Fixed‐dose low‐molecular‐weight heparin for secondary prevention of venous thromboembolism in patients with disseminated cancer: a prospective cohort study

Abstract

Summary. Introduction : Secondary prevention of venous thromboembolism (VTE) with vitamin K antagonists is often problematic in patients with cancer. We prospectively evaluated the effectiveness and safety of long‐term subcutaneous dalteparin in a series of consecutive patients with symptomatic VTE and metastatic cancer. Patients and Methods : The study included 203 patients, aged 36–96 years. The initial treatment consisted of a 7‐day course of subcutaneous dalteparin according to body weight. Then, patients received a fixed dose of 10 000 IU dalteparin once daily for at least 3 months. In patients developing transient thrombocytopenia the dose was reduced to 5000 IU daily while the platelet count remained <50 000; and to 2500 IU daily while it remained <10 000. Patients undergoing any surgical intervention during the study were put on 5000 IU daily during the first 4 days, switching thereafter to 10 000 IU. Patients undergoing any other invasive procedure (i.e. biopsies, punctures) received a 5000 IU dose the same day, instead of 10 000 IU. Results : Eleven patients (5.4%) developed major bleeding complications (6 fatal) during the 3‐month study period, and 18 patients (8.9%) developed VTE recurrences (2 patients died). There were no higher complication rates in patients with either liver or brain metastases, nor during thrombocytopenia, surgery or invasive procedures. Conclusions : Fixed dose 10 000 IU subcutaneous dalteparin once daily for 3 months was not associated with more complications in patients with liver or brain metastases. The dose adjustment for patients with thrombocytopenia, surgery or invasive procedures was safe too.

Management of anticoagulation for cancer‐associated thrombosis in patients with thrombocytopenia: A systematic review

“…Of these, six were excluded for failing to include patients undergoing management according to both treatment strategies,6, 10, 11, 12, 13, 14 one was excluded for failure to report outcomes of both strategies7 and one was excluded for study design (case series of only five patients) 15. The remaining two studies were included and are described below.…”

Tratamiento de la trombosis venosa profunda con heparinas de bajo peso molecular: Estudio comparativo con anticoagulación oral

“…Los pacientes con cáncer como factor predisponente de la enfermedad tromboembólica venosa, parecen beneficiarse particularmente del tratamiento con heparinas de bajo peso molecular comparado con antivitaminas K (12)(13)(14)(15)(16).…”

“…Varios de estos estudios comparativos son numé-ricamente pequeños, algunos de ellos son análisis de cohortes, no se cita la potencia estadística y debido a la diferente vía de administración de los fármacos anticoagulantes son ensayos abiertos, por todo ello la validez de las conclusiones publicadas puede ser pequeña. Donde mejores pruebas de eficacia y seguridad existen es en el tratamiento de la trombosis venosa profunda asociada a cáncer, habiéndose demostrado un mejor perfil de seguridad para las heparinas de bajo peso molecular y menor tasa de mortalidad (12)(13)(14)(15)(16).…”

Prevention and treatment of venous thromboembolism in patients with cancer

“…In contrast, Monreal and colleagues continued dalteparin therapy at a dose of 5000 U with a platelet count <50,000 and 2500 U if the platelets dropped below 10,000 [Monreal et al 2004]. Thrombocytopenia was associated with 7/16 patients with minor bleeding and 0/11 patients with major bleeding.…”

“…It is difficult to compare the individual study outcomes given the differences in the follow-up period and relatively small sample sizes of the studies, and relate these outcomes to drug dosing alone. One prospective cohort study reported outcomes of 203 consecutive patients with cancer-associated thrombosis treated with 10,000 U of dalteparin once per day for 3 months regardless of weight [Monreal et al 2004]. All patients had metastatic cancer.…”