Lipopolysaccharides at approximate plasma reactivities >3 ng/mL or β-glucans at >0.5-1 μg/mL are toxic for human blood; lipopolysaccharide interacts with membrane components of susceptible cells (eg, monocytes) activating phospholipase A2 that destroys the cell membrane. Cell fragments (microparticles or DNA) possess polynegative niches that activate intrinsic hemostasis. Pathologic disseminated intravascular coagulation arises. Blood vessels are obstructed by disseminated thrombi, and vital organ areas become ischemic. Multiorgan failure threatens life of the patient. Diagnosis and therapy of pathologic disseminated intravascular coagulation is of extreme clinical importance. For early diagnosis of pathologic disseminated intravascular coagulation, specific activation markers of coagulation (eg, plasmatic amidolytic thrombin activity) or the plasmatic lipopolysaccharide or glucan reactivity can be measured. A new treatment target might be kallikrein or factor XIIa; 10 to 20 mM arginine is the approximate 50% inhibitory concentration against the contact phase of coagulation. The complex interaction between cell fragments and hemostasis causes pathologic disseminated intravascular coagulation in sepsis.