Insulin and heparin challenge tests are useful for choosing an optimal insulin regimen in a case of subcutaneous insulin resistance

A 38‐year‐old woman with type 1 diabetes, whose fasting plasma glucose levels were >500 mg/dL under 176 U/day of subcutaneous insulin injection, was admitted to Nippon Medical School Hospital, Tokyo, Japan. When insulin was administered intravenously, she was able to maintain favorable glycemic control even under 24 U/day of regular insulin, showing that she was accompanied by subcutaneous insulin resistance. To choose an optimal insulin regimen, we carried out subcutaneous insulin challenge tests without or with heparin mixture, and found a cocktail of insulin lispro and heparin could reduce blood glucose levels markedly. As a consequence, she achieved favorable blood glucose control by continuous subcutaneous insulin infusion of the cocktail. In summary, the insulin and heparin challenge tests are useful for choosing an optimal insulin regimen in cases of subcutaneous insulin resistance.     

Low prevalence of heparin-induced thrombocytopenia after cardiac surgery in Thai patients

Introduction

Heparin induced-thrombocytopenia (HIT) has been well recognized in Western countries. However, there are no data in the Thai population. We therefore investigated the prevalence of anti-platelet factor 4 (PF4)/heparin antibodies, HIT, and its thrombotic complications in Thai patients undergoing cardiac surgery using unfractionated heparin.

Materials and methods

Seventy-three consecutive patients were prospectively enrolled in this study. Blood samples before operation and week 1, week 2, and week 3 after operation were collected from each patient for HIT antibody screening by enzyme-linked immunosorbent assay using IgG antibody specific to the PF4/heparin complex. Positive samples were further analyzed by ¹⁴C-serotonin release assay. Complete blood count was performed daily during the first week, then weekly for 3 weeks.

Results

No patient had detectable anti-PF4/heparin antibodies at baseline. Five patients sero-converted during the course of the study for anti-PF4/heparin IgG: 3 (4.1%) at week 1, 4 (5.5%) at week 2, and 5 (6.8%) at week 3 after surgery. However, none of these patients had anti-PF4/heparin antibodies that resulted in ¹⁴C-serotonin release to be considered clinically significant antibodies. Post-operative thrombocytopenia after the operation was found in 35 patients (47.9%), but was not considered to be caused by HIT. Thromboembolic events occurred in 3 patients (4.1%) during follow up; however, none of these patients had positive PF4/heparin antibody tests.

Conclusions

Our study represents the first study to examine Thai patients exposed to heparin in the context of cardiac surgery. We found a lower prevalence of positive anti-PF4/heparin antibodies and clinical HIT than previously published studies.     

Recurrent venous thromboembolism while on anticoagulant therapy

There has been immense progress in the management of venous thromboembolism in recent years with increased awareness and adequate thromboprophylaxis proving successful in reducing the morbidity and mortality associated with this condition. One of the commonest complications of an initial venous thrombosis is the development of recurrent thrombosis. Unlike in the case of the first clot, the diagnosis and management of the recurrent episode remain a difficult issue. Even more challenging is the clinical situation where a new thrombus develops while the patient is being treated with anticoagulant medication for a previous clot. The clinical approach and management of these patients are complex, and require understanding of the differences in thrombus development in the different clinical circumstances.     

Electrochemical Assay of Heparin to Monitor Anticoagulation Action in Cardiovascular Patients

Complications in anticoagulation therapy and long term consequences of the post thrombotic syndromes requires a fast and powerful therapy such as heparin therapy (anticoagulation) to minimize the thrombotic effects in patients. Thus, a simple approach via electrochemical method: Differential pulse polarography (DPP) has been developed for heparin analysis as a powerful clinical tool to monitor anticoagulation action in-patient undergoing heparin therapy. The method has been standardized for determination of heparin activity over the existing methods and a very well defined characteristic reduction peak at −1.25 V in 2 M NaOH was observed for heparin. A linear relation was observed with a regression equation as y = 0.3117x + 0.8069, for 0.1 to 2.0 units/ml heparin. The developed DPP method was observed with excellent precision, accuracy and recovery in human blood plasma samples and in pharmacological formulations. The limit of detection (LOD) and limit of quantification (LOQ) noticed to be 2.04 and 6.8 units/ml respectively. The DPP results compared with pharmacological screening through average thrombin time (TT) and applied to monitor invitro anticoagulation action of heparin in healthy human subjects. Statistical analysis done to validate developed DPP method for heparin analysis and its probable clinical use to monitor anticoagulation action to treat patients suffering from various cerebrovascular disorders (CVD) by proper dosing of heparin.     

POSSIBLE STRATEGIES TO PROLONG CIRCUIT LIFE DURING HEMOFILTRATION: THREE CONTROLLED STUDIES

Background and Aims: The prevention of filter clotting is an important goal in the management of continuous renal replacement therapy (CRRT). Anticoagulation is the mainstay of such prevention. However, other strategies might prolong filter life without increasing the risk of bleeding. We tested the effectiveness of three strategies (use of flat plate configuration, heparin administration into the air chamber and use of a larger membrane surface) aimed at prolonging circuit life without increasing the dose of anticoagulation. Methods: Thirty-one critically ill patients with acute renal failure (ARF) managed with continuous venovenous hemofiltration (CVVH) were studied. Filters were randomized in a crossover design to three consecutive studies: (1) filtration with either hollow-fiber or flat-plate hemofilters, (2) administration of heparin dose pre-filter or divided into pre-filter and directly into the bubble trap chamber and (3) use of two different surface areas with Filtral 8 (surface area 0.75 m²) vs. Filtral 12 (surface area 1.30 m²) hemofilters. Results: Mean circuit life for flat-plate and hollow-fiber hemofilters (cohort 1) was 14.7 ± 4.7 h and 17.1 ± 2.8 h respectively (NS). Mean circuit life for single heparin administration site vs. double site administration (cohort 2) was 17 ± 3.2 h and 18 ± 3.1 h respectively (NS). Mean circuit lifespan for 0.75 m² and 1.30 m² hemofilters was 16 ± 12.2 h and 15.7 ± 14.3 h respectively (NS) (cohort 3). Visible clot formation in the bubble trap chamber was a frequent cause of circuit failure. Conclusion: Neither flat plate membrane configuration nor increasing membrane surface area, nor heparin administration in the air chamber prolong circuit life during CVVH. The bubble trap chamber is a frequent site of circuit clotting.     

Dalteparin Vs Low-Dose Unfractionated Heparin for Prophylaxis Against Clinically Evident Venous Thromboembolism in Acute Traumatic Spinal Cord Injury: A Retrospective Cohort Study

Background: When venous thromboembolism (VTE) includes deep-vein thrombosis (DVT) and pulmonary embolism (PE), patients with acute traumatic spinal cord injury (SCI) have the highest incidence of VTE among all hospitalized groups, with PE the third most common cause of death. Although low-molecular-weight heparin (LMWH) outperforms low-dose unfractionated heparin (LDUH) in other patient populations, the evidence in SCI remains less robust.

Objective: To determine whether the efficacy for LMWH shown in previous SCI surveillance studies (eg, routine Doppler ultrasound) would translate into real-world effectiveness in which only clinically evident VTE is investigated (ie, after symptoms or signs present).

Methods: A retrospective cohort study was conducted of 90 patients receiving LMWH dalteparin (5,000 U daily) or LDUH (5,000 U twice daily) for VTE prophylaxis after acute traumatic SCI. The incidence of radiographically confirmed VTE was primarily analyzed, and secondary outcomes included complications of bleeding and heparin-induced thrombocytopenia.

Results: There was no statistically significant association (p = 0.7054) between the incidence of VTE (7.78% overall) and the type of prophylaxis received (LDUH 3/47 vs dalteparin 4/43). There was no significant differences in complications, location of VTE, and incidence of fatal PE. Paraplegia (as opposed to tetraplegia) was the only risk factor identified for VTE.

Conclusions: There continues to be an absence of definitive evidence for dalteparin (or other LMWH) over LDUH as the choice for VTE prophylaxis in patients with SCI. Novel approaches to VTE prophylaxis are urgently required for this population, whose risk of fatal PE has not decreased over the last 25 years.     

Use of Heparin-bonded Circuits in Cardiopulmonary Bypass Improves Clinical Outcome

Objective : The use of heparin-coated surfaces in cardiopulmonary bypass has been shown to decrease the inflammatory response imposed by the contact between blood and artificial surfaces. One would expect this reaction to improve clinical outcome. However, this has been difficult to verify. This investigation is based on an aggregation of two randomized studies from our institution and highlights possible effects of heparin coating on a number of clinically oriented parameters. Design : Departmental analysis of patients subjected to coronary artery bypass surgery using heparin-coated circuits. Cardiopulmonary bypass was employed using either the Carmeda or Duraflo heparin coatings compared with a control. The systemic heparin dose was reduced in the heparin-coated groups (ACT > 250 s) vs control group patients (ACT > 480 s). The effects of heparin coating related to clinical outcome were studied. Results : The use of heparin-coated circuits reduced the mean length of stay in hospital from 7.8 &#45 2.5 to 7.3 &#45 1.8 days ( p = 0.040) and postoperative ventilation time from 9.7 &#45 9.2 to 8.2 &#45 8.5 h ( p = 0.018), blood loss 8 h post surgery from 676 &#45 385 to 540 &#45 245 ml ( p = 0.001), individual perioperative change of haemoglobin loss ( p = 0.001), leukocyte count ( p = 0.000) and creatinine elevation ( p = 0.000), proportion of patients exposed to allogenous blood transfusions 39.2 vs 23.9% ( p = 0.001), postoperative coagulation disturbances 4.4 vs 0.4% ( p = 0.006), postoperative deviations from the normal postoperative course 47.2 vs 36.7% ( p = 0.035), neurological deviations 9.4 vs 3.9% ( p = 0.021) and atrial fibrillation 26.4 vs 18.0% ( p = 0.041). No effects were found with respect to perioperative platelet count, postoperative fever reaction and 5-year survival. Conclusion : Based on several indicators, the use of heparin coating in cardiopulmonary bypass is associated with improved clinical results.     

注射用血凝酶术前给药对低分子肝素抗凝患者髋关节置换术围术期出血量及凝血功能的影响

目的 探讨注射用血凝酶术前给药对低分子肝素抗凝患者髋关节置换术围术期出血量及凝血功能的影响.方法 本试验为随机、对照、单盲的临床研究.择期全麻下单侧髋关节置换术患者40例,美国麻醉医师协会(ASA)分级为Ⅰ或Ⅱ级,年龄60岁～75岁,体重45 kg ～75 kg.术前1d皮下注射低分子肝素(low-molecular-weight heparin,LMWH)4 000单位,采用随机数字表法,将患者随机分为2组(每组20例):注射用血凝酶组(H组)和生理盐水组(C组).切皮前10 min,H组静脉给予注射用血凝酶2单位(5ml生理盐水稀释),C组静脉注射等量生理盐水.记录术中出血量及术后24h引流量,记录术毕及术后24 h凝血功能的各项指标.术后第5d通过下肢深静脉彩超观察下肢深静脉血栓形成的发生情况. 结果 C组术中出血量及术后24h引流量分别为(629±97) ml和(273±87) ml,H组分别为(312±79) ml和(213±74) ml.与C组比较,H组术中出血量及术后24h引流量减少(P＜0.05).与术前比较,两组术毕、术后24h血红蛋白、红细胞、红细胞积压分别减少(P＜0.05).与术前比较,两组术毕及术后24 h凝血常规各项指标差异无统计学意义(P＞0.05).两组术后深静脉血栓形成发生率分别为13％和7％,差异无统计学意义(P＞0.05). 结论 注射用血凝酶术前给药能减少低分子肝素抗凝下髋关节置换术患者围术期出血量,并不影响患者的凝血功能.