恶性肿瘤并发静脉血栓栓塞症的临床分析

目的分析并发静脉血栓栓塞症(VTE)恶性肿瘤患者的原发肿瘤种类、分期、分化程度等,以识别高危患者,提高防治意识,减少VTE的发生。方法回顾性分析北京医院2003年1月至2013年1月期间并发静脉血栓栓塞症的恶性肿瘤患者的年龄、性别、基础疾病、原发肿瘤种类、病理类型、分化程度、TNM分期、化疗方案及预后等临床信息。结果在所有18 531例恶性肿瘤患者中,280例并发VTE,其中男性157例,女性123例,年龄(66.60±12.60)岁。包括单纯肺栓塞(PTE)41例,单纯下肢深静脉血栓形成(DVT)189例,PTE合并DVT 50例。肺癌82例,消化道肿瘤78例,泌尿系肿瘤32例,妇科肿瘤27例,血液科肿瘤27例,乳腺癌12例,其他部位肿瘤22例。相比未并发VTE肿瘤患者,并发VTE多见于肺癌、妇科肿瘤和其他肿瘤患者,差异有统计学意义(P0.05)。151例(53.9%)并发VTE肿瘤患者病理类型为腺癌;206例(73.6%)患者发生VTE时,肿瘤处于进展期;247例有明确TNM分期患者中Ⅲ~Ⅳ期患者187例(66.8%);144例有明确病理组织分化程度报告,中、低度分化程度者120例(85.4%)。至随访结束,共有130例患者死亡,中位生存时间为(24.0±7.8)个月,明确诊断VTE后3,6,9,12个月的累积死亡率分别为46.9%、69.2%、80.0%和82.3%。导致死亡的主要原因是肿瘤本身、肺栓塞和感染。结论肿瘤与VTE密切相关,腺癌、进展期肿瘤、分化程度低的肿瘤患者和化疗方案中含铂类药物者更易发生VTE,临床医师应注意对这部分患者进行VTE风险评估,采取必要的预防措施,减少VTE的发生。     

High D-dimer levels are associated with poor prognosis in cancer patients

Background

Systemic activation of hemostasis is frequently observed in cancer patients, even in the absence of thrombosis. Moreover, this activation has been implicated in tumor progression, angiogenesis and metastatic spread. Increased levels of D-dimer, which is a degradation product of cross-linked fibrin, indicate a global activation of hemostasis and fibrinolysis.

Design and Methods

In a prospective and observational cohort study, we assessed the prognostic value of D-dimer levels for overall survival and mortality risk in 1178 cancer patients included in the Vienna Cancer and Thrombosis Study (CATS). Patients were followed over 2 years at regular intervals until occurrence of symptomatic venous thromboembolism or death. D-dimer levels were measured with a quantitative D-dimer latex agglutination assay

Results

The main solid tumors were malignancies of the lung (n=182), breast (n=157), lower gastrointestinal tract (n=133), pancreas (n=74), stomach (n=50), kidney (n=37), prostate (n=133), and brain (n=148); 201 of the patients had hematologic malignancies; 63 had other tumors. During a median follow-up of 731 days, 460 (39.0%) patients died. The overall survival probabilities for patients with D-dimer levels categorized into four groups based on the 1^st, 2^nd and 3^rd quartiles of the D-dimer distribution in the total study population were 88%, 82%, 66% and 53% after 1 year, and 78%, 66%, 50% and 30% after 2 years, respectively (P<0.001). The univariate hazard ratio of D-dimer (per double increase) for mortality was 1.5 (95% confidence interval: 1.4–1.6, P<0.001) and remained increased in multivariable analysis including tumor subgroups, age, sex and venous thromboembolism.

Conclusions

High D-dimer levels were associated with poor overall survival and increased mortality risk in cancer patients.     

Treatment of venous thromboembolism with low-molecular-weight heparin

Summary There is now ample evidence to indicate that certain low-molecular-weight heparins given subcutaneously can replace continuous intravenous unfractionated heparin for the initial treatment of venous thromboembolism. The low-molecular-weight heparins have a predictably high absorption rate when given subcutaneously and a prolonged duration of action, permitting them to be given by a once or twice daily injection for the prevention or treatment of venous thrombosis. Furthermore, treatment does not require laboratory monitoring, thus eliminating the need for continuous IV infusion and permitting the early discharge of patients with venous thromboembolism. This should eventually lead to the outpatient treatment of venous thromboembolism. Studies to date indicate that low-molecular-weight heparin is more cost-effective than unfractionated heparin in the treatment of venous thromboembolism and the cost effectiveness will be increased by out-of-hospital treatment. At the present time, the findings associated with any individual lowmolecular-weight heparin preparation cannot be extrapolated to different low-molecular-weight heparins, and therefore each must be evaluated in separate clinical trials. The information to date is that low-molecular-weight heparin is safer and more effective than continuous intravenous unfractionated heparin in the treatment of proximal venous thrombosis. The decreased mortality rate seen in two clinical trials, particularly in patients with metastatic cancer, was quite unexpected. This requires further confirmation in larger prospective randomized trials.     

胰腺炎导致门静脉系统血栓形成发病机制及其防治方法的探讨

胰腺炎是多种病因导致胰酶在胰腺内被激活后引起胰腺组织自身消化、水肿、出血、坏死的炎症反应,或导致胰腺局部、节段性、弥漫性慢性进展性炎症。在急性胰腺炎（acute pancreatitis,AP）早期,胰腺细胞损伤导致局部的炎症反应,随着炎症细胞因子对胰腺组织的第二次打击,     

尿激酶延迟溶栓治疗下肢深静脉血栓形成的安全性和有效性

目的：探讨尿激酶延迟溶栓疗法下肢深静脉血栓形成（ＬＥＤＶＴ）的安全性和有效性。方法：在静脉造影确诊后,采用尿激酶延迟溶栓疗法（５０万ｕ１０ｍｉｎ内推入,随后１ｈ内静脉输液１０万ｕ,２－３ｄ每天静脉输液１００万ｕ,４－１４ｄ每天静脉输液２５－５０万ｕ）加每天皮下注射肝素钙５０ｍｇ（每１２ｈ１次）和口服阿司匹林１００ｍｇ（每天１次）治疗ＬＥＤＶＴ患者９例,结果：血栓完全溶解１例（１１．１１％）,部分溶     

Warfarin induction at 5 mg daily is safe with a low risk of anticoagulant overdose: results of an audit of patients with deep vein thrombosis commencing warfarin

BACKGROUND: Conventionally warfarin therapy is initiated using a loading dose given over several days. Daily international normalised ratio (INR) monitoring is recommended to prevent overdose; however, with a large proportion of patients with deep vein thrombosis now receiving treatment out of hospital daily blood tests are inconvenient. We introduced a low-dose protocol for starting anticoagulant therapy that only required INR testing on days 4 and 6 and audited the results to assess safety and efficacy. METHODS: Two-hundred and forty-eight patients with confirmed deep vein thrombosis were started on warfarin therapy at 5 mg daily for 3 days. INR measurements were taken at day 4 and day 6. RESULTS: Of these patients, 21% had an INR within the therapeutic range on day 4 and 52% had a therapeutic INR on day 6. The risk of overdose was small with only one case with an INR above 4.0 on day 4 and nine cases on day 6. There were no reported cases of bleeding. CONCLUSION: The low-dose protocol with infrequent testing is safe and convenient for outpatient management. However, our results suggest that patients on this protocol take between 6-10 days to achieve a stable INR.     

Concurrent protein C deficiency and lupus anticoagulants.

An inherited deficiency of protein C, a recognized hypercoagulable state, may cause a clinically significant deep venous thrombosis. Only some persons with a deficiency of protein C experience thrombosis, and almost always the thrombotic event occurs in the venous circulation. Warfarin-induced skin necrosis, a rare event observed in some patients soon after treatment with warfarin is begun, is believed to be another manifestation of this deficiency. We describe a young woman whose basal functional and antigenic levels of protein C were about 45% and who experienced both deep venous thrombosis and warfarin-induced skin necrosis in a clinically severe course. Evidence for lupus anticoagulants was present, with prolonged activated partial thromboplastin time that was corrected when lysed platelets were added, prolonged Russell's viper venom time, anticardiolipin antibodies, and other laboratory evidence. Lupus anticoagulants are associated also with a significant incidence of thrombosis, including arterial thrombosis, and this patient developed concurrently arterial thrombosis. The combined effects of protein C deficiency and lupus anticoagulants, exacerbated by other potentially thrombogenic conditions, are believed responsible for the severe thrombotic events experienced by this patient.     

创伤患者深静脉血栓形成与D-Dimer的相关性

目的分析创伤患者深静脉血栓形成（DVT）的发生率以及D-二聚体（D-Dimer）水平对DVT的诊断价值。方法选取单发股骨颈骨折、股骨转子间骨折、股骨干骨折、股骨髁间骨折予以静脉造影术检查的患者,以D-Dimer作为特异性纤溶过程标记物,采用胶体金免疫渗透试验定量检测,对D-Dimer浓度进行统计学分析。结果创伤患者DVT的发生率为11.4%。创伤患者DVT（＋）组D-Dimer浓度高于DVT（-）组（P〈0.05）。选取500μg/L作为正常参考值,其灵敏度为93.1%,特异度为63.6%,阳性预测值为24.8%,阴性预测值为98.6%。术前不同制动时间对D-Dimer浓度的影响差异有统计学意义（P〈0.05）。结论 D-Dimer浓度正常对排除创伤患者DVT具有临床意义,D-Dimer浓度升高对诊断创伤患者DVT不具有临床意义。术前制动时间对D-Dimer浓度具有影响。     

肝硬化患者门静脉血栓形成的临床表现和危险因素

目的研究肝硬化患者门静脉血栓(PVT)形成的临床表现及危险因素。方法收集2008年4月-2015年4月宁夏医科大学总医院收治的肝硬化患者资料541例。其中76例肝硬化合并PVT的患者为研究组,同阶段通过匹配患者的性别、年龄及肝功能Child-Pugh分级,76例肝硬化不合并PVT为对照组。对比分析两组患者的临床资料及相关检查指标。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验,并应用非条件Logistic回归模型筛选肝硬化PVT形成的独立危险因素。结果肝硬化PVT患者中,42.1%(32/76)隐匿起病,57.9%(44/76)有明显临床表现。大部分患者肝功能分级为Child-Pugh B和C级。血小板、血糖、中性粒细胞百分比、重度食管胃底静脉曲张、血浆D-二聚体、门静脉宽度、脾脏厚度在两组患者中差异有统计学意义(P值均0.05)。进一步非条件Logistic回归模型分析显示中性粒细胞百分比[比值比(OR)=1.044,P=0.040]、血浆D-二聚体(OR=0.091,P0.001)、门静脉宽度(OR=0.030,P=0.008)、脾脏厚度(OR=0.427,P=0.003)为PVT形成的危险因素。结论肝硬化PVT可隐匿起病,也可伴有不同的临床表现。肝硬化PVT常发生在晚期肝硬化患者中,血浆D-二聚体、门静脉宽度、脾脏厚度、中性粒细胞百分比为肝硬化PVT形成的独立危险因素。     

Venous thromboembolism associated with the management of acute thrombotic thrombocytopenic purpura

Venous thromboembolism (VTE) is not a feature of thrombotic thrombocytopenic purpura (TTP), but there has been a recent report of VTE in association with plasma exchange (PEX) treatment for TTP using the solvent detergent (SD) plasma, PLAS+SD. We reviewed the occurrence of VTE in 68 consecutive patients with TTP (25 men, 43 women). Eight documented VTE events [six deep venous thromboses (DVTs), three pulmonary emboli] were identified in seven patients (all female) during PEX therapy. All six DVTs were associated with central lines at the site of thrombosis. Other known precipitating factors included pregnancy, immobility, obesity and factor V Leiden heterozygosity. VTE occurred at a mean of 53 d following the first PEX. The European SD plasma, Octaplas was the last plasma to be used in PEX prior to the VTE in 7/8 events. This is the first report of VTE following Octaplas infusion. VTE is a multifactorial disease and, although several known precipitating factors were present in all patients in this study, the use of large volumes of SD plasma in PEX may be an additional risk factor. We recommend prevention of VTE with graduated elastic compression stockings (class I) at diagnosis and prophylactic low-molecular-weight heparin once the platelet count rises above 50 x 10(9)/l.     

Percutaneous transluminal coronary angioplasty in a patient with paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired chronic hemolytic anemia associated with an unusual susceptibility to hemolytic crisis, infection, and venous thrombosis which would be aggravated by a number of factors including surgery. We report a case of PNH undergoing percutaneous transluminal coronary angioplasty and discuss the corresponding perioperative management.     

原发性门静脉、肠系膜静脉广泛血栓伴发小肠梗阻1例治疗体会

肠系膜静脉血栓(mesenteric venous thrombosis,MVT)缺乏特异性的临床症状及体征,病情复杂,难于早期准确诊断,易误诊误治。对于有可疑诱发因素导致的无法用其他疾病解释的腹痛、腹胀、恶心、呕吐,需要考虑到MVT的可能,行腹部增强CT可明确诊断,给予积极的抗凝溶栓治疗,预防肠坏死、休克、多脏器功能衰竭等严重并发症,改善患者预后。及时跟踪患者病情,对于可能出现的并发症,应给予高度重视。     

Direct oral anticoagulant use in patients with thrombophilia,antiphospholipid syndrome or venous thrombosis of unusual sites: A narrative review

Direct oral anticoagulants (DOACs) are indicated in the treatment and prevention of venous thromboembolism (VTE). However, the use of DOACs in unusual VTE, including cerebral venous thrombosis (CVT) and splanchnic venous thrombosis (SVT), and in patients with biological thrombophilia including minor thrombophilia (Factor V Leiden and prothrombin G20210A), major innate thrombophilia (protein C and S deficiency, and antithrombin) and major acquired thrombophilia (antiphospholipid syndrome [APS]), remains controversial due to the paucity of available data. There are some reports of DOACs use in the initial treatment or long-term maintenance of patients with either CVT or SVT, but their efficacy remains unclear. The efficacy of DOACs may be suitable in patients with biological minor or major thrombophilia. The use of DOACs for the long-term maintenance of patients with APS is more contentious. Randomized clinical trials, which are currently underway, should offer definitive insight into the efficacy and safety profiles of DOACs in these patient populations.     

One-Month versus Six-Month Therapy with Oral Anticoagulants after Symptomatic Deep Vein Thrombosis

ABSTRACT. The length of time for which deep vein thrombosis (DVT) should be treated with oral anticoagulants (OA) is controversial. In this study, 135 patients with symptomatic first period DVT (83 % with proximal DVT) were randomly allocated to OA for one or six months. The diagnosis of initial and recurrent DVT was confirmed by phlebography or plethysmography and thermography, or by a combination of all these methods. Pulmonary emboli were confirmed by lung scans or at autopsy. The patients were followed for at least one year. One patient had to discontinue OA prematurely because of haemorrhage. Seventeen patients left the project for other reasons, ten during and seven after therapy; in one of these DVT recurred. The recurrence rate during the first year was high (17% symptomatic recurrences) irrespective of whether OA had been given for one or six months.     

44例恶性肿瘤并发下肢深静脉血栓形成的发病时间与原因探讨

目的探讨恶性肿瘤并发下肢深静脉血栓形成(DVT)的发病时间和原因.方法回顾性分析44例恶性肿瘤并发DVT的恶性肿瘤部位,手术与DVT发病的时间以及诊治方法等.结果经统计恶性肿瘤并发下肢DVT者,可发生在肿瘤根治术后的任何时间或非手术者中,非手术患者占41%(18/44).发生于术后6个月以内的手术患者中,多数发生于术后1～3个月内(9/14,占64%),发生于1周之内者较少(2/14).术后1年以上并发DVT者,大多同时发现有肿瘤转移病灶.经各类药物治疗,肢体肿胀均有明显消退.DVT的发生绝大多数与肿瘤局部压迫无关.结论对DVT患者应高度警惕有否恶性肿瘤发生,如有相关症状,应作相应肿瘤检查,以便尽早治疗.恶性肿瘤行根治术后1～3个月是并发DVT的高峰期,恶性肿瘤多年后并发DVT,常提示可能有肿瘤转移发生.     

Upper-extremity deep venous thrombosis: a review

Upper-extremity deep venous thrombosis is less common than lower-extremity deep venous thrombosis. However, upper-extremity deep venous thrombosis is associated with similar adverse consequences and is becoming more common in patients with complex medical conditions requiring central venous catheters or wires. Although guidelines suggest that this disorder be managed using approaches similar to those for lower-extremity deep venous thrombosis, studies are refining the prognosis and management of upper-extremity deep venous thrombosis. Physicians should be familiar with the diagnostic and treatment considerations for this disease. This review will differentiate between primary and secondary upper-extremity deep venous thromboses; assess the risk factors and clinical sequelae associated with upper-extremity deep venous thrombosis, comparing these with lower-extremity deep venous thrombosis; and describe an approach to treatment and prevention of secondary upper-extremity deep venous thrombosis based on clinical evidence.