Henny H. Billett

Impact of Adherence, Knowledge, and Quality of Life on Anticoagulation Control

BACKGROUND: Patients receiving chronic warfarin therapy who have poor anticoagulation control are at increased risk for adverse events. However, it is unknown how adherence to warfarin, patient demographics, patient knowledge about therapy, and perceived impact of warfarin therapy on quality of life are associated with anticoagulation control. OBJECTIVE: To determine the association between these patient factors and anticoagulation control in patients attending 2 anticoagulation clinics in the Bronx, New York City. METHODS: A cross-sectional survey of 52 patients was conducted. The 4-item Morisky survey was used to assess self-reported adherence. Patient knowledge about warfarin therapy and the perceived impact of warfarin therapy on quality of life were determined by self-administered questionnaires. Associations between adherence, patient knowledge, impact of warfarin therapy on quality of life, and anticoagulation control were determined with t-tests, χ2 analysis, and logistic regression. RESULTS: Only 14% of patients had good anticoagulation control. Adequate adherence was reported by 50% of patients and was significantly associated with good anticoagulation control (p = 0.01). Thirty-seven percent of participants had good knowledge of anticoagulation, and 19% of participants reported that warfarin negatively impacted their quality of life. Knowledge about warfarin therapy and impact of warfarin on quality of life were not significantly associated with anticoagulation control. CONCLUSIONS: Adherence is one of many factors that contribute to anticoagulation control. Adequate adherence, as determined by the Morisky survey, was significantly associated with anticoagulation control. Patient demographic characteristics, knowledge about warfarin therapy, and perceived impact of warfarin on quality of life were not associated with anticoagulation control.

Primary cardiac lymphoma: an analysis of presentation, treatment, and outcome patterns.

Primary cardiac lymphoma (PCL) represents a rare subset of non‐Hodgkin lymphoma, characterized by poor outcomes. The authors aimed to construct a framework of known clinical presentations, diagnostic features, disease complications, treatment, and outcomes to improve prognostication.

Anticoagulation for stroke prevention in elderly patients with atrial fibrillation, including those with falls and/or early-stage dementia: A single-center, retrospective, observational study

BACKGROUND Anticoagulation for stroke prevention is underused in elderly patients with nonvalvular atrial fibrillation (AF). Those with falls and/or early dementia may be at particular risk for stroke and hemorrhage. OBJECTIVE The aim of this study was to determine the prescribing patterns, risks, and benefits of anticoagulation with warfarin or acetylsalicylic acid (ASA) in elderly patients with AF at risk for stroke and hemorrhage, including those with falls and/or dementia. METHODS In this single-center, retrospective, observational study, data from patients aged > or =65 years with chronic nonvalvular AF treated at an urban academic geriatrics practice over a 1-year period were included. Eligible patients were receiving noninvasive management of AF with warfarin or ASA. Data were assessed to determine the prevalences of stroke, hemorrhage, falls, and the possible effects of anticoagulation with dementia. Outcomes events at 12 months, including time-in-therapeutic range (TTR), stroke, hemorrhage, and death, were determined. The stroke risk in each patient was estimated using the CHADS(2) (congestive heart failure, hypertension, age > or =75 years, diabetes, history of stroke or transient ischemic attack) score, and the risk for hemorrhage was estimated using the Outpatient Bleeding Risk Index. RESULTS A total of 112 patients (mean age, 82 years) were identified; 106 were included in the present analysis (80 women, 26 men); 6 were not receiving antithrombotic therapy and thus were excluded from the analysis. Warfarin was prescribed in 85% (90 patients); ASA, 15% (16). International normalized ratio testing was done frequently, with a median interval of 13.7 days between tests (92% within 28 days). No association was found between an improved TTR and the number of tests per unit of time or the number of patients per clinician. The distributions of both the CHADS(2) and Outpatient Bleeding Risk Index scores were not significantly different between the warfarin and ASA groups. The proportions of patients treated with warfarin were not significantly different between the groups with a high risk for hemorrhage and the groups at lower risk. At 12 months in the 90 patients initially treated with warfarin, the rate of stroke was 2% (2 patients); major hemorrhage, 6% (5); and death, 20% (18). Mortality was greater in patients with falls (45% [5/11]) and/or dementia (47% [8/17]) compared with those without either falls or dementia (12% [8/65]). CONCLUSIONS In this well-monitored geriatric population with chronic AF, including patients with falls and/or dementia, a high percentage were prescribed warfarin (85%), with low rates of stroke, hemorrhage, and death at 12 months despite a low TTR. Patients with falls and/or dementia had a high mortality rate (approximately 45%).

Aspirin resistance associated with HbA1c and obesity in diabetic patients.

INTRODUCTION Diabetes is known to be a prothrombotic state. Since serotonin uptake plays a role in both platelet activation and depression, we undertook to examine a hypothesis that aspirin resistance (AR) may be associated with both HbA1c and depressive symptoms and to assess other potential determinants of AR in diabetic patients. METHODS A whole-blood desktop platelet function analyzer (PFA-100) with an epinephrine agonist was used to assess AR among patients with type 2 diabetes. AR was defined as PFA closure times <192 s. Depression symptoms were assessed with the Physicians Health Questionnaire. Patients being treated for type 2 diabetes (N=48) who took aspirin within the past 24 h constituted the study sample. Associations with AR were assessed with the use of the Mann-Whitney test and Fishers Exact Test as well as with logistic regression models. RESULTS AR was observed in 11 patients (23%) and was not significantly associated with age, sex, or race. AR was significantly associated with HbA1c > or = 8% (P=.002) and obesity (BMI> or = 30 kg/m(2); P=.01) and borderline associated with having > or = 1 depressive symptom (P=.07). Results were similar after multivariable adjustment in logistic regression models. No statistically significant associations of AR with age, sex, race, plasma glucose, blood pressure, cholesterol, or smoking were observed. CONCLUSION These data suggest that AR may be of special concern for diabetic patients with poor glucose control and obesity. Whether the PFA-100 or any other practical measure of AR can be used in clinical practice to identify added cardiovascular disease risk and to inform platelet inhibition therapy needs further study.

Elevated levels of Factor XI are associated with cardiovascular disease in women

Coronary artery disease (CAD) continues to be the most frequent cause of death among women in the United States. Although elevated levels of clotting factors have been associated with CAD, few of these studies have been performed in women. Elevated levels of Factor XI have previously been associated with venous thrombosis, but little is known about its effect on arterial thrombosis. We selected women referred for cardiac catheterization who were found to have either normal coronaries or evidence of severe CAD and compared levels of homocysteine, anticardiolipin IgG/IgM antibodies, fibrinogen, platelet count, Factor VII, Factor VIII and Factor XI. Women with severe CAD had significantly higher levels of Factor XI than those without CAD (128% vs. 82%, p<0.04). Statistical adjustment for age, diabetes, hypertension, total cholesterol (TC), current smoking, or BMI had no effect on the independent association between CAD status and Factor XI. Factor XI was higher in women with total cholesterol levels >6.18 mmol/l (>239 mg/dl) compared with normocholesteremic women and was also higher in the upper tertile of age, but even when adjusted for these, the association remained significant. This initial study suggests that Factor XI may be an important parameter in arterial as well as venous thrombosis.

Exchange versus simple transfusion for acute chest syndrome in sickle cell anemia adults

BACKGROUND: There are scant data regarding the relative efficacy of exchange transfusion (XC) versus simple transfusion (ST) for treatment of sickle cell anemia acute chest syndrome (ACS).

Coagulation abnormalities in patients with Gaucher's disease: effect of therapy.

Various coagulation defects have been associated with Gauchers disease, including factor IX deficiency and acquired von Willebrands disease (VWD). We performed repeated coagulation assays in 9 patients with Gauchers disease over a period of 2 years. The prothrombin time (PT) and fibrinogen levels were normal in 8 of 9 patients, while the partial thromboplastin time (PTT) was abnormal in 5 of 9; all mixing PTT tests showed correction. Factor IX was normal repeatedly in the 7 of 7 patients tested. In contrast, factor XI was decreased in 3 of 9 patients assayed. Anticardiolipin (ACL) IgM was normal in all patients. ACL IgG was highly variable; levels were abnormal at least once in 6 of 8 patients, but were also normal at least once in 7 of 8 patients. Factor VIII was also quite variable: levels were decreased at least once in 4 of 9 patients, and normal at least once in 8 of 9 patients. Von Willebrand factor antigen (VWF Ag) studies were normal in 7 of 8 patients, but VWF activity was decreased at least once in 4 of 8 patients. In some patients, these problems could be overcome by specimen dilution. In only 1 patient was VWF Ag decreased; this patient had a factor VIIIC level of 13%, and VWF activity of 18.7%. Coagulation assays performed before and after alglucerase administration failed to demonstrate any significant improvement in these assays, and neither was there a consistent improvement over the duration of therapy. We suggest that previously reported decreases in factor IX and VWF may be secondary to the interfering presence of increased cerebroside levels. Caution must be used in the interpretation of clotting assays in the patient with Gauchers disease.

Promising therapies in sickle cell disease

Despite the fact that sickle cell anemia was one of the first diseases to have a demonstrated genetic etiology, to date there is still only one approved therapy for this disease. Recent increases in our understanding of the pathophysiology of the disease should translate into improved and more rapid development of newer therapies. This review will focus on the following current and potential therapeutic strategies to reduce the morbidity of sickle cell anemia. 1) Therapies such as decitabine, hydroxyurea, butyrate, lenalidomide and pomalidomide, which decrease the polymerization rate of HbS by increasing the concentration of Hb F; 2) Drugs that decrease relative intracellular HbS concentration by increasing total cell volume via inhibition of normal membrane ion exchange channels, such as KCL Cotransporter and Gardos Channels. These inhibitors include magnesium pidolate, imidazole antimycotics, arginine and Senicapoc; 3) Treatment of sickle cell vasoocclusion through inhibition of endothelial or cell surface adhesion molecules, such ICAM 4 and alpha(v)beta(3) integrins, by drugs related to the GPII(b)III(a) inhibitors or adhesion molecule modulators, and 4) Attempts to achieve vasodilation by nitric oxide and antioxidant therapy. This review will discuss the status of these emerging therapies in the treatment of sickle cell anemia.

Peak Antifactor Xa Activity Produced by Dalteparin Treatment in Patients with Renal Impairment Compared with Controls

Study Objective. To evaluate the relationship between impaired renal function and antifactor Xa activity in patients receiving dalteparin.

Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis.

Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium and red blood cell‐neutrophil interactions in sickle cell mice undergoing vaso‐occlusion. In this Phase I clinical trial of sickle cell anemia (SCA) patients admitted with pain crisis, we evaluated the status of adhesion molecules on neutrophils in control and IVIG‐treated subjects pre‐ and post‐infusion up to 800 mg/kg, the same dose used in murine studies. Mac‐1 function significantly decreased from baseline in the low‐dose IVIG (200–400 mg/kg) cohorts. IVIG‐related adverse events may have occurred in the high‐dose (600–800 mg/kg) cohorts. There were no significant increases in neutrophil and leukocyte counts, suggesting that IVIG may more selectively inhibit Mac‐1 function as opposed to neutrophil adhesion. This study provides the first in‐human validation of pre‐clinical murine studies that IVIG can decrease Mac‐1 function. Am. J. Hematol. 90:381–385, 2015.