Nano‐evidence for joint microbleeds in hemophilia patients

The concept of joint microbleeding in hemophilia patients was first proposed over 10 years ago. This was based on unexpected abnormalities found in medical imaging studies of asymptomatic joints. Since then, there have been no published studies confirming the presence of joint microbleeds. This critique will review the evidence for and against joint microbleeding in hemophilia patients and the potential implications.     

Ventricular Assist Devices: The Basics

As the cases of heart failure continue to rise, more ventricular assist devices are likely to be implanted. Providers in a variety of care environments are more likely to see patients with ventricular assist devices because they are living longer; therefore, it is necessary for providers to understand the unique care and complications related to these devices, such as thrombosis, stroke, bleeding, right-sided heart failure, ventricular dysrhythmias, and infection. The current literature regarding the complications and management of patients with these devices was reviewed and summarized, with a focus on HeartWare (HeartWare International Inc, Framingham, MA) and HeartMate II (Thoratec Corp, Pleasanton, CA).     

Rivaroxaban reversal with prothrombin complex concentrate or tranexamic acid in healthy volunteers

Essentials

• Specific reversal agents for managing severe factor Xa inhibitor‐associated bleeding are lacking.
• We assessed 4‐factor‐prothrombin complex concentrate (4F‐PCC) and tranexamic acid (TXA).
• 4F‐PCC, but not TXA, reduced the prothrombin time and increased endogenous thrombin potential.
• These agents may be viable options for reversal of therapeutic doses of rivaroxaban.

Summary

Background

Oral activated factor X inhibitors such as rivaroxaban are widely used, but specific reversal agents are lacking. Although four‐factor prothrombin complex concentrate (4F‐PCC) and tranexamic acid (TXA) are sometimes used to manage serious bleeding, their efficacy is unknown. Prior studies in healthy subjects taking rivaroxaban revealed that 4F‐PCC partially reverses the prolonged prothrombin time (PT), and fully restores the endogenous thrombin potential (ETP). The effect of TXA has not been evaluated.

Methods

In this double‐blind, parallel‐group study, 147 healthy volunteers given rivaroxaban 20 mg twice daily for 3 days were randomized after their morning dose on day 4 to receive intravenous 4F‐PCC (50 IU kg^?1), TXA (1.0 g), or saline. Standardized punch biopsies were performed at baseline and after 4F‐PCC, TXA or saline administration. Reversal was assessed by measuring bleeding duration and bleeding volume at biopsy sites, and by determining the PT and ETP.

Results

As compared with saline, 4F‐PCC partially reversed the PT and completely reversed the ETP, whereas TXA had no effect. Neither 4F‐PCC nor TXA reduced bleeding duration or volume. All treatments were well tolerated, with no recorded adverse events.

Conclusions

Although 4F‐PCC reduced the PT and increased the ETP in volunteers given supratherapeutic doses of rivaroxaban, neither 4F‐PCC nor TXA influenced punch biopsy bleeding.

     

The influence of thyroid function on the coagulation system and its clinical consequences

Summary

Several studies indicate that low plasma levels of thyroid hormone shift the hemostatic system towards a hypocoagulable and hyperfibrinolytic state, whereas high levels of thyroid hormone lead to more coagulation and less fibrinolysis. Low levels of thyroid hormone thereby seem to lead to an increased bleeding risk, whereas high levels, by contrast, increase the risk of venous thromboembolism. Hypothyroidism leads to a higher incidence of acquired von Willebrand's syndrome and with increasing levels of free thyroxine, levels of fibrinogen, factor VIII and von Willebrand factor, amongst others, increase gradually, to the extent that they may lead to symptomatic venous thromboembolism in patients with hyperthyroidism. Here, we discuss the literature on the effect of thyroid hormone on the hemostatic system and the associated risk of bleeding and venous thromboembolism. Patients with hypothyroidism are at increased risk of developing bleeding complications, which could be relevant in patients undergoing invasive procedures. Furthermore, physicians should be aware of the possibility of hyperthyroidism as an underlying risk factor for venous thromboembolism, especially in unexplained cases. Clinical studies are needed to further investigate the significance for general practice of these findings. Besides the effects of hyperthyroidism on venous thromboembolism, its effects on embolism secondary to atrial fibrillation are described.

     

神经内镜下治疗基底节区高血压脑出血的效果研究

目的探讨传统开颅手术与神经内镜手术在治疗基底节区高血压脑出血(HICH)患者中的疗效与安全性,为其临床治疗提供一定依据。方法 86例基底节区HICH患者,根据手术方式不同将患者分为神经内镜组(40例)和开颅手术组(46例),开颅手术组采用开颅血肿清除手术治疗,神经内镜组采用神经内镜微创血肿清除手术治疗,对比两组基底节区HICH患者皮肤切口大小、骨窗大小、皮层切口大小、手术时间、术中出血量、血肿清除率、术后并发症、近期与远期疗效和病死率。结果神经内镜组患者的皮肤切口大小、骨窗大小、皮层切口大小、手术时间、术中出血量均明显低于开颅手术组(P 0.01);两组患者血肿清除率差异无统计学意义(P0.05);神经内镜组患者术后并发症发生率为10.0%,明显低于开颅手术组的28.3%(P 0.05);神经内镜组患者近期疗效良好率为90.0%明显高于开颅手术组的60.9%(P 0.01);神经内镜组患者远期疗效良好率为92.5%明显高于开颅手术组的63.0%(P 0.01);开颅手术组患者死亡3例,病死率6.5%;神经内镜组患者死亡2例,病死率5.0%;两组患者病死率差异无统计学意义(P0.05)。结论神经内镜手术治疗基底节区HICH可以减小手术创伤,缩短手术时间,降低出血量,提升近期与远期疗效,降低并发症发生率。     

Adenylate cyclase activity during development and reversal of cardiac hypertrophy

Inotropic responses to isoproterenol of hypertrophied hearts have been shown to be decreased. We have previously reported that in 13-week-old spontaneously hypertensive rats (SHR) this decrease is probably due to decreased beta-adrenergic receptor number, while in hearts from two kidney-one clip renal hypertensive rats (2K-1C RHR), this is due to a decreased nucleotide regulatory protein activity. We now show that changes in 2K-1C RHR are time dependent. One week after instituting development of hypertension the heart is already hypertrophied. Biochemical changes consistent with decreased glucagon receptors are seen, as well as beginning changes consistent with decreases in the nucleotide regulatory protein activity. By two weeks this is more evident. Hypertrophy and biochemical changes can be reversed up to six weeks, but by ten weeks the activity of the catalytic subunit of the adenylate cyclase system is decreased. In 1K-1C RHR, biochemical changes in the cyclase system are accelerated as compared with the 2K-1C model. In SHR, changes in 24-week-old rats are the same as in the 13-week-old rats. It is concluded that in cardiac hypertrophy associated with different models of hypertension the decreased inotropic responsiveness to isoproterenol is associated with different biochemical defects in the beta-adrenergic receptor response coupling pathway, and that reversal in function occurs only when there is no apparent change in the catalytic subunit of the adenylate cyclase complex.     

地尔硫(艹卓)对自发性高血压大鼠左心室舒张功能的影响及其可能机制

目的:观察地尔硫(艹卓)对自发性高血压大鼠(SHR)左心室舒张功能的影响,并探讨这种影响是否与肌浆网钙ATP酶(SERCA2)蛋白的表达、活性及心肌纤维化相关. 方法:将22只12周龄SHR随机分为地尔硫(艹卓)组(25 mg·kg-1·d-1,SHR-D),苯那普利组(10 mg·kg-1·d-1,SHR-B)和SHR空白对照组(蒸馏水灌胃,SHR-C);另设WKY大鼠7只为正常对照组(WKY).灌胃法给药18周后测定左心室心功能,计算左心室/体重比(LVW/BW),Western印迹杂交测定左心室心肌SERCA2的表达,无机磷比色法检测心肌肌浆网Ca2 ATPase活性.饱和苦味酸天狼星红染色分析胶原容积分数(CVF)和血管周围胶原面积(PVCA),估计心肌纤维化程度. 结果:SHR-D组和SHR-B组的LVEDP显著低于SHR-C组,SHR-D组和SHR-B组之间差异无统计学意义(P＞0.05).与SHR-C组相比,SHR-D组与SHR-B组的-dp/dtmax/MAP增加.地尔硫(艹卓)和苯那普利治疗明显增加SERCA2蛋白的表达(SHR-D:0.38±0.07,SHR-B:0.42±0.06,SHR-C:0.47±0.07)与活性(SHR-D:8.2±0.07,SHR-B:10.5±1.95,SHR-C:6.3±0.75).SHR-D组左心室内膜及心肌小动脉周围的胶原减少,其作用类似于SHR-B组. 结论:地尔硫(艹卓)可改善SHR左心室舒张功能,其机制可能与增加SERCA2蛋白的表达及活性,抑制心肌纤维化有关.     

亚低温在蛛网膜下腔出血急性期的脑保护作用

亚低温对脑动脉瘤性蛛网膜下腔出血急性期脑损伤保护作用的研究报道较少。在动脉瘤性蛛网膜下腔出血急性期,有多种脑损伤机制参与脑损伤的发生。亚低温在脑梗死早期能对抗多种脑损害因素,应用于动脉瘤性蛛网膜下腔出血急性期,有可能发挥脑保护作用。     

A case of systemic lupus erythematosus complicated by alveolar hemorrhage and cytomegalovirus colitis

We report a rare case of systemic lupus erythematosus (SLE) complicated by alveolar hemorrhage and cytomegalovirus (CMV) colitis. Despite the successful treatment of lupus nephritis by steroid pulse therapy, the patient developed an acute alveolar hemorrhage 2 months later. Cyclophosphamide pulse therapy ameliorated the hemorrhage. One month later, she suddenly developed melena secondary to CMV colitis. Antiviral therapy was successful. We emphasize the importance of timely and precise differential diagnosis for successful management of complicated SLE.     

A Noncontrast CMR Risk Score for Long-Term Risk Stratification in Reperfused ST-Segment Elevation Myocardial Infarction

ObjectivesThis study compared the prognostic value of a noncontrast CMR risk score for the composite of all-cause death, nonfatal myocardial infarction, and new congestive heart failure.BackgroundA cardiovascular magnetic resonance (CMR) risk score including left ventricular ejection fraction (LVEF), myocardial infarct (MI) size, and microvascular obstruction (MVO) was recently proposed to risk-stratify patients with ST-segment elevation myocardial infarction (STEMI).MethodsThe Eitel CMR risk score and GRACE (Global Registry of Acute Coronary Events) score were used as a reference (Score 1: acute MI size ≥19% LV, LVEF ≤47%, MVO >1.4% LV and GRACE score). MVO was replaced by intramyocardial hemorrhage (IMH) in Score 2 (acute MI size ≥19% LV, LVEF ≤47%, IMH, and GRACE score). Score 3 included only LVEF ≤45%, IMH, and GRACE score.ResultsThere were 370 patients in the derivation cohort and 234 patients in the validation cohort. In the derivation cohort, the 3 scores performed similarly and better than GRACE score to predict the 1-year composite endpoint with C-statistics of 0.83, 0.83, 0.82, and 0.74, respectively. In the validation cohort, there was good discrimination and calibration of score 3, with a C-statistic of 0.87 and P = 0.71 in a Hosmer-Lemeshow test for goodness of fit, on the 1-year composite outcome. Kaplan-Meier curves for 5-year composite outcome showed that those with LVEF ≤45% (high-risk) and LVEF >45% and IMH (intermediate-risk) had significantly higher cumulative events than those with LVEF >45% and no IMH (low-risk), log-rank tests: P = 0.02 and P = 0.03, respectively. The HR for the high-risk group was 2.3 (95% CI: 1.1-4.7) and for the intermediate-risk group was 2.0 (95% CI: 1.0-3.8), and these remained significant after adjusting for the GRACE score.ConclusionsThis noncontrast CMR risk score has performance comparable to an established risk score, and patients with STEMI could be stratified into low risk (LVEF >45% and no IMH), intermediate risk (LVEF >45% and IMH), and high risk (LVEF ≤45%). (A Trial of Low-dose Adjunctive alTeplase During prIMary PCI [T-TIME]; NCT02257294) (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction [BHF MR-MI]; NCT02072850)