Why there is absence of blood coagulation in anthrax disease?

In anthrax disease, the absence of blood coagulation is primarily caused by a virulence factor produced by the bacterium *Bacillus anthracis* known as anthrax lethal factor (LF). LF is one of the three main components of the anthrax toxin, along with edema factor (EF) and protective antigen (PA).

Mechanism of action:

Binding to Protective Antigen (PA): LF binds to PA, which is the cell surface receptor for the anthrax toxin, forming a complex called LF-PA.

Entry into the Host Cell: The LF-PA complex is then internalized into the host cell through receptor-mediated endocytosis.

Cleavage of Mitogen-Activated Protein Kinase Kinases (MAPKKs): Once inside the cell, LF targets and proteolytically cleaves several members of the MAPKK family, such as MEK1, MEK2, and MEKK1.

Inhibition of MAPK Signaling: Cleavage of MAPKKs disrupts the downstream signaling pathways, particularly the mitogen-activated protein kinase (MAPK) pathway. The MAPK pathway plays a crucial role in various cellular processes, including cell growth, differentiation, and apoptosis.

Effects on Blood Coagulation:

Impaired Platelet Function: The disruption of MAPK signaling by LF affects the activation and aggregation of platelets, which are essential for blood coagulation.

Dysregulation of Fibrin Formation: Fibrin is a protein that forms the structural framework of blood clots. LF interferes with the production and stabilization of fibrin by inhibiting the activity of factors involved in the coagulation cascade.

Lack of Thrombin Generation: Thrombin is a key enzyme in the coagulation process, responsible for converting fibrinogen into fibrin. LF impedes thrombin generation and prevents the formation of stable blood clots.

As a result of these effects, individuals infected with anthrax may suffer from an absence of blood coagulation, leading to a condition known as disseminated intravascular coagulation (DIC). This abnormal coagulation can result in excessive bleeding and internal hemorrhaging.