Using ROTEM® Thromboelastometry: A Case Series

Luckner¹,

Mayr²,

Fries³

et al. 2008

TOCCMJ

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This case series presents three patients with sepsis/septic shock in whom standard coagulation tests (international normalized ratio, activated partial thromboplastin time, fibrinogen, antithrombin, thrombocytes) and ROTEM ® thromboelastometry (InTEM, ExTEM, FibTEM) were simultaneously performed. Although all patients showed significantly prolonged plasmatic coagulation times with a putatively increased risk of bleeding, ROTEM ® thromboelastometry revealed normal clotting times and even signs of hypercoagulability. Therefore, no coagulation active therapy was performed in any patient, not even before invasive procedures or major surgical interventions. No bleeding occurred in any study patient during surgery or the subsequent stay on the intensive care unit. These observations suggest that some critically ill patients with sepsis and abnormal standard coagulation tests may in fact have hypercoagulability. ROTEM ® thromboelastometry can add important information in these patients and enable that blood products are used targeted and only for substitution of relevant deficencies. Future studies are necessary to validate these preliminary findings.

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C1-inhibitor in patients with severe sepsis and septic shock: Beneficial effect on renal dysfunction

Abstract: C1-inhibitor administration attenuated renal impairment in patients with severe sepsis or septic shock.

Cited by 92 publications

References 27 publications

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Von Willebrand factor–cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura

Uncovering Hypercoagulability in Sepsis Using ROTEM® Thromboelastometry: A Case Series

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