Human acute Chagas disease: changes in factor VII, activated protein C and hepatic enzymes from patients of oral outbreaks in Pará State (Brazilian Amazon)

Oral transmission of Chagas disease has been increasing in Latin American countries. The present study aimed to investigate changes in hepatic function, coagulation factor levels and parasite load in human acute Chagas disease (ACD) secondary to oral Trypanosoma cruzi transmission. Clinical and epidemiological findings of 102 infected individuals attended in the State of Pará from October 2013 to February 2016 were included. The most common symptoms were fever (98%), asthenia (83.3%), face and limb edema (80.4%), headache (74.5%) and myalgia (72.5%). The hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of 30 ACD patients were higher compared with controls, and this increase was independent of the treatment with benznidazole. Moreover, ACD individuals had higher plasma levels of activated protein C and lower levels of factor VII of the coagulation cascade. Patients with the highest parasite load had also the most increased transaminase levels. Also, ALT and AST were associated moderately (r = 0.429) and strongly (r = 0.595) with parasite load respectively. In conclusion, the present study raises the possibility that a disturbance in coagulation and hepatic function may be linked to human ACD.

A lung image reconstruction from computed radiography images as a tool to tuberculosis treatment control

Background: Tuberculosis (TB) is an infectious lung disease with high worldwide incidence that severely compromises the quality of life in affected individuals. Clinical tests are currently employed to monitor pulmonary status and treatment progression. The present study aimed to apply a three-dimensional (3D) reconstruction method based on chest radiography to quantify lung-involvement volume of TB acute-phase patients before and after treatment. In addition, these results were compared with indices from conventional clinical exams to show the coincidence level. Methods: A 3D lung reconstruction method using patient chest radiography was applied to quantify lung-involvement volume using retrospective examinations of 50 patients who were diagnosed with pulmonary TB and treated with two different drugs schemes. Twenty-five patients were treated with Scheme I (rifampicin, isoniazid, and pyrazinamide), whereas twenty-five patients were treated with Scheme II (rifampicin, isoniazid, pyrazinamide, and ethambutol). Acute-phase reaction: Serum exams included C-reactive protein levels, erythrocyte sedimentation rate, and albumin levels. Pulmonary function was tested posttreatment. Results: We found strong agreement between lung involvement and serum indices pre- and posttreatment. Comparison of the functional severity degree with lung involvement based on 3D image quantification for both treatment schemes found a high correlation. Conclusions: The present 3D reconstruction method produced a satisfactory agreement with the acute-phase reaction, most notably a higher significance level with the C-reactive protein. We also found a quite reasonable coincidence between the 3D reconstruction method and the degree of functional lung impairment posttreatment. The performance of the quantification method was satisfactory when comparing the two treatment schemes. Thus, the 3D reconstruction quantification method may be useful tools for monitoring TB treatment. The association with serum indices are not only inexpensive and sensitive but also may be incorporated into the assessment of patients during TB treatment.(AU)

Alterações da proteína C reativa e fator reumatoide em cães naturalmente infectados por Leishmania spp / Changes in C-reactive protein and rheumatoid factor in dogs naturally infected by Leishmania spp

A leishmaniose visceral canina é uma zoonose considerada doença tropical de prioridade. A leishmaniose afeta vários sistemas do corpo dos cães, incluindo vísceras e pele. A proteína C reativa (PCR) e o fator reumatoide (FR) são exames realizados na medicina para detecção de inflamação e artrites em seres humanos, no entanto, há poucos trabalhos voltados para cães com leishmaniose que demonstrem as alterações ocorridas na PCR e FR. Este trabalho teve como objetivo demonstrar as alterações de PCR e FR e sua correlação com a hiperproteinemia e hiperalbuminemia, além da compararação com o desvio a esquerda presente no exame hematológico. O trabalho foi realizado no Hospital Veterinário do Centro Universitário da Grande Dourados/MS e Centro de Controle de Zoonoses, no qual foram avaliados 34 cães, de diversar raças e idade e submetidos a colheita de sangue venosa para realização de exames em imuno-látex, bioquímica sérica e hemograma, em cães naturalmente infectados por Leishmania spp. Foram utilizados somente cães positivos ao teste rápido DPP® para leishmaniose, juntamente com resultado positivo no exame parasitológico, depois de diagnosticados foram realizados exames hematológicos e bioquímicos. Quando realizado o teste para quantificação de FR em soro sanguíneo, para os 34 animais estudados, foi observado positividade em apenas 1 animal, enquanto que os cães foram positivos para a PCR em 38,23% dos casos estudados. Em casos de animais com leishmaniose é possível estabelecer níveis inflamatórios precocemente, enquanto que o FR demonstrou não ser um bom marcador para animais soropositivos para a doença.(AU)

Canine visceral leishmaniasis is a zoonosis considered a priority tropical disease. The disease affects various body systems of dogs, including viscera and skin. C-reactive protein (CRP) and rheumatoid factor (RF) are tests performed in medicine for the detection of inflammation and arthritis in humans, however, there are few studies aimed at dogs with leishmaniasis that demonstrate changes in CRP and RF. This work aimed to demonstrate the changes of CRP and RF and its correlation with hyperproteinemia and hyperalbuminemia, in addition to the comparison with the left deviation present in the hematological examination. The work was carried out at the Veterinary Hospital of the University Center of Grande Dourados/MS and Zoonoses Control Center, in which 34 dogs of different breeds and ages were submitted to venous blood collection for immuno-latex exams, Biochemistry and blood count in dogs naturally infected with Leishmania spp. Only dogs to the DPP® rapid test for leishmaniasis were used, together with a positive result in parasitological examination, after hematological and biochemical tests were performed. When the test for the quantification of FR in serum was performed, for the 34 animals studied, positivity was observed in only 1 animal, while the dogs were PCR positive in 38.23% of the cases studied. In cases of animals with leishmaniasis it is possible to establish inflammatory levels early, whereas the FR showed not to be a good marker for animals seropositive for the disease.(AU)

Trastornos asociados y factores de riesgo aterogénicos en escolares y adolescentes obesos / Associated disorders and atherogenic risk factors in obese school children and adolescents

Introducción: la obesidad en la edad pediátrica predispone a la enfermedad aterosclerótica precoz en la adultez, independientemente del peso futuro. Objetivo: caracterizar el patrón antropométrico, morbilidad asociada y factores de riesgo aterogénico en obesos. Métodos: se realizó un estudio descriptivo y prospectivo con 62 pacientes obesos atendidos en la consulta de Endocrinología del Hospital Pediátrico William Soler , entre enero y diciembre de 2016. Fueron analizadas variables demográficas, antropométricas y de riesgo aterogénico por medio de prevalencia (por ciento) y pruebas de hipótesis (significativo: p< 0,05 o coeficiente Eta 1). Resultados: la obesidad fue significativa en escolares y el sexo masculino (p= 0,000). La obesidad abdominal (n= 48/77,4 por ciento) predominó en el sexo femenino (n= 20/90,9 por ciento), y entre los 6 y 10 años (n= 14/63,6 por ciento). La obesidad generalizada tuvo diagnóstico significativamente superior que la obesidad abdominal (p= 0,001) y fue independiente del sexo (Eta= 0,049) y la edad (p= 0,066). La prevalencia de acantosis nigricans (n= 39/62,9 por ciento) fue significativa (p= 0,042). Las alteraciones humorales, clínicas y ecográficas analizadas se manifestaron por encima de 70 por ciento en presencia de obesidad abdominal y la generalizada, ambas asociadas con elevación de proteína C reactiva (p< 0,05), y a su vez, la generalizada con remodelación ventricular izquierda (p= 0,049). Conclusión: la obesidad es distintiva de los escolares y del sexo masculino, pero la de tipo abdominal caracteriza a las niñas; existe una baja prevalencia de factores de riesgo aterogénico en los pacientes estudiados. La adiposidad abdominal y la generalizada implican un incremento de la proteína C reactiva plasmática; se evidencia el remodelado ventricular izquierdo cuando existe obesidad generalizada(AU)

Introduction: obesity in the pediatric age predisposes to early atherosclerotic disease in adulthood, regardless of future weight. Objective: to characterize the anthropometric pattern, associated morbidity and atherogenic risk factors in obese patients. Methods: a descriptive and prospective study was carried out with 62 obese patients attended in the Endocrinology clinic of William Soler Pediatric Hospital, from January to December 2016. Demographic, anthropometric and atherogenic risk variables were analyzed by means of prevalence (percent) and hypothesis testing (significant: p< 0.05 or Eta coefficient 1). Results: obesity was significant in schoolchildren and male sex (p= 0.000). Abdominal obesity (n= 48/77.4 percent) predominated in females (n= 20/90.9 percent), and among 6 and 10 years old (n= 14/63.6 percent). Generalized obesity had a significantly higher diagnosis than abdominal obesity (p = 0.001) and didn´t have relation with sex (Eta= 0.049) and age (p= 0.066). The prevalence of acanthosis nigricans (n= 39 / 62.9 percent) was significant (p= 0.042). The humoral, clinical and ultrasonographic alterations analyzed were above 70 percent in the presence of abdominal and generalized obesity, both associated with elevated C-reactive protein (p< 0.05), and at the same time, the generalized with left ventricular remodeling (p= 0.049). Conclusions: obesity is distinctive among school children and males, but abdominal type characterizes girls. There is a low prevalence of atherogenic risk factors in the patients studied. Abdominal and generalized adiposity imply an increase in plasma C-reactive protein. Left ventricular remodeling is evidenced when there is generalized obesity(AU)

La resistina se asocia con la proteína C reactiva y marcadores de riesgo cardiovascular en niños obesos / Resistin is associated with C reactive protein and cardiovascular risk markers in obese children / A resistina associa-se à proteína C reativa e aos marcadores de risco cardiovascular em crianças obesas

El objetivo del trabajo fue evaluar los niveles de resistina sérica y su asociación con la proteína C reactiva (PCR-hs), óxido nítrico (NO) y lípidos plasmáticos (LP) en sujetos de edad pediátrica. Participaron 366 niños y adolescentes (10-16 años), agrupados en eutróficos (n=162) y obesos (n=204). Se les estudió peso, talla, circunferencia de la cintura, resistina sérica, glucosa e insulina basal, LP, NO, PCR-hs, malondialdehído y tensión arterial. Se calculó el IMC, el índice cintura-talla (IC/T) y el HOMA-IR. Se utilizaron las pruebas t de Student, ANOVA, U de Mann y Whitney o Kruskal- Wallis para comparar entre grupos y la correlación de Spearman para determinar asociación entre variables. Los obesos masculinos presentaron niveles superiores de resistina (p<0,05). El género femenino presentó valores más altos de resistina en eutróficos (p=0,012) y con IC/T normal (p=0,011). A mayor concentración de resistina los eutróficos presentaron niveles más altos de triacilglicéridos, pero los obesos mostraron niveles más bajos de triacilglicéridos, HDLc y NO, más altos de PCR-hs y mayor IMC. Los resultados sugieren que la resistina podría ser un factor de riesgo para la enfermedad cardiovascular por su asociación positiva con la PCR-hs e inversa con el NO y la HDLc, parámetros involucrados en la inflamación y la disfunción endotelial.

The aim of this study was to evaluate seric levels of resitin and their association with high-sensitivity C Reactive Protein (hs-CRP), nitric oxide (NO) and plasmatic lipids (PL) in a pediatric age population. A total of 366 children and adolescents (between 10-16 years old) participated, and were grouped into eutrophic (n=162) and obese (n=204). Weight, height, waist circumference, resistin, fasting blood glucose and insulin levels, PL, hs-CRP, NO, malondialdehyde and blood pressure were measured. BMI, waist to height ratio (W/HR) and HOMA-IR were calculated. T-student, ANOVA, Mann-Whitney U-value or Kruskal-Wallis were used to compare between groups and Spearman correlation was used to determine association among variables. Male obese subjects showed higher resistin levels (p<0.05). Female subjects showed higher resistin values in the eutrophic group (p=0.012) and in the normal W/HR (p=0.011). At higher levels of resistin, the eutrophic group showed higher levels of triacylglycerides, but the obese group showed lower triacylglycerides, HDLc and NO levels and higher hs-CRP levels and BMI. These results suggest that resistin could be a risk factor for cardiovascular disease because of its positive association with hs-CRP and inverse association with NO and HDLc, parameters involved in inflammation and endothelial dysfunction.

O objetivo da pesquisa foi avaliar os níveis séricos de resistina sérica e sua associação com a proteína C-reativa (PCR-hs), óxido nítrico (NO) e lipídios plasmáticos (LP) em crianças e adolescentes. O estudo envolveu 366 crianças e adolescentes (10-16 anos), agrupados em eutróficos (n=162) e obesos (n=204). Os sujeitos foram estudados em relação ao peso, altura, circunferência da cintura, resistina sérica, glicose e insulina basal, LP, NO, PCR-hs, malondialdeído e pressão arterial. Os IMC, índice cintura-altura (IC/A) e HOMA-IR foram calculados. Foram utilizados os Testes t de Student, ANOVA, U de Mann e Whitney ou Kruskal-Wallis para comparar entre os grupos e a correlação de Spearman para verificar a associação entre variáveis. Os obesos masculinos mostraram níveis mais elevados de resistina (p<0,05). O sexo feminino apresentou valores mais altos de resistina em eutróficos (p=0,012) e com IC/T normal (p=0,011). À maior concentração de resistina, os eutróficos apresentaram maiores níveis de triacilglicerídeos, mas os obesos apresentaram níveis mais baixos de triacilglicerídeos, HDLc e NO, mais altos de PCR-hs e maior IMC. Os resultados sugerem que a resistina poderia ser um fator de risco para a doença cardiovascular devido à sua associação positiva com a PCR-hs e inversa com o NO e a HDLc, parâmetros envolvidos na inflamação e disfunção endotelial.

C-reactive protein serum level in patients with psoriasis before and after treatment with narrow-band ultraviolet B

Abstract: Background: C-reactive protein is an inflammatory biomarker and its level increases in the serum of psoriatic patients. Its level is also associated with Psoriasis Area and Severity Index score. Objective: The aim of this study was to assess the decrement of serum C-reactive protein level with narrow-band ultraviolet B (NB-UVB) therapy. Methods: C-reactive protein serum levels in psoriasis patients were measured before and after treatment with NB-UVB and the data were analyzed in relation to the Psoriasis Area and Severity Index score improvement. Results: Baseline C-reactive protein levels among psoriatic patients were higher than normal. These levels decreased significantly after treatment (P<0.001). At the beginning of the study, patients with higher levels of C-reactive protein also had more extensive and severe skin involvement. The highest decrease in C-reactive protein was observed in patients who responded better to the treatment and achieved a higher Psoriasis Area and Severity Index 75%. There was an association between baseline Psoriasis Area and Severity Index scores and C-reactive protein levels. Conclusion: Patients with moderate to severe plaque-type psoriasis had active systemic inflammation, which was demonstrated by increased levels of C-reactive protein. Furthermore, skin disease severity was correlated with C-reactive protein levels. Phototherapy healed the psoriatic skin lesions and reduced inflammation, while decreasing C-reactive protein levels.

Proteína C ultrasensible como factor independiente de riesgo en población con y sin antecedentes cardiovasculares / High sensitivity C protein as an independent risk factor in people with and without history of cardiovascular disease

Entre los nuevos biomarcadores del riesgo de eventos cardiovasculares (ECV), la proteína C reactiva detectada mediante técnicas de alta sensibilidad (PCRus) ha sido uno de los más evaluados. En esta revisión se exploró la evidencia existente sobre la utilidad de la PCRus como factor independiente del riesgo de eventos en sujetos sin antecedentes cardiovasculares, y como marcador pronóstico en sujetos con enfermedad cardiovascular crónica o aguda. Se realizó un overview (revisión de revisiones) con búsqueda en las principales bases bibliográficas suplementada por buscadores genéricos de Internet. En una primera etapa se detectaron revisiones sistemáticas, guías de práctica clínica, evaluaciones de tecnologías sanitarias y políticas de cobertura, y en una segunda etapa se identificaron estudios primarios publicados posteriormente a las fechas de búsqueda de las revisiones sistemáticas. Fueron recuperadas 774 citas, de las cuales se incluyeron 36 publicaciones que evaluaron el papel de la PCRus en poblaciones sanas o con antecedentes coronarios. Se encontró evidencia de alta calidad señalando a la PCRus, tanto como factor de riesgo en población general, como pronóstico en aquellos con ECV en todas las poblaciones evaluadas. Su mayor utilidad residió en sujetos sin historia de ECV y riesgo intermedio de eventos a 10 años, en donde la adición de la PCRus a modelos clásicos de estimación del riesgo de eventos mejora la estratificación del riesgo. No se identificó, en cambio, consenso sobre su utilidad clínica como marcador pronóstico en sujetos con enfermedad coronaria crónica o aguda.

Among the new cardiovascular event (CVE) risk biomarkers, C-reactive protein detected using high sensitive techniques (hs-CRP) has been one of the most commonly evaluated. In this review, the available evidence on the usefulness of hs-CRP was explored as an independent risk event factor in subjects with no cardiovascular history and as prognosis in case of chronic or acute cardiovascular condition. An overview (revision of revisions) was carried out searching in the main bibliographic databases and in other general Internet search engines. During the first stage, systematic reviews, clinical practice guidelines, health technology assessments and coverage policies were found and, during the second stage primary studies published after the systematic review search dates were added. Seven hundred and seventy four quotes were found, including 36 papers assessing the role of hs-CRP in healthy populations or with cardiovascular history. High quality evidence was found pointing out hs-CRP, both as risk factor in the general population and as prognostic factor in those with CVE, in all the populations assessed. It was most useful in subjects with a history of CVE and intermediate risk of events at 10 years; where adding hs-CRP to the classical models for event risk estimation improves risk staging. There was no consensus on its clinical usefulness as a prognostic marker in subjects with chronic or acute disease.

Changes in Plasma Levels of Natural Anticoagulants in Disseminated Intravascular Coagulation: High Prognostic Value of Antithrombin and Protein C in Patients with Underlying Sepsis or Severe Infection

BACKGROUND: Dysfunctional natural anticoagulant systems enhance intravascular fibrin for mation in disseminated intravascular coagulation (DIC), and plasma levels of natural anti coagulants can be used in the diagnosis and prognosis of DIC. Herein, the diagnostic value of 4 natural anticoagulants was assessed, and the prognostic value of antithrombin and protein C were validated in a large population. METHODS: Part 1 study included 126 patients with clinically suspected DIC and estimated plasma levels of 4 candidate anticoagulant proteins: antithrombin, protein C, protein S, and protein Z. Part 2 comprised 1,846 patients, in whom plasma antithrombin and protein C levels were compared with other well-known DIC markers according to the underlying dis eases. The 28-day mortality rate was used to assess prognostic outcome. RESULTS: Antithrombin and protein C showed higher areas under the ROC curve than pro tein S and protein Z. In part 2 of the study, antithrombin and protein C levels significantly correlated with DIC score, suggesting that these factors are good indicators of DIC severity. Antithrombin and protein C showed significant prognostic power in Kaplan-Meier analyses. In patients with sepsis/severe infection, antithrombin and protein C showed higher hazard ratios than D-dimer. Platelet count showed the highest hazard ratio in patients with hemato logic malignancy. In patients with liver disease, the hazard ratio for antithrombin levels was significantly high. CONCLUSIONS: Decreased plasma anticoagulant levels reflect florid consumption of the phys iologic defense system against DIC-induced hypercoagulation. Plasma antithrombin and protein C levels are powerful prognostic markers of DIC, especially in patients with sepsis/severe infection.

Distúrbios de coagulação em pacientes com osteonecrose da cabeça femoral / Coagulation disorders in patients with femoral head osteonecrosis

Objetivo: Comparar a ocorrência de trombofilias em pacientes com osteonecrose idiopática da cabeça femoral em relação aos pacientes com osteonecrose secundária da cabeça femoral. Métodos: Um total de 24 pacientes consecutivos foram avaliados, sendo oito portadores de osteonecrose idiopática e 16 de osteonecrose secundária. Os exames realizados na detecção de trombofilias foram as dosagens de proteína C, proteína S e antitrombina e as pesquisas de mutações nos genes da protrombina e do fator V. Comparamos estatisticamente os resultados através do cálculo da razão de chances ou odds ratio das diferentes trombofilias entre os dois grupos. Resultados: O odds ratio para a deficiência da proteína S e deficiência da proteína C entre os grupos idiopático e secundário foram respectivamente 5 e 2,14. Desta maneira, um indivíduo com osteonecrose idiopática possui uma chance 5 vezes maior de apresentar deficiência da proteína S e 2,14 vezes maior de apresentar deficiência da proteína C do que um indivíduo com osteonecrose secundária. Conclusão: Pacientes com osteonecrose idiopática têm maiores chances de apresentar trombofilias do que aqueles com osteonecrose secundária, sugerindo que estes distúrbios de coagulação podem desempenhar um papel importante na patogênese dos casos de osteonecrose onde não há inicialmente nenhum fator de risco identificável. Nível de Evidência III, Estudo de Caso-Controle.

Objective: To compare the occurrence of thrombophilic disorders in patients with idiopathic osteonecrosis of the femoral head and patients with secondary osteonecrosis of the femoral head. Methods: Twenty-four consecutive patients were enrolled, with eight of them presenting idiopathic osteonecrosis and 16 presenting secondary osteonecrosis. The tests for detection of thrombophilic disorders were measurements of protein C, protein S and antithrombin levels and detection of prothrombin and factor V gene mutations. We compared the results using the odds ratio statistics for the thrombophilic disorders between the two groups. Results: The odds ratio for the protein S deficiency and protein C deficiency between the idiopathic and secondary groups were 5 and 2.14, respectively. Thus, an individual with idiopathic os teonecrosis has 5 times more chance of presenting protein S deficiency and 2.14 times more chance of presenting protein C deficiency than an individual with secondary osteonecrosis. Conclusion: Patients with idiopathic osteonecrosis have more chances of presenting thrombophilias than those with secondary osteonecrosis, suggesting these coagulation disorders can play an important role in the pathogenesis of the osteonecrosis in cases where there was no initial risk factor recognized. Level of Evidence III, Case-Control Study.

A Case of Intestinal Tuberculosis with Perianal Fistula Diagnosed after 30 Years / 대한소화기학회지

Tuberculosis can occur anywhere in the gastrointestinal tract. However, anorectal tuberculosis has rarely been reported. A 46-years-old male presented with abdominal pain and perianal discharge of 30 years' duration. The patient had received operations for anal fistula and inflammation three times. Although he had been taking mesalazine for the past three years after being diagnosed with Crohn's disease, his symptoms persisted. Colonoscopy performed at our hospital revealed cicatricial change of ileocecal valve and diffuse ulcer scar with mild luminal narrowing of the ascending, transverse, and descending colon without active lesions. Multiple large irregular active ulcers were observed in the distal sigmoid and proximal rectum. An anal fistula opening with much yellowish discharge and background ulcer scar was observed in the anal canal. However, cobble-stone appearance and pseudopolyposis were not present. Therefore, we clinically diagnosed him as having intestinal tuberculosis with anal fistula and prescribed antituberculosis medications. Follow-up colonoscopy performed 3 months later showed much improved multiple large irregular ulcers in the distal sigmoid colon and proximal rectum along with completely resolved anal fistula without evidence of pus discharge.

Determination of serum C and S protein and factor V leiden in sickle cell disorder in Khozestan province

Sickle cell disease [SCO] is due to beta chain mutation and substitution of valine for glutamic acid in sixth position,that is cause increasing polymerization and vaso-occlusion. Decrease of protein C, protein S and increase in factor V leiden activity contribute to hypercoagulation state in SCO, recently.The aim of this study was to determinate the differences of serum C and S protein and factor V leiden between sickle cell patients and control subjects. In this randomized case-control study, protein C, protein S and factor V leiden activity were measured in 100 SCO patients in crisis phase. And were compared between 50 age- gender -race- matched controls and SCD patients in, hydroxyurea intake, blood transfusion, levels of HbF, age and gender by Chi-Square and Anova statistical tests in SPSS software. In 100 patients 47 were males and 53 females, mean age was20.2 [range 3-58, 1SD +/- 1.03]. Protein C and protein S levels were significantly low [both P<0.0001] in 35% and 24% patient; respectively. But in controls it was not like this. Factor V leiden was increased significantly [P<0.00l] in 27% of patient and 4% of controls. A significant [P=0.02] correlation was detected between protein S levels and age groups. Protein C and protein S levels reduced and factor V leiden activity increased in SCD patients and cause hypercoagulable state in these patients

Warfarin-Induced Penile Necrosis in a Patient with Heparin-Induced Thrombocytopenia

A 56-yr-old man with lung adenocarcinoma presented with subsegmental pulmonary thrombosis. Platelet count on presentation was 531x10(9)/L. The patient was anticoagulated with subcutaneous low molecular weight heparin (LMWH). Next day, oral anticoagulation was initiated with 5 mg of warfarin once daily with LMWH and LMWH was discontinued at third hospital day. On the third day of oral anticoagulation therapy, he complained of left leg swelling and prolonged painful penile erection of 24 hr-duration. His platelet count reached a nadir 164x10(9)/L at that time, and the patient had a deficiency of protein C and S, with an activity level of 16% and 20% of normal value. Warfarin was stopped and he underwent penile aspiration. The next day, left leg edema and penile erection was disappeared, but penile and glans penis necrosis was started. This case illustrates that processes underlying heparin-induced thrombocytopenia (HIT) may also underlie warfarin-induced skin necrosis.

Placental histomorphology in unexplained foetal loss with thrombophilia.

BACKGROUND & OBJECTIVES: Acquired and genetic thrombotic conditions, both organ and non organ specific, are associated with increased foetal wastage. This study was carried out to examine the placenta from women with abnormal pregnancies and a history of unexplained foetal loss, and to associate with maternal thrombophilia status. METHODS: Placentas from eight women with history of unexplained foetal loss were analyzed for histopathological characteristics. All the women were simultaneously screened for the common acquired and genetic thrombophilia markers i.e., lupus anticoagulants ( LA), IgG / IgM antibodies for anticardiolipin (ACA), beta2 glycoprotein 1 (beta2GPI) and annexin V, protein C (PC), protein S (PS), antithrombin III (AT III), factor V Leiden ( FVL) mutation, prothrombin (PT) gene G20210A, methylene tetrahydrofolate reductase (MTHFR) C 677T, endothelial protein C receptor (EPCR) 23 bp insertion and plasminogen activator inhibitor ( PAI-1 4G/5G) polymorphisms RESULTS: Six of eight women were positive for one or more thrombophilia markers. The placenta in all the cases except one, showed the characteristic features of infarct fibrin deposition and calcification. Among two women who were negative for thrombophilia, one showed clear evidence of thrombus in the placental sections while the other did not show any characteristic infarcts in the placental sections. INTERPRETATION & CONCLUSION: Our findings showed that the histopathological examination of the placentas confirmed thrombophilia as the aetiological cause of thrombosis in 6 of the 8 women. The presence of thrombus in a negative thrombophilia woman suggests yet unidentified thrombophilia markers or probably non-haemostatic factors causing thrombosis.

Etiological profile of stroke and its relation with prothrombotic states.

OBJECTIVE: To study the etiological profile of childhood stroke and its relation with prothrombotic states. METHODS: Children with acute stroke with no evidence of CNS infection or head injury were studied. Stroke was confirmed by CT scan and further evaluated by MRI. Cardiac status was assessed with transthoracic echocardiography. Test for hypercoagulable state (antithrombin III, protein C, protein S, anticardiolipin antibody IgG and IgM and lupus anticoagulant) were done in all patients. RESULTS: A total of 66 children were enrolled--36 cases and 30 controls. Presenting symptoms were motor deficit (72%), seizure (66%), altered sensorium (36%), aphasia (27%). Causes identified were antiphospholipid antibody syndrome (25%), Moya Moya disease (16.6%), cardiac disease (11.1%), vasculitis (5.5%), ATIII deficiency (5.5%), Protein C deficiency (2.7%). Etiology remained unknown in 25% of cases with infarction. Hemorrhage was seen in 8.2% of cases and they had DIC or liver disease as the underlying cause. CONCLUSIONS: Magnetic Resonance Angiography and ELISA for antiphospholipid antibody should be done in all patients with stroke without an obvious cause.

Evaluation of hemostatic factors in children with nephrotic syndrome

Thromboembolism [TE] is one of the serious complications of nephrotic syndrome [NS]. The aim of this study was to evaluate the haemostatic factors in children with nephrotic syndrome. Plasma Level of protein C, Protein S, fibirinogen and antithrombin III [AT III] were evaluated in thirty nephrotic children at relapse and remission period and the results were compared with those of 30 healthy children. The mean age of patients was 5.38 +/- 3.07 years. Plasma Level of protein S and AT III during relapse were significantly lower than their level in remission period and in control group. The mean fibrinogen level during relapse was significantly higher than its level in remission period and in control group. There was no significant difference in protein C levels at relapse with remission period and with control group. Serum albumin levels during relapse were positively correlated with AT III levels. There was no correlation between urinary protein excretion and the haemostatic factors. Despite reduced levels of AT III and protein S and increased levels of fibrinogen, none of our patients revealed thromboembolism. It seems that coexistence of several factors is necessary to induce TE

Trombofilia primaria: 41 nuevos casos / Primary thrombophilias: 41 new cases

Se presentan 37 casos de trombosis, en su mayoría jóvenes, con antecedentes trombóticos familiares y con diagnóstico de trombofilia primaria o hereditaria además de cuatro familiares de primer grado de estos pacientes en los cuales se confirmó la portación familiar de trombofilia. La anamnesis reveló que el 82 por ciento presentó la primera trombosis antes de los 45 años; tuvo más de una trombosis en un 59 por ciento y tenía antecedentes familiares en 49 por ciento. Los defectos trombofílicos determinantes encontrados fueron: deficiencia de proteína S (27 por ciento); resistencia a proteína C activada por factor V Leiden (24,3 por ciento); deficiencia proteína C (21,6 por ciento) y antotrombina III (16,2 por ciento); mutación G20210 A del gen protrombina (8,1 por ciento). Entre los defectos adquiridos estudiados simultáneamente, un 27,2 por ciento de los casos presentaron anticoagulante lupico y ninguno hiperhomocisteína. La existencia de mas de un factor de riesgo trombofílico se observó en el 24.3 por ciento de los pacientes. En el estudio de los 4 parientes de primer grado se encontró factor V Leiden en uno; factor V Leiden mas anticoagulante lupico en uno y deficiencia proteína S en dos. El trabajo anterior publicado en 2004 motivó a los pacientes que no se hicieron el estudio a tomar conciencia de su situación y de la necesidad de controlarse, lo que demuestra la importancia de difundir esta patología aún poco conocida.

Assessment of anticardiolipin antibodies, circulating lupus anticoagulant, protein C, protein S, antithrombin III and activated protein C resistance and their relation to thomboembolic and other clinical manifestations in Behcet's disease

Venous and arterial thrombosis occurs in patients with Behcet's disease and is associated with significant morbidity and mortality. Studies on a possible association between the occurrence of thrombosis and thrombophilia in patients with this disease have been controversial. The objective of this study was to assess the frequency and clinical relevance of anticardiolipin antibodies [aCL] and other thrombophilic factors and their relationship to thromboembolic and clinical manifestations in Behcet's disease [BD]. IgG, IgM and IgA anticardiolipin antibodies [aCL] isotypes, presence of circulating lupus anticoagulant [LAC], protein C, protein S, antithrombin III and activated protein C resistance were investigated in 25 patients with BD and 25 patients with various rheumatic diseases not known to be associated with venous or arterial thromboembolic phenomena served as controls. Twelve of the patients with BD [48%] had either deep vein thrombosis [8 patients], arterial thromboembolic phenomena [4 patients], or both [2 patients]. The IgA aCL elevated in14 [56%] patients with BD compared with one [4%] patient in the control group [P<0.01]. IgG aCL levels were elevated in 13 [52%] patients with Behcet's disease [BD] compared with one [4%] patient in the control group [P<0.01].Also patients with BD do not have decreased protein S, or antithrombin III activity, activated protein C resistance, circulating lupus anticoagulant [LAC], or elevated LgM aCL. No significant differences were found between any variable in both groups. No association between elevated IgMaCL levels and venous or arterial thrombosis and no statistical correlation was found between any factor and clinical manifestations of the disease. A significant number of patients have elevated levels of IgA and IgG aCL but they are not associated with venous or arterial thrombosis. These results do not suggest a primary role for aCL in BD and do not support the role of coagulation abnormalities in the pathogenesis of thromboembolic complications of Behcet's disease but suggest vascular inflammation as the main pathogenetic event in the vascular lesions in Behcet's disease

Protein S deficiency is common in a healthy Thai population.

Currently, venous thromboembolism is a growing menace in Asians, approaching to that of Western countries. The most common genetic mutations causing thrombosis in Caucasians are factor V Leiden and prothrombin mutation. However both are very rare in Asians. On the other hand, natural anticoagulant protein (protein S, protein C and antithrombin) deficiencies are more common in Asian than in Western thrombotic patients. The prevalence of these deficiencies is very low in healthy Caucasians (0.02-0.3%). It is possible that the prevalence is higher in an Asian general population. However there have been very few prevalence studies to prove this hypothesis. Protein S deficiency was found in 3.7% (13/352, 95% confident interval 1.72-5.66) healthy Thais. Seven of them were type III deficiency. Similar to previous studies, total and free protein S levels were lower in females, but positively and negatively correlated with age, respectively. In contrast, one protein C deficiency (0.27%, 1/370) and no antithrombin deficiency (0/206) were detectable in our population. Furthermore, the authors found that antithrombin was significantly lower in women and there was a positive correlation between protein C activity and age. In conclusion, protein S deficiency is more common in Thais than in Caucasians. This result remains to be confirmed by a large population-based study.