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。     

Regular arrangement of collecting venules under endoscopy for predicting a Helicobacter pylori-negative stomach: A systematic review and meta-analysis

Background and aimsThe regular arrangement of collecting venules (RAC) refers to the appearance of multiple regular tiny veins in the body of the stomach and is considered to be very effective for identifying gastric mucosa with non-Helicobacter pylori infection. This meta-analysis was conducted to systematically evaluate the value of the sign in predicting a Helicobacter pylori-negative stomach and the relevant factors that may affect the performance of this prediction.MethodsTwo biomedical databases (PubMed and EMBASE) were systematically searched through April 20, 2020. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the SROC curve (AUC) were calculated.ResultsFourteen articles with 4070 patients were included. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC for the RAC in predicting non-Hp infection were 0.80 (0.67–0.89), 0.97 (0.93–0.98), 24.8 (12.2–50.8), 0.21 (0.12–0.36), 120 (47–301) and 0.97 (0.19–1.00), respectively.ConclusionsThe RAC is a valuable endoscopic feature for the prediction of patients without Hp infection.     

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.

     

Influence of Renal Function on the Pharmacokinetics,Pharmacodynamics, Efficacy,and Safety of Non–Vitamin K Antagonist Oral Anticoagulants

With the growing integration of non–vitamin K antagonist oral anticoagulants (NOACs) into clinical practice, questions have arisen regarding their use in special populations, including groups that may have been underrepresented in clinical trials. Patients with renal impairment, particularly in the lower echelons of renal function, are one such group. In an effort to elucidate the current evidence regarding the use of NOACs in patients with renal impairment, a systematic assessment of the literature was performed. The MEDLINE database was interrogated for studies and analyses evaluating the influence of renal function on the pharmacokinetics, pharmacodynamics, efficacy, and safety of NOACs published from January 1, 2000, through August 2, 2017. The 82 relevant publications retrieved highlight the diversity in the NOAC class regarding the impact of renal function on drug clearance, drug exposures, and clinical trial outcomes. In several large clinical trials, subgroup analyses revealed no significant differences when patients were stratified by creatinine clearance as a measure of renal function. Efficacy findings, in particular, were largely aligned with the overall population in the included studies. However, relative risks of bleeding were shown to vary, sometimes driven by changes in bleeding event rates in the comparator arm (eg, warfarin, enoxaparin). With few exceptions, minimal influence of mild renal impairment was observed on the relative efficacy and safety of NOACs. Taken together, the evidence suggests that the presence of renal impairment merits careful consideration of anticoagulant choice but should not deter physicians from appropriate use of NOACs.     

Utilization of anticoagulants and outcomes in STEMI patients undergoing PPCI in the US hospitals: Bivalirudin,heparin plus GPI or heparin alone?

Objective. Despite major trials showing the opposite, one of three small randomized trials conducted outside the US has raised questions about whether heparin alone is a viable antithrombotic strategy for primary percutaneous coronary interventions (PPCI). We determined the frequency and in-hospital outcomes of anticoagulation strategies in patients undergoing PPCI. Methods. We analyzed records from 2008 through 2013 in the Premier Research Database of patients hospitalized with ST-segment elevation myocardial infarction (STEMI) undergoing PPCI. Patients were categorized into one of four anticoagulation strategies: bivalirudin alone, bivalirudin plus glycoprotein IIb/IIIa inhibitors (GPI), unfractionated or low-molecular-weight heparin alone or heparin plus GPI. In-hospital clinical outcomes were compared between treatment groups after propensity score matching. Results. Among 114,134 eligible STEMI patients, heparin alone was the least frequent anticoagulation strategy, used in 14.4% to 18.1% of cases per year. Bivalirudin alone nearly tripled during the study period, from 12.7% to 37.8% and surpassed that of heparin plus GPI by 2013. Bivalirudin alone performed better than heparin alone for mortality (4.7% vs 5.3%, p = 0.010), clinically apparent bleeding (5.7% vs 6.7%, p < 0.001), transfusion rates (4.1% vs 4.8%, p = 0.003) and mean length of stay (4.1 vs 4.2 days, p < 0.001). The in-hospital death rate was lower with heparin plus GPI than with heparin alone (4.9% vs 5.9%, p < 0.001), but clinically apparent bleeding was higher in heparin plus GPI than in heparin alone (9.4% vs 7.1%, p < 0.001). Conclusion: In patients hospitalized for STEMI undergoing PPCI, heparin alone is not commonly used and is inferior to bivalirudin for mortality, bleeding and length of stay outcomes. Heparin is also inferior to heparin plus GPI for ischemic protection but associated with less bleeding.     

An occult finding in heparin drip order set

Background: In 1998, the Institute of Medicine (IOM) noted that the American healthcare system had many problems. A major concern was the pervasiveness of medical errors. Electronic medical records (EMR) were introduced for myriad of reasons, one being to reduce these errors. Within the EMR, order sets have been shown to reduce variation in clinical practice and improve the quality of care. However, the lack of standardization in these sets enables peculiar orders, such as fecal occult blood test (FOBT) in the heparin drip order set at our hospital, to be surprisingly included. Our study was conducted to evaluate the consequences associated with having FOBT in this order set. Methods: A retrospective study of 898 adult hospitalized patients over a 6-month period, who had a heparin drip ordered at a single academic center, was conducted. The main focus of our study was the 130 patients for whom the FOBT was sent. Results: Fifteen percent (n = 130) of patients started on IV heparin had FOBT sent, of which 33 (25%) came back positive. Approximately one-third (36%) of the positive results were documented by a provider, either in a progress note or discharge summary. In eight instances of a positive FOBT (24%), the heparin drip was stopped. For 10 patients with a positive test (30%), gastroenterology was consulted, and 4 (12%) patients had inpatient endoscopy. Five patients with positive FOBT died while in the hospital (15%) as compared to seven patients (7%) in the negative FOBT group, p < 0.05. Conclusions: Most patients started on heparin did not have FOBT tested, and the results changed management infrequently, even when positive. The regular review of all order sets is imperative to ensure that they remain evidenced-based and sensible.