Single vs multivessel treatment during primary angioplasty: results of the multicentre randomised HEpacoat™ for cuLPrit or multivessel stenting for Acute Myocardial Infarction (HELP AMI) Study

DESIGN: Prospective randomized, multicentre study. RATIONALE: Recanalisation of the culprit lesion is the main goal of primary angioplasty for acute myocardial infarction. With the exception of cardiogenic shock, staged procedures are performed in the presence of multivessel disease. The study hypothesis is that with modern non-thrombogenic stents (heparin coated) complete revascularization with multivessel treatment can be safely achieved during the primary angioplasty procedure with a lower need of subsequent revascularization procedures and at a lower cost. ENDPOINTS: PRIMARY: 12-month incidence of repeat revascularization (any revascularization, infarct related artery as well as non-infarct-related artery). SECONDARY: (1) in hospital repeat revascularization, reinfarction and death; (2) total hospital cost (including a 12 months follow-up period). METHODS: 69 patients with ST elevation Acute Myocardial Infarction (AMI), <12 hours after symptoms onset, undergoing primary angioplasty, with documented multivessel disease and both culprit lesion and 1 to 3 other lesions suitable for stent implantation. Unbalanced randomization between culprit lesion treatment only ( n??=?17) and complete multivessel treatment (n?=?52, with 71 additional lesions treated).RESULTS: The two groups were well balanced in terms of clinical characteristics, number of diseased vessels and angiographic characteristics of the culprit lesion. In the complete multivessel treatment group 2.36?±?0.64 lesions per patient were treated using 2.73?±?0.78 heparin coated stents (1.00 lesions and 1.29?±?0.61 stents in the culprit treatment group, bothp?<?0.001). The duration of the procedure increased from 53?±?21?min (culprit treatment group) to 69?±?32?min (p?=?0.032) and the amount of contrast used from 242?±?102?ml (culprit treatment group) to 341?± 163?ml (multivessel complete treatment),p?=?0.025. A similar low incidence of in-hospital major adverse cardiac events was observed in the 2 groups (0 and 3.8% in culprit and multivessel treatment groups,p?=?0.164). The increase in the incidence of new revascularisation in the culprit treatment group at 12 month follow-up was not significant (35 vs 17%,p?=?0.247) but was sufficient to compensate the initial higher in-hospital cost, with a similar 12 month hospital cost in the 2 groups (€22 330?±?€13 653 vs €20 382?±?€11 671,p?=?0.231).CONCLUSION: Multivessel treatment during primary PTCA was safe in this controlled trial. However, when only the culprit lesion was initially treated, the need for subsequent clinically driven revascularization remained low and no clinical or economical advantages were obtainable with a more aggressive initial approach. In clinical practice, a staged approach to multivessel treatment during primary angioplasty avoids to treat unnecessarily non clinically relevant lesions. (Int J Cardiovasc Intervent 2004; 6: 128-133)     

Transcapillary escape rate and albuminuria in Type II diabetes. Effects of short-term treatment with low-molecular weight heparin (Short Communication)

Summary The relation between urinary albumin excretion rate (UAE), transcapillary escape rate of albumin (TER_alb), haemostatic factors, ambulatory blood pressure, and metabolic variables was investigated in 45 Type II (non-insulin-dependent) diabetic patients without overt nephropathy or uncontrolled blood pressure. We enrolled 44 patients in a placebo controlled study to test the effects of 3 week long treatment with low-molecular weight heparin (tinzaparin) on the same variables. BMI, 24 h systolic and diastolic blood pressure, plasma concentrations of triglycerides, fasting glucose, factor VIII, von Willebrand factor (vWf), fibrinogen, α-2 macroglobulin, and fibronectin were notably higher in patients with increased albuminuria compared with normoalbuminuric patients, whereas the TER_alb was similar in the two groups. TER_alb correlated with fasting plasma glucose. UAE correlated more closely than TER_alb with 24 h ambulatory blood pressure, vWf, and factor VIII. Urinary albumin excretion rate was unchanged during tinzaparin [28.9 ± 5.6 vs 28.1 ± 6.0 μg/min (geometric mean (antilog SD)] vs placebo (18.0 ± 5.4 vs 17.6 ± 5.3 μg/min), and no change was found in TER_alb [6.3 ± 1.6 vs 6.0 ± 1.5 %/h (means ± SD), and 6.3 ± 1.5 vs 5.6 ± 1.8 %/h; tinzaparin versus placebo, respectively]. Only minor changes were observed in blood pressure, lipids, glycaemic control and haemostatic factors. This study shows no correlation between albuminuria and transcapillary escape rate in Type II diabetic patients without overt nephropathy or uncontrolled blood pressure. UAE is related to markers of atherosclerosis, endothelial injury and dysfunction, and haemostatic factors. Moreover, UAE correlates much more than TER_alb with 24 h ambulatory blood pressure, von Willebrand factor, and factor VIII. Finally, short-term treatment with tinzaparin does not change the transvascular or glomerular leakage of albumin. These results indicate that TER_alb is not a sensitive marker of microvascular dysfunction in such patients and that factors other than abnormal glycosaminoglycan metabolism may contribute to the vascular damage of these patients. [Diabetalogia (1999) 42: 60–67] Received: 2 February 1998 and in final revised form: 1 September 1998     

探讨低分子肝素预防下肢静脉曲张术后深静脉血栓形成的临床效果

目的：分析低分子肝素预防下肢静脉曲张术后深静脉血栓形成的临床效果。方法随机选择2012年1月-2014年1月在该院行分段剥脱术+腔内激光闭合术+大隐静脉高位结扎的下肢静脉曲张患者400例,将其随机分成实验组和对照组各200例,对照组患者术后不给于抗凝药物,实验组患者术后给予低分子肝素进行预防治疗,对两组患者深静脉血栓形成和并发症发生情况进行对比分析。结果在浸透敷料出血、切口出血、血小板减少以及肝功能异常发生率方面,两组患者比较差异无统计学意义(P>0.05);实验组患者深静脉血栓形成发生率显著低于对照组患者,两者比较差异有统计学意义(P<0.05)。术后随访发现,两组患者在下肢静脉曲张复发率和隐神经损伤发生率方面比较差异无统计学意义(P>0.05)。结论在对下肢静脉曲张术后深静脉血栓形成进行预防时,低分子肝素具有比较好的临床效果,而且安全性高,应该进行临床推广和应用。     

血清肝素辅助因子II 活性与下肢动脉硬化闭塞症介入术后再狭窄相关

目的：观察血清肝素辅助因子II(heparin cofactor II,HC II)活性与下肢动脉硬化闭塞症介入术后再狭窄的 关系。方法：因股浅动脉闭塞性疾病而成功施行支架植入术的患者62例,根据患者血清HC II活性高低,将患者分为 两组：HC II活性≥100%组(n=40)及HC II活性<100%组(n=22)。收集患者相关临床资料,随访观察6个月,观察术后 支架内狭窄、闭塞情况。结果：两组患者基线资料比较差异无统计学意义(P>0.05)。随访至第6个月月末时,HC II活 性<100%组支架内再狭窄程度较HC II活性≥100%组严重(P<0.05)。HC II活性<100%组支架内再狭窄发生率较HC II活 性≥100%组高(P<0.05)。进一步对危险因素行多元回归分析,结果显示血清HC II活性升高是减少术后再狭窄发生的 独立因素(OR=0.982,P=0.048)。结论：血清HC II活性与下肢动脉硬化症介入术后再狭窄相关;HC II活性越低,术后 发生再狭窄的危险越大。     

肝素联合低分子肝素预防动静脉内瘘术后早期血栓形成

摘 要 目的： 研究肝素联合低分子肝素对预防动静脉内瘘（AVF）术后早期血栓形成的影响。方法: 采用前瞻性研究方法,将299例行AVF术的患者随机分为两组,对照组患者术后给予低分子肝素5 000 IU皮下注射qd×7 d;观察组术中在游离动脉端与静脉端分别推注1 500 u肝素钠,术后给予低分子肝素5 000 IU皮下注射qd×7 d。观察两组患者术后1周和4周AVF血栓形成率及药品不良反应（ADR）发生情况。结果: 术后1周,对照组和观察组的AVF血栓形成率分别为3.4%和0;术后4周分别为4.8%和0.67%,观察组均明显低于对照组（P<0.05）。两组ADR发生率差异无统计学意义（P>0.05）,未发生严重不良反应。结论: 肝素联合低分子肝素可降低AVF术后早期血栓形成率,提高手术成功率,安全性较好。     

Fraxiparin, a low-molecular-weight heparin, stimulates megakaryocytopoiesis in vitro and in vivo in mice

Summary. The effect of a low-molecular-weight heparin, faxiparin (Nadroparinŕ;), on murine megakaryocytopoiesis in vitro and in vivo was studied in comparison with unfractionated heparin. The addition of fraxiparin at 1–20 IU/ml into plasma clot cultures but not serum-free agar culture significantly enhanced MK colony growth. Furthermore, fraxiparin was found to potentiate the stimulating activity of aplastic anaemia serum (AAS) but not stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo), on MK colony growth in vitro , and to neutralize the inhibitory effect of platelet factor 4 (PF4) in vitro and in vivo . Fraxiparin also acted synergistically with heparin confactor II and antithrombin III to promote megakaryocyte colony formation. Intraperitoneal administration of fraxiparin twice daily for 4d at 0.1–25IU/injection increased in mice the level of blood platelet counts and the number of single MKs and CFU-MK in bone marrow. These data demonstrate that fraxiparin is able to positively regulate megakaryocytopoiesis.     

The mechanism of heparin-induced platelet aggregation

When heparin was added to platelet-rich plasma, mild but irreversible platelet aggregation was demonstrated. This platelet response was not accompanied by release of alpha-granules and dense body constituents, nor by prostaglandin biosynthesis. It did, however, require metabolic energy and divalent cations as metabolic inhibitors (anti-mycin A and 6-deoxyglucose) and EDTA blocked the reaction. Bernard-Soulier syndrome platelets, which lack glycoprotein (GP) Ib, but not Glanzmann's Thrombasthenia platelets, which lack GP IIb/IIIa, were aggregated by heparin. Monoclonal antibody (mAb) against GP IIb/IIIa, but not mAb against GP Ib, strongly inhibited the reaction. These combined results suggest the participation of GP IIb/IIIa but not GP Ib in heparin-induced platelet aggregation. Fibrinogen was a cofactor in the reaction as gel-filtered platelets were unreactive to heparin but addition of fibrinogen restored their reactivity. Antithrombin III and fibronectin inhibited platelet response to heparin, suggesting that these proteins may protect platelets from aggregation by heparin.     

Molecular actions of heparin and their implications in preventing pre‐eclampsia

Summary

Pre‐eclampsia, a hypertensive disorder of pregnancy, continues to be a significant cause of global maternal morbidity. Low‐dose aspirin remains the only standard‐of‐care prophylactic therapy for preventing pre‐eclampsia, but is limited in efficacy. Heparin and its derivatives may further enhance the efficacy of aspirin therapy to prevent pre‐eclampsia, but the mechanisms mediating this augmentative effect are not known. Although heparin is an anticoagulant agent, it also possesses many anticoagulant‐independent properties that may be relevant in the prevention of pre‐eclampsia, including effects on placental, vascular and inflammatory function. This review summarizes the non‐anticoagulant properties of heparin, and extrapolates how these actions may influence the trajectory of pre‐eclampsia pathogenesis as a means of pathway‐specific therapy.