Wolfgang Miesbach’s Top 10 Picks for TTP and Thrombosis from ASH 2025
Wolfgang Miesbach, Professor of Medicine at Frankfurt University Hospital, shared on LinkedIn:
”ASH 2025: TTP and Thrombosis — My Top 10 Picks:
TGD001 – Novel VWF-Targeting Thrombolytic
Kristof Vercruysse et al. Two-step breakthrough mechanism: antibody fragment binds von Willebrand Factor (VWF) in all clot types, then locally activates plasmin to degrade both VWF and fibrin. Dissolves clots of all sizes without systemic bleeding risk.
UK TTP Registry – Multi-Ethnic Longitudinal Cohort
marie Marie Scully et al. — 104 confirmed cTTP cases; 71 ADAMTS13 variants identified. Plasma prophylaxis: stroke/TIA reduced 19.0%→1.5%, acute episodes dropped 0.68→0.06/year. Importantly, 58.9% switched to recombinant ADAMTS13 for superior symptom control.
ADAMTS13 Mutations – Genotype-Phenotype Insights
Paul Coppo et al. — Phase 3 cohort mutation analysis using Variant Effect Predictor: N-terminal mutations associate with earlier disease onset. Missense mutations (60% of variants) cluster in the 5′-half encoding the catalytic domain.
ADZYNMA (Recombinant ADAMTS13) – Phase 3
Bérangère Joly et al. — ADAMTS13 activity sustained at ~100% normal on prophylaxis. Zero acute TTP events on rADAMTS13 (n=45) vs one on plasma (n=46). Adverse events: 9% vs 48%.
TTP Pathway QI – Standardised Multidisciplinary Care
Samuel A. Merrill et al — Rural Appalachian tertiary centre: implementing standardised TTP pathway reduced 90-day relapse/death 56%→6% (P=0.022) and isolated relapse 50%→0% (P=0.0011).
Milvexian Reversal – Addressing FXIa Inhibitor Safety Gap
Victor Dishy et al. — First data on reversal strategies for oral FXIa inhibitors. Tested 4-factor PCC and recombinant FVIIa reversing milvexian in healthy volunteers.
Abelacimab (AZALEA-TIMI 71) – FXIa Inhibitor Bleeding Reduction
Daniel Bloomfield et al. — 1,287 AF patients: subcutaneous abelacimab 150 mg or 90 mg monthly (vs rivaroxaban 20 mg daily). 72% bleeding reduction (150 mg cohort): 3.22 vs 8.3 events/100 patient-years. Achieves 99% FXI suppression within 1 hour, sustained 30 days.
VTE Recurrence – Molecular Determinants for Personalisation
Gaëlle MUNSCH et al. — 6,355 VTE patients; 28 molecular markers identified predicting recurrence. SLC4A1 p.Glu40Lys is PE-specific(recurrence HR=3.13) but not DVT (HR=0.91). Elevated FVIII, FXI, VWF in recurrent cases and 7 druggable proteins identified.
Reduced-Dose DOACs – Extended VTE Treatment Meta-Analysis
Ahmed Mohammed et al. — 8,781 patients (5 RCTs): reduced-dose DOACs equivalent efficacy (RR 0.94) but significantly lower bleeding (RR 0.71, 95% CI 0.61–0.82). 5-year cumulative bleeding: 9.9% (reduced) vs 15.2% (full-dose). 33% fewer net adverse events with reduced dosing.
OKL-1111 – Universal Anticoagulant Reversal Agent
Joost Meijers et al. — γ-Cyclodextrin derivative reverses all anticoagulants (DOACs, warfarin, LMWH) and antiplatelet agents (clopidogrel) without drug identification needed. Phase 1: safe, rapid reversal via procoagulant mechanism with minimal thrombotic overshoot.”
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