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This review describes some natural proteins, which can be employed, either as factor concentrates derived from human plasma or as recombinant drug, to modulate the coagulation system. I will address some biochemical characteristics and the physiological role of von Willebrand factor, the coagulation factors of the extrinsic and intrinsic pathways, and the physiological anticoagulant protein C. In addition, I will detail the pharmacological compounds, which are available for influencing or substituting the coagulation proteins: desmopressin (DDAVP), single coagulation factor concentrates, prothrombin complex concentrates, and protein C concentrate. In particular, I will address some treatment topics of general medical interest, such as the treatment of massive bleeding, the correction of the coagulopathy induced by vitamin K-antagonists in patients with cerebral haemorrhage, and of the coagulopathy of meningococcemia. Finally, I will describe some properties and practical clinical applications of the recombinant anticoagulans lepirudin and bivalirudin, which are derived from hirudin, the natural anticoagulant of the medical leech.

There is uncertainty whether surgical patients with severe sepsis have a benefit from therapy with Drotrecogin alfa (activated). In the PROWESS and ENHANCE studies 4,068 patients were included and 3,228 were treated with Drotrecogin alfa (activated). Approximately 28% of the PROWESS patients and 41% of the ENHANCE patients were surgical patients. The subgroup of surgical patients showed the same benefit from therapy with Drotrecogin alfa (activated) as the overall cohort. The relative risk was 0.9 (95% CI 0.7-1.25, absolute risk reduction 3.2%). Patients with intraabdominal infections have a special benefit and here the relative risk was 0.7 (95% CI 0.5-1.0, absolute risk reduction 9.1%). Serious bleeding was more frequent in patients treated with Drotrecogin alfa (activated): 2.4-3.6% vs. 1.0% in the placebo group. In surgical patients bleeding was not more frequent than in non-surgical patients (3.1% vs. 2.1%, difference not significant). Surgical patients with severe sepsis, especially with peritonitis, should receive therapy with Drotrecogin alfa (activated), if severely ill.

A systemic inflammation with the release of multiple cytokines plays an important role in the pathophysiology of sepsis. During the last years, several anti-inflammatory substances have been investigated with respect to their effects on mortality in patients with sepsis. However, only the antibody fragment of the TNFalpha binding antibody afelimomab and the recombinant human activated protein C (drotrecogin alpha [activated]) were capable of improving the outcome in controlled studies with large sample sizes. The possible administration of these substances should be restricted to patients who meet the inclusion criteria of these studies. In particular, the tight time window, which usually ends 24 h after the onset of sepsis, should be taken into consideration before starting an anti-inflammatory medication. In addition to the anti-inflammatory treatment, the control of the infectious focus and an aggressive hemodynamic stabilization must not be neglected. Ibuprofen, interleukin-1 receptor antagonists and soluble TNFalpha-receptors as well as high dosages of corticosteroids and antithrombin III do not have a place in the anti-inflammatory treatment of sepsis.

Following several disappointing approaches to decrease the mortality of septic patients using various adjuncts, protein C is the first substance leading to a significant reduction of the mortality rate (PROWESS). The increased risk for bleeding complications in patients receiving protein C, however, limits its use in septic surgical patients. Administration of AT III in septic patients (KYBERSEPT) reduced the mortality rate solely in patients which were not treated with heparin. Although hydrocortisone reduced the amount of vasoactive katecholamines the effect of hydrocortisone administration on the survival rate remains unknown. In summary, early intervention to eliminate the septic focus and the use of antibiotics according to an antibiogramm still remains the most efficient basis for the treatment of septic patients.