Does the link between the laboratory abnormality and VTE make biologic sense?
The association should be plausible and consistent with current knowledge. a. Does it fit with a known pathogenic mechanism? Although for some abnormalities biologic plausibility is obvious (e.g., AT deficiency), for others it is unclear (e.g., antiphospholipid antibodies). There is a clear and strong association between antiphospholipid antibodies and VTE,30,31 and several “cause-and-effect” mechanisms have been suggested,30 however, none has emerged as the “final answer.” In this situation, if a clinical association is convincing, it is important to determine whether the abnormality may cause VTE, through an as yet undetermined mechanism, or whether the abnormality is merely associated with VTE. b. Is the temporal relationship correct? The laboratory abnormality should precede the episode and be predictive of VTE, rather than be a consequence of VTE. c. Is there a biologic gradient? Demonstrating a graded effect on outcome with different degrees of exposure often increases the probab
