High variability in Factor IX one-stage assay in samples spiked with nonacog beta pegol among different pairs of reagent/detection system.

INTRODUCTION: Haemophilia B (HB) is an X-linked hereditary bleeding disorder characterized by coagulation factor IX (FIX) deficiency. To improve the quality of life of patients and adherence to treatment, recombinant factor concentrates modified to extend their half-life have been developed, called extended half-life factors (EHL: extended half-life). Nonacog beta pegol (N9-GP) is a glycopegylated recombinant human FIX molecule that has a half-life of 93 h with a single dose and has shown a higher recovery percentage than other molecules. To diagnose and monitor the treatment of haemophiliac patients, FIX activity is determined with the one-stage clotting assay (OSA) and/or the chromogenic assay. The objective of this work, carried out in three centres, was to measure the recovery of N9-PG with 10 different activated partial thromboplastin time (APTT) reagents on three platforms, in samples spiked in vitro with N9-GP, at four different concentration levels. METHODS: It was measured the recovery of N9-GP with 10 different APTT reagents (polyphenol, ellagic acid, silice dioxide, colloidal silica as APTT activator on three platforms, in sample spiked in vitro with N9-GP. RESULTS: The results show heterogeneity in the activity of N9-GP measured by OSA with the different APTT reagents when the calibrations were performed with the specific calibrator of each coagulometer. A recovery percentage between 87% and 108% was obtained only with polyphenol and ellagic acid as activator in the three platforms evaluated. The other reagents studied overestimate or underestimate, with no clear profile. When a calibration curve was performed with a calibrator prepared from the N9-GP vial, all APTT reagents met the established recovery requirement. CONCLUSION: APTT reagents with polyphenol or ellagic acid as activator would be the only ones appropriate when using the commercially available OSA with specific calibrator to monitor patients treated with N9-GP.

The fibrinogen prothrombin time-derived method is not useful in patients anticoagulated with low molecular weight heparins or rivaroxaban.

Essentials Fibrinogen prothrombin time-derived (FIBPT-d) behavior in anticoagulated patients is under studied. FIBPT-d method overestimates fibrinogen in rivaroxaban and low molecular weight heparin samples. Unfractionated heparin and dabigatran samples showed similar bias to the control group. Rabbit brain and human recombinant thromboplastin behavior was different in rivaroxaban samples. SUMMARY: Background The fibrinogen prothrombin time-derived (FIBPT-d) method with photo-optical coagulometers is easy and economical. However, there are few reports on the behavior of this test on samples from patients anticoagulated with direct oral anticoagulants or low molecular weight heparin (LMWH). Objective To compare fibrinogen results obtained with the Clauss (FIB C) method and the FIBPT-d method with two thromboplastins in anticoagulated patients. Population The study population comprised 295 consecutive anticoagulated patients: 99 treated with vitamin K antagonists (VKAs), 49 treated with unfractionated heparin (UFH), 47 treated with LMWH, 50 treated with rivaroxaban, 50 treated with dabigatran, and 100 normal controls (NCs). Methods Dabigatran samples were analyzed by the use of FIB C with HemosIL Fibrinogen C or 100 NHI thrombin units mL-1 reagents; rabbit brain and human recombinant thromboplastins with HemosIL PTFibrinogen HS plus (HS) and Recombiplastin 2G (RP) were used for FIBPT-d method. Heparin and rivaroxaban levels were assessed with HemosIL Liq antiXa with specific calibrators; dabigatran levels were determined with the HemosIL Direct Thrombin Inhibitor Assay. All assays were performed on the ACL TOP platform in two laboratories. Percentage biases for the FIBPT-d method versus the FIB C method were calculated by the use of Bland-Altman plots. Results Positive biases of the FIBPT-d method versus the FIB C method with both thromboplastins were seen in NC samples (13.7% and 18.9% for HS and RP, respectively), but biases with HS in rivaroxaban and VKA patient samples were higher than that in NC samples, at 31.9% and 34.0%, respectively. LMWH patient samples showed higher bias than NC samples: 26.5% and 29.3.0% with HS and RP, respectively. UFH and dabigatran patient samples showed similar bias as NC samples. Conclusion The FIBPT-d method should not be used in anticoagulated patients, because the FIBPT-d mathematical algorithm has been validated only in normal subjects, so overestimation could occur in these patients.

Agentes antitrombóticos en Terapia Intensiva: manejo práctico de los nuevos anticoagulantes orales directos / Antithrombotic agents in Intensive therapy: management practical of the new oral oral anticoagulants

Los nuevos anticoagulantes orales compiten actualmente, con alguna ventaja, con la terapéutica tradicional en la prevención de la cardioembolia en fibrilación auricular, y en la prevención y el tratamiento de la enfermedad tromboembólica venosa. Estudios recientes han demostrado una eficacia equivalente a la de los antagonistas de la vitamina K, con un mejor perfil de seguridad. Además, superan algunos inconvenientes de estos antagonistas, como la necesidad de ajuste de dosis y el monitoreo frecuente de la RIN, las múltiples interacciones farmacológicas y los cuidados con la dieta. Pero con los nuevos agentes debemos ser cautos, porque el riesgo de sangrado puede aumentar significativamente en ciertos grupos de pacientes con insuficiencia renal, añosos o muy frágiles. Aunque se emplean usualmente en dosis fijas, en casos especiales (peso <50 kg, edad avanzada, disfunción renal, alto riesgo de sangrado), esta dosis se debe modificar. Si bien, en la práctica clínica, no es necesario hacer pruebas de monitoreo de la coagulación, no contamos con pruebas adecuadas para evaluar su eficacia clínica y tampoco tenemos hoy, en nuestro medio, un antídoto eficaz en caso de sangrado importante. Sin embargo, se están realizando estudios con nuevas pruebas de hemostasia que pueden ayudarnos a interpretar el nivel de anticoagulación en estos pacientes y ya se han desarrollado antídotos para algunos de los anticoagulantes de acción directa que pronto estarán disponibles en nuestro medio.(AU)

New oral anticoagulants represent an interesting alternative to traditional therapy for the prevention of stroke in atrial fibrillation, and the thromboprophylaxis and treatment of venous thromboembolic disease. Several studies demonstrated equivalent efficacy to that of vitamin K antagonists with a more favourable safety profile. New oral anticoagulants overcome some of the main problems of these antagonists: the need of tailoring dosing, frequent interactions with other drugs and diet. But physicians have to keep in mind that new oral anticoagulants are not absolutely free of complications, and must be cautious with patients at high risk of bleeding. Also in special cases (<50 kg, advanced age, renal impairment) the usual dose must be adapted. At present there are not specific tests to evaluate the effect of these new anticoagulants, although it is usually not necessary to do any coagulation test in clinical practice. Another concern regarding new oral anticoagulants is the absence of specific antidotes, although specific antidotes are under clinical investigation and are soon going to be available in our country.(AU)

Factor XIII en transplante de médula ósea / Factor XIII in Bone Marrow Transplantation

La subunidad A del Factor XIII (FXIII), parte activa del FXIII, es sintetizada casi exclusivamente por megacariocitos y precursores de monocitos-macrófagos. Determinándose la actividad del FXIII en pacientes sometidos a transplante de médula ósea autólogo (TAMO) y alegeneico (TMO). En 52 pacientes, 30 TAMO y 22 TMO, la actividad del FXIII fue estudiada en días fijos (basal, mitad de régimen condicionante, día 0, día +7, día +15 y día +30). Un descenso del FXIII fue encontrado en todos los casos, cuando se comparó con los niveles basales, alcalzando el nadir de la actividad al día +7. La caída del FXIII fué significativamente más pronunciada en TMO que en TAMO. Se demostró correlación entre la actividad del FXIII y el tiempo de recuperación hematopoyética. Siete de los 52 ptes. (13, 4 porciento) tuvieron niveles de actividad del FXIII inferiores al 10 porciento, sólo 3 sufrieron sangrados asociados. En TMO, los niveles de PAI estaban significativamente aumentados en los días +7, +15 y +30. En conclusión, la actividad del FXIII está siempre desminuída post-trasplante y el restablecimiento de los niveles basales se relaciona directamente con la velocidad de reconstitución hematopoyética. Diferencias en los tiempos de "engraftment" podrían explicar las diferencias encontradas entre TAMO y TMO. Finalmente, la ausencia de sangrado en ptes. con actividad del FXIII por debajo de niveles hemostáticos(<10 porciento) podría deberse a hipofibrinolisis concominante asociada a aumento del PAI

Factor XIII en transplante de médula ósea / Factor XIII in Bone Marrow Transplantation

La subunidad A del Factor XIII (FXIII), parte activa del FXIII, es sintetizada casi exclusivamente por megacariocitos y precursores de monocitos-macrófagos. Determinándose la actividad del FXIII en pacientes sometidos a transplante de médula ósea autólogo (TAMO) y alegeneico (TMO). En 52 pacientes, 30 TAMO y 22 TMO, la actividad del FXIII fue estudiada en días fijos (basal, mitad de régimen condicionante, día 0, día +7, día +15 y día +30). Un descenso del FXIII fue encontrado en todos los casos, cuando se comparó con los niveles basales, alcalzando el nadir de la actividad al día +7. La caída del FXIII fué significativamente más pronunciada en TMO que en TAMO. Se demostró correlación entre la actividad del FXIII y el tiempo de recuperación hematopoyética. Siete de los 52 ptes. (13, 4 porciento) tuvieron niveles de actividad del FXIII inferiores al 10 porciento, sólo 3 sufrieron sangrados asociados. En TMO, los niveles de PAI estaban significativamente aumentados en los días +7, +15 y +30. En conclusión, la actividad del FXIII está siempre desminuída post-trasplante y el restablecimiento de los niveles basales se relaciona directamente con la velocidad de reconstitución hematopoyética. Diferencias en los tiempos de "engraftment" podrían explicar las diferencias encontradas entre TAMO y TMO. Finalmente, la ausencia de sangrado en ptes. con actividad del FXIII por debajo de niveles hemostáticos(<10 porciento) podría deberse a hipofibrinolisis concominante asociada a aumento del PAI (AU)

[Bone marrow transplantation for severe aplastic anemia]. / Transplante de Médula osea en anemia aplástica severa.

Severe aplastic anemia is a hematological disease with a high mortality rate, for which bone marrow transplantation is the treatment of choice, specially in children and young adults. The number of transfusions undergone before the transplant is the most important factor to predict the possibility of graft failure. Twenty patients with severe aplastic anemia, most of them already multiple transfused, were transplanted utilizing cyclophosphamide combined with antilymphocyte globulin as a conditioning regiment. All the evaluable patients engrafted and there were no episodes of graft failure. Three patients died, and 17 (85%) are alive with hematopoietic recovery at a median of 27.7 months post-transplant. Bone marrow transplantation was an excellent therapeutic option in this series of patients with severe aplastic anemia and the conditioning regiment appeared to be sufficiently myeloablative and immunosuppressive to avoid early or late graft failure.

Total lymphoid irradiation for treatment of drug resistant chronic GVHD.

We report our experience with total lymphoid irradiation (TLI) in three patients with GVHD which had failed to respond to standard drug treatment. The clinical manifestations of GVHD markedly improved with TLI treatment.

[Acute monoarthritis and laryngeal obstruction as extralymphatic manifestations of non-Hodgkin's lymphoma]. / Monoartritis aguda y obstrucción laríngea como manifestaciones extraganglionares de linfoma no Hodgkin.

Joints and larynx are uncommonly involved by non-Hodgkin's lymphoma (NHL). Synovial involvement has been reported in only 7 cases, mainly located in the knees. When this is the first location of NHL it is usually misdiagnosed. The treatment of choice is local radiotherapy followed by systemic chemotherapy. Laryngeal lymphoma can be either primary or forming part of multifocal disease. The prognosis of the primary form is usually good only with radiotherapy, whereas the prognosis of the laryngeal location of advanced disease is rather poor. The symptoms include dysphonia and slowly progressive dyspnea. A case of NHL is presented who showed initial arthritis of the knee, later evolving into severe laryngeal obstruction, an association not previously reported.