From “rhe25“:
Hi, George, glad to find your resourceful website! Question for you: when the D-dimer is very very high, but the soluble fibrin monomer complex (SFMC) is negative, does that mean primary fibrinolysis in a systemic amyloidosis patient who has bleeding? I have seen a case like this, but the fibrinogen level is elevated, going against primary fibrinolysis. Doesn’t look like overt DIC clinically. Could the very high D-dimer be a lab artifact? Thanks!
Hello, and thank you for your question, which calls for a multi-part (make that windy!) answer.
The SFMC, similar or perhaps identical to thrombus precursor protein (TPP), is the first product of the action of thrombin upon fibrinogen. SFMC is the fibrin molecule that forms just after fibrinopeptides A and B are cleaved from fibrinogen. In normal coagulation, fibrin monomer rapidly assembles, through covalent bonds, to form insoluble fibrin polymer, however the monomer may become elevated during thrombotic events.
The assay for SFMC or TPP is an enzyme-linked or hemagglutination immunoassay that employs a polyclonal antibody; unlike D-dimer, which employs a monoclonal antibody. Immunoassay techniques for SFMC replaced the old qualitative “ethanol gel” or “protamine sulfate paracoagulation” assays in the late 1980s. In rapid thrombosis, characteristic of venous thromboembolic disease, myocardial infarction, and stroke, the SFMC result becomes elevated. The SFMC is also elevated in disseminated intravascular coagulation (DIC), and is more specific for DIC than D-dimer, which rises during any acute inflammatory event or chronic inflammation. Although I find no recorded evidence, I’ll speculate that D-dimer could be elevated as a result of the severe chronic inflammation inherent in amyloidosis, whereas the SFMC is unaffected.
From our knowledge of fibrinolysis physiology, it seems as though D-dimer should not rise in primary (systemic) fibrinolysis (PF). PF is a relatively rare condition in which fibrinolysis is triggered in the absence of coagulation. In theory, factor XIII remains inactive, consequently fibrin is not crosslinked. Since the D-dimer complex is a result of factor XIIIa crosslinking, it should be absent. This is not true.
While PF is rare, it is a component of thrombolytic “clotbuster” therapy. In 1997 my friend and colleague Gordon Ens, CEO of Colorado Coagulation Consultants, now Esoterix Coagulation, experienced a mild heart attack and had the presence of mind to request that blood be collected at serial intervals during administration of recombinant tissue plasminogen activator. Gordon and his cardiologist published the data in Clinical Hemostasis Review. They demonstrated that fibrinogen dropped to unmeasurably low levels while D-dimer rose to an extreme peak. Apparently, D-dimer rises in PF, perhaps as a marker of inflammation, or perhaps because some fibrin crosslinking does occur.
So, I suggest the elevated D-dimer is evidence of amyloidosis-related inflammation, and that the normal SFMC indicates no thrombotic event is in progress. I’d be happy to hear from colleagues on this subject.
Just one detail to add. For SFMC detection if you’re using F
Just one detail to add. For SFMC detection if you’re using FS test reagent, it’s not an immunological reagent based but fibrin monomer coated on erythrocytes. And perhaps a second one: to check if it’s a laboratory artifact it will be of interest to know if some other immunological tests have been disturbed.