Table 2.
Causes and Mechanisms and Proposed Stroke Phenotypes.
| Causes | Mechanisms | Examples of contributing pathology | Examples of vascular damage | Activated hemostatic path | Examples of clinical phenotype stroke |
|---|---|---|---|---|---|
| Vascular disease or injury: In-situ stroke
Embolic stroke |
Vascular wall damage causing hemorrhage into vascular lumen | Atherosclerotic lesion(s) Physical vascular damage | Detachment of small plaque or large atheroma | ULVWF path and/or TF path | Stroke phenotypes |
| Level 1 (L1): ECs | Small plaque (L1) | Detached focal plaque | ULVWF | TIA | |
| Level 2 (L2): ECs +SET | Large atheroma (L1, L2) | Detached local atheroma | ULVWF + TF | AIS | |
| Level 3 (L3): ECs + SET + EVT | Hypertension (L1, L2, L3) | Damaged small vessel wall | ULVWF + TF | THS; embolic stroke (AIS) | |
| Vascular damage with EVT hemorrhage into brain tissue or between coverings | Vascular anomaly Obtuse head/brain trauma |
||||
| Level e (Le): Mainly EVT | Vascular anomaly (Le) | Ruptured vessel wall | TF | AHS (eg, ICH) | |
| Severe trauma (Le) | Obtuse head/brain injury | TF | AHS (ie, SAH, IVH, SDH, EDH) | ||
| Endotheliopathy due to diseases | Complement activation | ECs damage | Systemic endotheliopathy sepsis; post-surgery; pregnancy; transplant | ULVWF | TTP-like syndrome (EA-VMTD) with encephalopathic stroke |
| Oxidative stress | ECs damage | Recurrent focal endotheliopathy | |||
| Diabetes Hyperhomocysteinemia |
ULVWF (?) | Diabetic stroke | |||
| Protease enzyme disorder | ADAMTS13 deficiency | TTP | NA | ULVWF | TTP (AA-VMTD; GA-VMTD) with encephalopathic stroke |
| Other vasculopathy | Endothelial dysfunction | Genetic disease | Endotheliopathy | ULVWF | HERNS syndrome with stroke Susac syndrome with stroke |
| Vascular dysfunction | Acquired vasculopathy | Vasculopathy | ULVWF +/-TF |
Abbreviations: AF, atrial fibrillation; AHS, acute hemorrhagic stroke; AIS, acute ischemic stroke; EC, endothelial cells; EDH, epidural hematoma; EVT, extravascular tissue; HERNS syndrome, hereditary endotheliopathy, retinopathy, stroke syndrome; ICH, intracerebral hemorrhage; IVH, intraventricular hemorrhage; NA, not applicable; SAH, subarachnoidal hemorrhage; SDH, subdural hematoma; SET, subendothelial tissue; TF, tissue factor; THS, thrombo-hemorrhagic stroke; TIA, transient ischemic attack; TTP, thrombotic thrombocytopenic purpura; ULVWF, unusually large von-Willebrand factor multimers; VMTD, vascular microthrombotic disease; antibody-associated VMTD (AA-VMTD); endotheliopathy-associated VMTD (EA-VMTD); gene mutation-associated VMTD (GA-VMTD).