Recent research on platelet-leukocyte aggregates and their role in the pathogenesis of Kawasaki disease / 中国当代儿科杂志

Activated platelets may interact with various types of leukocytes such as monocytes, neutrophils, dendritic cells, and lymphocytes, trigger intercellular signal transduction, and thus lead to thrombosis and synthesis of massive inflammatory mediators. Elevated levels of circulating platelet-leukocyte aggregates have been found in patients with thrombotic or inflammatory diseases. This article reviews the latest research on the formation, function, and detection methods of platelet-leukocyte aggregates and their role in the onset of Kawasaki disease, so as to provide new ideas for studying the pathogenesis of Kawasaki disease.

Study on related substances of TSD-1 — a novel P2Y12 receptor antagonist / 药学学报

For quantitative analysis of related substances in TSD-1 active pharmaceutical ingredient, structures of prepared impurities were confirmed by NMR and UHPLC-MS, and a high performance liquid chromatographic method was established to determine the related substances in TSD-1. The analytical column was an Agilent ZORBAX Eclipe XDB-C8 (250 mm × 4.6 mm, 5 µm). The mobile phase A was 50 mmol·L-1 ammonium acetate solution (adjusted pH to 5.8 with acetic acid) and the mobile phase B was acetonitrile. The whole run was carried out by gradient elution at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 240 nm and the column temperature was 30 ℃. The resolutions among peaks of TSD-1, impurity A, impurity B, TSD-D, and TSD-F were good. The calibration curves (n = 7) of TSD-1, impurity A, impurity B, TSD-D and TSD-F were linear in their respective weight ranges of 0.242-48.4 µg·mL-1 (r = 1.000 0), 0.244-9.75 µg·mL-1 (r = 0.999 9), 0.244-4.80 µg·mL-1 (r = 0.999 9), 0.254-1.02 µg·mL-1 (r = 0.999 9), and 0.247-0.987 µg·mL-1 (r = 0.999 9). The lower limits of quantitation were 0.244, 0.244, 0.254, and 0.247 µg·mL-1 for impurity A, impurity B, TSD-D, and TSD-F, respectively, and the average recovery of each impurity ranged from 99.08% to 103.00% with high accuracy. TSD-D and TSD-F were not detected in the three batches of TSD-1 active pharmaceutical ingredients, and impurity A and impurity B were not detected beyond the limit. The established HPLC method is simple, accurate, and suitable for determination of related substances of TSD-1, which can provide a valuable reference for the subsequent development of TSD-1.

Management of Antithrombotics before Endoscopy and Biopsy

Antithrombotics are increasingly used for the management and prevention of cardiovascular diseases, and endoscopists often have to decide whether to continue or stop these medications before endoscopy. The development of novel antithrombotics, such as direct oral anticoagulants, has complicated their management before endoscopy. Although the discontinuation of anticoagulants may decrease the incidence of bleeding after endoscopic procedures, discontinuation may also lead to more serious cardiovascular complications. Although the majority of current practice guidelines recommend continuation of antithrombotics before elective endoscopy and biopsy, surveys have shown that many endoscopists do not adhere to these guidelines, probably due to legal aspirations from post endoscopic bleeding. Thus, we examined the current guidelines for the management of antithrombotics before endoscopy.

NOAC for Patients with AF and ACS

Atrial fibrillation (AF) can occur in acute coronary syndrome (ACS), which is a serious medical condition and may require the use of antiplatelet agents in addition to anticoagulants for stroke prevention. Recently, novel or non-vitamin K antagonist oral anticoagulants (NOACs) have been increasingly used for stroke prevention in patients with AF instead of traditional OACs. The duration of treatment or treatment with a stepwise approach (e.g. triple, double, or monotherapy) is determined depending on the clinical setting and the balance between the risks of ischemic stroke and bleeding. However, some concerns and controversies in the use of NOACs in patients with AF and ACS need to be addressed. Here, the current management for NOAC therapy in patients with ACS and AF will be reviewed based on recently published guidelines.

Effects of Cerebral Microbleeds on the Incidence of Cerebral Events in Patients with Ischemic Cerebrovas-cular Disease at the Last Stage of Antiplatelet Agent / 中国药房

OBJECTIVE:To compare the incidence of cerebral events in patients with ischemic cerebrovascular disease compli-cating with cerebral microbleeds(CMBs)at the last stage of antiplatelet agent use. METHODS:140 patients with ischemic cerebro-vascular disease were selected from Beijing Anzhen Hospital Affilicated to Capital Medical University during Jan. 2013-Jan. 2014, and then divided into CMBs group and non-CMBs group according to whether complicated with CMBs,with 70 cases in each group. After followed up for 1 year(regular use of aspirin 100 mg/d and/or clopidogrel 75 mg/d),the incidence of recurrent cere-bral infarction and cerebral bleeding and mortality were compared. RESUTLS:The incidence of recurrent cerebral infarction was 12.9% in CMBs group and 8.6% in non-CMBs group,without statistical significance(P=0.412);the incidence of cerebral bleed-ing was 10.0% in CMBs group and 1.4% in non-CMBs group,with statistical significance(P=0.029);the mortality of cerebro-vascular event at the last stage was 5.7% in CMBs group and 4.3% in non-CMBs group,without statistical significance (P=0.698). CONCLUSIONS:The risk of cerebral bleeding increase in patients with ischemic cerebrovascular disease complicating with CMBs after the application of antiplatelet agent. For patients with ischemic cerebrovascular disease complicating with CMBs,the application of antiplatelet agent should be based on the complete judgment and weighing of benefit and bleeding risk.

Is Taking an Antiplatelet Agent a Contraindication for Early Surgery in Displaced Femur Neck Fracture? / 대한고관절학회지

PURPOSE: The purpose of this study was to evaluate whether we have to stop the antiplatelet agents prior to hemiarthroplasty surgery in patients with displaced femur neck fractures to reduce postoperative complications. MATERIALS AND METHODS: We enrolled forty-three patients with displaced femur neck fractures who were treated by bipolar hemiarthroplasty and were taking antiplatelet agents. Group I included 21 patients who discontinued antiplatelet agents and had delayed operations at an average 5.7 days and group II included 22 patients who had had early operations within 24 hours without stopping the antiplatelet agents. We compared the pre- and postoperative levels of hemoglobin, the volume of postoperative transfusion requirement and complications. Student's t-test and chi-square test were used for statistical analysis. RESULTS: The average differences between preoperative and postoperative hemoglobin was 1.4+/-0.4 g/dL decrease in group I and 2.1+/-0.5 g/dL decrease in group II (P<0.001). Patients who received a blood transfusion were 11 in group I and 13 in group II (P=0.66). Total number of blood transfusion was 13 pints in group I and 18 pints in group II (P=0.23). Pneumonia occurred in one patient in each group. Four pressure sores and three diaper rashes were developed in group I. But there were no patients requiring massive transfusion, reoperation due to hematoma and infection in each group. CONCLUSION: Although continuous taking of antiplatelet agents in displaced femur neck fracture is associated with an increased risk of postoperative bleeding, taking an antiplatelet agent itself is not a contraindication of early surgery.

Pharmacological Secondary Prevention of Ischemic Stroke

The causes of ischemic stroke are widely diverse, ranging from large artery atherosclerosis to cardioembolism, and it is important to use preventive therapy toward the goal reducing the future risk of recurrent ischemic stroke, myocardial infarction, and vascular death. Antithrombotic therapy is one of the fundamental medical approaches for secondary prevention of ischemic stroke, which is broadly divided into two general categories, those that exert their effect via platelet inhibition (antiplatelet agents), and those that influence various factors in the clotting cascade (anticoagulants). In general, the clinical guidelines recommend antiplatelet agents for patients with non-cardioembolic stroke, while anticoagulants is indicated for patients with presumed or proven cardioembolic stroke. Many clinical trials have attempted to test the efficacy and safety of antithrombotics in ischemic stroke. This review will discuss on currently available antithrombotic agents that have demonstrated efficacy for secondary prevention of ischemic stroke.

Predictors of Antiplatelet Treatment Failure in Noncardioembolic Stroke

BACKGROUND: The purpose of this study is to identify the differences of risk factors and stroke mechanism between early and late recurrence in patients with long-term antiplatelet therapy for stroke prevention. METHODS: We enrolled 114 consecutive patients with recurrent infarction who had been taking antiplatelet agents regularly since previous noncardioembolic cerebral infarction. Total 81 patients (49 men and 32 women) were met to the inclusion criteria through standardized evaluation. Subjects were classified into two groups depending on the time-to-recurrence after antiplatelet therapy: early antiplatelet failure (within 2 years, n=41, hereafter as "EAF") and later antiplatelet failure (after 2 years, n=40, hereafter as "LAF"). We investigated the differences of clinical factors between two groups using univariate and multivariate analysis. RESULTS: Family history of stroke (29.3% in EAF vs. 10% in LAF, p=0.029) was more frequent in EAF group. Low HDL-cholesterol and High total cholesterol/HDL-cholesterol ratio were associated with the LAF group (p=0.042, 0.005 respectively). Multivariate analysis showed that family history of stroke (OR=5.283, 95%CI 1.178-23.699, p=0.030) and previous infarction classified as large artery atherosclerosis (OR=8.497, 95%CI 1.444-50.015, p=0.018) were significant predictors for EAF whereas total cholesterol/HDL-cholesterol ratio (OR=2.002, 95%CI 1.183-3.389, p=0.010) was for LAF. CONCLUSIONS: This study suggests that family history of stroke and cerebral infarction due to large artery atherosclerosis are more responsible for the early recurrence while dyslipidemic condition is more related to the late recurrence during long-term antiplatelet therapy in patients with previous cerebral infarction.

Acute spontaneous spinal epidural hematoma: A report of two cases

A spontaneous spinal epidural hematoma (SSEH) is a rare disease that accompanies severe axial pain in the spine with various levels of paralysis depending on the location of the hematoma. A SSEH is mainly caused by a coagulating disorder or anticoagulants medication, while certain cases relate this disease with spinal inflammatory conditions. The early diagnosis of a SSEH is important for its treatment. Most cases with neurologic symptoms can be treated with an immediate laminectomy and decompression. If the neurologic symptom improves within 12 hours, a conservative treatment is effective; however few cases have been reported. We report this case with a review of the relevant literature.

Stroke Update 2011: New Antithrombotics / 대한뇌졸중학회지

Several new antithrombotic drugs have been developed and approved to use in clinical practice recently. Dabigatran, a direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor, have been approved in many countries including Korea to prevent stroke in patient with atrial fibrillation. Apixaban, another factor Xa inhibitor, showed good results in clinical trial and is waiting for approval for clinical use. New antiplatelet agent, terutroban, selective thromboxane A2 receptor inhibitor, failed to prove the efficacy over the aspirin in secondary stroke prevention. Vorapaxar, a new antiplatelet agent that inhibits thrombin through PAR-1 antagonism, showed a high incidence of intracranial hemorrhage in patient with a history of stroke.

Effect of Premedication Method and Drug Resistance of Antiplatelet Agent on Periprocedural Thromboembolic Events During Coil Embolization of an Unruptured Intracranial Aneurysm

OBJECTIVE: A retrospective review of premedication method and drug resistance of aspirin and clopidogrel in association with thromboembolic events during and after coil embolization of an unruptured intracranial aneurysm was conducted. METHODS: Our premedication policy for coil embolization of an unruptured intracranial aneurysm has changed from administration of the loading dose before the procedure (i.e. loading group) to repeated administration of the maintenance dose for several days (i.e. preparation group). The loading group (27 patients with 29 aneurysms) and the preparation group (30 patients with 35 aneurysms) were compared for identification of the effect of premedication method on periprocedural thromboembolic events. The results of drug response assays of the preparation group were analyzed with respect to periprocedural thromboembolic events. RESULTS: No statistically significant difference in incidence of thromboembolic events was observed between the loading group and the preparation group. Analysis of the results of the drug response assay showed high prevalence (56.7%, 73.3%) of clopidogrel resistance and relatively low prevalence (6.7%) of aspirin resistance. Patients who had thromboembolic events tended to have lower responsiveness to both aspirin and clopidogrel than patients without it. CONCLUSION: The method of antiplatelet premedication does not affect the rate of periprocedural thromboembolic events in coil embolization for treatment of an unruptured intracranial aneurysm. Nevertheless, considering the high prevalence of drug resistance, it is reasonable to premedicate antiplatelet agents in the preparation method for the drug response assay. Use of a higher dose of aspirin and clopidogrel or addition of an alternative drug (cilostazol or triflusal) can be applied against antiplatelet agent resistance. However, because the hemorrhagic risk associated with this supplementary use of antiplatelet agent has not been well-documented, the hemorrhagic risk and the preventive benefit must be weighed.

Traumatic Acute Subdural Hematoma Extending from the Posterior Cranial Fossa to the Cerebellopontine Angle

Posterior cranial fossa subdural hematomas and extension of the subdural hematoma to the cerebellopontine angle is rarely seen and the concurrent development of acute peripheral facial palsy and the management strategy have not previously been reported in this pathology because of its rarity. We present this case to emphasize that minor head trauma may lead to a posterior cranial fossa hematoma extending to the cerebellopontine angle and cause peripheral facial palsy in patients using aspirin (acetylsalicylic acid). In addition, partial evacuation and waiting for the resorption of the hematoma may help to prevent damage to the 7th and 8th cranial nerves.

Retrospective Study of Clinical Features and Courses of Raynaud's Phenomenon

PURPOSE: Raynaud's phenomenon is characterized by recurrent episodes of arterial vasospasm of the digits upon exposure to cold, and this can occur alone or in association with other underlying conditions. The aim of this study was to investigate the clinical course of Raynaud's phenomenon and the effects of treatment. METHOD: Between September 1994 and December 2004, 69 patients with Raynaud's phenomenon were retrospectively evaluated. The symptoms of the patients and the results of photoplethysmography were reviewed before and after medical treatment. RESULT: The mean age of the patients was 47.4 years and 33 patients (47.8%) were in their 30s and 40s. Thirty seven patients (53.6%) were male and 32 patients (46.4%) were female. Twelve patients (17.4%) had combined disease and the majority of the total patients (n=58, 84%) presented with bilateral lesions. After treating with aspirin, cilostazol, PGI2 and PGE1, the symptoms improved in 27 cases (39.1%) and the photoplethysmographic findings improved in 20 cases (45.5%). However, there was no association between the period of treatment and the clinical results or the results of performing photoplethysmography. CONCLUSION: The majority of patients with Raynauds phenomenon develop bilateral symptoms without the presence of any underlying diseases. Antiplatelet agents and vasodilator drugs can have a positive effect on the management of Raynaud's phenomenon.

Medical Treatment of Cerebral Infarction / 대한뇌혈관외과학회지

Anticoagulants and antiplatelet agents have been widely used and studied in both the management of acute stroke and for stroke prevention. The use of anticoagulants and antiplatelet agents in acute ischemic stroke is aimed at preventing stroke recurrence and reducing stroke progression. Studies examining unfractionated heparin following acute ischemic stroke failed to show an overall benefit. Reductions in thromboembolic events and progression of stroke were offset by an increased risk of major bleeding including intracerebral hemorrhage. Low molecular weight heparin compounds and hepanoids in acute ischemic stroke similarly have failed to prove overall benefit when bleeding complications, especially intracerebral hemorrhage, are considered along with reductions in thromboembolic complications. Ancrod, an agent capable of reducing circulating fibrinogen levels has been shown in clinical trials to improve outcome following stroke when administered within three ours of stroke onset. Antiplatelet agents have been evaluated in acute ischemic stroke. The largest studies have examined the role of aspirin therapy (IST, CAST). Studies have shown a small but statistically significant improvement in the aspirin-treated patients treated within 48 hours. Abciximab, a IIB/IIIA inhibitor, has been studied in acute ischemic stroke with an acceptable safety profile and encouraging findings of potential benefit. These studies have led to an ongoing trial of Abciximab (ReoPro) in acute ischemic stroke. Other ongoing clinical trials in acute ischemic stroke include studies of clopidogrel following TIA and unfractionated heparin in acute ischemic stroke. Antithrombotic agents are widely used for stroke prevention. Long-term oral anticoagulation has been proven of benefit in the prevention of stroke in high risk patients with atrial fibrillation. Two large clinical trials in high risk patients with atrial fibrillation have examined a direct thrombin inhibitor, Ximelagatran, compared to warfarin for stroke prevention. These studies have shown similar thromboembolic events with Ximelagatran comparable to warfarin. The risks of bleeding were reduced with Ximelagatran as compared to warfarin treatment. Ximelagatran does not require regular monitoring of coagulation or dose adjustments. There is an increased risk of liver enzyme abnormalities in some patient receiving Ximelagatran. Antiplatelet agents are the mainstay of antithrombotic therapy for secondary stroke prevention with four agents currently approved for use (aspirin, ticlopidine, clopidogrel, and extended release dipyridamole plus aspirin). A number of studies are underway examining the role of antiplatelet agents in combination or for additional indications. These studies include MATCH, CHARISMA, SPS3, ARCH, CARESS, PROFESS, and WASID.

Management of Acute Stroke

New insights in the pathophysiology of stroke have been developed in the past few years. The progress in this area has led the development of diagnostic devices and new treatments. No specific therapy has proven efficacious in treating acute ischemic stroke, because of major differences between animal models and human stroke, the heterogeneity of stroke pathogenesis, and the lack of consensus on stroke management in each subtypes of stroke. A good general management is an important factor for the better prognosis than specific therapy in different types of stroke. General management of stroke includes cardiac and pulmonary care, metabolic maintenance, blood pressure control, and prevention of bedsores and phlebitis. Thrombolytic therapy, anticoagulation and antiplatelet agent therapy are kinds of specific therapies in acute ischemic stroke. It has to be emphasized that patients be referred early. In animal studies, focal ischemic insult requires 3-4 hours to progress to cerebral infarction. Six hours after onset of stroke has been arbitrarily defined as the limit to initiate reperfusion on positron emission tomography in human. The entry of calcium into the cells via receptor-mediated membrane channels is an important factor in ischemic neuronal death. Oxygen free radical is an another factor in the ischemic damage. Calcium channel antagonists and scavengers of oxygen free radicals will have beneficial roles to prevent ischemic neuronal injury.