Other neutrophil secretions, such as proteolytic enzymes, which cleave coagulation inhibitors, also bolster the process.In case of imbalance throughout the regulation of immunothrombosis, this process can quickly become aberrant. Regulatory defects in immunothrombosis are suspected to be major factor in causing pathological thrombosis in many forms, such as disseminated intravascular coagulation (DIC) or deep vein thrombosis. DIC in sepsis is a prime example of both dysregulated coagulation process as well as undue systemic inflammatory response resulting in multitude of microthrombi of similar composition to that in physiological immunothrombosis – fibrin, platelets, neutrophils and NETs. Inflammation
Platelets are rapidly deployed to sites of injury or infection, and potentially modulate inflammatory processes by interacting with leukocytes and by secreting cytokines, chemokines and other inflammatory mediators. Platelets also secrete platelet-derived growth factor (PDGF). Platelets modulate neutrophils by forming platelet-leukocyte aggregates (PLAs). These formations induce upregulated production of αmβ2 (Mac-1) integrin in neutrophils. Interaction with PLAs also induce degranulation and increased phagocytosis in neutrophils. Platelets are also the largest source of soluble CD40L which induces production of reactive oxygen species (ROS) and upregulate expression of adhesion molecules, such as E-selectin, ICAM-1 and VCAM-1, in neutrophils, activates macrophages and activates cytotoxic response in T and B lymphocytes.Recently, the dogma that mammalian platelets lacking nucleus are unable of autonomous locomotion was broken. In fact, the platelets are active scavengers, scaling walls of blood vessels and reorganising the thrombus. They are able to recognize and adhere to many surfaces, including bacteria.
They are even able to fully envelop them in their open canalicular system (OCP), leading to proposed name of the process being "covercytosis", rather than phagocytosis, as OCS is merely an invagination of outer plasma membrane. These platelet-bacteria bundles are then used as an interaction platform for neutrophils which destroy the bacteria using the NETosis and phagocytosis. Platelets also participate in chronic inflammatory diseases, such as synovitis or rheumatoid arthritis. Platelets are activated by collagen receptor glycoprotein IV (GPVI). Proinflammatory platelet microvesicles trigger constant cytokine secretion from neighboring fibroblast-like synoviocytes, most prominently Il-6 and Il-8. Inflammatory damage to surrounding extracellular matrix continually reveals more collagen, maintaining the microvesicle production. Adaptive immunity
Activated platelets are able to participate in adaptive immunity, interacting with antibodies. They are able to specifically bind IgG through FcγRIIA, receptor for constant fragment (Fc) of IgG. When activated and bound to IgG opsonised bacteria, the platelets subsequently release reactive oxygen species (ROS), antimicrobial peptides, defensins, kinocidins and proteases, killing the bacteria directly. Platelets also secrete proinflammatory and procoagulant mediators such as inorganic polyphosphates or platelet factor 4 (PF4), connecting innate and adaptive immune responses. Signs and symptoms of disorders
Spontaneous and excessive bleeding can occur because of platelet disorders. This bleeding can be caused by deficient numbers of platelets, dysfunctional platelets, or very excessive numbers of platelets: over 1.0 million/microliter. (The excessive numbers create a relative von Willebrand factor deficiency due to sequestration.