{"doi":"10.1002/ajh.27636","title":"Steady‐State Ratio of <scp>von</scp> Willebrand Factor Antigen to <scp>ADAMTS13</scp> Activity Predicts Low Platelet Count at Hospitalization for Sickle Cell Disease Vaso‐Occlusive Episodes","abstract":"A vaso-occlusive episode (VOE) is the most common reason for emergency room visits and hospitalizations in patients with sickle cell disease (SCD). During a VOE, sickled red blood cells occlude the microvasculature causing ischemic injury and potential organ damage. We previously reported that in 130 adult patients, a > 20% decline in platelet count from steady state to presentation to the emergency room (ED) predicted an increased risk of severe complications during the VOE admission, defined as an acute pulmonary event, acute kidney or liver injury, stroke, venous thromboembolism, death, requirement for exchange blood transfusion, or transfer to the intensive care unit [1]. In other studies, a 33% increase of active von Willebrand Factor (VWF) in VOE relative to steady state coincided with a low platelet count and the development of acute chest syndrome in 24 patients [2], and a decline in platelet count of over 300 × 103/μL in less than 15 h preceded adherence of large VWF aggregates to the pulmonary vascular endothelium in 3 out of 10 patients who died from acute chest syndrome [3]. VWF is synthesized in endothelial cells and released as large glycoprotein multimers that mediate adhesion of platelets to sites of vascular damage [4]. Newly secreted VWF multimers undergo limited cleavage by the metalloproteinase, ADAMTS13, on the endothelial surface [4]. Here we investigated plasma VWF antigen level and ADAMTS13 activity at steady state as predictors of platelet count decline and severe complications in VOE admissions. VWF antigen and ADAMTS13 activity were measured [4] at outpatient visits when the patient was not experiencing a VOE (i.e., steady state). VWF antigen was expressed as fold increase or decrease from the concentration of 12.2 μg/mL in normal pooled plasma (Precision BioLogic Inc., Canada), which equals 122 IU/dL and is within the normal 50–200 IU/dL range; ADAMTS13 activity was expressed as the fold change of the value from normal pooled plasma, which was considered to have 100% activity. Electronic records of VOE admissions to the inpatient sickle cell disease service from 7/1/2017 to 6/30/2018, all occurring > 21 days after the steady-state evaluation, were reviewed. Ninety-seven admissions involving 55 patients were selected based on inclusion/exclusion criteria [1]. Platelet counts were collected at steady state and at presentation to the ER leading to the admissions under study. Severe complications during admission were defined as (1) acute pulmonary events including acute chest syndrome, new infiltrate on chest X-ray, or use of a ventilator; (2) acute kidney injury; (3) acute liver injury; (4) thrombotic or hemorrhagic stroke; (5) thromboembolism including deep vein thrombosis, pulmonary embolism, or arterial thrombosis; (6) need for transfer to the intensive care unit; (7) need for exchange blood transfusion; and (8) death during hospitalization [1]. The median (range) age at steady state was 37 (21–66) years; 53% of the patients were female, 89% had severe hemoglobin genotype SS and 11% had SC. At steady state, 58% of patients were receiving hydroxyurea (HU), 7.3% were on chronic blood transfusion, and 31% were taking aspirin, anticoagulants, or nonsteroidal anti-inflammatory drugs (Table S1). Of the 55 patients, 36 had single admission and 19 had multiple (2–5) admissions. The median (range) time interval between steady state and the 97 admissions was 1.9 (0.063–6.9) years. Severe complications (Table S2) occurred in 34 (35%) of the admissions involving 26 (47%) of the patients, 21 admissions with a single complication and 13 with 2–5 complications. We first focused on the 55 first admissions so that each patient had equal weight in the analysis. Higher steady-state VWF antigen-to-ADAMTS13 activity ratio correlated with lower ER platelet count (Pearson's r = −0.49, p = 0.00013), as did higher VWF antigen (r = −0.48, p = 0.00022). The correlation of higher steady-state VWF antigen with lower ER platele","journal":"American Journal of Hematology","year":2025,"id":562257,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9672,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":269842,"name":"Binal N. Shah","orcid":"0000-0001-5169-7301","position":1,"is_corresponding":false},{"id":351695,"name":"Jin Han","orcid":"0000-0003-0662-006X","position":2,"is_corresponding":false},{"id":299571,"name":"José A. López","orcid":"0000-0002-2478-1767","position":3,"is_corresponding":false},{"id":299570,"name":"Dominic W. Chung","orcid":"0000-0002-2645-5703","position":4,"is_corresponding":false},{"id":1425805,"name":"Junmei Chen","orcid":"0000-0002-6227-4088","position":5,"is_corresponding":false},{"id":292968,"name":"Santosh L. Saraf","orcid":"0000-0002-8584-4194","position":6,"is_corresponding":false},{"id":269831,"name":"Victor R. Gordeuk","orcid":"0000-0003-4725-7295","position":7,"is_corresponding":false},{"id":351694,"name":"Xu Zhang","orcid":"0000-0002-7732-1385","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-19T02:56:05.550545Z","pmid":"39962905","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}