Symptomatic thrombotic events among Egyptian patients with systemic lupus erythematosus: special consideration for renal vein thrombosis

OBJECTIVE: To evaluate the prevalence of symptomatic thrombotic events among Egyptian patients with systemic lupus erythematosus (SLE), and to evaluate the frequency and the risk factors associated with renal vein thrombosis in those patients. METHODS: Fifty-four patients with SLE, 51 (94.4%) females, were involved in this study. All of them were submitted for abdominal sonography, chest X-ray, echocardiography, and Doppler of renal, abdominal and lower limb veins, with examination of data on clinical and laboratory profile. Abdominal CT, brain MRI, MRI both hips, CT chest and pulmonary scintigraphy were used when needed. RESULTS: Sixteen patients (29.6%) were diagnosed with symptomatic thrombotic events. Eight patients had more than one type of thrombosis. Two patients (3.7%) were diagnosed by Doppler as having renal vein thrombosis (RVT). This was confirmed by abdominal CT. One of them presented with nephrotic syndrome, graded by renal biopsy as World Health Organization (WHO) class V, and had positive anticardiolipin antibodies (ACL). The other patient had RVT and inferior vena cava (IVC) thrombosis, nephrotic syndrome, positive ACL, and died before renal biopsy was performed. Both of them were without history of peripheral thrombotic events. One patient was diagnosed with IVC thrombosis, lupus nephritis grade II, positive ACL, and diagnosed by abdominal CT. One patient was diagnosed with portal vein thrombosis and had positive ACL. One patient with retinal vessel thrombosis and positive ACL. Four patients had deep vein thrombosis (DVT). Recurrent miscarriages were reported in 4 patients (7.4%), skin ulcerations in 3 (5.6%), avascular necrosis of the hips in 4 (7.4%), stroke in 1 (1.9%), and pulmonary hypertension in 2 patients (3.7%). CONCLUSION: Sixteen SLE patients (29.6%) were diagnosed with symptomatic thrombotic events. RVT was detected in 2 patients representing 3.7% of all patients, and 12.5% of patients with thrombosis. Both patients with RVT presented with nephrotic syndrome.     

Fibrinolytic therapy for bilateral renal vein thrombosis

A patient with nephrotic syndrome due to membranous glomerulonephritis experienced painful bilateral renal vein thrombosis (RVT) complicated by pulmonary emboli. He was treated with systemic fibrinolysis with streptokinase for 72 hours. Rapid clinical improvement of his condition, a fall in his serum creatinine level, and a sharp rise in his platelet count were observed. Venography verified complete lysis of the thrombus within the vena cava and reperfusion of the right renal vein. The left renal vein remained chronically occluded. Thrombolytic therapy should be further investigated as initial therapy for patients with clinical evidence of RVT.     

Simultaneous urokinase perfusion in renal artery and vein in a case of renal vein thrombosis]

We present he case of a young man with nephrotic syndrome, caused by membranous glomerulonephritis, who developed renal vein thrombosis with extension to the inferior vena cava is presented. Renal vein thrombosis was diagnosed by echo Doppler and confirmed by angio-CT scan. At the hospitalization the patient presented a severe left flank pain, edema of the lower limbs and painful left testicular tumefaction. The treatment consisted of: 1) systemic anticoagulation with sodic heparin, 2) placement of temporary vena cava filter through the right jugular vein, 3) direct thrombolysis into endocaval thrombus with early lysis of thrombus, and 4) renal thrombolysis with selective simultaneous renal artery and renal vein infusion of urokinase. Angiography performed after 24 hours of loco-regional thrombolysis showed complete lysis of renal thrombus; clinically there was a regression of left flank pain. We conclude that, face to renal vein thrombosis, thrombolytic treatment with simultaneous renal artery and renal vein perfusion is mandatory. Furthermore it is very important, in presence of caval extension of renal thrombus, to place a temporary vena cava filter before starting thrombolysis, considering the high risk of pulmonary embolism related to this pathology.     

Renal vein thrombosis in nephrotic syndrome--a prospective study of 54 cases

Recent advance of radiographic technique makes antemortem diagnosis of renal vein thrombosis (RVT) possible. However the incidence of RVT in patients with nephrotic syndrome(NS) is still not known. This study was designed to investigate the incidence, clinical presentation and radiological features of RVT in NS patients in China. A prospective study including clinical, and pathological examination as well as renal venogram was carried out in all our hospitalized NS patients except those having contradiction for renal venogram. RVT was found in 23 of the 54 cases (42%) and there was obstruction in 34 renal vein branches. RVT was more common in left (19) than right side (15), in upper (19) than middle and lower branches (10). It is interesting that in our group not only membranous but also minimal change as well as mesangium proliferative glomerulonephritis had high incidence of RVT (47%, 45% and 36% respectively) Only 6 cases (26%) had a typical acute presentation with severe loin pain, significant increase of urinary protein, enlargement of involved kidney. Occasionally fever, deterioration of renal function and sterile urinary white cells were also present. The remaining patients (74%) had latent onset of RVT which could hardly be identified in the clinical course of the underlying NS. For the high incidence and atypical clinical course of RVT shown in our study, it is recommended that due attention should be paid of this complication during management of NS and interpretation of therapeutic response.     

Anomalies of the inferior vena cava in patients with iliac venous thrombosis

BACKGROUND: Cases of deep venous thrombosis in the lower extremities triggered by abnormalities of the vena cava have been reported. OBJECTIVE: To describe anomalies of the inferior vena cava in patients with deep venous thrombosis. DESIGN: Prospective, consecutive case series. SETTING: University Hospital, Graz, Austria. PATIENTS: 97 patients with deep venous thrombosis. INTERVENTION: Sonography, venography, or both to diagnose deep venous thrombosis; magnetic resonance angiography to image the inferior vena cava. MEASUREMENTS: Anomalies of the inferior vena cava imaged by magnetic resonance angiography. RESULTS: 31 of 97 patients showed thrombotic occlusion of iliac veins (common and external iliac vein [ n = 29] or external iliac vein [ n = 2]). Five of 31 patients (3 men, 2 women) had an anomaly of the inferior vena cava. Anomalies were missing inferior vena cava, hypoplastic hepatic segment, and missing renal or postrenal segments. Patients with anomalies were significantly younger than the 92 patients without (mean age+/-SD, 25+/-6 years vs. 53+/-19 years; P = 0.002). In 2 patients with anomalies, the thrombotic occlusion was recurrent. CONCLUSIONS: An anomaly of the inferior vena cava should be suspected if thrombosis involving the iliac veins is seen in patients 30 years of age or younger. Patients with both an anomaly and thrombosis may be at higher risk for thrombotic recurrence.     

Renal vein thrombosis and selective arterial or venous thrombolytic therapy

Summary Background: Renal vein thrombosis (RVT) complicating the nephrotic syndrome is associated with a poor prognosis. Methods/Results: RVT was diagnosed in 12 of 60 patients with a diagnosis of nephrotic syndrome suggested by computed tomography (CT) and subsequently confirmed by selective renal angiography. Fifty patients carried a diagnosis of primary glomerulonephritis with various pathological findings, and 10 patients had lupus nephritis. Renal vein and peripheral vein blood samples were collected in the 12 patients with RVT and were assayed for fibrin(ogen) degradation products (FDP), antithrombin III (AT III), VIIIR:AG, and fibrinogen. The results suggested a state of hypercoagulation. Of these 12 patients, 7 were given 200,000 units of urokinase (UK) over 60 minutes in divided doses selectively via the renal vein. Five patients were given 200,000 units UK selectively into the renal artery. All patients also received 2.5 mg/day warfarin and 75 mg/day persantine. Except for three patients with focal glomerulosclerosis, all patients received 40 mg/day prednisone. After 1 month, the CT scan and blood samples for FDP, AT III, VIIIR:AG, and fibrinogen were repeated. Patients receiving intra-arterial UK had complete resolution of their thrombi. Complete resolution was also suggested in 2 of the 7 patients receiving UK by renal vein, and there was partial resolution in the other five. The hypercoagulation state decreased in all patients. Conclusions: We conclude that RVT is not an uncommon event in patients with nephrotic syndrome. The diagnosis can be supported reliably using abdominal CT scanning. Although a small number of patients were included in this nonrandomized study, it appeared that intra-arterial thrombolytic therapy yielded better results. The patients with minimal change disease have a good prognosis.     

Acute kidney injury as the first sign of spontaneous renal vein thrombosis: report of 2 cases

Spontaneous renal vein thrombosis (RVT) is very rare in the absence of nephrotic syndrome. It is more common in newborns and infants. RVT should always be included in the differential diagnosis of flank pain and hematuria, and because RVT can induce acute renal injury. A 19-year-old man was admitted to our hospital because he complained of right flank pain and oliguria for 3 days. Another patient, a 24-year-old man, complained of a severe and sudden onset of bilateral flank pain and anuria for a day. They were both healthy before they developed the described symptoms and had different levels of decrease in renal function when they visited the hospital. Color Doppler ultrasonography revealed RVT in both the patients. The patients received therapy, including anticoagulation and thrombolysis, following their diagnoses, and they recovered in a few days.     

Urokinase and AT-III concentrate treatment in inferior vena cava thrombosis associated with nephrotic syndrome

A patient with an inferior vena cava thrombosis in nephrotic syndrome was treated with heparin, AT-III concentrates and urokinase. After a few days on treatment he showed a complete resolution of the thrombosis. We suggest that this therapeutic combination may be a good approach to the treatment of thrombosis in nephrotic syndrome.     

A fulminant case of renal vein thrombosis in a patient with autoimmune disorder and membranous nephropathy

A previously healthy middle-aged woman noted a rapid onset of flank pain with gross hematuria. Enhanced CT scan showed thrombosis of the inferior vena cava and right renal vein. Laboratory findings revealed nephrotic proteinuria, Sjogren's syndrome (SjS), and Graves' disease (GD). A right nephrectomy was performed because of progressive and refractory renal necrosis. Renal specimens showed venous infarction with diffuse hemorrhagic and severe congestive renal necrosis, and membranous nephropathy (MN). The present case was diagnosed as acute renal necrosis due to catastrophic thrombosis in a patient with SjS, GD, and MN. It was thought that sudden development of thrombosis may have been caused by the status of the autoimmune disorders, and the associated MN.     

Incidence of vena cava thrombosis in the United States

From 1979 through 2005, vena cava thrombosis (either superior or inferior) was diagnosed in 99,000 hospitalized patients. Most, 78%, had isolated vena cava thrombosis. From 2000 to 2005, 5,000 patients were diagnosed yearly with vena cava thrombosis (1.5% of patients hospitalized with deep venous thrombosis). The population-based incidence of diagnosis of vena cava thrombosis from 2001 to 2005 was 1.7 in 100,000. The incidence increased with age. It was rare in Asian Americans. Pulmonary embolism occurred in 12% of patients with isolated vena cava thrombosis. Cancer was frequently associated with vena cava thrombosis (37.5%). Among all patients hospitalized with cancer, however, it was an uncommon complication (0.07%). In conclusion, isolated vena cava thrombosis is an uncommon cause of pulmonary embolism but may be considered if the veins of the extremities show no deep venous thrombosis.     

Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein thrombosis of the lower limbs: the extended DACUS study

The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT, 33.2% (136 of 409 patients) did not have RVT and VKA was stopped. The remaining 273 (66.8%) patients with RVT received anticoagulants for an additional 21 months; during this period of treatment, recurrent venous thromboembolism and major bleeding occurred in 4.7% and 1.1% of patients, respectively. After VKA suspension, the rates of recurrent thrombotic events were 1.4% and 10.4% in the no-RVT and RVT groups, respectively (relative risk = 7.4; 95% confidence interval = 4.9-9.9). These results indicate that in patients without RVT, a short period of treatment with a VKA is sufficient; in those with persistent RVT, treatment extended to 2 years substantially reduces, but does not eliminate, the risk of recurrent thrombosis.     

Familial risks of unusual forms of venous thrombosis: a nationwide epidemiological study in Sweden

Zöller B, Li X, Sundquist J, Sundquist K. (Center for Primary Health Care Research, Lund University, Malmö, Sweden; Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA). Familial risks of unusual forms of venous thrombosis: a nationwide epidemiological study in Sweden. J Intern Med 2011; 270 : 158–165.

Abstract.

Objective. This is the first nationwide study to determine familial risks of unusual forms of venous thrombosis amongst offspring of affected parents and amongst siblings. Design and settings. The Swedish Multigeneration Register of 0‐ to 75‐year‐old subjects was linked to the Hospital Discharge Register for the period 1987–2007. Standardized incidence ratios (SIRs) were calculated for individuals whose relatives were hospitalized for venous thromboembolism (VTE), as determined by the International Classification of Diseases, compared to those whose relatives were not affected by VTE. Results. The total number of hospitalized patients with VTE was 45 362, of which 1824 (4.0%) were affected by a rare thrombotic condition. The familial SIRs in cases with a history of VTE in parents or siblings were significantly increased for migrating thrombophlebitis (1.81; 95% confidence interval (CI) 1.40–2.31), portal vein thrombosis (2.35; 95% CI 1.77–3.06), vena cava thrombosis (1.96; 95% CI 1.42–2.64) and cerebral venous thrombosis (1.74; 95% CI 1.30–2.28). Budd–Chiari syndrome (SIR, 0.92; 95% CI 0.24–2.38) and renal vein thrombosis (SIR, 1.72; 95% CI 0.62–3.77) were not significantly associated with parental or sibling history of VTE; however, these two conditions were very rare, and therefore, we cannot draw any definite conclusions from this finding. Conclusions. Family history is an important risk factor for most unusual forms of VTE. Moreover, even the paraneoplastic phenomenon, migrating thrombophlebitis (Trousseau’s syndrome), is associated with a family history of VTE. Thus, our data suggest that most rare forms of VTE have a familial background.     

系统性红斑狼疮合并静脉血栓栓塞症临床相关危险因素分析

目的探讨系统性红斑狼疮（SLE）合并发生静脉血栓栓塞症（VTE）的临床相关危险因素。方法回顾性连续收集2008年1月至2012年2月期间在解放军总医院住院治疗的27例SLE并发VTE的患者入血栓组,并募集同期27例与血栓组性别、年龄、体质量指数（BMI）、生活方式等环境因素相匹配的不伴有VTE的SLE患者作为对照组,利用单因素统计学分析两组患者的静脉血栓形成相关临床危险因素（血小板计数、免疫功能、补体、合并低蛋白血症、狼疮肾炎、肾功能不全、肾病综合征、肾性高血压、蛋白尿、血尿等）及实验室诊断指标[C-反应蛋白（CRP）、D-二聚体,白细胞计数、活化部分凝血活酶时间（APTT）、血浆凝血酶原时间（PT）、血浆纤维蛋白原（FIB）1的差异。结果与对照组相比,血栓组合并低蛋白血症（70．37％）、狼疮肾炎（74．07％）、肾功能不全（70．37％）、肾病综合征（55．56％）、肾性高血压（66．67％）的发生率均显著升高（P值分别为0．003,0．000,0．000,0．027,O．029）。血栓组患者的实验室检测指标CRP（7．19±9．23）mg／L和D．二聚体（6．32±5．75）mg／L均显著高于对照组（P值分别为0．004,0．000）。结论低蛋白血症、狼疮肾炎、肾功能不全、肾病综合征及肾性高血压可能是SLE合并VTE的临床相关危险因素;CRP及D-二聚体可能成为SLE合并VTE的实验室诊断指标。     

Superficial venous thrombosis associated with congenital absence of the inferior vena cava and previous episode of deep venous thrombosis

Congenital malformations of the inferior vena cava (IVC) are uncommon and may be associated with an increased risk of venous thrombosis. We report the case of a man with congenital absence of the IVC and remote history of deep venous thrombosis who now presents with severe abdominal wall superficial thrombophlebitis. To our knowledge, this is the first report of a patient with IVC absence who has developed both deep and superficial venous thromboses.     

Lupus anticoagulant,Factor V Leiden,and methylenetetrahydrofolate reductase gene mutation in a lupus patient with cerebral venous thrombosis

We describe the case of a young Lebanese woman with systemic lupus erythematosus (SLE) and a positive lupus anticoagulant (LAC) who developed right internal jugular vein and sigmoid sinus thrombosis. Coagulation studies showed that in addition to the LAC the patient was heterozygous for the factor V (FV) Leiden mutation, and C677T mutation of the methylenetetrahydrofolate reductase gene. The high prevalence of FV Leiden in the eastern Mediterranean region suggests that we should probably screen our SLE patients in this area, especially those with anticardiolipin antibodies and/or LAC who have no history of thrombosis, for this and other thrombophilia markers. The detection of such abnormalities may have major practical consequences for the long-term management of these patients to prevent further thrombotic episodes.Abbreviations APS Antiphospholipid syndrome - CVT Cerebral venous thrombosis - LAC Lupus anticoagulant - DVT Deep vein thrombosis - SLE Systemic lupus erythematosus - SVC Superior vena cava     

Venous thromboembolism in patients hospitalized with nephrotic syndrome

Purpose

Whether pulmonary embolism in patients with the nephrotic syndrome is caused by deep venous thrombosis or renal vein thrombosis is controversial. To determine which is the likely cause of pulmonary embolism in patients with the nephrotic syndrome, we investigated data from the National Hospital Discharge Survey.

Methods

The number of patients discharged from nonfederal short-stay hospitals in the United States with a diagnostic code of nephrotic syndrome, deep venous thrombosis, renal vein thrombosis, and pulmonary embolism was obtained using ICD-9-M (International Classification of Diseases, Ninth Revision, Clinical Modification) codes.

Results

From 1979 to 2005, 925,000 patients were discharged from hospitals with the nephrotic syndrome and 898,253,000 patients did not have the nephrotic syndrome. With the nephrotic syndrome, 5000 (0.5%) had pulmonary embolism, 14,000 (1.5%) had deep venous thrombosis, and fewer than 5000 had renal vein thrombosis. The relative risk of pulmonary embolism comparing patients with the nephrotic syndrome to those who did not have it was 1.39, and the relative risk of deep venous thrombosis was 1.72. Among patients aged 18-39 years, the relative risk of deep venous thrombosis was 6.81. From 1991-2005, after venous ultrasound was generally available, the relative risk of deep venous thrombosis (all ages) was 1.77.

Conclusion

The nephrotic syndrome is a risk factor for venous thromboembolism. This is strikingly apparent in young adults. Renal vein thrombosis was uncommon. Therefore, pulmonary embolism, if it occurs, is likely to be due to deep venous thrombosis and not renal vein thrombosis.     

Budd-Chiari syndrome with inferior vena cava obstruction associated with systemic lupus erythematosus

The Budd-Chiari syndrome is an uncommon condition in which hepatic venous outflow is obstructed by thrombosis of the major hepatic veins. Many of the cases are idiopathic, but it has been described in association with vena caval webs, abdominal trauma, retroperitoneal neoplasms, and hypercoagulable states. A patient with systemic lupus erythematosus (SLE) who developed the Budd-Chiari syndrome with inferior vena cava thrombosis led to a review of the possible association between SLE and the Budd-Chiari syndrome. The therapy of the Budd-Chiari syndrome with associated vena cava thrombosis is also discussed.     

Inferior vena caval tumor thrombus extending into the right atrium in a patient with pancreatic cancer

Venous thromboembolism is a common complication in patients with cancer and an important cause of morbidity and mortality. Idiopathic thrombosis, migratory or recurrent thrombophlebitis may be the first manifestation of an occult malignancy. While deep venous thrombosis and pulmonary embolism are the most common thrombotic conditions in patients with malignant disease, tumor thrombus may be seen in inferior vena cava, mainly in patients with renal cell carcinoma, hepatocellular carcinoma, testicular tumors or adrenal carcinoma. Although pancreatic cancer is one of the cancers that are most strongly associated with thrombotic complications along with cancers of ovary and brain, there has been no report about presence of thrombus in the inferior vena cava in pancreatic cancer. We report a female patient with pancreatic cancer associated with tumor thrombus extending from the inferior vena cava to the right atrium     

Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis: the Duration of Anticoagulation based on Compression UltraSonography (DACUS) study

Residual vein thrombosis (RVT) indicates a prothrombotic state and is useful for evaluating the optimal duration of oral anticoagulant treatment (OAT). Patients with a first episode of deep vein thrombosis, treated with OAT for 3 months, were managed according to RVT findings. Those with RVT were randomized to either stop or continue anticoagulants for 9 additional months, whereas in those without RVT, OAT was stopped. Outcomes were recurrent venous thromboembolism and/or major bleeding. Residual thrombosis was detected in 180 (69.8%) of 258 patients; recurrent events occurred in 27.2% of those who discontinued (25/92; 15.2% person-years) and 19.3% of those who continued OAT (17/88; 10.1% person-years). The relative adjusted hazard ratio (HR) was 1.58 (95% confidence interval [CI], 0.85-2.93; P = .145). Of the 78 (30.2%) patients without RVT, only 1 (1.3%; 0.63% person-years) had a recurrence. The adjusted HR of patients with RVT versus those without was 24.9 (95% CI, 3.4-183.6; P = .002). One major bleeding event (1.1%; 0.53% person-years) occurred in patients who stopped and 2 occurred (2.3%; 1.1% person-years) in those who continued OAT. Absence of RVT identifies a group of patients at very low risk for recurrent thrombosis who can safely stop OAT. This trial was registered at http://www.ClinicalTrials.gov as no. NCT00438230.     

Cavernous Transformation of the Portal Vein: A Common Manifestation of Behcet's Disease

Behcet's disease (BD) is a chronic, multisystem inflammatory disorder of unknown etiology, which is characterized by recurrent aphthous ulcers of the mouth and genitalia, uveitis with hypopyon, and a diffuse vasculitis that involves the arterial and venous systems.
From January 1968 to July 1993, 66 of 844 patients with BD seen at the Hacettepe University Hospital, Ankara, Turkey, experienced a vascular complication other than peripheral thrombophlebitis. The vascular complication in each case was identified based upon a combination of clinical data, digital subtraction angiography, CT, and ultrasonography findings. Six of these 66 (9.1%) had cavernous transformation of the portal vein. Five of these six had additional large vein involvement resulting in the Budd-Chiari syndrome with or without inferior vena caval obstruction.
Based upon this experience, it can be concluded that portal vein thrombosis is not a rare complication of BD. When patients with BD are found to have or develop splenomegaly, portal vein thrombosis should be suspected and investigated. If hepatomegaly and ascites are detected, Budd-Chiari syndrome due to hepatic vein thrombosis should be suspected. Finally, if hepato-splenomegaly, ascites, and dependent edema of the lower body are present, thrombosis of the inferior vena cava should be suspected.