Previous Thrombosis Research Articles

Risk-based secondary prevention of obstetric antiphospholipid syndrome

Treatment of pregnant women with antiphospholipid syndrome (APS) should be set apart from that from thrombotic APS patients. Patients with a history of pregnancy morbidity but no vascular thrombosis are usually treated with a prophylactic dose of heparin plus low-dose aspirin; whereas, those with previous vascular thrombosis alone or associated with previous pregnancy morbidity, are commonly treated with a therapeutic dose of heparin generally combined with low-dose aspirin. However, in about 20% of pregnant APS women these regimens fail. In this context, we conducted a case-control study on a large multicentre cohort of conventionally treated pregnancies to verify whether specific laboratory profiles and/or clinical characteristics are predictive of unsuccessful pregnancy outcome during conventional treatments. Multivariate analysis showed that pregnancy failure during conventional therapies was independently associated with a history of both thrombosis and pregnancy morbidity, the presence of systemic lupus erythematosus (SLE) or other systemic autoimmune diseases and triple antiphospholipid antibody positivity. With the aim to discover the most effective and safe treatments in high-risk pregnant APS women a large-scale multicentre study focusing on the effect of treatments on pregnancy outcome in women with APS and further risk factors for pregnancy failure has been designed.

Depressive symptoms, perceived social support, and prothrombotic measures in patients with venous thromboembolism

IntroductionPsychosocial factors have been associated with both a prothrombotic state and an increased risk of venous thromboembolism (VTE). We examined the relation of depressive symptoms and social support with D-dimer, an integrative measure of enhanced coagulation activity, and several additional prothrombotic measures in patients with VTE. MethodsWe studied 173 patients with a previous deep venous thrombosis and/or pulmonary embolism (mean age±SD 45±14years, 55% men). Clinical and lab assessments took place ≥3months after VTE and ≥1month after discontinuation of oral anticoagulants. The patients rated depressive symptoms and social support by validated questionnaires. ResultsAfter adjusting for sociodemographic and medical covariates, interactions emerged between depressive symptoms and social support for D-dimer (p=0.012) and aPTT (p=0.002). As opposed to patients with high levels of social support, those with low levels of social support showed a direct association of depressive symptoms with D-dimer (r=0.19, p=0.014) and an inverse relationship with aPTT (r=-0.14, p<0.09). Depressive symptoms were associated with levels of thrombin-antithrombin complex (r=0.19, p=0.016). Greater social support was associated with prolonged aPTT (r=0.16, p=0.046). There were no significant associations of depressive symptoms and social support with D-dimer, fibrinogen, FII:C, FV:C, FVII:C, FVIII:C, FX:C, INR, and thrombin time. ConclusionsDepressive symptoms are associated with enhanced coagulation activity in patients with VTE, particularly so in those who perceive low levels of social support. Conversely, high levels of social support may contribute directly and through buffering the effect of depressive symptoms to attenuated clotting activity in VTE patients.

Success of Endovenous Saphenous and Perforator Ablation in Patients With Symptomatic Venous Insufficiency Receiving Long-Term Warfarin Therapy

Endovenous ablation of great (GSV) and short saphenous vein (SSV) reflux has become the initial procedure for most patients with symptomatic venous insufficiency, and perforator ablation is increasingly used to assist in healing venous ulceration. Many patients have comorbid conditions, which require long-term anticoagulation with warfarin; however, the impact of a long-term anticoagulation therapy on endovenous ablation procedures is not understood. This study aims to determine the effects of chronic anticoagulation on the outcomes of endovenous ablation procedures in patients with chronic venous insufficiency (CVI). Consecutive patients undergoing endovenous ablation for to Clinical severity (CEAP) class 2 through 6 CVI between January 1, 2005 and May 1, 2011 were evaluated; 781 patients with chronic venous reflux underwent 1,180 endovenous ablation procedures. We identified 45 patients receiving long-term anticoagulation therapy who underwent 71 endovenous ablation procedures, including 37 GSVs, 12 SSVs, and 22 perforator vein procedures. All patients underwent wound examination and duplex ultrasonography within 48 to 72 hours. Outcomes evaluated included closure rate and postoperative complications. The mean age of the patients was 69.7 ± 13 years. Most patients treated presented with active venous ulceration (59% CEAP 6). Indications for anticoagulation included atrial fibrillation (n = 9, 20%), previous deep venous thrombosis (n = 16, 36%), hypercoagulable state (n = 9, 20%), prosthetic valve (n = 2, 4%), and others (n = 9, 20%). All patients receiving warfarin therapy (100%) underwent a postprocedure ultrasonography, which confirmed the successful closure of the GSVs and SSVs; successful initial perforator closure was achieved in 59% of patients (13/22). Repeat perforator ablation yielded a closure rate of 77%. Compared with a matched cohort group of 35 patients (61 perforators) undergoing perforator ablation without anticoagulation, treated during the same period, there was no significant difference in the rates of successful closure between the groups. No patients developed postoperative deep venous thrombosis or pulmonary embolus. No additional thrombotic complications were noted. Three patients (4.2%) developed a small hematoma after the procedure, which resolved with conservative treatment. No patients required postoperative hospital admission, and no postprocedure deaths occurred. Based on our protocol, patients with severe CVI who were receiving long-term warfarin therapy can be treated safely and effectively with endovenous radiofrequency ablation for incompetent GSVs, SSVs, and perforator veins. Long-term warfarin therapy did not have a significant effect on perforator closure rates compared with no anticoagulation.

Impaired responsiveness to clopidogrel and aspirin in patients with recurrent stent thrombosis following percutaneous intervention for peripheral artery disease

Patients with peripheral artery disease (PAD) following peripheral percutaneous transluminal angioplasty (PTA) with stent implantation are prone to stent thrombosis despite treatment with aspirin and clopidogrel. Impaired clopidogrel responsiveness is associated with increased risk of ischemic events in patients following coronary stent implantation. We sought to assess platelet responsiveness to clopidogrel and aspirin in patients with PAD and recurrent stent thrombosis. Platelet aggregation induced by 5 and 20 µmol/l adenosine diphosphate (ADP) and 0.5 mmol/l arachidonic acid (AA), together with platelet reactivity index (PRI) and serum thromboxane B2 (TXB2), were determined in 11 patients with PAD and a history of stent thrombosis (mean, 3.1 ± 1.14) after PTA and in 15 patients with PAD with no such history, also in 11 controls with coronary artery disease (CAD) and previous stent thrombosis. Platelet aggregation to 5 µmol/l ADP was higher in subjects with PAD and stent thrombosis than in those without stent thrombosis (p = 0.0003) and CAD subjects (p = 0.002). Aggregation induced by 20 µmol/l ADP was higher in PAD group with stent thrombosis than in PAD subjects without thrombosis (p = 0.004). The PAD group with stent thrombosis had higher AA-induced platelet aggregation than CAD controls (p = 0.007) and serum TXB2 concentrations higher than PAD group without thrombosis (p = 0.002) and CAD group (p = 0.02). Concluding, platelet responsiveness to clopidogrel and aspirin is impaired in patients with PAD and recurrent stent thrombosis following PTA, as compared with similar individuals with CAD, and PAD with no history of stent thrombosis. This indicates that atherosclerosis burden affects platelet function and might contribute to stent thrombosis following percutaneous intervention in peripheral arteries.

An acute groin lump: surgical exploration is not always the best option

This is a case of a very unusual cause of an acute groin lump in a 71-year-old woman that was presumed initially to either be an incisional or inguinal hernia. However, with subsequent computed tomography it was shown to be thrombophlebitis of collateral vessels secondary to a previous deep vein thrombosis. This case demonstrates how surgical exploration of acute groin lumps is not without its dangers.

Grossesse et syndrome des antiphospholipides

Antiphospholipid syndrome (APS) is associated with a risk of obstetrical complications, affecting both the mother and the fetus. Obstetrical APS is defined by a history of three consecutive spontaneous miscarriages before 10 weeks of gestation (WG), an intra-uterine fetal death after 10 WG, or a premature birth before 34 WG because of severe pre-eclampsia, eclampsia or placental adverse outcomes (intrauterine growth retardation, oligohydramnios). Pregnancy in women with a diagnosis of obstetric APS is at increased risk for placental abruption, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome and thrombosis that may be part of a catastrophic antiphospholipid syndrome (CAPS). A previous thrombosis and the presence of a lupus anticoagulant are risk factors for pregnancy failure. A multidisciplinary approach, associating the internist, the anesthesiologist and the obstetrician, is recommended for these high-risk pregnancies. Preconception counseling is proposed to identify pregnancy contraindications, and to define and adapt the treatment prior and during the upcoming pregnancy. Heparin and low-dose aspirin are the main treatments. The choice between therapeutic or prophylactic doses of heparin will depend on the patient's medical history. The anticoagulant therapeutic window for delivery should be as narrow as possible and adapted to maternal thrombotic risk. There is a persistent maternal risk in the postpartum period (thrombosis, HELLP syndrome, CAPS) justifying an antithrombotic coverage during this period. We suggest a monthly clinical and biological monitoring which can be more frequent towards the end of pregnancy. The persistence of notches at the Doppler-ultrasound evaluation seems to be the best predictor for a higher risk of placental vascular complications. Treatment optimization and multidisciplinary antenatal care improve the prognosis of pregnancies in women with obstetric APS, leading to a favorable outcome most of the time.

Guidelines on the investigation and management of antiphospholipid syndrome

This guidance updates and replaces the previous guideline on the investigation and management of antiphospholipid syndrome (APS) published in 2000 (Greaves et al, 2000), though where there have not been changes we refer back to them when appropriate. The guidance is updated with reference to relevant publications since 2000. Publications known to the writing group were supplemented with additional papers identified by searching PubMed for publications in the last 11 years using the key words: lupus anticoagulant, anticardiolipin, antiphospholipid, b2–glycoprotein I, antiprothrombin and limits (clinical trial, randomized control trial, meta-analysis, humans, core clinical journals, English language). The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the Royal College of Obstetricians and Gynaecologists (RCOG), and the British Committee for Standards in Haematology (BCSH) Committee and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found at http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMEN DATION/43_GRADE.html. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of patients with antiphospholipid syndrome though individual patient circumstances may dictate an alternative approach.

Cerebral Infarct in a Patient with a History of Systemic Arterial and Venous Thrombosis from Essential Thrombocythemia

Although essential thrombocythemia (ET) may involve thrombotic complications, including arterial or venous thrombosis, there are no reports of major vascular complications, including both arterial and venous thrombosis, in a patient with ET. We report on a patient with a cerebral infarction affecting the right lateral thalamus and a stenotic lesion of the right posterior cerebral artery. This arterial thrombotic event may be related to ET, which was based on results of a bone marrow biopsy specimen. The patient had experienced previous events of thrombosis, splenic infarction with venous thrombosis, and myocardial infarction. The cause of recurrent ischemic events involving both arterial and venous systems may be sustained elevation of platelet counts. Previous thrombosis is an established risk factor for rethrombosis in patients with ET. Efficient cytoreductive therapy with an antiplatelet agent should be considered for the prevention of recurrent thrombosis.

Pediatric Systemic Lupus Erythematosus: More Than a Positive Antinuclear Antibody

Based on strong research evidence and consensus, the most common disease manifestations at diagnosis of pSLE are constitutional symptoms, arthritis, and malar rash. Based on some research evidence and consensus, patients with pSLE tend to have major organ system involvement (renal/central nervous system) and a greater disease burden compared with adults. Despite these findings, mortality is low. Based on some research evidence and consensus, the diagnosis of pSLE is unlikely if the ANA is negative, and most patients with SLE have a positive ANA at a titer ≥1:160. Based on strong research evidence, both MMF and cyclophosphamide can be used for induction therapy in class III and IV lupus nephritis. Based on strong research evidence, patients with SLE and anticardiolipin antibodies or LA have a two and six times greater risk of venous thrombosis, respectively, compared with patients with SLE without antiphospholipid antibodies. Based on strong research evidence, patients with pSLE have a higher risk for subclinical atherosclerosis when there is weight-adjusted prednisone use, azathioprine use, increasing age, male gender, high BMI, abnormal creatinine clearance, and elevated lipoprotein(a) levels.

Atypical Vascular Involvement in a Case of Behçet's Disease

Introduction. Behçet's disease (BD) is a form of vasculitis of unknown etiology which is rare in our environment. It is characterized by a variety of clinical manifestations and usually affects young adults. Recurrent oral and genital ulcers are a characteristic and extremely frequent symptom, but mortality is linked with more significant symptoms such as aortic pseudoaneurysm, pulmonary pseudoaneurysm, and cerebral venous thrombosis. Patient and Method. We present a case of a young male with atypical BD and severe polyvascular involvement (previous cerebral venous thrombosis and current peripheral venous thrombosis, acute ischemia, and peripheral arterial pseudoaneurysm) who required urgent surgical intervention due to a symptomatic external iliac pseudoaneurysm. Result. The pseudoaneurysm was successfully treated, we performed an iliofemoral bypass, and we treated it with steroids and immunosuppressive therapy. Conclusions. These rare clinical manifestations highlight the importance of considering BD in young patients, even in usual cases of vascular intervention, whether arterial or venous in nature.

Optimal Management of Antiplatelet Therapy and Proton Pump Inhibition Following Percutaneous Coronary Intervention

Dual antiplatelet therapy (aspirin and a P2Y(12) antagonist) is required after the insertion of a coronary artery stent. If the stent has been inserted in the context of an acute coronary syndrome (ACS), then clopidogrel or a high-potency P2Y(12) antagonist such as prasugrel or ticagrelor should be considered. Current indications for the use of prasugrel in this situation include ST elevation, diabetes, or previous stent thrombosis on clopidogrel therapy. If the stent has been inserted electively for stable ischemic heart disease, then the patient should normally receive clopidogrel. Next, it is important to consider the patient's bleeding risk. The CRUSADE score can be used to determine the likelihood of a subsequent gastrointestinal (GI) bleed. For patients treated with aspirin and clopidogrel who are at high risk of a GI bleed, the current evidence suggests that a proton pump inhibitor (PPI) is the most effective way to reduce this risk. There is evidence that omeprazole may attenuate the pharmacodynamic effect of clopidogrel and, therefore, it would be reasonable to use an alternative PPI that has less risk of negative pharmacokinetic and pharmacodynamic interaction, such as pantoprazole. If a patient is at moderate or low risk of bleeding, then a PPI should be avoided in combination with clopidogrel as the risk of negative interaction is greater than the risk of GI bleeding. There is no substantive evidence that PPIs attenuate the therapeutic effect of prasugrel or ticagrelor; therefore, patients at moderate or high risk of GI bleeding should be offered a PPI.

Heparin-Induced Thrombocytopenia in Liver Transplant Recepients

Abstract 4668 Background:Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated drug reaction, resulting in a platelet count decrease of 50% within 5 to 10 days after heparin administration. HIT is often associated with venous and/or arterial thrombosis (HITT). The clinical course of HIT developing after liver transplantation (LT) had not been reported. Direct thrombin inhibitors (DTI) were reported to be safe and efficacious in patients who developed HIT yet their safety and efficacy had not been determined in patients who had LT. Also, the optimal management of HIT developing after LT has not been defined. Objectives:To evaluate the incidence and the clinical course of patients who developed HIT after LT and the safety of use of DTI in this population. Methods:We performed a retrospective analysis of all patients who had a LT and had clinical HIT confirmed by the anti-PF4/heparin (HIT) antibody by ELISA at our institution between January 2006 and July 2011. A positive test is defined as optical density of > 0.4 with > 50% inhibition. Bleeding was defined per GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) scale. Alternate causes of thrombocytopenia were excluded by relevant hematologic testing. Results:During the study period, 438 patients received LT and163 patients were diagnosed with clinical HIT in our 689 bed hospital. Clinical HIT was confirmed in 11 LT patients (2.5%) based on a positive HIT antibody. LT cases constitute 11/163 (6.75%) of all HIT diagnosed in our center. Clinical characteristics of these are described in attached table. Previous thrombosis was reported in 7/11 (63%) patients, of these 5/11 (46%) received prior therapeutic anticoagulation. Baseline thrombocytopenia below 150K was present in 10/11 (90%) cases and 7/11 (63%) had INR prolongation ≥ 1.5. HIT was documented in 2 patients before LT, in 3 patients within 14 days of surgery and in 6 patients more than 14 days post LT. Six (54%) developed HITT and 7/11 (63%) were treated with a DTI (bivalirudin in 6 cases and argatroban in 1 case). On discharge 2/11 (18%) received fondaparinux and 5/11 (45%) received warfarin. Median dose of IV bivalirudin was 0.3 (0.09-0.89) mg/kg/hr. Platelet recovery was noted in all patients at mean of 9.8 (3-30) days. Progressive thrombosis was noted in 2/11 (18%). Moderate bleeding events within 40 days of LT included 2 gastrointestinal bleeds and one episode of epistaxis. Two traumatic bleeds occurred with prolonged anticoagulation for HITT. No deaths or amputations were documented as a direct consequence of HIT. Only one patient with HIT and LT died as a complication of sepsis.Clinical characteristics of HIT in LT patients: n=11M:F8:3Median age48 (18–75)%Platelet decline57% (16–94)Days from heparin exposure8 (3–20)Nadir platelet count40 (4–94)*4T score calculation:≤354–536–83Bleeding GUSTO scale:mild1 (9%)moderate3 (27%)severe0Progressive thrombosis2 (18%)*-one patient with myeloproliferative disease excluded. Conclusion:HIT is common (2.5%) in LT recipients despite low rates of deep venous thromboprophylaxis with heparin due to underlying coagulopathy. Basal thrombocytopenia is frequent in these patients and widely accepted 4T probability score has low predictive value. The risk of HITT and progressive thrombosis is high. Despite baseline coagulopathy, in our experience the use of DTI, especially bivalirudin, seems to be well tolerated and efficacious in this population. Future studies are needed to optimize dosing to reduce bleeding risk. Disclosures:Off Label Use: Use of bivalirudin and fondaparinaux in the treatment of heparin-induced thrombocytopenia.

No Thrombotic Risk in Patients with Asymptomatic Antiphospholipid Antibodies

Abstract 5254 Aim of the study.Antiphospholipid antibodies (APA) are well known risk factor for thromboembolic events and/or obstetric complications. They may be found incidentally in patients without thrombotic complications (asymptomatic APA), and they often lead to an incorrect suspicion of hemorrhagic diathesis, as well as to an unnecessary disqualification from surgical procedures or withdrawal from a proper antithrombotic prophylaxis during these procedures. The aim of the study was to register venous and/or thrombotic events in a group of patients with asymptomatic APA, diagnosed according to the international guidelines (Myakis et all. 2006). Material and methods.The study group consisted of 25 patients (18 women and 7 men) of the mean age of 46 years (20 – 75 years). Concomitantly 9 of them had other autoimmune disorders (no systemic lupus erythematosus) and 4 had neoplasms. Among risk factors for arterial thrombosis 5 patients had hypercholesterolemia, 5 – hypertension, 4 were smokers and 4 were obese (BMI >30 kg/m2). None of the patients had hereditary thrombophilia (antithrombin, protein C or protein S deficiency, factor V Leiden, prothrombin G20210A mutation, increased activity of factor VIII). Family history of venous thromboembolic disease has been noticed in 4 patients and of arterial thrombosis in 6 patients. The observation lasted for 3 to 127 months (mean 35 months). Results.The number and percent of patients (n = 25) with abnormal results 997337of different laboratory diagnostic assays for APA:AssessmentaPTT - n (%)dRVVT - n (%)ACA - n (%)anti-β2-GPI - n (%)initial24 (96)23 (92)11 (44)10 (40)after 12 weeks24 (96)22 (88)9 (36)11 (44)aPTT-activated partial thromboplastin time; dRVVT - diluted Russell viper venom time; ACA-anticardiolipin antibodies; β2-GPI – anti-β2–glycoprotein I antibodiesAbnormal results of more than one assay in any combination were found in 16 patients, lupus anticoagulant alone in 9 patients. Only 4 out of 25 patients have taken aspirin - 75mg daily, in the other 4 a prophylactic dose of low molecular weight heparin was administered temporarily because of surgery.During observation time no venous or arterial thrombotic events occurred in the study group. On a basis of a limited number of previous studies that predominantly included systemic lupus erythematosus patients, aPL-positive patients without previous thrombosis have a 0% to 3.8% annual incident thrombosis risk (Barbhaiya M, Erksan D. Curr Rheumatol Rep. 2011; 13: 59–69).In two patients asymptomatic APA disappeared. Conclusion:independently of the type and quantity of asymptomatic antiphospholipid antibodies, there were no venous or arterial thromboembolic events in the group of patients observed for meanly 35 months. Disclosures:No relevant conflicts of interest to declare.

Thrombosis in MPN with Thrombocythemia Is Associated with Higher Platelet Count At the Time of the Event: Data From the Czech Registry of Patients Treated with Anagrelide,

Abstract 3857▪▪This icon denotes a clinically relevant abstract Background:Recent studies of prognostic parameters in Ph- myeloproliferative neoplasms with thrombocythemia (MPN-t) indicate that WBC counts at diagnosis, rather than platelet (Plt) counts, determine the risk of thrombosis. We have studied these and other risk parameters in our patient cohort. Patients:843 prospectively assigned patients from the Czech segment of the International registry of patients treated with anagrelide (ANG; Thromboreductin®) were studied. The male: female ratio was 2:3, the median age was 51 (0–96) years. The majority of patients (68.1%) was pretreated by other cytoreducing drugs. According to PVSG criteria, the diagnoses were the following: essential thrombocythemia – 569, primary myelofibrosis – 155, polycythemia vera – 92, or other – 27 patients. Data from the time of diagnosis, from the time of registry entry (at the start of ANG therapy) and from the time of the thrombotic event were evaluated. The median follow-up since registry entry was 33 (0–117) months and the follow-up comprised 2505 patient-years. All patients were treated with ANG and in 80% of follow-up reports, acetylsalicylic acid (ASA) was mentioned to be given in parallel. In 18% of entries (from registration and follow-up), administration of another cytoreducing drug (mainly hydroxyurea or interferon) in combination with ANG was noted. Results:Of 449 thrombotic events reported, 335 occurred in history (i.e. before registry entry) and 114 during follow-up. The numbers of arterial, venous, and microcirculatory events in history were 147, 124 and 64, respectively. Of the 114 thrombotic events in 88 patients during follow-up (3.79 events/100 patient-years), 45 were classified as major. There were 61 arterial, 16 venous and 37 microcirculatory events. ANG ± ASA therapy dramatically decreased the number of venous events (7.8-fold), while arterial and microcirculatory events were reduced 2.4-fold and 1.7-fold, respectively.At diagnosis, the strongest predictors of all thrombotic events jointly were JAK2 V617F mutation (P=0.001), hereditary or acquired thrombophilia (P<0.001), hypertension (P=0.006), smoking (P=0.02) and diabetes mellitus (P=0.04). Also previous thrombosis predicted a subsequent thrombotic event (P=0.002). Age >65 yrs was a less powerful predictor (P=0.08). WBC and hematocrit levels positively correlated with the thrombotic risk (P=0.002 and P=0.006, respectively), whereas Plt counts correlated inversely with all thrombotic events (P=0.012) but correlated positively with microcirculatory events (P=0.01). Some of the factors (age, hypertension, diabetes, and smoking) powerfully predicted rather arterial events, whereas others (f.V “Leiden” mutation, protein C deficiency, elevated f.VIII levels, presence of antiphospholipid antibodies) were connected preferentially with venous events.However, when full blood cell counts from the time of the thrombotic events were studied and compared to mean levels of all entries during follow-up, we could detect higher platelet counts at the time of the thrombotic event (454 vs 420 G/L, P=0.007), while we could not demonstrate any significance of the WBC counts at the time of the event. The correlation of the Plt count was marked in all types of events and was most conspicuous in microcirculatory events. Thrombotic events during follow-up were also associated with lack of ASA therapy: only 6/16 (37.5%) patients at the time of the venous event, 35/61 (57.4%) patients at the time of the arterial event and 11/37 (29.7%) patients at the time of the microcirculatory event received ASA therapy (whereas ASA administration was reported in 80.0% of follow-up entries). Conclusions:The current study indicates that during ANG ± ASA therapy, the incidence of thrombosis is very low in MPN-t and especially the rate of venous events is extraordinarily low. The predictors of the thrombotic events are similar as previously published by others. Above that, we have proven the usefulness of detection of the so-called thrombophilic states. However, in contrast with the prevailing current opinion, we have shown that higher platelet counts (and not WBC counts) are important at the time of thrombosis, albeit at diagnosis the Plt counts may inversely and WBC counts positively correlate with the thrombotic risk. This discrepancy may result from treatment: patients with higher Plt counts at diagnosis may receive more cytoreducing and/or antiaggregation therapy. Disclosures:Schwarz:AOP Pharmaceuticals: Consultancy.

How to manage essential thrombocythemia

I use the hematological, morphological and molecular criteria recently established by the World Health Organization to diagnose essential thrombocytemia. In these patients, major causes of morbidity and mortality are represented by thrombosis and bleeding, whereas progression to myelofibrosis and transformation to acute leukemia are more rare. Myelosuppressive therapy can reduce the rate of vascular complications, but there is some concern about treatment-related toxicity. Therefore, I follow a risk-oriented therapeutic approach to avoid inappropriate exposure to cytotoxic drugs on one side or suboptimal treatment on the other. Established predictors of cardiovascular events are represented by older age and previous thrombosis, whereas recent data suggest a prognostic role for novel risk factors, including leukocytosis and JAK2V617F mutational status. There is no indication for therapeutic intervention in asymptomatic, low-risk patients, while I treat high-risk patients with hydroxyurea (HU) first. Other therapeutic options, such as interferon alpha or anagrelide, may find place in selected patients including those who are resistant or intolerant to HU. I follow a risk-oriented approach also for management of pregnancy. Low-risk women are given low-dose aspirin throughout pregnancy and prophylactic low-molecular-weight heparin (LMWH) post partum, whereas LMWH throughout pregnancy and/or interferon-alpha can be required in high-risk cases.

Post-thrombotic Syndrome Patient Education Based on the Health Belief Model

This study was designed to evaluate patient responses to a patient education handout on post-thrombotic syndrome prevention based on the Health Belief Model. This quasi-experimental pilot study involved a patient survey to be completed after reviewing a patient education handout. A convenience sample of 25 patients with deep vein thrombosis confirmed by venous Doppler assessment with a lower extremity deep vein thrombosis admitted to a Midwestern community hospital was identified. Seven patients were excluded and 5 declined participation; 13 completed the survey patients. Subjects were older than 18 years and able to read and understand English. Patients with hospice or palliative care service or life expectancy less than 6 months were excluded. Subjects were provided with the post-thrombotic syndrome (PTS), patient education handout, and the PTS patient education survey. The PTS patient education handout consisted of a 1-page informational sheet based on PTS and Health Belief Model literature. The 24-item PTS Patient Education Survey required approximately 15 minutes to complete; items included demographic information, questions regarding previous deep vein thrombosis and Likert scale opinion statements regarding PTS based on Health Belief Model components. Patients meeting inclusion criteria were approached by the investigator, invited to participate in the study, and offered the option of having the investigator collect the survey or return in an addressed, stamped envelope. Respondents tended to agree that PTS was a serious condition and that it would negatively affect their life, primarily in relation to comfort and the ability to engage in leisure activities. Ten participants (76.9%) acknowledged that they were susceptible to PTS, and that elastic graduated compression stockings were effective. The most commonly cited barrier to wearing the stockings was difficulty with application. Five patients (38.5%) agreed that they had the ability to prevent PTS and 9 (69.2%) indicated that they intended to wear the stockings. Patient education for post-thrombotic syndrome prevention based on the Health Belief Model resulted in self-reported intention to comply with recommendations to wear graduated elastic compression stockings. Compliance may be enhanced by specifically addressing individual risk factors and barriers to stocking application.

Primary antiphospholipid syndrome: morphofunctional penile abnormalities with normal sperm analysis

To perform a global gonadal and sexual functions assessment in primary antiphospholipid syndrome (PAPS) patients. A cross-sectional study was conducted in 12 male PAPS patients and 20 healthy controls. They were assessed by demographic data, clinical features, systematic urological examination, sexual function, testicular ultrasound, seminal parameters according to the World Health Organization (WHO), seminal sperm antibodies, and hormone profile, including follicle stimulating hormone (FSH), luteinizing hormone (LH), morning total testosterone, and thyroid hormones. The median of current age and age of spermarche were similar in PAPS patients and controls (37.5 vs. 32.4 years, p = 0.270, and 13.1 vs. 12.85 years, p = 0.224, respectively), with a higher frequency of erectile dysfunction in the former group (25% vs. 0%, p = 0.044). Further analysis of PAPS patients with and without previous arterial thrombosis demonstrated that the median penis circumference was significantly lower in PAPS with arterial thrombosis than in PAPS without this complication (8.1 [6-10] vs. 10.2 [10-11] cm, p = 0.007). In addition, the median penis circumference was significantly lower in PAPS patients with erectile dysfunction than in patients without this complication (7.5 [6-9.5] vs. 9.5 [7.5-11] cm, p = 0.039). Regarding seminal analysis, the median sperm concentration, sperm motility, and normal sperm forms by WHO guidelines were comparable in PAPS patients and controls (141.5 [33-575] vs. 120.06 [34.5-329] × 10(6)/ml, p = 0.65; 61.29 [25-80] vs. 65.42 [43-82]%, p = 0.4; 21.12 [10-42.5] vs. 23.95 [10-45]%, p = 0.45, respectively), and none of them had oligo/azoospermia. No differences were observed between PAPS patients and controls regarding the frequency of antisperm antibodies, testicular volume by ultrasound, or hormone profile (FSH, LH, morning total testosterone, and thyroid hormone) (p > 0.05). Normal testicular function has been identified in PAPS patients, in spite of morphofunctional penile abnormalities. Previous arterial thrombosis may underlie penile anthropometry alteration.

Impact of altered venous hemodynamic conditions on the formation of platelet layers in thromboemboli

Although it is generally believed that the structure of venous thromboemboli is a homogeneous red blood cell-fibrin clot, their structure may be heterogeneous, with non-uniformly distributed platelet layers, known as the lines of Zahn. We tested (a) whether venous thromboemboli ex vivo contained platelet layers, i.e. the lines of Zahn, and (b) whether, according to mathematical modeling, eddies can arise in the venous system, possibly contributing to platelet aggregation. The structure of venous thromboemboli ex vivo was determined by high-resolution magnetic resonance imaging (MRI) and by immunohistochemistry (IHC). High-resolution ultrasound (US) imaging was employed to determine the popliteal vein geometry and hemodynamics in healthy subjects and in subjects with previous venous thrombosis. The US data were then used as input for numerical simulations of venous hemodynamics. MRI and IHC confirmed that 42 of 49 ex vivo venous thromboemboli were structurally heterogeneous with platelet layers. The peak venous flow velocity was higher in patients with partly recanalized deep vein thrombosis than in healthy subjects in the prone position (46 ± 4 cm/s vs. 16 ± 3 cm/s). Our numerical simulation showed that partial venous obstruction with stenosis or malfunctioning venous valves creates the conditions for eddy blood flow. Our experimental results and computer simulation confirmed that the heterogeneous structure of venous thromboemboli with twisted platelet layers may be associated with eddy flow at the sites of their formation.

Risk, Clinical Features, and Outcomes of Thrombosis Associated With Pediatric Cardiac Surgery

Thrombosis, usually considered a serious but rare complication of pediatric cardiac surgery, has not been a major clinical and/or research focus in the past. We noted 444 thrombi (66% occlusive, 60% symptomatic) in 171 of 1542 surgeries (11%). Factors associated with increased odds of thrombosis were age <31 days (odds ratio [OR], 2.0; P=0.002), baseline oxygen saturation <85% (OR, 2.0; P=0.001), previous thrombosis (OR, 2.6; P=0.001), heart transplantation (OR, 4.1; P<0.001), use of deep hypothermic circulatory arrest (OR, 1.9 P=0.01), longer cumulative time with central lines (OR, 1.2 per 5-day equivalent; P<0.001), and postoperative use of extracorporeal support (OR, 5.2; P<0.001). Serious complications of thrombosis occurred with 64 of 444 thrombi (14%) in 47 of 171 patients (28%), and were associated with thrombus location (intrathoracic, 45%; extrathoracic arterial, 19%; extrathoracic venous, 8%; P<0.001), symptomatic thrombi (OR, 8.0; P=0.02), and partially/fully occluding thrombi (OR, 14.3; P=0.001); indwelling access line in vessel (versus no access line) was associated with lower risk of serious complications (OR, 0.4; P=0.05). Thrombosis was associated with longer intensive care unit (+10.0 days; P<0.001) and hospital stay (+15.2 days; P<0.001); higher odds of cardiac arrest (OR, 4.9; P<0.001), catheter reintervention (OR, 3.3; P=0.002), and reoperation (OR, 2.5; P=0.003); and increased mortality (OR, 5.1; P<0.001). Long-term outcome assessment was possible for 316 thrombi in 129 patients. Of those, 197 (62%) had resolved at the last follow-up. Factors associated with increased odds of thrombus resolution were location (intrathoracic, 75%; extrathoracic arterial, 89%; extrathoracic venous, 60%; P<0.001), nonocclusive thrombi (OR, 2.2; P=0.01), older age at surgery (OR, 1.2 per year; P=0.04), higher white blood cell count (OR, 1.1/10(9) cells per 1 mL; P=0.002), and lower fibrinogen (OR, 1.4/g/L; P=0.02) after surgery. Thrombosis affects a high proportion of children undergoing cardiac surgery and is associated with suboptimal outcomes. Increased awareness and effective prevention and detection strategies are needed.

Acquired dysfibrinogenemia in atherosclerotic vascular disease

Acquired qualitative abnormalities of fibrinogen molecules, termed acquired dysfibrinogenemia, have been demonstrated in several disease states mostly related to prothrombotic tendency, including multiple myeloma and liver disease. Fibrin is abundant in atherosclerotic plaques. Altered plasma fibrin properties, reflected usually by reduced clot permeability and impaired fibrinolysis, have been reported in patients with acute or prior myocardial infarction, ischemic stroke, and peripheral artery disease. Moreover, prothrombotic clot phenotype has been observed in patients with previous no-reflow phenomenon and stent thrombosis. Growing evidence indicates that acquired dysfibrinogenemia contributes to the progression of atherosclerotic vascular disease and the occurrence of its thrombotic manifestations. The review summarizes current knowledge on the links between fibrin clot phenotype and atherosclerotic vascular disease and describes a wide spectrum of cardiovascular risk factors as modifiers of fibrin network characteristics.