By W. Kamak. California Institute of Technology.
Patient-reported outcomes are surveys used to assess a patient’s well-being from the patient’s perspective cheap loratadine 10mg on-line. These surveys often include health-related quality of life or symptom assessment and are appropriate for assessing a surgical intervention intended to improve quality of life or relieve symptoms purchase discount loratadine on-line. However cheap 10mg loratadine visa, currently buy loratadine 10mg mastercard, there are no validated quality of life instruments solely focused on palliative surgical outcomes, making it difficult to identify patients who benefit from these interventions, and the use of patient-reported outcomes in palliative surgery is limited [1,9]. One prospective pilot study using standardized, validated instruments demonstrated the challenges of interpreting outcomes after palliative interventions due to the continued loss of global health status during the end of life . In a second study, the authors found that the death rate of 40% prior to study completion at 90 days post-procedure had a significant impact on the questionnaire response, clearly demonstrating the challenge of measuring the success of interventions in actively dying patients . However, validating these interventions is essential given the high proportion of interventions that are palliative and the relatively high mortality rate which can significantly impact the overall operative mortality of an institution. In this age of quality-based reimbursement, this impact cannot be ignored and a means of incorporating palliative intent as a specific data element for comparing surgical outcomes needs to be devised. As with any treatment—surgical or medical—another opportunity for improving the outcomes of palliative surgery is through optimal patient selection. The end of life setting presents a unique set of circumstances requiring difficult decisions with limited data. Of 98 patient enrolled in this prospective study, 54 were treated nonoperatively and 44 were treated with surgery. Symptom relief and/or quality of life was the reason for the treatment choice in only 46% of patients, and 40% said that they made their choice based on the doctor’s recommendation. This study demonstrates the powerful influence of the physician in the decision-making of patients at this stage of life, and the need for clear communication about goals and expectations between all parties. Through the dynamics of the triangle, the patient’s complaints, values, and emotional support are taken into account while weighing the medical and surgical alternatives. In addition, the triangle offers an opportunity to learn about and address a patient’s and/or family’s expectations regarding the intent of the proposed procedure helping to moderate any incongruent expectations between surgeon, patient, and family members. This is one of the few studies that included both patients who did and did not undergo a palliative procedure. Reasons cited included low symptom severity, decision for nonoperative palliation, patient preference, and concerns about complications. The authors concluded that use of the palliative triangle can help improve patient selection which is associated with significantly better symptom resolution and few postoperative complications compared with previously published results. The authors have also postulated that building this strong relationship may explain the observation of high patient satisfaction toward surgeons after palliative operation—even if there is no demonstrable benefit . The palliative triangle facilitates interactions between patients, families, and surgeons, and helps guide patients to the best decisions regarding palliative surgery. While this list is not comprehensive, it does offer a framework for approaching any palliative surgery situation. When surgery is not an option, it is important to know how to palliate common symptoms in patients with advanced illness (see Chapter 35). Bowel obstructions can occur at any level of the gastrointestinal tract from the stomach to the rectum. Depending upon the etiology (adhesions, cancer, stricture), the management can vary from nonoperative nasogastric decompression and bowel rest to bowel resection and/or intestinal diversion. Regardless of the etiology, initial management of a patient with a bowel obstruction should include appropriate intravenous fluid resuscitation based upon the degree of dehydration and the site of the obstruction and correction of any metabolic abnormalities. The bowel should be decompressed with a nasogastric tube if the patient is vomiting, and the patient should not be allowed to eat or drink to decrease gastrointestinal stimulation and secretions. Imaging studies, such as an abdominal series and/or a computed tomography scan of the abdomen and pelvis, are helpful to determine the level and nature of the obstruction. They can also demonstrate the presence of extraluminal air suggesting a perforation, and the presence or absence of ascites. Patients who are hemodynamically stable, who do not have peritonitis and have a normal or only mildly elevated white blood count (especially in the setting of dehydration), can initially be monitored closely (with the measures mentioned above) and given a chance for the obstruction to resolve without surgery. Signs and symptoms of peritonitis or an imaging study suggesting a “closed loop” obstruction (a loop of intestine twisted around its mesentery) are indications for a more urgent surgical intervention. Often the exact nature of that intervention cannot be determined until the time of surgery—adding an additional element of cognitive and emotional uncertainty that must be borne by the patient, family, and surgeon. Surgery may include resecting the section of obstructed intestine if it appears to be an isolated site, performing an intestinal bypass if the site cannot be resected, performing a diverting ostomy (either small or large bowel depending on the location of the obstruction), or placing a decompression gastrostomy tube for venting the stomach if the obstruction cannot otherwise be relieved. In the setting of a malignancy, these operations can be challenging, both technically as well as with regard to the decision-making, and they pose a high risk for perioperative morbidity and mortality . If the obstruction is located in the rectum or rectosigmoid colon or duodenum, it is reasonable to consider an endoscopic stent placement rather than surgery as the initial intervention. While the presence of carcinomatosis has been shown to increase the risk of failure of endoscopic stent placement for colonic obstruction, there is a 77% to 85% success rate [14–17]. For patients with a limited prognosis, an opportunity to avoid an operation that could involve either an intestinal diversion and ostomy or venting gastrostomy tube is an important consideration. For patients in whom it is felt that surgical or endoscopic relief of the bowel obstruction is not feasible, it is reasonable to evaluate them for a percutaneous endoscopic gastrostomy tube placement for gastric drainage. Surgical decision-making becomes more challenging for end of life patients who are not stable and require a decision regarding an emergent operation. It may be argued that this is not a purely palliative surgery consult as the surgical intervention has the potential to rescue the patient from a life-threatening complication of their life-limiting illness. On the other hand, it may also be considered palliative as it will not cure the patient of the underlying disease process. Needless to say, this is often an emotionally charged time, even for patients with long-standing illness such as advanced cancer, because they are now faced with the imminent risk of dying. Of the 376 patients who underwent emergency surgery for obstruction, the 30-day mortality rate was 18% with a 41% morbidity rate and 60% were discharged to an institution. While most patients will survive the initial operation, a substantial number will die soon after the surgery and many experience postoperative complications, reoperations, stays in nursing homes, or hospital readmissions. While these data are helpful for surgeons and caregivers to advise patients of the risks of surgery, set expectations for the postoperative experience, discharge location and overall survival, both at the time when the decisions is made for surgery and if complications occur, important data regarding whether the goals of the patients and families were met and whether or not they would make the same choice again are still severely lacking at this time. As with a lower intestinal obstruction, acute symptoms should be initially managed with nasogastric decompression, bowel rest, and intravenous resuscitation, including aggressive electrolyte repletion. Options for managing upper gastrointestinal obstructions include intraluminal stenting, surgical bypass, and decompression gastrostomy with possible feeding jejunostomy. Similar to colonic stenting, the potential benefits of duodenal stenting include immediate palliation of nausea and vomiting with a less invasive procedure than surgical bypass and earlier return to oral nutrition [20,21]. Stenting has been shown to provide a comparable survival outcome and equivalent morbidity and mortality to surgical bypass . In a systematic review of the literature from 1990 to 2008 comparing endoscopic stenting with open surgical bypass, Ly et al. The major limiting factor for the endoscopic approach is being unable to pass the scope through the obstruction. The major complications reported are gastric ulceration, bowel perforation, biliary obstruction, stent dysfunction, and stent migration. Stent placement would be contraindicated in patients with multiple levels of intestinal obstruction and should be considered carefully for patients with peritoneal carcinomatosis who are at risk of more distal obstructions. For patients in whom stenting is not an option, surgical bypass can relieve both the symptoms of the obstruction and allow the patient to resume enteral nutrition. Surgical bypass, most commonly in the form of a gastrojejunostomy, can either be performed laparoscopically or through a relatively small upper midline incision. The estimated risk of morbidity and mortality from these procedures is 25% to 60% and 0% to 25%, respectively [22,23]. While surgical bypass is usually technically successful, patient selection with regard to preoperative nutritional status and life expectancy is imperative to the palliative success of this approach. For example, in addition to general surgical risks such as bleeding or infection, a patient with chronic gastric outlet or duodenal obstruction who is malnourished is at increased risk of a leak from the intestinal anastomosis. Other potential complications specific to gastric bypass include dumping syndrome, alkaline reflux gastritis, and delayed gastric emptying. Placement of a gastrostomy tube for decompression is another option for palliation of gastric outlet, duodenal and nonoperable small bowel obstruction or profound gastrointestinal dysmotility from carcinomatosis. Gastrostomy tubes can be placed either endoscopically, fluoroscopically, or surgically (either laparoscopic or open).
Fusion of villous placental oxidative stress: a possible factor in human trophoblast can be visualized by localizing active early pregnancy failure buy loratadine 10mg. A quantitative analysis of transcriptionally active 28 Basic Science syncytiotrophoblast nuclei across human gestation buy loratadine 10 mg otc. Excess diagnosing abnormally invasive placenta and syncytiotrophoblast microparticle shedding is a feature quantifying the risk best buy for loratadine. High Altitude adverse perinatal outcome in high‐risk women with Med Biol 2003;4:171–191 buy discount loratadine on-line. Rheological and physiological consequences of 26 Committee on Obstetric Practice, American College of conversion of the maternal spiral arteries for Obstetricians and Gynecologists. Two‐ Developmental biology of the placenta and the origins dimensional sonographic assessment of maximum of placental insufficiency. Semin Fetal Neonat Med placental length and thickness in the second trimester: 2004;9:357–369. Endothelial restriction in women with low pregnancy‐associated dysfunction in severe preeclampsia is mediated by plasma protein‐A. Further reading Structural characteristics of the placenta, see  Impact of oxygen on placental development and placental‐ Definition of fibrinoid, see  related disorders of pregnancy, see  Trophoblast and its changes during pre‐eclampsia, Composition and characteristics of fetal membranes, see  see  Rupture of fetal membranes, see  Detailed descriptions of pathologies and their impact on Placental assessment by ultrasound, see  macroscopic features of the placenta, see  Placental Doppler, see [19,25] Classification of villi and the types of villi, see  Developmental placental pathology, see  Stereological parameters of the growing placenta, Placental biochemistry in clinical practice, see [26,29] see  Role of a placenta clinic, see www. Initially, fetal weight increases mainly due to 90th centiles, and above the 90th centile, respectively. After 20 weeks of ges- fetus from the abnormal, three things must be known: (i) tation there is deposition of fetal adipose tissue, which accurate gestational age; (ii) measurement of the fetus; occurs alongside increases in fatty acid transport; later, and (iii) whether the measurements of size (or growth) fetal growth and adipose tissue deposition coincide with are within the normal range compared to a standard or increasing conversion of glucose into fat . Assessment of fetal size (at one point during preg- nancy) and fetal growth (a dynamic process that assesses change of size over a time interval) are key elements of Summary box 3. The aim of this assessment is to identify ● Assessment of fetal size, at one point during preg- babies that are too small or too large, due to an abnormal nancy, is different from assessment of fetal growth (i. These are practical cut‐offs and Estimation of gestational age useful for international comparisons, and are linked to adverse outcome; for example, newborns weighing less Accurate estimation of gestational age is not only than 2500 g are approximately 20 times more likely to die important in the assessment of fetal size and growth, but than heavier babies and are also at higher risk of a range also guides decisions regarding other obstetric interven- of poor health outcomes . This is because they are una- cases of preterm labour, or when labour induction in ble to distinguish those babies that are small due to pre- prolonged pregnancy should occur . In order to discriminate between these pheno- combination of nuchal translucency, pregnancy‐associated types, the gestational age must be known. For instance, there is an underlying ● interpretation of prenatal screening tests; assumption that all fetuses of the same size are of the ● assessment of fetal growth; same gestation, ignoring physiological differences and ● decision‐making that requires knowledge of gestation, biological variability in size. In addition, aberrations in for example around the limits of viability, and post term. It is generally the case that assessment of gestational age in late pregnancy is less accurate than late pregnancy dating. This is because fetal ultrasound measurements are associated with a larger absolute error with advanc- Measurement of the fetus ing gestation, and because fetal growth disturbances become more prevalent, meaning that an abnormally the most common methods for estimating fetal size at small fetus could be misjudged to have lower gestational any one time are by measuring fetal biometry using ultra- age (while a macrosomic fetus may be ascribed a more sound; or clinically, but also less accurately, by measure- advanced gestational age). It has been shown that relevance in women who attend for their first antenatal universal third‐trimester ultrasound (compared with care visit late in pregnancy and where no other reliable selective ultrasound, which is only carried out based on estimation of gestational age is available. Thus, the potential for error failed to demonstrate benefit of routine late pregnancy should be taken into account in order to ensure safe ultrasound in low‐risk or unselected populations, in terms obstetric practice: for example, in preterm labour where of perinatal mortality, preterm birth less than 37 weeks, late estimation of gestational age suggests a value above caesarean section rates, and induction of labour rates . First, the earliest reliable ultrasound scan taken using standard ultrasonographic planes. The landmarks are (1) centrally positioned, continuous midline echo (falx cerebri); (2) midline echo broken anteriorly at one‐third of its length by the cavum septum pellucidum; (3) thalami located symmetrically on each side of the midline. The landmarks are (1) a short segment of umbilical vein in the anterior third of the abdomen; (2) the stomach bubble is visible; (3) the (c) spine is seen. Note that the bladder and kidneys should not be visible in this axial cross‐section. The marked heterogeneity in these studies is helpful in counselling parents and enabling paediatri- thought to be due to the variety of methodologies cians to make management decisions), there are disad- applied, including the use of different fundal height vantages of using only a single summary measure of size. The single randomized pounded, resulting in 95% confidence intervals for ran- trial in the literature, involving 1639 women, showed no dom error in the region of 14% of birthweight. A more difficult scenario occurs in fetuses that exhibit a relative decrease in size over time by ‘cross- ing centiles’ but which remain above this cut‐off of the Summary box 3. In these cases careful clinical assessment is required; it is not known how many centiles (or standard ● Fetal growth charts should be based on ultrasound, deviations) can be crossed before the risk of adverse out- not on charts of birthweight; this is because in birth- come increases significantly. Birthweight charts should not be used for should be assessed using prescriptive standards which assessment of fetuses. This is because in birthweight show how fetuses should grow when nutritional, envi- charts those with poor growth are over‐represented at ronmental and health constraints on growth are mini- preterm gestations, even when excluding those births that mal. This is different from references that represent the are indicated for growth restriction; in other words, babies distribution of biometry within a population. However, this too is not the World Health Organization recommends the use 5000 of standards to assess human growth . While refer- ences describe how fetuses (or newborns or infants) have grown at a particular time and/or place, standards 4000 describe how they should grow when nutritional, envi- ronmental and health constraints on growth are mini- mal. Thus, standards are prescriptive: they demonstrate 3000 how growth should occur under near optimal condi- tions. It is important to note that the distribution of biometry within a population does not constitute a 2000 standard; this is because populations at high risk may exhibit growth that is suboptimal and is associated 1000 with higher rates of adverse perinatal outcome. While the concept of growth standards has been widely accepted in paediatrics , until recently there has 0 been a relative lack of knowledge regarding optimal 26 28 30 32 34 36 38 40 fetal growth. Selection was firstly based at population was applied to measure the weight, length and head cir- level: eight diverse urban populations living in demar- cumference of all newborns born in the entire popula- cated geographical or political areas were selected based tion . Infants were then followed up to the age of 2 on healthy environments free from pollutants, altitude years for detailed assessment of growth and less than 1600m, and low perinatal morbidity and mor- neurodevelopment. These standards challenge the perception of Fetal biometry was measured every 5 weeks by ultra- optimal fetal growth and also how growth problems sound using highly standardized, blinded and scientifi- should be identified and defined. Screening for fetal growth restriction with universal 2 World Health Organization. A systematic review of the ultrasound Antenatal Care for Uncomplicated Pregnancies. J Epidemiol translucency thickness, free beta‐human chorionic Community Health 2013;67:999–1005. Routine introducing the symphyseal–fundal height‐ ultrasound screening for the prediction of gestational measurement. Ultrasound Obstet Gynecol Cochrane Database of Systematic Reviews 2012, Issue 1999;14:23–28. International standards for early fetal size and pregnancy 17 Royal College of Obstetricians and Gynaecologists. The dating based on ultrasound measurement of crown– Investigation and Management of the Small‐for‐ rump length in the first trimester of pregnancy. Acta Paediatr impact of choice of reference charts and equations on 2015;104:987–996. Broadly, for any medical condition, there should be a Pre‐conception or pre‐pregnancy counselling involves discussion about whether becoming pregnant has risks seeing women several months prior to conception in for the mother or fetus. Pre‐pregnancy counselling will inform women of their risks, empowering them to make an informed decision Purpose of pre‐conception whether or not to proceed with pregnancy. It will allow counselling planning or prevention of pregnancy, and access to the appropriate multidisciplinary specialized services if nec- All women considering having a baby should see their essary. Pre-conception Counselling 39 Who needs pre‐conception Healthcare professionals who counselling? Specialists also have a role, particularly conditions that may be aggravated by pregnancy, in diabetologists, neurologists and cardiologists, who will particular the commoner conditions including epilepsy, be seeing adolescents and women of reproductive age diabetes, congenital or known acquired cardiac disease, for regular checks of their diabetes, epilepsy or heart autoimmune disorders, obesity with body mass index disease. The recommendation especially Unfortunately some specialists may be reluctant to dis- applies to women prior to having assisted reproduction cuss the implications of medical disease and the associ- and other fertility treatments. They are well informed as to the effects vated to see a doctor prior to getting pregnant, even if of various medical diseases in pregnancy and are aware they have a medical illness. Many will clinics or pre‐pregnancy health check clinics would be have dedicated pre‐conception clinics in tertiary care. Many maternal medicine specialists will also be able to Additionally, it is estimated that 25–40% of pregnancies offer detailed contraceptive advice and in many instances are unplanned.
The operator then activates the video clip function of the machine with a preset of 4-second duration buy cheap loratadine 10mg. Although the venous system of these areas can be examined generic 10mg loratadine with visa, it requires specific training and adds considerable time to the examination loratadine 10 mg overnight delivery, particularly for the calf veins loratadine 10 mg otc. Direct observation of the thrombus is diagnostic and allows the team to take immediate life-saving action, because a visible intracardiac thrombus is often associated with severe hemodynamic failure (Video 92. This is a difficult area to image in the critically ill patient who is generally in supine position, so their results have uncertain application for the intensivist. Lim W, Meade M, Lauzier F, et al: Failure of anticoagulant thromboprophylaxis: Risk factors in medical-surgical critically ill patients. Douay X, Lucas C, Caron C, et al: Antithrombin, protein C and protein S levels in 127 consecutive young adults with ischemic stroke. Liumbruno G, Bennardello F, Lattanzio A, et al: Recommendations for the use of antithrombin concentrates and prothrombin complex concentrates. Eichinger S, Stumpflen A, Hirschl M, et al: Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism. Sweetland S, Green J, Liu B, et al: Duration and magnitude of the postoperative risk of venous thromboembolism in middle aged women: prospective cohort study. Chopra V, Anand S, Hickner A, et al: Risk of venous thromboembolism associated with peripherally inserted central catheters: a systematic review and meta-analysis. Carrier M, Lazo-Langner A, Shivakumar S, et al: Screening for occult cancer in unprovoked venous thromboembolism. Hillmen P, Muus P, Duhrsen U, et al: Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Forastiero R, Martinuzzo M, Pombo G, et al: A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and risk of thrombosis. Galli M, Luciani D, Bertolini G, et al: Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Pengo V, Ruffatti A, Legnani C, et al: Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. Finazzi G, Marchioli R, Brancaccio V, et al: A randomized clinical trial of high-intensity warfarin vs. Strakhan M, Hurtado-Sbordoni M, Galeas N, et al: 36-year-old female with catastrophic antiphospholipid syndrome treated with eculizumab: a case report and review of literature. Cervera R: Update on the diagnosis, treatment, and prognosis of the catastrophic antiphospholipid syndrome. Kucher N, Koo S, Quiroz R, et al: Electronic alerts to prevent venous thromboembolism among hospitalized patients. Barbar S, Noventa F, Rossetto V, et al: A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the padua prediction score. Nendaz M, Spirk D, Kucher N, et al: Multicentre validation of the geneva risk score for hospitalised medical patients at risk of venous thromboembolism. Coutance G, Cauderlier E, Ehtisham J, et al: the prognostic value of markers of right ventricular dysfunction in pulmonary embolism: a meta-analysis. Vuilleumier N, Le Gal L, Verschuren F, et al: Cardiac biomarkers for risk stratification in non-massive pulmonary embolism: a multicenter prospective study. Lankeit M, Jimenez D, Kostrubiec M, et al: Predictive value of the high-sensitivity troponin T assay and the simplified pulmonary embolism severity index in hemodynamically stable patients with acute pulmonary embolism: a prospective validation study. Jimenez D, Kopecna D, Tapson V, et al: Derivation and validation of multimarker prognostication for normotensive patients with acute symptomatic pulmonary embolism. Konstantinides S, Geibel A, Heusel G, et al: Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. Meyer G, Vicaut E, Danays T, et al: Fibrinolysis for patients with intermediate-risk pulmonary embolism. Chatterjee S, Chakraborty A, Weinberg I, et al: Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. Birn J, Vedantham S: May-thurner syndrome and other obstructive iliac vein lesions: Meaning, myth, and mystery. Usoh F, Hingorani A, Ascher E, et al: Prospective randomized study comparing the clinical outcomes between inferior vena cava greenfield and TrapEase filters. Decousus H, Leizorovicz A, Parent F, et al: A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Iorio A, Kearon C, Filippucci E, et al: Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review. Jang T, Docherty M, Aubin C, et al: Resident-performed compression ultrasonography for the detection of proximal deep vein thrombosis: fast and accurate. Vieillard-Baron A, Page B, Augarde R, et al: Acute cor pulmonale in massive pulmonary embolism: incidence, echocardiographic pattern, clinical implications and recovery rate. Nazerian P, Vanni S, Volpicelli G, et al: Accuracy of point-of-care multiorgan ultrasonography for the diagnosis of pulmonary embolism. Mathis G, Blank W, Reissig A, et al: Thoracic ultrasound for diagnosing pulmonary embolism: a prospective multicenter study of 352 patients. While these patients are at high risk for developing arterial and venous thrombosis due to underlying comorbidities, central venous catheter placement, and immobility, they are also at high risk for hemorrhagic complications resulting from gastrointestinal stress ulcerations, invasive procedures, liver dysfunction, uremia, or coagulopathy . These divergent features often complicate antithrombotic treatments for the prevention or management of thrombosis. Limitations in administration routes, hemodynamic instability, alterations in renal and hepatic function, and drug interactions further complicate the administration of these high-risk medications . This chapter focuses on the mechanisms of action, pharmacokinetics, pharmacodynamics, clinical indications, complications of therapy, and reversal options for antithrombotic pharmacotherapy in critically ill patients. Platelet activation involves four mechanisms: adhesion to sites of vascular injury, release of stimulatory compounds, aggregation, and priming of coagulation. Antiplatelet ‘resistance’ and ‘nonresponse’ are terms applied to clinical outcomes characterized by failure to prevent a thrombotic event due to inadequate platelet inhibition . While several methods are available for measuring the overall and drug-specific platelet aggregation, standard testing protocols have yet to be established . Aspirin and Aspirin Derivatives Pharmacology, Pharmacodynamics, and Monitoring Aspirin, or acetylsalicylic acid, is a prodrug of salicylic acid that blocks platelet activation. Consequently, there is a 50- to 100-fold variation between the daily doses required to suppress inflammation and inhibit platelet function . Enteric-coated and delayed release formulations have diminished bioavailability, take 3 to 4 hours to reach peak plasma levels, and have delayed onset. Rectally administered aspirin has variable absorption with a bioavailability of 20% to 60% over a 2- to 5-hour retention time . There are currently no data suggesting inferiority of lower (75 to 100 mg) to higher (>100 mg) maintenance dosing in preventing thromboembolic events [9,10]. Recurrent vascular thrombotic episodes despite aspirin therapy occur at rates between 2% and 6% of patients per year  Aspirin resistance occurs in 5. Possible mechanisms of aspirin resistance include extrinsic factors (adherence, absorption, dosage formulation, and smoking) and intrinsic factors (pharmacodynamic alterations, receptor polymorphisms, up regulation of nontargeted platelet activation pathways). Clinical Indications Aspirin is indicated for the primary and secondary prevention of arterial and venous thrombosis (Table 93. Aspirin provides effective thromboprophylaxis in patients on warfarin with prosthetic heart valves and in patients with nonvalvular atrial fibrillation . The recommended interval for discontinuation of aspirin prior to elective surgery or procedures is 7 to 10 days. Therapy can be resumed approximately 24 hours or the next morning after surgery when there is adequate hemostasis . For patients exhibiting clinically significant bleeding or requiring emergent surgery, platelet transfusion may be warranted (Table 93. Intravenous desmopressin antagonizes aspirin’s effect, suggesting a role in emergent situations as well . Aspirin produces gastrointestinal ulcerations and hemorrhage through direct irritation of the gastric mucosa and via inhibition of prostaglandin synthesis. Enteric-coated and buffered aspirin doses ≤325 mg do not reduce the incidence of gastrointestinal bleeding . Aspirin-induced gastric toxicity can be prevented with concurrent use of acid-suppressive therapy .