Episode Of Deep Vein Thrombosis Research Articles

O-13 Parathyroid carcinoma - a rare and challenging entity

Abstract Background Parathyroid carcinoma is a rare malignancy, accounting for less than 1% of all cases of primary hyperparathyroidism (HPT). This entity affects both men and women equally and is usually diagnosed in the fourth or fifth decade of life. It can occur sporadically or be associated with genetic syndromes such as hyperparathyroidism-jaw tumor syndrome. Its clinical presentation can overlap with that of primary HPT, with hypercalcemia that can lead to a range of symptoms, such as fatigue, weakness, bone pain, kidney stones, and gastrointestinal disorders. Distinguished by its rarity and clinical challenges, this condition requires a high level of suspicion and its initial surgical approach correlates with long-term prognosis. Clinical Case This is the case of a male patient, 39 years old, Caucasian, with a previous history of hypertension diagnosed 5 months earlier, deep vein thrombosis (DVT) diagnosed 2 months earlier, and active tobacco use. Additional study performed after the DVT episode found severe hypercalcemia (14.3 mg/dL, N 8.6-10.0), hypophosphatemia (2.2 mg/dL, N 2.5-4.5), and renal dysfunction (Creatinine 1.43 mg/dL). The patient was asymptomatic and was admitted to the Internal Medicine department, to correct the hypercalcemia and further investigation. Increased PTH levels (1555 pg/mL, N 15-65) were found, and a cervical ultrasound revealed, on the left thyroid lobe, a bilobed nodule, mainly solid, hypoechogenic, with irregular margins and macrocalcifications, with 34×22 mm. Full body CT showed osteolytic lesions on several ribs and both iliacs and kidney stones. A bone scintigraphy was also done, showing a diffuse fixation on the axial and appendicular skeleton, compatible with diffuse osteomedullary infiltration. Due to these findings, the collaboration of the Endocrinology department was requested. Based on the PTH levels and the characteristics of the cervical mass, suspicion arose regarding a potential case of parathyroid carcinoma. Subsequently, a parathyroid scintigraphy using Sestamibi was conducted, whose report revealed an intense hyperfixation at a nodular formation projecting on the lower two-thirds of the thyroid left lobe, without unequivocal identification of its origin - thyroid nodule vs. parathyroid tissue. Based on intraoperative findings and clinical suspicion, en bloc resection of the tumor along with the thyroid lobe and unilateral neck exploration was performed by the Surgery department, with the pathological assessment confirming the malignancy diagnosis. The patient was referred to an oncologic tertiary center, for follow-up and genetic testing. Conclusion We want to shed light on this rare entity and the importance of multidisciplinary critical thinking, alongside imaging. Markedly elevated PTH and/or calcium levels on a patient with a cervical mass should arouse suspicion of a parathyroid carcinoma, which must not be biopsied and warrants a more extensive surgery to ensure the best possible prognosis.

Protein C Deficiency with Recurrent Deep Vein Thrombosis Complicated with Post Thrombotic Syndrome- A Case Report and Mini Review

Protein C is a vitamin K dependent glycoprotein produced by the liver. Protein C acts as a naturally occurring anticoagulant and its deficiency, predisposes the individual to a state of thrombosis, particularly venous thromboembolism. Post-thrombotic syndrome (PTS) is a chronic venous insufficiency manifestation following an episode of deep-vein thrombosis (DVT). We presented a case of 56 year old Malay man who was diagnosed with Protein C deficiency and presented with recurrent DVT complicated with PTS.

Persistently High Levels of Coagulation Factor XI as a Risk Factor for Venous Thrombosis.

Coagulation factor XI (FXI) promotes fibrin formation and inhibits fibrinolysis. Elevated plasma FXI levels, limited to a single measurement, are associated with a higher thrombotic risk. Our case-control study aimed to identify the effect of persistently increased plasma FXI levels on the risk of deep vein thrombosis (DVT). All patients evaluated between January 2016 and January 2018 for a first episode of proximal DVT of the lower extremity were considered for enrolment. Plasma FXI levels were measured at least 1 month after the discontinuation of anticoagulant treatment (T1). The patients with increased plasma FXI levels (>90th percentile of controls) were tested again 3 months later (T2). Among the 200 enrolled patients (M/F 114/86, age range 26-87 years), 47 patients had increased plasma FXI levels at T1 and16 patients had persistently increased plasma FXI levels at T2. The adjusted odds ratio for DVT was 2.4 (95% CI, 1.3 to 5.5, p < 0.001) for patients with increased FXI levels at T1 and 5.2 (95% CI, 2.3 to 13.2, p < 0.001) for patients with persistently high FXI levels at T2. Elevated FXI levels constitute a risk factor for deep vein thrombosis, and this risk nearly doubled in patients with persistently increased plasma FXI levels. Larger prospective studies are needed to confirm our findings.

Systematic search for the UBA1 mutation in men after a first venous thrombotic episode

VEXAS syndrome (acronym for Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is an autoinflammatory disease, described in adults in 2020, caused by a somatic mutation of the Ubiquitin like modifier activating enzyme 1 (UBA1) gene located on the X chromosome. VEXAS syndrome is mainly described in men after 50 years of age with a systemic inflammatory disease associated with febrile episodes, but also hematological, pulmonary, cutaneous, vascular, cartilaginous and articular involvement. Thrombotic complications have been reported in approximately 40% of VEXAS patients, with a predominance of venous thromboembolic events (VTE) rather than arterial thromboembolic events. Among the VTEs, deep vein thrombosis (DVT) was more frequent than pulmonary embolism (PE). The pathophysiology of VTE in VEXAS remains unknown. The objective of the study was to determine the frequency of UBA1 mutations in a cohort of men over 50 years of age with a first VTE. Our study included male patients aged > 50 years included in our center between January 2003 and January 2009, as part of the multicenter FARIVE study. The FARIVE case-control study included consecutive patients treated as inpatients or outpatients for a first episode of proximal DVT and/or PE. All patients were sampled for genetic study. In this study, exon 3 of UBA1 was sequenced. A total of 97 patients were included with a median age of 65 years and a median body mass index of 25.5. Of the patient cohort, 49 (50.5%) presented with an unprovoked VTE. Thrombophilia testing was available for 56 (57.7%) of the 97 patients and no severe thrombophilia was diagnosed among the patients tested. In the end, no UBA1 mutations were detected among the 97 patients (Table 1). VEXAS syndrome is associated with a high incidence of VTE but our study does not encourage its investigation in all men over 50 years of age with a first VTE without considering other clinical symptoms related to VEXAS. Routine screening for UBA1 exon 3 mutations should not be recommended after a first VTE.

Safety of discontinuation of anticoagulants after venous thromboembolism: whether D-dimer level should be taken into account?

Due to the continued risk of recurrence after a first episode of proximal deep vein thrombosis (DVT) of the lower extremities and/ or pulmonary embolism (PE) occurring without major transient risk factors, long-term use of anticoagulants is indicated in many cases. One attractive way to individualize the duration of treatment in these cases appears to be the assessment of blood D-dimer concentration. However, according to the prospective studies PROLONG, PROLONG II and REVERSE II, even persistent normalization of blood D-dimer concentration does not guarantee the absence of relapse. The available evidence also does not allow a differentiated approach to the assessment of the role of D-dimer for cases where proximal DVT and/or PE occurs in patients without identifiable risk factors or with minor risk factors. An attempt to clarify some of these uncertainties was made in the prospective APIDULCIS study, which included 732 patients who first had proximal DVT and/or PE, with symptoms occurring in the absence of obvious provoking factors (75.6% of cases) or associated with minor (weak) and transient risk factors (24.4%). The prerequisites included a normal blood D-dimer concentration. Patients were discontinued anticoagulants and blood D-dimer concentration measurements were repeated after 15, 30, and 60 days. If it remained low, the anticoagulant was not resumed (39.1% of cases), and when it first increased, apixaban was administered in a dose of 2.5 mg twice daily. The APIDULCIS study confirmed that anticoagulants cannot be discontinued after 1 year of use after the first unprovoked episode of proximal DVT and/or PE, even with persistent normal blood D-dimer concentration; it was shown that recurrence rate after the first episode of proximal DVT and/or PE, provoked by a minor transient risk factor, is high enough even after at least 1 year of anticoagulant treatment and at stable normal blood D-dimer concentration after their cancellation; comfirmed the effectiveness and safety of a reduced dose of apixaban (2.5 mg 2 times a day) during prolonged treatment of the first episode of proximal DVT and/or PE.

Prevalence and Associated Factors of Post-Thrombotic Syndrome in Patients With Deep Vein Thrombosis

Background: Post-thrombotic syndrome (PTS) occurs as a long-term complication of deep vein thrombosis (DVT). The aim of this study was to evaluate the prevalence of PTS and its associated factors in a cohort of patients with lower extremity DVT in Sri Lanka. Methods: A descriptive cross-sectional study was conducted in 80 patients who were assessed 6 months to 2 years after the acute episode of DVT. They were assessed using Vilalta scale to diagnose and grade the severity of PTS, anthropometry to calculate body mass index (BMI), duplex ultrasound scans, patients’ clinic record including international normalized ratio (INR) charts and an interviewer administered questionnaire. Categorical data were analyzed using Chi-square test and continuous variables were analyzed using analysis of variance (ANOVA) to determine association. Results: Prevalence of PTS was 45.5% (36/80) according to Villalta scale. Recurrent DVT (P = 0.0002), high BMI (P = 0.073), and previous venous in competence (P = 0.032), showed significant association with PTS. Proximal DVT demonstrated a strong association with PTS (P = 0.002). Residual thrombosis at 3 months was strongly associated with PTS (P &lt; 0.001), however, with a bias of very low sample with repeat duplex at 3 months post event. Awareness of PTS was extremely low (n = 0, 0%). Practice of elastic compression stockings (ECSs) use as a preventative measure of PTS failed to show any significant association (P = 0.61). Conclusions: This study showed a significant prevalence of PTS among patients with previous DVT. Development of PTS is probably multi factorial. A validated risk assessment tool should be used to identify at-risk patients as prevention is the best approach to this irreversible morbidity. J Curr Surg. 2022;12(2):38-44 doi: https://doi.org/10.14740/jcs459

Use of JAK 2 v617f As a Hypercoagulable Test in a Community Hospital

Introduction: We have anecdotally noticed that hypercoagulable workups are often performed unnecessarily within our community hospital in Orlando Florida. Some providers have a tendency to include JAK2 v617f, a test associated with high cost and one that can take weeks to have results return, as part of their panels. We hypothesize that this test is over utilized and will rarely be helpful in the workup of thrombosis without other reasons to suspect myeloproliferative disorders. We opted to look back at ordering patterns of JAK2 v617f and chart review the reasons it was ordered. Methods: Using a chart review, we pulled hundreds of charts in which a JAK2 v617f was ordered. We then scrolled through the charts to determine if thrombosis was an ordering reason. If so, we documented a positive or negative result and if the thrombotic event could be explained by other factors. Results: 120 charts were reviewed. Of the 120, 10 (8%) had JAK 2 v617f as part of a hypercoagulable panel. The remainder of testing was relegated to patients with erythrocytosis, thrombocytosis, or leukocytosis. When the JAK 2 test was used for hypercoagulable workup, it was negative in every case. The thrombosis included:Splanchnic vein in two casesSplenic infarct in one caseSingle episode of deep vein thrombosis or pulmonary embolism in three casesRecurrent deep vein thrombosis or pulmonary embolism in three casesCerebral vascular accident in one case Risk factors for thrombotic events were documented in seven cases. Conclusion While the majority of JAK2 v617f testing was done for reasons beyond thrombotic workup, when used of part of a thrombophilia workup, the testing was not useful. While there may be a limited role for testing in clots at unusual sites or unexplainable thrombotic events at a young age, most of the testing done at our institution did not fit this pattern. Routine testing should be looked at and discouraged in inappropriate situations. The cost of the test and the concerns about delaying hospital discharge or raising patient anxiety while awaiting results do not justify the limited utility of this test.

Protein S Deficiency with Recurrent Deep Vein Thrombosis and Post Thrombotic Syndrome: A Case Report

deep vein thrombosis; protein S deficiency; rivaroxaban.

Surgical Specifics of Lower Limb Superficial Thrombophlebitis Combined with Undifferentiated Connective Tissue Disease

Background. Superficial thrombophlebitis of lower extremities is among the most frequent acute vascular pathologies. Concomitant undifferentiated connective tissue dysplasia exerts specific changes in its clinical course.Aim: A study of the specific dynamics of acute lower limb superficial thrombophlebitis (ST) and its surgical treatment in patients with undifferentiated connective tissue dysplasia (UCTD).Materials and methods. The case histories, surgery reports and follow-up examinations of patients treated at the Vascular Surgery Unit during 2012–2020 were analysed. A total of 86 patients had signs of UCTD and underwent classical crossectomy of the great saphenous vein (Troyanov operation).Results and discussion. Duplex ultrasound of lower limb veins in 34 (39.53 %) patients revealed a discrepancy between the upper localisation of thrombotic masses in the great saphenous lumen and the external boundary registered for clinical manifestations, hyperaemia and tissue thickening. In 69 (80.23 %) patients, four or more phenotypic UCTD markers were exposed. In 74 (86.05 %) cases, a classical Babcock phlebectomy was performed as a next stage within one year after an acute thrombophlebitis attack had subsided. Of 12 (13.95 %) patients not having had a second-stage phlebectomy within one year: 4 people had UCTD signs — they refused surgery due to absent significant complaints or marked saphenous reflux; 3 had a deep vein thrombosis episode; 5 had no saphenous reflux of lower extremities in ultrasound examination.Conclusion. The registration of phenotypic signs of undifferentiated connective tissue dysplasia is recommended in choosing a surgical tactic to treat acute ascending thrombophlebitis of lower limb saphenous veins.

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.

Assessment of the lymphatic system by indirect lymphography in patients with post-thrombotic syndrome

ObjectiveAlterations in lower extremity lymph drainage caused by chronic venous obstruction (CVO) have not been well studied, partially because of a lack of standardized imaging modalities to assess the quality of lymphatic drainage in the lower extremities of patients with post-thrombotic syndrome (PTS). However, these changes are likely to have an impact on the severity of the disease and clinical outcomes of interventions. In the present study, we investigated the feasibility and diagnostic value of preintervention indirect lymphography in patients with CVO and their pre- and postintervention Villalta scores. MethodsA total of 17 patients (21 limbs) with iliofemoral and caval CVO were included in the study between 2017 and 2018. The deep and superficial lymphatic vessels in both legs were assessed before venous recanalization and stenting. The quality of lymphatic flow was compared between the legs with CVO and healthy legs. Moreover, the correlation between the lymphatic changes and clinical severity of PTS was evaluated using the Villalta score and CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) classification. ResultsThe mean patient age was 44 ± 12 years, and 10 patients (59%) were women. The patients had undergone treatment at a mean of 25 ± 6 months after their first episode of deep vein thrombosis. Five patients (29%) had had recurrent deep vein thrombosis. The mean pre- and postinterventional Villalta score was 10.5 ± 1.46 and 9.27 ± 1.12, respectively (P = .0096). Using the CEAP classification, four legs were class 5, seven were class 4, and three each were class 3 and 2. The primary and secondary patency rate was 70.5% and 82.5% after a mean follow-up of 18 months, respectively. Indirect lymphography of the superficial and deep lymphatic systems was completed before intervention in both legs for all 17 patients (21 legs). According to the qualitative criteria, abnormal lymphatic vessel function was found in 35.2% of the superficial and 58.8% of the deep lymphatic vessels of the affected legs. Further analysis revealed abnormal function of the deep lymphatic vessels in all patients with moderate to severe PTS according to the Villalta score. ConclusionsIndirect lymphography is a feasible diagnostic tool to use for the evaluation of the function of lymphatic vessels. Impaired drainage of the deep lymphatic system was found in all our patients with moderate to severe PTS. The clinical significance of these lymphatic changes is not clear; however, an association between clinical severity and outcomes is possible.

Fitness to Serve in the Armed Forces and Internal Medicine: A Retrospective Study.

Assessment of the medical fitness to serve in the armed forces has two objectives: to prevent the military operations from being jeopardized by a medical issue, and to protect soldiers from the sequelae of diseases that could become complicated in the operational field, especially in overseas operations where soldiers are exposed to a remote setting and a long evacuation time. Little is known about fitness decisions for soldiers with systemic or autoimmune diseases. Therefore, we conducted a single-center retrospective study of internal medicine fitness decisions. All the fitness decisions discussed from September 2019 to December 2020 in our department of internal medicine were reviewed. Gender, age, army or service, rank, garrison and health topic were collected from the medical files. Our Military Hospital local ethics committee, in accordance with the French law, approved this study. There were 41 cases, involving 31 men and 10 women (mean age: 31 years), presenting with autoimmune or systemic diseases, metabolic disorders, thrombophilia, congenital or acquired malformations or organ failure, miscellaneous nephropathies, or hemogram abnormalities. Four patients were taking immunosuppressive agents, 3 biologics, and 4 anticoagulants. Among the 15 civilians requiring medical fitness assessment to enlistment, 6 were declared fit. They presented with a history of juvenile idiopathic arthritis with intermediate uveitis without relapse for 7 years, Mayer-Rokitansky-Küster-Hauser syndrome type II with ectopic kidney, solitary kidney with normal renal function and with hypertension, isolated proteinuria, proteinuria with microscopic hematuria, and muscular fibrolipoma with a history of surgical treatment of a vascular malformation. Among the 26 patients already enlisted in the armed forces, 9 were referred for assessment of medical fitness to serve overseas. Two soldiers were assessed as fit without restrictions; one presented with a history of a single episode of deep vein thrombosis after surgery, and the other had a history of monoclonal gammopathy of renal significance without relapse and without treatment for 8 years. Four soldiers were assessed as fit only for overseas territories with sanitary structures similar to mainland France. They presented with immunoglobulin A (IgA) nephropathy and treatment with angiotensin-converting enzyme inhibitor, mevalonate kinase deficiency and treatment with anakinra, chronic idiopathic thrombocytopenic purpura, and history of unilateral partial renal infarction. The 17 other soldiers were referred for dispensation, long-sickness leave granting, or for specification toward administrative coding of their disease. We have described the first exhaustive study of specialized fitness decisions referred to an internal medicine department. One-third of the referred patients were declared fit to serve in the armed forces. Further studies are needed to confirm these results, as our study was monocentric. Fitness decisions must take into account the disease, the treatment, and the operational field characteristics. Soldiers with systemic diseases controlled by immunosuppressive agents can serve in tropical areas if they can reach adequate sanitary structures in a short time. The knowledge of systemic diseases as well as the skillfulness of the internists, which are regularly projected to the operational fields, allows them to provide pragmatic fitness expertise to myriad complex situations.

Risk Factors for Post-Thrombotic Syndrome in Patients With a First Proximal Deep Venous Thrombosis Treated With Direct Oral Anticoagulants.

The incidence of post-thrombotic syndrome (PTS) in patients with deep vein thrombosis (DVT) treated with direct oral anticoagulants (DOACs) remains a matter of debate. Hence, our endeavor to investigate a large cohort of patients with a first episode of proximal DVT treated with DOACs to ascertain the incidence and predisposing risk factors for PTS. All consecutive patients referred to the Thrombotic and Haemorrhagic Diseases Unit of Padova University Hospital (Italy) between January 2014 and January 2018 for a first episode of proximal DVT were considered for enrollment. Participants received DOACs for a minimum period of 3months. PTS was assessed using the Villalta score up to 36months after DVT diagnosis. Among 769 enrolled patients (M/F 353/416, age range 26-87years), 152 (19.8%) developed PTS and 30 (3.9%) developed severe PTS. The adjusted hazard ratio was significant for obesity (1.64, 95% CI 1.28-2.39) and DVT site (femoral and/or iliac veins vs popliteal vein) (1.23, 95% CI 1.15-3.00). The incidence of PTS is not negligible in patients with proximal DVT despite the use of DOACs. We identified obesity and iliofemoral DVT as possible risk factors for PTS. Larger prospective studies are needed to confirm our findings and optimize therapeutic strategies.

Predictors of recurrence of venous thromboembolic disease after discontinuing of anticoagulation: a prospective cohort study.

We aim to evaluate factors associated with the recurrence of thromboembolic episodes among patients with a first episode of venous thromboembolic disease during anticoagulation treatment and at least one year after treatment suspension. A prospective cohort of patients with a first episode of deep vein thrombosis confirmed by Doppler ultrasound and initiated anticoagulation treatment. Participants were registered in the Institutional Registry of Thromboembolic Disease between June 2015 and March 2019. Patients with cancer, with permanent inferior vena cava filter implant, and those who refused to participate or did not provide informed consent were excluded. All patients were evaluated within treatment at 30 days and at least one year after the suspension of anticoagulation with a D-dimer study and an ultrasound. All patients were evaluated for recurrence, bleeding (major and minor), and death. A total of 304 patients were recruited during the study period. Seventy-three percent were female, and the median age was 80 years. The rate of recurrence rate during anticoagulation treatment was 5% (N = 16/303; 95% confidence interval: 3 to 8), and 5% during post-suspension follow-up (N = 11/202; 95%CI: 3 to 9). The overall bleeding rate was 13% (N = 39; 95%CI: 9 to 17), and 5% for major bleeding. Patients who recurred had higher basal D-dimer mean, higher neutrophils and monocytes, and a higher prevalence of age-adjusted D-dimer ratio greater than 0.5 before discontinuation. In addition, they more frequently had complete leg involvement by ultrasound and received a shorter treatment. Although some baseline and pre-suspension parameters had a higher recurrence incidence, statistical significance was not reached, probably due to small statistical power and a short-term follow-up.

Is Nature Truly Healing Itself? Spontaneous Remissions and Clonal Replacement in Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is considered to be curable only through the means of allogeneic HSCT. One of the many fascinating and scientifically instructive aspects of the pathogenesis of this disease is the rare possibility of its spontaneous remission with disappearance of PNH clone and abatement of clinical symptoms, which has always captivated the research community. Due to the orphan nature of the condition, no clinical predictors have been identified so far as harbingers of this phenomenon. In a classical scenario, exhaustion of PNH clone may be associated with reappearance of aplastic anemia (AA), in which PNH clone reflects a semi-maladaptive attempt of recovery. Consequently, one could stipulate that the retraction of PNH clone(s) would have to be associated with a compensatory re-expansion of normal hematopoiesis should normal counts be maintained. The recent insights into the AA/PNH pathobiology shed light onto molecular underpinnings of polyclonal vs oligoclonal hematopoiesis and their dynamics. Here, through application of NGS we attempted to better discern the mechanism of PNH spontaneous remission taking advantage of our internal cohort of PNH patients.Among 92 patients with a diagnosis of hemolytic PNH (M:F ratio 0.88, median age 38 years, range 9-84) 41% were primary PNH (pPNH) while 59% were secondary to AA (sPNH). Overall, patients were clinically followed-up for a median time of 68 months (2-339). Median granulocyte clone size was 73% (22-99) with the majority of cases being classified as having a type III dominant red blood cells (RBCs) clone (80%) while 20% type II. Within this cohort, a total of 3 patients underwent spontaneous remission.UPN1 was a 69-year-old male diagnosed with pPNH at the age of 46 after an episode of deep vein thrombosis. He had been managed with prednisone, transfusions and anti-coagulation because of recurrent thrombotic episodes. Once available, he was started on eculizumab and later continued on ravulizumab. His initial flow cytometry study revealed the presence of a type III RBCs clone of 40% and a granulocyte clone of 89%. After 9 years of anti-complement therapy, the patient's clone started a slow decrease and the most recent study revealed a granulocyte clone of 0.02%. Molecular analysis performed at the time of eculizumab start showed a co-dominant mutational configuration by variant allelic frequency (VAF) with PIGA deletion (p.94_95del; VAF 29%) and a BCOR nonsense (p.Y1446X; VAF 27%). No HLA class I/II mutations were found in two longitudinal samples collected 1 year before and after eculizumab start. However, at the last sequencing performed after the complete disappearance of the PNH clone, the patient developed ASXL1 (p.E635Rfs*, VAF 26%) and ZRSR2 (p.E120Gfs*, VAF 42%) mutations along with retraction of the previous PIGA lesion. No decrease in blood counts was noted.UPN2 was a 58-year-old male initially diagnosed with severe AA at the age of 48 and treated with ATG + CsA. At that time, he had a co-existing PNH granulocyte clone of 28%. After 1 year from IST his PNH clone dropped to 1% and since then has been consistently below 1%. Patient has never received anti-complement therapy. At the time of PNH clone retraction, no HLA class I/II or myeloid driver mutations were found and PIGA mutations were not detectable. However, longitudinal molecular studies performed after disappearance of PNH clone revealed the acquisition of ASXL1 p.Q512X mutation at an initial VAF of 23%, which doubled (45%) at last follow-up 5 years later while normal counts persisted.UPN3 was instead a 59-year-old lady diagnosed with pPNH at the age of 30. She had a granulocyte clone as high as 43% with a type II RBCs clone of 17% and a typical PIGA splice site c.981+1G>A mutation (VAF 15%). She was initially treated with transfusions and steroids and her course was complicated by a cerebral venous sinus thrombosis. Patient was eventually given eculizumab and her PNH clone started decreasing until it vanished (last 0.04%) after 8 years. Analysis of samples prior to and after PNH disappearance did not show any HLA class I/II nor myeloid driver gene mutations with absence of PIGA alterations at last sequencing.PNH spontaneous remissions are rare events. In addition to be replaced by polyclonal hematopoiesis, PIGA clones may be swept by CHIP lesions in myeloid genes (e.g. ASXL1) characterized by improved fitness advantage in a process of Darwinian selection. [Display omitted] DisclosuresMaciejewski: Regeneron: Consultancy; Novartis: Consultancy; Bristol Myers Squibb/Celgene: Consultancy; Alexion: Consultancy.

Post-thrombotic syndrome.

Post-thrombotic syndrome (PTS) is a chronic venous insufficiency manifestation following an episode of deep-vein thrombosis (DVT). It is an important and frequent long-term adverse event of proximal DVT affecting 20-50% of patients. This position paper integrates data guiding clinicians in deciding PTS diagnosis, treatment and follow-up.

Influence of intravenous laser blood irradiation on lymphovenous outflow and the state of humoral and cellular immunity in patients with postthrombophlebitic disease of the lower extremities

Post-thrombophlebitis of lower extremities occurs in 14–29 % of cases and develops within the fi rst two years after the episode of deep vein thrombosis of lower extremities in 20–50 % of patients. Objective: to apply intravenous laser blood irradiation (ILBI) for optimizing outcomes in patients with post-thrombophlebitic disease of their lower extremities. Materials and methods. 52 patients were treated with ILBI. They were randomized into two groups by the following clinical criteria: stage of occlusion – 18 patients (Group 1) and stage of recanalization – 34 patients (Group 2). ILBI course included 7 sessions: irradiation power – 3–15 mW, pulse frequency – 80–3000 Hz, exposure time – 5–15 minutes. Parameters of venous outfl ow and inguinal lymph nodes were monitored by ultrasound examination. Radial immunodiffusion was used to determine levels of IgG, IgM and IgA in blood plasma and serum; turbidimetry – to determine immune complexes; T-lymphocytes – by the receptors to erythrocytes. B-lymphocyte level was monitored with luminescence-serological and complementary rosette formation techniques. Results and discussion. A statistically signifi cant increase in linear and volumetric blood fl ow in great vessels was revealed in both groups. In Group 1, linear blood fl ow in the great saphenous vein increased by 5.2 %; volumetric blood fl ow increased up to 113.0 ± 2.14 mL/min (p &lt; 0.01). In Group 2, volumetric blood fl ow slowed down by 4.1 %. Lymph nodes contracted statistically signifi cantly; the medullary layer narrowed up to 0.32 ± 0.05 cm (p &lt; 0.05), level of IgG, IgM and CIC decreased; number of T-lymphocytes increased up to 60.2 ± 1.7 % (p &lt; 0.05). Conclusion. The revealed effects of intravenous laser blood irradiation at the venous outfl ow, lymph nodes and humoral and cellular immunity in patients with post-thrombophlebitic disease of lower extremities give a reason to recommend the implementation of the discussed technique into a wide clinical practice.

Nonvitamin K Antagonist Oral Anticoagulant in Patients With Venous Thromboembolism and Polycythemia Vera or Essential Thrombocythemia: A Cohort Study.

Thrombosis is the most common adverse event in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Little is known about the use of nonvitamin K antagonist oral anticoagulants (NOACs) in patients with myeloproliferative neoplasms. We sought to evaluate the efficacy and safety of NOAC in a cohort of patients with PV and ET, who experienced venous thromboembolism (VTE). We enrolled 48 consecutive patients with PV (70.8%) and ET [median age 67.0 (interquartile range, 58.5-72.0) years], who experienced VTE. Patients received apixaban (39.6%), rivaroxaban (33.3%), or dabigatran (27.1%). During a median follow-up of 30 (interquartile range, 20.5-41.5) months, recurrent thrombotic events and bleeding were recorded. Four thrombotic events (3.3 per 100 patient-years) were reported. Three deep vein thrombosis episodes (2.5 per 100 patient-years) were experienced by 2 patients with PV, who received apixaban (5 mg bid) and dabigatran (150 mg bid), and 1 patient with ET, who received dabigatran (150 mg bid). One ischemic stroke occurred in a patient with PV on rivaroxaban (20 mg/d). There was 1 major bleeding (0.8 per 100 patient-years) in a patient with ET on dabigatran (150 mg bid) and 3 clinically relevant nonmajor bleeding (2.5 per 100 patient-years): 2 on rivaroxaban (20 mg/d) and 1 on apixaban (5 mg bid). We did not observe significant differences related to the type of NOAC. Three deaths (2.5 per 100 patient-years) unrelated to either VTE or bleeding were recorded. This study shows that NOACs may be effective and safe as secondary prevention of VTE in patients with myeloproliferative neoplasms.

Role of Hematological Parameters in Predicting Severity of Acute Venous Thromboembolism

Background- Many studies have shown that inflammation and clotting mechanisms are closely related. Hence, inflammatory markers such as Neutrophil-Lymphocyte ratio(NLR) and Platelet-Lymphocyte ratio (PLR) can be elevated in patients with acute venous thromboembolism (VTE) including deep vein thrombosis(DVT) and pulmonary embolism(PE) In this retrospective study, we evaluated the significance of NLR & PLR in predicting the severity of VTE.Methods -We retrospectively analyzed data of all patients who were diagnosed with first episode of DVT and PE from 01/2005 to 06/2015. Clinical data for 212 patients with DVT and PE and 58 random healthy controls (outpatient well visit) were collected from the electronic medical record system database of our 850 bed tertiary care center hospital.Results: The number of patients with VTE and healthy controls (C) were (DVT-115(54%), PE 97(46%)) and 58 respectively. The mean age DVT was 61.3 ± 16.3, PE 61.6 ± 16.2 & C 55.2 ± 16.6 years. The mean NLR VTE and C was 6.6±7.24 & 5.89±8.8 respectively. Mean PLR VTE and C was 17.15±17.18 & 17.49±17.5. Increased age was significantly associated with DVT (p=0.012) and PE (p=0.001). Odd for DVT in females were 1.7 (1.04-2.78; p=0.03) compared to males. Though there were no differences in odds of PE between sexes. In patients with DVT, PLR was higher in proximal v/s distal (p=0.014). Also, platelet counts were significantly lower in extensive DVT compared with either distal or proximal DVT (p=0.039). NLR was significantly higher in patients with central v/s distal PE (p=0.042). No significant differences were noticed in NLR, PLR or platelet counts between PE, DVT and C.Conclusion: In this study, inflammatory markers like NLR , PLR were increased with acute thrombosis. Moreover, the ratios were higher with proximal thrombosis both in central and peripheral venous system.Platelet counts were lower in extensive DVT probably from increased consumption. Thus the inflammatory markers when combined with traditional risk factors for DVT and PE can increase the probability of its diagnosis and predict the severity of thrombosis. DisclosuresNo relevant conflicts of interest to declare.

Reversal of cardiopulmonary exercise intolerance in patients with post-thrombotic obstruction of the inferior vena cava

BackgroundIt is unclear whether cardiopulmonary exercise intolerance in patients with chronic obstruction of the inferior vena cava (IVC) is reversible following endovascular IVC reconstruction. MethodsIn 17 patients (mean age 45 ± 15 years, 71% men) with post-thrombotic syndrome due to IVC obstruction and preserved left ventricular ejection fraction (mean 58 ± 3%), we performed cardiopulmonary exercise testing before and 3 months after IVC reconstruction (mean 4.1 ± 1.5 implanted stents). The median time from latest episode of deep vein thrombosis to intervention was 150 (interquartile range 102–820) days. ResultsAt baseline, 12 (71%) patients reported New York Heart Association (NYHA) class II or III symptoms, 76% did not achieve >85% of predicted oxygen uptake at peak exercise (mean 61.8 ± 13.7%). After IVC reconstruction, the following changes were observed at anaerobic threshold: work rate increased by 14.6 W, 95%CI (−0.7; 30.0), oxygen uptake increased by 1.8 ml/kg, 95%CI (0.3; 3.3). Oxygen pulse increased by 1.95 ml per beat, 95%CI (1.12; 2.78), corresponding to a mean relative increase of 22.5%, 95%CI (12.4; 32.7) (p < 0.001). The following changes were observed at peak exercise: work rate increased by 48.1 W, 95%CI (27.8; 68.4), oxygen uptake increased by 6.4 ml/kg, 95%CI (3.8; 9.1). Oxygen pulse increased by 2.68 ml per beat, 95%CI (1.60; 3.76), corresponding to a mean relative increase of 29.4%, 95%CI (17.7; 41.2) (p < 0.001). At follow-up, 5 (29%) patients remained in NYHA class II. ConclusionsIn patients with chronic IVC obstruction, cardiopulmonary exercise intolerance as a result of impaired cardiac filling is at least partially reversible following endovascular IVC reconstruction. Study registrationURL: https://clinicaltrials.gov. Unique identifier: NCT02433054.