Hemorrhage In Individuals Research Articles

Risk for intracranial hemorrhage in individuals after mild traumatic brain injury who are taking serotonergic antidepressants.

Serotonergic antidepressants may predispose to bleeding, but little is known of the risk for traumatic intracranial bleeding. This was a prospective case-control study of 218 patients with mild traumatic brain injuries (TBI) who were treated at a Finnish tertiary trauma hospital. Injury-related information and clinical findings were prospectively collected in the emergency department. Detailed pre-injury health history was collected from electronic medical records. Information on the use of serotonergic antidepressants was attained from the Finnish national prescription registry. All head CT scans were reviewed by a neuroradiologist based on the Common Data Elements. Cases were patients with traumatic intracranial hemorrhage on head CT. Controls were patients from the same cohort, but without traumatic intracranial lesions on CT. The proportion with traumatic intracranial bleeding for patients on serotonergic antidepressant medication was compared to the proportion for patients not on serotonergic medication. The study cohort consisted of 24 cases with traumatic intracranial bleeding and 194 injured controls. The median age of the sample was 70 years (interquartile range = 50-83). One fifth (21.6%) of all the patients were taking a serotonergic antidepressant. Of the patients on an antidepressant, 10.6% (5/47) had an acute hemorrhagic lesion compared to 11.1% (19/171) of those who were not on an antidepressant (p = 0.927). In the regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use. Serotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage after a mild TBI. The patients in this relatively small cohort were mostly middle-aged and older adults. These factors limit the generalizability of the results in younger patients with mild TBI.

The Relationship Between Caffeine and Caffeinated Drinks in Causing Intracranial Hemorrhage in the Elderly Aspirin-Taking Population: A Systematic Review.

Caffeinated drinks are the most widely consumed beverages globally and their intake has increased in the elderly. Caffeine exhibits dose-dependent adverse effects. Low to moderate doses cause anxiety, restlessness, irritability, and nausea. High doses of 3-5g can affect different physiological systems and lead to detrimental effects like palpitations, hypertension, agitation, seizures, and coma. Low-dose aspirin is the most used anticoagulant in preventing ischemic vascular events. An increased risk of intracranial hemorrhage is associated with low-dose aspirin with an intensified intracerebral hemorrhage risk. The aim of this research is to explore the association between caffeine and aspirin in causing lethal intracranial hemorrhage in the older population. Because of the devastating nature of intracranial hemorrhages and the inconsistent published data on the risk of intracranial hemorrhage in individuals taking both aspirin and caffeine, we conducted a systematic review considering the elderly population.We conducted the study following the reporting guidelines for systematic review and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. Inclusion and exclusion criteria were determined. Data was collected from PubMed, PubMed Central® (PMC), National Library of Medicine (MEDLINE), Google Scholar, Multidisciplinary Digital Publishing Institute (MDPI), and Web of Science by applying keywords and Medical Subject Headings (MeSH) terms individually. Our initial search yielded 155,270 articles, which were scrutinized, and duplicates were removed for accuracy. Of these, a total of 13 research papers were finally extracted using the PRISMA recommendations and applying other inclusion and exclusion criteria. With the help of our systematic review, we could determine that both aspirin and caffeine portrayed a role in causing intracranial hemorrhage independently, but further studies are recommended to evaluate if both could lead to similar adverse effects when taken collectively.

Gastrointestinal Hemorrhage: A Manifestation of the Telomere Biology Disorders

To describe the clinical features, therapeutic interventions, and patient outcomes of gastrointestinal (GI) hemorrhage in individuals with a telomere biology disorder, including dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome, Revesz syndrome, and Coats plus. Clinical Care Consortium for Telomere Associated Ailments members were invited to contribute data on individuals with telomere biology disorders at their institutions who experienced GI bleeding. Patient demographic, laboratory, imaging, procedural, and treatment information and outcomes were extracted from the medical record. Sixteen patients who experienced GI hemorrhage were identified at 11 centers. Among 14 patients who underwent genetic testing, 8 had mutations in TINF2, 4 had mutations in CTC1 or STN1, and 1 patient each had a mutation in TERC and RTEL1. Ten patients had a history of hematopoietic cell transplantation. The patients with Coats plus and those without Coats plus had similar clinical features and courses. Angiodysplasia of the stomach and/or small bowel was described in 8 of the 12 patients who underwent endoscopy; only 4 had esophageal varices. Various medical interventions were trialed. No single intervention was uniformly associated with cessation of bleeding, although 1 patient had a sustained response to treatment with bevacizumab. Recurrence was common, and the overall long-term outcome for affected patients was poor. GI bleeding in patients with telomere biology disorders is associated with significant morbidity and with vascular ectasias rather than varices.

Statins and Risk of Intracerebral Hemorrhage in Individuals With a History of Stroke.

Background and Purpose- It has been suggested that statins increase the risk of intracerebral hemorrhage in individuals with a history of stroke, which has led to a precautionary principle of avoiding statins in patients with prior intracerebral hemorrhage. However, such prescribing reticence may be unfounded and potentially harmful when considering the well-established benefits of statins. This study is so far the largest to explore the statin-associated risk of intracerebral hemorrhage in individuals with prior stroke. Methods- We conducted a population-based, propensity score-matched cohort study using information from Danish national registers. We included all individuals initiating statin treatment after a first-time stroke diagnosis (intracerebral hemorrhage, N=2728 or ischemic stroke, N=52 964) during 2002 to 2016. For up to 10 years of follow-up, they were compared with a 1:5 propensity score-matched group of statin nonusers with the same type of first-time stroke. The difference between groups was measured by adjusted hazard ratios for intracerebral hemorrhage calculated by type of first-time stroke as a function of time since statin initiation. Results- Within the study period, 118 new intracerebral hemorrhages occurred among statin users with prior intracerebral hemorrhage and 319 new intracerebral hemorrhages in users with prior ischemic stroke. The risk of intracerebral hemorrhage was similar for statin users and nonusers when evaluated among those with prior intracerebral hemorrhage, and it was reduced by half in those with prior ischemic stroke. These findings were consistent over time since statin initiation and could not be explained by concomitant initiation of other medications, by dilution of treatment effect (due to changes in exposure status over time), or by healthy initiator bias. Conclusions- This large study found no evidence that statins increase the risk of intracerebral hemorrhage in individuals with prior stroke; perhaps the risk is even lower in the subgroup of individuals with prior ischemic stroke.

Tolerance to a haemorrhagic challenge during heat stress is improved with inspiratory resistance breathing.

What is the central question of this study? Does inspiratory resistance breathing improve tolerance to simulated haemorrhage in individuals with elevated internal temperatures? What is the main finding and its importance? The main finding of this study is that inspiratory resistance breathing modestly improves tolerance to a simulated progressive haemorrhagic challenge during heat stress. These findings demonstrate a scenario in which exploitation of the respiratory pump can ameliorate serious conditions related to systemic hypotension. Heat exposure impairs human blood pressure control and markedly reduces tolerance to a simulated haemorrhagic challenge. Inspiratory resistance breathing enhances blood pressure control and improves tolerance during simulated haemorrhage in normothermic individuals. However, it is unknown whether similar improvements occur with this manoeuvre in heat stress conditions. In this study, we tested the hypothesis that inspiratory resistance breathing improves tolerance to simulated haemorrhage in individuals with elevated internal temperatures. On two separate days, eight subjects performed a simulated haemorrhage challenge [lower-body negative pressure (LBNP)] to presyncope after an increase in internal temperature of 1.3±0.1°C. During one trial, subjects breathed through an inspiratory impedance device set at 0cmH2 O of resistance (Sham), whereas on a subsequent day the device was set at -7cmH2 O of resistance (ITD). Tolerance was quantified as the cumulative stress index. Subjects were more tolerant to the LBNP challenge during the ITD protocol, as indicated by a>30% larger cumulative stress index (Sham, 520±306mmHgmin; ITD, 682±324mmHgmin; P<0.01). These data indicate that inspiratory resistance breathing modestly improves tolerance to a simulated progressive haemorrhagic challenge during heat stress.

Association of Novel Oral Antithrombotics With the Risk of Intraocular Bleeding

ImportanceNovel oral anticoagulation and antiplatelet therapies have become a mainstay of treatment for thromboembolic disease. However, the safety profile of these medications has not been completely characterized.ObjectiveTo determine the risk of developing intraocular hemorrhages with novel oral antithrombotic therapy compared with that of traditional antithrombotic agents.Design, Setting, and ParticipantsIn this retrospective cohort study, a large national insurance claims database was used to generate 2 parallel analyses. All patients with incident use of dabigatran etexilate or rivaroxaban between January 1, 2010, and September 30, 2015, were compared with patients with incident use of warfarin sodium. Similarly, patients with new use of prasugrel hydrochloride were compared with those with new use of clopidogrel bisulfate. Both analyses required the patient to be in the insurance plan for at least 24 months prior to initiation of therapy and excluded patients with any previous diagnosis of intraocular hemorrhages or any prescription for the comparator medications. Furthermore, the antiplatelet analysis required a diagnosis of acute coronary syndrome or a myocardial infarction within 60 days of initiation of pharmacologic therapy. The anticoagulant analysis excluded patients with end-stage renal disease, renal transplants, and those with heart valve disease.Main Outcomes and MeasuresIncident intraocular hemorrhages at 90 and 365 days. Multivariate Cox proportional hazards regression models were used to compare the hazard ratio (HR) of developing an intraocular hemorrhage in individuals taking novel agents compared with those taking traditional medications.ResultsA total of 146 137 patients taking warfarin (76 714 women and 69 423 men; mean [SD] age, 69.8 [11.8] years) were compared with 64 291 patients taking dabigatran or rivaroxaban (31 576 women and 32 715 men; mean [SD] age, 67.6 [11.7] years). Cox proportional hazards regression revealed a decreased hazard for developing an intraocular hemorrhage with dabigatran or rivaroxaban at 365 days (HR, 0.75; 95% CI, 0.58-0.97; P = .03), but not at 90 days (HR, 0.73; 95% CI, 0.22-2.63; P = .13). A total of 103 796 patients taking clopidogrel (37 578 women and 66 218 men; mean [SD] age, 68.0 [11.3] years) were compared with 8386 patients taking prasugrel (1988 women and 6380 men; mean [SD] age, 61.0 [9.6] years) and no increased hazard for developing an intraocular hemorrhage with prasugrel was seen at 90 days (HR, 0.75; 95% CI, 0.29-1.92; P = .55) or 365 days (HR, 1.19; 95% CI, 0.69-2.04; P = .53).Conclusions and RelevanceThese results suggest a decreased risk of intraocular hemorrhage associated with novel direct thrombin inhibitors and direct factor Xa inhibitors, but no difference for P2Y12 inhibitors compared with traditional vitamin K anticoagulation and antiplatelet therapy, respectively.

Warfarin prescription in patients with nonvalvular atrial fibrillation and one non-gender-related risk factor (CHA2 DS2 VASc 1 or 2): A treatment dilemma.

The issue of anticoagulation in individuals with nonvalvular atrial fibrillation (NVAF) and 1 non-gender-related (NGR) risk factor is subject to debate. The reported risk of stroke in untreated individuals is not uniform, and the rate of hemorrhage associated with anticoagulation in this group of individuals is not well defined. To this end, we assessed the rate of stroke and major hemorrhage in individuals treated with warfarin. individuals were extracted from the START register, an observational, multicenter, dynamic inception cohort study that collects data on NVAF individuals starting anticoagulation therapy. Risk of stroke is stratified using the CHA2 DS2 VASc score upon entry into the registry. Overall, 431 individuals with 1 NGR risk factor were followed up for 604 person-years. One nonfatal ischemic stroke was recorded (0.17 per 100 person-years) during follow-up. On the other hand, there were 9 major bleeding events (1.49 per 100 person-years), with 4 being intracranial hemorrhage (0.66 per 100 person-years), 1 of which was fatal. No difference in patient characteristics, bleeding risk factors, and quality of treatment were found between individuals who bled versus those who did not. However, a trend toward more bleeding events was observed in individuals <65years old. We found an elevated risk of major bleeding and intracranial hemorrhage in NVAF individuals treated with warfarin with 1NGR risk factor for stroke. These data call for caution when treating with warfarin these individuals.

Elevated rates of intracerebral hemorrhage in individuals from a US clinical care HIV cohort.

To compare rates of intracerebral hemorrhage (ICH) in HIV-infected and uninfected individuals in a large clinical care cohort and to assess risk factors associated with ICH. We identified incident ICH in HIV-infected and uninfected control cohorts from the Partners Health Care system using ICD-9-CM codes. We constructed Cox proportional hazards models to estimate adjusted hazard ratios for HIV infection and other predictors of ICH. The incidence rate of ICH was 2.29 per 1,000 person-years in HIV-infected individuals compared with 1.23 per 1,000 person-years in uninfected individuals, with an unadjusted incidence rate ratio of 1.85 (95% confidence interval 1.37-2.47, p < 0.001). In a multivariable model, HIV infection was independently associated with a higher hazard of ICH, although its effect diminished with increasing age. Female sex was associated with a lower hazard of ICH in the uninfected cohort but not in the HIV cohort. CD4 count <200 × 10(6) cells/L and anticoagulant use were predictive of ICH. HIV infection conferred an increased adjusted hazard of ICH, which was more pronounced in young patients and in women.

Tolerance to a hemorrhagic challenge during heat stress is improved with inspiratory resistance breathing

The mechanism(s) by which heat stress alters blood pressure control and tolerance to a simulated hemorrhagic challenge is multifaceted; however, heat‐induced reductions in central blood volume play a key role. Inspiratory resistance breathing improves blood pressure control and tolerance during simulated hemorrhage in normothermic individuals. It is unknown if similar improvements occur with this maneuver in heat stress conditions. This study tested the hypothesis that inspiratory resistance breathing improves tolerance to simulated hemorrhage in individuals with elevated internal temperatures. On 2 separate days, 8 subjects performed a simulated hemorrhage challenge (lower body negative pressure, LBNP) to pre‐syncope following an increase in internal temperature of 1.5 °C. During one trial subjects breathed through an inspiratory impedance device set at 0 cmH20 of resistance (Sham) while on the other day the device was set at −7 cmH20 of resistance (Experimental). Tolerance was quantified as cumulative stress index (CSI). Subjects were more tolerant to the LBNP challenge during the Experimental protocol as indexed by a larger CSI (Sham: 520±306 mmHg × min; Experimental: 682±324 mmHg × min, P&lt;0.01). These data indicate that inspiratory resistance breathing modestly improves tolerance to a simulated hemorrhagic challenge during heat stress.Support NIH‐HL61388 &amp; HL84072

Perceived recovery after aneurysmal subarachnoid haemorrhage in individuals with or without depression

The aims of the study were to describe what patients with no or only minor neurological deficits after aneurysmal subarachnoid haemorrhage (SAH) perceived to be important for recovery, and perceived consequences of the illness. Quantitative studies indicates unfavourable outcomes after aneurysmal SAH, concerning for example mental health and return to everyday life, among patients expected to recover completely. Thus, it is important to investigate the perceptions of patients and to give them the opportunity to communicate what they consider important for recovery. Qualitative descriptive design. Semi-structured interviews with 20 aneurysmal subarachnoid haemorrhagic patients were conducted approximately 12 months after the onset. Analyses were carried out in two steps, beginning with a qualitative content analysis. Due to the findings in the initial content analysis, a structured clinical interview for psychiatric disorders was used as a second step to verify the presence or absence of depression in the participants. Two patterns were identified. One pattern revealed that informants without depression experienced a 'confident perception of recovery', which included perceptions of meaningfulness. Another pattern revealed that depressed informants experienced a 'pessimistic perception of recovery', which included perceptions of hopelessness. Expectations regarding care after departure from the neurointensive care unit were not met. Individuals suffering from depression after aneurysmal SAH have a pessimistic view of their recovery in contrast to those without depression. These findings highlight the importance of better recognition and treatment of depression in the aftermath of SAH. These findings highlight the importance of better recognition and treatment of depression after aneurysmal SAH, where nurses play an active role. Nurses should seek to take actions to better meet patient's needs after departure from neurointensive care units.

Bleeding in the brain: Amyloid-beta may keep clots away.

Bleeding in the brain: Amyloid-beta may keep clots away.

Rate of nitric oxide scavenging by hemoglobin bound to haptoglobin

Cell-free hemoglobin, released from the red cell, may play a major role in regulating the bioavailability of nitric oxide. The abundant serum protein haptoglobin, rapidly binds to free hemoglobin forming a stable complex accelerating its clearance. The haptoglobin gene is polymorphic with two classes of alleles denoted 1 and 2. We have previously demonstrated that the haptoglobin 1 protein–hemoglobin complex is cleared twice as fast as the haptoglobin 2 protein–hemoglobin complex. In this report, we explored whether haptoglobin binding to hemoglobin reduces the rate of nitric oxide scavenging using time-resolved absorption spectroscopy. We found that both the haptoglobin 1 and haptoglobin 2 protein complexes react with nitric oxide at the same rate as unbound cell-free hemoglobin. To confirm these results we developed a novel assay where free hemoglobin and hemoglobin bound to haptoglobin competed in the reaction with NO. The relative rate of the NO reaction was then determined by examining the amount of reacted species using analytical ultracentrifugation. Since complexation of hemoglobin with haptoglobin does not reduce NO scavenging, we propose that the haptoglobin genotype may influence nitric oxide bioavailability by determining the clearance rate of the haptoglobin–hemoglobin complex. We provide computer simulations showing that a twofold difference in the rate of uptake of the haptoglobin–hemoglobin complex by macrophages significantly affects nitric oxide bioavailability thereby providing a plausible explanation for why there is more vasospasm after subarachnoid hemorrhage in individuals and transgenic mice homozygous for the Hp 2 allele.

Challenges in the Therapeutic Use of a “So-Called” Universal Hemostatic Agent: Recombinant Factor VIIa

Recombinant factor VIIa (rFVIIa) was developed in the early 1990s to provide "bypassing" hemostatic therapy for hemophilia A and B patients with inhibitors. More recently, it has been licensed for use in patients with inherited deficiency of factor VII. Since it was licensed for use in hemophilia with inhibitors in the US, Europe, and other countries for these specific indications, it has been used selectively but in a wide array of clinical settings for uncontrolled hemorrhage in individuals without an inherited bleeding disorder. Many of these uses have been described in the medical literature as case reports or small, uncontrolled series. Several randomized clinical trials (RCT) for these "off-label" medical uses have been published in recent months and will serve as the focus of this review. In particular, a review of an RCT for spontaneous intracranial hemorrhage that has demonstrated clinical efficacy in reducing both mortality and volume of central nervous system hemorrhage will be offered. A brief discussion of hypothesized physiologic mechanisms of supraphysiologic doses of rFVIIa will introduce the clinical discussion of these broad off-label uses. Since rFVIIa is a very expensive therapy, possible strategies for optimizing its use in the these settings will be presented.

Should asymptomatic patients with hereditary haemorrhagic telangiectasia (HHT) be screened for cerebral vascular malformations? Data from 22 061 years of HHT patient life

Background: The frequency of haemorrhage in individuals with hereditary haemorrhagic telangiectasia (HHT), 10% of whom will have cerebral arteriovenous (AV) malformations, could be high enough to justify screening. This would...

Diurnal and seasonal variations in the onset of primary intracerebral hemorrhage in individuals living in Izumo City, Japan.

Little is known about the temporal patterns of primary intracerebral hemorrhage (ICH) among the general population. The aim of this study was to examine diurnal and seasonal variations in the onset of ICH in a community-based series. The study population consisted of 350 patients who presented with primary ICH for the first time and were treated between 1991 and 1998 in Izumo City, Japan. Among the entire patient population, the onset of hemorrhage was rarely observed during the night and a peak was observed in the late afternoon. In men 69 years of age or younger, the onset of ICH exhibited a bimodal distribution, with an initial high peak between 8:00 and 10:00 a.m. and a second, lower peak between 6:00 and 8:00 p.m. In contrast, in men 70 years of age or older and in women regardless of age, only a single evening peak, between approximately 6:00 and 10:00 p.m., was found, and no morning peak was observed. For the entire patient population (for both sexes), and for men alone, seasonal variations--a peak in winter and a trough in summer-were significant for all age groups combined. This factor was significant for patients 69 years of age or younger, during the daytime hours (8:00 a.m.-8:00 p.m.), and for patients with untreated hypertension; however, it was not significant for patients 70 years of age or older, during nighttime hours (10:00 p.m.-8:00 a.m.), or for treated hypertensive and normotensive patients. In women, no significant seasonal patterns were found, regardless of patient age, time of day at onset of ICH, or the presence of risk factors. Seasonal variations were statistically significant for patients with hematomas larger than 5 ml, but not for those with hematomas 5 ml or smaller. Temporal distributions in the onset of ICH seem to be influenced by patient sex and age. The seasonal patterns of ICH occurrence may result mainly from changes that occur during the daytime, and may also be modified by the presence of untreated hypertension and by the volume of the hematoma.

Shock Rules and Their Use During Triage

In a mass casualty situation after airplane accidents, it is not unusual that physicians with only limited experience in emergency medicine need to perform initial triage. In their day to day work, they may not usually be confronted with the problems of hypovolemic shock. The same holds true for a proportion of the paramedical personnel employed.Speedy assessment and immediate, purposeful therapy is of the utmost importance in a mass casualty situation to increase the survival prospects of the victims. Timeconsuming and elaborate examinations are naturally precluded.The estimation of blood loss from profusely bleeding open wounds should not be too difficult. The extent, however, of the total blood loss associated with the insidious development of fracture hematomas is more frequently underestimated. This error can be avoided during triage at a mass casualty situation by means of a quick approximate calculation of the probably internal bleeding volumes:More difficulty is presented by internal hemorrhage in individuals appearing uninjured or only slightly injured. In such cases, the personnel employed in the early phase after an airplane accident should use simple and proven rules as criteria for their evaluation.The quotient of the pulse frequency and the systolic blood pressure has been called the shock index (Allgöwer and Burryi) (1). Disregarding the later and more complicated pathophysiological processes such as cardiogenic shock or septic shock, this index has been suggested as a method of assessment of the seveity of the hypovolemic shock in an injured person (Figure 1).