Apo-H appears to completely inhibit serotonin release by the platelets^[4] and prevents subsequent waves of the ADP-induced aggregation. The activity of Apo-H appears to involve the binding of agglutinating, negatively charged compounds, and inhibits agglutination by the contact activation of the intrinsic blood coagulation pathway.^[5] Apo-H causes a reduction of the prothrombinase binding sites on platelets and reduces the activation caused by collagen when thrombin is present at physiological serum concentrations of Apo-H suggesting a regulatory role of Apo-H in coagulation.^[6]

Apo-H also inhibits the generation of factor Xa in the presence of platelets.^[7] Apo-H also inhibits that activation of factor XIIa.^[8]

In addition, Apo-H inhibits the activation of protein C blocking its activity on phosphatidylserine:phosphatidylcholine vesicles^[9] however once protein C is activated, Apo-H fails to inhibit activity. Since protein C is involved in factor Va degradation Apo-H indirectly inhibits the degradation of factor Va.^[10] This inhibitory activity was diminished by adding phospholipids suggesting the Apo-H inhibition of protein C is phospholipid competitive.^[11] This indicates that under certain conditions Apo-H takes on a procoagulation properties.

Anti-cardiolipin antibodies are found in both infectious and some systemic autoimmune diseases (eg. systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE)).^[12] One having anti-cardiolipin antibodies shows false positivity in the syphilis test as it is performed with the antigen bound to cardiolipin surface, which anti-cardiolipin antibodies can cross-react with. The activity of anti-cardiolipin antibodies in autoimmune antiphospholipid syndrome requires apolipoprotein H.^[13][14] The subset of antibodies that bind Apo-H and alter its activity are considered different from antibodies that bind thrombin, serum phospholipids and are called anti-apolipoprotein antibodies. In autoimmune disease, anti-apolipoprotein antibodies (Anti β₂ glycoprotein I antibodies) strongly associate with thrombotic forms of lupus and sclerosis.

In molecular biology, the protein domain Sushi 2 is also known as the fifth protein domain of beta-2-glycoprotein-1 (b2GP-1). This protein domain is only found in eukaryotes. The first four domains found in Apolipoprotein H resemble each other, however the fifth one appears to be different.^[15]

This protein domain is composed of four well-defined anti-parallel beta-strands and two short alpha-helices, as well as a long highly flexible loop.^[16] Additionally, the fifth protein domain appears to resemble the other four in Apolipoprotein with the exception of three internal disulfide bonds and an extra C-terminal loop.^[15]

Its exact function remains to be fully elucidated, however it is known to play an important role in the binding of b2GP-1 to negatively charged compounds and subsequent capture for binding of anti-b2GP-1 antibodies.^[16] Problems such as a mutation in this protein would lead to Antiphospholipid syndrome which often leads to pregnancy complications.^[15]

• Apolipoprotein+H at the US National Library of Medicine Medical Subject Headings (MeSH)
• Apolipoprotein H and Applied Research
• Human APOH genome location and APOH gene details page in the UCSC Genome Browser.