A Case of Thrombotic Vasculopathy in the Setting of High-Dose Hydroxyurea Use

2021 ◽  
Vol 33 (12) ◽  
pp. E79-E84
Author(s):  
Jill Michalak ◽  
Richard Simman ◽  
Drew Oostra

This case study describes the presentation of a 76-year-old male with a past medical history that included atrial fibrillation, essential hypertension, coronary artery disease status post cardiac stent placement, heart failure, hyperlipidemia, thyroid cancer (with thyroid resection resulting in hypothyroidism), prostate cancer status post brachytherapy (in remission), and a history of JAK2-positive myeloproliferative disease. He presented with painful areas of hyperpigmentation appearing as purple discoloration to his neck, lower abdominal skinfold, and bilateral groin areas that progressed to painful ulcerations a few weeks after a myocardial infarction. Due to the patient’s multiple medical conditions and uncommon presentation of wounds, a multidisciplinary team was involved in his care. Differential diagnosis included antiphospholipid syndrome, symmetrical drug-related intertriginous and flexural exanthema, warfarin-induced necrosis, cutaneous thrombotic vasculopathy, myeloproliferative disorder, and high-dose hydroxyurea therapy. It was determined by the authors that the high-dose hydroxyurea therapy was the cause of the wounds. Because of the patient’s initial health status, treatment of the wounds included use of collagenase and sodium hypochlorite solution to reduce the risk of infection and attempt to promote autolytic debridement until surgical wound debridement could be done. The patient required multiple hospital stays, but ultimately his health status improved and the wounds resolved with the assistance of the combined efforts of the multidisciplinary team to diagnose and treat this complex patient and his uncommon wound presentation.

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Takahashi ◽  
K Tsuchida ◽  
Y Sato ◽  
S Iimuro ◽  
K Kario ◽  
...  

Abstract Background/Introduction The REAL-CAD study identified that aggressive lipid lowering with high-dose statin reduced cardiovascular events also in Japanese patients with coronary artery disease (CAD). However, data from the SPARCL trial found that the benefits of high-dose atorvastatin treatment were partially offset by an increase in haemorrhagic stroke (HS). Although meta-analysis showed statin does not increase HS in Western countries, the evidence about the relation between statin and HS in Asian countries is still conflicting. In addition, the CREDO-Kyoto score is one of the prediction scorings for bleeding after coronary revascularization and might be a useful tool for the prediction of HS in this cohort. Recognizing the risk of HS and predicting of HS in the Asian cohort is clinically important. Purpose This study examined the factors associated with HS using the REAL-CAD cohort. Furthermore, we evaluated the performance of the CREDO-Kyoto bleeding risk score to predict HS in this cohort. We also performed the corresponding analysis of ischaemic stroke for reference purposes. Methods We sub-analysed the REAL-CAD study, prospective, multicentre, randomized, open-label, blinded endpoint study, in which 13,054 Japanese patients with stable CAD were randomized to high-dose (4 mg/day) or low-dose (1 mg/day) pitavastatin. Associations for stroke were determined using competing risk models: the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of haemorrhagic and ischaemic stroke in REAL-CAD trial. Patients were categorized to low (score 0), moderate (score 1–2), and high (score&gt;3) according to CREDO-Kyoto bleeding score for predicting of HS. Results The HS events in high-dose group tended to be higher than low-dose group (4mg vs. 1mg: 43 (0.7%) vs. 30 (0.5%)). The associated factors of HS on univariate analysis were non-prior myocardial (hazard ratio (HR): 0.62, 95% CI: 0.39–0.99) and non-prior cerebral (HR: 0.25, 95% CI: 0.09–0.70) infarction, atrial fibrillation (HR: 2.4, 95% CI: 1.2–4.7), prior HS (HR: 4.2, 95% CI: 1.5–11.8), anaemia (HR: 2.4, 95% CI: 1.4–4.1), and non-statins use before run-in period (HR: 0.52, 95% CI: 0.28–0.99). High-dose pitavastatin was not a correlate with HS. The multivariate analysis revealed anaemia might have a relation with HS (HR: 4.3, 95% CI: 0.90–20.6). The number of HS was the highest in the high CREDO-Kyoto bleeding score group (Figure 1, HR: 2.4, 95% CI: 1.3–4.6), whereas there was no significant difference in the number of HS between the moderate- and low-risk groups (HR: 1.4, 95% CI: 0.84–2.3). Conclusions High-dose pitavastatin was not associated with the incidence of HS in this large Japanese cohort with stable CAD. High CREDO-Kyoto bleeding score was associated with HS as compared with low or moderate scores, even each of the variables consisting of CREDO-Kyoto score was not associated with HS. Figure 1 Funding Acknowledgement Type of funding source: None


2011 ◽  
Vol 162 (3) ◽  
pp. 501-506 ◽  
Author(s):  
Kevin R. Bainey ◽  
Colleen M. Norris ◽  
Milan Gupta ◽  
Danielle Southern ◽  
Diane Galbraith ◽  
...  

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 257-257
Author(s):  
Caroline Jones ◽  
David Riley ◽  
Amy Morris ◽  
Jeremy Michael Sen ◽  
Alana Ferrari ◽  
...  

257 Background: For patients receiving high dose cytarabine (HiDAC) at University of Virginia (UVA) Health between 10/2019 and 10/2020, median length of stay (LOS) from time of clinic appointment to hospital discharge was 119.35 hours. Standard treatment time should be 112 hours from premedication to end of chemotherapy. There are no national standards for duration of inpatient stay for planned chemotherapy, but only 50% of these patients were discharged after noon (over 3 hours post-chemotherapy completion). LOS that extends beyond the standard treatment time results in increased cost, overutilization of hospital resources, delayed admissions for future patients, and patient dissatisfaction. Methods: A multidisciplinary team comprised of licensed providers, pharmacists, and nurses was formed. The team focused on percentage of patients discharged by noon as a surrogate marker for LOS due to inconsistency of admission times; the aim was to increase patients discharged by noon to 65%. Reviewing the baseline data revealed an unstable process with a 3-sigma X-bar statistical process control chart. The team developed current and ideal process state maps, a Pareto chart, and a priority matrix to determine an action plan. The most common identified causes for delay in discharge included: lack of standardized discharge checklist, discharge order placed after 10 am, medications dispensed from the outpatient pharmacy after 11 am, licensed providers not prioritizing discharge patients, and medication reconciliation not completed prior to day of discharge. Results: From 10/2020 to 5/2021, the first PDSA cycle focused on standardizing the discharge process to correct the instability in the process. A discharge checklist was created based on the ideal process map, which allowed the providers to have a consistent process at discharge. 3-sigma Xbar chart demonstrated a now stable process and an increase of patients discharged by noon to 58%. During the second PDSA cycle starting in 6/2021, providers completed medication reconciliation the day before discharge, prioritized HiDAC discharges first during rounds, and ensured discharge orders were placed by completion of the last chemotherapy bag. Data collection is ongoing, and will be analyzed by August 2021. Future tests of change are planned to focus on the pharmacy medication delivery service. Hospital LOS has also decreased after the first PDSA cycle. Conclusions: Using quality improvement methodology, a multidisciplinary team developed an action plan for patients receiving HiDAC which to date has increased the percentage of patients discharging by noon and decreased length of stay. This outcome may lead to reduce hospitalization costs and increase bed availability for other oncology patients. Further PDSA cycles are scheduled and continuous evaluation of the process is ongoing.


2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Marlene Grenon ◽  
Christopher Owens ◽  
Hugh Alley ◽  
Karen Chong ◽  
Priscilla Yen ◽  
...  

OBJECTIVES: Patients with peripheral artery disease (PAD) experience significant morbidity and mortality, at least partially related to vascular inflammation and endothelial dysfunction. The OMEGA-PAD I Trial (NCT01310270), a randomized, double-blinded, placebo-controlled trial addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function (EF) and inflammation in subjects with PAD. METHODS: Eighty patients with stable, mild-severe claudication and ABI<0.9 received 4.1gm of fish oil (FISH) vs placebo capsules (CTL) for 1 month. The primary endpoint was EF as measured by brachial artery flow-mediated vasodilation (FMD). Secondary endpoints included biomarkers of inflammation, generation of n-3 fatty acid-derived lipid metabolites, lipid profile and walking impairment questionnaires. RESULTS: The FISH and CTL group were no different with regards to age, baseline EF, inflammation and lipid profiles. Following treatment, there was a significant reduction in triglycerides (-34 ± 46, p=0.0001) and an improvement in HDL (+2 ± 6, p=0.03) in the FISH group. These changes were accompanied by an increase in the omega-3 index of 4 ± 1% (p<0.00001). We observed a significant increase in the production of downstream metabolites of n-3 fatty acids including 18-, 15- and 5-hydroxy eicosapentaenoic acids and 4-hydroxy docosahexaenoic acid in the FISH group. n-3 PUFA led to a significant improvement in FMD in the FISH group (+0.7 ± 4.0%, p=0.04) and a non-significant improvement in the CTL (+0.6 ± 2.5, p=0.18) group. There were no significant differences between groups in pro-inflammatory markers or walking parameters post-treatment. CONCLUSIONS: High-dose, short-duration n-3 PUFA supplementation significantly improves the metabolo-lipidomic profile of patients with PAD. Longer studies are needed to assess the effects of n-3 PUFA on inflammation, vascular function, and clinical endpoints in patients with established PAD and to determine whether generation of n-3 fatty acid-derived bioactive lipid mediators is related to clinical outcomes.


1981 ◽  
Vol 9 (3) ◽  
pp. 247-254 ◽  
Author(s):  
S. E. Kaye ◽  
W. Dimai ◽  
R. Gattiker

Intravenous infusions of nitroglycerin decreased systemic systolic, pulmonary systolic and wedge pressures in β-blocked patients anaesthetised for coronary artery surgery with high dose of fentanyl without changing heart rate, diastolic pressure, or cardiac index, thus leading to an improvement in endocardial viability ratio. The use of a nitroglycerin bolus to abort an acute myocardial ischaemic episode is described.


2006 ◽  
Vol 5 (1_suppl) ◽  
pp. 4-5
Author(s):  
Mattie Lenzen ◽  
Wilma Scholte Op Reimer ◽  
Tone M. Norekvål ◽  
Sabina De Geest ◽  
Bengt Fridlund ◽  
...  

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