Bleeding in acute coronary syndrome: from definitions, incidence, and prognosis to prevention and management.

INTRODUCTION: In patients with acute coronary syndrome (ACS), the ischemic benefit of antithrombotic treatment is counterbalanced by the risk of bleeding. The recognition that bleeding events have prognostic implications (i.e. mortality) similar to recurrent ischemic events led to the development of treatment regimens aimed at balancing both ischemic and bleeding risks. AREAS COVERED: This review aims at describing definitions, incidence, and prognosis related to bleeding events in ACS patients as well as bleeding-avoidance strategies for their prevention and management of bleeding complications. EXPERT OPINION: Management of ACS patients has witnessed remarkable progress after the shift in focusing on the trade-off between ischemia and bleeding. Efforts in standardizing bleeding definitions will allow for better defining the prognostic impact of different types of bleeding events and enable to identify the high-bleeding risk patient. Such efforts will allow to balance the trade-off between the thrombotic and bleeding risk of the individual patient translating into better downward diagnostic and therapeutic decision-making. Novel strategies aiming at maximizing the safety and efficacy of antithrombotic regimens as well as the development of novel antithrombotic drugs and reversal agents and technological advances will allow for optimization of bleeding-avoidance strategies and management of bleeding complications.

Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS.

AIMS: The aim of this study was to determine the effect of ticagrelor monotherapy on clinically relevant bleeding and major ischaemic events in relation to clinical presentation with and without non-ST elevation acute coronary syndromes (NSTE-ACS) among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS AND RESULTS: We conducted a pre-specified subgroup analysis of The Ticagrelor With Aspirin or Alone in High Risk Patients After Coronary Intervention (TWILIGHT) trial, which enrolled 9006 patients with high-risk features undergoing PCI with DES. After 3 months of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin, 7119 adherent and event-free patients were randomized in a double-blind manner to ticagrelor plus placebo versus ticagrelor plus aspirin for 12 months. The primary outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding while the composite of all-cause death, myocardial infarction (MI), or stroke was the key secondary outcome. Among patients with NSTE-ACS (n = 4614), ticagrelor monotherapy reduced BARC 2, 3, or 5 bleeding by 53% [3.6% vs. 7.6%; hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.36-0.61; P < 0.001) and in stable patients (n = 2503) by 24% (4.8% vs. 6.2%; HR 0.76; 95% CI 0.54-1.06; P = 0.11; nominal Pint = 0.03). Rates of all-cause death, MI, or stroke among those with (4.3% vs. 4.4%; HR 0.97; 95% CI 0.74-1.28; P = 0.84) and without (3.1% vs. 3.2%; HR 0.96; 95% CI 0.61-1.49; P = 0.85) NSTE-ACS were similar between treatment arms irrespective of clinical presentation (Pint = 0.96). CONCLUSION: Among patients with or without NSTE-ACS who have completed an initial 3-month course of DAPT following PCI with DES, ticagrelor monotherapy reduced clinically meaningful bleeding events without increasing ischaemic risk as compared with ticagrelor plus aspirin. The benefits of ticagrelor monotherapy with respect to bleeding events were more pronounced in patients with NSTE-ACS. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02270242.

Role of platelets and antiplatelet therapy in cardiovascular disease.

Platelets have a key role in normal hemostasis and in the pathogenesis of atherothrombotic events, such as acute coronary syndrome. Following plaque rupture, platelets adhere to the subendothelial matrix, become activated and then aggregate to form a prothrombotic surface that promotes clot formation and subsequently vascular occlusion. Multiple pathways are involved in platelet activation, including those activated by adenosine diphosphate (ADP), thromboxane A2, epinephrine, serotonin, collagen, and thrombin. Currently, two groups of inhibitors of platelet activation are approved for clinical use in patients with acute coronary syndromes: cyclooxygenase-1 inhibitors, namely aspirin, and oral ADP receptor antagonists such as clopidogrel. These agents have shown improved short- and long-term clinical outcomes but are associated with increased bleeding risk, and the rates of recurrent ischemic events remain high. These considerations underscore the need for novel antiplatelet agents that can provide greater reduction in recurrent atherothrombotic events without increasing the risk of bleeding. Several novel antiplatelet agents are currently under clinical development, such as more potent ADP receptor antagonists and protease-activated receptor-1 antagonists. This article provides an overview of the basic principles of platelet biology and the current status of knowledge on available oral antiplatelet therapy, as well as those under clinical development.

Accurately assessing elderly fall deaths using hospital discharge and vital statistics data.

Historically, fatal injury monitoring and surveillance have relied on mortality data derived from death certificates (DC). However, problems associated with utilizing DC have been well documented. Recently, access to and utilization of hospital discharge data (HDD) have offered a new and important secondary source of data regarding in-hospital deaths. However, studies have shown that discrepancies between the HDD and the corresponding DC often exist. This discrepancy was especially evident when comparing HDD to the vital statistics data (VSD) for deaths by falls among those aged 65 and over in 19 states. This was a retrospective forensic review of elderly (age 65 and over) fall-associated fatalities (E880-E888) identified from HDD and VSD in Allegheny County, Pennsylvania, between 1997 and 1998. Seventy-seven cases were identified, with the original manner of death listed as natural (34), suicide (1), and accidental (42) on the DC. Following a forensic review of the cases, the manner of the death on the DC should have been changed from natural to accidental in 28% (n = 12) of the cases, representing an undercount in the VSD. Undercounts were due to a failure of clinicians to account for the significance of a fall event that contributed to subsequent pathology and death. In addition, in that 22% (n = 17) of the HDD fall-associated deaths, the fall did not contribute directly or sequentially to the underlying cause of death, thereby representing an overcount in the HDD. Based on these findings we recommend (1) elderly fall surveillance systems should only count HDD E-coded falls that demonstrate a serious traumatic injury which directly or subsequently results in death, (2) all in-hospital fall-associated deaths should be reported to and reviewed by coroner/Medical Examiner offices for determination of the cause and manner of death, and (3) physicians should be better educated in properly completing death certificates.

The risk of body packing: a case of a fatal cocaine overdose.

The process of swallowing or inserting illegal packets of drugs for the purpose of evading law enforcement officers carries risks other than criminal charges. It can be fatal. Individuals engaged in such activities are called "Body Packers" or "Mules". The most frequent cause of the death among body packers is acute drug intoxication due to rupture of the package(s) within the gastrointestinal tract. We present the first documented case of a body packer that died from cocaine intoxication following the rupture of packets of cocaine in Western Pennsylvania.

A case of a death by explosives: the keys to a proper investigation.

Suicidal deaths involving an explosive, unrelated to a terrorist act, are rare. The rarity of such events presents a unique environment for those investigating such a death. We report a case of suicide involving a 29-year-old white male who detonated a firework in his mouth, resulting in massive craniocerebral destruction. He was discovered in his residence shortly after the explosion. Initially, the case was believed to be a fatal gunshot wound by the paramedics and homicide detectives at the scene. Several small pieces of red colored paper and a possible end cap were located throughout the scene. Analysis of the paper and end cap showed trace components consistent with flash powder. The victim had used a pyrotechnic device to commit suicide. Therefore, it is critical for those who investigate deaths be able to identify cases that involve explosives in order to properly collect and analyze the evidence.

Age-based factors in femicide.

Homicide is a topic of interest not only because of its severity but because it is a fairly reliable barometer of all violent crime, especially as it affects women. This exploratory study compared a group of murdered women over age 60 with a group of murdered women 30-59 and included age-based factors for both groups. Discussion focuses on forensics as insight to crime scene dynamics and homicidal behavior.

Death by chainsaw: fatal kickback injuries to the neck.

Each year over 3 million new chainsaws are sold in the United States. The operation of these newer saws combined with the millions of older chainsaws in circulation results in over 28,000 chainsaw-related injures annually. The majority of the injuries involve the hands and lower extremities with less than 10% involving injuries to the head and neck regions. Deaths while operating a chainsaw are extremely rare. The most common hazards associated with chainsaws are injuries caused by kickback, pushback, and pull-in. Kickback is the most common and poses the greatest hazard. Kickback occurs when the rotating chain is stopped suddenly by contact with a more solid area throwing the saw rapidly backward toward the operator. The cause of most injuries can be traced to improper use of the saw or poor judgment on part of the operator. We present two fatal chainsaw deaths; one with an older style saw, and the other with a modern type. In both cases the victims died from fatal injuries received to the neck region from a chainsaw kickback. The first case involved a 49-year-old white male operating an older style chainsaw with limited safety features. The second case involved a 38-year old white male who was operating a newer model chainsaw equipped with a low kickback chain in an unsafe manner.

Deaths among criminal suspects, law enforcement officers, civilians, and prison inmates: a coroner-based study.

During the interaction between a criminal suspect and a law enforcement officer, the risk of death to the suspect, police, or civilians is increased. Unfortunately, very little information is available on the death risks arising from this interaction. This study provides an assessment of the risk of death to law enforcement officers, suspects, and bystanders by separating the interactions into the following 4 phases: (1) events prior to and during arrest; (2) police pursuits or chases; (3) transport of the suspects; and (4) during incarceration. A 5-year (1994-1998) retrospective coroner-based study of all deaths that occurred during these 4 phases was conducted in Allegheny County, Pennsylvania. A total of 77 cases were identified; 14 deaths (18.1%) occurred prior to or during arrest, 10 (12.9%) during police chases, 2 (2.6%) occurred while the actors were being transported, and 51 (66.2%) during incarceration. The majority of cases (98.7%) were males, blacks (63.6%), and single (50.6%). The respective risks of death by phase were prearrest/arrest, 6.5 per 100,000 arrests; transport, 0.93 deaths per 100,000 arrests; and incarceration, 268 deaths per 100,000 inmates. Study showed the following: (1) risk of death to offenders was greatest during police pursuits; (2) the risks during arrests are not insignificant and involved an officer being threatened with a weapon in one-third of the events; and (3) deaths among inmates were primarily due to natural causes.

Death during transforaminal epidural steroid nerve root block (C7) due to perforation of the left vertebral artery.

Treatment for individuals suffering from migraines and pain due to an inflammation or impingement of a nerve range from noninvasive methods such as massage, physical therapy, and medications to invasive methods such as epidural steroid injections and surgery. Each method of treatment has an associated level of risk. While minor to moderate complications from such procedures do occur, deaths are very rare. We report the first cited case of a death associated with the pain management procedure called nerve root block, also referred to as a transforaminal epidural steroid injection. We present the medical history and autopsy findings of a 44-year-old white female who died of massive cerebral edema secondary to the dissection of the left vertebral artery and subsequent thrombosis due to the perforation of that artery by a 25-gauge spinal needle during a C-7 nerve root block.

Acute stent thrombosis after early withdrawal of platelet glycoprotein IIb/IIIa antagonists: potential rebound prothrombotic effect?

We report on two cases of acute coronary stent thrombosis after early withdrawal of different competitive inhibitors of the platelet glycoprotein IIb/IIIa receptor, eptifibatide and tirofiban. Differences in pharmacokinetics between different types of glycoprotein IIb/IIIa receptor blockers and a potential rebound prothrombotic effect with the use of these antiplatelet drugs are reviewed.