Dosing Patterns and Outcomes in African American, Asian, and Hispanic Patients with Heparin-Induced Thrombocytopenia Treated with Argatroban.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3403-3403
Author(s):  
Marcie J Hursting ◽  
Ik-Kyung Jang

Abstract Nonwhites, as compared with whites, have increased risk for thromboembolic complications in heparin-induced thrombocytopenia (HIT) (Lewis et al, Chest 2006). To better characterize the risk in nonwhite patients, we retrospectively evaluated dosing patterns and clinical outcomes in African American, Asian, and Hispanic patients administered argatroban therapy for clinically diagnosed HIT. Patients were from previously reported, multicenter, prospective studies of argatroban therapy (2 mcg/kg/min, adjusted to achieve aPTTs 1.5–3 times baseline) in HIT (defined as an otherwise unexplained platelet count <100 x109/L, or 50% reduction in platelet count, following heparin therapy). For African American (n=52), Asian (n=13), and Hispanic (n=14) patient groups, baseline characteristics, therapeutic argatroban dose and duration, aPTTs during therapy, and clinical outcomes (death, including death due to thrombosis; amputation, including amputation secondary to ischemic complications of HIT; new thrombosis; and major bleeding within a 37-day period) were summarized and compared. Among groups, no differences were detected in demographic or baseline features, excepting weight (median values: 62, 77 and 85 kg, respectively, for Asians, African Americans, and Hispanics). Median baseline platelet counts were 45–71 x109/L, and approximately 50% of patients in each group had HIT-related thrombosis before argatroban was initiated. Each group received a similar duration of argatroban therapy (4.0–5.5 days), yet Asians needed a lesser dose (1.0 mcg/kg/ min, versus 1.9 mcg/kg/min in other groups) to achieve comparable aPTTs (61–69 s). New thrombosis occurred most often in African Americans (21%, versus 7–8% in other groups) and when baseline HIT-related thrombosis was present (9/13 events, 69%). Amputation occurred most often in Hispanics (21%, versus 0–12% in other groups) and when diabetes was present (6/9 events, 67%). Mortality was 21–31%, and mortality due to thrombosis was 0–7%. Asians had the lowest frequency of any thrombotic-related outcome (composite of death due to thrombosis, amputation secondary to ischemic complications of HIT, or new thrombosis: 8%, versus 27–29% in other groups). Two patients, each African American, experienced major bleeding (gastrointestinal), for an overall major bleeding rate of 2.5% and by-group rates of 0–4%. Although limited by small group sizes, our study is among the first to characterize outcomes in minority patients administered nonheparin therapy for HIT. Our findings suggest that, despite achieving comparable levels of anticoagulation with argatroban, African Americans and Hispanics are higher risk patients than Asians for poor outcomes in HIT and also that in minority patients with adverse outcomes, baseline HIT-related thrombosis or diabetes is often present.

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Thomas L. Ortel

Abstract Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Anas M Al Zubaidi ◽  
Graham Bevan ◽  
Mariam Rana ◽  
Abdul Rahman Al Armashi ◽  
Mustafa Alqaysi ◽  
...  

Background: African Americans are at increased risk of fatal cardiac arrests, but population-based studies exploring contemporary epidemiology are not available. We sought to identify the trend in race-specific mortality from cardiac arrest in the United States. Methods: Using the multiple cause of death database, we identified all patients (Caucasians or African Americans) who died of cardiac arrest (International Classification of Diseases, 10th revision code I46.x listed as underlying cause of death) between 1999 and 2018. Age-adjusted mortality rates were standardized to the 2000 US census data, and stratified by age group (<35 years, 35-64 years, and ≥ 65 years). Results: A total of 311,065 cardiac arrest deaths were identified, with an overall age-adjusted mortality of 53.6 per million (Caucasian: 49.1 per million, African American: 90.6 per million). Overall, age-adjusted mortality decreased from 80.1 per million persons (1999) to 44.3 per million persons (2012), followed by 8.8% increase to 48.2 (2018). Between 2012 and 2018, African Americans had higher rates of increase (10.9%) compared with Caucasians (6.9%). Largest disparities in relative changes between 2012 and 2018 occurred in patients younger than 35 years (African American: 35%, Caucasians -11%), and patients ≥ 65 years (African Americans: 8%, Caucasians 4%), figure. Conclusions: Although the mortality due to cardiac arrest has declined in the US between 1999 and 2012, a recent increase has been noted between 2012 and 2018, particularly among younger African Americans. Studies should focus on identifying causes of disparities and identifying methods to reduce the racial gap.


2020 ◽  
Vol 4 (4) ◽  
pp. 776-783 ◽  
Author(s):  
Leslie Skeith ◽  
Lisa Baumann Kreuziger ◽  
Mark A. Crowther ◽  
Theodore E. Warkentin

Abstract Identifying the cause(s) of postoperative thrombocytopenia is challenging. The postoperative period includes numerous interventions, including fluid administration and transfusion of blood products, medication use (including heparin), and increased risk of organ dysfunction and infection. Understanding normal thrombopoietin physiology and the associated expected postoperative platelet count changes is the crucial first step in evaluation. Timing of thrombocytopenia is the most important feature when differentiating causes of postoperative thrombocytopenia. Thrombocytopenia within 4 days of surgery is commonly caused by hemodilution and increased perioperative platelet consumption prior to thrombopoietin-induced platelet count recovery and transient platelet count overshoot. A much broader list of possible conditions that can cause late-onset thrombocytopenia (postoperative day 5 [POD5] or later) is generally divided into consumptive and destructive causes. The former includes common (eg, infection-associated disseminated intravascular coagulation) and rare (eg, postoperative thrombotic thrombocytopenic purpura) conditions, whereas the latter includes such entities as drug-induced immune thrombocytopenia or posttransfusion purpura. Heparin-induced thrombocytopenia is a unique entity associated with thrombosis that is typically related to intraoperative/perioperative heparin exposure, although it can develop following knee replacement surgery even in the absence of heparin exposure. Very late onset (POD10 or later) of thrombocytopenia can indicate bacterial or fungal infection. Lastly, thrombocytopenia after mechanical device implantation requires unique considerations. Understanding the timing and severity of postoperative thrombocytopenia provides a practical approach to a common and challenging consultation.


Author(s):  
Hisashi Ogawa ◽  
Yoshimori An ◽  
Kenjiro Ishigami ◽  
Syuhei Ikeda ◽  
Kosuke Doi ◽  
...  

Abstract Aims Oral anticoagulants reduce the risk of ischaemic stroke but may increase the risk of major bleeding in atrial fibrillation (AF) patients. Little is known about the clinical outcomes of patients after a major bleeding event. This study assessed the outcomes of AF patients after major bleeding. Methods and results The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Analyses were performed on 4304 AF patients registered by 81 institutions participating in the Fushimi AF Registry. We investigated the demographics and outcomes of AF patients who experienced major bleeding during follow-up period. During the median follow-up of 1307 days, major bleeding occurred in 297 patients (6.9%). Patients with major bleeding were older than those without (75.6 vs. 73.4 years; P &lt; 0.01). They were more likely to have pre-existing heart failure (33.7% vs. 26.7%; P &lt; 0.01), history of major bleeding (7.7% vs. 4.0%; P &lt; 0.01), and higher mean HAS-BLED score (2.05 vs.1.73; P &lt; 0.01). On landmark analysis, ischaemic stroke or systemic embolism occurred in 17 patients (3.6/100 person-years) after major bleeding and 227 patients (1.7/100 person-years) without major bleeding, with an adjusted hazard ratio (HR) of 1.93 [95% confidence interval (CI), 1.06–3.23; P = 0.03]. All-cause mortality occurred in 97 patients with major bleeding (20.0/100 person-years) and 709 (5.1/100 person-years) patients without major bleeding [HR 2.73 (95% CI, 2.16–3.41; P &lt; 0.01)]. Conclusion In this community-based cohort, major bleeding is associated with increased risk of subsequent all-cause mortality and thromboembolism in the long-term amongst AF patients. Trial registration https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834. (last accessed 22 October 2020)


EP Europace ◽  
2019 ◽  
Vol 22 (4) ◽  
pp. 547-557 ◽  
Author(s):  
Daehoon Kim ◽  
Pil-Sung Yang ◽  
Eunsun Jang ◽  
Hee Tae Yu ◽  
Tae-Hoon Kim ◽  
...  

Abstract Aims To investigate the association between adherence to non-vitamin K antagonist oral anticoagulant (NOAC) and clinical outcomes and to determine the optimal cut-off level of NOAC adherence among patients with atrial fibrillation (AF). Methods and results Using the Korean National Health Insurance Service database, we identified 96 197 patients with non-valvular AF who initiated NOAC or warfarin in 2013–16. We compared clinical outcomes between adherent [proportion of days covered (PDC) ≥80%] vs. non-adherent (PDC &lt;80%) NOAC users, and further with warfarin users. We assessed the outcomes according to different levels of adherence. The proportion of adherent NOAC users was 64.0%. Compared with non-adherent NOAC users, adherent NOAC users were at lower risks of ischaemic stroke/systemic embolism (SE) [adjusted hazard ratio (aHR) 0.73, 95% confidence interval (CI) 0.69–0.79], and myocardial infarction (aHR 0.82, 95% CI 0.72–0.93), whereas there was no significant risk alteration for major bleeding (aHR 1.01, 95% CI 0.91–1.11). Compared with warfarin, non-adherent NOAC use failed to have better efficacy against ischaemic stroke/SE (aHR 0.99, 95% CI 0.93–1.05) and rather had increased risk of myocardial infarction (aHR 1.13, 95% CI 1.03–1.25). In NOAC users, the risks of adverse outcomes decreased according to gradual increase of adherence rates with the lowest risks in ≥90%, except for major bleeding in which there were no significant associations. Conclusions In an adherence level-dependent fashion, adherent use of NOAC showed better clinical outcomes without increasing bleeding risk. Maintaining ≥90% of adherence optimizes effectiveness of NOAC therapy without compromising its safety.


2019 ◽  
Vol 49 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Kabir O. Olaniran ◽  
Nwamaka D. Eneanya ◽  
Andrew S. Allegretti ◽  
Sophia H. Zhao ◽  
Maureen M. Achebe ◽  
...  

Background: Sickle cell trait (SCT) is common among African Americans and has been historically considered to be benign. Recently, SCT has been associated with an increased risk for chronic kidney disease (CKD) and cardiovascular disease in the general population. Our understanding of SCT has been extrapolated largely from data of patients with sickle cell disease (SCD). Notably, in SCD, the outcomes differ by sex. The effect of SCT on cardiovascular risk in the African American CKD population is unknown, and the interaction between SCT and sex on cardiovascular risk has not been investigated. Methods: We performed a 2-center retrospective cohort study of all African American patients with SCT using international classification of disease diagnosis codes and CKD (using the 2012 Kidney Disease Improving Global Outcomes criteria) with at least 1 year of follow-up between January 2005 and December 2017. A reference group of ­African American CKD patients without SCT was used as a comparator during the same period. SCT patients and the reference patients were matched at baseline for age, sex, comorbidities, and proteinuria. Primary outcomes were incident coronary artery disease (CAD), incident stroke, and all-cause mortality. Analysis of effect modification between sex and SCT on primary outcomes was performed. Results: We identified 621 African American CKD patients, 217 SCT patients, and 404 reference patients. The mean age was 56 ± 13 years and 66% were female. The mean estimated glomerular filtration rate was 69 ± 30 mL/min. The mean follow-up time was 8 ± 4 years. There were no significant differences in the primary outcomes comparing SCT patients to matched controls. The interaction term between SCT and sex, however, was significant in the CAD model (p < 0.01). Stratification by sex showed no increased risk in females but a significantly increased risk for CAD in male SCT patients (hazard ratio [HR] 2.14; 95% CI 1.18–3.86), which persisted after multivariable analysis (HR 2.13; 95% CI 1.17–3.86). Conclusion: SCT is associated with an increased risk for CAD in African American males with CKD. The excess risk in males with SCT appears to follow the same pattern as risk in males with SCD. Larger studies are needed to confirm these findings.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4547-4547
Author(s):  
Deimante Tamkus ◽  
Ahmad Jajeh ◽  
Ebenezer Berko ◽  
David Osafo ◽  
Decebal Griza ◽  
...  

Abstract Inferior survival of African American and Hispanic patients with acute lymphoblastic leukemia (ALL) has been reported. The reason for this is unclear. A retrospective analysis was conducted to see if abnormal cytogenetics account for the differences. We have analyzed cytogenetic studies of 39 adults (16 year and older) with newly diagnosed ALL who were consecutively treated at John Stroger Hospital of Cook County between 1997 and 2005. The study population included 13 (33%) African Americans, 18 (46%) Hispanics, 6 (16%) Caucasians, and 2 (5 %) other ethnic background adults. Male to female ratio was 2:1. Mean age at diagnosis was 26 (range between 16 and 71 years). A clonal cytogenetic abnormality was detected in 27 patients, and 12 patients had normal karyotype. Patients with t (9;22)(q34;q11), BCR-ABL + by FISH, t (4;11)(q21;q23), +8, −7 cytogenetic abnormalities were assigned to an unfavorable cytogenetic group. This group was composed of 14 patients. None of our study patients had favorable cytogenetics: del (12p), t(12p), t(14q11-q23), inv(14)(q11;q32) or t(10;14)(q24;q11). Remaining 25 patients with normal karyotype (n=12) or miscellaneous cytogenetic abnormalities (n=13) were classified as normal risk group. 54 % of African Americans had unfavorable cytogenetics, compared with 33 % Caucasians and 17 % Hispanics. Translocation t (9;22) alone or in association with other cytogenetic abnormalities was most commonly seen. 9 patients had single, and 18 had multiple chromosomal changes. Hispanic group had more complex cytogenetic changes when compared with the African American or Caucasian groups. Unfavorable cytogenetic abnormalities may account for inferior survival in African Americans, but other factors such as compliance or pharmacogenetics should be evaluated, especially in the Hispanic patient population.


Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 904-906 ◽  
Author(s):  
Ola Landgren ◽  
Gloria Gridley ◽  
Ingemar Turesson ◽  
Neil E. Caporaso ◽  
Lynn R. Goldin ◽  
...  

Abstract The age-adjusted incidence of multiple myeloma (MM) is 2-fold higher in African Americans than in whites. A few small studies have reported a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS) in African Americans versus whites. Etiologic factors for MGUS and determinants for transformation of MGUS to MM are unknown. We quantified the prevalence of MGUS and subsequent risk of MM among 4 million African American and white male veterans admitted to Veterans Affairs (VA) hospitals. The age-adjusted prevalence ratio of MGUS in African Americans compared with whites was 3.0 (2.7-3.3 95% confidence interval). Among 2046 MGUS cases, the estimated cumulative risk of MM during the first 10 years of follow-up was similar (P = .37) for African Americans (17%) and whites (15%). In the largest study to date, we suggest that the excess risk of MM in African Americans results from an increase in risk of MGUS rather than an increased risk of progression from MGUS to MM.


2021 ◽  
Author(s):  
Nuzulul Kurniansyah ◽  
Matthew O Goodman ◽  
Tanika Kelly ◽  
Tali Elfassi ◽  
Kerri Wiggins ◽  
...  

Background: We used summary statistics from previously-published GWAS of systolic and diastolic BP and of hypertension to construct Polygenic Risk Scores (PRS) to predict hypertension across diverse populations. Methods: We used 10,314 participants of diverse ancestry from BioMe to train trait-specific PRS. We implemented a novel approach to select one of multiple potential PRS based on the same GWAS, by optimizing the coefficient of variation across estimated PRS effect sizes in independent subsets of the training dataset. We combined the 3 selected trait-specific PRS as their unweighted sum, called "PRSsum". We evaluated PRS associations in an independent dataset of 39,035 individuals from eight cohort studies, to select the final, multi-ethnic, HTN-PRS. We estimated its association with prevalent and incident hypertension 4-6 years later. We studied hypertension development within HTN-PRS strata in a longitudinal, six-visit, longitudinal dataset of 3,087 self-identified Black and White participants from the CARDIA study. Finally, we evaluated the HTN-PRS association with clinical outcomes in 40,201 individuals from the MGB Biobank. Results: Compared to other race/ethnic backgrounds, African-Americans had higher average values of the HTN-PRS. The HTN-PRS was associated with prevalent hypertension (OR=2.10, 95% CI [1.99, 2.21], per one standard deviation (SD) of the PRS) across all participants, and in each race/ethnic background, with heterogeneity by background (p-value < 1.0x10-4). The lowest estimated effect size was in African Americans (OR=1.53, 95% CI [1.38, 1.69]). The HTN-PRS was associated with new onset hypertension among individuals with normal (respectively, elevated) BP at baseline: OR=1.71, 95% CI [1.55, 1.91] (OR=1.48, 95% CI [1.27, 1.71]). Association was further observed in age-stratified analysis. In CARDIA, Black participants with high HTN-PRS percentiles developed hypertension earlier than White participants with high HTN-PRS percentiles. The HTN-PRS was significantly associated with increased risk of coronary artery disease (OR=1.12), ischemic stroke (OR=1.15), type 2 diabetes (OR=1.19), and chronic kidney disease (OR=1.12), in the MGB Biobank. Conclusions: The multi-ethnic HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up across adulthood and is associated with clinical outcomes.


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