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2483 Steady-State Von Willebrand Factor Antigen Levels Predict Low Platelet Counts and Risk for Complications in Hospitalizations for Painful Sickle Cell Vaso-Occlusive Episodes

Program: Oral and Poster Abstracts
Session: 113. Sickle Cell Disease, Sickle Cell Trait and Other Hemoglobinopathies, Excluding Thalassemias: Basic and Translational: Poster II
Hematology Disease Topics & Pathways:
Sickle Cell Disease, Hemoglobinopathies, Diseases
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Xu Zhang, PhD1*, Binal Shah, PhD1*, Jin Han, PharmD2*, Jose A. Lopez, M.D3, Dominic W. Chung, Ph.D3*, Junmei Chen, PhD3, Victor R. Gordeuk, MD4 and Santosh L. Saraf, MD5

1Department of Medicine, University of Illinois At Chicago, Chicago, IL
2College of Pharmacy, University of Illinois Chicago, Chicago, IL
3University of Washington, Bloodworks Research Institute, Seattle, WA
4Department of Medicine, University of Illinois Chicago, Chicago, IL
5Department of Medicine, University of Illinois College of Medicine, Willowbrook, IL

We previously reported that a >20% decline in platelet counts from steady state to presentation predicted severe complications during hospitalization for vaso-occlusive pain crisis (VOC) in 130 adult sickle cell disease (SCD) patients.1 Sharp platelet decline in acute chest syndrome was reported to be accompanied by large von Willebrand Factor (VWF) aggregates adherent to pulmonary vascular endothelium in SCD.2 A prospective study of 24 SCD patients found a significant increase of VWF reactivity in VOC admissions relative to steady state, which correlated with low platelet counts and the development of acute chest syndrome.3 We aimed to investigate the role of steady-state VWF antigen level and ADAMTS13 activity as predictors of platelet count decline and severe complications in VOC admissions.

Plasma levels of VWF antigen and ADAMTS13 activity were measured4 for 56 patients at steady-state outpatient visits (Baseline). VWF antigen was expressed as fold increase or decrease from the concentration in normal pooled plasma of 12.2 ug/ml; ADAMTS13 activity was expressed as fold of the value from normal pooled plasma which was considered 100% activity.

Electronic records of VOC admission that occurred >21 days after Baseline were reviewed. Exclusion criteria included non-VOC admissions defined as elective admission for surgery, admission for accident or injury, admission for delivery of an infant, or admission with a pain score <8/10 at presentation.5 A total of 98 qualifying admissions were identified. Severe complication during the admission was defined as having any of the following: 1) acute chest syndrome, new infiltrate on chest X-ray, or use of ventilator; 2) acute kidney injury;6 3) acute liver injury;7 4) thrombotic or hemorrhagic stroke; 5) venous thromboembolism including deep vein thrombosis, atrial thrombosis, and pulmonary embolism; 6) need for transfer to the intensive care unit; 7) need for exchange blood transfusion; 8) death during hospitalization. Platelet counts at presentation to the emergency room (ER) leading to the admissions under study were recorded, as well platelet counts at Baseline.

The 56 patients had a median (range) age of 37 (21-66) years; 52% are female, 89% with hemoglobin SS or Sβ0-thalassemia, and 57% on hydroxyrea (HU). Severe complication occurred in 35 (36%) of the 98 admissions involving 27 (48%) of the patients.

Focusing on the first admissions, higher steady-state VWF antigen levels correlated strongly with lower ER platelet counts (ρ= -0.50, P=0.00011, Figure 1A) and higher steady-state ADAMTS13 activity correlated weakly with ER platelet counts (Spearman’s ρ= 0.30, P=0.025). The ratio of VWF antigen to ADAMTS13 activity ratio also correlated strongly with lower ER platelet counts (ρ= -0.52, P=0.000052, Figure 1B). In contrast, steady-state VWF antigen level (ρ= -0.17, P=0.23), ADAMTS13 activity (ρ= 0.19, P=0.17), and VWF antigen to ADAMTS13 activity ratio (ρ= -0.23, P=0.098) showed no significant correlation with steady-state platelet counts. The correlations remained by adjusting for age, gender, Hb genotype severity, HU, and treatment of anticoagulant, aspirin, or non-steroidal anti-inflammatory drugs at VOC visits.

In analyses restricted to admissions >1 year after Baseline, the correlation between steady-state VWF antigen level and ER platelet counts appeared to persist. Focusing on the 28 first admissions, steady-state VWF antigen level (ρ= -0.50, P=0.0071) and VWF antigen to ADAMTS13 activity ratio (ρ= -0.44, P=0.018) correlated negatively with ER platelet counts. Steady-state ADAMTS13 activity did not correlate with ER platelet counts in admissions that occurred >1 year after Baseline (ρ= 0.16, P=0.43).

We further examined the association of steady-state VWF antigen level, ADAMTS13 activity, and their ratio with risk for severe complication in admission. Focusing on the first 56 admissions, which involved 23 complications, steady-state VWF antigen level in the top quartile (1.63) associated with risk for severe complications (OR=6.5, 95% CI 1.4-31, P=0.018, n=56), adjusting for age, gender, Hb genotype severity, and HU.

Our observations suggest that steady-state VWF antigen level and the ratio of VWF antigen level to ADAMTS13 activity predict low platelet counts at presentation to VOC admissions, and that steady-state VWF antigen level in SCD patients may be a relatively stable marker for risk of severe VOC complications.

Disclosures: Gordeuk: Takeda: Consultancy; GBT/Pfizer: Consultancy, Research Funding; CSL-Behring: Consultancy; Emmaus: Consultancy, Research Funding; Incyte: Research Funding; Novartis: Research Funding; Modus Therapeutics: Consultancy; Forma: Consultancy, Research Funding. Saraf: Novartis: Consultancy, Other: Advisory board, Research Funding; Forma Therapeutics: Consultancy, Other: Advisory board, Research Funding; GBT/Pfizer: Consultancy, Other: Advisory board, Research Funding, Speakers Bureau; BEAM Therapeutics: Consultancy, Other: Advisory board; Agios: Consultancy, Other: Advisory board.

*signifies non-member of ASH