Spontaneous Venous Thrombosis Research Articles

Is thrombophilia a major risk factor for deep vein thrombosis of the lower extremities among Lebanese patients?

Factor V Leiden (R506Q) mutation is the most commonly observed inherited genetic abnormality related to vein thrombosis. Lebanon has one of the highest frequencies of this mutation in the world with a prevalence of 14.4% in the general population. The aim of this study is to define risk factors including inherited genetic abnormalities among Lebanese patients with lower extremity deep vein thrombosis. We report the clinical outcome of patients with thrombophilia. From January 1998 to January 2008, 162 patients (61 males and 101 females) were diagnosed with lower extremity deep vein thrombosis. Mean age was 61 years (range: 21 to 95 years). The most frequent risk factors for vein thrombosis were surgery, advanced age, obesity, and cancer. Twenty-five patients had thrombophilia, 16 patients had factor V Leiden (R506Q) mutation, and seven patients had MTHFR C677T mutation. Ninety-two percent of patients screened for thrombophilia were positive. Screening was requested in young patients (16), patients with recurrent (11), spontaneous (8), and extensive (5) venous thrombosis, familial history (5), pregnancy (4), estroprogestative treatment (3), and air travel (1). Nine patients had one, 11 patients had two, and five had three of these conditions. Follow-up (6 to 120 months) of these 25 patients treated with antivitamin K did not reveal recurrences or complications related to venous thromboembolism. Factor V Leiden mutation followed by MTHFR mutation are the most commonly observed genetic abnormalities in these series. Defining risk factors and screening for thrombophilia when indicated reduce recurrence rate and complications. Recommendations for thrombophilia screening will be proposed.

Cerebral Venous Thrombosis in Spontaneous Intracranial Hypotension

The occurrence of cerebral venous thrombosis has been reported among patients with spontaneous intracranial hypotension, but a causal relationship has not been clearly established. We reviewed our experience with spontaneous intracranial hypotension and cerebral venous thrombosis and we reviewed the relevant literature to evaluate the relationship between these 2 entities. We reviewed the medical records and imaging studies of a consecutive group of patients with spontaneous intracranial hypotension evaluated at a tertiary care center between 1/1/2001 and 12/31/2007. The main search strategy was a systemic review of journal articles in MEDLINE (1966 to January 2008). Among 141 patients with spontaneous intracranial hypotension, 3 (2.1%) were also diagnosed with cerebral venous thrombosis. Among these 3 patients and the 17 reported in the literature there were 11 men and 9 women with a mean age of 39.5 years. Radiographic or clinical evidence for spontaneous intracranial hypotension preceding cerebral venous thrombosis was found in most patients, while there was no evidence for cerebral venous thrombosis preceding spontaneous intracranial hypotension in any patient. Eight (40%) of the 20 patients were found to have a change in their headache pattern believed to be due to the development of cerebral venous thrombosis. Complications of cerebral venous thrombosis, eg, cerebral venous infarction, occurred in 8 patients (40%). Spontaneous intracranial hypotension is a risk factor for cerebral venous thrombosis, but cerebral venous thrombosis is found in only about 2% of patients with spontaneous intracranial hypotension. A change in headache pattern is not a reliable predictor of the development of cerebral venous thrombosis in patients with spontaneous intracranial hypotension.

Internal jugular vein thrombosis due to distant malignancies: two case reports and literature review

The internal jugular vein is an uncommon site of spontaneous venous thrombosis. Most cases usually result from intravenous drug abuse, jugular vein catheterisation, neck dissection, a hypercoagulable state associated with malignancy (Trousseau's syndrome), neck injury or ovarian overstimulation syndrome. In this paper, we present and discuss two cases of spontaneous jugular vein thrombosis associated with breast and lung malignancies. The possibility of Trousseau's syndrome due to distant malignancy should be considered by otolaryngologists and appropriately investigated.

The influence of the age in the risk of the prothrombin G20210A mutation for spontaneous venous thrombosis

Factor V Leiden mutation (FVL), and the prothrombin G20210A mutation (PT G20210A) are polymorphisms with a weak risk factor for venous thromboembolic disease. The probability of spontaneous venous thrombosis in carriers of thrombophilic mutations (FVL and PT G20210A) was analyzed. We studied 735 individuals (407 were healthy controls and 328 patients with venous thrombosis) with respect to FVL and PT G20210A, determined by polimerase chain reaction in liquid phase, real time. chi2 test and logistic regression analysis were used to evaluate the results. The dates were analyzed with the statistical program SPSS v. 14.0. The carrier patients of PT G20210A mutation whose age was over 40 years had a risk factor for spontaneous venous thrombosis which was 9.28 (odds ratio [OR]) (95% confidence interval [CI], 3.01-28.60; p < 0.0005) times greater than carriers of the PT G20210A mutation who were 40 year-old or younger. In our patients, being male meant a weak risk factor for venous spontaneous thrombosis (p = 0.021; OR = 1.64; 95% CI, 1.08-2.51) . Our results demonstrate a potentiation of the thrombotic risk by an increase of age in the carriers of the PT G20210A mutation.

Cirrhosis, Spontaneous Venous Thromboses, and Splenic Gas Gangrene

Cirrhosis, Spontaneous Venous Thromboses, and Splenic Gas Gangrene

Postoperative dural sinus thrombosis in a patient in a hypercoagulable state

Spontaneous cerebral venous sinus thrombosis is a rare problem that may be encountered in patients with underlying thrombophilic disorders. It has also been reported as a postoperative complication following suboccipital, transpetrosal, and transcallosal approaches. The authors report on a 67-year-old man with two prior episodes of lower-extremity deep venous thrombosis who underwent transcallosal resection of a colloid cyst and in whom sagittal sinus thrombosis developed 2 weeks thereafter. Results of a subsequent hematological workup revealed both a factor V Leiden mutation and the presence of antiphospholipid antibodies, two thrombophilic risk factors that likely contributed to the development of delayed postoperative sinus thrombosis. Although the safety of low-molecular-weight heparin (LMWH) after craniotomy has not been established in a randomized, controlled study, there is sufficient evidence to justify its use for prophylactic anticoagulation therapy in patients at high risk for postoperative cerebral venous thrombosis. The authors propose using LMWH prophylaxis in patients with thrombophilic disorders who undergo neurosurgical procedures in proximity to dural sinuses in an effort to prevent catastrophic venous infarction.

Co-Inheritance of FV Leiden and High Levels of FIX Results in Novel Models for Thrombophilia and Spontaneous Fetal Loss.

High levels of FIX is emerging as a risk factor for spontaneous venous thrombosis, affecting ~20% of unselect patients and increasing rates of recurrent thromboembolic events. We have generated mice expressing supraphysiological levels of human FIX (up to 400% of normal) but these animals did not develop thrombosis. Therefore, we decided to test whether an additional risk for thrombosis would trigger a prothrombotic phenotype in these mice. Because the FVL mutation is also present in 20% of thrombophilia subjects, we chose FVL mice as model. Breedings included both parents being heterozygous FVL(+/−) but only one was transgenic for FIX (tFIX: 4–8μg/ml plus the endogenous murine FIX). All mice were on C57Bl/6 background. More than 200 newborns were obtained but surprisingly no animal of FVL(+/+)/tFIX genotype was identified. When pregnancies were interrupted at embryonic age of E9.5 to E16.5, no deviation from the expected/observed embryos genotypes was observed. However, the number of reabsorbed embryos increased significantly from 13% (E9.5) to 33% (E.16.5), p<0.02. All FVL(+/+)/tFIX embryos exhibited extensive bruises and hemorrhagic areas which colocalize with markedly fibrin deposition, findings consistent with disseminated intravascular coagulation. Placental analysis (n=18) of FVL(+/+)/tFIX embryos harvested at E12.5 or later demonstrated abnormalities such as excessive fibrin deposition and innumerous apoptotic cells, determined by TUNEL assay, mainly in the labyrinthine trophoblast zone. The maternal genotype clearly influenced the pregnancy outcome since the number of newborns per litter was 2-fold lower when the mother carried tFIX compared with father tFIX (average 4.3 vs. 8.3, respectively; p<0.02). No mice of other genotypes analyzed (n=112) presented similar abnormalities neither in embryos nor in placental tissue. Mice that achieve adulthood developed normally. However, FVL(+/−)tFIX mice (>7 months of age) presented high rate of thrombotic episodes (3/40; 7.5%) followed by 5.2% FVL(−/ −)/tFIX mice, whereas no other age-matched mice (n=74) developed such complication. Monitoring for coagulation activation by serial aPTT, PT, thrombin-antithrombin (TAT) and D-Dimers demonstrated genotype-dependent procoagulant activity. In FVL(+/−)/tFIX or FVL(−/ −)/tFIX mice, levels of TAT (70ng/ml, n=28/group) and D-dimers (230ng/ml, n=17/group) were ~ 2-fold higher (P<0.04), when compared to mice (TAT: 30ng/ml and D-Dimer: 100ng/ml) of other genotypes. Furthermore, FVL(+/−)/tFIX mice presented the highest fibrin deposition determined by Western blot analysis of tissues harvested, followed by FVL(−/ −)/tFIX mice when compared to the other animals (P<0.05). To exclude the possibility of abnormal interaction of human (h) FIX with murine antithrombin (AT), we compared the rate of inactivation of hFIXa by murine or human AT using purified proteins. The results showed that murine AT efficiently inactivated hFIXa in a similar fashion of that determined for human AT. Moreover, early work showed that hFIX efficiently corrected the phenotype of FIX-deficient mice. Therefore, these data revealed that gene-dosage dependent interaction of FVL and high levels of FIX in mice increase rates of spontaneous fetal loss and adulthood thrombosis. These models provide opportunities to better understand and to test therapeutics for thrombophilia-related complications due to common risk factors identified in humans.

Platelet Activation Markers in Patients with Venous Thromboembolism without Predisposing Factors

A constant in vitro hypersensitivity of platelets (adenosine diphosphate) has been suggested as a risk factor for arterial and even venous thrombosis. Our aim was to determine phenotypic and functional alterations of platelets by flow cytometry as potential prothrombotic risk factors in patients with a history of unexplained spontaneous venous thrombosis. Forty-nine patients with a history of spontaneous venous thrombosis and no inherited or acquired thrombophilic risk factors were compared with a reference group of 39 healthy volunteers. Flow cytometry (FACS) was used to analyze the surface expression of CD62 (P-selectin) and CD63 in nonactivated platelets and after in vitro stimulation with adenosine diphosphate and thrombin receptor activator peptide 6. Mean fluorescence intensity of CD62 and CD63 surface expression as well as percentage of CD62 and CD63 positive cells and binding index differed in patients with a history of thrombosis compared with the reference group, but failed to reach statistical significance. Similar results were observed after in vitrostimulation with adenosine diphosphate and thrombin receptor activator peptide 6. In conclusion, the expression of CD62 and CD63 of resting and in vitro activated platelets could not be established as a risk factor for spontaneous venous thromboembolism.

Images in emergency medicine

Spontaneous proximal lower extremity deep venous thrombosis. Spontaneous (or idiopathic) deep venous thrombosis is defined as occurring in a patient without known risk factors for deep venous thrombosis, such as recent surgery or malignancy. “Proximal” implies that thrombus is located within, or proximal to, the popliteal vein, where it poses an immediate risk of pulmonary embolism. Most of the physical examination signs of deep venous thrombosis that appear in the rule by Wells et al1 (for assessing likelihood of deep venous thrombosis) were present: dilated superficial collateral veins, asymmetric pitting edema, entire limb swelling (versus calf only), and focal tenderness over the popliteal and femoral veins.

A methodological study of computerized venous strain‐gauge plethysmography of the upper extremities

This study was performed to assess the efficiency of computerized strain-gauge plethysmography for evaluation of venous volume (VV) and outflow capacity of the upper extremities and to receive reference values. For this purpose, we investigated 34 healthy controls; 16 males and 18 females with a mean age of 45 years (range 31-58 years). These results were compared with those obtained in 32 patients with earlier spontaneous deep venous thrombosis (DVT) in the upper extremities. In the control group, there was no difference between right and left arm and none of the variables were influenced by age and gender. Venous volume and rate of venous emptying (VE) were significantly lower in arms with earlier DVT than in those without (VV: DVT arms 3.7+/-0.96 ml 100ml-1 and controls 4.6+/-0.81 ml 100 ml-1; VE: DVT arms 79+/-24 ml 100 ml-1 min-1 and controls 110+/-21 ml 100 ml-1 min-1). Repeated measurements had a coefficient of variation of approximately 10% in both groups. We found the device easy to handle and the results demonstrates that this is a useful method to study venous function in upper extremities. This implicates that computerized strain-gauge plethysmography is an efficient method both for clinical diagnostic routine and research studies of circulatory changes in acute and chronic DVT in the upper extremity.

Inferior Vena Cava Agenesis with Paravertebral Muscle Collateralisation

Developmental anomalies of the inferior vena cava (IVC) have an estimated prevalence of 0.5%, and may be the common aetiology in young patients presenting with bilateral lower limb iliofemoral thrombosis. We report a case of spontaneous bilateral iliofemoral deep venous thrombosis secondary to infrahepatic IVC agenesis. The patient had associated thrombosis of the azygous and hemiazygous venous system and collateralisation via the venous plexus of the paravertebral muscles. To our knowledge, this is the first such case reported of IVC agenesis dependent upon collateral return via the paravertebral muscles.

Acute pulmonary embolism: part I: epidemiology, pathophysiology, and diagnosis.

This New Frontiers article reviews the epidemiology, pathophysiology, diagnosis, treatment, and prevention of pulmonary embolism (PE) in 2 parts. In this first section we summarize the mechanisms of right ventricular dysfunction, arterial hypoxemia, and other abnormalities of gas exchange. For diagnosis, we streamline and expedite the work-up. For the second part we provide a contemporary approach to risk stratification to determine which patients may warrant intervention beyond use of heparin and warfarin alone. We conclude with an overview of contemporary concepts in optimizing prophylaxis. PE is a common cardiovascular and cardiopulmonary illness with an incidence in the United States that exceeds 1 per 1000 and a mortality rate 15% in the first 3 months after diagnosis. 1 This makes PE possibly as deadly an illness as acute myocardial infarction. Nevertheless, the lay public has not been well educated about PE. Consequently, early detection and prompt presentation for medical evaluation have lagged far behind the public awareness of acute coronary syndromes and stroke. Although discussion of the etiology of PE has classically focused on acquired and inherited causes of hypercoagulability, there is also an association between atherosclerotic disease and spontaneous venous thrombosis.2 The most common reversible risk factor for PE is obesity, an increasing pandemic in our society. Other common reversible risk factors include cigarette smoking and hypertension. Nevertheless, public fascination with PE has centered on long-haul air travel, a rare cause of venous thromboembolism. 3 PE also occurs in the context of illness attributable to surgery, trauma, immobilization, cancer,4 oral contraceptives,5 pregnancy, and postmenopausal hormone replacement therapy, 6 as well as medical conditions such as pneumonia and congestive heart failure. Genetic predisposition to venous thrombosis is being increasingly recognized, 7 and twin studies have demonstrated the important contribution of an inherited prothrombotic state. 8 Increased levels of clotting factors and activation peptides contribute to the risk of PE. Deficiencies of anticoagulant factors also increase thrombotic risk.9 Pathophysiology

SHOULDER PAIN AND ARM SWELLING - VOLLEYBALL

HISTORY A previously healthy right-handed 15 year-old female high school volleyball player presented to the emergency room with acute right arm swelling and discoloration. She had a two-week history of intermittent right shoulder pain that only hurt her after spiking balls during practice. The pain was relieved by icing her shoulder after practice and taking ibuprofen. One week prior to presentation, a physician diagnosed her with a right scapular/shoulder strain and prescribed physical therapy. There were no labs or radiographs taken at that time. When she awoke on the morning of presentation, she noticed diffuse swelling and a purple discoloration of her entire right arm and hand. Because of these symptoms, her parents took her to the hospital. She denied any trauma, pain, or paresthesias. PHYSICAL EXAMINATION The patient was a well-developed female in no distress. Temperature 97.4, heart rate 74, respiratory rate 18, blood pressure 115/49, pulse oximetry revealed an oxygen saturation of 100% on room air. Weight was 64.3 kg, height 170 cm. HEENT exam was normal. Neck was supple, no lymphadenopathy. Chest was clear to auscultation, normal heart sounds without murmur, rub, or gallop. Abdomen was soft, nontender, and nondistended with no organomegaly. Examination of her extremities revealed diffuse swelling and erythema of her right arm, hand, and fingers. There was increased warmth of the arm without discrete or point tenderness or palpable cords. Distal pulses were present, and sensation was intact. There was diffuse shoulder tenderness and decreased range of motion of the shoulder in all directions secondary to pain. Her other extremities were normal without erythema or edema. There was no rash, and neurologic exam was normal. DIFFERENTIAL DIAGNOSIS Infection of the soft tissue of the shoulder and arm Deep venous thrombosis of the upper extremity Superficial thrombophlebitis Extrinsic compression of the venous drainage by tumor or enlarged lymph nodes Muscle strain with reflex sympathetic dystrophy Fracture TESTS AND RESULTS Ultrasound with Doppler of the upper extremity – revealed an obstructing deep venous thrombosis in the upper brachial vein, axillary vein, and subclavian vein to the area of the first rib Chest radiograph – normal Laboratory data – CBC, blood chemistries, PT, PTT all normal FINAL/WORKING DIAGNOSIS Paget-Schroetter syndrome (spontaneous upper extremity venous thrombosis) TREATMENT AND OUTCOMES 1. Hospitalization and anticoagulation with enoxaparin. 2. Work-up for a hypercoagulable state was normal and included the following: Factor V Leidin, Protein C and S, antithrombin III, plasma homocysteine, antiphospholipid antibodies, prothrombin gene mutation 20210. 3. Her symptoms improved, and after five days of therapy a repeat Doppler ultrasound revealed only a small thrombus in the right subclavian vein at the level of the first rib with good venous flow through collateral vessels. 4. Venogram performed at the time of the repeat Doppler confirmed the results of the ultrasound, but proof of a compressive phenomenon of the subclavian vein at the level of the first rib could not be established. 5. The patient was discharged home after the venogram revealed her DVT was resolving and her symptoms were improving. She is being restricted from all sports and is continuing her enoxaparin as an outpatient. The duration of her anticoagulation therapy will be about three months. 6. The patient was asymptomatic at a one-month follow-up, and repeat Doppler showed almost complete resolution of the thrombus. 7. After completion of her anticoagulation period, she will undergo further imaging (venogram, MRI) to help determine if surgical intervention (removal of first rib) may help to prevent future deep venous thrombosis and allow her to return to volleyball.

An association between atherosclerosis and venous thrombosis.

In about a third of patients with venous thromboembolism, the cause of the disorder is unexplained. In patients with atherosclerosis, activation of both platelets and blood coagulation and an increase in fibrin turnover are detectable, which may lead to thrombotic complications. Whether atherosclerosis is associated with an increased risk of venous thrombosis is unknown. We performed ultrasonography of the carotid arteries in 299 unselected patients who had deep venous thrombosis of the legs without symptomatic atherosclerosis and in 150 control subjects. Patients with spontaneous thrombosis, patients with secondary thrombosis from acquired risk factors, and control subjects were assessed for plaques. At least one carotid plaque was detected in 72 of the 153 patients with spontaneous thrombosis (47.1 percent; 95 percent confidence interval, 39.1 to 55.0), 40 of the 146 with secondary thrombosis (27.4 percent; 95 percent confidence interval, 20.2 to 34.6), and 48 of the 150 control subjects (32.0 percent; 95 percent confidence interval, 24.5 to 39.5). The odds ratios for carotid plaques in patients with spontaneous thrombosis, as compared with patients with secondary thrombosis and with controls, were 2.3 (95 percent confidence interval, 1.4 to 3.7) and 1.8 (95 percent confidence interval, 1.1 to 2.9), respectively. In a multivariate analysis that accounted for risk factors for atherosclerosis, the strength of this association did not change. There is an association between atherosclerotic disease and spontaneous venous thrombosis. Atherosclerosis may induce venous thrombosis, or the two conditions may share common risk factors.

The risk of recurrent venous thromboembolism in heterozygous carriers of factor V Leiden and a first spontaneous venous thromboembolism.

Factor V (FV) Leiden is a risk factor for venous thrombosis (VT). Data on its influence on the risk of recurrent venous thromboembolism (VTE) are controversial owing to different study designs and patient cohorts. We reevaluated the risk of recurrence among heterozygous carriers and noncarriers of FV Leiden with a first spontaneous proximal VT of the leg and/or pulmonary embolism. Patients with secondary VTE, homozygous FV Leiden, natural inhibitor deficiencies, lupus anticoagulant, cancer, or long-term anticoagulation were excluded. The study end point was objectively documented, symptomatic, recurrent VTE. After discontinuation of oral anticoagulant therapy for a first VTE, we prospectively observed 287 patients, 83 (29%) of whom were heterozygous for FV Leiden. Recurrent VTE was seen in 17 (20%) of 83 patients with and 44 (21.6%) of 204 without FV Leiden. The probability of recurrence among heterozygotes was 12% (95% confidence interval [CI], 8%-16%), 27% (95% CI, 21%-33%), and 27% (95% CI, 21%-33%) after 2, 4, and 6 years, respectively, and was not higher than that among patients without the mutation (16%, 23%, and 34%, respectively). The relative risk of recurrence in heterozygotes was 0.9 (95% CI, 0.5-1.6; P =.60) after adjustment for confounding variables. The risk of recurrence among patients with and without FV Leiden was not different when sex distribution or duration of anticoagulation therapy was taken into account. The risk of recurrence is similar among carriers and noncarriers of FV Leiden. Heterozygous patients should receive secondary thromboprophylaxis for a similar length of time as patients without FV Leiden.

Conservative management of epiploic appendagitis based on CT scan findings

Dear Editor, Epiploic appendagitis is a relatively rare, often underdiagnosed condition affecting young adults. A 31-year-old male presented with a 12-hour history of acute left iliac fossa pain of increasing severity, which had become constant and aggravated by movement. There was no history of gastrointestinal disturbance. On examination, there was marked tenderness and guarding in the left iliac fossa. The white cell count was raised (11.23x10/l) with a neutrophilia (7.9x10/l). Initially, a clinical diagnosis of diverticulitis was made in spite of the patient’s age. An abdominal CT showed an abnormality of the descending and sigmoid junction with a peripheral hyperattenuated ring, a central area of hypoattenuation of the anterior peritoneal lining and thickening and stranding of fat surrounding the lesion (see Figures 1 and 2). These findings confirmed the diagnosis of epiploic appendagitis. The patient was managed conservatively and by day 5 his symptoms had resolved and he was discharged home. Primary epiploic appendagitis (PEA) results from torsion and inflammation of an epiploic appendix, or less commonly following spontaneous venous thrombosis. While formerly thought to be relatively rare, recent literature suggests it is being underdiagnosed. Patients present with localised abdominal tenderness which may mimic the acute surgical emergencies of diverticulitis or appendicitis. Gastrointestinal symptoms are uncommon. The patient is typically apyrexial with a normal leucocyte count. Clinical diagnosis is difficult. Previously diagnosed at laparotomy for presumed diverticulitis or appendicitis, and treated by ligation and excision of the appendage, it may now be diagnosed reliably on characteristic CT findings. PEA should be considered in the differential diagnosis of acute abdominal pain, particularly in young patients presenting with atypical features.

Prothrombotic Risk Factors in Children with Spontaneous Venous Thrombosis and Their Asymptomatic Parents: A Family Study

The present study was designed to assess to what extent single and combined clotting abnormalities influence spontaneous vascular accidents in pediatric patients, and how the children affected differ in their prothrombotic risk profiles from their biological first-degree family members. In addition, this study was performed to investigate if relatively mild thrombophilic polymorphisms not leading to thrombosis in the parents cause severe clinical expression when coinherited with an established prothrombotic risk factor. The factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, the methylenetetrahydrofolate reductase (MTHFR) T677T genotype, the plasminogen activator inhibitor (PAI)-1 promoter polymorphism, lipoprotein (Lp)(a), antithrombin, protein C, and protein S were investigated in 48 childhood patients aged neonate to <18 years (median 0.5 years) with spontaneous venous thromboembolism (SVT) compared with the carrier status of their first-degree family members. In 19 of the 48 patients (39.6%), one prothrombotic risk factor was diagnosed, and in 27 of the 48 subjects (56.3%) at least two prothrombotic defects/alleles. In the majority of cases with SVT, the FV G1691A mutation was involved either with a second mutated allele or combined with elevated Lp(a), the 4G/4G genotype of the PAI -1 promoter polymorphism, and the T677T MTHFR genotype. The rate of combined prothrombotic risk factors was significantly higher in childhood patients compared with their parents p=0.0004 . In conclusion, based on the data presented here we suggest that early-onset SVT in childhood patients is mainly caused by combinations of at least two prothrombotic risk factors.

Factor V G1691A and prothrombin G20210A in childhood spontaneous venous thrombosis--evidence of an age-dependent thrombotic onset in carriers of factor V G1691A and prothrombin G20210A mutation.

Risk factors for venous thrombosis in adults are the prothrombin (PT) G20210A, the factor (F) V G1691A mutations and hereditary deficiencies of protein C, protein S and antithrombin. However, data are limited on the relevance of these risk factors for thrombosis in children and adolescents. We therefore investigated 119 patients aged 0-18 with spontaneous venous thrombosis and controls (n = 100) for the presence of the factor V G1691A mutation and the prothrombin G20210A variant with respect to thrombotic onset and thrombosis location. The following frequencies (patients vs. controls), odds ratios (OR), 95%-confidence intervals (CI) and p-values were found: FV G1691A, 19.3% vs. 5%, OR/CI 4.55/1.66-12.5, p = 0.0038 and prothrombin G20210A, 8.4% vs. 3%, OR/CI 2.96/0.8-11, p = 0.17. A combination of the FV G1691A mutation with the PT G20210A variant was found in 3 children (2.5% of cases) but only once in the controls. With a median (range) age of 2 years (0-17), carriers of the FV mutation were significantly younger compared with patients carrying the PT variant (16 years: 0-18, p < 0.001). Vascular accidents in carriers of the FV mutation occurred in deep veins of the leg (n = 11), cerebral veins (n = 4), renal veins (n = 3) and portal veins (n = 2). Patients with the PT mutation showed spontaneous thrombosis in the majority of cases in the deep veins of the leg (n = 5) and in the central nervous system (n = 2). Combined defects were found in a neonate with renal venous thrombosis and in two adolescents with deep vein thrombosis. Data presented here suggest that the heterozygous FV mutation is the most commonly found prothrombotic risk factor responsible for spontaneous thrombosis during infancy and early childhood. In contrast, the PT G20210A variant is likely to be more important during puberty and adolescence.

Long-term sequelae of spontaneous axillary-subclavian venous thrombosis.

The frequency and severity of post-thrombotic sequelae after spontaneous axillary-subclavian venous thrombosis remain poorly known. To determine the late sequelae of conventionally treated spontaneous axillary-subclavian venous thrombosis. Cross-sectional study. University department of vascular medicine. 54 patients seen during an 18-year period (mean follow-up, 5 years). Scores for the severity of post-thrombotic symptoms were graded on a numerical rating scale ranging from 0 to 10 and on a 6-point verbal rating scale. Ultrasonographic sequelae were classified as grade 0, normal flow; grade 1, moderate obstruction; or grade 2, severe obstruction or occlusion. Verbal scores were "nil/negligible" in 47% of patients and "severe/intolerable" in 13%; numerical scores were 0 to 3 in 78% of patients and 7 to 10 in 9%. Grade 2 ultrasonographic sequelae were found in 22% of cases. No relation was seen between ultrasonographic sequelae and symptom severity scores. The overall clinical outcome of spontaneous axillary-subclavian venous thrombosis is good, and there is no relation between the severity of late symptoms and ultrasonographic sequelae.

Spontaneous venous thrombosis in a young patient with combined factor V Leiden and lupus anticoagulant

We describe a case of a 28-year-old man who developed an extensive spontaneous deep venous thrombosis. Testing revealed heterozygotic factor V Leiden mutation, and the presence of both lupus anticoagulant (LA) and elevated IgM anticardiolipin antibody (ACA). Several family members were found to be heterozygous for factor V Leiden. A paternal aunt had the factor V Leiden mutation, an elevated plasma homocysteine and a borderline increased IgG ACA level. No other family member had a history of a venous thrombotic event. This case illustrates that evaluation of young patients who present with venous thrombosis should be performed for both hereditary and acquired thrombophilic defects. The family studies suggest that the presence of a lupus anticoagulant may be more clinically significant than elevated ACA in risk assessment. Although screening family members when the proband carries factor V Leiden is controversial, psychological reassurance of those who test negative and simple advice on occupations or social habits (e.g., smoking) for those who test positive may be important benefits.