Profilaxia da trombose venosa profunda em cirurgia bariátrica: estudo comparativo com doses diferentes de heparina de baixo peso molecular / Deep venous thrombosis prevention in bariatric surgery: comparative study of different doses of low weight molecular heparin

Contexto: A cirurgia bariátrica é considerada a melhor opção para o tratamento da obesidade, cujos pacientes são considerados de alto risco para fenômenos tromboembólicos. Objetivos: Comparar o uso de doses diferentes de heparina de baixo peso molecular (HBPM) na profilaxia da trombose venosa profunda (TVP) em pacientes candidatos à cirurgia bariátrica em relação ao risco de TVP, alteração na dosagem do fator anti-Xa e sangramento pré ou pós-operatório. Métodos: Estudo comparativo transversal em pacientes submetidos à cirurgia bariátrica distribuídos em dois grupos, que receberam doses de HBPM de 40 mg (grupo controle, GC) e 80 mg (grupo de estudo, GE). Foram avaliados por ultrassonografia vascular e dosagem de KPTT, TAP, plaquetas e fator anti-Xa. Resultados: Foram avaliados 60 pacientes, sendo 34 no GC e 26 no GE. Foi observada diferença significativa somente no peso (p = 0,003) e índice de massa corporal (p = 0,018) no GE em relação ao GC. Não houve diferença na dosagem de KPTT, TAP, plaquetas e fator anti-Xa entre os grupos. Não foram detectados TVP ou sangramentos significativos em ambos os grupos. Conclusões: Não houve diferença estatisticamente significativa na utilização de doses maiores de HBPM na profilaxia da TVP em pacientes candidatos à cirurgia bariátrica em relação ao risco de TVP, dosagem do fator anti-Xa e sangramento pré ou pós-operatório

Background: Bariatric surgery is considered the best treatment option for patients with obesity who are classed as high risk for thromboembolic events. Objectives: To compare two different doses of low weight molecular heparin (LWMH) for prevention of deep venous thrombosis (DVT) in candidates for bariatric surgery, in terms of DVT risk, abnormal anti-Xa levels, and preoperative and/or postoperative bleeding. Methods: A cross-sectional comparative study of bariatric surgery patients divided into two groups given different doses of LWMH; 40 mg of LWMH (control group, CG) and 80 mg of LWMH (study group, SG), both evaluated by vascular ultrasonography (VU) and according to the results of PTT, PT, platelets, and anti-Xa factor assays. Results: Sixty patients were evaluated, 34 in the CG and 26 in the SG. The only significant differences between the patients in the SG and the CG were weight (p = 0.003) and body mass index (p = 0.018). There were no differences between the groups in PTT, PT, platelets, or anti-Xa factor levels. There was no DVT or significant bleeding in either group. Conclusions: There were no statistical differences when higher doses of LWMH were used for prevention of DVT in bariatric surgery patients, in terms of DVT risk, anti-Xa factor levels, or preoperative and postoperative bleeding

Administración oral de preparado parenteral de vitamina K en anticoagulación excesiva por warfarina / Oral administration of intravenous preparation of Vitamin K for excessive anticoagulation due to warfarin

La warfarina es frecuentemente usada en la terapia anticoagulante actual, su acción debe ser monitorizada usando el tiempo de protrombina expresado como International Normalized Ratio (INR); cuando se excede el rango de seguridad se puede administrar vitamina K (Vit-K), preferentemente por vía oral. Dicha presentación no está disponible en Venezuela. Se realizó un ensayo clínico, doble ciego, donde a 20 pacientes, edad 18-60 años, sin sangrado e INR inicial de 6 a 10 inclusive; les fue suspendida la warfarina e inmediatamente agrupados al azar a recibir dosis única de Vit-K (oral 1.25mg de Vit-K fraccionada de una presentación parenteral) o placebo. El punto final primario, INR < 3.5 a las 24 horas de administrar la dosis, se alcanzó en 70% de los pacientes en Vit-K y 20% en placebo. La reducción absoluta del riesgo y su intervalo de confianza de 95%: RAR (IC95%) = 50% (14.4 a 85.6) ρ = 0.028; NNT (IC95%) = 2(1.3 a 6.9); no se registraron eventos adversos, ni INR < 2 luego de 24 horas de tratamiento. Los resultados obtenidos son consistentes con estudios donde se administró Vit-K en preparación específica para vía oral. Así la Vit-K en presentación parenteral, administrada por vía oral, es más efectiva y segura que simplemente detener la administración de warfarina para revertir la excesiva anticoagulación, en donde no exista presentación específica oral de Vit-K o ésta sea muy costosa.

Anticoagulation therapy with warfarin, a common clinical practice, needs to be monitored using protombine time expressed as the International Normalized Ratio (INR); when safety range is exceeded, Vitamin K (Vit-K) could be administered with preference orally. In Venezuela the specific oral preparation for Vit-K is not available. This is a double blinded, randomized, placebo controlled, clinical trial; 20 patients, age 18-60 year with initial INR ≥ 6, ≤10, were randomized to oral Vit-K 1.25mg (prepared from intravenous presentation) or placebo plus withholding warfarin. INR < 3.5 at 24 hours of treatment (the primary end point) was achieved by 70% among Vit-K, and 20% among placebo patients; given an absolute risk reduction (ARR), of 50% (CI95%: 14.4-85.6) ρ = 0.028, NNT 2 (CI95%: 1.3 - 6.9). No adverse events were recorded including INR < 2 at 24 hours of treatment administration. Our results are consistent with studies where specific oral presentation of Vit-K was used. The results indicate that oral administration of Vit-K, prepared from an intravenous Vit-K preparation, is safe and more effective to revert excessive anticoagulation than simply withholding warfarin, in places where specific preparation of oral Vit-K is not available or too expensive.

Diagnosis and treatment of congenital hemophilia with inhibitors: A Latin American perspective / Diagnóstico y tratamiento de la hemofilia congénita con inhibidores: Una perspectiva latinomericana

The Committee of Latin America on the Therapeutics of Inhibitor Groups (CLOTTING) is composed of a number of hemophilia specialists from Latin America. The group aims to encourage the adoption of a good standard of care for Latin American patients with hemophilia. The occurrence of inhibitors in patients with hemophilia poses clinical challenges, and it is estimated that between 1000 and 3 000 patients in Latin America are affected by hemophilia with inhibitors. There is an urgent need to establish a regional consensus and clinical guidelines for the diagnosis and treatment of these patients. We present an extensive review based on best current clinical practice and published literature, as seen from a Latin American perspective, taking into account the variable nature of hemophilia care available in the various countries in this Region.

El Comité Latinoamericano sobre la Terapéutica de Personas con Inhibidores (CLOTTING) está compuesto por un grupo de especialistas en hemofilia de Latinoamérica. El objetivo del grupo es promover la adopción de un estándar de tratamiento óptimo para los pacientes con hemofilia en Latinoamérica. La prevalencia de inhibidores en pacientes con hemofilia en Latinoamérica determina desafíos clínicos y se estima que de 1000 a 3000 pacientes en esta región están afectados con hemofilia e inhibidores. Existe una necesidad urgente de establecer un consenso regional y guías clínicas para el diagnóstico y tratamiento de estos pacientes. Nosotros presentamos una revisión exhaustiva basada en las mejores prácticas clínicas vigentes y en los datos publicados en la literatura, con una perspectiva latinoamericana, tomando en cuenta la variabilidad existente de los tratamientos de la hemofilia disponibles en los diferentes países de esta Región.

Isolation and characterization of a serine proteinase with thrombin-like activity from the venom of the snake Bothrops asper

A serine proteinase with thrombin-like activity was isolated from the venom of the Central American pit viper Bothrops asper. Isolation was performed by a combination of affinity chromatography on aminobenzamidine-Sepharose and ion-exchange chromatography on DEAE-Sepharose. The enzyme accounts for approximately 0.13 percent of the venom dry weight and has a molecular mass of 32 kDa as determined by SDS-PAGE, and of 27 kDa as determined by MALDI-TOF mass spectrometry. Its partial amino acid sequence shows high identity with snake venom serine proteinases and a complete identity with a cDNA clone previously sequenced from this species. The N-terminal sequence of the enzyme is VIGGDECNINEHRSLVVLFXSSGFL CAGTLVQDEWVLTAANCDSKNFQ. The enzyme induces clotting of plasma (minimum coagulant dose = 4.1 µg) and fibrinogen (minimum coagulant dose = 4.2 µg) in vitro, and promotes defibrin(ogen)ation in vivo (minimum defibrin(ogen)ating dose = 1.0 µg). In addition, when injected intravenously in mice at doses of 5 and 10 µg, it induces a series of behavioral changes, i.e., loss of the righting reflex, opisthotonus, and intermittent rotations over the long axis of the body, which closely resemble the `gyroxin-like' effect induced by other thrombin-like enzymes from snake venoms.

Use of recombinant factor VIIa for emergency reversal of anticoagulation.

CONTEXT: There is limited data regarding the use of activated recombinant factor VII (rFVIIa) in anticoagulated patients requiring reversal. Aims: To identify and describe characteristics of subjects who received rFVIIa as part of emergency treatment aimed at improving hemostasis. SETTINGS AND DESIGN: Data was obtained from an international peer-reviewed registry haemostasis.com. This registry contains data reported by physicians, who had elected to use rFVIIa to control bleeding in an emergency clinical situation. The contributors' approval for inclusion in the study was obtained and they were requested to validate and update information. MATERIALS AND METHODS: Database review of cases receiving rFVIIa to manage bleeding coherent with the use of anticoagulant therapy. Statistical Analysis: The Wilcoxon signed rank test was used to compare requirements for blood products and crystalloids/colloids during the 24h preceding and following rFVIIa administration, as well as changes in the levels of clotting factors during that period. RESULTS: Eighteen patients were treated with rFVIIa (median dose: 87.35 microg/kg; range: 20.0-106.0 microg/kg) for bleeding. Anticoagulants requiring reversal included low-molecular-weight heparin (n = 6), unfractionated heparin (n =8), coumarin (n =3) and warfarin (n=1). All patients had failed to respond to traditional antidotes and blood products. Following administration, bleeding stopped in 10, markedly decreased in five and slowed in the remaining three. Amongst 12/16 patients, a response was observed within 2.0 h of first administration. The requirement for blood products and crystalloids/colloids decreased ( P < 0.05) after rFVIIa administration. rFVIIa was well tolerated. CONCLUSIONS: rFVIIa may play a role in control of untoward bleeding in subjects receiving anticoagulation therapy.