Concentrado de plaquetas de donante único en pacientes plaquetopénicos / Single Donor Platelet Concentrate in Platelettopenic Patients

CONTEXTO CLÍNICO: Se define plaquetopenia como un recuento de plaquetas menor a 150.000/mm3. Dentro de las causas se destacan la infección aguda, las enfermedades oncohematológicas, enfermedades hepáticas, la inducida por drogas (diez casos por millón personas-año, en Estados Unidos y Europa), la púrpura trombocitopénica inmune (100 casos por millón de personas-año, en Estados Unidos), la púrpura trombótica trombocitopénica (cuatro a 11 casos por millón de personas-año en Estados Unidos), el síndrome urémico hemolítico y la coagulación intravascular diseminada, entre otras. Los pacientes con un recuento plaquetario mayor a 50.000/mm3 raramente presentan síntomas. Un recuento entre 30.000 y 50.000/mm3 puede llegar a manifestarse con púrpura. Valores de plaquetas entre 10.000 a 30.000/mm3 puede causar sangrado ante un traumatismo mínimo, mientras que un recuento inferior a 5.000/mm3 puede producir sangrado espontáneo y constituir una emergencia hematológica. TECNOLOGÍA: A partir de una donación de sangre total, mediante centrifugaciones sucesivas se obtienen diferentes componentes sanguíneos, que pueden infundirse a varios enfermos (típicamente concentrados de hematíes, concentrado de plaquetas y plasma fresco). Los procedimientos más utilizados para preparar los CP estándar de sangre total pueden dividirse en aquellos que emplean el método del plasma rico en plaquetas obtenido tras centrifugación inicial débil de las unidades de sangre, o métodos de buffy coat (capa leucocítica), por centrifugación inicial intensa. En ambos casos, inmediatamente después del fraccionamiento se pueden emplear filtros para obtener un producto leucorreducido. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de aféresis de plaquetas de donante único para pacientes con plaquetopenia y requerimiento de transfusiones. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron una RS, dos estudios observacionales, cinco GPC, y cuatro informes de políticas de cobertura de aféresis de plaquetas de donante único. CONCLUSIONES: Evidencia de muy baja calidad no permite establecer si los concentrados de plaquetas de donante único reducen las infecciones virales y bacterianas, y reacciones alérgicas menores relacionadas con la transfusión, en comparación con los concentrados plaquetarios provenientes de sangre entera de donantes múltiples. En cuanto a la injuria pulmonar relacionada con la transfusión, ambos preparados, tendrían un riesgo similar. La mayoría de las guías de práctica clínica consideran a las dos alternativas como válidas. La mayoría de las políticas de cobertura relevadas no hacen mención específica respecto a la aféresis de plaquetas de donante único. Si bien no se encontraron estudios de costo efectividad, impacto presupuestario ni organizacional, el costo no es alto en relación con su comparador y el impacto presupuestario esperado es pequeño lo que hace creer que podría tener una costo-efectividad razonable.

Assessment of TRPM7 functions by drug-like small molecules.

Transient receptor potential cation channel subfamily M member 7 (TRPM7) is a plasma membrane ion channel linked to a cytosolic protein kinase domain. Genetic inactivation of this bi-functional protein revealed its crucial role in Ca2+ signalling, Mg2+ metabolism, immune responses, cell motility, proliferation and differentiation. Malfunctions of TRPM7 are associated with anoxic neuronal death, cardiac fibrosis, tumour progression and macrothrombocytopenia. Recently, several groups have identified small organic compounds acting as inhibitors or activators of the TRPM7 channel. In follow-up studies, the identified TRPM7 modulators were successfully used to uncover new cellular functions of TRPM7 in situ including a crucial role of TRPM7 in Ca2+ signaling and Ca2+ dependent cellular processes. Hence, TRPM7 has been defined as a promising drug target. Here, we summarize the progress in this quickly developing field.

MIF-Mediated Hemodilution Promotes Pathogenic Anemia in Experimental African Trypanosomosis.

Animal African trypanosomosis is a major threat to the economic development and human health in sub-Saharan Africa. Trypanosoma congolense infections represent the major constraint in livestock production, with anemia as the major pathogenic lethal feature. The mechanisms underlying anemia development are ill defined, which hampers the development of an effective therapy. Here, the contribution of the erythropoietic and erythrophagocytic potential as well as of hemodilution to the development of T. congolense-induced anemia were addressed in a mouse model of low virulence relevant for bovine trypanosomosis. We show that in infected mice, splenic extramedullary erythropoiesis could compensate for the chronic low-grade type I inflammation-induced phagocytosis of senescent red blood cells (RBCs) in spleen and liver myeloid cells, as well as for the impaired maturation of RBCs occurring in the bone marrow and spleen. Rather, anemia resulted from hemodilution. Our data also suggest that the heme catabolism subsequent to sustained erythrophagocytosis resulted in iron accumulation in tissue and hyperbilirubinemia. Moreover, hypoalbuminemia, potentially resulting from hemodilution and liver injury in infected mice, impaired the elimination of toxic circulating molecules like bilirubin. Hemodilutional thrombocytopenia also coincided with impaired coagulation. Combined, these effects could elicit multiple organ failure and uncontrolled bleeding thus reduce the survival of infected mice. MIF (macrophage migrating inhibitory factor), a potential pathogenic molecule in African trypanosomosis, was found herein to promote erythrophagocytosis, to block extramedullary erythropoiesis and RBC maturation, and to trigger hemodilution. Hence, these data prompt considering MIF as a potential target for treatment of natural bovine trypanosomosis.

Role of platelet volume indices in the differential diagnosis of thrombocytopenia: a simple and inexpensive method.

Thrombocytopenia may result from hypoproliferation in marrow, or peripheral destruction of platelets. Distinction between these two categories is usually made by bone marrow examination. Some studies in literature hint that platelet volume indices are differentially altered in various causes of thrombocytopenia. The present study was aimed at investigating the role of platelet volume indices in the differential diagnosis of thrombocytopenia. Sixty healthy controls and 60 patients (study group) with thrombocytopenia (platelet count < 150 x 10(9)/l) were included in the study. The study group was divided into two categories: hypoproliferative (megaloblastic and non-megaloblastic) and destructive thrombocytopenia. Clinical features, platelet counts and platelet indices were studied in both these categories, and statistical analysis was performed. Platelet counts in the three categories of thrombocytopenia were statistically not different. All the three platelet volume indices were significantly higher in megaloblastic group as compared to the non-megaloblastic hypoproliferative category. Platelet distribution width (PDW) was significantly different between destructive thrombocytopenia and non-megaloblastic hypoproliferative groups. In conclusion, we recommend the division of hypoproliferative category of thrombocytopenia into megaloblastic and non-megaloblastic types. Alterations in platelet indices, especially PDW can differentiate non-megaloblastic hypoproliferative category from both the destructive and megaloblastic thrombocytopenia category. These simple indices can be routinely used in the initial evaluation of a patient with thrombocytopenia.

Relationship between platelet count and bleeding risk in thrombocytopenic patients.

Platelets are lost from circulation by 2 mechanisms: senescence and random loss. Approximately 7.1 x 10(3) platelets/microL/d are postulated to be randomly used in maintaining vascular integrity. Thus, in clinically stable patients, major bleeding is unusual unless the platelet count is

Lack of increased bleeding after liver biopsy in patients with mild hemostatic abnormalities.

Prophylactic transfusions of fresh frozen plasma and platelets are sometimes given to patients with mild elevations in prothrombin time (PT) and partial thromboplastin time (PTT) and mild thrombocytopenia before percutaneous liver biopsy. To determine whether PTs and PTTs 1.1-1.5 times midrange normal levels and platelet counts 50-99 x 10(9)/L are associated with increased bleeding complications, hospital records of all patients who underwent percutaneous liver biopsy during 56 consecutive months (n = 291) were reviewed. Complete information was available for 177 inpatient procedures (155 standard, 22 fine needle). Overall, the frequency of bleeding complications in patients with platelet counts greater than or equal to 50 X 10(9)/L was 3.4% (6 of 175), with no significant difference between patients with mild hemostatic abnormalities and patients with normal parameters. These data suggest that prophylactic transfusions may not be necessary. One factor was highly associated with bleeding complications: a patient diagnosis of malignancy, 14% (7 of 50) compared with 0.8% (1 of 127) among other patients (P less than 0.001). These patients should be monitored closely after biopsy.

An appraisal of bone marrow biopsy in assessment of sick dogs.

Dogs were classified into a number of disease categories according to hematological, cytological and serochemical changes. Aspiration and core bone marrow biopsies were examined in 128 dogs in the various disease categories and compared to marrow samples in 36 dogs which appeared clinically normal. Differential cell counts on bone marrow smears were examined in relation to the blood variables in all animals. Blood and bone marrow data (group means) were compared among the normal and disease groups. Anemia, responsive and poorly responsive was the most frequent blood abnormality. Most dogs in the thrombocytopenia group had increased numbers of megakaryocytes in the marrow but two dogs had a marked decrease. The frequency of serious alteration of marrow production of the erythroid, myeloid and megakaryocytic series was less than anticipated. Marrow hemopoiesis was not significantly compromised in dogs with lymphoma or in dogs with other types of cancer. Bone marrow examination was necessary for the diagnosis of myelofibrosis and pancytopenia and was very helpful in the groups with insufficient change in the blood to permit a definitive diagnosis to be made. The myeloid-erythroid ratio was a useful indicator of marrow response while the erythroid maturation index and the myeloid maturation index were useful for identification of altered patterns of maturation (ineffective hemopoiesis). The reticulocyte response in absolute numbers is the most efficient and clinically relevant measure of erythroid response.