The relationship between anticardiolipin antibodies and vascular access occlusion in patients on hemodialysis

Vascular access occlusion is frequently seen in some patients on hemodialysis. There are different opinions about pathogenesis of recurrent access thrombosis. Anticardiolipin (aCL) antibodies have been suggested to be involved in thrombosis and can be found in a high proportion of patients with chronic renal failure. We investigated the relationship between vascular access occlusion and the level of aCL antibodies in hemodialysis patients. We measured serum IgG and IgM aCL antibodies and protein C levels in 50 patients on hemodialysis having no fistule thrombosis (group 1), in 33 patients on hemodialysis with fistule thrombosis (group 2), and 20 nondialyzed patients with chronic renal failure (group 3). There were no differences in age and duration on hemodialysis (p > 0.05). No significant correlation was found between protein C and platelet counts in all groups (p > 0.05). In group 1, aCL IgG and IgM were 2%. In group 2, aCL IgG and IgM were 6.06% and 0%, respectively. In group 3, aCL IgG and IgM were negative. We did not find any significant difference between aCL IgG and IgM in all groups (p > 0.05). No association was found between aCL antibodies and vascular access thrombosis in our patients on hemodialysis.     

急性下肢动脉缺血程度分级相关因素探讨

目的探讨影响急性下肢动脉缺血分级的相关因素。方法回顾性分析笔者2005年5月至2010年6月收治的73例经造影证实为急性下肢动脉栓塞或急性下肢动脉血栓形成的患者,其中男性40例,女性33例;年龄35~90岁,平均年龄68.5岁。采集临床相关资料,对性别、年龄、缺血时间、吸烟史、其他合并症、肢体动脉栓塞史、梗阻原因(栓塞/血栓形成)等可能影响急性缺血分级的因素,使用SPSS 11.5软件进行多因素逻辑回归分析。结果该组患者73例,79条患肢,急性缺血分级:Ⅰ级2例(3条患肢);Ⅱ级65例,其中Ⅱa级32例(34条患肢),Ⅱb级33例(36条患肢);Ⅲ级6例(6条患肢)。缺血时间、糖尿病及梗阻性质可影响患者缺血程度(P<0.05)。随着缺血时间的延长,缺血程度逐渐加重;糖尿病患者下肢缺血程度倾向于Ⅱa级以下;急性动脉血栓形成缺血程度倾向于Ⅱa级,急性动脉栓塞缺血程度更趋向于Ⅱb级。结论缺血时间、糖尿病及梗阻性质与急性肢体缺血分级有相关性。     

Prevention of thrombosis in patients on hemodialysis by low-dose aspirin.

Since platelet cyclo-oxygenase is much more sensitive to inactivation by aspirin than is the enzyme in the arterial wall and low doses of aspirin may prevent thrombosis by blocking thromboxane synthesis, we conducted a randomized, double-blind trial of aspirin (160 mg per day) vs. placebo in 44 patients on chronic hemodialysis. The study was continued until there were 24 patients with thrombi and both groups had been under observation for a mean of nearly five months. Thrombi occurred in 18 of 25 (72 per cent) of patients given placebo and 16 of 19 (32 per cent) of those given aspirin (P less than 0.01). The incidence of thrombosis was reduced from 0.46 thrombi per patient month in the placebo group to 0.16 thrombi per patient month in the aspirin group (p less than 0.005). A dose of 160 mg of aspirin per day is an effective, nontoxic antithrombotic regimen in patients on hemodialysis.     

Cerebral infarction leading to hemiplegia: A rare complication of acute pancreatitis

Peripancreatic vascular thrombosis is a known complication of acute pancreatitis (AP) and chronic pancreatitis. However, hemiplegia resulting from cerebral infarction due to cerebral arterial thrombosis is a rare complication of AP. Here, we report a case of alcohol related severe AP with multi-organ dysfunction, which was complicated by large left sided middle cerebral artery territory infarct - leading to right sided hemiplegia in a 48-year-old male patient. The neurological and vascular thrombotic complications of pancreatitis, their pathogenesis and management are discussed in brief.     

Argatroban in HIT type II and acute coronary syndrome

Prior to initiation of the ARG-911 and ARG-915 clinical trials, there was no optimal replacement for heparin anticoagulation in patients with heparin-induced thrombocytopenia (HIT) type II. These prospective, historical controlled studies were designed to determine the usefulness of argatroban, a direct thrombin inhibitor (DTI) that is not immunogenic and does not interact with heparin antibody, in answering this clinical need. Clinical outcomes (37-day period) for 568 argatroban-treated and 193 control patients demonstrated significantly reduced risks of the primary efficacy composite endpoint (all-cause death, all-cause amputation, new thrombosis) and the secondary endpoints (death due to thrombosis, new thrombosis) with argatroban. Argatroban patients also experienced a more rapid recovery of platelet count. Bleeding events were similar among both groups. It was concluded that argatroban anticoagulation, compared with historical controls, improves clinical outcomes without increasing bleeding risk in patients having HIT with or without thrombosis. Argatroban has since been approved in the US for both prophylaxis and treatment of thrombosis in patients with HIT. Argatroban has been used in percutaneous coronary interventions in patients with and without HIT, for peripheral vascular procedures in both large and small vessels in HIT patients, and as an adjunct to thrombolytic therapy for the treatment of AMI. Treatment success rates and the same or less bleeding was demonstrated with argatroban compared to heparin controls. These pilot studies suggest that argatroban will provide reliable anticoagulation during interventional procedures. A consistent safety profile of argatroban has been demonstrated in all studies to date. The main attributes of argatroban are its rapid onset of action, fast reversibility of its anticoagulant effect, inhibition of clot-bound thrombin, easily monitored by the aPTT and ACT and no dosage adjustment in renal-impaired individuals. These properties make argatroban a predictable and useful anticoagulant for HIT and non-HIT patients.     

Large-vessel occlusion in sickle cell disease: pathogenesis, clinical consequences, and therapeutic implications

Much of the morbidity and mortality in sickle cell disease (SCD) is caused by tissue ischemia and infarction resulting from vascular occlusion. Research in this area has been dominated by the hypothesis that vascular occlusion in SCD is due primarily to microvascular obstruction by sickle erythrocytes (SS RBC), yet there is no direct evidence that microvascular occlusion is responsible for any of the vasocclusive complications of SCD. In this paper an alternate hypothesis is proposed: that thrombotic occlusion of larger arteries and veins is an important factor in many of the vasocclusive complications of SCD. Large-vessel cerebral arterial disease (intimal hyperplasia with superimposed thrombosis) has clearly been established as the most important cause of stroke in SCD, and considerable evidence suggests that pulmonary arterial thrombosis/embolism is a major cause of pulmonary infarction and hypertension. The involvement of large-vessel thrombosis in painful crisis, aseptic necrosis of bone, priapism, leg ulcers, retinopathy, and miscarriage has not been adequately investigated. Large-vessel occlusion in SCD is probably a consequence of the abnormal adhesive and procoagulant properties of SS RBC, which produce endothelial damage, secondary intimal proliferation, and thrombosis. Techniques currently used to treat large-vessel occlusion in other disorders (antiplatelet and anticoagulant agents, thrombolytic therapy, angioplasty, endarterectomy, and vascular bypass surgery) should be considered in sickle cell subjects with large-vessel occlusion, especially in the cerebral vasculature.     

An overview of the direct thrombin inhibitor argatroban

Argatroban is a small molecule direct thrombin inhibitor. The main attributes of this synthetic drug are its rapid onset of anti-thrombin action, rapid reversibility of its anticoagulant effect, potent inhibition of clot-bound thrombin, absence of antibody formation and no need for initial dosage adjustment in patients with renal impairment. It is eliminated by hepatic metabolism. These properties make argatroban a predictable anticoagulant with intravenous use in a routine clinical setting. Argatroban is approved in the US and Canada for both prophylaxis and treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT); and it is approved in Japan and Korea for treatment of various thrombotic disorders. Argatroban has been shown in limited trials to provide reliable anticoagulation during percutaneous coronary interventions on HIT and non-HIT patients. Preliminary reports document the feasibility of using argatroban for anticoagulation during peripheral vascular interventions, hemodialysis and as adjunct to thrombolysis for treatment of myocardial infarction. Current recommendations for argatroban monitoring are to use the activated partial thromboplastin time for low doses and the activated clotting time for high doses. The ease of monitoring argatroban, its 'turn-on/turn-off' characteristic and its consistent safety profile provide the rationale to continue studies of argatroban as an anticoagulant in clinical settings.     

四肢动脉内血栓形成的动脉内溶栓治疗

目的 :探讨四肢动脉内血栓形成的动脉内溶栓治疗价值。方法 :2 8例四肢动脉内血栓形成者 ,按治疗方式分三组 :16例行单纯动脉内导管溶栓 (A组 ) ;7例急性血栓者行单纯超声溶栓 (B组 ) ;5例慢性血栓者行超声溶栓结合动脉内导管溶栓 (C组 )。结果 :2 8例肢体动脉阻塞均溶栓成功 ,无 1例产生并发症。A、B、C三组的平均溶栓时间分别为 6.4± 5 .9h、0 .9± 0 .3h和 8.4± 4.5h ,A组的溶栓时间明显长于B、C组 (P <0 .0 5 )。对于慢性血栓形成者 ,超声溶栓结合导管溶栓的疗效较单纯动脉内导管溶栓或单纯超声溶栓者好。超声溶栓还能加快溶栓进程。结论 :动脉内溶栓治疗是四肢动脉内血栓形成的安全有效的治疗方法     

Congenital thrombophilia caused by protein C deficiency

To clarify the prevalence of protein C deficiency in patients with cardiovascular problems, we identified 54 patients with protein C deficiency by screening approximately 26,800 patients. The observed prevalence of protein C deficiency was 1 in 500. From the results of genetic analysis of 67 Japanese families with protein C deficiency, the recurrent defects of Phe139Val, Arg169Trp, Val297Met, Met364Ile substitutions and a G8857 deletion were accounting 49% of Japanese families with protein C deficiency. The defects including Phe139Val and Met364Ile substitutions and a G8857 deletion were only found in Japanese subjects and seemed to be a founder effect. Protein C deficiency is associated with a predisposition to venous thrombosis. It is not clear whether the deficiency is involved in arterial occlusion. We identified 34 patients with protein C deficiency manifested 45 episodes of arterial occlusive disease. We compared the onset age of arterial occlusive disease between patients with protein C deficiency and a group of patients with normal protein C levels. We found the early onset of acute myocardial infarction and atherothrombotic cerebral infarction in patients with protein C deficiency. Thus, our study suggests that congenital protein C deficiency contributes to earlier onset of arterial occlusive diseases in Japanese subjects.     

慢性肾功能衰竭血液透析患者皮肤瘙痒原因及护理对策

目的 分析慢性肾功能衰竭血液透析患者皮肤瘙痒原因及护理对策。方法 选择2018年3月~2019年3月在我院进行血液透析合并皮肤瘙痒的56例慢性肾功能衰竭患者临床资料,分析皮肤瘙痒原因,并给予并发症针对性护理对策,观察临床治疗总有效率,比较护理前后瘙痒症状评分。结果 56例患者中34例为电解质代谢障碍,占60.71%;17例为氮质代谢产物刺激皮肤,占30.35%,5例为过敏反应,占8.92%;通过对症护理后,总有效率为91.07%;护理后瘙痒症状评分为（2.11±0.33）分,低于护理前的（3.77±0.18）分,差异有统计学意义（P＜0.05）。结论 皮肤瘙痒是慢性肾功能衰竭血液透析患者常见的并发症,主要与电解质代谢障碍、氮质代谢产物刺激皮肤以及过敏反应相关,临床给予针对性护理对策,治疗总有效率高,瘙痒症状明显减轻。     

Bilateral extensive cerebral infarction and mesenteric ischemia associated with segmental arterial mediolysis in two young women

Segmental arterial mediolysis (SAM) is a rare non-atherosclerotic non-inflammatory vascular disease that affects mainly muscular arteries of the splanchnic and cerebral territories. Reported herein are two cases of SAM in young women with fatal outcome. One of the patients had an atypical form of the disease, which primarily affected small intestinal submucosal and subserosal arteries, and resulted in acute mesenteric ischemia. The other had bilateral brain infarction with SAM of internal carotid arteries (ICA). Pathological examination of both cases did not reveal the cause of blood flow disturbance: large mesenteric branches of the former and ICA of the latter were free of either dissection or thrombosis; in addition, small intestinal arteries of the first patient did not show signs of vasculitis. These findings suggest that unusual pathways of arterial occlusion and dissection may occur in the context of SAM.     

Effect of hemoglobin vesicle,a cellular-type artificial oxygen carrier,on middle cerebral artery occlusion- and arachidonic acid-induced stroke models in rats

Hemoglobin vesicle (HbV), which is also called liposome-encapsulated hemoglobin, functions as a hemoglobin-based oxygen carrier and is expected to be utilized in emergency situations including hemorrhagic shock and several kinds of ischemic diseases. In the present study, we evaluated the efficacy of HbV for improving stroke-related symptoms induced by middle cerebral artery (MCA) occlusion/reperfusion and an intra-internal carotid arterial injection of arachidonic acid (AA) in rats. When HbV (10 mL/kg, i.v.) was administered to rats immediately after the MCA occlusion, it reduced the cerebral infarct volumes of the cortex and total of the cortex plus sub-cortex significantly as compared with saline as a vehicle. In AA-induced stroke model, HbV (10 mL/kg, i.v.) improved the motor dysfunction score and inhibited the increase in cerebral water content suggesting it could suppress cerebral edema. These results strongly suggest that HbV would provide a novel beneficial option for the treatment of stroke, especially acute ischemic stroke.     

DADLE对大鼠急性全脑缺血再灌注继发肺损伤的作用

 目的：通过建立大鼠急性全脑缺血再灌注模型,观察肺组织超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量及肺组织光镜、电镜病理变化,探讨δ阿片受体激动剂DADLE对急性肺损伤的保护作用。方法：SD大鼠30只随机分为假手术（sham）组、模型（I/R）组和DADLE处理组。采用改良的二血管阻断加低血压法建立全脑缺血再灌注模型。DADLE处理组（n=10）于再灌注前经左侧颈静脉注射DADLE 5 mg/kg,再灌注120 min后,取肺组织,光镜、电镜观察其病理学改变及检测肺组织SOD活性、MDA含量。右侧股动脉取血测定氧分压,计算氧合指数。结果：I/R组与 sham组比较,肺脏表现为肺泡间隔增宽,毛细血管扩张充血,肺胞腔内及血管周围中性粒细胞浸润,Ⅱ型上皮细胞表面微绒毛明显减少,肺胞腔及气管腔均有浆液渗出,大鼠肺组织SOD活性降低和MDA含量升高。DADLE处理组与I/R组比较肺脏充血减轻,肺组织损伤程度明显减轻,中性粒细胞浸润有所减少,SOD活性升高和MDA含量降低。DADLE处理组动脉血氧分压和氧合指数有升高趋势,与I/R组比较差异有统计学意义。结论：大鼠急性全脑缺血再灌注模型对肺有不同程度的损伤,DADLE可减轻急性肺损伤,对肺组织提供一定的保护作用。     

肾功能衰竭患者血透和抗凝治疗后血液高凝状态的变化

目的:检测肾透析患者纤维蛋白单体聚合速率(FMPV)、纤维蛋白原(Fbg)、D-二聚体(D-D)和血浆因子Ⅷ相关抗原(vWFAg)变化,评价速避凝(Fraxiparine)抗凝治疗后高凝状态的改变和意义。方法:用纤维蛋白单体聚合功能动力学方法和酶联免疫吸附法(ELISA)测定健康人和肾透析患者透析前、后及抗凝治疗后的FMPV、Fbg、D-D及vWFAg。结果:患者透析前、后血浆FMPV、Fbg、D-D及vWFAg水平显著增高(P<0.05或P<0.01),且透析后较透析前更高(P<0.05),抗凝治疗后FMPV较治疗前显著降低(P<0.05),D-D和vWFAg较治疗前显著升高(P<0.05)。结论:急、慢性肾功衰患者透析前、后和抗凝治疗后采用FMPV、Fbg、D-D及vWFAg等指标进行监测有重要临床应用价值。     

脑梗死相关蛋白与ACI患者脑血管狭窄程度的多因素分析

目的研究脑梗死相关蛋白在评估急性脑梗死（ACI）患者脑血管狭窄程度中的作用。方法选取2010—2012年在珠江医院因ACI住院的患者,选取脑动脉造影结果狭窄程度〉70％及闭塞者为试验组（n=29）,≤70％者及正常者为对照组（n=23）。检测所有患者外周血脑梗死相关蛋白含量。结果试验组患者超敏C反应蛋白（hs—CRP）、血栓前体蛋白（TpP）、脂蛋白α（Lpα）外周血中含量分别为（3．51±2．25）mg／L、（1797．08±162．35）μg／L、（363．81±218．34）mg／L,均较对照组明显升高,差异有统计学意义（P〈0．05）。D-二聚体（DDI）、纤维蛋白原（Fg）、血小板凝聚因子（vWF）的含量无明显变化。hs-CRP（P=0．029,OR=2．232）、TpP（P=0．032,OR=1．014）、Los（P=0．024,OR=1．009）与脑大动脉粥样硬化病变导致的脑血管狭窄程度相关,DDI（P=0．671）、Fg（P=O．248）、vWF（P=0．090）与脑血管的狭窄程度相关性不明显。高血压（P=0．029,OR=4．582）是脑血管狭窄的危险因素。结论hs—CRP、TpP、Lpα、高血压是脑大动脉粥样硬化病变导致的ACI患者脑血管重度狭窄的危险因素,血清中hs．CRP、TpP、Lpα含量升高同时伴有高血压的ACI患者脑血管重度狭窄的可能性增大。     

Inhibition of arterial baroreceptor reflex during coronary artery occlusion.

The sensitivity of baroreceptor reflex during myocardial ischemia induced by acute occlusion of left anterior descending coronary artery (LAD) was studied in anesthetized, artificially ventilated, and thoracotomized dogs. Occlusion of LAD attenuated the baroreflex mediated changes in heart rate (HR) in response to changes in arterial pressure (AP) in the animals with intact autonomic nervous system (ANS). The HR increased significantly with the time of occlusion of LAD in control (ANS) as well as in beta-blocked group, suggesting vagal inhibition. In atropinized and vagotomized animals, the HR remained unchanged following LAD occlusion. In control group, the sensitivity of baroreflex mediated tachycardia response to hypotension and bradycardia response to hypertension, after 4 h of LAD occlusion, was reduced. In beta-blocked animals, the tachycardia response after LAD occlusion was drastically reduced to almost zero. The peak sensitivity of baroreflex bradycardia response was reduced in atropinized and vagotomized animals while the peak sensitivity of baroreflex tachycardia response increased after vagotomy. In contrast, bradycardia response was increased after beta-blockade. These data indicate that acute LAD occlusion attenuates arterial baroreflex control of HR and reduction of baroreflex sensitivity is mediated by parasympathetic efferents.     

Distribution and features of infection with hepatitis viruses B and C during hemodialysis treatment

The prevalence of hepatitides B and C was evaluated in 140 patients treated by hemodialysis. Almost half of patients (48%) had acute hepatitis B which completely resolved. Acute hepatitis B was detected in 6% in the course of observation. In 6% chronic hepatitis B was diagnosed, and in 24% chronic hepatitis C. A combination of hepatitides B and C was diagnosed in 2% patients. Only 12% patients were not infected with hepatitis. Genotype 1b predominated in patients with HCV infection (73%); genotypes 1a, 21, and 3a were equally incident (9%). Replication of HBV and HCV in patients with uremia under conditions of hemodialysis was detected in 83 and 86% patients, respectively. Relationship between HBV and HCV infection and the duration of hemodialysis treatment was analyzed. The percentage of non-infected patients persistently decreased, and the time course of HBV and HCV infection was different. Infection with HBV after the beginning of hemodialysis occurred sooner (16.0 +/- 4.0 months) than with HCV (30.2 +/- 4.6 months, p < 0.04). The levels of SGPT and SGOT in patients with various manifestations of HBV and HCV infection treated by hemodialysis were followed up.     

Effects of estradiol and raloxifene on arterial thrombosis in ovariectomized mice

OBJECTIVE: The effects of estrogen and selective estrogen receptor modulators (eg, raloxifene) on arterial thrombosis are not well defined. This study assessed the manner and mechanism by which estrogen and raloxifene affect homeostatic pathways in ovariectomized mice after acute arterial injury. DESIGN: Female mice (3 weeks old) underwent ovariectomy or sham operation. Five days after surgery, mice were assigned to treatment with estradiol (5.3 nmol/kg), raloxifene (2.7 micromol/kg), or placebo (n = 10-12/group). The biological effects of both treatments were assessed by measurements of bone mass and the degree of uterine atrophy. After 4 months of therapy, carotid artery thrombosis was induced by photochemical injury, and the time to vascular occlusion was measured. RESULTS: Both treatments increased bone mineral density (4.1%-7.85%). Reversal of macroscopic uterine atrophy was observed only in estrogen-treated mice. Ovariectomized mice had a shorter time to occlusion compared with sham-operated mice (70.8 +/- 7.4 vs 103 +/- 11.3 min), suggesting accelerated thrombosis. Both estradiol and raloxifene significantly inhibited intra-arterial thrombosis in ovariectomized mice, prolonging the time to occlusion to 136.33 +/- 13.5 and 141.43 +/- 9.26 min, respectively. Cyclooxygenase-2 levels in the lung tissue were significantly increased by both raloxifene and estradiol with endothelial nitric oxide synthase expression being unaltered. Platelet adhesion (measured by surface coverage under a shear rate of 1,800 s for 2 min) was significantly reduced in ovariectomized animals, being 4.63% +/- 1.47%, 5.78% +/- 1.58%, and 10.04% +/- 1.33% for raloxifene, estradiol, and placebo, respectively. CONCLUSIONS: Ovariectomy amplifies thrombosis. We found that 4 months of treatment with both estradiol and raloxifene attenuates intravascular thrombosis. The antithrombotic effect was accompanied by increased expression of cyclooxygenase-2 and suppression of platelet surface adhesion.     

Clinical results with direct thrombin inhibitors

Direct thrombin inhibitors inactivate thrombin without the need for antithrombin and some inactivate not only thrombin but also fibrin-bound thrombin. Hirudin has been shown to be more effective than low-dose unfractionated heparin and low molecular weight heparin for the prevention of deep vein thrombosis in high-risk orthopaedic patients. Major studies are assessing the value of direct thrombin inhibitors in patients with acute coronary syndromes. Currently, argatroban is the drug of choice in patients with heparin-induced thrombocytopenia.     

Extracellular glutamate levels and neuropathology in cerebral white matter following repeated umbilical cord occlusion in the near term fetal sheep

Umbilical cord occlusion causes fetal hypoxemia which can result in brain injury including damage to cerebral white matter. Excessive glutamate release may be involved in the damage process. This study examined the relation between extracellular glutamate levels in the cerebral white matter of the ovine fetus during and after intermittent umbilical cord occlusion and the degree of resultant fetal brain injury. Fetal sheep underwent surgery for chronic catheterisation and implantation of an intra-cerebral microdialysis probe at 130 days of gestation (term approximately 147 days). Four days after surgery (day 1), seven fetuses were subjected to 5x2 min umbilical cord occlusions, and on the following day (day 2) they were subjected to either 4 or 5x4 min umbilical cord occlusions; seven fetuses served as controls. Microdialysis samples were collected before, during and after the umbilical cord occlusions to determine extracellular glutamate levels in the cerebral white matter. Fetal blood gas status was measured and the fetal electrocorticogram was recorded continuously. During the periods of umbilical cord occlusions on both days 1 and 2, fetal arterial oxygen saturation, arterial partial pressure of oxygen and arterial pH decreased (P<0.05) while arterial partial pressure of carbon dioxide increased (P<0.05). All fetuses showed episodes of isoelectric electrocortical activity during umbilical cord occlusions on both days 1 and 2. In fetuses with patent microdialysis probes there were marked increases of glutamate efflux in the cerebral white matter following umbilical cord occlusion. Fetal brains were removed at autopsy on day 5 and subjected to histological assessment. Brain damage was observed in all fetuses exposed to cord occlusion, particularly in the periventricular white matter, with the most extensive damage occurring in the fetuses with the greatest increases in glutamate levels. We conclude that, in the unanesthetised fetus in utero, glutamatergic processes are associated with umbilical cord occlusion-induced brain damage in the cerebral white matter.