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Investigational use for primary Raynaud's phenomenon; mechanism via local vasodilation and rheologic improvement. No RCT evidence.

Investigational use for primary livedo reticularis; very limited evidence. Secondary causes (lupus, APLAS) require rheumatology referral.

Investigational use to soften and remodel insulin injection-related lipohypertrophy nodules; very limited evidence.

Investigational use for stable-phase Peyronie's disease; case-report-level evidence only. Standard treatments (verapamil, collagenase, surgery) remain first-line.

Investigational adjunctive use for Ménière's disease; very limited evidence. Standard management (diet, betahistine, intratympanic therapy) remains primary.

Investigational adjunct for peripheral vertigo persisting after Epley maneuvers or during prolonged vestibular neuritis recovery; anecdotal.

Investigational use for posterior tibial nerve entrapment at the medial ankle; very limited case-report evidence.

Investigational use for non-pregnancy-related pubic symphysis dysfunction including athletic osteitis pubis; anecdotal evidence.

Highly investigational use for episodic cluster headache between attack cycles; very limited anecdotal data, not for active attacks.

Highly investigational use for severe nodulocystic acne refractory to isotretinoin; very limited anecdotal evidence and significant scarring risk concerns.

Investigational use for localized cutaneous lichen planus refractory to topical corticosteroid; very limited case-report evidence.

Investigational adjunct for chronic anal fissure refractory to medical therapy; very limited case-report evidence; surgical sphincterotomy remains gold standard.

Platelet GP IIb/IIIa antagonist family member — RGD-motif containing.

ADP-degrading enzyme — prevents platelet aggregation by hydrolyzing ADP at bite site.

Inhibitor of tissue factor / Factor VIIa complex — blocks extrinsic coagulation pathway.

Modulates the thrombin-thrombomodulin axis — implications for protein C pathway.

Direct thrombin inhibitor from the Asian buffalo leech — hirudin homolog described in Hirudinaria manillensis secretome.

Anticoagulant peptide described in the terrestrial Asian leech Haemadipsa zeylanica.

Direct thrombin inhibitor homolog cataloged in the Chinese medicinal leech Whitmania pigra secretome.

Small direct thrombin inhibitor described in the fish leech Piscicola geometra secretome.

Anticoagulant peptide described in the North American medicinal leech Macrobdella decora.

Second isoform of destabilase — lysozyme / isopeptidase activity targeting cross-linked fibrin.

Alternate fibrin-cleaving enzyme reported in Hirudo medicinalis salivary secretions.

Dual-function protease degrading both fibrin clot scaffolds and collagen extracellular matrix.

Substrate-mimetic peptide segment identified in leech salivary transcriptome — putative thrombin substrate / competitive inhibitor variant.

Thrombospondin-type repeat (TSR)-domain protein identified in leech salivary transcriptome — putative platelet / matrix interactor.

Whitmania pigra salivary anticoagulant gene family (Huang 2026 transcriptome) — seven coagulation-related transcripts including fibrinolytic enzymes, neutrophil-elastase inhibitors, factor Xa inhibitors.

Novel anticoagulant factor identified in the Hirudo nipponia salivary-gland transcriptome — Kim 2024 de novo assembly + in situ hybridisation.

Novel ghilanten family anticoagulant in the Hirudo nipponia salivary-gland transcriptome — Kim 2024 spatial expression mapping.