Global/integral assays in hemostasis diagnostics: promises, successes, problems and prospects

Laboratory testing in hemostasis is a subject of growing concern among the specialists. To put it plainly, the standard assays that have been in widespread use for more than 40 years (APTT and PT assays for clotting, aggregometry for platelets) are not sensitive and specific for too many major disorders of hemostasis; their parameters can remain within normal ranges when patient is in acute danger of thrombosis or bleeding; even if they do detect some abnormality they do not indicate the severity of the clinical manifestations; in rare cases they are even abnormal in a clinically asymptomatic individual. Admittedly, as already recognized by Virchow in his famous Virchow’s triad, thrombosis can arise from disorders in either vessel wall, blood flow, or blood composition and laboratory diagnostics only concerns the latter. If the origin of a thrombotic or bleeding disorder is not in the blood, as in myocardial infarction caused by atherosclerotic plaque rupture, there is no need for the blood to be in a hyper-coagulable state before the event and laboratory diagnostics of coagulation or platelet function can be completely normal (although some non-hemostatic biomarkers for e.g. atherosclerotic plaque instability do exist [1]). The same holds for hemostasis: the extent of bleeding is determined by the state of the tissue (type and degree of damage, tissue composition at the injury site), physical parameters of the wound and blood flow (geometry of the wound, blood flow patterns there) as well as blood biochemistry. No functional assay of blood clotting is likely to be able to predict hemorragic stroke resulting from aneurism rupture or bleeding in a person with hereditary hemorrhagic telangiectasia or Ehlers–Danlos syndrome, exactly because there is originally nothing wrong with their blood in these cases.