Secondary Thrombosis Research Articles

Prevalence and significance of clonal hematopoiesis of indeterminate prognosis (CHIP) in multiple myeloma.

8542 Background: Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the presence of leukemia-associated somatic mutations in clonally expanded hematopoietic stem cells with a VAF of ≥2%. CHIP has been associated with myeloid malignancies and increased all cause mortality largely from atherovascular disease. The prevalence and impact of CHIP in patients with myeloma (MM) is yet to be defined. Aims: Evaluate the prevalence and significance of CHIP in 101 lenalidomide exposed patients with multiple myeloma. Methods: 101 MM patients, the majority exposed to > 2 years of lenalidomide (Len), with stored mononuclear blood samples were identified for Next Generation Sequencing (NGS) using a panel encompassing 42 gene mutations associated with CHIP. Electronic medical records were reviewed and outcomes of secondary malignancy, macrocytosis, thrombosis and mortality were extracted. Results: Thirty of 101patients were found to have CHIP with the most frequent mutations: DNMT3A (12%), TET2 (5%), and TP53 (4%). One third of patients with CHIP had > 1 mutation (37%). At 68 months median follow up over a quarter of patients experienced thrombosis (31%) and 13% developed subsequent malignancy/premalignant condition including myelodysplastic syndrome (3%). There was no significant difference in age, gender, duration of Len prior to NGS testing, thrombosis complication, or survival in those with versus without a CHIP mutation. At last F/U 30% had died, 25% remained on therapy, 27% were on maintenance therapy and 11% were on observation alone. Conclusions: CHIP mutations are common in plasma cell neoplasms, with 30% of patients in this study retrospectively found to have CHIP mutations by NGS testing. CHIP mutations have been associated with cardiovascular events and malignancy development, however no associations were identified in this small study. Limitations to this study include small sample size, retrospective nature and duration of follow up. Further study of this very common finding in MM patients regarding timing of development and subsequent impact of these mutations could help risk stratify and inform therapy selection. [Table: see text]

Antiphospholipid syndrome: a clinical perspective.

Antiphospholipid syndrome (APS) is a thromboinflammatory disease with a variety of clinical phenotypes. Primary thrombosis prophylaxis should take an individualized risk stratification approach. Moderate-intensity vitamin K antagonist such as warfarin remains the primary strategy for secondary thrombosis prophylaxis among APS patients, especially for patients with predominantly venous disease. For now, direct oral anti-coagulants should be avoided in most APS patients, especially those with history of arterial manifestations. Obstetric APS management should be tailored based on an individual patient's antiphospholipid antibody profile, and obstetric and thrombotic history. Pharmacological agents beyond anticoagulants may be considered for the management of microthrombotic and nonthrombotic manifestations of APS, although more data are needed. A relatively recent discovery in the area of APS pathogenesis is the implication of neutrophil extracellular traps in thrombin generation and initiation of inflammatory cascades. APS is a complex thromboinflammatory disease with a broad clinical spectrum. Personalized therapy according to an individual's unique thrombosis and obstetric risk should be advocated.

Abstract TP73: Heterogeneity of Occlusive Thrombus Investigated on Pretreatment Imaging in Acute Ischemic Stroke

Background and Purpose: Investigation of occlusive thrombus in ischemic stroke is expected to clarify the etiology and mechanism of stroke fueling an optimal treatment strategy. However, in situ propagation due to secondary thrombosis after initial embolic occlusion could obscure the characteristics of initial emboli. Differentiation of the initial embolus and secondary thrombosis using retrieved specimens might be difficult due to fragmentation of whole thrombi. We aimed to investigate the heterogeneity of occlusive thrombi using pretreatment imaging of ischemic stroke. Methods: Among consecutive stroke patients with acute embolic occlusion of the anterior circulation eligible for endovascular reperfusion therapy, we retrospectively reviewed 81 patients who underwent both brain non-contrast CT (NCCT) and CT angiography (CTA) on admission from June 2015 to May 2018. Region of interest (ROI) was set on the whole thrombus on NCCT, which was identified referring to the filling defect on CTA, and the size of thrombus was measured. ROI was then divided equally into proximal and distal segments and Hounsfield Unit (HU) densities of those segments were measured respectively. Difference of HU between proximal and distal segments (ΔHU; HU in proximal segment - HU in distal segment) was calculated and analyzed. Results: HU density on NCCT in proximal segment was higher than in distal segment (mean difference: 3.75, 95% CI: 2.69-4.80, p<0.01). ΔHU was correlated positively with the length of thrombus (ρ=0.32, p<0.01), and correlated inversely with the time from last-known-well (LKW) to imaging (ρ=-0.29, p=0.01) and blood platelet level (ρ=-0.27, p=0.02). Stroke subtype and vascular risk factors had no significant correlation with ΔHU. On multivariate regression analysis, the length of thrombus (β=0.31, p=0.01) and the time from LKW to imaging (β=-0.30, p=0.01) were associated with ΔHU. Conclusions: Density of occlusive thrombi in the proximal segment is higher than in the distal segment. This difference increases as thrombi grow longer and decreases as thrombi get older after embolic occlusion. This time/length-dependent thrombus heterogeneity is suggestive of secondary thrombosis, occurring initially at the proximal side of occlusion.

A randomized trial of surgery alone versus surgery plus compression in the treatment of venous leg ulcers in patients with primary venous insufficiency

Background/Aim.Venous leg ulcers (VLU) are a significant health problem worldwide. It is well known that VLU are difficult to treat and that they have high tendency for recurrence. Compression therapy is the preferred treatment modality but there is growing evidence that correction of underlying venous disorder in early stages of the disease in addition to compression treatment may improve ulcer healing and reduce recurrence rate. Methods. An open, prospective, randomized, single-center study, with a 6-months follow-up was performed to determine the efficacy of two different treatment modalities (surgery alone versus surgery plus compression) in the treatment of VLU in patients with primary venous insufficiency. Patients with secondary venous insufficiency and/or thrombosis were excluded from the study. Overall, 71 patients were randomized (37 men, 34 women; mean age 60 years) into two groups: the group A ? 34 patients who underwent surgical intervention (stripping) and postoperatively were treated with simple wound dressing only, and the group B ? 37 patients who underwent surgical intervention (stripping) and wore a heelless open-toed elastic class III compression device knitted in tubular form ?Tubulcus? (Laboratoires Innothera, Arcueil, France). All patients in group B were instructed to wear compression device continuously during the day and night. The study was performed at the Clinic for Cardiovascular and Transplant Surgery, Clinical Centre Nis (Serbia) with primary endpoint of the study being complete ulcer healing at 180 days. Results. The healing rate was 29.41% (10/34) in the group A, and 56.76% (21/37) in the group B (p < 0.01). Mean healing time in the group A was 141 ?15 days, and in the group B it was 98 ?12 days (Log-rank life table analysis: p < 0.001). Conclusion. This study suggests that for VLU in patients with primary venous insufficiency, surgery plus compression therapy provides higher healing rate and faster healing time compared to surgery only.

Deep Vein Thrombosis Due to Fecal Impaction

Deep vein thrombosis (DVT) can occasionally be secondary to mechanical compressions, such as in May-Thurner syndrome. To our knowledge, no cases of DVT associated with mechanical compression by fecal impaction in a pediatric patient have been previously reported. An 18-year-old developmentally delayed female presented to the emergency department with swelling involving her left lower extremity. Cross-sectional imaging revealed a significant stool burden in the rectosigmoid colon compressing the left external iliac vein and causing secondary thrombosis. Thrombectomy successfully alleviated the clot burden. This case underscores the potentially serious implications of severe fecal impaction in the pediatric and adolescent populations.

Endovascular treatment of fusiform aneurisms of brain vessels

Objective – to determine the effectiveness of endovascular treatment of fusiform arterial aneurysms of cerebral vessels.Materials and metods. The results of endovascular treatment of 25 patients with fusiform cerebral aneurysms who were treated at the Center in the period from 2011 to 2018 were analyzed. There were 12 men (48 %), women – 13 (52 %). The average age of patients is 48 years. In 17 (68 %) cases were vertebrobasilar aneurysms, in 2 (8 %) cases – aneurysms of the anterior cerebral artery, in 3 (12 %) cases – aneurysms of the middle cerebral artery, in 3 (12 %) cases – aneurysms of internal carotid arteries. For the treatment of patients we used various stents: flow diversion (FRED (Microvention, USA), Pipeline (ev3, USA)), Derivo (Acandis, Germany)) and protection stents (Leo (Balt, France), Solitaire (Medtronic, USA)), in deconstructive interventions – detachable coils.Results. It were performed 25 surgical interventions: in 23 (92 %) cases – reconstructive shutdown, in 2 (8 %) – deconstructive shutdown. There were no technical problems during surgical interventions. Complications were noted in two cases with VBB aneurysms in the early postoperative period stem disorders appeared due to the increasing mass effect. Both patients were dead. Control examination in a period from 6 months to 3 years 13 (52 %) patients were performed. The results of excluding aneurysms were evaluated on a Raymond–Roy scale. The type 1 was detected in 7 (53.8 %) patients, the type 2 – 1 (7.7 %), the type 3 – 5 (38.5 %). In 2 (15.4 %) patients bearing artery thrombosis was detected.Conclusions. Extrasacular endovascular methods of treating fusiform arterial aneurysms of cerebral vessels are effective and relatively safe. They can expand the indications for endovascular treatment of these aneurysms, however compared with the treatment of saccular aneurysms hemodynamic changes and secondary aneurysm thrombosis are unpredictable and require further study.

Vepoloxamer Enhances Fibrinolysis of tPA (Tissue-Type Plasminogen Activator) on Acute Ischemic Stroke.

Background and Purpose- Thrombolytic treatment of acute ischemic stroke with tPA (tissue-type plasminogen activator) is hampered by its narrow therapeutic window and potential hemorrhagic complication. Vepoloxamer is a nonionic surfactant that exerts potent hemorheologic and antithrombotic properties in various thrombotic diseases. The current study investigated the effect of vepoloxamer on tPA treatment in a rat model of embolic stroke. Methods- Male Wistar rats subjected to embolic middle cerebral artery occlusion were treated with the combination of vepoloxamer and tPA, vepoloxamer alone, tPA alone, or saline initiated 4 hours after middle cerebral artery occlusion. Results- Monotherapy with tPA did not reduce infarct volume, and adversely potentiated microvascular thrombosis and vascular leakage compared with the saline treatment. Vepoloxamer monotherapy reduced infarct volume by 25% and improved brain perfusion. However, the combination treatment with vepoloxamer and tPA significantly reduced infarct volume by 32% and improved neurological function, without increasing the incidence of gross hemorrhage. Compared with vepoloxamer alone, the combination treatment with vepoloxamer and tPA robustly reduced secondary thrombosis and tPA-augmented microvascular leakage and further improved brain perfusion, which was associated with substantial reductions of serum active PAI-1 (plasminogen activator inhibitor-1) level and tPA-upregulated PAI-1 in the ischemic brain. Mechanistically, exosomes derived from platelets of ischemic rats treated with tPA-augmented cerebral endothelial barrier permeability and elevated protein levels of PAI-1 and TF (tissue factor) in the endothelial cells, whereas exosomes derived from platelets of rats subjected to the combination treatment with vepoloxamer and tPA diminished endothelial permeability augmented by tPA and fibrin and reduced PAI-1 and TF levels in the endothelial cells. Conclusions- The combination treatment with vepoloxamer and tPA exerts potent thrombolytic effects in rats subjected to acute ischemic stroke. Vepoloxamer reduces tPA-aggravated prothrombotic effect of platelet-derived exosomes on cerebral endothelial cells, which may contribute to the therapeutic effect of the combination treatment.

Cardiovascular Disease in Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by venous, arterial or microvascular thrombosis or obstetric events in the presence of persistently positive antiphospholipid antibodies and constitutes a major cause of cardiovascular events in young people. Τhis review highlights the pathophysiology of cardiovascular complications in patients with APS and possible treatment options. Patients with APS have endothelial dysfunction, accelerated endothelial proliferation and intimal hyperplasia, atherogenesis, platelet activation, inflammatory products secretion and coagulation-fibrinolytic dysregulation. Cardiovascular complications include accelerated atherosclerosis, acute coronary syndrome, Libman-Sacks endocarditis, cardiomyopathy and venous, arterial or intracardiac thrombi. Moreover, pulmonary hypertension and peripheral microvascular dysfunction are common findings. Management of these patients is not well documented. The role of primary thrombosis prevention remains controversial in individuals with positive antiphospholipid antibodies. Treatment of traditional cardiovascular risk factors according to current guidelines for the prevention of cardiovascular disease in the general population is recommended for primary prevention of APS. Anticoagulation therapy with unfractionated or low-molecular-weight heparin overlapped with a vitamin K antagonist remains the mainstay of the treatment for APS patients with venous thrombosis, whereas direct oral anticoagulants are not yet recommended. Data are scarce regarding the secondary arterial thrombosis prevention and it is not clear whether dual or triple antithrombotic therapy is necessary. To date, it is recommended to follow current guidelines for the management of acute coronary syndrome in the general population. New treatment targets are promising options for patients with catastrophic APS.

Single-Stage Treatment of AngioJet Rheolytic Thrombectomy and Stenting for Iliac Vein Compression Syndrome with Secondary Acute Iliofemoral Deep Vein Thrombosis

We sought to evaluate the feasibility, safety, and effectiveness of single-stage endovascular treatment with AngioJet rheolytic thrombectomy followed by stenting for iliac vein compression syndrome (IVCS) with secondary acute iliofemoral deep vein thrombosis (DVT). We conducted a multiple-center prospective nonrandomized study to enroll patients with left-sided acute iliac-common femoral DVT secondary to IVCS. We performed AngioJet rheolytic thrombectomy followed by stenting to evaluate the success rate, periprocedural complications, hospital stay, clinical outcomes, and stent-patency rate. A prospective cohort study of 19 consecutive patients diagnosed with IVCS and secondary acute iliac-common femoral DVT from October 2014 to April 2017 was conducted. The technique success rate was 94.7%, and the mean procedure time was 77minutes. The 1-year primary and secondary patency rate was 84.2% and 94.7%, respectively. Single-staged endovascular treatment with AngioJet rheolytic thrombectomy and stenting is feasible, safe, and effective for IVCS with secondary acute iliofemoral DVT.

PCN168 GLOBAL BURDEN OF WALDENSTRÖM MACROGLOBULINEMIA (WM): A SYSTEMATIC LITERATURE REVIEW (SLR) AND EVIDENCE GAP ANALYSIS

To review the global clinical, economic, and humanistic burden of WM and evaluate current evidence data gaps. A SLR using PubMed to identify WM-related interventional, observational, qualitative, and economic studies published January 2013-September 2018. Inclusion criteria: human clinical studies, N>40, non-case reports or editorials, English manuscripts available. Of 1146 evaluable publications, 51 were included based on above search criteria. WM incidence ranged from 0.3-0.57/100,000 person-years in US studies, with most data showing decreased or stable incidence over time. WM incidence appeared similar in Japan and Taiwan but higher in Sweden (1.05/100,000). Recent data trends suggest significantly increased WM-related survival, though 5-year survival rates vary (52%-78%) in US studies. European data demonstrate similar survival rates and trends (5-year survival ∼70%) but lower survival in China (61.8%). Across countries, WM appears to be more common in men and in elderly. Mortality rates are also shown to be higher in elderly and male patients. US data suggest higher incidences in Caucasian patients but reduced survival for African American and Hispanic patients. Compared to Westerners, Chinese patients demonstrated a higher male-to-female ratio, younger diagnosis age, higher rates of leukocytopenia, thrombocytopenia, and pancytopenia, and reduced asymptomatic WM. WM-related serious complications are reported, including secondary malignancies, thrombosis, renal diseases, symptomatic hyperviscosity, and autoimmune manifestations. Although novel treatments contribute to improved survival, they significantly increase costs (mean Medicare costs in first treatment year: $9,464 before 2000 to $29,490 after 2008; most recent data available). Data on the humanistic burden of WM are lacking. This study reviewed the burden of WM across the regions (US, EU, and China). Although rare, WM results in significant clinical (e.g., incidence, complications, survival) and economic burden and unmet needs, with new treatments associated with clinical benefits but increased costs. Data gaps on WM-burden exist, future studies are suggested.

Fn-EDA (Fibronectin Containing Extra Domain A) in the Plasma, but Not Endothelial Cells, Exacerbates Stroke Outcome by Promoting Thrombo-Inflammation.

Background and Purpose- Cellular Fn-EDA (fibronectin containing extra domain A) is expressed in activated endothelial cells and elevated in circulation in patients with cardiovascular diseases. Although global deficiency of Fn-EDA in mice improves stroke outcome, the specific contribution of plasma versus endothelium Fn-EDA in stroke outcome is currently unknown. We investigated the role of plasma versus endothelial Fn-EDA in stroke exacerbation in the comorbid condition of hyperlipidemia. Methods- We generated novel plasma Fn-EDA-/- ( Fn-EDA fl/fl Alb Cre) and endothelial Fn-EDA-/- ( Fn-EDA fl/fl Tie2 Cre) strains on hyperlipidemic apolipoprotein E-deficient ( ApoE-/-) background. By following the Stroke Therapy Academic Industry Roundtable guidelines, we evaluated stroke outcome in male and female mice. Susceptibility to ischemia/reperfusion injury was evaluated in 2 different models of stroke: intraluminal monofilament and embolic model on days 1, 3, and 7. Quantitative assessment of stroke outcome was evaluated by measuring infarct volume (by magnetic resonance imaging), cerebral blood flow (by laser speckle imaging), neurological and sensory-motor outcome, and postischemic thrombo-inflammation (platelet thrombi, fibrin, neutrophil, phospho-NFκB [nuclear factor κB], TNFα [tumor necrosis factor α], and IL1β [interleukin 1β]). Results- Stroke outcome was comparable in ApoE-/- Fn-EDA fl/fl Tie2 Cre and control ApoE-/- Fn-EDA fl/fl mice suggesting endothelial Fn-EDA does not contribute to stroke. ApoE-/- Fn-EDA fl/fl Alb Cre mice exhibited significantly smaller infarcts and improved neurological and sensory-motor outcome at days 1, 3, and 7 in monofilament and embolic models of stroke. Improved stroke outcome was concomitant with enhanced survival, and decreased postischemic thrombo-inflammatory response ( P<0.05 versus ApoE-/- Fn-EDA fl/fl). No sex-based differences were observed. Laser speckle imaging revealed significantly improved regional cerebral blood flow at 1 hour in ApoE-/- Fn-EDA fl/fl Alb Cre mice suggesting plasma Fn-EDA promotes postischemic secondary thrombosis. Coinfusion of anti-Fn-EDA antibody with r-tPA (recombinant tissue-type plasminogen activator) in ApoE-/- mice, 1 hour after embolization, improved stroke outcome with enhanced survival, and improved neurological outcome ( P<0.05 versus r-tPA). Conclusions- Genetic evidence suggests that plasma Fn-EDA exacerbates stroke outcome by promoting postischemic thrombo-inflammation. Interventions targeting plasma Fn-EDA may reduce brain damage after reperfusion.

Primary upper extremity deep vein thrombosis in a Caucasian woman

Abstract Compared to deep vein thrombosis in the lower limbs, upper extremity deep vein thrombosis is uncommon and therefore much less explored or even neglected. We present the case of a 40-year-old female working in the bakery industry, who was admitted for acute onset of upper limb oedema accompanied by pain and functional impairment, affirmative secondary to the sustained and intense effort of the dominant arm. The diagnosis was confirmed by Duplex Ultraso nography on the eighth day after the onset of symptoms. Since clinical examinations and laboratory work excluded any cause of secondary thrombosis, the diagnosis of primary thrombosis was established. The only possible cause of this episode was linked to the woman’s work. The trigger for the thrombotic event was represented most likely by strenuous physical activity with temporary obstruction of the thoracic outlet in the work field. Under anticoagulant treatment, the signs and symptoms gradually resolved. Unfortunately, at the one-year follow-up exam, the patient was diagnosed with post-thrombotic syndrome of the right, dominant arm.

CTRP3 Alleviates Ox-LDL-Induced Inflammatory Response and Endothelial Dysfunction in Mouse Aortic Endothelial Cells by Activating the PI3K/Akt/eNOS Pathway.

C1q/tumor necrosis factor-related protein-3 (CTRP3) is a novel, certified, adipokine that beneficially regulates metabolism and inflammation in the cardiovascular system. Atherosclerotic plaque rupturing and secondary thrombosis cause vascular disorders, such as myocardial infarction and unstable angina. However, the underlying role of CTRP3 in atherosclerosis remains unclear. In this study, we aimed to elucidate whether and how CTRP3 ameliorates inflammation and endothelial dysfunction caused by oxidized low-density lipoprotein (ox-LDL). We first confirmed that CTRP3 expression was inhibited in ApoE-/- mice, compared to normal mice. Then, pcDNA-CTRP3 and siCTRP3 were transfected into mouse aortic endothelial cells after ox-LDL stimulation, and we observed that enhanced CTRP3 remarkably downregulated CRP, TNF-α, IL-6, CD40, and CD40L. We also observed that overexpression of CTRP3 elevated cell activity and decreased lactated hydrogenase release, accompanied by a marked reduction in cell apoptosis induced by ox-LDL. Meanwhile, overexpressed CTRP3 caused a decrease in Ang II, ICAM-1, and VCAM-1 expression, and it restored the balance between ET-1 and NO. Mechanism analysis confirmed that incremental CTRP3 upregulated p-PI3K, p-Akt, and p-eNOS expression, indicating that CTRP3 facilitated activation of the PI3K/Akt/eNOS pathway. On the contrary, siCTRP3 exerted the opposite effect to this activation. Blocking these pathways using LY294002 or L-NAME attenuated the protective role of CTRP3. Overall, these results suggest that CTRP3 can efficiently inhibit the inflammatory response and endothelial dysfunction induced by ox-LDL in mouse aortic endothelial cells, perhaps by activating the PI3K/Akt/eNOS pathway, indicating a promising strategy against atherosclerosis.

Коагуляционный гемостаз у крыс линии Вистар после кратковременной транзиторной ишемии головного мозга

Hemocoagulation properties in rats following a single short-term transient cerebral ischemia were studied for 21 days of the postischemic period using the coarulometric methods involving the automatic optical determination of fibrin clot formation time in the blood plasma. On the 3rd day we observed the lowered activity of the external, internal and general hemocoagulation pathways: the activated partial thromboplastin time (aPTT), prothrombin time (PT) and thrombin time (TT) were increased, indicating the hypocoagulation in the hemostatic system. These changes were accompanied by the increase of the blood fibrinogen levels, probably due to the post-ischemic inflammation. Subsequently, the fibrinogen levels were increased again on the 14th day of the post-ischemic period. That increase was accompanied by the shortening of the aPTT, indicating hypercoagulation following the internal blood clotting pathway mechanisms. At the same day, we observed the increased TT, indicating the acceleration of the fibrin clot formation in the final stage of blood coagulation. Hypercoagulative changes in the hemostasis system developing along the internal and external hemocoagulation pathways were evidenced by the shortening of the aPTT and PT in comparison with the values in the control rats on the 21st day of the post-ischemic period. Thus, the risk of secondary thrombosis persists for 2-3 weeks after a single short-term transient cerebral ischemia.

Direct Oral Anticoagulants As Secondary Prophylaxis in Classical Myeloproliferative Neoplasms

Introduction: Thrombosis is a major cause of morbidity and mortality in patients with classical myeloproliferative neoplasms (MPN), which include polycythemia vera, essential thrombocythemia and primary myelofibrosis. One third of patients with MPN suffer a thrombotic event, either arterial or venous. Despite this, there are no strong data to guide either the selection or duration of anticoagulants for MPN. Warfarin has been primarily used for long-term anticoagulation and is associated with a clear reduction in overall thrombotic events, however 20% of patients will have a recurrent thrombotic event despite ongoing warfarin anticoagulation, corresponding to a failure rate of 4-8% pt-yrs (AnnHematol 2015;94:911-918, Haematologica2008;93:372-380). The overall objective of this study was to evaluate recurrent thrombotic and major bleeding events in MPN-associated thrombosis treated with DOAC versus warfarin.Methods: The primary outcome was to compare the rate of thrombotic events in patients treated with DOAC versus warfarin for secondary thromboprophylaxis (treatment of first clot) among MPN patients. The secondary outcome compared the rate of bleeding events between the two groups. Electronic medical records for patients with a classical MPN diagnosis by PSVG criteria at the University of North Carolina Hospitals were queried to evaluate DOAC or warfarin medication orders between January 1, 2010 and May 31, 2017. Demographic laboratory data, concomitant medications, and incidence and severity of thrombotic or bleeding events were recorded for each MPN patient treated with a DOAC, warfarin, or aspirin. Descriptive statistics were used to characterize the population. Categorical variables were summarized as counts and percentages, while continuous variables were summarized as medians with first to third quartiles. The annual incidence of secondary thrombosis (ie: recurrent event) was calculated by dividing the number of events by the total number of patient-years (pt-yrs). 95% confidence intervals and comparisons were made using a Mid-P exact test. For all analyses, results were deemed significant if P<0.05.Results: We identified 38 total patients diagnosed with a classical MPN, who started either warfarin (n=33), a DOAC (n=4), or aspirin (n=1) for secondary thromboprophylaxis. Median age was 56 years (range 15-98), 40% were male, and 90% Caucasian. No significant differences in the baseline characteristics were observed (Table). For all patients, the initial thrombotic event occurred two years or less prior to the MPN diagnosis. Cytoreductive therapy with either hydroxyurea or anagrelide was used as additional secondary therapy in 28 patients. Patients who received cytoreductive therapy had similar rates of a second thrombus compared to those who did not. Six of the 34 patients who started on either warfarin or aspirin switched to a DOAC, where two of the six were switched after a bleeding event, and none experienced a second thrombus. Seventeen of the 33 patients who started on warfarin, experienced a clot while on therapy with total follow-up of 116.7 pt-yrs. Of those 17 patients, 4 switched to a DOAC and none experienced another thrombotic event at follow-up of 23.7 pt-yrs. The rate of secondary thrombus while on DOAC was 4.2 per 100 pt-yrs (95% CI: 0.2-20.8) compared with a warfarin rate of 14.6 per 100 pt-yrs (95% CI: 8.8-22.9), P=0.2. Eleven bleeding events occurred at a rate of 4.2 per 100 pt-yrs (95% CI: 0.2-20.8) on DOAC compared to 8.6 per 100 pt-yrs (95% CI: 4.4-15.3) on warfarin. This did not lead to a therapy switch in the one DOAC patient, but did lead to a switch in three of 10 warfarin patients (Table).Conclusion: These data suggest that DOACs are comparable to warfarin for preventing recurrent thrombotic events in MPN patients, with a similar risk of bleeding. There was a trend toward fewer thrombotic events in real world MPN-associated thrombosis treated with DOAC versus warfarin, though the small patient numbers do not allow definitive conclusions. Our data adds to the limited published experience using DOACs in MPN and strengthen rationale to pursue future prospective lines of inquiry that evaluate DOACs for secondary thromboprophylaxis in MPN patients. DisclosuresNo relevant conflicts of interest to declare.

A guideline for the management of specific situations in polycythaemia vera and secondary erythrocytosis: A British Society for Haematology Guideline.

The previous BSH guideline for the management of erythrocytosis was published in 2005 (McMullin et al, 2005) and amended in 2007 (McMullin et al, 2007). Here, we re‐evaluate the literature formulate guidance on the management of specific situations encountered in polycythaemia vera (PV) and the management of the other types of secondary erythrocytosis. Recommendations for the diagnostic pathway of investigation of an erythrocytosis, risk stratification and management of PV are in the accompanying guideline (McMullin et al, 2018). We review evidence and outline guidance on management of acute thrombotic events and secondary prevention of thrombosis in PV. The unusual thrombotic events, splanchnic vein and cerebral vein thromboses are discussed and haemorrhage. The specific situations of surgery and pregnancy and guidance on management of pruritus are included. The evidence for the management of other causes of erythrocytosis, including idiopathic erythrocytosis, congenital erythrocytosis, hypoxic pulmonary disease and post‐transplant erythrocytosis, is reviewed and recommendations made.

Research progress of risk factors of pulmonary thromboembolism

Pulmonary embolism is a clinical and pathophysiological syndrome caused by endogenous or exogenous emboli obstructing the pulmonary artery, and its branches causing acute pulmonary circulatory disturbances.Venous thromboembolism is a complex multifactorial disease that involves the interaction of secondary or hereditary thrombosis and various risk factors such as trauma and surgery.With the characteristics of high incidence, misdiagnosis and high mortality, this study explored the risk factors for pulmonary thromboembolism.Finding its risk factors is the main method to reduce the incidence of pulmonary embolism and reduce the severity of pulmonary embolism. Key words: Pulmonary embolism; Thromboembolism; Upper extremity deep vein thrombosis; Venous thromboembolism; Thrombophilia; Risk factors; Review; Databases, bibliographic

The mid/long-term follow-up of endovascular treatment of dissecting aneurysms of the posterior cerebellar artery

Objective To investigate the safety and efficacy of endovascular treatment of dissecting aneurysms of the posterior cerebellar artery (PCA). Methods We retrospectively analyzed 19 consecutive patients with 19 dissecting aneurysms of PCA who underwent endovascular treatment at Department of Neurosurgery, Tangdu Hospital, Air Force Military Medical University between July 2012 and June 2017. Among those, 9 cases received stent-assisted coiling, 2 cases received double stents implanting and 8 cases received occlusion of parent artery. The post-intervention results were evaluated by Raymond Classification. We followed up all cases after discharge by imaging and telephone. Telephone follow-up results were about the clinical outcome and DSA results were evaluated by Raymond Classification. Results All patients in this series were treated successfully. Following initial treatment, there were 11 cases that were graded as class Ⅰ, 5 as class Ⅱ and 3 as class Ⅲ based on Raymond classification. Hemorrhagic event of aneurysmal rupture occurred in 2 cases (1 case with secondary in-stent thrombosis) during treatment and secondary cerebral infarction occurred in 1 case after treatment. All of the 3 cases recovered well at discharge. All cases were followed up for 6-28 months (mean: 13.4±3.1 months). Two patients recovered well based on telephone follow-up. Follow-up imaging results were evaluated by Raymond scale in 17 cases, which reported class Ⅰ in 13 aneurysms, class Ⅱ in 2 aneurysms. The other 2 case with recurrence received second endovascular treatment and had no more recurrence during long-term follow-up. Conclusions The endovascular treatment of dissecting aneurysms of PCA at a single center seems satisfactory and the mid-long term follow-up results are favorable. The endovascular treatment of dissecting aneurysms of PCA seems safe and feasible, which still needs to be confirmed by longer follow-up and controlled studies with larger sample size. Key words: Aneurysm, dissecting; Posterior cerebral artery; Embolization, therapeutic; Follow-up studies; Treatment outcome

Change of Inflammatory Factors in Patients with Acute Coronary Syndrome.

Background:Acute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance.Methods:A total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score <26 (n = 36), moderate CHD group with its Gensini score being 26–54 (n = 48) and severe CHD group with its Gensini score >54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed.Results:The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score <26), moderate CHD group (Gensini score 26–54), and severe CHD group (Gensini score >54) (all P > 0.05).Conclusions:The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.

Principles of pharmacological correction of pulmonary arterial hypertension

Definition and classification: Pulmonary hypertension (PH) is a group of life-threatening progressive diseases of various genesis, characterized by a progressive increase in arterial pressure (AP) in the pulmonary artery (PA), the remodeling of pulmonary vessels, which leads to an increase in pulmonary vascular resistance and pulmonary arterial pressure and more often leads to right ventricular heart failure and premature death. Pulmonary hypertension is clinically divided into five groups: patients in the first group have idiopathic pulmonary arterial hypertension (IPAH), whereas in patients of other groups secondary PH associated with cardiopulmonary or other systemic diseases is observed. The development of secondary LH is caused by congenital heart defects, collagenoses, presence of thrombus in the pulmonary artery, prolonged high pressure in the left atrium, hypoxemia, chronic obstructive pulmonary diseases (COPDs). In case of secondary PH, thrombosis and other changes in the pulmonary veins occur.&#x0D; Ways of pharmacological correction of pulmonary hypertension: Over the last decade pharmacotherapy of PH has been developing rapidly, and the introduction of modern methods of treatment, especially for primary PAH, has led to positive results. However, despite the progress in treatment, the functional limitations and survival of patients remain unsatisfactory. Currently, there are two levels of treatment for pulmonary hypertension: primary and specific pathogenetic therapies. Primary therapy is aimed at the main cause of PH. It also includes supportive therapy. Pathogenetic therapy includes prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. Tactics of therapy can be established on the basis of either clinical classification, or functional class. Prostanoids are a promising group of drugs for the treatment of pulmonary arterial hypertension (PAH), since they possess not only vasodilating, but also antiplatelet and antiproliferative actions. Therefore, it seems logical to use prostacyclin and its analogs to treat patients with various forms of PAH.