DIC in sepsis

Here are some key points from a recent review. The review is available as free full text.

DIC is characterized by activation of procoagulant factors (with an important role of tissue factor expression from activated monocytes and endothelial cells) and down regulation of natural anticoagulants and fibrinolytics (protein C, plasminogen activator and others).

Thus, while clotting may dominate the picture early on clotting factors are consumed, moving the picture toward the bleeding end of the clinical spectrum. At the point of patient presentation either side of the spectrum may dominate, and often both do.

The spectrum of severity is quite variable.

From the article:

Sepsis is almost invariably associated with coagulation abnormalities. These deviations range from delicate activation of coagulation that can only be identified by highly sensitive assays for coagulation factor activation to somewhat more severe hemostatic activation that may be noticeable by a subtle fall in platelet count and sub-clinical elongation of global clotting assays to fulminant disseminated intravascular coagulation (DIC), manifested by widespread microvascular thrombosis in small and mid-size vessels and simultaneous profuse hemorrhage from various sites [[4], [5]]. Patients with sepsis and extensive forms of DIC may develop overt thrombo-embolic complications or clinically less apparent microvascular clot formation that may contribute to multiple organ failure [[5], [6]]. In other cases, severe hemorrhage may be the dominant presentation [7], and frequently sepsis and DIC leads to simultaneous thrombosis and bleeding. Hemorrhage is due to consumption and subsequent depletion of coagulation factors and platelets, caused by ongoing activation of the hemostatic system [8]. In its most extreme manifestation this combination may present as the Waterhouse-Friderichsen syndrome, typically observed during fulminant meningococcal septicemia, although many other microorganisms may cause this clinical situation as well [9].

How often is sepsis accompanied by DIC?

Some degree of coagulation disturbance is present in virtually all patients but it may be subclinical. According to the article 50-70% of patients will have clinically relevant coagulation changes and about 35% will meet criteria for DIC. (Published criteria for overt DIC and non overt DIC are based on scoring systems and are found here).

A drop in platelets occurs in almost all patients with sepsis and the mechanisms are multiple and complex.

From the article:

The vast majority of patients with sepsis will develop thrombocytopenia (platelet count less than 150 × 109/l) [[11], [12]]. Commonly, platelet count drops in the first four days following admission to the hospital [13]. The severity of sepsis correlates strongly with the decrease in platelet count [14]. Crucial factors that cause thrombocytopenia in sepsis are decreased platelet production, enhanced consumption, obliteration, or sequestration in the spleen. Impaired production of megakaryocytes in the bone marrow may seem incongruous with the high levels of platelet production-stimulating pro-inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, and elevated levels of thrombopoietin in patients with sepsis, which theoretically should stimulate megakaryopoiesis [15]. However, in a large number of patients with sepsis substantial hemophagocytosis occurs, consisting of active phagocytosis of platelet precursors and other hematopoietic cells by mononuclear cells, presumably caused by elevated concentrations of macrophage colony stimulating factor (M-CSF) in sepsis [16]. Platelet consumption is presumably also important in sepsis, due to platelet activation secondary to continuous formation of thrombin.