Risk Factor For Recurrent Thrombosis Research Articles

Low recurrent thrombosis rates in single positive antiphospholipid syndrome regardless of type of anticoagulation

Thrombotic antiphospholipid syndrome (TAPS) is characterized by thrombosis and persistently positive tests for antiphospholipid antibodies or lupus anticoagulant (LAC). Triple-positive APS has the highest risk of recurrent thrombosis, but no studies have focused on recurrent thrombosis in patients with single-positive TAPS. We conducted a retrospective cohort study of patients with single-positive TAPS diagnosed at Lifespan Health System, Rhode Island, to determine the rates and risk factors for recurrent thrombosis. Between January 2001 and April 2022, 128 patients were assessed who had single-positive APS (LAC = 98, aCL = 21, aβ2GPI = 9) and who had been followed for a total of 1453.8 patient-years (median follow-up 3.04 years). The initial antithrombotic regimen was warfarin in 44 %, a direct oral anticoagulant (DOAC) in 34 %, enoxaparin in 2 %, and no antithrombotic therapy or antiplatelet therapy only in 20 %. Recurrent thrombosis occurred in 16 (12.5 %) with a recurrent thrombosis rate of 3.08 per 100 patient-years. Systemic lupus erythematosus was the only variable significantly associated with recurrent thrombosis in a model adjusted for age, sex, body mass index, and type of positive APS test. All 16 patients with recurrent thrombosis were initially treated with warfarin, and, at the time of recurrent thrombosis, 13 patients remained on warfarin and three were off anticoagulation. In conclusion, the recurrent thrombosis rate in single-positive APS is low, and not all patients with a single-positive test may need indefinite anticoagulation with warfarin. Larger prospective studies are required to confirm this finding and establish optimal anticoagulation regimens for low-risk TAPS.

From the Editor’s Desk…

From the Editor’s Desk…

High Incidence of Bleeding Found with Direct Oral Anticoagulant Use in Myeloproliferative Neoplasm Patients

▪ BACKGROUNDPatients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are at increased risk of arterial (ATE) and venous thromboembolism (VTE). There are no clear guidelines regarding selection of anticoagulation (AC) in MPN patients. Direct oral anticoagulants (DOACs) are increasingly used in the general population to treat a variety of conditions including VTE, ATE, and atrial fibrillation (AF). Data on the safety and efficacy of DOACs in MPNs limited. We conducted a multi-center, retrospective analysis of DOAC use in MPN patients to characterize real-world practice patterns and evaluate thrombosis and bleeding risks. METHODSWe retrospectively analyzed 133 MPN patients prescribed DOACs across the Massachusetts General Brigham / Dana Farber Harvard Cancer Center system from 1995 to 2020. Patients were identified using ICD-9 and 10 codes in the electronic medical record. Patient and treatment characteristics were described with summary statistics. We calculated cumulative incidence functions of VTE and ATE, and major and clinically relevant non-major bleeding (CRNMB) by ISTH criteria, using death on DOAC as a competing risk. A Gray's test was used to compare cumulative incidence between groups. Analysis of risk factors associated with bleeding/thrombosis was carried out by univariate and multivariable Fine-Gray models. RESULTSBaseline characteristics are displayed in Table 1. Seventy-five (56.4%) MPN patients were prescribed DOAC for VTE, 46 (34.6%) for AF, 7 (5.3%) for stroke, and 5 for other ATE (3.8%). The median age at DOAC initiation was 71; the AF population was significantly older than patients with VTE (75 vs 59, p<0.001). Fifty-seven percent of patients (N = 76) had a diagnosis of PV, with 89% (N = 118) of patients carrying a JAK2 driver mutation. Apixaban was the most commonly prescribed DOAC (N = 83, 62.4%). Nearly half (N = 59, 45%) of patients had a prior VTE/ATE at DOAC initiation, and 23% (N = 31) of patients were switched from warfarin. Among the VTE-treated patients, 43% of events were deep vein thrombosis (N = 39), 31% (N = 28) were pulmonary embolism, 21% (N = 19) were splanchnic vein thrombosis (SVT), and 4.4% (N=4) were other VTE.Table 2 displays practice patterns of DOAC use in MPN patients. The median duration of AC was 37.0 months for all patients, with no difference (p=0.01) between patients treated for AF (42.3 months) and VTE (37.0 months). Twenty-one percent of VTE-treated patients completed a finite course of AC of 6 months median duration. Fifteen percent (N = 11) of VTE-treated and 4.3% (N = 2) of AF patients had reduction to prophylactic dosing. Fifty percent (N = 66) of patients took aspirin and AC concurrently; 83% (N = 110) of patients took cytoreduction with AC.After a median follow-up of 37 months, we found 12 thrombotic (7 arterial, 3 venous, 2 TIPS occlusions) and 28 bleeding (6 major with 4 contributing to patient death, 2 CRNMB) events on DOAC. The estimated 1-year cumulative incidence of thrombosis and bleeding on DOAC was 5.5% (1.5%-9.5%) and 12.3% (6.4%-18.2%), respectively (Figure 1). Thrombosis and bleeding rates were not significantly different between patients treated for VTE versus AF.Prior history of thrombosis and use of dabigatran or edoxaban were significantly associated with increased thrombosis on both univariate and multivariable analysis (p<0.05). Age ≤ 65 also emerged as a risk factor for recurrent thrombosis in multivariate analysis (p=0.04). Use of dabigatran or edoxaban trended toward increased bleeding, but otherwise we found no significant risk factors for bleeding at α=0.05 level, including concomitant aspirin use. DISCUSSIONDOACs are increasingly prescribed in MPN patients for a wide range of indications, with heterogeneity in practice patterns. In our cohort, 1-year thrombosis and bleeding incidence rates on DOAC were 5.5% and 12.3%, respectively. While our 5.5% thrombosis rate is similar to recurrent thrombosis rates reported in MPN patients on DOACs and VKA, our 12.3% bleeding rate appears much higher. This may be related to the complexity of patients seen at our tertiary referral center. The higher-than-expected bleeding rate found in our study indicates the continued need for rigorous evaluation of DOACs in this population, with the gold standard being randomized controlled trials comparing DOAC with warfarin. [Display omitted] DisclosuresNeuberg: Madrigal Pharmaceuticals: Other: Stock ownership; Pharmacyclics: Research Funding. Rosovsky: Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hobbs: Bayer: Research Funding; Merck: Research Funding; AbbVie.: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; Novartis: Consultancy; Incyte Corporation: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding. Connors: Abbott: Consultancy; Bristol-Myers Squibb: Honoraria; takeda: Honoraria; Alnylam: Consultancy; Pfizer: Honoraria; CSL Behring: Research Funding.

Risk factors for recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia

目的分析并探讨真性红细胞增多症（PV）和原发性血小板增多症（ET）患者发生再次血栓事件（再栓）的临床特点及危险因素。方法回顾性分析首都医科大学附属北京安贞医院2001年2月至2016年11月诊治的38例发生再栓事件的ET和PV患者的临床资料，采用Logistic回归分析再栓事件危险因素。结果共计104例首次血栓事件的ET和PV患者中，38例（36.5%）患者发生再栓，年发生率为9.8%/人，ET组、PV组再栓年发生率分别为12.3%/人、5.7%/人。再栓事件共56次，42.1%发生在首次血栓形成后1年内；动脉血栓症占97.4%（以急性冠脉综合征最为多见），静脉血栓症占2.6%。ET组再栓以急性冠脉综合征最多见（18例，64.3%），PV组以脑梗死最常见（7例，70.0%）。2次及以上再栓患者中，PV（9例，90.0%）明显多于ET（7例，25.0%）。再栓组初诊WBC>12.5×109/L（52.6%对31.8%，P=0.036）、红细胞比容（Hct）>45%（50.0%对30.0%，P=0.046）、既往血栓史（86.8%对13.6%，P<0.001）、脾肿大（84.2%对33.3%，P<0.001）、治疗未缓解（52.6%对15.2%，P<0.001）、血栓事件分层高危患者占比（94.7%对53.0%，P<0.001）高于单次血栓组；Logistic回归分析显示，既往血栓史（OR=13.697，P=0.025）、脾肿大（OR=13.301，P=0.034）和血栓事件分层高危（OR=44.618，P=0.025）为ET/PV再栓的独立危险因素。结论ET和PV患者有较高的再栓发生率，ET患者再栓发生率高于PV患者，急性冠脉综合征多见；PV多次再栓发生率多于ET，脑梗死较多见。既往血栓史、脾肿大和血栓事件分层高危是再栓的独立危险预测因素。

High risk of recurrent venous thrombosis in patients with lower‐leg cast immobilization

Essentials The risk of recurrent venous thrombosis (VT) after leg-cast in patients with prior VT is unknown. In a nested case-control study within the MEGA follow-up study we aimed to estimate this risk. Patients with a history of VT who require lower-leg cast have a 4.5-fold risk for recurrence. This relative risk translates to an absolute risk for recurrent VT of about 3.2% within 3months. SUMMARY: Background Patients with lower-leg cast immobilization have a substantially increased risk of developing a first venous thrombosis (VT), whereas the risk in patients with a history of VT is as yet unknown. Aims To estimate the risk of recurrent VT after lower-leg cast immobilization in patients with a history of VT. Methods A case-control study nested within a cohort of 4597 patients with a first VT who were followed over time for recurrence from 1999 to 2010 (MEGA follow-up study). Participants completed a questionnaire on risk factors for recurrent thrombosis, including having a cast in the first 3 months before a recurrence (cases) or a random 3-month period during follow-up for participants without recurrence (controls). In total, 2723/4597 (59%) participants returned the questionnaire. Odds ratios (ORs), adjusted for age and sex, were calculated to compare risks of recurrence between subjects with and without a cast. Results A total of 2525/2723 participants (93%) filled out information on cast immobilization and were included in the analysis (451 cases; 2074 controls). Twenty (1.0%) controls and 10 (2.2%) cases reported having had a lower-leg cast in the 3months before the control or recurrence date (adjusted OR, 2.4; 95% confidence Interval [CI], 1.1-5.3). We cross-checked the data with these patients' medical records. Cast application within 3 months was verified in seven (0.3%) controls vs. six (1.3%) cases, leading to an adjusted OR of 4.5 (95% CI, 1.5-14.0) and corresponding cumulative incidence of 3.2%. Conclusions Lower-leg cast immobilization increases the risk of recurrent VT in the 3months after its application in patients with a history of VT.

Intracardiac and intracerebral thrombosis associated with methylenetetrahydrofolate reductase A1298C homozygote mutation in paediatric steroidresistant nephrotic syndrome

Thromboembolic complications are a significant cause of morbidity and mortality in cases of nephrotic syndrome. Hereditary thrombophilias are also known to increase vascular thrombosis. We present a case that has been followed up for steroid-resistant nephrotic syndrome (NS) in which intracardiac and intracranial thrombosis subsequently developed. The patient was found to have a homozygote mutation in the methylenetetrahydrofolate reductase (MTHFR) gene as an additional risk factor for recurrent thrombosis. MTHFR mutation with NS was considered to have an important effect on the development of life-threatening thrombosis.

Elevated partial antiphospholipid score is a strong risk factor for thrombosis in patients with systemic lupus erythematosus: a validation study.

This study aims to identify risk factors for thrombosis in patients with systemic lupus erythematosus (SLE) and to validate the efficacy of the partial antiphospholipid (aPL) score for thrombosis prediction and diagnosis of antiphospholipid syndrome (APS). This study included 325 SLE patients, 188 of whom completed a follow-up of 31.01 months (range 23-48 months). Partial aPL score was calculated by adding up the individual scores for activated partial thromboplastin time (APTT), lupus anticoagulant, IgG/IgM anticardiolipin antibodies (aCL), and IgG/IgM anti-β2-glycoprotein I (anti-β2GPI). A simplified aPL score was developed using only APTT, IgG/IgM aCL, and IgG/IgM anti-β2GPI. Partial aPL scores were significantly higher in SLE patients with thrombosis (p < 0.0001). A history of thrombosis (p < 0.0001), a partial aPL score >10 (p < 0.0001), and immunosuppressant use (p = 0.012) were independent risk factors for thrombosis. For patients with a history of thrombosis, partial aPL score was the strongest risk factor for recurrent thrombosis (p < 0.0001, odds ratio = 30.34 (95 % CI 7.70-118.81)). For APS diagnosis, the area under the receiver-operating characteristic curve (AUC) was 0.809 (95 % CI 0.73-0.89) using the partial aPL score. Similarly, the simplified aPL score was significantly associated with thrombosis (p < 0.0001) and was acceptable for APS diagnosis (AUC 0.797, 95 % CI 0.72-0.88). An elevated partial aPL score is a strong risk factor for thrombosis in SLE patients and is a useful tool to predict recurrent thrombosis. Partial aPL score and simplified aPL score, although comprising fewer items than the original aPL score, also represent valuable quantitative indices for APS diagnosis.

A Comprehensive Review of IVC Filters in a Community Tertiary Center

Introduction Retrievable inferior vena cava (IVC) filters are frequently used to prevent pulmonary embolus (PE). Indwelling filters can be associated with complications; timely removal is recommended. In our institution, activated trauma (AT) patients are enrolled in a prospective protocol and tracked by the trauma team, who refer for retrieval as soon as feasible. Interventional radiology maintains a database for traumatic injury (TI) and medical (M) patients and calls them for retrieval at 90 days. To this end, the primary goal of this study was to assess different retrieval patterns between Level 1 and 2 trauma patients, traumatic injury patients not triggering trauma response, and those with medical indications for IVC filters. An additional analysis to examine rates of recurrent thrombosis stratified for filter retention and anticoagulation status was performed.MethodsA retrospective chart review was performed for all patients who had an IVC filter placed between January 2005 and March 2015 at Gundersen Medical Center in La Crosse, WI. Data were collected regarding patients' demographics, risk factors for thrombosis, indications for and details of filter type and placement, post-placement anticoagulation, filter retrieval, and complications arising from filter placement, retention, and retrieval. Patients were divided into AT, TI, and M groups. AT consisted of Level 1 or 2 traumas triggering management by trauma service, TI patients had lesser trauma not triggering trauma team referral, and M patients had filters for medical indications. Those who were lost to follow up or died within 30 days were excluded from all analysis except demographics. Those with permanent filters were omitted from retrieval analysis.ResultsOf the 633 charts reviewed, 4 were excluded for lack of data, 41 were lost to follow-up and 68 died within 30 days. Table 1 summarizes patient category characteristics. Activated trauma patients were younger and had their filter retrieved more often (p<0.0001) than medical or TI patients. The medical population were older, had more risk factors for recurrent thrombosis (median 2 risk factors, range 0-8) and more likely to remain on chronic anticoagulation (27.9%). Those receiving anticoagulation after filter placement had greater rates of recurrent thrombosis (p<0.0001), but more risk factors (p<0.0001)for thrombosis compared to those receiving no anticoagulation. No significant differences were observed in thrombosis-free survival with regard to filter retention. However, rates of DVT after filter placement were 8% higher if the filter was retained rather than removed across all 3 groups(p=0.0011, McNemar's Chi-square).DiscussionHigher rates of DVT in patients with a filter in place are in line with current research associating IVC filters with DVT formation. We observed that patients on lifelong anticoagulation had a higher rate of recurrent thrombosis but increased risk factors for thrombosis, thus identifying a higher risk group for thrombotic events.AT patients in a protocol setting had higher IVC filter retrieval rates compared to the M and IT patients with routine efforts at retrieval. The large gap between M/TI and AT filter retrieval is associated with but not fully explained by the increased risk factors and age of the M and IT groups. Protocolized retrieval of IVC filters increases retrieval rates. Further research is warranted in assessing the impact of protocolized retrieval in the medical and traumatic injury populations.Table 1Patient Category CharacteristicsPatient CategoryN (%)Age (median, range)Retrieval Rate (%)Activated trauma (AT)195 (31%)41 (15-92)78%Traumatic injury (TI)74 (11.8%)44 (16-93)43%Medical (M)360 (57.2%)68 (17-101)38% DisclosuresParsons:Celgene: Speakers Bureau.

Postintervention duration of anticoagulation in venous surgery

For a substantial proportion of patients with deep venous thrombosis (DVT), current treatment strategies are suboptimal and new treatment options are needed. Especially for the group of patients who are at the highest risk for post-thrombotic syndrome, new treatment modalities such as catheter-directed thrombolysis and additional stenting are being investigated. With current clinical studies addressing new technical options, the medical management of patients following these interventions deserves attention. The duration of anticoagulant treatment following surgical or radiological interventions for DVT seems not to be influenced by the presence of a venous stent. According to recent ACCP 2012 guidelines the anticoagulant management in patients who have had any method of thrombus removal performed, the same intensity and duration of anticoagulant therapy as in comparable patients who do not undergo thrombosis removal is recommended (Grade 1B). In the acute phase of thrombosis, irrespective of the technique and whether or not stenting is applied, immediate anticoagulation following the procedure is pertinent to reduce the risk of recurrent thrombosis and thrombus propagation. The long-term treatment duration after venous interventions therefore may be tailored based on common risk factors for recurrent thrombosis and the individual risk for bleeding. Selected thrombophilia factors, d-dimer assessment and residual venous thrombosis provide markers for recurrent DVT. Currently, vitamin K antagonists) provide the main anticoagulants for (prolonged) anticoagulation, while the new oral anticoagulants emerge as promising alternatives. In case prolonged anticoagulation after unprovoked DVT is not indicated, cardiovascular risk management is warranted because of an increased rate of arterial thrombotic events after DVT; aspirin may be indicated as secondary prevention against recurrent thrombosis (while providing primary prevention against arterial thrombosis).

Risk factors and recurrent thrombotic episodes in patients with cerebral venous thrombosis.

The prevalence of thrombophilic abnormalities in patients with cerebral vein thrombosis has been reported to be similar to that in patients with deep vein thrombosis of the lower limb. The role of gender-specific risk factors (pregnancy, oral contraceptives) is well established, whereas that of other acquired risk conditions is debated. We screened 56 patients with cerebral vein thrombosis and 184 age- and sex-matched apparently healthy controls for prothrombin (factor II, FII) G20210A and factor V Leiden polymorphisms; protein S, protein C, and antithrombin deficiency; anticardiolipin antibodies; hyperhomocysteinaemia and other putative risk factors. The G20210A polymorphism was found in 29.1% of patients and in 5.7% of controls (odds ratio [OR] 7.1; P<0.0001; adjusted OR 12.67, P<0.0001). Frequencies of factor V Leiden and hyperhomocysteinaemia were not significantly different in patients and controls, nor were the other thrombophilic tests and some established cardiovascular risk factors, such as smoking, obesity or overweight and arterial hypertension. Conversely, 53.7% of the women who developed cerebral vein thrombosis did so while assuming oral contraceptives (OR 6.12; P<0.0001), with a further increase of risk in FII G20210A carriers (OR 48.533). Some associated diseases (onco-haematological disorders and infections) also had a significant role. Over a median 7-year follow-up, irrespective of the duration of antithrombotic treatment, 9/56 (16%) patients had further episodes of venous/arterial thrombosis. No significant risk factor for recurrent thrombosis was identified. In spite of the limitations of the sample size, our data confirm the role of FII G20210A mutation in this setting and its interactions with acquired risk factors such as oral contraceptives, also highlighting the risk of recurrent thrombosis in cerebral vein thrombosis patients.

Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia

There is evidence that leukocytosis is associated with an increased risk of first thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Whether it is a risk factor for recurrent thrombosis too is currently unknown. In the frame of a multicenter retrospective cohort study, we recruited 253 patients with PV (n = 133) or ET (n = 120), who were selected on the basis of a first arterial (70%) or venous major thrombosis (27.6%) or both (2.4%), and who were not receiving cytoreduction at the time of thrombosis. The probability of recurrent thrombosis associated with the leukocyte count recorded at the time of the first thrombosis was estimated by a receiver operating characteristic analysis and a multivariable Cox proportional hazards regression model. Thrombosis recurred in 78 patients (30.7%); multivariable analysis showed an independent risk of arterial recurrence (hazard ratio [HR] 2.16, 95% CI 1.12-4.18) in patients with a leukocyte count that was >12.4 x 10(9)/L at the time of the first thrombotic episode. The prognostic role for leukocytosis was age-related, as it was only significant in patients that were aged <60 years (HR for arterial recurrence 3.35, 95% CI 1.22-9.19).

Recurrent Thromboembolism in a Tertiary Care Pediatric Center.

Abstract 2987Poster Board II-963 Background:Thrombosis in children, though rare, is being increasingly recognized in pediatric tertiary care centers. Most data on children have largely been extrapolated from adults. Comprehensive data about the incidence and risk factors for recurrence of pediatric thrombosis are scarce. Aim:1) To estimate the incidence of recurrence of thrombosis at a single pediatric tertiary care center and 2) To determine the risk factors for recurrent thrombosis in children. Methods:After local IRB approval, charts of patients (pts) with documented venous or arterial thrombosis admitted or referred to the hematology service from 2001-2008, were reviewed and pertinent data obtained. Data were analyzed using the 17.0 version of SPSS. Results:Preliminary analysis revealed 238 pts (ages 0-30 years) with 183 deep venous (DVT, 75%), 53 arterial (22%) and 2 combined (0.8%) episodes of thrombosis at initial presentation. Of the 183 pts with DVT there were 110 females, 128 males; of pts with arterial strokes there were 21 females, 32 males. Overall 11 pts (4.6%, 6 females, 5 males) had a recurrence, with 91% venous and 9% arterial. Three (27%; 2 females, 1 male) out of the 11 pts had a third recurrence, which were all venous. Sites for recurrence were lower extremity (82%), neck (9%) and thorax (9%).Risk factors for recurrence were positive family history of DVT (7/11; 63.6%), elevation in factor VIII (5/11; 45.5%), proximal lower extremity thrombosis as primary site (5/11; 45.5%), obesity (4/11; 36.4%), the presence of PTTLA (4/11; 36.4%) and the presence of inflammatory bowel disease (27.3%). Heterozygous factor V Leiden and congenital AT III deficiency was present in one pt each (9%) with recurrence. Other congenital thrombophilia traits were not seen in patients with recurrent events. Interestingly, gender, duration of treatment and residual clot after treatment (partial resolution) were not significantly associated with risk of recurrence. Conclusion:Recurrent thrombosis is infrequent in children and a positive family history, elevated factor VIII, and other acquired factors such as obesity and inflammatory bowel disease were identified as risk factors for recurrence. Inherited thrombophilia and partial resolution of thrombosis were not associated with recurrence in this series of patients. Larger multi-center trials are needed to identify risk factors for recurrence in children. To our knowledge this is the first pediatric study that has systematically evaluated the incidence and risk factors associated with recurrent pediatric thrombosis. Disclosures:No relevant conflicts of interest to declare.

Increased risk of recurrent thrombosis in patients with essential thrombocythemia carrying the homozygous JAK2 V617F mutation

Evidence suggests that the JAK2 V617F mutation is associated with an increased risk of first thrombosis in patients with essential thrombocythemia (ET). Whether this mutation is also a risk factor for recurrent thrombosis is currently unknown. To investigate the impact of the JAK2 V617F mutation on the risk of recurrent thrombosis in patients with ET, we carried out a multicentre retrospective cohort study. We recruited 143 patients with previous arterial (64.4%) or venous major thrombosis (34.8%) or both (0.8%); 98 of them (68.5%) carried the mutation. Thrombosis recurred in 43 of the patients (30%); overall, after adjustment for sex, age, presence of vascular risk factors, and treatment after the first thrombosis, the presence of the JAK2 mutation did not predict recurrence (multivariable hazard ratio, HR, 0.88, 95% CI 0.46-1.68). Indeed, the individuals homozygous for the JAK2 V617F (allele burden >50%) mutation had an increased risk of recurrence in comparison with wild-type patients (HR 6.15, 95% CI 1.51-24.92). In conclusion, a homozygous JAK2 V617F mutation is an independent risk factor for recurrent thrombosis in patients with ET.

Cystic fibrosis as a risk factor for recurrent venous thrombosis at a pediatric tertiary care hospital

To evaluate risk factors for recurrent thrombosis in pediatric patients. This prospective observational cohort study enrolled 120 patients with acute venous thromboembolism from January 2003 to April 2005. Data collection included medical and family history, radiologic and laboratory studies, therapy, and follow-up. The overall prevalence of recurrent thrombosis in our cohort was 19/120 (15.8%). Patients with recurrence were older, with a median age of 14.8 years (range 2 weeks-23.6 years), compared with 10.1 years (range newborn 23.4 years) in patients without recurrence (P = .03). Six of the 19 patients with recurrent thrombosis had cystic fibrosis (CF), compared with 0/101 without recurrence (P < .001). Five of these 6 patients were colonized with Burkholderia cepacia in their sputum. Central venous catheters were associated with most, but not all, of the thromboses in patients with CF. In this study, patients with CF had a high risk of recurrent venous thrombosis, as well as a high prevalence of colonization with B cepacia. The cause of this risk has not been defined. This observation may have important implications for thromboprophylaxis, particularly in the setting of central venous catheters.

Risk Factors for Recurrent Thrombosis: Prospective Study of a Cohort of Japanese Systemic Lupus Erythematosus

Not only antiphospholipid antibodies (aPLs) but also other factors should be considered in assessing the risk of thrombosis development in patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPLs). The kinds of risk factors, including past history of thrombotic event (PHTE), hypertension, hypercholesterolemia, diabetes mellitus (DM), obesity, and smoking, in conjunction with aPLs, that contribute to the development of new thrombotic events in patients with SLE and aPLs were studied prospectively over a 5-year observation period. One-hundred and sixty-six Japanese patients with SLE (55 patients with aPLs and 111 patients without aPLs) were examined and followed up for 5 years. Five major risk factors for ischemic coronary disease and stroke according to the Framingham heart cohort study were evaluated objectively in these patients. A significant difference was seen for 4 factors: past history of thrombotic event (PHTE; odds ratio: 101.93; 95% confidence interval: 12.29-845.22; p < 0.0001), hypertension (odds ratio: 8.87; 95% CI: 2.58-30.53; p < 0.001), DM (odds ratio: 5.42; 95% CI: 1.44-20.46; p < 0.05), and lupus anticoagulant (LAC; odds ratio: 47.41; 95% CI: 5.88-382.03, p < 0.0001) as aPLs, when the incidence of these risk factors was compared between patients with and without new thrombotic events. Furthermore, PHTE (odds ratio: 30.19, 95% CI: 1.33-683.13), hypertension (odds ratio: 15.44; 95% CI: 1.77-134.80), and LAC (odds ratio: 14.11; 95% CI: 0.48-412.42) showed higher odds ratios than DM (odds ratio: 11.53; 95% CI: 0.83-159.94) on multivariate logistic analysis as well as analysis of the combination of risk factors, suggesting that these are important risk factors for the development of new thrombotic events in patients with SLE and aPLs.

A prospective study of antibodies to β2‐glycoprotein I and prothrombin, and risk of thrombosis

Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterized by thrombosis/pregnancy morbidity associated with the persistence of lupus anticoagulant (LA) and/or anticardiolipin (aCL) antibodies. We assessed the contribution of antibodies to beta2-glycoprotein I (anti-beta2GPI) and prothrombin (anti-PT) to the thrombotic risk in a cohort of 194 consecutive patients with persistent LA and/or aCL. Median follow-up was 45 months. A total of 39 patients (20.1%) had one documented episode of thrombosis during follow-up. Eleven of these patients had no previous thrombosis before enrollment in the study and 28 had recurrences of thrombosis. There were 21 venous and 18 arterial thrombotic events and the overall incidence of thrombosis was 5.6% per patient-year. After multivariate analysis, the male sex (P = 0.025), a previous thrombosis (P < 0.01), the presence of anti-beta2GPI (P = 0.001), and the presence of anti-PT (P = 0.03) remained as independent risk factors for recurrent thrombosis. Only IgG anti-beta2GPI and anti-PT were associated with an increased risk of thrombosis (P < 0.01 and P = 0.005). Patients testing positive for anti-beta2GPI had a higher rate of thrombosis than did antiphospholipid patients without anti-beta2GPI (8.0% vs. 3.1% per patient-year). Similarly, a higher rate of thrombosis was found in patients with positive anti-PT compared with patients without anti-PT (8.6% vs. 3.5% per patient-year). Considering only the group of 142 LA positive patients, the highest incidence of thrombosis was found in LA patients positive for both anti-beta2GPI and anti-PT (8.4% per patient-year). In conclusion, the presence of IgG anti-beta2GPI and anti-PT in patients with LA and/or aCL and mainly in those with LA predicts a higher risk of thromboembolic events.

Deep Venous Thrombosis

Venous thromboembolism (VTE), manifested as either deep venous thrombosis (DVT) or pulmonary embolism (PE), is an extremely common medical problem, occurring either in isolation or as a complication of other diseases or procedures. Yet, despite its frequency, much remains to be learned regarding the pathogenic mechanisms that initiate VTE, about tailoring its treatment to the individual with her/his specific set of risk factors for recurrence, and about its medical management when associated with specific disease entities, such as cancer. These three topics are addressed in this chapter. In Section I, Drs. López and Conde discuss the mechanisms by which venous thrombi may be initiated on the vessel wall in the absence of anatomically overt vessel wall injury. The authors propose a model whereby tissue factor (TF)-bearing microvesicles that arise from cells of monocyte/macrophage lineage can fuse with activated endothelial cells in regions of vessel activation or inflammation and initiate blood coagulation. Key components of this model include docking of the microvesicles to the stimulated endothelium through P-selectin glycoprotein ligand-1 on their surfaces binding to either P-selectin or E-selectin on the endothelium, and the role of hypoxia during blood stasis in initiating local endothelial activation. Elevations in the levels of TF-bearing microvesicles associated with inflammatory conditions would help to explain the increased risk of thrombosis associated with infections and inflammatory states such as inflammatory bowel disease. In Section II, Dr. Clive Kearon discusses the risk factors for recurrent thrombosis and strategies for determining length of therapy and tailoring specific therapies through risk stratification. Those patients who experience VTE in association with a major reversible risk factor such as surgery are much less likely to experience a recurrence when anticoagulation is discontinued than are patients with a persistent risk factor, such as thrombophilia or cancer unresponsive to therapy. Those with a minor reversible risk factor, such as prolonged air travel, have an intermediate risk of recurrence after discontinuance of anticoagulant therapy. The author provides an algorithm for using risk assessment as a means of determining the length and type of therapy to be used to minimize the rate of recurrence while simultaneously diminishing the risk of bleeding associated with anticoagulation. In Section III, Dr. Agnes Lee updates the topic of VTE associated with malignancy. Patients with cancer make up approximately 20% of those presenting with first time VTE, and the presence of VTE forebodes a much poorer prognosis for patients with cancer, likely because of the morbidity associated with VTE itself and because VTE may herald a more aggressive cancer. Recent evidence indicates that low-molecular weight heparins (LMWHs) improve survival in patients with advanced cancer through mechanisms beyond their effect as anticoagulants. Because of their improved efficacy and safety and potential anti-neoplastic effect, the LMWHs have become the anticoagulants of choice for treating VTE associated with cancer.