Protein C,S and antithrombin III levels in patients with acute mechanical valve thrombosis

BACKGROUND: Mechanical prosthetic heart valve thrombosis is a serious complication with an incidence of 1-6%. The reduction in active vitamin-K dependent protein C and S levels caused by warfarin treatment also results in a prothrombotic state. This study was conducted to investigate the connection between protein C (PC), protein S (PS), antithrombin III (ATIII) deficiency and prosthetic mechanical valve thrombosis. METHODS: Twenty-nine of the 283 patients who underwent valve replacement with St. Jude medical prosthesis had mechanical valve thrombosis (group 2). The rest were considered as group 1. Twelve of the 29 patients (41.4%) had isolated aortic valve replacement, 12 had isolated mitral valve replacement (41.4%) and 5 patients had double valve replacement (17.2%). Most of the patients had rheumatic valve disease at their 1st operation. The mean time of occurrence for mechanical valve occlusion was 4.1+/-1.0 years following surgery. RESULTS: The values of PC, PS and ATIII were obtained when the mechanical valves stuck or at routine follow-up. PC, PS and ATIII levels were significantly lower in the mechanical valve thrombosis group. PC levels were 75.4+/-37.6% and 49.9+/-32.2% in group 1 and 2, respectively (p=0.001). PC, PS and ATIII values were mostly lower in the 2nd group but this difference only became significant after at least 2 years of warfarin usage. CONCLUSIONS: Natural anticoagulant levels can be low during the use of warfarin. In which case the dose can be increased in order to hold the international normalized ratio (INR) at 3-3.5. However, more frequent follow-up is required and patients should be investigated for hypercoagulation states or deficiency in anticoagulant proteins. Patients referred to hospital with any mechanical valve thrombosis or recurrent thromboembolism should be evaluated for hypercoagulant proteins.     

Neurological complications of infective endocarditis: New breakthroughs in diagnosis and management

Neurological complications are frequent in infective endocarditis (IE) and increase morbidity and mortality rates. A wide spectrum of neurological disorders may be observed, including stroke or transient ischemic attack, cerebral hemorrhage, mycotic aneurysm, meningitis, cerebral abscess, or encephalopathy. Most complications occur early during the course of IE and are a hallmark of left-sided abnormalities of native or prosthetic valves. Ischemic lesions account for 40% to 50% of IE central nervous system complications. Systematic brain MRI may reveal cerebral abnormalities in up to 80% of patients, including cerebral embolism in 50%, mostly asymptomatic. Neurological complications affect both medical and surgical treatment and should be managed by an experimented multidisciplinary team including cardiologists, neurologists, intensive care specialists, and cardiac surgeons. Oral anticoagulant therapy given to patients presenting with cerebral ischemic lesions should be replaced by unfractionated heparin for at least 2 weeks, with a close monitoring of coagulation tests. Recently published data suggest that after an ischemic stroke, surgery indicated for heart failure, uncontrolled infection, abscess, or persisting high emboli risk should not be delayed, provided that the patient is not comatose or has no severe deficit. Surgery should be postponed for 2 to 3 weeks for patients with intracranial hemorrhage. Endovascular treatment is recommended for cerebral mycotic aneurysms, if there is no severe mass effect. Recent data suggests that neurological failure, which is associated with the location and extension of brain injury, is a major determinant for short-term prognosis.     

Old burdens and new perspectives of the long-term anticoagulant therapy

Old burdens and new perspectives of the long-term anticoagulant therapy. Long-term anticoagulant therapy (LAT) has increasingly improved the prognosis in various diseases thus becoming an indispensable tool in our day-to-day therapeutic arsenal. However its use is influenced by various uncertainty factors. The optimal range of anticoagulation can unfortunately only be partially achieved due to the several factors influencing it. Thromboembolic and bleeding episodes occur mainly at times when the state of anticoagulation diverges from the ideally set therapeutic range. Quality of the ongoing therapy can only partially be improved by increasing the frequency of the controls. This however is also inherent partly in the treatment indication and also in the personality of the given patient (compliance). Heparin preparations are rarely used for long-term anticoagulant therapy due to the inevitable injectable form of administration. The more easily applicable LMWH-s' actions are also influenced by several uncertainty factors. In cases of idiopathic deep vein thrombosis, extension of the LAT therapy could be beneficial and is recommended beyond 6 months in order to prevent recurrence of the acute event and postthrombotic syndrome, irrespective of the proof of the genetic predisposition. Several clinical observations suggest that LAT could hinder propagation of malignant tumors and this presumption has already been supported by experimental data. The favourable effect has primarily been associated with and experienced with the use of LMWH-s. Prolonged LAT may even change the perspectives of thrombolytic therapy in venous thrombosis, improving its late efficacy. A new and simply applicable anticoagulant may help further spreading of LAT.     

心脏换瓣术后妊娠分娩36例临床观察

目的:探讨心脏换瓣术后妇女妊娠分娩的处理方案。方法:对近十余年来收住的36例孕妇,观察其分娩方式、妊娠结局及分娩前抗凝药物应用方案。结果:36例预后均良好,其中34例行硬膜外麻醉下剖宫产术,术前24～48h停用抗凝药,必要时注射维生素K120mg,术后24h恢复抗凝药的应用,产妇均未出现严重并发症,婴儿无畸形等发生。结论:换瓣术后以剖宫产为首选方式,术前及时停用抗凝药物,术后24h恢复用药,对产妇及新生儿是一种安全的处理方案。     

血栓弹力图在预防肺癌患者PICC相关性静脉血栓中的应用

目的 探讨血栓弹力图在预防肺癌患者经外周静脉置入中心静脉导管（peripherally inserted centralcatheters,PICC）相关性静脉血栓中的作用。方法 将264例肺癌患者按随机数字表法分为干预组和对照组各132例。干预组患者分别于PICC置管前1 d、置管后4周内每周检测1次血栓弹力图（thromboelastography,TEG）,血液高凝者行抗凝治疗。对照组患者按常规PICC置管,并于置管前1 d、静脉血栓形成后行TEG检测。2组患者均于PICC置管后4周内每周行血管超声检测1次,比较2组PICC相关性静脉血栓发生率、观察血液高凝状态者抗凝治疗前后TEG参数变化及静脉血栓者血栓形成前后TEG参数变化。结果 67例置管后血液高凝状态者行抗凝治疗后,TEG各参数与治疗前比较,均P＜0.05,差异有统计学意义;干预组PICC相关性静脉血栓发生率为0.76%、对照组为19.70%,2组相关性静脉血栓比较,χ2 = 25.791,P＜0.01,差异有统计学意义。26例静脉血栓形成者TEG参数与PICC置管前比较,均P＜0.05,差异有统计学意义。结论 采用TEG预测肺癌PICC患者静脉血栓,并建立个体化的抗凝治疗,可有效预防PICC相关性静脉血栓的形成,保证PICC临床应用安全。     

Experience in the care of patients with artificial heart valves

Author reports of 164 cases, 145 of whom received mechanic artificial valves and 19 bioprosthesis. 76 valves were implanted in mitral position, 65 in aorta position, 19 in mitral and aorta position, and 4 valves were localized in other positions. Follow-up was 5.9 years meanly. During care paravalvular insufficiency (11 cases) and infectious endocarditis (9 cases) were observed most frequently. Thromboembolic complications developed in 6 patients, artificial-valve-thrombosis and severe haemorrhage occurred in four cases respectively. During care 32 patients died. This is a 5.4 p.c. mortality. The most frequent causes of death were left-ventricle insufficiency (10) and infectious endocarditis (8). Artificial valve thrombosis and subdural haemorrhage lead to death in three cases respectively. Author discusses anticoagulant treatment and emphasizes the importance of regular control to avoid complications and to discover them at an early stage.     

Systemic thrombolysis in acute obstruction of an artificial valve

Prosthetic valve thrombosis is a characteristic, but fortunately not frequent complication of surgical valve replacement. Its occurrence may lead to haemodynamic catastrophe. Three cases involving prosthetic valve thrombosis are presented. Two patients suffered from thrombosis after tricuspid valve replacement (St. Jude Medical), while the third occurred after mitral valve replacement (Sorin). In the acute phase, systemic thrombolysis was initiated (2 MU Streptokinase during 22-28 hours). The obstruction of one of the tricuspid valves and the mitral valve was eliminated. Lysis of the other tricuspid valve was not complete, but it helped the patient to survive the acute phase until reoperation. Embolization occurred in the inferior extremity after thrombolysis of the mitral prosthetic valve, but it was cured. Two-dimensional and Doppler echocardiography (conventional and colour-coded) played an important role in the diagnosis of the obstruction and in the follow-up of the effectivity of thrombolysis. Systemic thrombolysis may be a lifesaving procedure in acute prosthetic valve thrombosis. In spite of the potentially dangerous complications, it has to be attempted.     

Menstrual problems and contraception in women of reproductive age receiving oral anticoagulation

Background

Oral anticoagulation is associated with increased bleeding complications. The aim of this study was to assess the changes in menstrual loss and pattern in women taking anticoagulant treatment.

Study Design

Women on oral anticoagulant (OA) treatment at the Royal Free Hospital were interviewed and completed a questionnaire about their menstrual cycle before and after commencing oral anticoagulation treatment. They were then asked to complete a pictorial bleeding assessment chart (PBAC) during their next menstrual bleeding episode.

Results

Fifty-three women between the ages of 20 and 50 years participated in the study. Of these, 47 women completed a PBAC. The mean duration of menstruation increased from 5 days before starting OA therapy to 7 days after the commencement of treatment. Thirty-one (66%) of the 47 women who completed the PBAC had a score that was greater than 100. The number of women who experienced flooding or clots during menstruation and intermenstrual or postcoital bleeding also increased. In total, 29 (54.7%) women changed their method of contraception during OA treatment. Seventeen women who did not want to become pregnant were not using contraception, including 10 women who were on hormonal contraception prior to starting anticoagulant therapy.

Conclusion

Women of reproductive age experience heavy and prolonged menstrual bleeding whilst on OA therapy. Women of reproductive age on OA therapy should be monitored for menstrual disorders to ensure that prompt and appropriate treatment is instituted. Advice about appropriate contraception should also be part of the medical care provided for these women. Barrier contraception, sterilization and progestin-only contraception are all suitable methods of contraception in this patient group.     

Anticoagulation during pregnancy

Anticoagulation of a pregnant woman is a complex issue for both the treating physician and the patient. In patients with mechanical prosthetic valves, long-term anticoagulation is mandatory to prevent thromboembolic complications; and in those with thrombophilic disorders and history of thromboembolism, anticoagulation is strongly indicated. With an increase in the number of patients with prosthetic heart valves, as well as the increase in maternal age, the issue of anticoagulation has become a very important one. Despite the widespread use of warfarin and unfractionated heparin during pregnancy, the optimal use of anticoagulants during pregnancy remains controversial because of a lack of appropriate prospective randomized clinical trials. In fact, even retrospective data on heparin provide miserably inadequate information for those making a decision on the correct dosing regimen. More recently, low molecular weight heparin has been proposed as a safer method of anticoagulation. This review summarizes current data and recommendations on anticoagulation during pregnancy.     

心脏人工瓣膜术后真菌性心内膜炎2例报告及治疗策略文献综述

目的探讨心脏人工瓣膜置换术后真菌性心内膜炎的治疗策略。方法对2例心脏人工瓣膜术后并发严重真菌感染病例进行回顾性分析,并进行相关文献复习。结果 2例患者术后并发真菌性心内膜炎,均影响瓣膜功能,术后均反复住院,病例一,心脏术后45 d出现发热,返院复诊,予以急诊在体外循环下行再次二尖瓣置换术,术后赘生物培养为黄曲霉菌;病例二,心脏术后5个月在体外循环下行主动脉壁赘生物清除,术后赘生物病理提示毛霉菌。2例患者均及时手术清除感染灶并进行规范抗真菌治疗,曲霉菌感染患者抢救无效,毛霉菌感染患者治愈,后者抗真菌治疗强度更大。结论心脏人工瓣膜置换术后并发真菌性心内膜炎,预防是关键,治疗要及时、有效,抗真菌药物必须足量、足疗程。     

Use of contraceptive methods by women with current venous thrombosis on anticoagulant therapy: a systematic review

Background

As nearly all women with venous thromboembolism (VTE) will be treated with anticoagulant therapy, it is important to consider how anticoagulation affects the safety of contraceptive use.

Study design

We conducted a systematic review of the literature regarding use of contraceptive methods in women with current VTE on anticoagulant therapy. Due to the limited direct evidence that was identified, we expanded our search to include women on anticoagulant therapy for indications other than VTE and women with bleeding disorders.

Results

Six articles met our inclusion criteria. Three observational studies found the levonorgestrel-releasing IUD (LNG-IUD) was an effective treatment for menorrhagia for women on anticoagulation therapy or with bleeding disorders. Prevention of recurrent hemorrhagic ovarian cysts was seen in women on chronic anticoagulation treated with depot-medroxyprogesterone acetate (DMPA) in one small observational study. Among women with bleeding disorders, no complications were seen in 16 women with placement of the LNG-IUD. One pharmacokinetic study found no statistically significant interaction between combined oral contraceptives and warfarin. Other than one case report, no evidence was found regarding the risk of recurrent thrombosis in women on anticoagulation therapy using a contraceptive method.

Conclusion

The majority of studies in this review examined treatment effects of the LNG-IUD or DMPA on complications of anticoagulation and found overall beneficial effects of their use in these circumstances. Minimal evidence in women with inherited bleeding disorders suggests that insertion of the LNG-IUD does not pose major bleeding risks in these women with appropriate management.     

Deep venous thrombosis of the arm: etiology, diagnosis and treatment

Thrombosis of the upper extremity is frequently (30-52%) related to the use of an indwelling venous catheter, but it can also occur in healthy individuals after exercise. In the past it was considered a relatively benign thrombotic event, which was treated conservatively, sometimes even without anticoagulant therapy. Recent studies have shown that complications of deep venous thrombosis of the upper extremity occur frequently: pulmonary embolism (8-36%), recurrence thrombosis after cessation of anticoagulant treatment (2-15%) and post-thrombotic syndrome (up to 50%). Therefore when thrombosis of the upper extremity is clinically suspected, it should be objectively diagnosed by compression echography followed if negative by phlebography, with anticoagulant treatment directly afterward, preferably with low-molecular heparin and then acenocoumarol or phenprocoumon.     

Syncumar induced toxic liver damage

The authors present a case of chronic hepatitis presumably due to Syncumar treatment. The patient should be maintained on anticoagulant therapy due to combined prosthetic valve insertion. Chromatin activation of blood lymphocytes was investigated to justify the drug induced liver injury. In this test system Syncumar and other anticoagulant derivates gave a positive reaction to a different extent. The increased serum bilirubin and transaminase levels, which indicated liver injury showed regression in the course of the treatment and after changing Syncumar to Marcoumar (Phenprocoumon).     

Oral contraceptives in the immediate postpartum period

Although there is a critical need for effective contraception in the immediate postpartum period for women who are not breastfeeding, this need must be balanced against the inherent risks. The most effective form of contraceptive protection--oral contraceptives (OCs)--can present an increased risk of thromboembolism in the period after delivery. The thrombotic changes associated with pregnancy, and the statistics and vascular damage following a delivery, can combine to create greater potential for thromboembolism after delivery than during pregnancy. Reported here is the case of a 21-year-old woman who, 4 weeks postpartum, developed pain and swelling in the right lower calf and mottled discoloration extending from the proximal thigh to the toes. A diagnosis of deep venous thrombosis was made and heparin was administered. In the hospital, the patient experienced pleuritic chest pain and diaphoresis. A ventilation-perfusion scan indicated a pulmonary embolism. 1 week after delivery, the patient had initiated use of Triphasil. Although this woman had other risk factors (obesity, light cigarette smoking, and a sedentary life-style), OC use in the immediate postpartum period may have been the final factor precipitating the thromboembolic event. It is recommended that OC use should be delayed until at least 2 weeks postpartum in women without other risk factors for thromboembolism and until 4-6 weeks postpartum in those with such factors.     

The effect of levonorgestrel-releasing intrauterine device on menorrhagia in women taking anticoagulant medication after cardiac valve replacement

Background

This study was conducted to evaluate the effect of levonorgestrel-releasing intrauterine devices (LNG-IUDs) on menorrhagia in patients receiving anticoagulant therapy after cardiac valve replacement.

Study Design

Forty women with menorrhagia who underwent cardiac valve replacement and were taking anticoagulant medication were enrolled in the study. The women were randomly divided into two groups: LNG-IUDs were inserted into 20 women in Group 1 over the first 3 days of menstrual bleeding, while the women in Group 2 were followed without any intervention. The activated partial thromboplastin time, prothrombin time, international normalized ratio, hematocrit level, hemoglobin level, ferritin level and pictorial bleeding assessments for the quantity of menstrual bleeding were recorded.

Results

Three months after insertion of LNG-IUDs, the women in Group 1 had a significant decrease in blood loss and higher hemoglobin, hematocrit and ferritin values. No difference was detected for these parameters in the control group at the third and sixth months of the study. Coagulation parameters did not differ between the two groups.

Conclusion

LNG-IUDs can be considered as an effective non-surgical treatment for menorrhagia in women receiving anticoagulant therapy after cardiac valve replacement.     

Doppler echocardiography in the examination of normally functioning artificial mitral and aortic valves

Patients with prosthetic valves were investigated by Doppler echocardiography in 902 cases between November 1987 and February 1990. The parameters of 209 of 344 mitral and 258 of 299 aortic prosthetic valves were evaluated. No significant correlation was found between the type of aortic or mitral prosthetic valves and the measured gradient. As concerns the size of the valve and the measured gradient, a close correlation for aortic valve replacement was detected. For a normally functioning mitral prosthetic valve, a maximum early diastolic velocity of less than 2 m/s (16 mm Hg gradient) and a pressure half-time of less than 130 ms (mitral valve area 1.8 cm2) were characteristic. In cases of aortic valve replacements, the maximum velocity was less than 3 m/s (36 mm Hg gradient), except for the small-diameter valves. More than 95% of the cases met these criteria. (Even if small-diameter valves were included, a maximum velocity of more than 3 m/s occurred only in 8.9%.) Doppler echocardiography is a suitable tool for detecting normal prosthetic valve function, while colour Doppler allows the optimal alignment of jet direction and Doppler beam.     

中西医结合治疗急性期下肢深静脉血栓形成60例

目的研究中西医结合治疗下肢深静脉血栓形成的效果。方法60例下肢深静脉血栓形成患者经过彩超多普勒超声的无创诊断后，采用小剂量尿激酶等西药溶栓抗凝治疗结合活血化瘀、清热利湿中药治疗并评定效果。结果60例患者．临床治愈44例，显效11例，有效3例，无效2例，临床有效率为96．67％。结论中西医结合治疗下肢深静脉血栓形成有显著疗效。     

Radiation-induced arterial disease

Arterial occlusive disease developed after radiation therapy in three patients: a woman aged 56 had a sensation of heaviness in her right arm and bluish-black discolorations of fingers 3 years after radiation therapy for breast carcinoma, and two men aged 46 and 45 years had intermittent claudication 23 and 14 years, respectively, after radiation therapy for testicle malignancy. After creation of a bypass, the symptoms subsided. Radiation-induced arterial disease is a rare complication after radiotherapy and usually presents after a latent period of several years. Arterial lesions induced by radiotherapy may be distinguished from atherosclerotic lesions by their atypical localization, limited to the irradiated sites, and occurrence at an earlier age. Symptoms may be masked by pain, limitation of motion, nerve root damage and lymphoedema and may therefore not always be recognized. Indications for treatment are identical to those for atherosclerotic occlusive disease, but due to increased risk of restenosis, rethrombosis and graft infection, percutaneous transluminal angioplasty (with or without stent), endarterectomy or venous bypass surgery should be preferred to prosthetic bypass material.     

Optimizing the use of 17P in pregnant managed Medicaid members

OBJECTIVE: To evaluate the effect of 17 alpha-hydroxyprogesterone caproate (17P) on reducing the rate of neonatal intensive care unit (NICU) admissions and premature births in a managed Medicaid population that has a history of preterm delivery. Specifically, to measure the effect of initiating 17P treatment during the recommended time frame of 16-21 weeks gestation versus after 21 weeks gestation. DESIGN: A 2004-2007 observational, causal comparative study reviewed birth outcomes in 104 pregnant women with a confirmed history of preterm delivery. Women whose 17P treatment was initiated during the recommended time frame of 16-21 weeks gestation were compared to those whose treatment was initiated after 21 weeks gestation. METHODOLOGY: Intervention included offering 17P as a benefit to pregnant women who had a history of preterm delivery and who were deemed to be appropriate candidates for this treatment by their physician. RESULTS: No significant changes in birth outcomes were noted when comparing those members whose treatment was initiated during the recommended time frame of 16-21 weeks versus those whose treatment began after 21 weeks gestation. Members who received therapy of at least five injections of 17P, as opposed to those receiving fewer than five injections, experienced a statistically significant reduction in NICU admissions and in preterm birth at fewer than 37 weeks and at fewer than 32 weeks. CONCLUSION: The number of injections and not the time frame, which had been indicated by previous research, the initiation of 17P therapy is the factor in reducing preterm birth and decreasing NICU admissions for pregnant women with a history of preterm birth in a managed Medicaid population.     

The thrombosis service as a source of information for studies in patients with heart valve prostheses]

A new study design was evaluated for the estimation of the incidence of thromboembolic complications, bleeding complications and endocarditis in patients with prosthetic heart valves. Thromboembolism is a serious complication in patients with artificial heart valves. Consequently lifelong anticoagulation therapy is indicated for such patients. In the Netherlands the intensity of the anticoagulation is monitored by a network of regional anticoagulation services. The computerized patient information system of the Leiden anticoagulation service was used for a two year follow-up study of patients with mechanical heart valves. In these years anticoagulation was monitored in 273 patients with a total follow-up period of 442 patient-years. The incidence figures for thromboembolism, bleeding complications and endocarditis were 0.9/100 patient-years, 5.6/100 patient-years and 0.2/100 patient-years, respectively. The findings are similar to those of classical follow-up studies. This method is not suitable for detection of the direct early postoperative mortality or for follow-up of patient with heterografts. We conclude that the detection and follow-up by means of regional anticoagulation service offers an opportunity to investigate patients with mechanical heart valves in an efficient way without notable selection.