• Platelet serotonin (5-HT) is involved in body temperature regulation.

• 5-HT is a vasoconstrictor, vasodilator and pyrogen, which is a fever-inducing substance.

• Serotonin-mimetic drugs like Ecstasy (MDMA) affect body temperature regulation.

• Platelets activate when interacting with tumor cells.

• Tumor-informed platelets shed microparticles which contain tumor information.

• Platelets release CD40L in response to pathogens.

• High levels of soluble CD40L are associated with carcinoma lesions.

• CD62P is an activation marker.

• In resting platelets CD62P is part of the α-granule membrane.

• During activation and α-granule release it comes to the cell surface.

• CAR stands for chimeric antigen receptor.

• CAR T cells are laboratory modified T cells that have “relearned” to fight cancer.

• FcγRII expression and other changes in the outer membrane of platelets signal that activated platelets should be removed from the blood.

• Macrophages in the liver called Kupffer cells remove platelets activated by cold temperature.

• This process involves FcγRII.

Heparin-induced thrombocytopenia (HIT) is an example where Platelet-Factor 4 (PF4) from activated platelets forms a complex with heparin.

If pathologic antibodies are present from an earlier exposure to heparin or similar polysaccharides, immune complexes form.

These immune complexes bind to the FcγRII receptor which is exposed in higher copies on the surface of activated compared to resting platelets.

The binding of immune complexes to FcγRII receptors causes further activation, thrombosis and a consumptive thrombocytopenia (low platelet count).

• Human platelet antigens (HPA) are on the surface of all platelets and required for adhesion and aggregation.

• Conformational changes during platelet activation might make them antigenic, i.e., marked for attack.

• IgG stands for immunoglobulin Gamma which is the most prevalent class of antibodies.

• The adaptive immune system uses antibodies to build memory.

• This allows a faster response to the same or similar pathogen in the future.

• Platelets are part of the innate immune system.

• Activated platelets are known to stimulate the adaptive immune system.

• During infections, blood levels of interleukins and lipopolysaccharide (LPS) are elevated.

• Macrophages in the spleen are stimulated by these substances to remove activated platelets.

• After platelets engulf viruses like Dengue they are removed in the spleen.

• The immune system is tightly balanced between pro-inflammatory and anti-inflammatory strategies.

• Certain interleukins like IL-10 and IL-12 and other cytokines limit the immune response.

• MHC stands for major histocompatibility complex.

• Macrophages combine ingested foreign proteins with the MHC class II on their cell surface.

• This is called antigen presentation to other immune cells.

• Microparticles are also known as exosomes or extracellular vesicles.

• Platelet MPs are abundant in blood of patients with autoimmune and inflammatory conditions.

• MPs from tumor-informed platelets may be associated with tumor progression.

• Phagocytosis is the process by which macrophages "eat" platelets.

• Platelets bind IgG as well as complement so that they get recognized and “eaten” by macrophages (big eaters) both in the spleen and the liver.

• Conditions with chronic platelet activation can lead to thrombocytopenia (low platelet count) and splenomegaly (large spleen).

• When macrophages have eaten platelets they turn into antigen presenting cells, which means that they show on their surface what the reason for removing the platelets was.

• Macrophage MHC class II and antigen complexes stimulate T cells which in turn stimulate B cells to produce antibodies.

• Subsequently the antibodies will recognize whatever might have activated platelets.

• A repeat exposure to a previous stimulus leads to faster action (and potentially to acute thrombocytopenia). See also HIT as an example.

Splenomegaly is an enlarged spleen.

Thrombocytopenia and splenomegaly often occur together.

The association may be due to increased phagocytosis of platelets due to chronic infection.

• The platelet count is determined from a blood test.

• When the number of platelets is below a threshold, usually 140 000 / microL, the patient is diagnosed with thrombocytopenia, which means low platelet count.

• Both the immune and the hemostatic functions are impaired when not enough platelets are circulating.

• Platelets release TGFβ during activation from their α‐granules.

• TGFβ is an inhibitor of T cells and blocks the adaptive immune system.