Thrombosis during pregnancy: risk factors,diagnosis and treatment

Venous thromboembolism occurs infrequently but is a leading cause of illness and death during pregnancy and the puerperium and remains a diagnostic and therapeutic challenge. In the general population the incidence of pregnancy associated VTE has been estimated to vary from 1 in 1000 to 1 in 2000 deliveries. The risk of VTE is five times higher in a pregnant woman than in a nonpregnant woman of similar age. Postpartum VTE is more common than antepartum VTE. Women with congenital abnormalities or persistent presence of antiphospholipid antibodies have an increased risk of VTE during pregnancy and the puerperium. In individuals with well defined hereditary thrombosis risk factors, such as the factor V:R506Q mutation, the factor II:G20210A variation, antithrombin-deficiency or protein C-deficiency, a relative risk of pregnancy associated VTE between 3.4 and 15.2 has been found. Women with previous VTE have an approximately 3.5 fold increased risk of recurrent VTE during pregnancy compared to non-pregnant periods. Our ability to diagnose deep-vein thrombosis clinically is generally poor and is further hampered during pregnancy since dyspnea, tachypnea, swelling and discomfort in the legs are common. Objective diagnosis is essential for treatment decisions. Exposure to radiation of less than 50,000 microGy (5 rad) has not been associated with a significant risk of fetal injury. Therefore, besides sonography, routine diagnostic procedures should be performed, if clinically necessary. Heparin does not cross the placenta and is therefore the anticoagulant treatment of choice during pregnancy. In case of acute new onset of thrombosis during pregnancy, treatment is performed like in non-pregnant patients with acute deep vein thrombosis or pulmonary embolism. There is ongoing debate, whether or not pregnant women with previous venous thrombosis should routinely receive prophylactic anticoagulation. In patients who have hereditary antithrombin deficiency, antiphospholipid antibodies, a combined abnormality or a history of a severe thrombotic event (pulmonary embolism, extended deep vein thrombosis) should be advised to use prophylactic heparin during pregnancy, starting during the first trimester. Post partum prophylaxis should be given in all women with an increased risk for VTE.     

上肢创伤骨折围手术期并发深静脉血栓的诊治体会

目的探讨上肢创伤骨折并发深静脉血栓(DVT)的诊断和治疗方法。方法对16例上肢创伤围手术期合并DVT患者的诊断及治疗情况进行回顾性分析。诊断方法有上肢血管彩色多普勒超声、多层螺旋CT血管成像(CTA)、上肢动脉造影以及血浆D-二聚体检测,治疗方法以尿激酶溶栓联合低分子肝素钙抗凝为主。结果 16例患者中血清D-二聚体水平增高14例,经上肢血管彩色多普勒超声检查诊断8例,经CTA检查发现3例,经上肢血管造影诊断5例。6例术前并发DVT患者经治疗后5例血栓消失,行骨折切开复位术,术后痊愈出院;10例术后并发DVT患者经治疗后8例血栓消失,2例在住院期间并发肺栓塞,1例经积极抢救成功,1例患者抢救无效死亡。结论彩色多普勒超声检查是诊断上肢创伤骨折合并DVT的首选方法,一旦确诊应早期溶栓及抗凝治疗。     

Cytomegalovirus‐associated cerebral sinus vein thrombosis

Cytomegalovirus (CMV)‐associated thrombosis has been reported many times in the medical literature, and most patients had deep vein thrombosis and/or pulmonary embolism. CMV‐associated cerebral sinus vein thrombosis has been reported only twice. We present an immunocompetent patient with CMV‐associated cerebral sinus vein thrombosis and no other thrombosis risk factors. This is another example of the pro‐thrombotic features of CMV. Physicians should be alert for symptoms and signs of acute CMV infection in patients with thrombosis. J. Med. Virol. 84:1934–1936, 2012. © 2012 Wiley Periodicals, Inc.     

Activated protein C resistance, factor V Leiden and assessment of thrombotic risk

Venous thromboembolism comprises deep vein thrombosis (DVT) and pulmonary embolism (PE). Acute venous thromboembolism (VTE) is a serious and potentially fatal disorder which often complicates the course of hospitalized patients, but also affects ambulatory and otherwise healthy people. The annual incidence of venous thromboembolism is 1 to 2 cases per 1000 person and the risk of the disorder rises exponentially with age, from an annual rate of less than 5 per 100,000 children to greater than 400 per 100,000 adults older than 80 years.     

Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study

Background  

Venous thromboembolism (VTE) is a common complication during and after a hospital admission. Although it is mainly considered a complication of surgery, it often occurs in people who have not undergone surgery, with recent evidence suggesting that immune-mediated diseases may play a role in VTE risk. We, therefore, decided to study the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in people admitted to hospital with a range of immune-mediated diseases.     

Thromboprophylaxis in medical patients--why not for all?

Venous thromboembolism (VTE) is a major problem in non-surgical patients admitted to the hospital, both during the hospitalization period and after discharge. Risk factors for VTE are well known and scoring systems have been published. Nevertheless, prophylaxis against VTE is in many hospitals used less often than ideal and also inappropriately. Electronic tools to alert the physicians to provide prophylaxis and suggest suitable measures have shown promising results with a reduction of clinically relevant VTE. Large randomized clinical trials have demonstrated efficacy of low molecular-weight heparin (LMWH), pentasaccharide(fondaparinux) and unfractionated heparin. The results were, however, driven by asymptomatic deep vein thrombosis (DVT), including distal DVT in some studies. A reduction of pulmonary embolism is achieved, but without any significant effect on the mortality. The agents are generally safe, with only a small increase of major bleeding, less with LMWH than with unfractionated heparin. The challenge is still to direct the efforts to the most appropriate patients.     

Pulmonary embolism in course of deep vein thrombosis of lower extremities in patient wit bilateral femoral bone fracture after car accident injuries

The incidence of deep vein thrombosis in Western World is estimated at about 1 case/1000/year and of pulmonary embolism at 0.5 case/1000/year. Mortality in untreated pulmonary embolism is 30%. With adequate treatment (anticoagulation) it can be decreased to 2-8%. Deep vein thrombosis and pulmonary embolism are frequent complications of various surgical procedures, especially of orthopedic interventions on hip joint. When surgery has to be performed in patient with high risk of pulmonary embolism, anticoagulant prophylaxis should be performed. Venous thromboembolic disease is the most important cause of mortality in trauma patients. We present a case of 46 years old man with bilateral fracture of femoral bone after car accident injury in whom signs of deep venous thrombosis and pulmonary embolism were observed despite the use of anticoagulant prophylaxis.     

PHLECO: a multicenter study of the fate of 1647 hospital patients treated conservatively without fibrinolysis and surgery

Summary The PHLECO Study (phlebothrombosis conservative therapy) is a multicenter investigation of patients with deep vein thrombosis receiving conservative nonfibrinolytic hospital treatment. A second study (part II : PHLEFI, phlebothrombosis fibrinolytic treatment) to be published later deals with the outcome of fbrnolytic therapy. In both studies the incidence of life-threatening sequelae, such as pulmonary embolism, is of major interest. The 49 medical departments participating in the study mailed the relevant data to the Duisburg Coordination Center for further data analysis and the following information was gained: (a) In descending order of frequency, the clinical conditions of thrombosis were: immobility, postoperative status, malignancy, hormone treatment, posttraumatic conditions, and pregnancy. (b) In descending order of frequency, the sites of thrombosis were: femoral vein, calf vein, iliac vein, popliteal vein, and subclavian vein. Left-sided thrombosis predominated in the iliac and subclavian vein groups. (c) In descending order of frequency, the treatment regimens employed were: intravenous heparin+ oral anticoagulants, intravenous heparin+subcutaneous heparin, intravenous heparin alone, subcutaneous heparin alone, intravenous heparin+subcutaneous heparin+oral anticoagulants, subcutaneous heparin+oral anticoagulants, intravenous heparin + platelet aggregation inhibitors. (d) The average hospital stay was 23.7 + 15.6 days. No correlation existed between duration of hospital stay and particular types of therapy. (e) The incidence of nonfatal pulmonary embolism was 16.1% while that of fatal pulmonary embolism was 2.33%. (f) Women outnumbered men in the group with fatal pulmonary embolism, and the death rate among older patients was higher than that among younger patients. (g) Patients with fatal pulmonary embolism had a shorter history of thrombosis than patients in the unselected cohort (patients with and without pulmonary embolism). (h) Iliac vein thrombosis correlated with the highest incidence of fatal pulmonary embolism, with the right iliac vein predominating. (i) Calf vein thrombosis produced pulmonary embolism only very rarely, and pulmonary embolism was not observed in the group of patients with subclavian vein thrombosis.Abbreviations PHLECO phlebothrombosis conservative treatment - PHLEFI phlebothrombosis fibrinolytic treatment - DVT deep vein thrombosis PHLECO Coordination CenterThis study was supported by a grant from the Verein zur Förderung der Gesundheit im Alter e.V.The study center and the names of participating clinicians are listed at the end of this paper     

Little impact of antiplatelet agents on venous thromboembolism after hip fracture surgery

Since the late 1980s, low dose aspirin has been used to prevent stroke and ischemic heart disease. However, prophylactic effect of antiplatelets against venous thromboembolism (VTE), in patients who undergo hip fracture surgery (HFS) is controversial. Our purpose was to determine the incidence of symptomatic VTE after HFS and to evaluate whether antiplatelets reduce the development of symptomatic VTE following HFS. We retrospectively reviewed 858 HFS in 824 consecutive patients which were performed from May 2003 to April 2010 at an East Asian institute. We compared the incidence of symptomatic VTE in antiplatelet users and non-users using multivariate logistic regression analyses. Overall incidences of symptomatic pulmonary embolism including fatal pulmonary embolism, and symptomatic deep vein thrombosis in this study were 2.4% (21/858), and 3.5% (30/858), respectively. The incidence of symptomatic VTE was 4.8% (12/250) in antiplatelet users and 4.3% (26/608) in non-users (P = 0.718). It is suggested that antiplatelet agents are not effective in prevention of symptomatic VTE after HFS.     

腔静脉滤器置入联合胫后静脉置管溶栓治疗急性下肢深静脉血栓形成

目的：探讨腔静脉滤器置入联合胫后静脉途径置管直接溶栓治疗急性下肢深静脉血栓形成的临床应用价值。方法：18例急性下肢深静脉血栓形成患者,先行患肢血管造影明确诊断后,在下腔静脉滤器置入的基础上采用胫后静脉置管微泵持续推注尿激酶直接溶栓治疗,对其中髂静脉狭窄5例和闭塞1例患者在拔除溶栓导管后实施髂静脉球囊扩张成形术。结果：18例患者置管溶栓治疗后症状均得到明显改善,1例术前合并肺动脉栓塞者症状消失。溶栓后的健、患侧大腿周径差及小腿周径差比治疗前明显减小,差异均有统计学意义（P〈0．001）。治疗期间,无一例围手术期死亡,无肺动脉栓塞发生,无置管处渗血或血肿形成、神经损伤等置管相关并发症发生。术后17例获随访,随访时间1～12个月,平均5个月。15例肢体肿胀基本消退、肌张力减低、恢复正常劳动力;2例活动后肢体出现轻微肿胀伴沉重感,能进行正常家务劳动;17例均未出现患肢浅静脉曲张及静脉营养性障碍。结论：腔静脉滤器置入联合胫后静脉置管直接溶栓治疗急性下肢深静脉血栓形成具有疗效好、创伤小、安全性高、适应证宽,便于护理等优点,是一种安全、有效的治疗方法。     

Venous thromboembolism in Latin America: a review and guide to diagnosis and treatment for primary care

There are various region-specific challenges to the diagnosis and effective treatment of venous thromboembolism in Latin America. Clear guidance for physicians and patient education could improve adherence to existing guidelines. This review examines available information on the burden of pulmonary embolism and deep vein thrombosis in Latin America and the regional issues surrounding the diagnosis and treatment of pulmonary embolism and deep vein thrombosis. Potential barriers to appropriate care, as well as treatment options and limitations on their use, are discussed. Finally, an algorithmic approach to the diagnosis and treatment of venous thromboembolism in ambulatory patients is proposed and care pathways for patients with pulmonary embolism and deep vein thrombosis are outlined for primary care providers in Latin America.     

Progestogens and venous thromboembolism among postmenopausal women using hormone therapy

Hormone therapy (HT) is the most effective treatment for correcting menopausal symptoms after menopause. HT initially consisted of estrogens alone and progestogens were secondly added to estrogens for preventing the risk of endometrial cancer associated to estrogens use. Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a major harmful effect of HT. It is now well known that oral and transdermal estrogens are differentially associated with VTE risk but progestogens may be another important determinant of the thrombotic risk among HT users. Both randomized controlled trials and meta-analysis of observational studies suggested that the VTE risk was higher among users of estrogens plus progestogens than among users of estrogens alone. With respect to the different pharmacological classes of progestogens, there is evidence for a deleterious effect of medroxyprogesterone acetate on VTE risk. In addition, observational studies showed that norpregnane derivatives were significantly associated with an increased VTE risk whereas micronized progesterone could be safe with respect to thrombotic risk. The effect of tibolone on VTE risk remains uncertain. In conclusion, progestogens may have differential effects on VTE risk according to the molecules and therefore represent an important potential determinant of the thrombotic risk among postmenopausal women using estrogens.     

The influence of weather and environment on pulmonary embolism: pollutants and fossil fuels

Previous publications have highlighted seasonal variations in the incidence of thrombosis and pulmonary embolism, and that weather patterns can influence these. While medical risk factors for pulmonary thrombo-embolism such as age, obesity, hypercoagulable states, cancer, previous thrombo-embolism, immobility, limb paralysis, surgery, major illness, trauma, hypotension, tachypnoea and right ventricular hypokinesis are not directly implicated regarding environmental factors such as weather, they could be influenced indirectly by these. This would be especially relevant in polluted areas that are associated with a higher pulmonary embolism risk. Routine nuclear medicine lung ventilation/perfusion studies (V/Q scans) of 2071 adult patients referred to the nuclear medicine department of the Royal Surrey County Hospital in Guildford, UK, between January 1998 and October 2002 were reviewed and 316 of these patients were classified as positive for pulmonary embolism with high probability scan on PIOPED criteria. The occurrence of positive scans was compared to environmental factors such as temperature, humidity, vapour pressure, air pressure and rainfall. Multiple linear regression was used to establish the significance of these relations. The incidence of pulmonary embolism was positively related to vapour pressure and rainfall. The most significant relation was to vapour pressure (p=0.010) while rainfall was less significant (p=0.017). There was no significant relation between pulmonary embolism and air pressure, humidity or temperature. It is postulated that rainfall and water vapour may be contributary factors in thrombosis and pulmonary embolism by way of pollutants that are carried as condensation nuclei in micro-droplets of water. In particular, fossil fuel pollutants are implicated as these condensation nuclei. Pollutants may be inhaled by populations exposed to windborne vapour droplets in cities or airports. Polluted vapour droplets may be absorbed by the lung to hasten coagulation cascades in the blood. This may lead to thrombosis and increased pulmonary embolism under high vapour pressure conditions. With combined factors such as pre-existing ill health or immobility on long flights, the risk of thrombosis and consequent embolism might increase substantially.     

Vena cava filters and treatment of venous thromboembolism in cancer patients

Despite numerous publications, there is still only one randomised clinical trial with vena cava filter in the treatment of venous thromboembolism (VTE). This study has shown a potential and early benefit on the risk of pulmonary embolism (PE) (the first three months) but a late negative effect on the risk of deep vein thrombosis (DVT) recurrences (beyond the sixth month) especially on the risk of filter thrombosis. Consequently, the international recommendations are against a systematic use of vena cava filter to treat VTE (grade 1A) and they suggest to use them in case of a recurrence despite adequate treatment or in case of a contra-indication to anticoagulants (grade 2C). But these two conditions are frequent with VTE associated with cancer since, the risk of VTE recurrences is about 5 to 10% despite prolonged low-molecular-weight heparins (LMWH) treatment and the major bleeding risk is also about 5 to 10% in this case.These VTE recurrences are frequently early (first month of treatment) and contra-indications to anticoagulants due to major bleeding are mostly temporary. In this way, retrievable vena cava filters (possible retrieval until six months after placement) could be useful in order, to prevent recurrences during the thromboembolic risk period without any prolonged increasing risk of vena cava thrombosis. However, vena cava filters could be associated with some complications (tilt, migration sepsis...). So without any strong validation, they have still to be considered as a therapeutic strategy needing to be evaluated especially in cancer patient.     

The ethical decisions UK doctors make regarding advanced cancer patients at the end of life - the perceived (in) appropriateness of anticoagulation for venous thromboembolism: A qualitative study

ABSTRACT: BACKGROUND: Cancer patients are at risk of developing blood clots in their veins - venous thromboembolism (VTE) - which often takes the form of a pulmonary embolism or deep vein thrombosis. The risk increases with advanced disease. Evidence based treatment is low molecular weight heparin (LMWH) by daily subcutaneous injection. The aim of this research is to explore the barriers for doctors in the UK when diagnosing and treating advanced cancer patients with VTE. METHOD: Qualitative, in-depth interview study with 45 doctors (30 across Yorkshire, England and 15 across South Wales). Doctors were from three specialties: oncology, palliative medicine and general practice, with a mixture of senior and junior staff. Framework analysis was used. RESULTS: Doctors opinions as to whether LMWH treatment was ethically appropriate for patients who were symptomatic from VTE but at end of life existed on a shifting continuum, largely influenced by patient prognosis. A lack of immediate benefit coupled with the discomfort of a daily injection had influenced some doctors not to prescribe LMWH. The point at which LMWH injections should be stopped in patients at the end of life was ambiguous. Some perceived overcaution in their own and other clinicians treatment of patients. Viewpoints were divergent on whether dying of a PE was considered a "good way to go". The interventionalism and ethos of palliative medicine was discussed. CONCLUSIONS: Decisions are difficult for doctors to make regarding LMWH treatment for advanced cancer patients with VTE. Treatment for this patient group is bounded to the doctors own moral and ethical frameworks.     

关节置换后的深静脉血栓形成

背景：关节置换后形成深静脉血栓发病的概率为40%~60%,而深静脉血栓容易出现肺栓塞并发症而危及生命,死亡率高达20%~30%。 目的：对骨科关节置换后下肢深静脉血栓形成的病因与治疗及并发症肺栓塞的治疗进展进行阐述。 方法：以“关节置换,静脉栓塞,肺栓塞,病因,预防,治疗”为关键词应用计算机检索2000/2010万方数据库和中国期刊全文数据库。 结果与结论：关节置换后下肢深部静脉血栓形成的病因及发病机制有着多方面的因素,深静脉血管壁损伤,血流缓慢和高凝状态是静脉血栓形成的3个因素。患者的全身状况差,合并其他疾病,关节置换手术创伤,手术麻醉方法,手术时间延长,肢体固定以及长期卧床都是下肢深静脉血栓形成的高危因素。下肢深静脉栓塞和肺栓塞是导致关节置换后患者高致残率和高死亡率的主要原因。临床医生应于术前对关节置换患者形成深静脉血栓的危险因素进行系统评估,并采取相应措施,最大限度降低其发生率。     

Venous thromboembolic disease in Klinefelter's syndrome

In a series of 412 patients with Klinefelter's syndrome observed over periods ranging from 1 to 20 years, the frequency of hypostatic ulceration, deep vein thrombosis and pulmonary embolism was found to be raised. The prevalence of past or present hypostatic ulceration was 6 %, which is 20–50 times higher than in the general population. The incidence of deep vein thrombosis in subjects aged between 30 and 70 years was 22.8 cases per 10,000 patient-years at risk. In community studies the incidence of this condition is around 4 new cases per 10,000 men per year. The frequency of pulmonary embolism was 16 cases per 10,000 patient-years at risk, compared with an expected figure of 0.9 to 3 cases per 10,000 men per year.     

利伐沙班对髋、膝关节置换术后抗凝疗效的临床观察

目的 观察利伐沙班对髋、膝关节置换术后预防下肢深静脉血栓的疗效性和安全性.方法 回顾性分析髋、膝关节置换术的患者205例,将其分为两组,利伐沙班组94例,给予利伐沙班10 mg/d口服,连续14 d;依诺肝素组111例,每12 h给予依诺肝素30 mg皮下注射,连续10 d.入选患者术前均无下肢深静脉血栓,术后14 d行双下肢静脉彩超检查有无深静脉血栓形成,并观察两组用药期间有无肺动脉栓塞和严重出血事件的发生.结果 利伐沙班组深静脉血栓形成的发生率2.13%,显著低于依诺肝素组9.0%,两组均未发生肺动脉栓塞和严重出血事件.结论 应用利伐沙班较依诺肝素更有效预防髋、膝关节置换术后下肢深静脉血栓的形成,二者均较安全,出现严重出血事件很少.     

Evaluation of soleal vein thrombosis

Deep vein thrombosis (DVT) is closely associated with pulmonary thromboembolism. In approximately 90% of case, the lower limbs are the source of DVT. The detection rate for de novo and chronic thrombus of the soleal vein is highest in the embolism position of deep vein thrombosis. Because there are few symptoms characteristic for soleal vein thrombosis, its diagnosis by the clinical symptoms is very difficult. Recently, ultrasonography has become the first choice for the imaging and diagnosis of DVT, and is also useful for the diagnosis of soleal vein thrombus. In particular, it is very important for the detection of thrombus in the soleal vein return course.     

Prevalence of pulmonary embolism at necropsy in patients with cancer.

The series studied comprised 6197 patients who had died of or who had cancer at death and represents all patients with cancer from 21,530 necropsies performed at this department from 1960-84. Pulmonary embolism was significantly more common among cancer patients than in those with non-neoplastic diseases. Among those palliatively treated, patients with ovarian cancer, cancer of the extrahepatic bile duct system, and cancer of the stomach had the highest prevalence of pulmonary embolism (34.6%, 31.7%, and 15.2%, respectively). Necropsy patients with cancer of the oesophagus and larynx, together with leukaemia, myelomatosis, and malignant lymphoma had the lowest prevalence (0-5.6%). Palliatively treated cancers in organs of the peritoneal cavity had a significantly higher incidence than all other cancers combined. Cancer of the peritoneal cavity may impede venous drainage from the lower limbs and thus be an important factor in the onset of deep calf vein thrombosis and pulmonary embolism. It is concluded that cancer represents an increased risk factor for onset of pulmonary embolism, in particular in patients with ovarian cancer and cancer of the extrahepatic bile duct system.