Thrombotic Changes Research Articles

Aspirin with or without statin in the treatment of endotheliitis, thrombosis, and ischemia in coronavirus disease.

INTRODUCTION: In the genesis of coronavirus disease (COVID-19), there is a process of endotheliitis associated with thrombotic changes, no studies have reported the use of acetylsalicylic acid (ASA) as a possible therapeutic approach. Statins could potentiate the ASA therapy. METHODS: This is a series of 14 cases with a laboratory-confirmed diagnosis of COVID-19. All patients underwent the ASA therapy. Those who had risk factors for vascular disease also underwent the high-potency statin therapy. When symptoms were totally or practically resolved, patients were discharged and advised to continue medications for a complementary time, according to the clinical evolution of each patient. RESULTS: The mean age of monitored patients was 48.6 years. A total of 78.6% patients presented with at least one comorbidity, which could have contributed as a risk factor for a poor prognosis in the evolution of COVID-19. Four patients had secondary bacterial infections; three patients needed hospitalization. None of the cases progress to stage III, and all patients had remission of symptoms, with 100% survival. CONCLUSIONS: the process of endothelial dysfunction in COVID-19 involves disseminated thrombosis, initially microvascular and later expansion into larger vessels. ASA could act as a secondary prophylaxis and prevent thrombosis from developing and reaching stage III of the disease. As this was a case series, we cannot provide definitive conclusions; however, this study allows us to formulate hypotheses and support clinical trials to evaluate benefits of the ASA therapy in the treatment of COVID-19.

In silico and in vitro studies reveal complement system drives coagulation cascade in SARS-CoV-2 pathogenesis

The emergence and continued spread of SARS-CoV-2 have resulted in a public health emergency across the globe. The lack of knowledge on the precise mechanism of viral pathogenesis is impeding medical intervention. In this study, we have taken both in silico and in vitro experimental approaches to unravel the mechanism of viral pathogenesis associated with complement and coagulation pathways. Based on the structural similarities of viral and host proteins, we initially generated a protein-protein interactome profile. Further computational analysis combined with Gene Ontology (GO) analysis and KEGG pathway analysis predicted key annotated pathways associated with viral pathogenesis. These include MAPK signaling, complement, and coagulation cascades, endocytosis, PD-L1 expression, PD-1 checkpoint pathway in cancer and C-type lectin receptor signaling pathways. Degree centrality analysis pinned down to MAPK1, MAPK3, AKT1, and SRC are crucial drivers of signaling pathways and often overlap with the associated pathways. Most strikingly, the complement and coagulation cascade and platelet activation pathways are interconnected, presumably directing thrombotic activity observed in severe or critical cases of COVID-19. This is complemented by in vitro studies of Huh7 cell infection and analysis of the transcriptome and proteomic profile of gene candidates during viral infection. The most known candidates associated with complement and coagulation cascade signaling by KEGG pathway analysis showed significant up-regulated fold change during viral infection. Collectively both in silico and in vitro studies suggest complement and coagulation cascade signaling are a mechanism for intravascular coagulation, thrombotic changes, and associated complications in severe COVID-19 patients.

MORPHOLOGICAL AND IMMUNOGISTOCHEMICAL CHARACTERISTICS OF PLACENTAL DISORDERS IN WOMEN WITH PREECLAMPSIA IN PREGNANCY AFTER ART

Pregnancy resulting from the use of ART is classified as a high risk of preeclampsia. The etiology of preeclampsia is not well understood.The aim of the research was to study the morphological and immunohistochemical signs of placental abnormalities in women with preeclampsia during pregnancy after ART.Materials and research methods. A pathomorphological and immunohistochemical study was carried out on 20 placentas of women in the main group who became pregnant after using ART: 10 placentas of women with preeclampsia and 10 placentas without preeclampsia, 10 placentas of healthy women with spontaneous physiological pregnancy (control group). Monoclonal antibodies to the CD31 + factor, VEGF and von Willebrand factor were used.The results of the research. For women with preeclampsia, pronounced phenomena of degenerative changes in the tissue of the membranes of the placenta and placental tissue are characteristic. Cases with moderate inflammatory infiltration in the placental membranes were observed. Characteristic were manifestations of severe subtotal fibrinoid villi necrosis with severe degenerative-sclerotic changes in the presence of lipid metabolism disorders, the phenomenon of syncytiotrophoblast hyperplasia with the formation of nodules and manifestations of blood rheology disorders. On the fruit surface of the membranes, layering of fibrin with an admixture of lymphohistiocytic inflammatory infiltration is noted, in the lumens of the vessels - parietal formation of fibrin thrombi with the phenomena of erythrolimphostasis. In the majority (70%) of the placenta, hemorrhages were noted, located mainly around the vessels. An immunohistochemical study with monoclonal antibodies to CD31 + showed a marked decrease in the expression of endothelial cells after ART with preeclampsia of a relatively high level of expression in physiological pregnancy. The high and increased level of expression of von Willebrand factor after ART corresponds to the severity of sclerotic and thrombotic changes in the tissue of the placenta. A high level of VEGF expression during preeclampsia was revealed compared with a slight expression during physiological pregnancy.Findings. In the placenta of women with preeclampsia, immunohistochemical studies revealed pronounced changes indicating the presence of endothelial dysfunction, sclerotic and thrombotic changes, and instability of the vascular wall. Both pathomorphological and immunohistochemical changes in the placenta were more pronounced with the early development of preeclampsia, which corresponds tomodern views on the placental origin of early preeclampsia and non-placental - late.

Why Does Large Venous Pouch Thrombose after Cerebral Arteriovenous Shunts Embolization?

Why Does Large Venous Pouch Thrombose after Cerebral Arteriovenous Shunts Embolization?

Assessment of deep venous thrombosis in the lower extremity in Behçet's syndrome: MR venography versus Doppler ultrasonography.

Lower extremity venous thrombosis (DVT) is the most common vascular manifestation of Behçet's syndrome (BS). Currently, Doppler ultrasonography (USG) is the most commonly preferred imaging modality in the diagnosis and follow-up of patients with acute and chronic DVT. Magnetic resonance (MR) venography, a quick and a non-invasive imaging modality, is successfully used to detect DVT in various settings. We had been unaware of studies with MR venography in BS. The aim of this study is to compare the diagnostic value of true fast imaging with steady-state precession magnetic resonance (True-FISP MR) venography and Doppler USG in the assessment of chronic DVT among patients with BS. 28 BS patients with chronic lower extremity DVT were studied. Common femoral (CFV) and femoral vein (FV) on both right and left sides were examined for the presence of thrombosis, recanalisation, collaterals and reflux. There are findings of chronic DVT in all Doppler USG images of 28 patients (45 of 56 FV and 35 of 56 CFV), while MR venography detects chronic thrombotic changes in 26/28 (93%) patients (43 of 52 FV and 28 of 52 CFV). Collateral veins are detected in 19 patients (19/28) with MR venography, whereas they are present in only 7 (7/28) with USG (P = 0.003). Furthermore, patients with severe post-thrombotic syndrome are more likely to have collateral formation on the MR compared to those without (12/14 vs 7/14; P = 0.043). Among patients with BS, MR venography might be an alternative or additional method to detect chronic thrombosis in the lower extremities.

IS THERE A PLACE FOR HIGH-RESOLUTION ANOSCOPY IN THE DIAGNOSTICS OF INFLAMMATORY CHANGES IN PATIENTS WITH CHRONIC HEMORRHOIDS?

AIM: to evaluate the significance of high-resolution anoscopy (HRA) in diagnostics of inflammatory and thrombotic changes in hemorrhoid piles and to assess the efficacy of micronized purified favonoid fraction (MPFF) in patients with inflammatory thrombotic changes of hemorrhoids according to HRA results in the preoperative conservative treatment of hemorrhoids. PATIENTS AND METHODS: a prospective cohort study included 77 patients with grade III chronic hemorrhoids. Patients were divided into 3 groups depending on the degree of development of inflammatory and thrombotic changes according to the HRA. The 3 group included patients with preoperative conservative treatment by MPFF. All patients underwent Milligan-Morgan procedure with further histological study of removed piles. RESULTS: it was found that the diagnostic sensitivity of the HRA in detection of inflammatory thrombotic changes was 91.3 % (CI=83.6-96.2 %), and diagnostic specificity - 40 % (CI=19-64 %). HRA diagnostic accuracy was 82.1 % (p=0.001). A 30 % decrease in the number of removed piles with moderate inflammatory thrombotic changes after MOFF therapy has also been revealed. CONCLUSION: HRA permits to determine the severity of thrombotic inflammatory changes, which is extremely importantfor the management of patients with acute hemorrhoids.

Nanoparticles in endothelial theranostics.

The paper presents the recent advances in the development and studies of multifunctional nanoparticles which can be used to prevent/cure the cardiovascular diseases by detecting, treating and monitoring the early stages of atherosclerotic and thrombotic changes in endothelium.

203 Ticagrelor and Clopidogrel Attenuate the Prothrombotic State induced by Bacterial Endotoxaemia

Introduction In the PLATO study, the novel platelet P2Y 12 inhibitor ticagrelor was unexpectedly associated with fewer deaths following pulmonary infections and sepsis than clopidogrel. The risk of myocardial infarction or stroke is greatly increased following bacteremia, which can create an inflammatory environment associated with thrombotic changes in the fibrin network. We therefore aimed to determine whether greater P2Y 12 inhibition by ticagrelor compared to clopidogrel would result in greater reduction in platelet-leukocyte interactions, thereby reducing inflammatory responses and the prothrombotic state associated with inflammation. Methods Thirty healthy volunteers were randomised to ticagrelor 90 mg bd (n = 10), clopidogrel 75 mg od (n = 10) or no antiplatelet medications (controls; n = 10) for one week. E. coli endotoxin (LPS) 2 ng/kg was then administered intravenously. Plasma fibrin clot density was assessed ex vivo using a validated turbidimetric assay and D-dimer was measured using the INNOVANCE assay. Fibrin clot structure was investigated ex vivo using scanning electron microscopy. Fibrin network density and fibrin diameter were determined using imageJ software. Informed consent was obtained. The study was approved by a medical ethics committee and funded by the Medical Research Council (UK). Results In the control group, fibrin clot maximum absorbance (an indicator of fibrin clot density), increased by 109 ± 37% at 6 h after LPS administration compared to baseline (p Conclusion To our knowledge, this is the first study to show that ticagrelor reduces prothrombotic changes in fibrin clot structure induced by bacterial endotoxaemia in vivo . The greater potency of the effects of ticagrelor compared to clopidogrel provides a potential mechanism for the reduced mortality following sepsis observed in the PLATO study.

Aspirin therapy is associated with less compact fibrin networks and enhanced fibrinolysis in patients with abdominal aortic aneurysm

Thrombotic changes in fibrin networks contribute to increased cardiovascular risk in patients with abdominal aortic aneurysm (AAA). Given that aspirin modulates the fibrin network, we aimed to determine if aspirin therapy is associated with changes in ex-vivo fibrin clot characteristics in AAA patients and also conducted an exploratory analysis of 5-year mortality in these individuals. We recruited 145 male patients, divided into controls (aortic diameter <3cm, n=49), AAA not taking aspirin (AAA-Asp, n=50) and AAA on 75mgday(-1) aspirin (AAA+Asp, n=46), matched for aneurysm size. Characteristics of clots made from plasma and plasma-purified fibrinogen were investigated using turbidimetric analysis, permeation studies, and confocal and electron microscopy. Plasma fibrinogen, D-dimer and inflammatory marker levels were also measured. Maximum absorbance (MA) of plasma clots from controls was lower than that of AAA patients not on aspirin (AAA-Asp) at 0.30±0.01 and 0.38±0.02au, respectively (P=0.002), whereas aspirin-treated subjects had MA similar to controls (0.31±0.02 P=0.9). Plasma clot lysis time displayed an identical pattern at 482±15, 597±24 and 517±27s for control, AAA-Asp and AAA+Asp (P=0.001 and P=0.8). The lysis time of clots made from purified fibrinogen of AAA-Asp was longer than that of AAA+Asp patients (756±47 and 592±52s, respectively; P=0.041). Permeation studies and confocal and electron microscopy showed increased clot density in AAA-Asp compared with the AAA+Asp group. Mortality in AAA-Asp and AAA+Asp was similar, despite increased cardiovascular risk in the latter group, and both exhibited higher mortality than controls. Aspirin improves fibrin clot characteristics in patients with AAA, which may have important clinical implications.

Evaluation of the markers of inflammation in the umbilical cord blood of newborns of mothers with thrombophilia.

To answer the question as to whether the markers of thrombophilia in pregnant women, whose pregnancies ended in success, are reflected in the level of inflammation in the blood of the umbilical cord of the newborn. Umbilical cord blood and placenta after childbirth were secured from 16 patients with inherited (n=7), acquired (n=9) thrombophilia, and control group (n=20). The concentrations of cytokines IL1β, IL10, TNFα, C5a anaphylatoxin, and granzyme A were assessed. decay accelerating factor (DAF) and membrane cofactor protein (MCP) levels were determined in the placentas, and the incidence of thrombotic changes was evaluated. Higher levels of anaphylatoxin C5a (P=0.041), TNFα (P=0.016), and IL1β (P=0.037) were observed in the study group compared to the control group. In the study group, C5a levels correlated with the levels of TNFα (P=0.018) and IL1β (P=0.012). Higher levels of DAF and MCP proteins in study group were found in the control group (P<0.001). In placentas from study group, there was a more frequent occurrence of incidences of thrombotic changes. The observed, increased levels of pro-inflammatory factors in the cord blood of newborns of mothers with thrombophilia may result from a reaction of the prothrombotic and pro-inflammatory markers of thrombophilia present in maternal blood.

Late inflammatory and thrombotic changes in irradiated hearts of C57BL/6 wild-type and atherosclerosis-prone ApoE-deficient mice.

Radiation-induced heart disease represents a late complication of thoracic radiotherapy. We investigated the inflammatory and thrombotic response after local heart irradiation in wild-type and atherosclerosis-prone mice. Atherosclerosis-prone ApoE(-/-) and C57BL/6 wild-type mice were sacrificed 20, 40, and 60 weeks after irradiation with 0.2, 2, 8, or 16 Gy. The expression of CD31, vascular cell adhesion molecule-1 (VCAM-1), thrombomodulin (TM), and CD45 were quantified by immunofluorescence staining of heart tissue sections. Microvascular density decreased at 40 weeks after 16 Gy in C57BL/6 but not in ApoE(-/-) mice. CD31 expression declined in C57BL/6 mice at 40 weeks (8 Gy), but increased in ApoE(-/-) mice at 20 (2/8/16 Gy) and 60 weeks (16 Gy). Capillary area decreased in C57BL/6 at 40 weeks (8/16 Gy) but increased in ApoE(-/-) mice at 20 weeks (16 Gy). Endocardial VCAM-1 expression remained unchanged. TM-positive capillaries decreased at 40 weeks (8/16 Gy) in C57BL/6 and at 60 weeks (2/16 Gy) in ApoE(-/-) mice. Leukocyte infiltration transiently rose 40 weeks after 8 Gy (only ApoE(-/-)) and 16 Gy. After receiving a low irradiation dose of 0.2 Gy, no significant changes were observed in any of the mouse models. This study demonstrated that local heart irradiation affects microvascular structure and induces inflammatory/thrombotic responses in mice in a dose- and time-dependent manner. Thereby, significant prothrombotic changes were found in both strains, although they were progressive in ApoE(-/-) mice only. Proinflammatory responses, like the increase of adhesion molecules and leukocyte infiltration, were more pronounced and occurred at lower doses in ApoE(-/-) vs. C57BL/6 mice. These findings indicate that metabolic risk factors, such as decreased ApoE lipoproteins, may lead to an enhanced proinflammatory and prothrombotic late response in locally irradiated hearts.

Neurovascular complications of ovarian hyperstimulation syndrome (OHSS): from pathophysiology to recent treatment options.

Ovarian hyperstimulation syndrome (OHSS) is a severe iatrogenic complication of ovulation induction, which has a very serious impact on the patient's health, as it is often associated with a high morbidity and mortality risk. Indeed, patients classified as having severe OHSS presented with liquid imbalance signs (such as rapid weight gain, tense ascites, respiratory difficulty and progressive oliguria), which are related to the fluid shift from the intravascular space to third space compartments subsequent to an increased capillary permeability. In this way, cardiovascular system findings include decreased intravascular volume, decreased blood pressure, decreased central venous perfusion, and compensatory increased heart rate and cardiac output with arterial vasodilation might be found concomitantly. Notwithstanding that venous thromboembolic phenomena are a possible complication in advanced phases of OHSS, arterial ischemia involving the cerebral circulation is a rare but recently reported problem. The pathogenesis of thromboembolism in OHSS is not fully understood, even though hemoconcentration and blood hyperviscosity seem to play a role in developing thrombotic changes into both venous and arterial system. Interestingly, the presence of cardiac abnormalities in combination with inherited or acquired hypercoagulable state seems to increase the risk of cerebral infarct in these subjects, as recently shown by our group. This review is aimed at investigating the pathomechanism and the management of neurovascular complications related to OHSS, including new treatment options.

Cavernous carotid artery aneurysms: Epidemiology, natural history, diagnostic and treatment. An experience of a single institution

BackgroundCavernous carotid aneurysms (CCA) account for 2–9% of all intracranial aneurysms. They have been considered benign lesions, most often asymptomatic, and to have a natural history with a low risk of life-threatening complications. These aneurysms are unique, their rupture can present in many different forms, they can suffer spontaneous thrombotic changes and the symptomatology related to the mass effect involves the neuro-ophthalmologic system. In this scenario the natural history and clinical presentation are largely different from other intracranial aneurysms. Some investigators advocate treatment of both symptomatic and asymptomatic CCAs, others recommend no treatment. The reason for this controversy relates to a lack of information on the long term natural history of these aneurysms, as well as on the long term results of treatment. MethodsIn this article the authors discuss their single institution experience in diagnosis, natural history and management of 123 asymptomatic and oligosympotomatic aneurysms located in the cavernous portion of internal carotid artery. ConclusionsAccording to our results asymptomatic or olygosymptomatic (pain) CCAs should be conservatively managed with serial images while the others presentations should be analyzed by a multidisciplinary team, involving the neuroendovascular and microsurgical services.

Thrombotic safety of prothrombin complex concentrate (Beriplex P/N) for dabigatran reversal in a rabbit model

IntroductionIn vivo animal data have shown prothrombin complex concentrate (PCC) to be effective in preventing bleeding induced by excessive plasma levels of the direct thrombin inhibitor dabigatran. This animal model study was designed to determine the risk of thrombosis associated with administration of a PCC (Beriplex P/N) to reverse dabigatran-induced bleeding. Materials and methodsAnesthetized rabbits were treated with initial 0, 75, 200 or 450μgkg-1 dabigatran boluses followed by continuous infusions to maintain elevated plasma dabigatran levels. At 15min after the start of dabigatran administration, PCC doses of 0, 50 or 300IUkg-1 were administered. Thereafter, coagulation in an arteriovenous (AV) shunt was evaluated and histopathologic examination for thrombotic changes performed. Venous thrombosis was also assessed in a modified Wessler model. ResultsAt the suprapharmacologic dose of 300IUkg-1, PCC increased thrombus weight during AV shunting, but this effect could be prevented by dabigatran at all tested doses. AV shunt occlusion after PCC administration was delayed by 75μgkg-1 dabigatran and abolished by progressively higher dabigatran doses. High-dose treatment with 300IUkg-1 PCC resulted in histologically evident low-grade pulmonary thrombi; however, that effect could be blocked by dabigatran in a dose-dependent manner (p=0.034). In rabbits treated with high-dose PCC, dabigatran inhibited thrombus formation during venous stasis. PCC effectively reversed dabigatran-induced bleeding. ConclusionsIn this animal study, thrombosis after PCC administration could be prevented in the presence of dabigatran. PCC reversed dabigatran-induced excessive bleeding while retaining protective anticoagulatory activity of dabigatran.

Radiotherapy and anthracyclines - cardiovascular toxicity.

The subject of this paper is to analyze the impact of radiotherapy and anthracyclines on the cardiovascular system, based on a survey of contemporary literature. Currently, high efficiency of anticancer therapies has increased the rate of survival in patients treated for cancer. It should be emphasized, however, that these treatments damage not only the affected but also the healthy tissue. Consequently, with the increase of survival rate in these patients, the number of patients with complaints regarding numerous organs and systems also increases as a result of earlier treatment. Thus, during the first decade of the 21st century, a number of concerns about the relationship between cancer treatment and dysfunction of the cardiovascular system were resolved. Anthracyclines, as well as radiotherapy, are capable of damaging the cardiovascular system, both at the central level, by the deterioration of cardiac function, and at peripheral levels, by increasing the hemodynamic and thrombotic changes.

Arterial and venous thrombosis of the cerebral vasculature in GAPO syndrome

A 37-year-old male, previously diagnosed with GAPO syndrome, was admitted to our hospital complaining of recurrent episodes of transient weakness and numbness in his left arm for 3 months, and severe headache with progressive dysphagia for 15 days. His cranial magnetic resonance (MR) images showed multiple ischemic foci in the bilateral periventricular and supraventricular white matter. Cerebral MR-angiography showed total occlusion of the right internal carotid artery and moderate stenosis in the left internal carotid. We also detected chronic thrombotic changes in the distal left sigmoid sinus, proximal right sigmoid sinus, and bilateral jugular veins on cerebral MR-venography. He was diagnosed with dilated cardiomyopathy at age 31 years, which was reported as a novel association; and later he had a myocardial infarction at age 34 years. To the best of our knowledge, this is the first patient with GAPO syndrome and arterial atherosclerosis in cerebral-as well as coronary-arteries and intracranial venous thrombosis. We report the evolution of the disease in this patient, who died at age 38 years due to respiratory failure secondary to lower respiratory tract infection.

Update on Cardiac Tumors – review (RCD code: VI)

The prevalence of cardiac tumors is 0.021% (1 person in 5000). These data are based on a meta-analysis of pathological studies from the early decades of the twentieth century. It is likely that nowadays the incidence of cardiac tumors and primary tumors of the heart is greater. The cardiac tumors are very rare and histologically heterogeneous. These leads to, the lack of established diagnostic schemes, that would allow to distinguish cardiac tumors from metastatic tumors, intracardiac thrombus, vegetations on the valves in infective endocarditis or in the process of connective tissue diseases or thrombotic changes of the valves in the process of metastatic disease (called endocarditis marantica). Cardiac tumors may be symptomatic or found incidentally during evaluation for a seemingly unrelated problem or physical finding. In symptomatic patients, a mass can virtually always be detected by echocardiography, magnetic resonance imaging (MRI), and/or computed tomography (CT). Because symptoms may mimic other cardiac conditions, the clinical challenge is to consider the possibility of a cardiac tumor so that the appropriate diagnostic tests can be conducted. There are very few studies, assessing the results of cardiac surgery in the individual centers. There is also lack of set of standards in the chemotherapy of malignant cardiac tumors. Moreover its routine use is sometimes discussed. JRCD 2014; 1 (8): 5–10

Paroxysmal Nocturnal Hemoglobinuria and Magnetic Resonance Imaging

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare and complex disease characterized by a severe prothrombotic state caused by a complement system mediated hemolysis. The introduction of the anti-C5 antibody, Eculizumab, has been conducted in many Hematology units worldwide to adopt new diagnostic tools to evaluate new and old PNH patients in order to consider the adequacy of the adoption of this new drug in each case.Magnetic Resonance Imaging (MRI) allows a more adequate and profitable approach in PNH that other radiology techniques used for this purpose. In the last four years Hematology and Radiology units in our Hospital have collaborate in the clinical evaluation of PNH patients performing MRI (cranioencephalic, thoracic and/or abdominal) in acute complications of PNH patients (9 patients) or as a programmed protocoled evaluation previous to consider Eculizumab treatment (14 patients).The protocoled evaluation consists in thoracic and abdominal MRI evaluations in all cases, and cranioencephalic MRI (with independence of the presence of neurological symptoms) in 9 cases. The PNH patients were examined with 1.5 Teslas magnet for cranioencephalic,thoracic and abdominal MRI and with 3.0 Teslas magnet for some cranioencephalic MRI (Achieva Magnets; Philips Healthcare, Best, The Netherlands).Different protocols designed for the study of this pathology, using morphological sequences with different empowerment, functional sequences and angiographic studies after administration of intravenous contrast (gadobutrol) have been used. In the abdominal explorations had been performed calculations of T2 * for the quantification of deposit of iron in liver and kidney.The first group of patients (incidental studies in acute/chronic situations) included Classical and with other bone marrow failure syndrome (BMFS) Parker's types. The second group (protocoled studies previous consideration of Eculizumab therapy) consisted on 11 Classical Parker's type patients with active hemolysis (LDH increased 3-13 times over normal levels) and elevated PNH clone (73-99% negative GPI granulocytes by FLAER cytometry); and 3 with BMFS Parker's type patients (LDH increased 2-6 times over normal levels) with lower PNH clone (43-50% negative GPI granulocytes by FLAER cytometry). Thrombosis was found in four cases, one in the inferior cava and and three arterial (two cerebral and one in descendent aorta). In three patients this finding implied to initiate Eculizumab therapy. Minor ischemic brain changes were displayed by three patients. None of the eighteen patients explored with thoracic MRI, displayed pulmonary hypertension signs despite the elevation of pro-BNP in eight of them. Iron overload in the liver and/or kidneys were very frequent. The finding of a reversal of the normal cortical and medullary intensities on T1 and T2 weighted images of both kidneys was evident in the majority of patients with severe PNH types. Interestingly, one patient with a chronic PNH severe form displayed no renal iron cortical after two years on Eculizumab therapy. This finding was also evident in patients with active hemolysis in the past but with very low PNH clones and clinical remission of the disease.Many other incidental discoveries includes cholelithiasis, splenomegaly, kidney arterial vessel constriction, vascular anomalies, kidney and vesical stones, adrenal adenoma, atheromatosis at different levels, Tornwaldt cyst, hamartoma, hemangiomas and abnormal bone marrow signal.MRI is the best imaging technique to diagnose thrombosis in PNH patients and to control evolution. Moreover, in the cerebrovascular setting allows a more fine and precise diagnosis of the minor pathologic thrombotic changes. MRI is the only imaging technique that permits to evaluate the iron overload that in some PNH cases could be underestimated and needs quelation therapy. In our opinion all new patients with classical severe hemolytic PNH must be evaluated prospectively with MRI. The collaboration of the Radiology team with the Hematologist is fundamental to acquire expertise in this rare disease. Disclosures:Pastrana:Alexion Pharmaceuticals: Speakers Bureau. Ojeda:Alexion Pharmaceuticals: Consultancy, Speakers Bureau.

Posttraumatic Stress Disorder as a Risk Factor for Cardiovascular Disease: A Literature Review and Proposed Mechanisms

Emotional stress has long been associated with cardiovascular disease (CVD), however it is relatively recent that the evidence for a causal link has been more firmly established. While the term posttraumatic stress disorder (PTSD) has only been described since the 1970s, there is now substantial evidence, among various populations, that PTSD is associated with increased CVD risk, and that this risk is independent of other CVD risk factors. Although it is not possible to identify any one single mechanism responsible for the associations observed, it is likely that increased haemodynamic forces, inflammatory and thrombotic changes as well as elevated cholesterol levels are contributors. Despite the logistic difficulties in researching the physiological responses to PTSD, this should be a priority area for future research to guide therapies targeted at reducing CVD risk associated with this major stress disorder.

SAT0204 Fetal Placental Thrombotic Abnormalities Correlate with Anti-Centromeric Anti-Nuclear Antibody Pattern in Systemic Sclerosis Pregnancies

BackgroundSystemic sclerosis (SSc) is an autoimmune condition characterized by microvascular, skin and multi-organ involvement. As it usual arises in the reproductive years, a number of these patients plans (or achieves)...