Acute Lymphoblastic Leukemia With Near-haploid Karyotype and Philadelphia Chromosome.

BACKGROUND/AIM: In precursor B-cell lineage acute lymphoblastic leukemia (BCP-ALL), leukemic cells harbor genetic abnormalities that play an important role in the diagnosis, prognosis, and treatment. A subgroup of BCP-ALL is characterized by the presence of a Philadelphia (Ph) chromosome and a chimeric BCR::ABL1 gene, whereas in another subgroup, leukemic cells exhibit near-haploidy with chromosome number 24-30. This study presents the third documented case of BCP-ALL in which a near haploid clone concurrently displayed a Ph chromosome/BCR::ABL1. CASE REPORT: Bone marrow cells obtained at diagnosis from a 25-year-old man with BCP-ALL were genetically investigated using G-banding, fluorescence in situ hybridization, and array comparative genomic hybridization. Leukemic cells had an abnormal karyotype 28,X,-Y,+6,+10,+18,+21,+ der(22) t(9;22)(q34;q11)[13]/28,idem, del(10)(q24),der(12) t(1;12) (q21;p13)[2]/46,XY[3], retained heterozygosity of the disomic chromosomes 6, 10, 18, and 21, had breakpoints in introns 1 of ABL1 and BCR, and carried a BCR::ABL1 chimera encoding the 190 kDa BCR::ABL1 protein. CONCLUSION: The coexistence of the BCR::ABL1 chimera and near-haploidy in the same cytogenetic clone suggested a possible synergistic role in leukemogenesis, with the former activating signaling pathways and the latter disrupting gene dosage balance.

Increase in peg-asparaginase clearance as a predictor for inactivation in patients with acute lymphoblastic leukemia.

Asparaginase is an essential component of acute lymphoblastic leukemia (ALL) therapy, yet its associated toxicities often lead to treatment discontinuation, increasing the risk of relapse. Hypersensitivity reactions include clinical allergies, silent inactivation, or allergy-like responses. We hypothesized that even moderate increases in asparaginase clearance are related to later inactivation. We therefore explored mandatory monitoring of asparaginase enzyme activity (AEA) in patients with ALL aged 1-45 years treated according to the ALLTogether pilot protocol in the Nordic and Baltic countries to relate mean AEA to inactivation, to build a pharmacokinetic model to better characterize the pharmacokinetics of peg-asparaginase and assess whether an increased clearance relates to subsequent inactivation. The study analyzed 1631 real-time AEA samples from 253 patients, identifying inactivation in 18.2% of the patients. This inactivation presented as mild allergy (28.3%), severe allergy (50.0%), or silent inactivation (21.7%). A pharmacokinetic transit compartment model was used to describe AEA-time profiles, revealing that 93% of patients with inactivation exhibited prior increased clearance, whereas 86% of patients without hypersensitivity maintained stable clearance throughout asparaginase treatment. These findings enable prediction of inactivation and options for either dose increments or a shift to alternative asparaginase formulations to optimize ALL treatment strategies.

Transcriptome analysis of primary adult B-cell lineage acute lymphoblastic leukemia identifies pathogenic variants and gene fusions, and predicts subtypes for in depth molecular diagnosis.

BACKGROUND: B-cell acute lymphoblastic leukemia (B-ALL) is classified into subgroups based on known driver oncogenes and molecular lesions, including translocations and recurrent mutations. However, the current diagnostic tests do not identify subtypes or oncogenic lesions for all B-ALL samples, creating a heterogeneous B-ALL group of unknown subtypes. METHODS: We sorted primary adult B-ALL cells and performed transcriptome analysis by bulk RNA sequencing (RNA-seq). RESULTS: Transcriptomic analysis of an adult B-ALL cohort allowed the classification of four patient samples with subtypes that were not previously revealed by standard gene panels. The leukemia of two patients were of the DUX4 subtype and two were CRLF2+ Ph-like B-ALL. Furthermore, single nucleotide variant analysis detected the oncogenic NRAS-G12D, KRAS-G12D, and KRAS-G13D mutations in three of the patient samples, presenting targetable mutations. Additional oncogenic variants and gene fusions were uncovered, as well as multiple variants in the PDE4DIP gene across five of the patient samples. CONCLUSION: We demonstrate that RNA-seq is an effective tool for precision medicine in B-ALL by providing comprehensive molecular profiling of leukemia cells, identifying subtype and oncogenic lesions, and stratifying patients for appropriate therapy.

Acute Undifferentiated Leukemia With a Balanced t(5;10)(q35;p12) Resulting in Fusion of HNRNPH1 With MLLT10.

BACKGROUND/AIM: Acute undifferentiated leukemia (AUL) is leukemia which does not express lineage-specific antigens. Such cases are rare, accounting for 2.7% of all acute leukemia. The reported genetic information of AULs is limited to less than 100 cases with abnormal karyotypes and a few cases carrying chimeric genes or point mutation of a gene. We herein present the genetic findings and clinical features of a case of AUL. CASE REPORT: Bone marrow cells obtained at diagnosis from a 31-year-old patient with AUL were genetically investigated. G-Banding karyotyping revealed an abnormal karyotype: 45,X,-Y,t(5;10)(q35;p12),del(12)(p13)[12]/46,XY[5]. Array comparative genomic hybridization examination confirmed the del(12)(p13) seen by G-banding but also detected additional losses from 1q, 17q, Xp, and Xq corresponding to the deletion of approximately 150 genes from these five chromosome arms. RNA sequencing detected six HNRNPH1::MLLT10 and four MLLT10::HNRNPH1 chimeric transcripts, later confirmed by reverse-transcription polymerase chain reaction together with Sanger sequencing. Fluorescence in situ hybridization analysis showed the presence of HNRNPH1::MLLT10 and MLLT10::HNRNPH1 chimeric genes. CONCLUSION: To the best of our knowledge, this is the first AUL in which a balanced t(5;10)(q35;p12) leading to fusion of HNRNPH1 with MLLT10 has been detected. The relative leukemogenic importance of the chimeras and gene losses cannot be reliably assessed, but both mechanisms were probably important in the development of AUL.

Arterial events in cancer patients treated with apixaban for venous thrombosis.

INTRODUCTION: In a recent interventional study of cancer patients with newly diagnosed venous thrombosis (VT), we found a high risk of arterial thrombotic events (AT) during treatment with therapeutic doses of apixaban. METHODS: Total 298 cancer patients with VT received apixaban as treatment and secondary prophylaxis for up to 36 months. AT was registered as a serious adverse event, and this is a post hoc analysis of risk factors for AT. Clinical risk factors and concomitant medication were assessed through odds ratios (OR) with 95 % confidence interval using multivariate logistic regression. Biomarkers were assessed by non-parametric testing. RESULTS: AT occurred in 16/298 patients (5.4 %, 95 % confidence interval (CI) 3.1-8.6 %). Median leucocyte count at baseline was higher in patients with AT compared with patients without AT (11 vs. 6.8·109/L, p < 0.01). Clinical factors associated with AT were pancreatic cancer (OR 13.7, 95 % CI 4.3-43.1), ovarian cancer (OR 19.3, 95 % CI 2.3-164.4), BMI <25 percentile (OR 3.1, 95 % CI 1.1-8.8) and previous VT (OR 4.4, 95 % CI 1.4-13.7). Pancreatic cancer had a cumulative incidence of AT of 36 % compared with 0.8 % for all other cancers at 6 months (p < 0.01). Non-steroidal anti-inflammatory drugs (OR 4.9, 95 % CI 1.0-26) and antiplatelet treatment (OR 3.8, 95 % CI 1.2-12.2) were associated with AT. CONCLUSION: In cancer patients with apixaban treated VT, pancreatic cancer was strongly associated with AT. In addition, ovarian cancer, BMI < 25 percentile, previous VT, antiplatelet treatment, non-steroidal anti-inflammatory drug use and high leucocyte count at baseline were associated with AT. The CAP study is registered with the unique identifier NCT02581176 in ClinicalTrials.gov.

Measuring Quality of Life after Venous Thromboembolism: Who, When, and How?

There is a growing body of evidence revealing that many patients with a history of venous thromboembolism (VTE) suffer from long-lasting sequelae such as post-thrombotic syndrome and post-pulmonary embolism syndrome. These two syndromes are detrimental to patients as they affect their quality of life (QOL). From this perspective, monitoring QOL may play a crucial role to improve quality care in VTE patients. Many studies have explored possible temporal relations between VTE episodes and decreased functional status and/or QOL. However, studies exploring the implementation of QOL and functional status questionnaires in clinical practice are scarce. In this context, we discuss possible perspectives synthetized from available literature regarding in whom, when, and how QOL could be measured in clinical practice.

Thiopurine Enhanced ALL Maintenance (TEAM): study protocol for a randomized study to evaluate the improvement in disease-free survival by adding very low dose 6-thioguanine to 6-mercaptopurine/methotrexate-based maintenance therapy in pediatric and adult patients (0-45 years) with newly diagnosed B-cell precursor or T-cell acute lymphoblastic leukemia treated according to the intermediate risk-high group of the ALLTogether1 protocol.

BACKGROUND: A critical challenge in current acute lymphoblastic leukemia (ALL) therapy is treatment intensification in order to reduce the relapse rate in the subset of patients at the highest risk of relapse. The year-long maintenance phase is essential in relapse prevention. The Thiopurine Enhanced ALL Maintenance (TEAM) trial investigates a novel strategy for ALL maintenance. METHODS: TEAM is a randomized phase 3 sub-protocol to the ALLTogether1 trial, which includes patients 0-45 years of age with newly diagnosed B-cell precursor or T-cell ALL, and stratified to the intermediate risk-high (IR-high) group, in 13 European countries. In the TEAM trial, the traditional methotrexate (MTX)/6-mercaptopurine (6MP) maintenance backbone (control arm) is supplemented with low dose (2.5-12.5 mg/m2/day) oral 6-thioguanine (6TG) (experimental arm), while the starting dose of 6MP is reduced from 75 to 50 mg/m2/day. A total of 778 patients will be included in TEAM during ~ 5 years. The study will close when the last included patient has been followed for 5 years from the end of induction therapy. The primary objective of the study is to significantly improve the disease-free survival (DFS) of IR-high ALL patients by adding 6TG to 6MP/MTX-based maintenance therapy. TEAM has 80% power to detect a 7% increase in 5-year DFS through a 50% reduction in relapse rate. DFS will be evaluated by intention-to-treat analysis. In addition to reducing relapse, TEAM may also reduce hepatotoxicity and hypoglycemia caused by high levels of methylated 6MP metabolites. Methotrexate/6MP metabolites will be monitored and low levels will be reported back to clinicians to identify potentially non-adherent patients. DISCUSSION: TEAM provides a novel strategy for maintenance therapy in ALL with the potential of improving DFS through reducing relapse rate. Potential risk factors that have been considered include hepatic sinusoidal obstruction syndrome/nodular regenerative hyperplasia, second cancer, infection, and osteonecrosis. Metabolite monitoring can potentially increase treatment adherence in both treatment arms. TRIAL REGISTRATION: EudraCT, 2018-001795-38. Registered 2020-05-15, Clinicaltrials.gov , NCT04307576 . Registered 2020-03-13, https://clinicaltrials.gov/ct2/show/NCT04307576.

Post-thrombotic syndrome in patients with venous thromboembolism treated with dabigatran or warfarin: A long-term cross-sectional follow-up of RE-COVER study patients.

BACKGROUND: Studies suggest that the direct factor Xa inhibitor rivaroxaban compared to warfarin reduces the risk of post-thrombotic syndrome (PTS) after deep vein thrombosis (DVT), but this has not been evaluated for oral direct thrombin inhibitors. OBJECTIVES: To compare the long-term prevalence of PTS, recurrent venous thromboembolism (VTE), and health-related quality of life (HRQoL) in patients with acute DVT and/or pulmonary embolism (PE), randomized to treatment with dabigatran or warfarin in the phase III RE-COVER studies. METHODS: We conducted a cross-sectional follow-up study of patients randomized in Canada, Norway, and Sweden. PTS was assessed by the patient-reported Villalta scale (PRV) and HRQoL by EQ-5D and VEINES-QOL/Sym. RESULTS: We included 349 patients between December 2015 and November 2018; 166 were treated with dabigatran and 183 with warfarin. DVT (+/- PE) was index event in 255 patients, whereas 94 patients had PE only. Mean time from index event was 8.7 (standard deviation 1.4) years. PTS was diagnosed in 63% of patients with DVT and in 46% of patients with PE only, and did not differ between the treatment groups; the crude odds ratio (OR) for PTS in patients treated with dabigatran compared with warfarin was 1.1 (95% confidence interval [CI] 0.6-1.8) after DVT and 1.2 (95% CI 0.5-2.6) after PE only. The prevalence of recurrent VTE was 21% in both treatment groups. HRQoL scores did not differ between groups. CONCLUSION: In this long-term cross-sectional study, the prevalence of PTS, recurrent VTE, and HRQoL were similar in patients treated with dabigatran and warfarin.

Predictors of long-term post-thrombotic syndrome following high proximal deep vein thrombosis: a cross-sectional study.

BACKGROUND: Post-thrombotic syndrome (PTS) is a frequent chronic complication of proximal deep vein thrombosis (DVT) of the lower limb, but predictors of PTS are not well established. We aimed to examine predictors of PTS in patients with long-term PTS following proximal DVT. METHODS: During 2006-09, 209 patients with a first time acute upper femoral or iliofemoral DVT were randomized to receive either additional catheter-directed thrombolysis or conventional therapy alone. In 2017, the 170 still-living participants were invited to participate in a cross-sectional follow-up study. In the absence of a gold standard diagnostic test, PTS was defined in line with clinical practice by four mandatory, predefined clinical criteria: 1. An objectively verified DVT; 2. Chronic complaints (> 1 month) in the DVT leg; 3. Complaints appeared after the DVT; and 4. An alternative diagnosis was unlikely. Possible predictors of PTS were identified with multivariate logistic regression. RESULTS: Eighty-eight patients (52%) were included 8-10 years following the index DVT, and 44 patients (50%) were diagnosed with PTS by the predefined clinical criteria. Younger age and higher baseline Villalta score were found to be independent predictors of PTS, i.e., OR 0.96 (95% CI, 0.93-0.99), and 1.23 (95% CI, 1.02-1.49), respectively. Lack of iliofemoral patency at six months follow-up was significant in the bivariate analysis, but did not prove to be significant after the multivariate adjustments. CONCLUSIONS: In long-term follow up after high proximal DVT, younger age and higher Villalta score at DVT diagnosis were independent predictors of PTS.

Thrombosis and bleedings in a cohort of cancer patients treated with apixaban for venous thromboembolism.

INTRODUCTION: The direct oral anti-coagulants (DOAC) edoxaban and rivaroxaban are suggested treatment alternatives for cancer-associated venous thromboembolism (VTE) together with low molecular-weight heparins. New studies indicate that the DOAC apixaban also is an option for cancer-associated VTE. The current study assessed recurrent VTE, arterial thrombosis, bleedings and adverse events in a cohort of apixaban treated cancer patients with VTE. MATERIALS AND METHODS: Single-arm, interventional study of apixaban as treatment of cancer-associated VTE. Inclusion criteria were cancer with objectively verified VTE. Patients received apixaban 10 mg bid for seven days, then 5 mg bid for six months. Primary efficacy and safety outcomes were recurrent VTE and bleeding respectively. This trial is registered with ClinicalTrials.gov identifier NCT02581176. RESULTS: We recruited 298 cancer patients with VTE. During six months treatment, recurrent VTE or death related to VTE occurred in 12 patients (4.0%, 95% confidence interval (CI) 2.1-6.9%). Major bleeding occurred in 16 patients (5.4%, 95% CI 2.8-7.9), most frequently gastrointestinal bleeding. There were no overrepresentation of major bleedings among patients with gastrointestinal cancer (7/126, 5.5%, 95% CI 2.3-11%). Twenty-six patients experienced one or more clinically relevant non-major bleedings (8.9%, 95% CI 5.5-12%). Twelve patients had arterial thrombosis (4.0%, 95% CI 2.1-6.9%), of which the majority were strokes in patients with pancreatic cancer. Death occurred in 35 patients (12%, 95% CI 8.3-16%). CONCLUSION: The frequency of recurrent VTE and major bleedings are in line with other studies on apixaban in cancer-associated VTE. Arterial thrombosis was a frequent serious adverse event.

Limitations of the Villalta scale in diagnosing post-thrombotic syndrome.

INTRODUCTION: The Villalta scale is currently the recommended tool for diagnosing post-thrombotic syndrome (PTS) in clinical studies, but there is concern that the sensitivity and specificity of the scale might be low. We aimed to evaluate the diagnostic accuracy of the Villata scale using criteria in line with clinical practice as a reference. MATERIAL AND METHODS: We invited patients with a history of proximal DVT during 2006-09 to participate in a cross-sectional follow-up study of long-term complications after DVT. PTS was diagnosed by the Villalta scale, and by the following four mandatory and predefined clinical criteria used as a reference for PTS: 1. Objectively verified DVT; 2. chronic complaints (>1 month) in the DVT leg; 3. complaints appeared after the DVT; and 4. an alternative diagnosis was unlikely. RESULTS: We included 88 of 170 eligible patients (52%). With our clinical criteria as a reference the sensitivity and specificity of the Villalta scale for diagnosing PTS were 75% (95% CI 60-87%) and 66% (95% CI 50-80%), respectively. Fifteen patients were diagnosed with PTS by the Villalta scale only. These patients more often experienced pain or had comorbidity that could explain their leg symptoms and signs. Eleven patients diagnosed with PTS by the clinical criteria only, had more fluctuating heaviness and edema. CONCLUSIONS: Our findings indicate that the diagnostic accuracy of the Villalta scale has limitations. Incorporating chronicity, whether the leg problems appeared following the DVT, fluctuations of heaviness and edema, and comorbidity in PTS assessment may improve the diagnostic accuracy.

Does the Villalta scale capture the essence of postthrombotic syndrome? A qualitative study of patient experience and expert opinion.

BACKGROUND: The Villalta scale is recommended for diagnosing and grading of postthrombotic syndrome (PTS) in clinical studies, but with limitations in specificity and sensitivity. OBJECTIVES: To explore the typical complaints of PTS through patients experience and expert opinion and relate this to the items of the Villalta scale. PATIENTS/METHODS: A qualitative study design with focus group interviews including patients with PTS and health care workers experienced in PTS patient care. RESULTS: Typical PTS complaints were reflected within four main domains: (a) agonizing discomforts; patients without venous ulcers often described other discomforts than pain; (b) skin changes; these were common and sometimes present before deep vein thrombosis (DVT). Except for venous ulcers, skin changes were considered of less importance; (c) fluctuating heaviness and swelling during the day and with activity; (d) post-DVT concerns; fear of DVT recurrence, health services failing to meet the patients' expectations, and psychological and social restrictions. These findings are not necessarily captured or well reflected in the Villalta scale. CONCLUSION: Our findings indicate that the Villalta scale does not capture typical PTS complaints or their importance to the patients. A revision of the diagnosis and grading should be considered.

Elevated Complement C3 and C4 Levels are Associated with Postnatal Pregnancy-Related Venous Thrombosis.

High levels of complement C3 are associated with venous thrombosis (VT) in the general population. We investigated if high C3 and C4 levels were associated with pregnancy-related VT. We undertook the Norwegian VIP study, a case-control study of VT in pregnancy or within 3 months postpartum (cases, n = 313) and women without pregnancy-related VT (controls, n = 353). Determinants of C3 and C4 in the control women were investigated with linear regression and the odds ratio (OR) for pregnancy-related VT was calculated with logistic regression. We found that levels of C3 and C4 were associated with body mass index (BMI), C-reactive protein (CRP); with the coagulation factors (F) fibrinogen, FVIII, and FIX; and with the coagulation inhibitors antithrombin, protein C, protein S, and tissue factor pathway inhibitor. These associations were influenced by CRP levels. The crude OR for pregnancy-related VT was 1.8 (95% confidence interval [CI], 1.1-3.0) for C3 above the 90th percentile and 2.0 (95% CI, 1.2-3.2) for C4 above the 90th percentile. Stratification in antenatal and postnatal VT showed that C3 and C4 were only associated with postnatal VT with an OR for high C3 of 3.0 (95% CI, 1.8-5.0), and for high C4 of 2.6 (95% CI, 1.5-4.6). Adjustment for high FIX and BMI reduced the ORs. We conclude that the association between postnatal VT and C3 and C4 suggests that there is clinically relevant crosstalk between the complement and the coagulation system.

Diagnostic scales for the post-thrombotic syndrome.

Post-thrombotic syndrome (PTS) is the most common long-term complication after deep vein thrombosis (DVT) developing in up to 70% of the patients. PTS is diagnosed on the basis of typical symptoms and signs of the lower limb with a previous DVT, but no objective diagnostic test exists. A number of diagnostic scales have been developed primarily for research purposes. An optimal diagnostic test for PTS should be reliable and easy to use, sensitive and specific, able to grade PTS severity, and to identify changes over time. We have identified reports on seven diagnostic scales that have been used for the diagnosis of PTS; the Widmer classification, the Clinical-Etiological-Anatomical-Pathological (CEAP) classification, the Venous Clinical Severity Score (VCSS), the Brandjes scale, the Ginsberg measure, the Villalta scale, and the Patient-reported Villalta scale. The aim of this paper was to review and present the existing diagnostic scales for PTS in adults and their utility in clinical studies.

Late consequences of venous thromboembolism: Measuring quality of life after deep vein thrombosis and pulmonary embolism.

The identification of specific post-thrombotic complications as well as an increased appreciation of the importance of patient-reported outcome measures have triggered an interest in studying health-related quality of life (HRQoL) in patients with a history of venous thromboembolism (VTE). In order to enable a comprehensive assessment of HRQoL in clinical trials it is recommended that both generic and disease-specific questionnaires be used. SF-36 and EQ-5D are the most widely used generic questionnaires in VTE studies, whereas several disease-specific questionnaires have been developed to evaluate HRQoL following deep vein thrombosis (DVT) and in chronic venous disease (CVD). The most widely used of these is the VEINES-QOL/Sym, which was developed for CVD. VT-QOL and DVTQOL are both questionnaires developed to evaluate HRQoL after DVT, while PEmb-QoL is currently the only available disease-specific questionnaire developed specifically for pulmonary embolism (PE). Although studies show inconsistent results, patients who sustain DVT seem in general to report similar HRQoL compared to the general population. However, patients who develop PTS after DVT report poorer HRQoL using both generic and disease-specific questionnaires. HRQoL appears to be impaired in patients who sustain PE compared to the general population. In these patients, persistent dyspnea after PE has been shown to be a predictor of reduced HRQoL. Further work is needed to develop practical, patient-derived, valid, reliable and responsive disease-specific HRQoL instruments covering the specific aspects of these diseases.

Scoring Systems for Postthrombotic Syndrome.

Postthrombotic syndrome (PTS) is the most common long-term complication after deep vein thrombosis (DVT) and is associated with reduced quality of life. There is no single objective test to diagnose the presence of PTS and it is usually diagnosed on the basis of typical symptoms and signs in a limb previously affected by DVT. Scoring systems for PTS are primarily developed as research tools, but could possibly also be useful in the clinical setting. A main advantage of a good scoring system is standardization of the diagnostic process. An optimal scoring system should be both sensitive and specific for PTS, but this has been difficult to achieve because the symptoms and signs of PTS can be similar to other conditions leading to complaints in the lower limb. In an effort to standardize the definition of PTS, in 2009, the International Society on Thrombosis and Haemostasis Subcommittee on Control of Anticoagulation reviewed available scales and recommended use of the Villalta scale as the most appropriate measure to diagnose and grade the severity of PTS. The aim of this article is to review the existing scoring systems for PTS and to present our view on the advantages and disadvantages of these diagnostic tools.

Health-related quality of life after pulmonary embolism: a cross-sectional study.

OBJECTIVES: The psychological effects of acute pulmonary embolism (PE) have scarcely been studied. The aims of this study were to evaluate health-related quality of life (HRQoL) in patients with a history of PE compared with that of the general population and buddy controls, and to explore factors that may predict impaired HRQoL. DESIGN: Cross-sectional. SETTING: Haematology and thrombosis unit in Fredrikstad, Norway. PARTICIPANTS: 213 consecutive patients treated for PE were identified from hospital registries. Eligible patients were scheduled for a single study visit, including a functional capacity test (6 min walking test). HRQoL was assessed using the EuroQol 5D dimensions 3-level (EQ-5D-3L) questionnaire, of which the results were compared with Danish population norms and age-matched and sex-matched buddy controls. The buddy controls were recruited by asking every patient to hand over the EQ-5D questionnaire to 2 age-matched and sex-matched friends or relatives. Multivariable regression analyses were used to examine possible determinants of reduced HRQoL. RESULTS: Mean age was 61 years (SD 15), 117 (55%) were males, and median time since diagnosis was 3.8 years (range 0.3-9.5). Mean EuroQol visual analogue scale (EQ VAS) was 67 in PE as compared with 81 in the general population (p<0.005) and corresponding EQ-5D index values were 0.80 and 0.86 (p<0.005). Patients reported more problems in all 5 EQ-5D compared with both the buddy controls and the general population, p<0.05. Shorter 6 min walking distance (ß=0.09, p<0.005) and patient-reported dyspnoea (ß=11.27, p<0.005) were independent predictors of lower EQ VAS scores. CONCLUSIONS: Our findings show that patients with a history of PE have impaired HRQoL when compared with the general population and buddy controls. Reduced functional capacity and persistent dyspnoea were the main predictors of this impairment.

Health-related quality of life after deep vein thrombosis.

BACKGROUND: Health-related quality of life (HRQoL) is known to be impaired in patients who develop post-thrombotic syndrome (PTS) following deep vein thrombosis (DVT). However, there is limited knowledge of the long-term HRQoL after DVT compared to controls without DVT. The objectives of this study were to evaluate long-term HRQoL following DVT and to compare that with age and sex matched control group and to population norms as well as to investigate possible predictors for reduced HRQoL. METHODS: HRQoL was evaluated in 254 patients with confirmed DVT using the generic EQ-5D and the diseases specific VEINES-QOL/Sym questionnaire, whereas PTS was assessed by the Villalta scale. Patients were asked to give the EQ-5D questionnaire to two friends of same age- (±5 years) and sex (buddy controls). RESULTS: Patients scored significantly lower on all dimensions of EQ-5D compared to controls. EQ-5D index value was lower in patients compared with buddy controls; mean 0.79 (SD 0.17; IQR 0.72-1.00) versus 0.9 (SD 0.12; IQR 0.80-1.00), p < 0.001. EQ-5D index value was also significantly lower than age- and sex-adjusted population norms (p < 0.001). PTS and obesity (BMI >30/m(2)) were significantly associated with impaired HRQoL assessed by EQ-5D index value (odds ratio [OR] 11.0: 95 % confidence interval [CI] 4.6-29.7; and 2.3: 95 % CI 1.1-4.8, respectively) and VEINES-QOL (OR 28.2: 95 % CI 10.6-75.0; and OR 4.1: 95 % CI 1.7-9.7, respectively). CONCLUSION: Long-term HRQoL was significantly impaired in DVT patients compared with buddy controls and population norms. PTS and obesity were independently associated with impaired HRQoL.

The role of inflammation in post-thrombotic syndrome after pregnancy-related deep vein thrombosis: A population-based, cross-sectional study.

Previous studies suggest that inflammation may play a role in the pathophysiology of post-thrombotic syndrome (PTS). The aims of the present study were to evaluate markers of inflammation as possible predictors for PTS after pregnancy-related deep vein thrombosis (DVT). We included 182 women with a pregnancy-related DVT during 1990-2003 and 314 controls. All women answered a questionnaire and donated a blood sample in 2006. PTS was diagnosed when a self-reported Villalta score was above 4. The following predictors of PTS were included: high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-8, IL-10, monocyte chemotactic protein (MCP)-1, transforming growth factor (TGF)-ß1, platelet derived growth factor (PDGF)-BB, and the two adhesion molecules intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1. High values were defined as above median value among controls. We found that 41% of cases were diagnosed with PTS 3-16years after index pregnancy. In univariate analyses, high values of hsCRP, IL-6, and IL-10 were significantly associated with PTS with ORs 2.3 (95% CI; 1.2-4.2, p=0.008), 1.9 (1.0-3.5, p=0.04), and 10.8 (1.3-89.8, p=0.01), respectively. Only hsCRP, which has previously been found to be independently associated with PTS, was independently associated with PTS in a multivariate logistic regression model, when adjusting for proximal DVT occurring postpartum, age above 33years, and smoking (adjusted OR 2.4; 95% CI 1.2-4.8, p=0.01). We conclude that hsCRP was associated with PTS 3-16years after pregnancy-related DVT.