How to manage ITP with life-threatening bleeding.

While immune thrombocytopenia often presents with mild bleeding manifestations or surprising findings of thrombocytopenia on routine complete blood counts in patients without symptoms, some patients can present with new thrombocytopenia and life-threatening bleeding. Emergent assessment and treatment are needed to prevent substantial morbidity and even mortality. These patients present to the emergency room with bleeding, and hematologists are subsequently consulted. Understanding the approach to making the diagnosis and excluding other life-threatening illnesses is essential, as is rapid initiation of treatment in the bleeding patient even when the diagnosis of immune- mediated thrombocytopenia is tentative. Using a case-based format, we review how to approach and treat patients presenting with new thrombocytopenia and bleeding.

Cardiac device-induced right to left shunt causing significant hypoxemia: A case report and review of literature.

We describe a patient where a pacemaker lead induced tricuspid valve changes that caused a right to left shunt through a preexisting patent foramen ovale resulting in significant hypoxemia. This event occurred years after the pacemaker had been placed. Surgical closure of the patent foramen ovale resolved the patient's hypoxemia and dyspnea. We also reviewed the previous cases published in the medical literature concerning significant hypoxemia from cardiac device-induced right to left shunts. Three of the four reported cased occurred 4 or more years after device placement. Therefore, late onset hypoxemia in setting of cardiac device placement without an alternative cause should raise the possibility of this complication.

Definition of a critical bleed in patients with immune thrombocytopenia: Communication from the ISTH SSC Subcommittee on Platelet Immunology.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts and increased risk of bleeding. In preparation for an upcoming guideline, the ITP Emergency Management Guideline Panel, including clinical experts in hematology, emergency medicine, research methodology, and patient representatives, identified the need for a standardized definition of a critical ITP bleed. The goal of the definition was to distinguish critical bleeds from bleeds that may not require urgent treatment, typically in the context of severe thrombocytopenia. METHODS: The panel met in person and virtually to achieve consensus on the criteria for critical bleeding events among patients with ITP. Existing ITP bleeding scores and published definitions of major bleeds in patients receiving anticoagulation informed the definition of a critical ITP bleed. The Platelet Immunology Scientific Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis endorsed the definition. RESULTS: A critical ITP bleed was defined as: (a) a bleed in a critical anatomical site including intracranial, intraspinal, intraocular, retroperitoneal, pericardial, or intramuscular with compartment syndrome; or (2) an ongoing bleed that results in hemodynamic instability or respiratory compromise. CONCLUSION: The definition of a critical ITP bleed was developed by the ITP Emergency Management Guideline Panel and endorsed by the Platelet Immunology SSC. It incorporates both anatomic and physiologic risk and pertains to patients with confirmed or suspected ITP who typically have severe thrombocytopenia (platelet count below 20 × 109 /L).

Pericardial Effusion After Renal Transplantation: Timing and Clinical Characteristics.

BACKGROUND: Pericardial effusion and tamponade have been recognized as potentially serious complications in patients who have undergone renal transplantation. Our study aims to analyze the association between sirolimus and the development of pericardial effusion in renal transplant recipients. METHODS: This is a single-center retrospective study of 585 consecutive patients who underwent renal transplantation between 2005 and 2016. The study included 82 patients (14%) who developed new pericardial effusion after transplantation. Baseline demographics, medical comorbidities, medication use, echocardiographic parameters, and time to occurrence of effusion were assessed. Patients were divided into 2 groups based on timing of effusion development: early onset, ≤4 years after transplantation (51%); and late onset, >4 years after transplantation (49%). We examined the likelihood of immunosuppressant use and timing of effusion development using univariate and multivariate logistic regression analysis. RESULTS: The mean age of the cohort was 55.1 ± 11.5 years, 58.5% were men, 81.7% were white, and mean time from transplantation to the development of effusion was 4 ± 3.1 years. There were no significant differences between the early and late effusion groups in the demographic characteristics and medical comorbidities. However, sirolimus therapy was more common in the late effusion group. Furthermore, after adjusting for comorbidities, sirolimus use was associated with greater risk for developing late-onset effusion, adjusted odds ratio of 3.58 (95% confidence interval 1.25-10.20, P = .017). CONCLUSION: Pericardial effusion is prevalent in renal transplant recipients. In our cohort, treatment with sirolimus was associated with late-onset pericardial effusion. Awareness of pericardial disease in this population is important, and further studies are needed to identify predisposing factors.

Systems-based hematology: highlighting successes and next steps.

Systems-based hematology is dedicated to improving care delivery for patients with blood disorders. First defined by the American Society of Hematology in 2015, the idea of a systems-based hematologist arose from evolving pressures in the health care system and increasing recognition of opportunities to optimize the quality and cost effectiveness of hematologic care. In this review, we begin with a proposed framework to formalize the discussion of the range of initiatives within systems-based hematology. Classification by 2 criteria, project scope and method of intervention, facilitates comparison between initiatives and supports dialogue for future efforts. Next, we present published examples of successful systems-based initiatives in the field of hematology, including efforts to improve stewardship in the diagnosis and management of complex hematologic disorders (eg, heparin-induced thrombocytopenia and thrombophilias), the development of programs to promote appropriate use of hematologic therapies (eg, blood products, inferior vena cava filters, and anticoagulation), changes in care delivery infrastructure to improve access to hematologic expertise (eg, electronic consultation and disorder-specific care pathways), and others. The range of projects illustrates the broad potential for interventions and highlights different metrics used to quantify improvements in care delivery. We conclude with a discussion about future directions for the field of systems-based hematology, including extension to malignant disorders and the need to define, expand, and support career pathways.

Worsening Mitral Stenosis Due to Post-transcatheter Aortic Valve Replacement Improvement of Concomitant Aortic Insufficiency.

Transcatheter aortic valve replacement (TAVR) has become an alternative to surgical treatment in severe aortic valve stenosis, with expanding indications and rapidly growing number of performed procedures. Poor opposition of TAVR prosthesis to the aortic root causes paravalvular leak, while mitral regurgitation and stenosis have been associated with valve implantation low in the left ventricular outflow tract (LVOT). We report an unusual case of a patient with combined severe aortic stenosis and moderate aortic insufficiency who underwent elective TAVR, which resulted in significant increase of a pre-existing mitral valve gradient. Rapid post-TAVR increase in mitral valve gradient was likely due to improvement in aortic regurgitation and decreased left ventricular end-diastolic pressure (LVEDP).

Influence of mildly and moderately elevated pulmonary artery systolic pressure on post-renal transplantation survival and graft function.

BACKGROUND: Severe pulmonary hypertension (PH) has been associated with decreased post-kidney transplant survival and increased rate of long-term cardiovascular complications. Despite a high prevalence of PH in patients with end-stage renal disease, data on post-transplant renal allograft survival in recipients with pre-existing mild-to-moderate PH are limited. METHODS: The single-center retrospective study cohort consisted of 192 consecutive (2008-2015) renal transplant recipients with documented pretransplantation transthoracic echocardiogram (TTE) pulmonary artery systolic pressure (PASP). Mean age was 50.9 ± 12.4 years, 36.5% were females, and 81.25% were Caucasians. RESULTS: Elevated PASP ≥ 37 mm Hg was present in 51 patients. Elevated PASP was more common in patients with decreased <50% left ventricular ejection fraction (13.73% vs 3.55%, P = 0.010); otherwise, there were no significant differences in baseline demographic (age, ethnicity, gender, and donor status) and clinical parameters between patients with normal and elevated PASP. Four-year mortality (5.7%) was not significantly affected by elevated PASP. However, elevated PASP was associated with significantly decreased estimated glomerular filtration rate (eGFR) at 1 year (52.26 vs 60.13 mL/min, P = 0.019) and 2 years (51.04 vs 60.28 mL/min, P = 0.006) post-transplant. CONCLUSION: Mild and moderately elevated pre-kidney transplant PASP does not affect 4-year post-transplant mortality or graft loss. However, elevated pretransplant PASP is significantly associated with decreased 1 year and 2 years post-transplant eGFR. Preoperative echocardiographic evaluation for PH may be useful in predicting the probability of short-term renal graft and long-term graft dysfunction in these patients.

Successful percutaneous coronary intervention significantly improves coronary sinus blood flow as assessed by transthoracic echocardiography.

BACKGROUND: Transthoracic echocardiography (TTE) has been used to assess coronary sinus blood flow (CSBF), which reflects total coronary arterial blood flow. Successful angioplasty is expected to improve coronary arterial blood flow. Changes in CSBF after percutaneous coronary intervention (PCI), as assessed by TTE, have not been systematically evaluated. HYPOTHESIS: TTE can be utilized to reflect increased CSBF after a successful, clinically indicated PCI. METHODS: The study cohort included 31 patients (18 females, 62 ± 11 years old) referred for diagnostic cardiac catheterization for suspected coronary artery disease and possible PCI, when clinically indicated. All performed PCIs were successful, with good angiographic outcome. CSBF per cardiac cycle (mL/beat) was measured using transthoracic two-dimensional and Doppler flow imaging as the product of coronary sinus (CS) area and CS flow time-velocity integral. CSBF per minute (mL/min) was calculated as the product of heart rate and CSBF per cardiac cycle. In each patient, CSBF was assessed prospectively, before and after cardiac catheterization with and without clinically indicated PCI. Within- and between-group differences in CSBF before and after PCI were assessed using repeated measures analysis of variance. RESULTS: Technically adequate CSBF measurements were obtained in 24 patients (77%). In patients who did not undergo PCI, there was no significant change in CSBF (278.1 ± 344.1 versus 342.7 ± 248.5, p = 0.36). By contrast, among patients who underwent PCI, CSBF increased significantly (254.3 ± 194.7 versus 618.3 ± 358.5 mL/min, p < 0.01, p-interaction = 0.03). Other hemodynamic and echocardiographic parameters did not change significantly before and after cardiac catheterization in either treatment group. CONCLUSIONS: Transthoracic echocardiographic assessment can be employed to document CSBF changes after angioplasty. Future studies are needed to explore the clinical utility of this noninvasive metric.

Revascularization options in stable coronary artery disease: it is not how to revascularize, it is whether and when to revascularize.

Patients with acute coronary syndromes and severe multivessel or left main coronary artery disease have better outcomes when prompt revascularization is performed in addition to optimal medical therapy (OMT). However, in patients with stable ischemic heart disease, randomized strategy trials have revealed equipoise between initial strategies of OMT alone and OMT plus revascularization. Conducted in diverse stable ischemic heart disease patient populations and throughout the spectrum of atherosclerotic and ischemic burden, the RITA-2, MASS II, COURAGE, BARI 2D and FAME 2 trials demonstrate that OMT alone and OMT plus revascularization yield similar outcomes with respect to mortality and myocardial infarction. What remains unclear is whether there may be one or more subsets of patients with stable ischemic heart disease in whom revascularization may be associated with a reduction in mortality or myocardial infarction, which is to be addressed in the ongoing ISCHEMIA trial.

Disseminated intravascular coagulation with congestive heart failure and left ventricular thrombus: a case report with literature review of 7 cases.

BACKGROUND: Coagulation abnormalities can accompany acute congestive heart failure (CHF). However, disseminated intravascular coagulation (DIC) is rarely documented in such patients. DIC is characterized by generalized excessive activation of coagulation pathways followed by their depletion with secondary activation of anticoagulation and fibrinolysis. Treatment of the cause is an integral part of management of DIC; thus, recognition of the cause is critical. CASE REPORT: A 55-year-old previously healthy man presented with breathlessness, swelling of both legs, and left leg pain. His physical exam result was consistent with decompensated heart failure. Further testing revealed multiple deep venous thrombi in the upper and lower extremities, arterial occlusion in the left popliteal artery, and an unusual cyst-like left ventricular thrombus. His laboratory evaluation was consistent with severe acute DIC. The patient was managed aggressively with diuretics, transfusions of platelets, and cryoprecipitate and was subsequently anticoagulated. His platelet count and coagulation parameters normalized and coronary angiography did not reveal any obstructive lesions. On day 22, an echocardiogram revealed and MRI confirmed that the intracardiac thrombus had disappeared. He underwent revascularization of the left leg and was successfully discharged from the hospital. CONCLUSIONS: Severe biventricular non-ischemic cardiac dysfunction with intra-cardiac thrombi should be considered in patients presenting with DIC. In addition to anticoagulation, treatment of underlying heart failure is critical in such cases.

Accuracy of capsule colonoscopy in detecting colorectal polyps in a screening population.

BACKGROUND & AIMS: Capsule colonoscopy is a minimally invasive imaging method. We measured the accuracy of this technology in detecting polyps 6 mm or larger in an average-risk screening population. METHODS: In a prospective study, asymptomatic subjects (n = 884) underwent capsule colonoscopy followed by conventional colonoscopy (the reference) several weeks later, with an endoscopist blinded to capsule results, at 10 centers in the United States and 6 centers in Israel from June 2011 through April 2012. An unblinded colonoscopy was performed on subjects found to have lesions 6 mm or larger by capsule but not conventional colonoscopy. RESULTS: Among the 884 subjects enrolled, 695 (79%) were included in the analysis of capsule performance for all polyps. There were 77 exclusions (9%) for inadequate cleansing and whole-colon capsule transit time fewer than 40 minutes, 45 exclusions (5%) before capsule ingestion, 15 exclusions (2%) after ingestion and before colonoscopy, and 15 exclusions (2%) for site termination. Capsule colonoscopy identified subjects with 1 or more polyps 6 mm or larger with 81% sensitivity (95% confidence interval [CI], 77%-84%) and 93% specificity (95% CI, 91%-95%), and polyps 10 mm or larger with 80% sensitivity (95% CI, 74%-86%) and 97% specificity (95% CI, 96%-98%). Capsule colonoscopy identified subjects with 1 or more conventional adenomas 6 mm or larger with 88% sensitivity (95% CI, 82%-93) and 82% specificity (95% CI, 80%-83%), and 10 mm or larger with 92% sensitivity (95% CI, 82%-97%) and 95% specificity (95% CI, 94%-95%). Sessile serrated polyps and hyperplastic polyps accounted for 26% and 37%, respectively, of false-negative findings from capsule analyses. CONCLUSIONS: In an average-risk screening population, technically adequate capsule colonoscopy identified individuals with 1 or more conventional adenomas 6 mm or larger with 88% sensitivity and 82% specificity. Capsule performance seems adequate for patients who cannot undergo colonoscopy or who had incomplete colonoscopies. Additional studies are needed to improve capsule detection of serrated lesions. Clinicaltrials.gov number: NCT01372878.

Effects of obesity and subsequent weight reduction on left ventricular function.

Obesity is reaching epidemic proportions in the United States. Obesity adversely affects the circulatory system with resultant endothelial dysfunction, which promotes systemic hypertension, coronary artery disease, and vascular calcification. It is believed that the release of adipokines is responsible for this effect. In addition, obesity causes intrinsic changes in the heart including an increase in left ventricular (LV) mass, LV hypertrophy, LV dilatation, left atrial dilatation, and diastolic, as well as systolic dysfunction in some cases. The combination of increased adipose cells and an increase lean muscle mass in obese patients results in high cardiac output and an accompanying increased circulating volume leading to these adaptive changes. Weight loss by means of caloric restriction or surgery results in favorable hemodynamic changes referred to as "reverse remodeling." Regression of LV mass and chamber size has been shown universally. However, some studies have failed to reveal improvement in diastolic function possibly because of confounders such as nutritional deficiency that may occur after weight loss surgery. Some evidence seems to suggest that the greatest regression of LV mass and LV hypertrophy may occur when weight loss is combined with beta-adrenergic blocker therapy (in those who have an indication for the drug) when compared with other antihypertensive drugs versus weight loss alone.

Effect of comorbidities and medications on left ventricular mass regression after bariatric surgery.

Hypertension, diabetes, and obesity frequently coexist and significantly contribute to cardiovascular morbidity and mortality. Weight loss in obese individuals has been associated with improved blood pressure control and regression in left ventricular (LV) hypertrophy. The authors investigated the impact of comorbidity and medication on clinical and echocardiographic parameters after weight loss in obese patients. Serial echocardiography and clinical data were collected in 62 patients before bariatric surgery and after 6 months or 10% weight loss. Obese patients with diabetes or hypertension had higher baseline LV mass (LVM) (334 + or - 73 g in hypertension and diabetes vs 252 + or - 97 g in hypertension and 219 + or - 75 g in disease-free patients, P = .003; P = .089 for differences in LVM indexed by height), despite the lack of significant differences in body mass index or systolic blood pressure. There were no significant differences in baseline LVM or LVM index related to the medication used to treat hypertension. After weight loss, patients on beta-blocker therapy experienced the most significant LV hypertrophy regression (-76.5 + or - 79.1 g with beta-blockers, -17.8 + or - 43.7 g with diuretics, -4.5 + or - 46.6 g with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and -23.1 + or - 50.9 g in not treated patients, overall P = .538; beta-blockers vs no therapy P < .005; P = .145 for differences in LVM index). Bariatric surgery, combined with a weight loss program, provide substantial weight and LVM reduction regardless of comorbidities or blood pressure changes. beta-Blocker therapy appears to be associated with the greatest LVM regression after weight loss.

The impact of weight loss on cardiac structure and function in obese patients.

BACKGROUND: Obesity frequently results in structural and physiologic changes in the cardiovascular system. Whether weight reduction leads to reversal of these changes is not well-established. This investigation sought to identify the effect of a weight reduction program on right and left ventricular structure and function. METHODS: Sixty-two patients presenting to the eating disorders clinic at a single academic institution for weight loss programs were prospectively enrolled. Baseline and follow-up transthoracic echocardiograms were obtained after at least 10% weight reduction or 6 months after baseline echocardiogram. Complete 2-dimensional echocardiograms were performed with M-mode, flow Doppler, and tissue Doppler evaluation. RESULTS: Patients lost an average of 28.2 +/- 3 kg over a period of 266 +/- 36 days. Left ventricular mass decreased significantly from 255.87 +/- 12 to 228 +/- 11 gm. There were no statistically significant changes in contractility or diastolic indices. The ratios of early-to-late diastolic mitral inflow velocities (E/A) increased from 1.30 +/- 0.05 to 1.32 +/- 0.06. The ratio of early mitral flow to early annular velocity (E/Em) also increased from 5.57 +/- 0.22 cm to 5.82 +/- 0.23 cm. Deceleration time increased from 213.26 +/- 5.3 s to 228.47 +/- 5.7 s. CONCLUSIONS: Weight reduction is associated with decrease in left ventricular diastolic size and left ventricular mass. This weight reduction is not associated with statistically significant improvement in systolic or diastolic function.

Myocardial performance index correlates with right ventricular ejection fraction measured by nuclear ventriculography.

BACKGROUND: Assessment of right ventricular (RV) ejection fraction (EF) by two-dimensional echocardiography (2D ECHO) is practical but limited because of complex geometry of the RV. Techniques used for accurate measurement of RV EF are invasive or costly. However, derivation of 2D ECHO Doppler parameters to estimate RV function could be useful and inexpensive. METHODS: RV EF measured by nuclear ventriculography was compared with 2D ECHO estimates of myocardial performance index (MPI) and peak tricuspid annular systolic velocity (PTASV). Linear regression analysis and sensitivity analysis were used to analyze the data. RESULTS: RV EF measured by nuclear ventriculography correlated with MPI significantly (r =-0.55, P = 0.005) but not with PTASV (r = 0.09, P = 0.69). Using abnormal RV EF <45% measured by nuclear ventriculography, the sensitivity and specificity for MPI > 0.50 were 45.4% and 100%, respectively. The sensitivity and specificity of PTASV < or = 17.25 cm/sec in detecting abnormal RV EF were 100% and 35.4%. CONCLUSION: MPI greater than 0.50 indicates that RV function is abnormal and a value of PTASV > 17.25 cm/sec indicates normal RV function.

Ability of prospective assessment of personality profiles to predict the practice specialty of medical students.

Medical practice encompasses a diverse spectrum of specialties. Factors that impact selection of clinical disciplines by young physicians may have recently evolved associated with changes in medical school demographics. We assessed whether physicians gravitate to certain practice specialties due to preexisting personality traits. The Neuroticism-Extraversion-Openness Personality Inventory Revised Test was administered prospectively to 130 first-year students the week before they began medical school. Scores for five traits (neuroticism, extraversion, openness, agreeableness, conscientiousness) were compared with the selection among nine medical residencies at the conclusion of medical school. Personality scores for medical students selecting psychiatry residencies showed greater degrees of neuroticism (P < 0.01) and openness (P < 0.03). Students electing family practice also deviated from other specialties, showing a lower degree of neuroticism (P < 0.03). Unexpectedly, personality traits in prospective surgical residents did not differ from those of students choosing nonsurgical residencies. Personality profiles present before medical school appear to predict the selection of some residencies and clinical specialties but not others.

Lung cancer immunotherapy.

Recent insights into anti-tumor immunotherapy have led to a wave of clinical trials involving immunotherapy for lung cancer. Vaccines have evolved from nonspecific immune stimulants, like Bacillus Calmette-Guerin (BCG), to much more specific and potent strategies, some of which generate active immune responses against tumor-associated antigens. Understanding the mechanisms of anti-tumor immunity and identifying target antigens will likely improve these therapeutic strategies and provide them with a niche in the future of lung cancer therapy.

African Americans with LVH demonstrate depressed sensitivity of the coronary microcirculation to stimulated relaxation.

Excess coronary heart disease morbidity and mortality among African Americans remains an important yet unexplained public health problem. We hypothesized that adverse outcome is in part due to intrinsic or acquired abnormalities in coronary endothelial function and vasoreactivity. We compared dose-response curves relating changes in coronary blood flow and epicardial diameter to graded infusions of acetylcholine in 50 African American and 65 white subjects with hypertensive left ventricular hypertrophy (LVH) and normal coronary arteries. These groups were similar for age, body mass index, mean arterial pressure, and indexed left ventricular mass. The same protocol was conducted in 24 normotensive African American and 56 similar white subjects. We found significant depression in the coronary blood flow dose-response curve relation among African Americans when compared with white subjects with similar LVH (P<0.03). Racial differences were observed at all doses of acetylcholine but were less precisely estimated at the highest dose. The same testing among normotensive subjects revealed similar dose-response curves with no significant effect of race. Qualitatively similar results were found with respect to coronary diameter. Adenosine responses, a measure of endothelium-independent function, were similar after partitioning by LVH. Our study demonstrates that there are racial differences in sensitivity of coronary arteries to acetylcholine-stimulated relaxation among those with LVH. These results provide a mechanism whereby racial differences in coronary vasoreactivity might contribute to adverse coronary heart disease outcome among African Americans, a group in whom LVH is prevalent.