Unprovoked Deep Vein Thrombosis Research Articles

E030 Osteonecrosis of the spine in antiphospholipid antibody syndrome

Abstract Background/Aims Osteonecrosis (ON) is a well-known complication of several rheumatic diseases, affecting the hip, knee, shoulder, or ankle. The involvement of spine and other sites with ON has been reported with catastrophic APS, although the nature of this association is not completely clear. In antiphospholipid syndrome, thrombosis of blood vessels is considered a possible mechanism, along with other risk factors, such as active disease, thrombocytopenia, glucocorticoid use and associated autoimmune diseases, making the pathophysiology multifactorial. We report a case of a 66-year-old male with APS who developed bone infarcts/osteonecrosis after withdrawal of anticoagulation for APS, which was necessitated by a bleeding complication and introduction of steroids for immune thrombocytopenia. Methods A 66-year-old male came to us with history of unprovoked deep vein thrombosis (DVT) for which he was on antiplatelet and anticoagulation for over 20 years. He was diagnosed to have high titre anti cardiolipin antibody (ACA)(186 U/ml) without other autoimmune conditions. He had an episode of bladder hematoma in August 2022, needing his anticoagulation to be suspended temporarily. He was also found to have profound thrombocytopenia with raised inflammatory markers. Considering it to be immune mediated he was started on high dose oral corticosteroids and was later maintained with azathioprine while the oral prednisolone dose was gradually brought down to 10 mg daily in about 3 months’ time. His thrombocytopenia improved progressively however he developed an unprovoked DVT in October 2022 and was restarted on anticoagulation. He continued to have low dose steroids for about 6 months. Meanwhile, he started having a new onset of low back pain in December 2022. An MRI of the whole spine showed multilevel osteonecrosis with haemorrhagic cavities in a few vertebral bodies. Results This case highlights three interesting points. The first is the atypical presentation of the osteonecrosis involving vertebral bodies. Osteonecrotic lesions in the spine of a patient with catastrophic primary antiphospholipid syndrome has been reported. Our case signifies that although vertebral bodies are an uncommon site for avascular necrosis in patients with APS, it is not rare. Secondly, the pathogenesis of ON is complex. Whether ACA are directly responsible for this condition or whether they are the bystanders remains controversial. ACA have shown to be an independent risk factor for developing ON in many studies. Thirdly, steroids are known to be an important risk factor in patients presenting with osteonecrosis. The vascular compromise could be attributed to a steroid induced hypercoagulative state, abnormal lipid metabolism, or fat embolism. Conclusion ON in APS is unusual and its underlying pathophysiology remains multifactorial. However, when complicated by the high ACA levels, active disease, difficult anticoagulation (bleeding tendencies), thrombocytopenia or prolonged use of steroids, it can lead to hypercoagulable state causing micro thrombosis and avascularisation. Disclosure M. Shah: None. K. Putchakayala: None.

Management of Recurrent Venous Thromboembolism in Severe Immune Thrombocytopenia: A Case Report and a Review of the Literature.

We report a case of a 58-year-old man with recurrent unprovoked deep vein thrombosis (DVT) and severe immune thrombocytopenia (ITP) with a platelet count of 19 × 109/L. We further review studies reporting venous thromboembolism (VTE) in patients with severe ITP (≤ 35 × 109/L) and identified 14 patients highlighting VTE risk factors and management of these patients. The present case had several risk factors for VTE (previous DVT, obesity, heterozygosity for factor V Leiden mutation, and previous splenectomy). The patient was initially treated with low-molecular-weight heparin followed by long-term apixaban treatment. The literature review together with our case demonstrates that VTE in severe ITP (≤ 35 × 109/L) can occur in patients with VTE risk factors and antithrombotic management of these patients can be achieved without bleeding depending on severity of thrombocytopenia either by full or reduced dose of anticoagulation together with ITP therapy.

“What IVC?”: Deep Vein Thrombosis in the Context of IVC Dysgenesis

Among young, otherwise healthy adults with unprovoked deep vein thrombosis (DVT), uncommon causes like variation in the normal sequential development of the inferior vena cava (IVC), must be explored. Anomalous IVC conditions are estimated to occur in up to 9% of the general population, with the rarest anomaly being IVC agenesis at 0.0005% - 1% general population prevalence. DVTs are more likely to develop in this population due to venous stasis from decreased venous return, even with the formation of extensive collateral veins. Herein, the authorial team presents a 22-year-old patient with leg pain and swelling who was found to have acute DVT, and, incidentally, the absence of the suprarenal IVC with a robust collateral system on further imaging studies. The morbidity of DVTs in this population is very high, and attention should be given to young patients who present with new-onset DVT in the setting of normal coagulation studies and lack of personal or family history of clotting disorders, as the need for specialized imaging such as venograms is necessary to secure the proper diagnosis.

The risk for post-thrombotic syndrome of subjects with deep vein thrombosis in an Indonesian referral hospital: a retrospective cohort study

BackgroundPost-thrombotic syndrome (PTS) is a complication of deep vein thrombosis (DVT) and affects 20–40% of DVT subjects. The risk factor of PTS after DVT is difficult to determine. We aimed to evaluate the incidence of PTS after 3 months of DVT diagnosis and to determine the risk of PTS.MethodsA retrospective cohort study of subjects who developed DVT confirmed by Doppler ultrasound in Cipto Mangunkusumo Hospital from April 2014 until June 2015. The presence of PTS was assessed after 3 months of completed DVT treatment using the Villalta score. Risk factors for PTS were evaluated from medical records.ResultsThere were 91 subjects with DVT with mean age of 58 years. 56% were female. It was dominated by subjects aged ≥ 60 years (45.1%). Hypertension (30.8%) and diabetes mellitus (26.4%) were the major comorbidities in this study. Deep vein thrombosis occurred commonly in unilateral side (79.1%), proximal localization (87.9%), and unprovoked DVT (47.3%). The cumulative incidence of PTS after DVT was 53.8%, 69% of subjects had mild PTS. Heaviness of the leg (63.2%) and edema (77.5%) were the most common symptoms.ResultsThere were 91 subjects with DVT with mean age of 58 years. 56% were female. It was dominated by subjects aged ≥ 60 years (45.1%). Hypertension (30.8%) and diabetes mellitus (26.4%) were the major comorbidities in this study. Deep vein thrombosis occurred commonly in unilateral side (79.1%), proximal localization (87.9%), and unprovoked DVT (47.3%). The cumulative incidence of PTS after DVT was 53.8%, 69% of subjects had mild PTS. Heaviness of the leg (63.2%) and edema (77.5%) were the most common symptoms. Significant risk factors for PTS were unprovoked DVT (adjusted RR 1.67; 95%CI: 1.17–2.04; p = 0.01) and female gender (adjusted RR 1.55; 95%CI: 1.03–1.94; p = 0.04). Age, body mass index, thrombus location, immobilization, malignancy and surgery was not associated with PTS.ConclusionWe conclude that 53.8% of subjects suffered PTS after 3 months of DVT. Unprovoked DVT and female gender were significant risk factors for PTS.

Influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene in acute unprovoked deep vein thrombosis and residual vein thrombosis

BackgroundPlasminogen activator inhibitor-1 (PAI-1) is an important inhibitor of plasminogen activator, but the role of the PAI-1 4G/5G polymorphism in deep vein thrombosis (DVT) has been contradictory. In this study, we investigated the distribution of the PAI-1 4G/5G genotype in Chinese patients with DVT compared with healthy controls and the association between the PAI-1 4G/5G genotype and the persistence of residual venous occlusion (RVO) after different treatments. MethodsThe PAI-1 4G/5G genotype was determined by fluorescence in situ hybridization in 108 patients with unprovoked DVT and 108 healthy controls. The patients with DVT were treated with catheter-based therapy or anticoagulation only. RVO was assessed by duplex sonography during the follow-up. ResultsThirty-two patients (29.6%) were homozygous for 4G (4G/4G), 62 patients (57.4%) were heterozygous for 4G/5G, and 14 patients (13%) were homozygous for 5G (5G/5G). No significant difference in genotype frequency was found between patients with DVT and controls. A total of 86 patients completed follow-up of ultrasound examination with a mean follow-up of 13.4 ±7.2 months. The results of patients with RVO were significantly different between homozygous 4G carriers (76.9%), heterozygous 4G/5G (58.3%), and homozygous carriers of 5G (33.3%) (P <.05) at the end of follow-up. Catheter-based therapy showed a better result in patients who were noncarriers of 4G (P = .045). ConclusionsThe PAI-1 4G/5G genotype was not a relevant predictor for DVT in Chinese patients, but is a risk factor for persistent RVO after idiopathic DVT.

Iron Deficiency Anemia as a Potential Risk Factor for Unprovoked DVT in Young Patients: A Case Series.

Deep vein thrombosis (DVT) is a serious and potentially life-threatening condition due to the occurrence of pulmonary embolism (PEs) in the acute phase. DVT can be provoked or unprovoked. Provoked DVT can be associated with transient or persistent causes. Iron deficiency anemia (IDA) with reactive thrombocytosis can act as a prothrombotic condition. We present two case reports of lower limb DVT which was associated with moderate anemia. Association between IDA and thrombosis has been reviewed.

A CASE OF MALE SLE: AN UNUSUAL PRESENTATION

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune diseasein which tissue-binding auto-antibodies and immune complex depositioncause damage to multiple organs and systems.We report a rare case of SLE in a 31-year-old male patient. He has a past history of unprovoked deep vein thrombosis of right lower limb for 8 years, treated with anticoagulant therapy but not evaluated further. The patient went on to develop recurrent symptoms of fever, rashes and joint pains which were also overlooked. ANA profile and APLA antibodies were positive and the patient was diagnosed with SLE after 8 years since onset of symptoms. He now exhibits renal manifestations in the form of anasarca and proteinuria and CNS manifestations in the form of seizures. We attribute the severity of his current condition to the delayed diagnosis.

Direct Oral Anticoagulants for Inferior Vena Cava Agenesis.

Deep vein thrombosis (DVT) is common in the general population, with an annual incidence of 1 to 2 per 1000 people. Inferior vena cava agenesis (IVCA) increased the risk of developing DVT and is found in approximately 5% of young adults (20-40-year-olds) diagnosed with unprovoked proximal DVT. IVCA can be caused by a defective embryological process, or be a result of intrauterine or perinatal thrombosis. Its estimated incidence in the general population ranges from 0.0005% to 1%, usually involving a partial absence of one of the four segments of the inferior vena cava (IVC). The management during the extended phase of patients with DVT associated with IVCA is not yet harmonized, as it is poorly described in the literature. Patients with IVCA are considered to be at high risk of DVT occurrence, prompting physicians to continue extended anticoagulation, often using vitamin K antagonists. In this retrospective study, we present a cohort of 11 patients diagnosed with IVCA following a DVT, who subsequently received extended treatment with a direct oral anticoagulants. These findings offer reassuring insights into the extended utilization of direct oral anticoagulants, demonstrating both antithrombotic efficacy and a favorable safety profile.

Predictive Value for Increased Red Blood Cell Distribution Width in Unprovoked Acute Venous Thromboembolism at the Emergency Department.

Acute venous thromboembolism (VTE) is a common worldwide disease admitted to emergency departments (ED), usually presenting as pulmonary embolism or lower limb deep vein thrombosis (DVT). Due to the lack of typical clinical and biomarker diagnostic features of unprovoked VTE, early identification is challenging and has direct consequences on correct treatment delay. Longitudinal, prospective, observational study. Patients admitted to ED with a suspicion of unprovoked acute VTE between October 2020 and January 2021 were included. Clinical and laboratorial variables were compared between VTE positive and negative diagnoses. Red cell distribution width (RDW) cut point was determinate through a receiver operating characteristic analysis. RDW accuracy, sensitivity, and specificity were calculated. Fifty-eight patients were analyzed. And 82.8% of suspected patients with VTE were diagnosed with an acute thrombotic event confirmed by imaging examination. In patients with VTE, RDW at admission in ED was higher than with other diagnosis, respectively, 14.3% (13.2-15.1) and 13.5% (13.0-13.8). Platelet count was the only additional characteristic that revealed difference between the 2 groups (264×109/L for VTE and 209×109/L for non-VTE). Logistic regression models showed good discriminatory values for RDW≥14%, with an area under the curve (AUC) = 0.685 (95% confidence interval, 0.535-0.834). These findings were more pronounced in isolated DVT, with a sensitivity of 76.9%, specificity 100%, and accuracy 85.7%. Our study demonstrated a significant association between an early high RDW and the diagnosis of acute unprovoked DVT. RDW ≥ 14% has an independent predictor of unprovoked VTE in adult patients.

221 NONBACTERIAL THROMBOTIC ENDOCARDITIS WITH ATYPICAL PRESENTATION AS OVERT CONGESTIVE HEART FAILURE

Abstract Introduction Non-Bacterial Thrombotic Endocarditis (NBTE) is a form of endocarditis associated with malignancy or autoimmune disorders. Diagnosis remains a challenge as patients are often asymptomatic up to embolic events or, rarely, valve dysfunction. We report a case of NBTE with uncommon clinical presentation and identified with multimodal echocardiography. Case presentation An 82-year-old man presented to our outpatient clinic reporting dyspnea. Past medical history included hypertension, diabetes, kidney disease, and unprovoked deep vein thrombosis. On physical examination, he was apyretic, mildly hypotensive and hypoxemic, had a systolic murmur and lower limbs edema. Transthoracic echocardiography revealed severe mitral regurgitation due to verrucous thickening of the free margin of both leaflets, increased pulmonary pressure, and dilated inferior vena cava. Multiple blood cultures were negative. Transesophageal echocardiography confirmed “thrombotic” thickening of mitral leaflets. Nuclear investigations were highly suggestive of multi-metastatic pulmonary cancer. We did not further proceed in the diagnostic workup and prescribed palliative care. Discussion Lesions seen on echocardiography were suggestive of NBTE: they involved both sides of mitral leaflets, close to the edges, had irregular shape and echo-density, a broad base, and no independent motion. Criteria for infective endocarditis were not met and the final diagnosis was paraneoplastic NBTE due to underlying lung cancer. We remark the lack of definitive recommendations about treatment of NBTE and the only role of anticoagulation to prevent systemic embolism. Conclusions We report a case of NBTE presenting with atypical symptoms and likely related to the prothrombotic state induced by underlying lung cancer. Provided the unconclusive microbiological tests, multimodal imaging played a crucial role for the final diagnosis.

Resting Hypoxia and a Strongly Positive Bubble Test: Do Not Forget Hepato-Pulmonary Syndrome.

A 40-year-old male presented to the hospital with a tender right calf, right-sided pleuritic chest pain, and haemoptysis. He has a strong family history of anti-thrombin-3 deficiency and unprovoked deep-vein thrombosis in many of his paternal family members. Computed tomography (CT) pulmonary angiography demonstrated a segmental pulmonary embolism (PE) and associated pulmonary haemorrhage/infarct in the right middle lobe (Panel-A). X-ray chest demonstrated mild pulmonary congestion (Panel-B). Resting oxygen saturation on room air (RA) was 81%; disproportionately low for his presentation with PE, however, the patient did not complain of dyspnoea.

Hand grip strength and risk of incident venous thromboembolism: The Tromsø study

BackgroundHand grip strength (HGS), a common proxy of whole‐body muscular strength, is associated with a wide range of adverse health outcomes and mortality. However, there are limited data on the association between HGS and risk of venous thromboembolism (VTE). ObjectivesWe aimed to investigate the association between HGS and risk of incident VTE in a population‐based cohort. MethodsParticipants (n = 13,704) from the fourth to seventh surveys of the Tromsø study (Tromsø4–Tromsø7, enrollment: 1994–2016) were followed throughout 2020, and all incident VTEs were recorded. HGS of the nondominant hand was measured using a Martin Vigorimeter (Tromsø4–Tromsø6) and a Jamar Digital Dynamometer (Tromsø7). Hazard ratios (HRs) for VTE with 95% confidence intervals (CIs) according to weak HGS (less than 25th percentile) versus normal HGS (25th percentile or greater) were estimated using Cox regression models and adjusted for age, sex, body height, body mass index, physical activity, cardiovascular disease, and cancer. ResultsDuring a median of 6.5 years of follow‐up, 545 incident VTEs occurred. Participants with weak HGS had a 27% higher risk of VTE (HR, 1.27; 95% CI, 1.03–1.57) compared to those with normal HGS. Subgroup analyses revealed that the point estimates were higher for unprovoked VTE (HR, 1.35; 95% CI, 0.96–1.91) and deep vein thrombosis (DVT; HR, 1.52; 95% CI, 1.14–2.01). Similar results were found in analyses restricted to men, women, and elderly (aged greater than 75 years). ConclusionA weak HGS was associated with increased risk of VTE, and particularly unprovoked VTE and isolated DVT. Our findings suggest that weak muscle strength may be a risk factor for VTE.

Duration of Anticoagulation Therapy in Patients with Genetic Inherited Thrombophilia.

Background: Genetic factors play an important role in deep vein thrombosis (DVT). The duration of anticoagulation therapy in patients with verified genetic inheritance and previous events of DVT is still questionable. Case reports: We present three cases of siblings (two brothers and one sister) with verified Venous thromboembolism (VTE) and genetic inheritance. The first case is a 33 y.o. male who was admitted with bilateral massive pulmonary thromboembolism and DVT of the right femoral vein. He had an episode of DVT 4 years ago. Fibrinolytic therapy was introduced immediately. Afterwards, unfractionated heparin was introduced, and then switched to enoxaparin and acenocoumarol. Because of inappropriate INR, it was switched then to rivaroxaban. The imaging methods showed significant improvement, and the patient was discharged from the hospital with rivaroxaban at 2x15 mg/day for another 2 weeks and was instructed to continue 20 mg/day until his next control. In the meantime, the second case, a 36 y.o. male, brother to the first patient, came with vein thrombosis of vena saphena magna of the left leg. Treatment with Acenocoumarol was started and continued for 2 years until complete resolution of the thrombi, and then it was changed to Aspirin. The third case is the sister of the first 2 cases, a 38 y.o female with symptoms and findings almost similar to those in the second case. She was treated with Acenocoumarol for 6 months. Doppler ultrasound showed complete resolution of the thrombosis and anticoagulation therapy was stopped. Genetic investigations for mutation showed presence of homozygous gene mutation for Prothrombin (PTB G20210A) in the first patient, his brother (the second case) was compound heterozygote for PTB and for MTHFR C677T, and his sister (third case) was heterozygous only for the PTB mutation. According to the clinical (recurrent unprovoked DVT with thromboembolic complications) and genetic testing (homozygous gene mutation for PTB) in the first patient, we decided to continue the secondary thromboprophylaxis with rivaroxaban 10 mg/day indefinitely. Conclusion: Testing for genetically inherited thrombophilia should be included in the risk assessment for recurrence, and performed in all patients under 50 y.o. who have a first, non-provoked episode of thrombosis, in order to determine the duration of anticoagulation therapy.

Utility of hereditary thrombophilia testing among patients with lower extremity deep vein thrombosis

ObjectiveDespite a growing consensus that testing for hereditary thrombophilia (HT) is not recommended in the setting of venous thromboembolism (VTE), such testing is still often requested. We evaluated the effects of HT on the risk of recurrent VTE for patients with lower extremity deep vein thrombosis (DVT). MethodsWe conducted a multihospital retrospective study of 867 patients with first-time proximal lower extremity DVT who had undergone testing for HT. Patients with and without HT were compared regarding their VTE recurrence risk via Kaplan-Meier and multivariable analysis. ResultsHT was present in 166 patients (19%). The baseline characteristics were similar between the patients with HT and without HT. No significant difference was found in the recurrence rates between the two groups (HT, 17%; no HT, 15%; P = .345). A Kaplan-Meier survival analysis revealed no significant differences in VTE-free survival between the patients with and without HT (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.77-1.84; P = .421). On multivariable analysis, the presence of HT was not associated with recurrent VTE. A higher body mass index (HR, 1.06; 95% CI, 1.03-1.10; P = .004) and unprovoked DVT (HR, 2.48; 95% CI, 1.69-3.66; P < .001) were risk factors for recurrence. ConclusionsHT had no significant impact on the recurrence risk for patients with first-time lower extremity DVT. HT test results would, thus, not be expected to change clinical management and should therefore not be requested routinely for patients with DVT.

Assessment of fibrinolytic markers in patients with deep vein thrombosis

The association of the fibrinolytic markers with deep vein thrombosis (DVT) is still a matter of debate. The present study aimed to investigate the association between fibrinolytic markers and DVT. This observational study recruited 52 adult cases with lower limb DVT and 52 healthy adult volunteers as controls. The quantitative determination of plasminogen activator inhibitor-1 (PAI-1), plasminogen, thrombin activable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA) and α2-antiplasmin (α2-AP) was performed by ELISA. TAFI, plasminogen and t-PA were significantly higher in cases than controls and PAI-1 was significantly lower in cases than controls. In addition, TAFI, plasminogen and t-PA levels were significantly increased in unprovoked and idiopathic DVT cases than controls. The present study suggests that the fibrinolytic markers tested in patients with a remote history of DVT are different than in individuals with no history of DVT and, with further study, may prove useful as screening assays for DVT risk.

325 Dealing with cardiac amyloidosis diagnosis: keep calm and use the magnifying glasses!

Abstract Methods and results Case report— male, 71 years old. Past medical history—arterial hypertension, dyslipidemia, tobacco abuse. COPD on nocturnal CPAP therapy. Rheumatic polymyalgia on steroid therapy. Previous unprovoked deep vein thrombosis on anticoagulation with rivaroxaban. Bilateral carpal tunnel surgeries 8 years ago. Spontaneous left biceps tendon rupture 4 year ago. IgA kappa monoclonal gammopathy of undetermined significance (MGUS). Mild interventricular septum (IVS) hypertrophy on echocardiography since 2018. In 2019 IVS was 18 mm with granular sparkling appearance. In February 2020 he was hospitalized for initial heart failure and COPD exacerbation. In 2021 he developed worsening dyspnoea. He underwent cardiological evaluation in a spoke hospital and a cardiac magnetic resonance (CMR) suggested infiltrative cardiomyopathy. Bone scintigraphy showed moderate cardiac uptake (Perugini Score 2). Following haematological evaluation, fat pad biopsy was performed, and amyloid was detected on Congo red staining. Classification of the amyloid fibril protein was not performed. Bone marrow biopsy, even though of suboptimal quality, was negative for amyloid and for plasma cellular infiltration. Bone marrow aspirate showed 11% of plasma cells and multiple myeloma was therefore hypothesized. Recent medical history—he was evaluated in our Cardiac Amyloid Outpatient Clinic in May 2021. He was symptomatic for dyspnoea (NYHA class III) and exercise intolerance, diffuse osteo-muscolar pain, and extremities paresthesia. His blood pressure was on the low side of normality with necessity of anti-hypertensive therapy downgrading. Signs and symptoms of hematological disease were not present. We required to analyse the fat pad specimen in order to perform amyloid fibril protein typing; with immunoelectron microscopy, transthyretin (TTR) was identified as the amyloid fibrils precursor (no light chains could be identified). We considered performing endomyocardial biopsy to exclude the coexistence of ATTR amyloidosis and light chains (AL) amyloidosis in the heart but, given the history, clinical picture, and fat pad biopsy results, we felt that cardiac ATTR was the most probable diagnosis and we decided to proceed with a close cardiological and haematological follow-up. TTR genetic testing is ongoing. Conclusions ATTR cardiac amyloidosis is an emerging cause of heart failure, especially with preserved ejection fraction, in the older population. However, these patients frequently present with dysproteinemias and bone marrow abnormalities, up to multiple myeloma, raising the issue of differential diagnosis between ATTR and AL amyloidosis. According to the latest European Consensus Document, in the presence of cardiac uptake at bone scintigraphy (Grades 1–3) and positive haematologic tests, histological confirmation (usually cardiac) is necessary to subtype amyloid infiltration. In our case, the patient had positive Congo Red-stained fat pad biopsy, but the typing of the amyloid deposition was not performed. After referral to a Center with a Cardiac Amyloid Outpatient Clinic with a specialized Pathology Unit, we could further proceed with diagnostic workup and identify the amyloid deposition as ATTR; of note, fat pad biopsy is positive in just 15–25% of ATTR amyloidosis. Moreover, close collaboration with Hematology was necessary to assess the risk of AL amyloidosis and to provide a close and targeted follow-up. Endomyocardial biopsy was not performed after consideration of the various elements suggestive for ATTR cardiac amyloidosis, but the patient will be evaluated periodically and closely to potentially reassess this decision.

Identification of Patients with Unprovoked Venous Thromboembolism and a Low Risk of Recurrence Estimated By the Vienna Prediction Model: A Prospective Cohort Management Study

▪Introduction:Patients with unprovoked venous thromboembolism (VTE) have a high recurrence risk, and, according to guidelines, should receive extended oral anticoagulation (OAC). OAC prevents recurrence in most patients but may cause major bleeding. Patients with a low recurrence risk could therefore benefit from limited OAC duration. The Vienna prediction model (VPM) estimates the recurrence risk of patients with a first unprovoked deep vein thrombosis (DVT) of the leg and/or pulmonary embolism (PE) based on the patient's sex, site of index VTE and D-Dimer measured after stopping OAC (Eichinger et al., Circulation 2010). In a prospective cohort management study, we evaluated whether the VPM can identify patients with an unprovoked VTE at low recurrence risk.Methods: The study was performed between January 2013 and May 2021 at two tertiary Austrian hospitals. Patients >18 years with a first symptomatic DVT of the leg and/or symptomatic PE were eligible. The diagnosis of VTE was established by compression ultrasonography (CUS), spiral computed tomography, or lung scanning. We excluded patients with previous VTE, VTE provoked by a temporary risk factor including surgery, trauma, pregnancy, immobilisation, or female hormone intake, with cancer, OAC duration longer than 7 months or OAC for reasons other than VTE. OAC was discontinued 3 to 7 months after VTE diagnosis. D-Dimer was measured by a quantitative assay 3 weeks later and the probability of recurrence was estimated by the VPM. In patients with <180 risk points (corresponding to a predicted one-year recurrence risk of <4.4%), OAC was not resumed. CUS of both legs was performed at the time of discontinuation of OAC for reference baseline imaging in case of suspected recurrence. Patients were seen after 3, 12 and 24 months or at recurrence. Patients with a high recurrence risk (>180 VPM risk points) were excluded and their management was left to the discretion of their local practitioner. The main outcome measure was independently adjudicated recurrence of symptomatic DVT of the leg and/or symptomatic PE.The study was approved by the local ethics committees and all patients gave written informed consent.Statistical analysis:Baseline characteristics of patients were described by median and interquartile range (IQR) or by absolute frequency and percentage. The cumulative risk of recurrent VTE after discontinuation of OAC was estimated using the Kaplan-Meier method. Recurrence risk was also predicted with the VPM for each patient, and predictions were averaged over the study group.Results:Of 818 eligible patients, 520 (65%) had a risk score of <180 points and were classified as being at low risk of recurrence. They were included in the study and did not resume OAC. Their median age was 52 (42-65) years, and 289 (56%) were men. 226 (43%) patients had PE, 206 (40%) proximal and 88 (17%) distal DVT as index VTE. Median duration of anticoagulation was 3.9 (3.3-5.7) months, and the median time of follow-up was 23.9 (23.8, 23.9) months. Ten (1.9%) patients were lost to follow-up.52 patients (of which 30 were male) had non-fatal recurrent VTE (5.8 events per 100 patient-years, 95% CI 4.4-7.7). 28 (54%) patients had PE, 17 (33%) proximal and 7 (13%) distal DVT at recurrence.The cumulative risk of recurrence at one and two years was 5.2% (95% CI 3.2-7.2) and 11.2% (95% CI 8.3-14), respectively (Figure 1). The corresponding predicted recurrence risk for the study group was 4% and 7%, respectively.Conclusion: The VPM identifies patients with unprovoked VTE at low risk of recurrence. Applying the VPM refines risk stratification which could facilitate treatment decisions on the duration of OAC for patients and physicians. The model was well calibrated at one year. The apparent underestimation of the recurrence risk at two years could be countered by recalibration. [Display omitted] DisclosuresEichinger: Takeda: Speakers Bureau; Daiichi-Sankyo: Speakers Bureau; BMS: Speakers Bureau; Bayer: Speakers Bureau; Pfizer: Speakers Bureau; Boehringer-Ingelheim: Speakers Bureau; CSL Behring: Speakers Bureau.

Role of Vitamin D Levels in Venous Thrombosis

Venous thromboembolism (VTE) is a complex condition that impacts over 900,000 people in theUnited States annually. It is estimated that about 100,000 people in the US die from deep veinthrombosis (DVT) or pulmonary embolism (PE) annually. Several biomarkers, includingVitamin D most recently, have been investigated and linked to the risk of developing VTE orrecurrent VTE. Vitamin D is known to control the expression of over 200 genes and it has shownto have anti-thrombotic effects through various mechanisms. There is emerging data regardingits role in the coagulation pathway, platelet activation, inflammatory pathways and endothelialactivation (1). There have been a few international studies linking Vitamin D deficiency toVTE(2). However; no such study has been replicated in the North American population where the prevalence of Vitamin D deficiency is 40%. The focus of this study will be to determine theprevalence of Vitamin D deficiency in patients with VTE. Based on the role of Vitamin D in thepathway for thrombogenesis and antithrombin effects, there is likely a correlation between VTEand Vitamin D levels.This is a retrospective chart review of all patients admitted to Franciscan Health- Olympia Fieldswith VTE between July 2018 and June2020. A total of 181 patients with VTE were reviewed.Data such as age, gender, race, D-dimer, and Vitamin D levels were collected. Vitamin D levels<30ng/mL was defined as deficient. In addition, further data collection, included provoked vsunprovoked VTE, presence of malignancy, and the severity of DVT and PE based on locationand extent of the VTE (severity was scored on a scale of 1-3 with 1 being mild and 3 as severe).A regression analysis was done to find a correlation between several variables and T-test wasused to determine P-value.Of the 181 patients, 110 had a vitamin D level documented at the time of their VTE and datawas specifically analyzed for this subgroup. There were 46 males and 64 females, 53.6%AA,7.3% Hispanic, 38.2% Caucasian, and 0.9% unknown. 25.5% had an unprovoked VTE eventand 74.5% had a provoked event. 39 patients had a known active malignancy and a likelycancer associated thrombosis. 85.7% of patients with unprovoked DVT had a low Vitamin Dlevel. In patients with cancer associated thrombosis there was no significant correlation withvitamin D levels. A strong correlation was noted between vitamin D levels and the severity of PE(p value=0.036).This retrospective chart review from a patient population at a community hospital indicates thatthere is some correlation between venous thromboembolism and Vitamin D levels. Specifically,it appears that patients with an unprovoked VTE have low Vitamin D levels suggesting thatvitamin D deficiency may be a risk factor for VTE development as indicated by previousinternational studies (2). In addition, it appears that there is an inverse relationship between theseverity of PE and vitamin D levels. Perhaps Vitamin D may be used as a biomarker for VTErisk assessment and management. Large scale studies are needed in the future to determinethe exact relationship between VTE and Vitamin D and further studies are needed to test therole of vitamin D supplementation and risk of recurrent VTE. DisclosuresNo relevant conflicts of interest to declare.

CATAMENIAL CONUNDRUM: A CASE OF PULMONARY EMBOLISM IN A PATIENT WITH CATAMENIAL PNEUMOTHORAX

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Endometriosis is a common condition affecting about 10% of reproductive-age women, in which ectopic endometrial tissue is found outside of the uterine cavity [1]. While it most commonly affects the pelvis, rarely endometrial tissue can also be found in the chest, often presenting as catamenial pneumothorax [2]. There have also recently been reports of systemic effects of endometriosis such as supporting a pro-inflammatory and prothrombotic state, increasing the risk for deep vein thrombosis (DVT) and pulmonary embolism (PE) [3]. CASE PRESENTATION: A 32 year old woman with endometriosis presented to the hospital with several weeks of pleuritic chest pain, nausea, vomiting, and inability to tolerate oral intake. Several months prior, she was diagnosed with thoracic endometriosis after a hospitalization for chest pain and discovery of bilateral pneumothoraces and pleural effusions, necessitating bilateral chest tube placement. Her consequent outpatient course was complicated by an unprovoked DVT, for which she was started on apixaban. She was admitted to the hospital the next month for worsening dyspnea and underwent computed tomography angiography of the chest and was found to have a left lower lobe subsegmental pulmonary embolism and loculated bilateral pneumothoraces, leading to video-assisted thoracoscopic surgery with decortication, pleural biopsy, and chemical pleurodesis for catamenial pneumothorax, with improvement in symptoms (Image 1). Anticoagulation (AC) was switched from oral apixaban to enoxaparin injections 1.5mg/kg daily, with a plan for clinic follow up for further AC management. DISCUSSION: Extrathoracic involvement is a rare and challenging presentation of endometriosis, often necessitating invasive interventions, and associated with recurrence rates of up to 14% (4). Our patient presented the challenge of requiring AC for her PE while managing bleeding risk in the setting of endometriosis, all while being unable to tolerate oral medications due to nausea and vomiting associated with endometriosis. In such patients, injectable, quickly reversible options for AC such as enoxaparin should be considered. CONCLUSIONS: There have been several studies suggesting that endometriosis supports a prothrombotic state, making it imperative to remember this dual challenge when treating endometriosis patients, and to have a low threshold for suspecting PE in any patient with persistent chest discomfort even after treatment of catamenial pneumothorax. Management should be individualized, with attention to the effect of related systemic complications such as nausea and vomiting precluding oral medication success to prevent potentially devastating consequences. REFERENCE #1: Shafrir AL, Farland LV, Shah DK, et al. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol. 2018;51:1-15. REFERENCE #2: Mecha E, Makunja R, Maoga JB, et al. The Importance of Stromal Endometriosis in Thoracic Endometriosis. Cells. 2021;10(1):180. Published 2021 Jan 18. REFERENCE #3: Ding D, Liu X, Guo SW. Further Evidence for Hypercoagulability in Women With Ovarian Endometriomas. Reprod Sci. 2018;25(11):1540-1548. DISCLOSURES: No relevant relationships by Teressa Ju, source=Web Response No relevant relationships by Gina Villani, source=Web Response No relevant relationships by Angelina Voronina, source=Web Response

Expert Perspective: Management of Microvascular and Catastrophic Antiphospholipid Syndrome.

A 50-year-old male with antiphospholipid syndrome (APS) presents to your office for the first time with a three-month history of worsening dyspnea, dry cough, and early morning blood-tinged sputum. His APS diagnosis was based on an unprovoked left lower extremity deep vein thrombosis, four years prior to the presentation, with persistent (multiple occasions) triple antiphospholipid antibody (aPL)-positivity, defined as lupus anticoagulant (LA) test positive performed while off anticoagulation, high titer [≥80 U] IgG anticardiolipin antibodies (aCL), and high titer IgG anti-β2 -glycoprotein-I (aβ2 GPI). He has no other past medical history; and he is on warfarin with a target international normalized ratio (INR) of 2.5 to 3.