Platelet function testing, which began more than a hundred years ago, is a time-consuming and uncertain process. Simulating hemostasis and the blood vessel microenvironment in vitro is challenging, which poses a difficulty for diagnosing platelet dysfunction and mild von Willebrand disease (VWD). In an effort to simulate the rheological microenvironment within blood vessels, several blood flow devices have been introduced since the 1980s. These devices are capable of reproducing the shear rates found in arterioles and venules, and of incorporating endothelial cell monolayers and surfaces with adsorbed platelet-adhesive proteins. The authors will describe and review here the presently most well-known blood flow devices. The technologies inherent in these devices offer a combination of physiologic accuracy and small blood volume requirements in the evaluation of platelet disorders and mild VWD (or “symptomatic low von Willebrand factor”) in flowing whole blood, with the potential to individualize therapeutic options for and to achieve greater diagnostic accuracy in mild platelet disorders and VWD.

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Background Accurate diagnosis of symptomatic low von Willebrand factor (VWF) remains a major challenge in von Willebrand disease (VWD). However, present tests do not adequately take into account flow forces that, at very high shear rates, reveal a weakness in the VWF-platelet glycoprotein glycoprotein Ib bond in normal subjects. The degree of this weakness is greater in symptomatic, but not asymptomatic, low VWF. Objective The aim of this study is to distinguish patients with symptomatic low VWF (levels in the 30–50 IU/dL range) from those with asymptomatic low VWF and normal subjects. Methods We measured platelet adhesion (PA)/aggregation in our novel microfluidic flow system that permits real-time assessment of PA (surface coverage) and PA/aggregation (V, aggregate volume) using epifluorescence digital videomicroscopy in flowing noncitrated whole blood at 4,000 second−1. Blood samples from 24 low VWF patients and 15 normal subjects were collected into plastic tubes containing 4 U/mL enoxaparin. MetaMorph software was used to quantify rates of PA and V increase. Results Rates of PA increase showed a bimodal distribution, with values for 16/24 patients (Group I) all below the 2.5th percentile of normal, and values for 8/24 patients (Group II) similar to controls. Bleeding scores (mean ± standard error) were 5.50 ± 0.45 versus 2.75 ± 0.45 (p = 0.00077), and 10 clinically significant bleeding events were observed in seven versus zero (p = 0.0295) Group I and Group II subjects, respectively. Conclusion The present approach may offer a definitive means to distinguish symptomatic low VWF from either asymptomatic low VWF or normal controls.

BackgroundSystemic lupus erythematosus (SLE) causes significant disease burden. Racial and ethnic differences in outcomes have been recognized, with increased morbidity and mortality in Black and Hispanic individuals, compared to non-Hispanic White referents. Financial barriers to treatment, such as copayments (or copays), may affect adherence to essential pharmacologic therapies, contributing to increased health adversity. Determining the contribution of copays to adherence may identify disparities in medication access and pathways to improve adherence.ObjectivesTo examine the association between race or ethnicity and medication adherence.MethodsWe used administrative health claims data (Optum’s De-identified Clinformatics® Data Mart Database, 2007-2021) to identify individuals with incident SLE (2 ICD-9/10 codes within 30-365 days) between 2010-19 receiving hydroxychloroquine (HCQ), azathioprine (AZA), mycophenolate mofetil (MMF), methotrexate (MTX), or combination therapy (HCQ with AZA, MMF, or MTX). Race or ethnicity were categorized as Asian, Black, Hispanic, White, or unknown. We dichotomized copays as low (<$10/30 days) or high (≥$10/30 days). Adherence was defined as proportion of days covered (PDC) ≥80%. We examined the association between race or ethnicity and adherence with multivariable-adjusted logistic regression models, using White individuals as referent. Results were then stratified by copay categories.ResultsWe identified 12,510 individuals: age 54.2±15.5 years; 88.2% women; 63.2% (7910) White, 14.9% (1860) Black, and 13.8% (1729) Hispanic. A total of 9510 (76%) were on HCQ and 15% on combination therapy. Median (IQR) 30-day copays were $8 (4, 10) for HCQ, $7 (2, 10) for AZA, $10 (5, 20) for MMF, and $8 (3, 11) for MTX. Black individuals had 51% (95% CI 0.31-0.80), 30% (95% CI 0.61-0.81), and 35% (95% CI 0.45-0.94) lower odds of adhering to AZA, HCQ, and combination therapy, respectively. Hispanic individuals had 27% (95% CI 0.63-0.94) lower odds of adhering to HCQ. When stratified by low or high copay, the association between race or ethnicity and adherence did not change, and the interaction of copayment on the association between race or ethnicity and adherence was not significant (Table 1).ConclusionIn this large cohort, Black and Hispanic individuals had decreased odds of adherence to SLE medications even after adjusting for several socioeconomic factors and comorbidities. The detrimental associations between copay and adherence were consistent across copay strata, suggesting that other factors contribute to racial and ethnic disparities. Factors such as polypharmacy, pharmacy deserts, transportation, mental health, cultural barriers, and health care access merit examination for their relation to adherence.Table 1.Association of Race or Ethnicity and Odds of Medication AdherenceAsianBlackHispanicOR (95% CI); P valueAZA (n=690)0.67 (0.23-1.94);0.460.50 (0.30-0.80);0.0041.00 (0.57-1.75);0.99HCQ (n=8629)1.15 (0.87-1.53);0.330.70 (0.61-0.81); <0.00010.73 (0.63-0.85); <0.0001MMF (n=756)1.53 (0.66-3.53); 0.320.73 (0.50-1.13);0.160.82 (0.52-1.30); 0.40MTX (n=518)0.75 (0.20-3.43); 0.711.11 (0.57-2.15);0.771.36 (0.67-2.76); 0.41Combination Therapy* (n=1720)1.04 (0.53-2.02); 0.910.65 (0.55-0.94);0.020.70 (0.48-1.03); 0.97Reference group: White individuals.Table 2.Stratification by Copayment≥$10 vs <$10 CopayOR (95% CI); P valueAsianBlackHispanicInteraction p valueAZA0.18 (0.02-1.54); 0.180.37 (0.17-0.81); 0.010.43 (0.17-1.11); 0.080.79HCQ0.52 (0.30-0.90); 0.020.72 (0.56-0.93); 0.010.57 (0.44-0.73); <0.00010.51MMF0.68 (0.13-3.44); 0.640.85 (0.42-1.75); 0.660.83 (0.39-1.75); 0.620.78MTX0.41 (0.02-9.51); 0.580.75 (0.25-2.30); 0.622.00 (0.50-8.04); 0.330.67Combination Therapy1.70 (0.45-6.45); 0.431.25 (0.69-2.27); 0.460.61 (0.32-1.16); 0.130.14Adjusted for age, sex, Elixhauser comorbidities, tobacco use, antiphospholipid syndrome, educational attainment, annual household income, insurance type, and US geographic region.AcknowledgementsThis work is supported by K24HL160527.Disclosure of InterestsRaisa Lomanto Silva: None declared, Gretchen M Swabe: None declared, Sebastian E. Sattui Grant/research support from: Bristol Myers Squibb Foundation Robert A. Winn Diversity in Clinical Trials Career Development Award, outside of the submitted work., Jared W Magnani: None declared.