阿加曲班对下肢动脉硬化闭塞合并血栓形成老年患者的疗效及对凝血功能的影响

目的 探讨阿加曲班对下肢动脉硬化闭塞合并急性血栓形成的老年患者的治疗效果以及治疗过程中对凝血功能的影响。方法 回顾性选取2018年5月—2021年10月民航总医院收治的下肢动脉硬化闭塞合并急性血栓形成的年龄≥65岁的老年患者67例,随机分为对照组（n＝33）和试验组（n＝34）,对照组采用那屈肝素钙注射液（每次4 100 U,每12小时给药1次）抗凝,试验组采用阿加曲班注射液（20 mg加入到160 mL 0.9%氯化钠注射液中,泵速20 mL·h⁻¹,每天2次,2次之间间隔2 h）抗凝,两组患者均连续治疗7 d。比较两组患者治疗效果、凝血功能指标变化及治疗过程中并发症及不良反应发生的情况。结果 治疗后,对照组总有效率为78.79%;试验组总有效率为82.35%,两组总有效率比较,差异无统计学意义（P＞0.05）。与治疗前相比,治疗后两组患者D-二聚体、纤维蛋白原（FBG）、血小板计数（PLT）水平均显著降低（P＜0.05）,活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）明显延长（P＜0.05）,血浆黏度及红细胞比积均显著降低（P＜0.05）;治疗第3天试验组D-二聚体水平显著低于对照组（P＜0.05）;治疗后试验组FBG、血浆黏度、红细胞比积水平降低程度,APTT、PT延长程度与对照组比较差异无统计学意义（P＞0.05）。试验组不良反应发生率显著低于对照组（P＜0.05）。结论 阿加曲班治疗下肢动脉硬化闭塞合并急性血栓形成的老年患者临床疗效显著,对患者D-二聚体、FBG、APTT、PT指标改善有积极作用,并可调节血液流变学状态,安全性高。     

Management of heparin-induced thrombocytopenia

Background: Heparin-induced thrombocytopenia (HIT) is a rare but severe prothrombotic adverse effect of heparin treatment. The underlying cause is the formation of highly immunogenic complexes between negatively charged heparin and positively charged platelet factor 4 (PF4). Resulting antibodies against these PF4/heparin complexes can activate platelets via the platelet FcγIIa receptor, leading to thrombin generation and thus to the paradox of a prothrombotic state despite thrombocytopenia and application of heparin. Prompt diagnosis of HIT is important in order to change treatment to prevent severe thromboembolic complications. However, this is often difficult as thrombocytopenia is frequent in hospitalized patients and the commercially available laboratory tests for HIT antibodies have a high negative predictive value but only a poor positive predictive value. This leads to overdiagnosis and overtreatment of HIT, which also bear the risk for adverse outcomes.

Areas covered: This review aims at resuming recent data on HIT, thereby focusing on the role of new anticoagulants and providing a framework for diagnosis and treatment. Furthermore, it provides some insights into the pathogenesis of this peculiar adverse drug reaction and ventures a guess at its future relevance in clinical practice.

Expert opinion: New drugs which are strongly negatively charged should be assessed for their capacity to form complexes with PF4. If they do so, they bear the risk of inducing a HIT-like immune response. The immunology of HIT is still largely unresolved. Understanding HIT might provide insights into other immune and autoimmune response mechanisms.     

Advances in thrombolytic therapy

Summary Alteplase and saruplase are more fibrin-specific thrombolytic drugs than anistreplase. These and the thrombolytic drugs of the first generation (streptokinase and urokinase) have shortcomings and limitations. The prolonged intravenous maintenance infusions have been replaced by a bolus injection, accelerated infusions, or the combined intravenous administration of thrombolytic agents. Numerous truncated alteplase or saruplase molecules have been constructed by deletion and domain substitution or hybrids made of the two molecules without gaining in thrombolytic potency. Recombinant staphylokinase and plasminogen activator from bat saliva have some interesting properties and are being investigated. Thrombus-targeted thrombolytic drugs were constructed using monoclonal antibodies against fibrin fragments or against epitopes of activated platelets. Fibrin-specific thrombolytic drugs require the concomitant use of a potent antithrombotic drug to prevent reocclusion. Whether hirudin or synthetic thrombin inhibitors are superior to heparin and whether novel antiplatelet agents, including monoclonal antibodies to platelet receptors and disintegrins, are more effective than aspirin is under clinical investigation. The place of stable analogues of prostacyclin during thrombolytic treatment is still unsettled.     

阿加曲班治疗急性脑梗死的临床研究

目的观察阿加曲班治疗急性脑梗死患者的有效性和安全性.方法将98例轻中型急性脑梗死患者随机分为阿加曲班治疗组与对照组.对照组给予抗血小板、改善微循环、神经保护、他汀类药物调脂稳定斑块及支持对症治疗方案;治疗组在此基础上应用阿加曲班注射液.结果治疗组治疗后患者NIHSS评分较对照组明显下降(P<0.05);治疗组临床疗效明显优于对照组(91.6% vs 78.0%).结论阿加曲班可作为急性脑梗死早期安全、有效的治疗药物.     

Clinical experience with argatroban for heparin-induced thrombocytopenia in a large teaching hospital

Background:

Argatroban is a direct thrombin inhibitor approved for the prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT). The product monograph does not guide clinicians beyond specifying the initial dose of 2 μg/kg per minute (or 0.5 μg/kg per minute for patients with hepatic impairment). Some authors have suggested that in the intensive care unit (ICU) and for patients with acute cardiac disease and those with renal or hepatic dysfunction, this dose may result in a supratherapeutic activated partial thromboplastin time (aPTT).

Objectives:

To evaluate the efficacy and safety of argatroban in adult patients with suspected HIT in a large teaching hospital, and to review dosing for patients in the ICU, patients with acute cardiac disease, and patients with renal or hepatic dysfunction.

Methods:

Charts of patients with suspected HIT who had received argatroban for at least 24 h between October 1, 2005, and October 1, 2007, at the Foothills Medical Centre, Calgary, Alberta, were examined retrospectively.

Results:

Thirty patients met the inclusion criteria, with charts available for review. Of these, 21 (70%) patients had an initial argatroban dose of 2 μg/kg per minute and 4 (13%) had an initial dose of 0.5 μg/kg per minute. The median duration of therapy was 6 days, and the mean dose was 2.14 μg/kg per minute. There were 122 dosage adjustments, the most common change being 0.5 μg/kg per minute, followed by adjustments of 1 and 0.1 μg/kg per minute. Six patients had supratherapeutic aPTT values (above 100 s), and none experienced major bleeding.

Conclusions:

The results of this study suggest that an initial argatroban dose of 2 μg/kg per minute is appropriate for patients with no hepatic dysfunction. Patients with acute cardiac disease and critically ill patients may require lower doses of argatroban; however no dosage adjustments are required for patients with renal dysfunction.     

阿加曲班治疗急性脑梗死的有效性和安全性研究

目的：评价国产阿加曲班注射液治疗急性脑梗死的有效性及安全性.方法：观察急性脑梗死患者48例,采用随机、双盲、双模拟、阳性对照研究.将急性脑梗死患者随机分为阿加曲班注射液组和奥扎格雷钠组,分别用两种药物治疗,用药14 d,总观察时间为28 d.主要疗效指标采用MESSS评估;次要指标采用ADL评估.结果：（1）阿加曲班组患者治疗后第14天和第28天的主要疗效指标MESSS评分明显低于治疗前（P＜0.05或P＜0.01）;阿加曲班组的次要疗效指标ADL评分也低于治疗前（P＜0.01）,而奥扎格雷钠组的次要疗效指标与治疗前差异无统计学意义（P＞0.05）.（2）阿加曲班组治疗有效率为91.67%,奥扎格雷钠组有效率为87.50%,两组间比较差异无统计学意义（P＞0.05）.结果显示两种药物治疗急性脑梗死患者均有较好疗效;阿加曲班组疗效优于奥扎格雷钠组.患者在用药后未出现严重出血反应,无一例因不良事件停药.结论：国产阿加曲班注射液对急性脑梗死有肯定的疗效,对人体无明显的不良反应,是治疗急性脑梗死的安全、有效的药物.     

Cardiopulmonary bypass using argatroban as an anticoagulant for a 6.0-kg pediatric patient

A patient was born with transposition of the great arteries, double-outlet right ventricle, interrupted aortic arch, and a ventricular septal defect and underwent a Damus-Kaye-Stansel procedure with a modified Blalock-Taussig shunt at 14 days old. Three months later, this patient presented with hypoxia and bradycardia was found to have a thrombus present in the main pulmonary artery extending to right pulmonary artery. After initiation of thrombolytic therapy, the patient became severely hypoxic and required the institution of extracorporeal membrane oxygenation. As the result of unknown heparin resistance independent of adequate antithrombin III levels, argatroban therapy was used to achieve desired anticoagulation. The patient was taken to the operating room and converted to conventional cardiopulmonary bypass once adequate activated clotting times were achieved using argatroban. This case report summarizes the use of argatroban as an anticoagulant for a 6.0-kg pediatric patient undergoing cardiopulmonary bypass.     

Obstinate thrombosis during percutaneous coronary intervention in a case with heparin-induced thrombocytopenia with thrombosis syndrome successfully treated by argatroban anticoagulant therapy.

We describe a case of massive coronary thrombus after the coronary stenting due to heparin-induced thrombocytopenia with thrombosis syndrome (HITTS). Only argatroban was able to resolve the thrombus. This is the first case in which argatroban successfully treated massive thrombus during percutaneous coronary intervention in a patient with HITTS.     

Effect of argatroban on trinitrobenzene sulfonic acid-induced colitis

BACKGROUND: Recent studies have suggested that heparin is effective for treatment of inflammatory bowel disease (IBD) and its various effects (in addition to the anticoagulant effect). We evaluated the effects of argatroban as an antithrombin drug on trinitrobenzene sulfonic acid (TNB)-induced colitis, an established model of IBD. METHODS: Rats were randomly assigned to four groups in which mini-osmotic pumps containing saline (TNB-S), argatroban (TNB-A), or 100 U/kg heparin (TNB-H) were intraperitoneally implanted. Three days after the pumps were implanted, TNB was infused via the anus, and colitis was induced. After 5 days, prothrombin time (PT), activated partial prothrombin time (APTT), antithrombin III (AT-III), platelet, fibrinogen, colonic wet weight, macroscopic damage score, histological score, mucosal myeloperoxidase activity and mucosal leukotrien B4 (LTB4) levels were compared among the four groups. RESULTS: The APTT was prolonged in the heparin treatment group but only slightly prolonged in the argatroban treatment group. The platelet count and the fibrinogen level were higher in the TNB-S group than in the healthy control group and the AT-III level was slightly lower in the TNB-S group than in the healthy control group and lower still in the TNB-H group. CONCLUSIONS: The colonic wet weight was similar among the four groups while the macroscopic damage score, histological score, mucosal myeloperoxidase activity and the mucosal LTB4 level were significantly decreased in the TNB-A and TNB-H groups. Argatroban, as well as heparin may be effective for treatment of TNB-induced colitis.     

Efficacy and safety of argatroban in patients with heparin induced thrombocytopenia undergoing endovascular intervention for peripheral arterial disease

Objectives: This study aimed to evaluate the efficacy and safety of argatroban during percutaneous interventions for peripheral arterial disease (PAD). Background: Endovascular interventions are commonly used in patients with peripheral arterial disease. Heparin is routinely administered during these procedures, but cannot be used in patients with a history of heparin‐induced thrombocytopenia (HIT). Argatroban is an approved direct thrombin inhibitor for treatment of patients with HIT. There are currently few data on the efficacy and safety of argatroban during endovascular interventions for PAD. Methods: Patients who underwent endovascular interventions for PAD on argatroban between 2002 and 2005 were identified from out database. Efficacy was evaluated using a composite of death, urgent revascularization, and amputation, while safety was assessed by TIMI major bleeding during the index hospitalization. Results: A total of 48 patients undergoing lower extremity revascularization on argatroban were identified. Thirty two of these patients (67%) had antibody‐confirmed HIT and the other 16 (33%) had suspected HIT. A mean dose of argatroban was 173.5 ± 143 μg/kg bolus, followed by a 10.7 ± 9.64 μg/kg/min infusion during the procedure. Twelve patients (25%) met the composite end point (two deaths, one urgent revascularization, nine amputations because of progressive peripheral arterial disease). TIMI major bleeding occurred in three (6%) patients. Conclusion: In patients with confirmed or suspected HIT undergoing endovascular intervention for PAD, argatroban appears to be effective and safe. A larger study is warranted to confirm these findings from a single center. © 2008 Wiley‐Liss, Inc.