Diagnosis of deep vein thrombosis. / Diagnóstico de la trombosis venosa profunda.

Deep vein thrombosis (DVT) is part of the clinical spectrum of venous thromboembolism disease (VTE), whose estimated annual incidence rate is 1-2 episodes per 1000 individuals and represents the third leading cause of cardiovascular mortality in developed countries. Establishing an accurate diagnosis of DVT is essential for preventing acute complications (such as pulmonary embolism) and chronic complications associated with post-thrombotic syndrome. Currently, there are well-established diagnostic algorithms for lower extremity DVT, which include clinical probability models that help establish the risk of experiencing the disease based on the patients' history, clinical findings, D dimer measurements, fibrin degradation product tests with a high negative predictive value and imaging tests to confirm the diagnosis. Venous compression ultrasonography is currently the technique of choice because it is a non-invasive, easy-to-administer test that can make serial evaluations. There is much accumulated evidence that DVT can be safely ruled out in patients with a low or intermediate clinical probability and a negative D dimer (<500 ng/mL) without performing additional examinations. The consensus is not as clear about the need for a proximal or complete examination of the entire extremity. Other techniques may also be employed, such as magnetic resonance venography and venous phase computed axial tomography, although these should not be a substitute for compression ultrasonography as the initial diagnostic test. There are other special circumstances in which the diagnosis is more problematic and there are no diagnostic algorithms as consolidated, such as DVT during pregnancy, diagnosing rethrombosis and DVT that affects the upper extremities.

A prognostic score to identify low-risk outpatients with acute deep vein thrombosis in the upper extremity.

BACKGROUND: No studies have identified which patients with upper-extremity deep vein thrombosis (DVT) are at low risk for adverse events within the first week of therapy. METHODS: We used data from Registro Informatizado de la Enfermedad TromboEmbólica to explore in patients with upper-extremity DVT a prognostic score that correctly identified patients with lower limb DVT at low risk for pulmonary embolism, major bleeding, or death within the first week. RESULTS: As of December 2014, 1135 outpatients with upper-extremity DVT were recruited. Of these, 515 (45%) were treated at home. During the first week, three patients (0.26%) experienced pulmonary embolism, two (0.18%) had major bleeding, and four (0.35%) died. We assigned 1 point to patients with chronic heart failure, creatinine clearance levels 30-60 mL min(-1) , recent bleeding, abnormal platelet count, recent immobility, or cancer without metastases; 2 points to those with metastatic cancer; and 3 points to those with creatinine clearance levels < 30 mL min(-1) . Overall, 759 (67%) patients scored ≤ 1 point and were considered to be at low risk. The rate of the composite outcome within the first week was 0.26% (95% confidence interval [CI] 0.004-0.87) in patients at low risk and 1.86% (95% CI 0.81-3.68) in the remaining patients. C-statistics was 0.73 (95% CI 0.57-0.88). Net reclassification improvement was 22%, and integrated discrimination improvement was 0.0055. CONCLUSIONS: Using six easily available variables, we identified outpatients with upper-extremity DVT at low risk for adverse events within the first week. These data may help to safely treat more patients at home.

Leucopenia asociada al uso de risperidona: presentación de un caso y revisión de la literatura / Leukopenia associated to the use of risperidone: a case report and review of the literature

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Hepatitis isquémica en pacientes con insuficiencia cardiaca / Ischemic hepatitis in patients with heart failure

La hepatitis isquémica o hipóxica es una entidad clínica caracterizada por una importante elevación de las transaminasas de forma aguda y reversible que ocurre en aquellas situaciones que pueden ocasionar una reducción del flujo sanguíneo hepático, especialmente la insuficiencia cardiaca, siempre que se hayan descartado previamente otras causas potencialmente responsables de una hepatitis aguda, especialmente víricas y farmacológicas. Histológicamente se caracteriza por una necrosis centrolobulillar. Presentamos los 3 casos ingresados en un servicio de medicina interna durante un periodo de un año. Su incidencia fue del 2,7 por ciento entre todos los pacientes ingresados durante el mismo periodo con el diagnóstico de insuficiencia cardiaca (AU)

Clinical significance of acquired activated protein C resistance in patients with systemic lupus erythematosus.

Antiphospholipid antibodies (aPL) may induce acquired activated protein C resistance (acquired APCR). The role of acquired APCR in patients with systemic lupus erythematosus (SLE) is not well known. To evaluate the prevalence of acquired APCR and its association with clinical manifestations we studied 103 consecutive SLE patients and 103 matched controls. APCR in the undiluted test and after dilution in factor V deficient plasma, factor V Leiden, protein C and S, lupus anticoagulant, and anti-cardiolipin, anti-beta2-glycoprotein I and anti-prothrombin antibodies were determined. Factor V Leiden was found in 4% in both patients and controls. The prevalence of acquired APCR was 22% for the undiluted assay and 17% in the diluted test. In SLE patients, acquired APCR was associated with aPL (39 vs 13% in undiluted assay, P = 0.007; and 33 vs 7% in the diluted test, P = 0.001). Arterial thromboses were found in 24% of patients with acquired APCR and in 6% of patients without (P = 0.04). However, no relationship was found with venous thrombosis. Acquired APCR was also associated with pregnancy losses: miscarriages in 70% of women with acquired APCR vs 32% in those without (P=0.03). Thus, in SLE patients acquired APCR seems to be associated with increased prevalence of arterial thrombosis and pregnancy losses.

[Valvular heart disease in patients with anti-phospholipid syndrome]. / Cardiopatía valvular en pacientes con síndrome antifosfolipídico.

INTRODUCTION: Anti-phospholipid antibodies (APA) may involve heart and valvular heart disease seems to be the most common clinical manifestation. OBJECTIVES: To study the prevalence and characteristics of valvular heart disease in a large patient population with anti-phospholipid syndrome (APS) and also to analyze the clinical and immunological profile of patients with valvular involvement compared with those without involvement. Patients and methods. Retrospective analysis of 113 patients diagnosed of APS. Eighty-one percent were females and the mean age was 39 years (SD:14). Sixty-two percent of patients were diagnosed of primary APS (70 patients) and the remaining 38% (43 patients) corresponded to patients with APS associated with systemic lupus erythematosus (SLE). The median follow-up of patients was 55 months (range: 7-144 months). The cardiologic assessment was performed by means of transthoracic echocardiogram. The study of anti-lupus anticoagulant (AL) was performed by means of coagulometric assays and measurement of anticardiolipin antibodies (aCL), anti-beta2 glycoprotein I (abeta2-PGI) and anti-prothrombin (aPT) by ELISA. RESULTS: The prevalence of valvular heart disease was 19%. The mitral valve was mostly involved (91%) and the most common structural abnormality corresponded to mitral insufficiency. Valvular replacement was required in 24% of patients. In the subgroup of patients with valvular heart disease, a significantly higher prevalence was observed in the following parameters: total thrombosis (71% versus 49%; p = 0.05), arterial thrombosis (57% versus 23%; p = 0.002), stroke (38% versus 13%; p = 0.01), trombocitopenia (71% versus 45%; p = 0.02), hemolytic anemia (29% versus 9%; p = 0.02), and livedo reticularis (48% versus 3%; p < 0.0001). As for immunological differences, only a higher prevalence of LA was found (81% versus 59%; p= 0.04) and abeta2-GPI (IgG isotype) (43% versus 22%; p = 0.05) in patients with valvular heart disease. CONCLUSIONS: Valvular heart disease is more frequent in pa-tients with APS and mitral insufficiency is the most common lesion. In a patient with the diagnosis of APS, an echocar-digram should be obtained in his/her initial assessment and regular controls should be obtained in the follow-up.

Cardiopatía valvular en pacientes con síndrome antifosfolipídico / Valvular heart disease in patients with anti-phospholipid syndrome

Introducción. Los anticuerpos antifosfolipídicos (AAF) pueden afectar el corazón y la cardiopatía valvular parece ser la manifestación clínica más frecuente. Objetivos. Estudiar la prevalencia y las características de la valvulopatía en una amplia población de pacientes con síndrome antifosfolipídico (SAF), así como analizar el perfil clínico e inmunológico de los pacientes con afectación valvular respecto de aquellos que no la padecen. Pacientes y métodos. Análisis retrospectivo de 113 pacientes diagnosticados de SAF. El 81 por ciento fueron mujeres y la edad media fue de 39 años (DE: 14). El 62 por ciento de los pacientes estaba diagnosticado de SAF primario (70 pacientes) y el 38 por ciento restante (43 pacientes) correspondía a pacientes con SAF asociado a lupus eritematoso sistémico (LES). La mediana del tiempo de seguimiento de los pacientes fue de 55 meses (extremos: 7-144 meses). La valoración cardiológica se efectuó mediante ecocardiografía transtorácica. El estudio del anticoagulante lúpico (AL) se realizó mediante ensayos coagulométricos y la determinación de los anticuerpos anticardiolipina (aCL), anti2-glucoproteína I (a2-GPI) y antiprotrombina (aPT) se efectuó mediante ensayos de ELISA. Resultados. La prevalencia de cardiopatía valvular fue del 19 por ciento. La válvula más frecuentemente afectada fue la mitral (91 por ciento) y la anomalía estructural más común fue la insuficiencia. En el 24 por ciento de los pacientes fue necesario el recambio valvular. En el subgrupo de pacientes con valvulopatía se observó una prevalencia significativamente superior de trombosis totales (71 por ciento frente a 49 por ciento; p = 0,05), trombosis arteriales (57 por ciento frente a 23 por ciento; p = 0,002), accidentes vasculares cerebrales (38 por ciento frente a 13 por ciento; p = 0,01), trombocitopenia (71 por ciento frente a 45 por ciento; p = 0,02), anemia hemolítica (29 por ciento frente a 9 por ciento; p = 0,02) y lívedo reticularis (48 por ciento frente a 3 por ciento; p < 0,0001).Respecto a las diferencias inmunológicas, sólo se encontró una mayor prevalencia del AL (81 por ciento frente a 59 por ciento; p = 0,04) y de los a 2-GPI (isotipo IgG) (43 por ciento frente a 22 por ciento; p = 0,05) en los pacientes con valvulopatía. Conclusiones. La cardiopatía valvular es frecuente en pacientes con SAF y la insuficiencia mitral es la lesión más común. Es recomendable la práctica de una ecocardiografía en todo paciente diagnosticado de SAF en s u valoración inicial y efectuar controles periódicos (AU)

Myelodysplastic and myeloproliferative syndromes associated with giant cell arteritis and polymyalgia rheumatica: a coincidental coexistence or a causal relationship?

A variety of systemic autoimmune disorders have been reported in patients with myelodysplastic and myeloproliferative syndromes. A possible association with polymyalgia rheumatica and giant cell arteritis has also been recognised. We report another case of polymyalgia rheumatica and one of giant cell arteritis associated with a myelodysplastic syndrome and the two first cases of giant cell arteritis associated with essential thrombocytaemia and chronic myelomonocytic leukaemia, respectively. It seems that there is a relationship between these entities, but the nature of this association is still unknown.

Lupus eritematoso sistémico inducido por interferón alfa-2b en una paciente con infección crónica por el virus de la hepatitis C

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Antiphospholipid antibodies and thrombophilic factors in giant cell arteritis.

OBJECTIVES: To evaluate the prevalence of thrombophilic risk factors known to induce intravascular clotting and to assess their relationship with ischemic manifestations in giant cell arteritis (GCA). METHODS: Eighty consecutive patients with established GCA were included: 36 with isolated temporal arteritis (TA), 14 with isolated polymyalgia rheumatica (PMR), and 30 with TA and PMR. Forty-four patients (67%) had ischemic phenomena due to GCA. Twelve patients (15%) had thrombotic events unrelated to GCA (6 strokes, 5 deep venous thrombosis, and 1 myocardial infarction). A control group of 100 age- and sex-matched individuals without autoimmune disease, bleeding disorders, thrombosis, or clinical picture of TA or PMR also was analyzed. All participants were tested for the antiphospholipid antibody (aPL) profile, protein C, protein S, antithrombin activity, factor V Leiden mutation, and prothrombin gene G20210A mutation. We also studied fibrinolysis parameters: plasminogen, tissue-type plasminogen activator (t-PA) antigen, t-PA activity, type-1 plasminogen activator inhibitor (PAI-1) antigen, PAI-1 activity, and the 4G/5G polymorphism of the promoter region of the PAI-1 gene. RESULTS: Eleven patients (18%) tested positive for lupus anticoagulant, 24 (30%) for anticardiolipin antibodies, 9 (11%) for anti-beta 2-glycoprotein I antibodies, and 29 (36%) for antiprothrombin antibodies. No relationship was found between these autoantibodies and ischemic manifestations. None of the patients had decreased protein C, protein S or antithrombin activity. Two patients and 2 controls were heterozygous for factor V Leiden, and only 1 patient and 2 controls were heterozygous for the prothrombin gene G20210A mutation. No statistically significant correlation was found between any thrombophilic factor and GCA-related or GCA-unrelated ischemic events. CONCLUSION: GCA patients have a high prevalence of aPL that is not related to ischemic manifestations. Moreover, GCA-related or GCA-unrelated ischemic manifestations do not appear to be due to congenital thrombophilic risk factors. Semin Arthritis Rheum 31:12-20.

[The treatment and prognosis of sarcoidosis. Apropos 53]. / Tratamiento y pronóstico de la sarcoidosis. A propósito de 53 casos.

OBJECTIVE: We retrospectively studied 53 cases of sarcoidosis which have been diagnosed at our service during de last 14 years. The criteria for starting therapy with corticosteroids and recurrences were analyzed. METHOD: The patients mean (SD) age was 42 (15) years old (range 16-76) and the majority were female (72%). 15 patients (28.3%) received corticosteroids. The only differences with respect to patients not treated were the presence of respiratory symptoms (47% vs 18%; p = 0.04) and the abnormality of spirometric parameters (DLCO/VA p = 0.01; CV p = 0.002). RESULTS: 17 (32%) patients recurred. 14 (82%) of them required corticosteroids. This percentage was significantly greater than that of patients treated at first episode (82% vs 28%, p = 0.0002). All patients improved with treatment. The only difference with respect to patients without recurrences were to be treated at the first episode (53% vs 17%, p = 0.007).

The 4G/5G polymorphism of the type 1 plasminogen activator inhibitor gene and thrombosis in patients with antiphospholipid syndrome.

OBJECTIVE: To investigate the relationship between the 4G/5G polymorphism of the type 1 plasminogen activator inhibitor (PAI-1) gene and thrombotic manifestations in patients with antiphospholipid syndrome (APS). METHODS: We studied a total of 247 patients included in the following 4 groups: 70 patients with primary APS, 104 patients with systemic lupus erythematosus (40 with antiphospholipid antibodies [aPL] and clinical [secondary] APS, 13 with aPL but without clinical APS, and 51 with neither detectable aPL nor a history of thrombosis), 14 asymptomatic individuals with aPL, and 59 patients with thrombosis but without known thrombosis risk factors. A control group of 100 healthy individuals was also analyzed. PAI-1 4G/5G polymorphism was determined by polymerase chain reaction and endonuclease digestion. RESULTS: The allele frequency of 4G/5G in controls was 0.47/0.53. There were no differences in allele distribution among patient groups or between patients and controls. However, a higher frequency of the 4G allele was observed in APS patients with versus those without thrombosis (0.57 versus 0.39; P < 0.05) (odds ratio [OR] 2.83, 95% confidence interval [95% CI] 1.18-6.76). This higher frequency of the 4G allele was attributable to the higher frequency in patients with versus those without arterial thrombosis (0.64 versus 0.43; P < 0.01) (OR 5.96, 95% CI 1.67-21.32), while patients with venous thrombosis had an allele distribution similar to that of those without venous thrombosis (0.49 versus 0.50; P not significant). There was a trend toward higher PAI-1 antigen and activity levels in APS patients and controls with the 4G/4G genotype, but this did not reach statistical significance. CONCLUSION: The presence of the 4G allele of the 4G/5G polymorphism of the PAI-1 gene may be an additional risk factor for the development of arterial thrombosis in APS.

Tratamiento y pronóstico de la sarcoidosis. A propósito de 53 casos / Treatment and diagnosis of sarcoidosis: a serie of 53 cases

Objetivo: Se estudiaron retrospectivamente los 53 casos de sarcoidosis diagnosticados durante los últimos 14 años en nuestro servicio. Método: Se analizaron los criterios utilizados para administrar tratamiento corticoideo y las características de las recidivas. Su edad media (DE) fue de 42 (15) años (extremos 16-76) y predominaba el sexo femenino (72 porciento).15 pacientes (28,3 porciento) se consideraron tributarios de tratamiento corticoideo. Las únicas características diferenciadoras de este grupo de pacientes fueron la existencia de síntomas respiratorios (47 porciento vs 18 porciento; p = 0,04) y la alteración de parámetros espirométricos (DLCO/VA p = 0,01; CV p = 0,002). Resultados: recidivaron 17 pacientes (32 porciento). En total 14 de estos pacientes requirieron tratamiento corticoideo (82 porciento, porcentaje significativamente superior al de pacientes tratados durante el primer brote: 28 porciento, p = 0,0002). Todos mejoraron con el tratamiento. La única característica del primer brote que diferenciaba al grupo de pacientes que recidivaron era el haber recibido tratamiento corticoideo durante dicho brote (53 porciento vs 17 porciento, p = 0,007) (AU)

Prevalence and clinical significance of antiprothrombin antibodies in patients with systemic lupus erythematosus or with primary antiphospholipid syndrome.

BACKGROUND AND OBJECTIVE: Antibodies to prothrombin (aII) have been identified in patients with antiphospholipid antibodies, but their clinical significance is not well known. The aim of our study was to investigate their prevalence and association with clinical manifestations of the antiphospholipid syndrome (APS) in patients with primary APS or with systemic lupus erythematosus (SLE). DESIGN AND METHODS: A series of 177 patients with autoimmune diseases was studied: 70 with primary APS and 107 with systemic lupus erythematosus. A control group of 87 healthy volunteers were included in the study. aII were investigated in sera by an ELISA, using human prothrombin as antigen fixed in irradiated polystyrene plates. RESULTS: aII prevalence in patients with autoimmune disease was 47% (57% and 40% in patients with primary APS or with SLE, respectively) significantly higher than in controls (5%) (p<0.0001). In the whole series, thrombotic events were more prevalent in patients with aII (45% vs 28%; p=0.02). Moreover, aII was found to be an independent risk factor for arterial thrombosis (OR=2.4; p=0. 04). Similarly, in patients with SLE, aII were associated with both arterial and venous thrombosis (35% vs 14%; p=0.01), although only IgG-aII (OR=3.7; p=0.01) had an independent value as risk factor for thrombosis. However, a relationship between aII and thrombosis was not found in primary APS. aII were associated with thrombocytopenia only in patients with primary APS (OR=6.7; p=0.007). INTERPRETATION AND CONCLUSIONS: aII seem to be a serological marker of thrombosis in autoimmune diseases, mainly in SLE patients and/or in the arterial territory.

Prevalence of hepatitis C virus infection in patients with antiphospholipid syndrome.

BACKGROUND/AIMS: The aim of this study was to determine the prevalence and clinical significance of hepatitis C virus (HCV) infection in patients with the antiphospholipid syndrome (APS). METHODS: A series of 88 consecutive patients (78 female and 10 male), with a mean age of 39 years (range 15-79), was prospectively studied. All patients had been diagnosed with APS: 54 (61%) primary APS and 34 (39%) APS associated with systemic lupus erythematosus. A group of 200 apparently healthly blood donors was included in the study. Anti-HCV antibodies were investigated in the serum of all patients using a third-generation ELISA and confirmed by recombinant immunoblot assay. RNA-HCV was investigated in anti-HCV positive samples by polymerase chain reaction. Anticardiolipin, anti-beta2-glycoprotein I and antiprothrombin antibodies were evaluated by ELISA. Lupus anticoagulant was studied by coagulometric assays. RESULTS: Only 2 (2.2%) patients showed positivity for anti-HCV antibodies, but none of them had clinical or biochemical signs of liver disease. Furthermore, RNA-HCV was not detected in serum of any of these patients. Lupus anticoagulant was positive in 57% of patients. Anticardiolipin antibodies were positive in 60% of patients, anti-beta2-glycoprotein I antibodies in 43% of patients, and antiprothrombin antibodies in 56% of patients. The prevalence of anti-HCV in blood donors was 1%. CONCLUSIONS: The prevalence of anti-HCV in patients with APS is low and similar to that in healthy people in our area. HCV infection does not seem to be involved in the etiopathogenesis of this syndrome.

Clinical study and follow-up of 100 patients with the antiphospholipid syndrome.

OBJECTIVES: To study the clinical characteristics at diagnosis and during follow-up of patients with the antiphospholipid syndrome (APS) and to analyze the influence of treatment on their outcome. PATIENTS: One hundred patients with APS were included (86% female and 14% male; mean age, 36 years). Sixty-two percent had primary APS and 38% had APS associated with systemic lupus erythematosus (SLE). The median length of follow-up was 49 months. RESULTS: Fifty-three percent of the patients had thromboses, 52% had thrombocytopenia, and 60% of the women had pregnancy losses. Patients with APS associated with SLE had a higher prevalence of hemolytic anemia (P = .02), thrombocytopenia (platelet count lower than 100 x 10(9)/L) (P = .004), antinuclear antibodies (P = .0002), and low complement levels. Fifty-three percent of the patients with thrombosis had recurrent episodes (86% in the same site as the previous thrombotic event). Recurrences were observed in 19% of the episodes treated with long-term oral anticoagulation, in 42% treated prophylactically with aspirin, and in 91% in which anticoagulant/antiaggregant treatment was discontinued (P = .0007). Multivariate analysis showed that prophylactic treatment and older age had an independent predictive value for rethrombosis. Prophylactic treatment during pregnancy (usually with aspirin) increased the live birth rate from 38% to 72% (P = .0002). CONCLUSIONS: Patients with APS have a high risk of recurrent thromboses. Long-term oral anticoagulation seems to be the best prophylactic treatment to prevent recurrences. Prophylactic treatment with aspirin during pregnancy reduced the rate of miscarriages remarkably.

Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients.

We analyzed the clinical and laboratory characteristics of 50 patients with catastrophic antiphospholipid syndrome (APS) (5 from our clinics and 45 from a MEDLINE computer-assisted review of the literature from 1992 through 1996). Thirty-three (66%) patients were female and 17 (34%) were male. Twenty-eight (56%) patients had primary APS, 15 (30%) had defined systemic lupus erythematosus (SLE), 6 (12%) had "lupus-like" syndrome, and 1 (2%) had rheumatoid arthritis. Mean age of patients in this series was 38 +/- 14 years (range, 11-74 yr). Three (6%) patients developed the clinical picture of catastrophic APS under the age of 15 years, and 11 (22%) were 50 years old or more. In 11 (22%) patients, precipitating factors contributed to the development of catastrophic APS (infections in 3, drugs in 3, minor surgical procedures in 3, anticoagulation withdrawal in 2, and hysterectomy in 1). The presentation of the acute multi-organ failure was usually complex, involving multiple organs simultaneously or in a very short period of time. The majority of patients manifested microangiopathy--that is, occlusive vascular disease affecting predominantly small vessels of organs, particularly kidney, lungs, brain, heart, and liver--with a minority of patients experiencing only large vessel occlusions. Thrombocytopenia was reported in 34 (68%) patients, hemolytic anemia in 13 (26%), disseminated intravascular coagulation in 14 (28%), and schistocytes in 7 (14%). The following antibodies were detected: lupus anticoagulant (94%), anticardiolipin antibodies (94%), anti-dsDNA (87% of patients with SLE), antinuclear antibodies (58%), anti-Ro/SS-A (8%), anti-RNP (8%), and anti-La/SS-B (2%). Anticoagulation was used in 70% of the patients, steroids in 70%, plasmapheresis in 40%, cyclophosphamide in 34%, intravenous gammaglobulins in 16%, and splenectomy in 4%. Most patients, however, received a combination of nonsurgical therapies. Death occurred in 25 of the 50 (50%) patients. In most, cardiac problems seemed to be the major cause of death. In several of these, respiratory failure was also present, usually due to acute respiratory distress syndrome and diffuse alveolar hemorrhage. Among the 20 patients who received the combination of anticoagulation, steroids, and plasmapheresis or intravenous gammaglobulins, recovery occurred in 14 (70%) patients. The use of ancrod and defibrotide appeared to be effective in the 2 respective patients in whom they were used.