Trombolisis dirigida por catéter en paciente con oclusión arterial periférica aguda / Catheter-directed thrombolysis in patients with acute peripheral arterial occlusion

Introducción: Las oclusiones arteriales periféricas agudas de menos de 14 días y de causa embólica y trombótica están asociadas a una alta morbimortalidad. La trombólisis dirigida por catéter representa en la actualidad una modalidad de tratamiento efectivo para la oclusión de vasos distales infrageniculares, que históricamente ha tenido malos resultados mediante embolectomía convencional, debido a la oclusión preexistente de vasos colaterales y al daño mecánico al endotelio, que conlleva esta técnica tradicional. Se decidió presentar este caso por ser la primera vez que se practica esta modalidad de tratamiento en Cuba. Objetivo: Exponer los resultados obtenidos con la aplicación de la trombolisis fibrinolitica mediante catéter en un paciente afectado por trombosis arterial periférica aguda. Presentación del caso: Paciente masculino de 57 años de edad con diagnóstico de trombosis arterial aguda de la arteria poplítea del miembro inferior izquierdo, con más de 24 horas de evolución de la isquemia y del compromiso de la viabilidad de la extremidad. Se utilizó el tratamiento fibrinolítico, mediante infusión de 250 000 unidades de Heberkinasa® en tres horas y se logró la mejoría del nivel de amputación. Conclusiones: El tratamiento fibrinolítico con Heberkinasa® fue útil en el paciente tratado porque redujo el nivel de amputación en el paciente, que presentó isquemia irreversible y criterio inicial de amputación supracondílea alto, en la extremidad comprometida(AU)

Introduction: Acute peripheral arterial occlusions of less than 14 days and of embolic and thrombotic cause are associated with a high morbidity and mortality. Catheter-directed thrombolysis currently represents an effective treatment modality for the occlusion of infragenicular distal vessels, which has historically had poor results by conventional embolectomy, due to the pre-existing occlusion of collateral vessels and the mechanical damage to the endothelium, which this traditional technique entails. It was decided to present this case because it is the first time that this modality of treatment is practiced in Cuba. Objective: Present the results obtained with the application of fibrinolytic thrombolysis by catheter in a patient affected by acute peripheral arterial thrombosis. Case presentation: A 57-year-old male patient diagnosed with acute arterial thrombosis of the popliteal artery of the left lower limb, with more than 24 hours of evolution of ischemia and compromised viability of the limb. Fibrinolytic treatment was used, by infusion of 250,000 units of Heberkinase® in three hours and the improvement of the amputation level was achieved. Conclusions: Fibrinolytic treatment with Heberkinase® was useful in the treated patient because it reduced the level of amputation in the patient, who presented irreversible ischemia and initial criteria of high supracondylar amputation in the compromised limb(AU)

Internal carotid artery thrombosis in COVID 19 / Trombosis de arteria carótida interna en COVID 19

Abstract Case description: 37-year-old female with PCR-RT swab for COVID-19 positive, with neurological manifestation as a result of internal carotid artery occlusion. Clinical findings: Nasal congestion and sneezing of 5 days duration; pulsatile headache in the left hemicranium 3 days prior to admission, with intensity 6/10 according to the visual analogue scale, accompanied by phosphenes, photophobia and diplopia; with subsequent developing right hemiparesis over a 26-hour period. Treatment and result: She was given medical management with oral antiplatelet agents and anticoagulants (subcutaneous and oral) during his hospitalization, it was not possible to perform thrombolysis and thrombectomy due to the high risk of complications. He was discharged at 14 days, without functional limitation, symmetrical strength in upper and lower limbs, bilateral visual acuity 20/20, denying headache. Clinical relevance: The case presented here describes a pattern in how data supporting an association between COVID-19 and stroke in young populations with or without typical vascular risk factors, sometimes with only mild respiratory symptoms, is increasing. Prospective studies are required to further evaluate this association, as well as anticoagulation studies to prevent these potentially life-threatening events.

Resumen Descripción del caso: Mujer de 37 años con hisopado PCR-RT para COVID-19 positivo, con manifestación neurológica por oclusión de la arteria carótida interna. Hallazgos clínicos: Congestión nasal y estornudos de 5 días de duración; cefalea pulsátil en hemicráneo izquierdo 3 días antes del ingreso, con intensidad 6/10 según la escala visual analógica, acompañada de fosfenos, fotofobia y diplopía; con posterior desarrollo de hemiparesia derecha durante un período de 26 horas. Tratamiento y resultado: Se le brindó manejo médico con antiagregantes plaquetarios orales y anticoagulantes (subcutáneos y orales) durante su internación, no fue posible realizar trombólisis y trombectomía por alto riesgo de complicaciones. Fue dado de alta a los 14 días, sin limitación funcional, fuerza simétrica en miembros superiores e inferiores, agudeza visual bilateral 20/20, negando cefalea. Relevancia clínica: Se describe un patrón que indica cómo están aumentando los datos que apoyan una asociación entre COVID-19 y el accidente cerebrovascular en poblaciones jóvenes con o sin factores de riesgo vascular típicos, a veces con solo síntomas respiratorios leves. Se requieren estudios prospectivos para evaluar más a fondo esta asociación, así como estudios de anticoagulación para prevenir estos eventos potencialmente mortales.

Internal carotid artery thrombosis in COVID 19.

CASE DESCRIPTION: 37-year-old female with PCR-RT swab for COVID-19 positive, with neurological manifestation as a result of internal carotid artery occlusion. CLINICAL FINDINGS: Nasal congestion and sneezing of 5 days duration; pulsatile headache in the left hemicranium 3 days prior to admission, with intensity 6/10 according to the visual analogue scale, accompanied by phosphenes, photophobia and diplopia; with subsequent developing right hemiparesis over a 26-hour period. TREATMENT AND RESULT: She was given medical management with oral antiplatelet agents and anticoagulants (subcutaneous and oral) during his hospitalization, it was not possible to perform thrombolysis and thrombectomy due to the high risk of complications. He was discharged at 14 days, without functional limitation, symmetrical strength in upper and lower limbs, bilateral visual acuity 20/20, denying headache. CLINICAL RELEVANCE: The case presented here describes a pattern in how data supporting an association between COVID-19 and stroke in young populations with or without typical vascular risk factors, sometimes with only mild respiratory symptoms, is increasing. Prospective studies are required to further evaluate this association, as well as anticoagulation studies to prevent these potentially life-threatening events.

DESCRIPCIÓN DEL CASO: Mujer de 37 años con hisopado PCR-RT para COVID-19 positivo, con manifestación neurológica por oclusión de la arteria carótida interna. HALLAZGOS CLÍNICOS: Congestión nasal y estornudos de 5 días de duración; cefalea pulsátil en hemicráneo izquierdo 3 días antes del ingreso, con intensidad 6/10 según la escala visual analógica, acompañada de fosfenos, fotofobia y diplopía; con posterior desarrollo de hemiparesia derecha durante un período de 26 horas. TRATAMIENTO Y RESULTADO: Se le brindó manejo médico con antiagregantes plaquetarios orales y anticoagulantes (subcutáneos y orales) durante su internación, no fue posible realizar trombólisis y trombectomía por alto riesgo de complicaciones. Fue dado de alta a los 14 días, sin limitación funcional, fuerza simétrica en miembros superiores e inferiores, agudeza visual bilateral 20/20, negando cefalea. RELEVANCIA CLÍNICA: Se describe un patrón que indica cómo están aumentando los datos que apoyan una asociación entre COVID-19 y el accidente cerebrovascular en poblaciones jóvenes con o sin factores de riesgo vascular típicos, a veces con solo síntomas respiratorios leves. Se requieren estudios prospectivos para evaluar más a fondo esta asociación, así como estudios de anticoagulación para prevenir estos eventos potencialmente mortales.

Traumatic injury to the internal carotid artery by the hyoid bone: a rare cause of ischemic stroke

Central nervous system (CNS) ischemic events, besides being a common and devastating disease, are accompanied by severe disability and other morbidities. The cause of such events is not always that simple to diagnose, and among the young, a broad spectrum of possibilities should be considered. We present the case of a young man who presented two episodes of CNS ischemia with a 1 year gap between them, which occurred in the same situation while he was walking and carrying a heavy backpack. The second event first presented as a transient ischemic attack followed by a stroke the day after. The diagnostic work-up showed an indentation of the greater cornu of the hyoid bone over the internal carotid artery, which injured the media and intimal layers. At the arterial injury site, a micro thrombus was found, which explained the source of the embolic event to the CNS. The patient was operated on, and the procedure included the resection of the posterior horn of the hyoid bone, the resection of the injured segment of the internal carotid artery followed by carotid­carotid bypass with the great saphenous vein. The postoperative period and the recovery were uneventful as was the 5-month follow-up. We call attention to this unusual cause of stroke and present other cases reported in the literature.

Modulation of miR-26a-5p and miR-15b-5p exosomal expression associated with Clopidogrel-induced hepatotoxicity in HepG2 Cells

Clopidogrel is an essential antiplatelet drug used to prevent thrombosis complications associated with atherosclerosis. However, hepatotoxicity is a potential adverse effect related to clopidogrel therapy. Exosome-derived miRNAs may be useful for improved monitoring of drug response and hepatotoxicity risk. In the present study, the expression of several exosomal miRNAs (miR-26a-5p, miR-145-5p, miR-15b-5p, and miR-4701-3p) and cell-derived mRNA targets (PLOD2, SENP5, EIF4G2, HMGA2, STRADB, and TLK1) were evaluated in HepG2 cells treated with clopidogrel (6.25, 12.5, 25, 50, and 100 μM) for 24 and 48 h. Then, clopidogrel cytotoxicity was evaluated by analyzing DNA fragmentation and the cell cycle profile using flow cytometry. Differential expression of exosome-derived miRNAs and cell-derived mRNAs was analyzed by RT-qPCR. Exposure of HepG2 cells to high concentrations of clopidogrel (50 and 100 μM) for 24 h caused significant DNA fragmentation (17.6 and 44.4%, respectively; p < 0.05) and 48 h (26.8 and 48.9%, respectively; p < 0.05), indicating cellular toxicity...

Utilidad de la ecografía Doppler en el diagnóstico de la trombosis carotidea traumática / Usefulness of Doppler echography for the diagnosis of traumatic carotid thrombosis

Los traumatismos del sistema arterial carotideo son raros y tienen alta mortalidad. Se presenta un caso de trombosis de la arteria carótida interna derecha por una herida por arma de fuego a nivel del cuello con el objetivo de evidenciar en la práctica médica la utilidad de la ecografía Doppler para el diagnóstico temprano de estas lesiones, a pesar de reportarse en la literatura la angiografía, la resonancia magnética nuclear y la angiorresonancia como estudios de elección. Con este caso se pudo afirmar que la trombosis carotidea traumática tiene una incidencia baja, pero no descartable en los traumas de la región cervical. Por esta causa, son frecuentes las complicaciones neurológicas dadas por la oclusión arterial y la ecografía Doppler resultó muy útil en el diagnóstico temprano del paciente.

Carotid artery system traumas are rare and show high mortality rates. The case of right internal carotid artery thrombosis caused by a gunshot injury in the neck was presented in this report to show evidence of the usefulness of Doppler echography in the medical practice for the early diagnosis of these lesions in spite of the fact that literature highlights angiography, nuclear magnetic resonance and angioresonance as the imaging studies of choice. This case confirmed that carotid thrombosis due to trauma has low incidence but it can not be ignored in the cervical región traumas. For these reasons, the neurological complications stemming from artery occlusion are frequent and Doppler echography turned to be very useful for the early diagnosis of this illness in a patient.

Comportamiento de anticardiolipinas en gestantes / Anticardiolipins behavior in pregnant

Objetivo: Evaluar los niveles de anticuerpos anticardiolipina en gestantes portadoras del síndrome antifosfolipídico que fueron tratadas en la consulta de medicina interna durante el período 2001-2012. Métodos: Estudio de campo, descriptivo, longitudinal. La población que se estudió fue de 86 pacientes portadoras del síndrome antifosfolipídico. No se tomó en cuenta el criterio del intervalo de al menos 12 semanas para el diagnóstico definitivo. Resultados: En relación con los niveles de IgM e IgG de anticuerpos anticardiolipinas el promedio más alto (30,98) y (19,62) predominó en el primer trimestre del embarazo. El nivel mayor de IgM que se evidenció fue 198, mientras que el menor fue 0,6 durante toda la gestación. Los anticuerpos IgM en el tercer trimestre disminuyeron en 55,81 % con respecto al primer trimestre. Conclusiones: A pesar de que los niveles de anticuerpos son impredecibles, en las últimas etapas de la gestación los anticuerpos anticardiolipinas IgM disminuyeron con respecto a las primeras etapas.

Objective: Evaluate the levels of anticardiolipin antibodies for pregnant carrying the antiphospholipid syndrome that were treated in internal medicine, period 2001-2012. Methods: A descriptive, longitudinal non-experimental and field study. The population studied was 86 patients carrying the SAF, did not take into account the criteria in the interval of at least 12 weeks for definitive diagnosis. Results: In relation to the levels of IgM and IgG anticardiolipin antibodies the highest average (30.98) and (19.62) prevailed in the first trimester of pregnancy. The higher level of IgM was 198, while the lowest was 0.6 during the entire pregnancy. IgM anticardiolipin antibodies in the third quarter decreased by 55.81 % over the first quarter. Conclusions: Although antibody levels are unpredictable, in the latter stages of gestation IgM anticardiolipin antibodies decreased with respect to the early stages.

Dysregulated coagulation associated with hypofibrinogenaemia and plasma hypercoagulability: implications for identifying coagulopathic mechanisms in humans.

Identifying coagulation abnormalities in patients with combined bleeding and thrombosis history is clinically challenging. Our goal was to probe the complexity of dysregulated coagulation in humans by characterizing pathophysiologic mechanisms in a patient with both bleeding and thrombosis. The patient is a 56-year-old female with a history of haematomas, poor wound healing, and thrombosis (retinal artery occlusion and transient cerebral ischaemia). She had a normal activated partial thromboplastin time, prolonged thrombin and reptilase times, and decreased functional and antigenic fibrinogen levels, and was initially diagnosed with hypodysfibrinogenaemia. This diagnosis was supported by DNA analysis revealing a novel FGB mutation (c.656A>G) predicting a Q189R mutation in the mature chain that was present in the heterozygote state. However, turbidity analysis showed that purified fibrinogen polymerisation and degradation were indistinguishable from normal, and Bß chain subpopulations appeared normal by two-dimensional difference in-gel electrophoresis, indicating the mutated chain was not secreted. Interestingly, plasma thrombin generation testing revealed the patient's thrombin generation was higher than normal and could be attributed to elevated levels of factor VIII (FVIII, 163-225%). Accordingly, in an arterial injury model, hypofibrinogenaemic mice (Fgn(+/-)) infused with factor VIII demonstrated significantly shorter vessel occlusion times than saline-infused Fgn(+/-) mice. Together, these data associate the complex bleeding and thrombotic presentation with combined hypofibrinogenaemia plus plasma hypercoagulability. These findings suggest previous cases in which fibrinogen abnormalities have been associated with thrombosis may also be complicated by co-existing plasma hypercoagulability and illustrate the importance of "global" coagulation testing in patients with compound presentations.

Thrombomodulin is required for the antithrombotic activity of thrombin mutant W215A/E217A in a mouse model of arterial thrombosis.

INTRODUCTION: The thrombin mutant W215A/E217A (WE thrombin) has greatly reduced procoagulant activity, but it activates protein C in the presence of thrombomodulin and inhibits binding of platelet glycoprotein Ib to von Willebrand factor and collagen under flow conditions. Both thrombomodulin-dependent protein C activation and inhibition of platelet adhesion could contribute to the antithrombotic activity of WE thrombin. MATERIALS AND METHODS: To assess the role of thrombomodulin, we administered WE thrombin to thrombomodulin-deficient (TM(Pro/Pro)) mice and measured the time to occlusive thrombus formation in the carotid artery after photochemical injury of the endothelium. RESULTS AND CONCLUSIONS: Doses of WE thrombin ≥10µg/kg prolonged the thrombosis time of wild-type mice (>1.6-fold), while doses ≥100µg/kg only slightly prolonged the thrombosis time of TM(Pro/Pro) mice. We conclude that thrombomodulin plays a predominate role in mediating the antithrombotic effect of WE thrombin in the arterial circulation of mice after endothelial injury. Thrombomodulin-independent effects may occur only when high doses of WE thrombin are administered.

Trombose de artéria carótida interna relacionada a trauma de palato em criança / Internal carotid artery thrombosis related to trauma of palate in a child

Relatar um caso de trombose de artéria carótida interna secundária relacionada a trauma de palato mole em criança. DESCRIÇÃO DO CASO: Criança admitida com quadro de alteração do nível de consciência, sonolência, afasia e hemiplegia direita; tinha antecedente de trauma corto contuso leve em palato mole há oito horas. A investigação tomográfica evidenciou acidente vascular isquêmico secundário à interrupção do fluxo sanguíneo em território de artéria cerebral média esquerda. A arteriografia mostrou oclusão da artéria carótida interna imediatamente distal à sua origem, com aspecto radiológico de "ponta de lápis", obstruindo o fluxo sanguíneo na região. A paciente foi submetida à investigação para doença pró-trombótica e cardíaca, contudo, não foi detectada nenhuma alteração. A administração de enoxaparina em dose terapêutica por três semanas conduziu à melhora clínica progressiva. Após três semanas de seguimento, a paciente não mostrava sequelas motoras. COMENTÁRIOS: As lesões intraorais são frequentes em crianças e a maioria evolui sem complicações. A trombose da artéria carótida interna é uma complicação rara, mas bem documentada destas lesões e decorre da compressão do vaso com trombogênese localizada. A taxa de mortalidade relatada é de 30 por cento e as sequelas ocorrem em 85 por cento dos casos.

To describe a child with internal carotid artery thrombosis secondary to trauma of the soft palate. CASE DESCRIPTION: Child presented with altered level of consciousness, drowsiness, aphasia, right hemiplegia, and a history of trauma, with mild concussion of the soft palate eight hours prior to admission. CT scan showed ischemic stroke secondary to interruption of blood flow in the area of the left middle cerebral artery. Arteriography showed occlusion of the carotid artery just distal to its origin, with radiological appearance of "pencil tip", obstructing blood flow in the region. Patient underwent investigation for pro-thrombotic and heart diseases, which was negative. The child received enoxaparin at therapeutic dose for three weeks, showing progressive clinical improvement. After three weeks, the patient did not show motor problems. COMMENTS: Intraoral lesions are common in children, but most of them evolve without complications. However, the internal carotid artery thrombosis is a rare but well documented complication of these lesions and results from the vessel compression with localized thrombogenesis. The mortality rate is about 30 percent, and sequels are seen in 85 percent of cases.

Acute carotid occlusion and stroke due to antiphospholipid antibody syndrome: case report and literature review.

Neurologic events associated to antiphospholipoid syndrome (APLS) are not uncommon, but ischemic stroke due to acute carotid thrombosis, is a rare presentation of this syndrome. We report a case of a 48 years old female patient, without evidence of atherothrombosis or other vascular pathology, who presented an ischemic stroke due to acute thrombosis of the left internal carotid artery. The occlusion was diagnosed by Duplex scan and magnetic resonance angiography (Ds+MRA). The patient was anticoagulated and experienced total regression of her neurologic symptoms after a week. Ds+MRA were performed again and confirmed re-establishment of normal flow of internal carotid artery. A thorough clinical investigation confirmed the diagnosis of APLS (the association of a major thombotic event and high anticardiolipoid IgG antibody titers in three blood samples). The patient has been submitted to oral anticoagulation for three years and has not experienced new neurologic or thrombotic events.

Unique extracellular matrix heparan sulfate from the bivalve Nodipecten nodosus (Linnaeus, 1758) safely inhibits arterial thrombosis after photochemically induced endothelial lesion.

Heparin-like glycans with diverse disaccharide composition and high anticoagulant activity have been described in several families of marine mollusks. The present work focused on the structural characterization of a new heparan sulfate (HS)-like polymer isolated from the mollusk Nodipecten nodosus (Linnaeus, 1758) and on its anticoagulant and antithrombotic properties. Total glycans were extracted from the mollusk and fractionated by ethanol precipitation. The main component (>90%) was identified as HS-like glycosaminoglycan, representing approximately 4.6 mg g(-1) of dry tissue. The mollusk HS resists degradation with heparinase I but is cleaved by nitrous acid. Analysis of the mollusk glycan by one-dimensional (1)H, two-dimensional correlated spectroscopy, and heteronuclear single quantum coherence nuclear magnetic resonance revealed characteristic signals of glucuronic acid and glucosamine residues. Signals corresponding to anomeric protons of nonsulfated, 3- or 2-sulfated glucuronic acid as well as N-sulfated and/or 6-sulfated glucosamine were also observed. The mollusk HS has an anticoagulant activity of 36 IU mg(-1), 5-fold lower than porcine heparin (180 IU mg(-1)), as measured by the activated partial thromboplastin time assay. It also inhibits factor Xa (IC(50) = 0.835 microg ml(-1)) and thrombin (IC(50) = 9.3 microg ml(-1)) in the presence of antithrombin. In vivo assays demonstrated that at the dose of 1 mg kg(-1), the mollusk HS inhibited thrombus growth in photochemically injured arteries. No bleeding effect, factor XIIa-mediated kallikrein activity, or toxic effect on fibroblast cells was induced by the invertebrate HS at the antithrombotic dose.

Effects of polysaccharides enriched in 2,4-disulfated fucose units on coagulation, thrombosis and bleeding. Practical and conceptual implications.

Sulfated polysaccharides from marine invertebrates have well-defined structures and constitute a reliable class of molecules for structure-activity relationship studies. We tested the effects of two of these polysaccharides, namely a sulfated fucan and a fucosylated chondroitin sulfate, on coagulation, thrombosis and bleeding. The compounds share similar 2,4-disulfated fucose units, which are required for high anticoagulant activity in this class of polymer. These residues occur either as branches in fucosylated chondroitin sulfate or as components of the linear chain in the sulfated fucan. These polysaccharides possess anticoagulant activity but differ significantly in their mechanisms of action. The fucosylated chondroitin sulfate inhibits thrombin by heparin cofactor II, whereas sulfated fucan inhibits thrombin by both antithrombin and heparin cofactor II. In addition, these polysaccharides also have serpin-independent anticoagulant activities. Fucosylated chondroitin sulfate, but not sulfated fucan, activates factor XII. As a result of the complex anticoagulant mechanism, the invertebrate polysaccharides differ in their effects on experimental thrombosis. For instance, the sulfated fucan inhibits venous thrombosis at lower doses than fucosylated chondroitin sulfate. In contrast, fucosylated chondroitin sulfate is significantly more potent than sulfated fucan in arterial thrombosis. Finally, fucosylated chondroitin sulfate increases bleeding, while sulfated fucan has only a discrete effect. In conclusion, the location of 2,4-disulfated fucose units in the polysaccharide chains dictates the effects on coagulation, thrombosis and bleeding.

Spontaneous thrombosis of internal carotid artery: a natural history of giant carotid cavernous aneurysms.

OBJECTIVE: To describe five cases of giant carotid cavernous aneurysms which evolved with spontaneous thrombosis of internal carotid artery (STICA), with emphasis at epidemiology, clinical presentation, natural history, related factors and neurological outcome. METHOD: There were 711 consecutives patients with 802 aneurysms with and without surgical treatment during a period of 19 years. We selected 35 patients with 40 carotid cavernous aneurysms (5%) of which 20 (50%) were giant aneurysms. Among those cases, 5 patients evolved with STICA (25%). Symptoms and findings at presentation were recorded and compared with those at outcome. RESULTS: Clinical presentation was commonly related to atherosclerotic factors such as elevated blood pressure (80%), diabetes mellitus (40%) and dislipidemy (40%). All patients presented with hemicranial headache, ophthalmparesy and retro bulbar pain, and after STICA all presented improvement of symptoms. After STICA, 4 patients had regression of deficit, 2 partial and 2 complete. Four patients had sensorial trigeminal neuropathy in V1 and V2 territories, also showing improvement of symptoms after STICA. CONCLUSION: STICA is a common outcome in giant carotid cavernous aneurysms, and is related with significant improvement of symptoms; however, it may be catastrophic for those patients without efficient collateral circulation.