Table 2.
Two faces of deep venous thrombosis with pathologic, pathogenetic and laboratory differences based on two-path unifying theory of hemostasis and endothelial molecular pathogenesis.
| Phenotypes | Distal DVT (de novo Venous Macrothrombosis) | Proximal/Central DVT (Combined Venous Micro-Macro thrombosis) |
|---|---|---|
| Disease examples | ||
| Venous thrombosis | ||
| DVT | Distal DVT | Proximal/central(catheter) DVT |
| VTE | VTE; multiple PTE | |
| Other complex venous thrombosis | IVCT; SVT; PVT; BCS; SVCT; CVST | |
| Mechanisms of vascular injury | ||
| Event | Local trauma (rarely with surgery/vascular access) | Underlying disease (vEA-VMTD (e.g., sepsis)) + local trauma (commonly with surgery/vascular access) |
| Extent of vascular damage | Local ECs/SET injury | Disseminated ECs injury + local/regional ECs/SET injury |
| Pathogenesis | ||
| Activated thrombosis path | ULVWF and TF paths from local trauma | ULVWF path from systemic vEA-VMTD and TF path from regional trauma |
| Thrombi character | Macrothrombus | Combined micro-macrothrombi composed of “microthrombi strings–fibrin meshes” |
| Severity | Typically, solitary, benign, and self-limited | Serious and often with multiple/large thrombi |
| Severe inflammation | Absent | May be present and can be severe |
| Venous EA-VMTD | Absent | Commonly present (e.g., ITP-like syndrome) |
| MOIS | Absent | May be present |
| Diagnostic findings/markers | ||
| Consumptive thrombocytopenia | Does not occur | Sometimes occurs |
| ULVWF/VWF antigen | Normal | Overexpressed |
| FVIII activity | Normal | Increased |
| ADAMTS13 activity | Normal | Mild to moderately decreased |
| D-dimer | Normal | Markedly increased |
| Immune: ANA; APLA; Anti-DNA antibodies | Negative | May be positive |
| Therapeutic approach per theory | No treatment or short-term anticoagulant | Anticoagulant and antimicrothrombotic/anticomplement agent (?) |
Abbreviations: ANA, antinuclear antibodies; APLA, antiphospholipid antibodies; BCS, Budd-Chiari syndrome; CVST, cerebral venous sinus thrombosis; DNA, deoxyribonucleic acid; DVT, deep vein thrombosis; vEA-VMTD, venous endotheliopathy-associated vascular microthrombotic disease; ECs, endothelial cells; EVT, extravascular tissue; ITP, immune thrombocytopenic purpura; IVCT, inferior vena cava thrombosis, MOIS, multiorgan inflammatory syndrome; PTE, pulmonary thromboembolism; PVT, portal vein thrombosis; SET, subenthelial tissue; SVCT, superior vena cava thrombosis; SVT, splanchnic vein thrombosis; TF, tissue factor; ULVWF, unusually large von Willebrand factor; vEA-VMTD, venous endotheliopathy-associated vascular microthrombotic diseases; VTE, venous thromboembolism; VWF, Von Willebrand factor.