Incidence and severity of thrombocytopenia associated with use of intravascular microaxial ventricular assist devices for treatment of cardiogenic shock.

INTRODUCTION: The use of temporary mechanical circulatory support (MCS) for patients with refractory cardiogenic shock has increased over the past decade. Impella devices (intravascular microaxial ventricular assist devices [VADs]) have become common MCS options but reportedly cause thrombocytopenia. Limited published data regarding the incidence or severity of microaxial VAD-associated thrombocytopenia exists. OBJECTIVES: The goal of this study was to determine the incidence, timing, and severity of thrombocytopenia in a microaxial VAD population. METHODS: A retrospective multicenter review of electronic medical records identified all patients implanted with microaxial VAD at three US academic teaching hospitals between June 2015 and August 2017. Patients were excluded for short-term procedural microaxial VAD use during percutaneous coronary intervention. RESULTS: Sixty-four patients underwent microaxial VAD insertion (95% for left-sided support) during the observed time period. Support was in place for a median duration of 5.2 (interquartile range [IQR]: 2.4-10.0) days. Within 7 days postinsertion, 98.5% of patients developed thrombocytopenia (platelet count <150,000/µl) and 81.3% of patients experienced a >50% platelet decrease. Average platelet count nadir was 68,200/µl or 63.9% from baseline occurring on median day 3.8 (IQR: 2.4-5.4). Twenty-four patients (38.1%) were tested for heparin-induced thrombocytopenia by the heparin-dependent antibody (HDA) test. All HDAs were either negative or had serotonin release assay negative confirmation. Postdevice removal, platelet counts returned to baseline or >150,000/µl in 63% of patients by Day 5. CONCLUSION: Microaxial VAD-associated thrombocytopenia is common. Practitioners should consider this when evaluating supported patients for other causes of thrombocytopenia. Platelet counts return to preimplantation levels within days of device removal.

Enoxaparin Use and Adverse Events in Outpatients With a Continuous Flow Left Ventricular Assist Device at a Single Institution.

BACKGROUND: Patients with left ventricular assist devices (LVADs) are anticoagulated with warfarin and may receive enoxaparin bridging for a subtherapeutic international normalized ratio (INR). There is no guideline regarding enoxaparin bridging in LVAD patients and a dosing strategy to ensure efficacy and safety is uncertain. OBJECTIVE: The objective was to characterize the use of enoxaparin bridging for subtherapeutic INRs and its impact on thrombotic or major bleeding events (MBE) in patients with an LVAD. METHODS: A retrospective review from 6/1/17 to 6/30/18 was performed. Patients with an LVAD were excluded if they had less than 60 days of outpatient anticoagulation or age <18 years old. Patients were divided into 2 cohorts based on enoxaparin exposure. MBE and thrombotic events were classified as related to enoxaparin if events occurred while receiving enoxaparin and up to 7 days or 30 days, respectively, after discontinuation. RESULTS: Seventy-one LVAD patients met inclusion criteria and 50 patients received enoxaparin bridging. Therapeutic-dose enoxaparin was initiated at a mean INR of 1.8 for a mean duration of 2.8 days. In the enoxaparin exposure group, one MBE occurred 6 days after enoxaparin discontinuation, coinciding with an INR increase from 1.8 to 4.7. One thrombotic event occurred 2 days after enoxaparin discontinuation at an INR of 5.0. CONCLUSION: This institution's bridging strategy of therapeutic-dose enoxaparin with a short duration has a low rate of bleeding and thrombotic events. Additional prospective studies of anticoagulation bridging based on characteristics such as type of LVAD device are warranted.

Silodosin for benign prostatic hyperplasia.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trials, and safety of silodosin, a recently approved alpha(1A)-adrenergic receptor (AR) antagonist for benign prostatic hyperplasia (BPH). DATA SOURCES: English-only articles obtained from MEDLINE (1966-October 2009) using the search terms silodosin and KMD-3213 were reviewed. In addition, a search of International Pharmaceutical Abstracts (1970-October 2009) was conducted. STUDY SELECTION AND DATA EXTRACTION: Available English-language articles were reviewed, as well as abstracts from available non-English articles. DATA SYNTHESIS: Silodosin reduces urinary symptoms associated with BPH in as little as 1 day after initiation. The largest clinical trial conducted to date demonstrated a decrease in International Prostate Symptom Score of -6.4 +/- 6.63 points compared to -3.5 +/- 5.84 in patients receiving placebo (p < 0.0001). Silodosin also improved urinary flow rates by approximately 2.8 +/- 3.44 mL/sec, which is comparable to other alpha(1)-AR antagonists. The usual dose of silodosin is 8 mg once daily and should be reduced to 4 mg for patients with moderate renal dysfunction. Use is contraindicated in patients with severe renal and hepatic impairment or taking strong CYP3A4 inhibitors. In clinical trials, the most prevalent adverse effects were ejaculatory disturbances, occurring in approximately 28% of patients, although only 2.8% of patients discontinued treatment due to this adverse effect. Preliminary data suggest that, similar to other third-generation alpha(1A)-AR antagonists, silodosin has little potential to cause significant cardiovascular adverse effects such as orthostatic hypotension or syncope. To confirm these findings, long-term studies are still needed, especially in patients taking antihypertensive agents and in those with a history of intolerance to other alpha(1)-AR antagonists. CONCLUSIONS: Silodosin was approved by the Food and Drug Administration in 2008. Long-term studies demonstrating improvement in clinically important outcomes of BPH have yet to be published. In addition, pharmacoeconomic analyses would assist in defining its current place in therapy. Until this information is available, silodosin may be best reserved as an alternative to other second- and third-generation alpha(1)-AR antagonists.

Alvimopan for postoperative ileus.

PURPOSE: The efficacy, safety, pharmacology, pharmacokinetics, drug-drug interactions, and administration of alvimopan for postoperative ileus are reviewed. SUMMARY: Alvimopan is a selective mu-opioid receptor antagonist with no central nervous system activity. When orally administered after partial small- or large-bowel resection in patients with primary anastomosis, alvimopan shortened the return of bowel function and time to discharge by approximately one day without compromising analgesia. Alvimopan was not shown to be beneficial on these same outcomes after hysterectomy and has not been studied in other surgical populations. Alvimopan is generally well tolerated, with the frequency of adverse events being similar to placebo when used postoperatively for one week or less. Long-term studies of alvimopan in opioid-induced bowel dysfunction have shown an association with adverse cardiovascular outcomes, neoplasms, and fractures. Because of these concerns, the Entereg Access Support and Education program was developed. The recommended dosage of alvimopan is 12 mg administered with a sip of water 30 minutes to five hours before surgery, followed by 12 mg twice daily beginning the day after surgery for a maximum of seven days, 15 total doses, or until discharge. There is a limited amount of pharmacoeconomic analysis concerning alvimopan. CONCLUSION: Alvimopan, a peripherally acting mu-opioid receptor antagonist, is a novel agent for the treatment of postoperative ileus. It appears to decrease the duration of postoperative ileus and hospitalization by approximately one day, theoretically offsetting its acquisition costs. Unresolved long-term safety issues, a limited indication, and its restricted-access program are likely to hinder its widespread use in the surgical population.

Heparin-dependent antibodies and thrombosis without heparin-induced thrombocytopenia.

Although heparin-dependent antibodies (HDAs) typically manifest with thrombocytopenia as in heparin-induced thrombocytopenia (HIT), they may also manifest with preserved platelet counts. We describe a 35-year-old woman who developed severe thrombotic complications due to heparinization and unrecognized HDAs. She had received subcutaneous heparin as prophylaxis for deep vein thrombosis during a 5-day hospitalization for postpartum cardiomyopathy. Five days after discharge (day 1), she developed bilateral lower extremity arterial thrombi and underwent heparinization and successful lower extremity thrombectomies. A pulmonary embolus and hepatic and renal infarcts were then found. On days 2-6, the patient experienced a myocardial infarction, ischemic cerebrovascular accident, recurrent lower extremity arterial thrombus, and splenic infarct. On day 7, blood obtained on day 4 was found to be strongly positive for HDAs. In the interim, the patient had been transitioned to warfarin. Her platelet counts were never less than 75% of baseline and were consistently above 200 x 10(3)/mm(3). Hypercoagulability studies were negative. The patient's score on the Naranjo adverse drug reaction probability scale indicated that the relationship between this adverse reaction and heparin was probable. An extensive MEDLINE search located 22 other reports of patients who developed HDAs, sometimes associated with thrombosis, but whose platelet counts did not decrease. As with our patient, many of these case reports described clinicians who overlooked thrombosis due to HDAs because the patients did not have HIT. Clinicians should be cognizant of this possibility and consider a diagnosis of HDAs in patients with ongoing thrombosis who are receiving heparin therapy. It is strongly recommended that heparin be substituted with another anticoagulant in such cases until the presence of HDAs can be definitively ruled out.

Thrombocytopenia in patients treated with heparin, combination antiplatelet therapy, and intra-aortic balloon pump counterpulsation.

OBJECTIVES: Determine the incidence and timing of intra-aortic balloon pump (IABP)-associated thrombocytopenia, if concomitant antiplatelet agents increase the incidence of thrombocytopenia, and the incidence of heparin-induced thrombocytopenia (HIT) in a contemporary IABP population. BACKGROUND: Previous studies predate the current practice of treating acute coronary syndrome patients with heparin and aspirin plus thienopyridines and glycoprotein IIb/IIIa receptor antagonists such that data are unavailable to determine if their co-administration worsens IABP-associated thrombocytopenia. METHODS: A retrospective cohort study of adult IABP patients (n = 107) from 2002 to 2006 was performed to determine the indication for and duration of counterpulsation, platelet counts during and for 7 days postcounterpulsation, medications potentially contributing to thrombocytopenia, and HIT antibody results if obtained. RESULTS: Thrombocytopenia, defined as platelets <150,000/mL or >50% decrease from baseline, occurred in 57.9% of patients. Overall, platelets declined to 60.2 +/- 22.8% of baseline with the mean (+/- standard deviation) nadir on day 2.8 +/- 2.0. Comparing patients who received heparin, aspirin, thienopyridines, and glycoprotein IIb/IIIa antagonists (n = 44) versus heparinized patients +/- aspirin (n = 45), platelet nadirs were 62.7 +/- 20.9% versus 58.3 +/- 23.9% of baseline levels, respectively (P = 0.42). The incidence of HIT was 2.8% in the entire cohort. CONCLUSIONS: IABP-associated thrombocytopenia occurred in 57.9% of this cohort. HIT was diagnosed in 2.8% and should be considered as a diagnosis if platelet counts do not stabilize or continue to fall after 3-4 days of counterpulsation. Increased use of antiplatelet therapy does not impact the degree of thrombocytopenia although the current practice of prompt IABP removal may offset this effect.

Intraoperative floppy iris syndrome associated with alpha1-adrenergic receptor antagonists.

OBJECTIVE: To describe intraoperative floppy iris syndrome (IFIS) in association with alpha(1)-adrenergic receptor (alpha(1)AR) antagonists by conducting a thorough literature review. DATA SOURCES: Literature retrieval was accomplished by searching MEDLINE (2000-December 2007) using the terms intraoperative floppy iris syndrome (IFIS), adrenergic alpha-antagonist(s), tamsulosin, doxazosin, terazosin, and/or alfuzosin. In addition, reference lists from identified publications were reviewed to identify additional reports and studies of interest. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from data sources were reviewed for relevance and uniqueness prior to inclusion. DATA SYNTHESIS: IFIS was first described in 2005 as a clinical triad observed during cataract surgery that includes fluttering and billowing of the iris stroma, propensity for iris prolapse, and constriction of the pupil. IFIS increases the risk of complications during cataract surgery. Numerous reports have linked IFIS to use of alpha(1)AR antagonists, most notably tamsulosin, which is prescribed for benign prostatic hyperplasia. Tamsulosin blocks prostatic alpha(1A)ARs but may also selectively block alpha(1A)ARs in the iris dilator muscle, preventing mydriasis during cataract surgery. Other alpha(1)AR antagonists, including terazosin, doxazosin, and alfuzosin, have also been linked to IFIS; however, their relationship to the syndrome is not as definitive. When ophthalmologists are aware of a patient's previous alpha(1)AR antagonist exposure, specific steps can be taken to reduce the risk of surgical complications. Corrective measures used during surgery have included iris expansion hooks, intracameral phenylephrine, and preoperative atropine. CONCLUSIONS: IFIS is a clinical syndrome observed during cataract surgery reported in patients taking systemic alpha(1)AR antagonists. It has been most strongly linked to use of tamsulosin. Medication washout periods of up to 2 weeks and specific surgical procedures have been attempted to reduce risk of complications from alpha(1)AR antagonists in the setting of cataract surgery. Patients should be educated regarding potential risks of this drug class so that they can discuss them with their healthcare providers, specifically ophthalmologists, prior to cataract surgery.

Recent developments in the management of acute respiratory distress syndrome in adults.

PURPOSE: Recent developments in the management of acute respiratory distress syndrome (ARDS) in adults are reviewed. SUMMARY: Corticosteroids have been extensively studied in ARDS; however, they have not demonstrated clear benefit in patients with ARDS. Some trials have found increased complications and mortality related to corticosteroid use. The use of conservative fluid management has been associated with significant reductions in morbidity, highlighting the need to avoid fluid over-administration in patients with ARDS. A number of ventilatory strategies have also been studied. Studies have found that higher positive end-expiratory pressure settings do not appear to be harmful in patients with ARDS. In an effort to prevent alveolar overdistention, low tidal volume and plateau pressure ventilation is increasingly being used in patients with acute lung injury (ALI). Given the increasing evidence supporting the use of lower tidal volume ventilation, this strategy has become the new standard of care in patients with suspected ALI and ARDS. No clear benefit has been shown in the treatment of ARDS with nitric oxide and surfactant. Prostaglandins and acetylcysteine are not considered useful in the treatment of ARDS, while no conclusions can be drawn regarding the benefits of albuterol on mortality in patients with ARDS. The use of prone positioning should be discouraged in the treatment of ARDS based on its associated risks. CONCLUSION: Early administration of moderate-dosage corticosteroids likely helps decrease the time of ventilator dependence and duration of intensive care unit stay. Conservative fluid management and low tidal volume ventilation are becoming increasingly widespread in the management of patients with ARDS. Nitric oxide, surfactant, prostaglandins, albuterol, acetylcysteine, and prone positioning have not been shown to be beneficial in the treatment of ARDS.