[Long-term response to rituximab in a patient with acquired hemophilia]. / Respuesta a largo plazo con rituximab en una paciente con hemofilia adquirida.

A 28 year-old female without history of previous disease. In the seventh month of her first pregnancy she developed hemorrhagic tendency that worsened in the early postpartum period. Activated partial thromboplastin time was 110 sec (control=35.8 sec) with negative tests for lupus anticoagulant. Factor VIII was <1% and a factor VIII inhibitor titer was 84 Bethesda Units/mL (BU). Initial therapy included methylprednisolone, prednisone, and cyclophosphamide. After two weeks of treatment, clinical conditions of the patient improved slightly and she was discharged. Outpatient therapy included azathioprine, and prednisone for a period of 22 months but in-hospital management was several times required. We initiated rituximab 375 mg/m2/week/4 weeks. A clinical improvement and increased levels of factors VIII and XI were observed 10 weeks later and factor VIII inhibitor decreased to undetectable levels. After a 82-month follow-up period (since the first rituximab infusion), she is asymptomatic and factor VIII and factor XI plasma levels are 70% and 94%, respectively FVIII inhibitor level is still undetectable. Rituximab seems an alternative for the treatment of acquired hemophilia refractory to standard treatment.

Changes on hemostatic parameters induced by 17beta-estradiol, ethinylestradiol, and the 17beta-aminoestrogen pentolame in the male Wistar rat.

Oral contraceptives containing estrogens increases the incidence of thromboembolic events. In contrast, administration of 17beta-aminoestrogens prolonged blood clotting time (BCT) in rodents. We studied the effect of estradiol (E(2)), ethinylestradiol (EE) and pentolame on some screening hemostatic tests. BCT was evaluated 24, 48, 72 and 96 h post-treatment. Rats received subcutaneously (s.c.) for five consecutive days E(2) (0.1-1000 microg), EE (1-1000 microg), pentolame (0.1-1000 microg), or vehicle (propyleneglycol 0.3 ml). At 48 h post-treatment E(2) (1000 microg) diminished BCT (32%, P<0.01), in contrast pentolame (1000 microg) augmented BCT by 41% (P<0.01). After 72 h, E(2) showed procoagulant effects with 10, 100 and 1000 microg doses (-45, -30, and -21%, respectively). Significant effects on BCT of EE were observed 72 h after with 1000 microg (-12%, P<0.05). Animals were treated s.c. for two consecutive days with E(2) (3mg/100g), pentolame (4 mg), or vehicle (0.1 ml). BCT, bleeding time (BT), platelet aggregation (PA), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen concentration were determined. E(2) produced a significant diminution on BCT (-20%) after 72 h whereas pentolame increased BCT from 24 to 96 h (62%, maximal response at 48 h). APTT and PT coagulation times of the groups treated with E(2) and pentolame were lengthened (33 and 29%; 16 and 24%, respectively; P<0.05). Fibrinogen concentration increased (115%, P<0.01) only in the pentolame-treated group. Pentolame and E(2) produced any effects on BT and PA compared with control groups, indicating that platelet function was not modified. Our results indicate that E(2), EE and pentolame affects the plasmatic phase of the hemostatic mechanism.

Heparina de bajo peso molecular y embarazo. Tres pacientes con estenosis mitral pura / Low molecular weight heparin in pregnancy. Report of three cases with pure mitral stenosis

Se presentan 3 casos de mujeres portadoras de estenosis mitral pura con área valvular < 1 cm², que por falta de respuesta a tratamiento médico, se sometieron a valvuloplastía mitral percutánea (VMP) con técnica de Inoue antes de la semana 30 del embarazo. Desde su ingreso recibieron heparina de bajo peso molecular (HBPM; Enoxaparina) como profiláctico de formación de trombos intracavitarios y enfermedad embolígena sistémica secundaria, se realizó ecocardiogramas transtorácico y transesofágico (ETT y ETE) para demostrar efecividad del fármaco en evitar formación de trombos, sin causar efectos colaterales en la madre ni teratogénicos en el producto. La dosis utilizada fue de 40 mg. Subcutáneo cada 24 hs. durante 16 semanas en las tres pacientes, se repitió el ETT y ETE durante la VMP y se demostró ausencia de trombos intracavitarios. Ninguna paciente presentó alteraciones en la biometría hemática, ni en los tiempos de coagulación. Se obtuvieron productos sin malformaciones. En conclusión, aunque la serie de pacientes es pequeña, se demostró que la HBPM puede utilizarse como alternativa del uso de anticoagulante oral así como de la heparina convencional, como profiláctico durante el primer trimestre del embarazo sin provocar efectos secundarios indeseables