By: G. Treslott, M.B. B.CH. B.A.O., M.B.B.Ch., Ph.D.
Co-Director, Creighton University School of Medicine
Salvati F symptoms you are pregnant purchase amoxicillin line, Liani M: Role of platelet surface receptor abnormalities in the bleeding and thrombotic diathesis of uremic patients on hemodialysis and peritoneal dialysis medications memory loss order amoxicillin 650 mg amex. Castillo R symptoms and diagnosis purchase discount amoxicillin online, Lozano T medicine song best 1000mg amoxicillin, Escolar G, et al: Defective platelet adhesion on vessel subendothelium in uremic patients. Diaz-Ricart M, Estebanell E, Cases A, et al: Abnormal platelet cytoskeletal assembly in hemodialyzed patients results in deficient tyrosine phosphorylation signaling. Noris M, Todeschini M, Zappella S, et al: 17b-estradiol corrects hemostasis in uremic rats by limiting vascular expression of nitric oxide synthases. Zoja C, Vigano G, Bergamelli A, et al: Prolonged bleeding time and increased vascular prostacyclin in rats with chronic renal failure: Effects of conjugated estrogens. Himmelfarb J, Holbrook D, McMonagle E, et al: Increased reticulated platelets in dialysis patients. Gaspari F, Vigano G, Orisio S, et al: Aspirin prolongs bleeding time in uremia by a mechanism distinct from platelet cyclooxygenase inhibition. Diaz-Ricart M, Etebanell E, Cases A, et al: Erythropoietin improves signaling through tyrosine phosphorylation in platelets from uremic patients. Violi F, Ferro D, Basili S, et al: Prognostic value of clotting and fibrinolytic systems in a follow-up of 165 liver cirrhotic patients. Violi F, Ferro D, Basili S, et al: Hyperfibrinolysis increases the risk of gastrointestinal hemorrhage in patients with advanced cirrhosis. Violi F, Leo R, Basili S, et al: Association between prolonged bleeding time and gastrointestinal hemorrhage in 102 patients with liver cirrhosis: Results of a retrospective study. Laffi G, Cominelli F, Ruggiero M, et al: Altered platelet function in cirrhosis of the liver: Impairment of inositol lipid and arachidonic acid metabolism in response to agonists. Kunihiro N, Kawai B, Sanjo A, et al: Platelet aggregation and coagulation and fibrinolysis parameters in both portal and systemic circulations in patients with cirrhosis and hepatocellular carcinoma. Tripodi A, Primignani M, Chantarangkul V, et al: An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Cortelazzo S, Viero P, Casarotto C, et al: Bleeding on patients with autoimmune thrombocytopenic purpura and normal platelet count. Clancy R, Jenkins E, Firkin B: Qualitative platelet abnormalities in idiopathic thrombocytopenic purpura. Berchtold P, Muller D, Beardsley D, et al: International study to compare antigen-specific methods used for the measurement of antiplatelet autoantibodies. Takahashi R, Sekine N, Nakatake T: Influence of monoclonal antiplatelet glycoprotein antibodies on in vitro human megakaryocyte colony formation and proplatelet formation. Sugiyama T, Okuma M, Ushikubi F, et al: A novel platelet aggregating factor found in a patient with defective collagen-induced platelet aggregation and autoimmune thrombocytopenia. Deckmyn H, Van Houtte E, Vermylen J: Disturbed platelet aggregation to collagen associated with an antibody against an 85- to 90-Kd platelet glycoprotein in a patient with prolonged bleeding time. Toltl, Ishac Nazi, James Smith, and John Kelton Platelets are anucleate cells that are required for primary hemostasis. This primitive feedback system is very effective at maintaining the platelet count at a stable level. Immune-mediated platelet disorders disrupt normal regulation of platelet number because of cell-mediated or antibody-mediated platelet destruction or megakaryocyte injury. Antibodies that target self (autoimmune) or nonself (alloimmune) antigens on platelets can cause severe thrombocytopenia. These platelet disorders have related features yet are distinct clinical syndromes (Table 133-1). The pathophysiology, clinical manifestations, and management of each of these disorders are discussed in this chapter. Seasonal variability suggests that a viral infection may trigger the disease in many children. Most studies in children report an overall male predominance in early childhood and equalization or reversal to female predominance in older children. Relatively stable incidence rates were found in women up to the age of 60 years with a steady increase thereafter. The prevalence in women is reported to be nearly double that in men; however, this trend is attenuated in older age groups and may revert to a male predominance after the age of 65 years. Adult incidence and prevalence rates may reflect a true increase in risk of disease with age or measurement bias because of a higher likelihood of discovering incidental thrombocytopenia with more frequent medical visits. Recently, however, it has become evident that relative platelet underproduction is also an important feature of this disorder. Pregnancy-related vascular disorders are the next most common cause of thrombocytopenia during pregnancy. Platelet counts tend to be mildly reduced, and hypertension and other features are invariably present. Immune thrombocytopenia is an uncommon cause of thrombocytopenia in pregnancy, and when mild, it can be difficult to distinguish from incidental thrombocytopenia of pregnancy. Splenectomy is rarely indicated during pregnancy because most women can successfully be managed with less aggressive therapy.
Recurrent spontaneous abortions have been associated with dysfibrinogenemia in several families medications given im purchase amoxicillin 650mg fast delivery, and some pregnancies have been carried to term using replacement therapy with cryoprecipitate symptoms migraine order 650mg amoxicillin mastercard. Thrombin was generated from a precursor symptoms menopause amoxicillin 250 mg with visa, prothrombin medications quit smoking buy genuine amoxicillin on-line, by thrombokinase (probably factor Xa). Total prothrombin deficiency is probably not compatible with life, because complete absence of the protein has not been observed in humans and prothrombindeficient mice succumb to bleeding in utero or shortly after birth. Severe congenital deficiency associated with reduced plasma prothrombin antigen (hypoprothrombinemia) or circulating dysfunctional prothrombin (dysprothrombinemia) affects an estimated 1 in 2 million people (see Table 139-1). In the North American Rare Bleeding Disorder Registry, 62% of patients with prothrombin deficiency were Latino, possibly reflecting the prevalence of the Arg457Gln variant prothrombin Puerto Rico I. Prothrombin is a 72,000-Dalton protein that is converted to thrombin by factor Xa in complex with factor Va on phospholipid surfaces. Thrombin is a pivotal protease in hemostasis, with multiple procoagulant activities including cleavage of fibrinopeptides A and B from fibrinogen to form fibrin. Plasma prothrombin activity is typically 1% to 10% of normal in hypoprothrombinemia and 1% to 20% in dysprothrombinemia. Cephalosporins, particularly those with N-methyl-thiotetrazole side chains, can decrease prothrombin levels. Antiprothrombin antibodies are common phospholipiddependent antibodies found in patients with the lupus anticoagulant or the antiphospholipid antibody syndrome. More rarely, patients with a lupus anticoagulant or systemic lupus erythematosus have antibodies that enhance prothrombin clearance, causing true deficiency. No reports exist of neutralizing antibodies forming after replacement therapy in congenital prothrombin deficiency, consistent with severely affected patients having at least a trace of circulating prothrombin. Severe hypoprothrombinemia is inevitably associated with bleeding that may be life threatening, although the correlation between plasma prothrombin activity and clinical severity is not particularly strong. Central nervous system hemorrhage was reported in 8% to 12% of patients, and in 20% of those with prothrombin levels below 1% of normal activity. The bleeding diathesis can present at circumcision in neonates or as easy bruising, epistaxis, menorrhagia, or gastrointestinal hemorrhage, as well as with trauma or surgery. Heterozygotes occasionally have excessive bleeding with surgery or tooth extraction, but most are asymptomatic. Bleeding tends to be less severe in dysprothrombinemia, and some variants are particularly mild. For example, homozygosity for Arg67His causes severe reduction in plasma prothrombin activity (<20% of normal) but results in relatively few symptoms. Hemostatic levels of prothrombin are estimated to be 20% to 40% of normal for major surgery or trauma, but 10% to 15% may be adequate for milder hemostatic challenges. The half-life of prothrombin is about 3 days, and dosing every 2 to 3 days can maintain adequate levels until healing is complete. Alternatively, one-fourth of the loading dose each day should keep the level therapeutic. Dental procedures or minor hemorrhage may respond to antifibrinolytic therapy with -amino caproic acid. Because of the long half-life, additional doses may not be required in all situations. Treatment of acquired prothrombin deficiency associated with lupus anticoagulants requires immunosuppression, most commonly with steroids. This is effective in most patients, although many relapse during weaning or after stopping treatment. Subsequent treatment with azathioprine or cyclophosphamide has successfully eradicated the antibody. Rituximab has also been reported to be effective, and we have observed this in our own practice. In a rare case of quinidineinduced lupus anticoagulant with concomitant antiprothrombin antibody, cessation of the drug led to spontaneous resolution of acquired prothrombin deficiency, but not the lupus anticoagulant. The low prothrombin activity in these patients may protect them from thrombosis, as reports of thrombosis after successful eradication of the antiprothrombin antibody suggest. At the same time, Owren noted that a patient with a lifelong bleeding problem lacked a factor normally found in plasma that, in contrast to prothrombin, did not adsorb onto aluminum hydroxide. Severe congenital factor V deficiency has been estimated to occur in 1 in 1 million persons (see Table 139-1). Factor V is the 330,000-Dalton precursor of the cofactor factor Va, which facilitates prothrombin activation by factor Xa on phospholipid surfaces. Severe factor V deficiency is an autosomal recessive trait with plasma factor V activity of 1% to 10% of normal. Nonsense and frameshift mutations are distributed throughout the gene, whereas missense mutations cluster in the A2 and C2 domains. Most (80%) of the factor V in blood is in plasma, with the remainder stored in a partially activated form in platelet -granules. After being taken up from the plasma, factor V is modified by platelets so that it is more procoagulant than plasma factor V.
Cesarean delivery has multiple indications and is the most common operation performed in the United States medicine xifaxan purchase amoxicillin 650mg otc. Because the most common indication for cesarean delivery is a prior cesarean delivery medicine organizer box purchase 500mg amoxicillin amex, attempts should be made to achieve vaginal delivery in the first pregnancy symptoms concussion generic 250mg amoxicillin free shipping. Epidurals are commonly used during labor ombrello glass treatment order discount amoxicillin on line, whereas spinals are used more often for cesarean section. Epidural anesthesia leads to a longer second stage of labor, but offers better control during crowning. She pushes the head to the perineum and you deliver the head and shoulders without complication. You determine her membranes have ruptured and admit her for active management of labor. Which of the following presentations and positions would be most favorable to achieve a vaginal delivery The patient dilates without difficulty to 10 cm and the second stage of labor begins. She is pushing effectively, but during contractions you notice decelerations on fetal heart tracings. Absence of decelerations Vignette 2 A 26-year-old G2P2001 woman at 40 weeks and 2 days is seen in clinic for prenatal care. She is experiencing occasional contractions and has a sense of pressure in her vagina, but does not feel like she is in labor (as she experienced in her first delivery). Her first child was born at 41 weeks following an induction, resulting in a normal spontaneous vaginal delivery. Which of the following cervical examinations is the most favorable for induction of labor For women undergoing induction of labor with a Bishop score of 5 or less, which of the following is a commonly used first step Which of the following is not a contraindication to use of prostaglandins in labor induction Once the patient is in active labor and 6 cm dilated, you notice that on two subsequent examinations she is failing to make progress. Which of the following would be appropriate for evaluating the adequacy of contractions Stage 3 begins following the delivery of the infant and typically involves which of the following A delay of 60 minutes before the placenta is delivered Vignette 3 A 34-year-old G3P2002 woman at 38 weeks and 6 days was admitted to labor and delivery unit for active management of labor after it was determined that her membranes had ruptured and she was dilated to 3 cm. An episiotomy to hasten delivery Vignette 4 A 24-year-old G2P1001 woman at 39 weeks and 3 days is seen in clinic. She has been experiencing more frequent contractions and thinks she might be in labor. Earlier in the course of her current pregnancy she had desired a scheduled repeat cesarean, but now that she might be in labor she would like to try and delivery vaginally. After counseling and consent, the patient agrees to a trial of labor and after dilating to 10 cm, she begins to push. After 1 hour of pushing, the fetal heart tracing has absent variability and a baseline that has risen to the 180 beats per minute. Vignette 2 Question 2 Answer C: A Bishop score of 5 or less may lead to a failed induction as often as 50% of the time. Vignette 2 Question 3 Answer E: There are both maternal and obstetric contraindications for the use of prostaglandins. Maternal reasons include asthma and glaucoma, whereas obstetric reasons include having had a prior cesarean section and nonreassuring fetal testing. All of these are relative contraindications that allow individual clinicians to decide depending on the specific clinical situation. Abdominal ultrasound and speculum examinations are not used to assess adequacy of contractions. Vignette 3 Question 1 Answer E: A variety of relaxation techniques, including the Lamaze method, have been developed to ease the pain of labor. She is in active labor now that she has dilated past 4 cm and is therefore eligible for an epidural. Narcotics should not be used close to the time of delivery, as they may lead to decreased respiratory drive in the infant. General anesthesia is only rarely used in emergent situations for cesarean deliveries. Vignette 3 Question 2 Answer D: the correct order of the cardinal movements of labor is engagement, descent, flexion, internal rotation, and external rotation. Episiotomy is used to hasten delivery particularly in the case of impending or ongoing shoulder dystocia. If tests are equivocal, an ultrasound examination can evaluate the amount of fluid around the fetus. The tampon tests is used in situations where accurate diagnosis is necessary and involves using amniocentesis to inject dilute indigo carmine dye and looking for leaking of the blue fluid from the cervix onto a tampon. Vignette 1 Question 2 Answer A: the first stage of labor includes an active and latent phase. Braxton Hicks are irregular contractions that do not result in cervical change, which is common in the third trimester of pregnancy. Vignette 1 Question 3 Answer D: Fetal position in the vertex position depends on the relationship of the fetal occiput to the maternal pelvis.
In patients with large infarcts or in those with evidence of hemorrhagic transformation medications valium buy amoxicillin 500 mg fast delivery, progressing stroke treatment dry macular degeneration purchase amoxicillin now, or uncontrolled hypertension medications xr buy 250mg amoxicillin amex, initiation of warfarin should be delayed beyond 14 days medications 44 175 buy amoxicillin toronto. We stop aspirin once a therapeutic anticoagulant effect with warfarin is achieved, unless there is an indication for the combination of aspirin plus warfarin. Animal models of neuroplasticity suggest that training results in upregulation of growth-promoting factors primarily in the first 4 weeks after the stroke, but recovery can continue for months or years after stroke. Good outcomes from stroke rehabilitation are associated with high patient (and family) motivation and engagement. Substantial evidence supports well-coordinated multidisciplinary team care (nursing, physiotherapy, occupational therapy, speech therapy, dietetics, and social work) as the basis for delivery of stroke rehabilitation. For older patients with stroke, physical rehabilitation in long-term care facilities is effective and has been shown to improve independence. Chronic Secondary Prevention of Ischemic Stroke Case Study A 72-year-old man presented with right-sided weakness and expressive aphasia 4 weeks ago. He was admitted to a stroke unit, and after completing a rehabilitation program, he was discharged home. The combination of perindopril plus a diuretic produced greater reductions in blood pressure and larger risk reductions than therapy with perindopril alone. Lifestyle Modification Lifestyle modification remains a cornerstone of stroke prevention. These measures include smoking cessation, moderate physical activity, weight reduction in those who are overweight or obese, a hearthealthy diet with increased fruit and vegetable intake, reduced salt intake in those who consume high-salt diets, and moderate alcohol consumption. In a large cohort study that included 10,399 patients hospitalized with stroke in the United States, the 1- and 4-year mortality rates were 24. In that study, and in others, mortality was higher in patients with intracerebral or subarachnoid hemorrhage. Early causes of death are usually neurologic in origin (cerebral edema, raised intracranial pressure) or medical complications of dependence. In addition, patients with stroke are at increased risk for myocardial infarction, hip fracture, pneumonia, and repeated hospital admission. Other common chronic complications of stroke include seizure disorders, cognitive impairment and dementia, depression, and chronic pain syndromes. In addition, a number of large ongoing epidemiologic collaborative studies (International Stroke Genetics Consortium) will clarify the role of genetics in the pathogenesis of stroke. Population-based interventions to reduce the burden of stroke will be an important focus of future research and will include interventions to reduce excess salt intake and the use of combination cardioprotective therapies. Other ongoing trials will determine the role of acute interventions designed to reduce the severity of stroke. Antithrombotic drugs are also used to prevent thrombus formation on catheters and stents and to prevent and treat left ventricular thrombus formation. Instead, they develop infarction as a consequence of distal embolization of thrombus. Lipid accumulation and the recruitment of macrophages, smooth muscle cells, and fibroblasts to the site of injury results in the formation of increasingly complex and unstable plaques with a necrotic core and fibrous cap. Disruption of the fibrous cap by shear forces and its degradation by enzymatic and cellular processes expose the plaque contents to the blood. Platelets adhere to exposed subendothelial proteins and become activated and aggregate. Exposed tissue factor promotes thrombin generation on cellular surfaces, further promoting the formation of a platelet-fibrin thrombus that can occlude coronary blood flow. The clinical manifestations of coronary atherothrombosis are influenced by the extent and duration of obstruction to blood flow and the presence or absence of a collateral circulation. Patients with minor plaques that do not significantly impair blood flow generally remain asymptomatic. If myocardial ischemia results in ventricular fibrillation, sudden cardiac death supervenes. Plasmin degrades fibrin resulting in clot lysis and recanalization of thrombotic occlusion. Restoration of coronary blood flow limits infarct size and improves myocardial function and survival. Streptokinase was the first agent to be evaluated in large-scale randomized controlled trials. Reteplase and tenecteplase have longer half-lives than alteplase, enabling them to be given by double- or single-bolus injection, respectively, which simplifies administration. Fibrinolytic drugs were evaluated on a background of aspirin, but the addition of clopidogrel to aspirin was subsequently shown to provide incremental benefit. High-risk patients include those with large or anterior myocardial infarction, atrial fibrillation, known left ventricular thrombus, or previous thromboembolism. Consequently, these agents produce a less marked systemic lytic state than streptokinase, which has no fibrin affinity. Avoidance of a systemic lytic state is an important potential advantage of fibrinspecific drugs because this can be expected to be associated with a lower risk of bleeding complications. Streptokinase Streptokinase is a single-chain polypeptide derived from -hemolytic streptococcus cultures. Because plasmin nonspecifically degrades circulating fibrinogen as well as fibrin, streptokinase induces a systemic lytic state. Streptokinase induces the formation of antistreptokinase antibodies and can cause allergic reactions, particularly with repeated administration. Severe reactions are rare, but rash, shivering, pyrexia, and mild hypotension occur in up to 10% of patients.
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