RESUMEN
Hereditary spherocytosis is a common hemolytic anemia with an estimated incidence of 1 / 2500 births. It is caused by a molecular defect in one or more of the proteins of the red blood cell cytoskeleton. Mutations in the ABCB11 gene, encoding the bile salt export pump, can entail progressive familial intrahepatic cholestasis and benign recurred intrahepatic cholestasis. A 18 year old Turkish patient with hereditary spherocytosis was admitted to hospital with pruritus and severe jaundice. Ultrasound examination presented stones in gallbladder and bile duct. After endoscopic retrograde cholangiography with extraction of small bile duct stones abdominal pain resolved and liver enzymes normalized within a few days, but bilirubin and bile acids remained highly elevated. Liver biopsy revealed a severe canalicular cholestasis. Genetic analysis showed the compound heterozygous variants ABCB11 A 444V and 3084A > G. Treatment with ursodesoxycholic acid and intermittent therapy with prednisone reduced pruritus and jaundice with concomitant improvement of blood test. Here we report the first case of a patient with combined hereditary spherocytosis and compound heterozygous ABCB11 gene variants predisposing to intrahepatic cholestasis. Therefore, patients with hemolytic disorders should be investigated for bile acid transporter diseases in case of hyperbilirubinemia and severe cholestasis.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Alelos , Bilirrubina/sangre , Colestasis Intrahepática/sangre , Colestasis Intrahepática/genética , Esferocitosis Hereditaria/sangre , Esferocitosis Hereditaria/genética , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP , Adolescente , Antiinflamatorios/uso terapéutico , Ácidos y Sales Biliares/sangre , Biopsia , Colestasis Intrahepática/tratamiento farmacológico , Colestasis Intrahepática/patología , Análisis Mutacional de ADN , Cálculos Biliares/sangre , Cálculos Biliares/tratamiento farmacológico , Cálculos Biliares/genética , Cálculos Biliares/patología , Tamización de Portadores Genéticos , Variación Genética/genética , Humanos , Hígado/patología , Masculino , Prednisona/uso terapéutico , Isoformas de Proteínas/genética , Esferocitosis Hereditaria/tratamiento farmacológico , Esferocitosis Hereditaria/patologíaRESUMEN
The aim of the proposed concept is to use anticoagulant therapy in prophylaxis and therapy of thromboembolic events only to an extent that the coagulation activation is just not any longer detectable. It results an individualized anticoagulation tailored to the coagulation activation of the patient (individualized "minimal invasive" anticoagulation). Intensity and control of efficiency are to be monitored by measurement of in vivo coagulation activation, e.g. by D-dimer-antigen measurement. Especially with the use of the new oral anticoagulants such a saver anticoagulant therapy - as far as possible from bleeding risk - could open up new indications, which so far are not used because of safety reasons. More patients at risk could be prevented from thromboembolic events. The proposed concept is based on pathophysiological considerations and own clinical experience. It should be evaluated for efficiency in clinical studies.
Asunto(s)
Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Antifibrinolíticos/uso terapéutico , Productos de Degradación de Fibrina-Fibrinógeno/uso terapéutico , Tromboembolia/tratamiento farmacológico , Administración Oral , Anticoagulantes/administración & dosificación , Antifibrinolíticos/administración & dosificación , Antifibrinolíticos/efectos adversos , Ensayos Clínicos como Asunto , Productos de Degradación de Fibrina-Fibrinógeno/administración & dosificación , Reducción del Daño , Humanos , Riesgo , Tromboembolia/fisiopatología , Trombosis/tratamiento farmacológicoRESUMEN
Based on the concept that the so-called resistance to anti-platelet drugs is meant to describe a phenomenon where the drug does not hit its direct pharmacodynamic target, assays, used to evaluated the effects of anti-platelet drugs, should as closely as possible measure the direct pharmacodynamic effect of a particular drug. Thus, for the detection of aspirin effects, thromboxane concentrations or arachidonic acid-induced responses (light aggregometry, whole-blood aggregometry) should be measured. For the detection of clopidogrel actions, VASP phosphorylation (flow cytometry) or ADP-induced responses (light aggregometry, whole blood aggregometry) should be analysed.
Asunto(s)
Aspirina/uso terapéutico , Resistencia a Medicamentos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Ticlopidina/análogos & derivados , Clopidogrel , Humanos , Ticlopidina/uso terapéuticoRESUMEN
In cardiopulmonary bypass (CPB) surgery high dose heparin is necessary to inhibit the clotting cascade which is activated through damage to the vessels (extrinsic pathway) as well as contact activation of the blood with the various artificial surfaces of the CPB machine (intrinsic pathway). In most European heart surgery centres, the fibrinolytic activation that always occurs in CPB due to contact activation is reduced by the proteinase inhibitor aprotinin. Monitoring of anticoagulation during CPB is performed with the activated whole blood clotting time (ACT). The two machines commonly used for this purpose, Hemotec and Hemochron, use different contact system activators, kaolin and celite. These activators displayed highly significant differences, in both in vitro tests (modified APTT with whole blood in a neutral coagulometer), and ACT in both machines where aprotinin and heparin were used, as well as with parallel measurements with the two machines with blood from patients undergoing CPB with high dose aprotinin therapy (P < 0.001). The Hemotec machine with kaolin as activator was not affected by aprotinin throughout surgery, while the Hemochron clotting times almost doubled as soon as aprotinin and heparin were combined. Our studies show that for the determination of ACT in CPB were high dose aprotinin therapy is used only ACT determinations with machines using kaolin as activator yield accurate results.
Asunto(s)
Aprotinina/química , Tiempo de Sangría , Coagulación Sanguínea/efectos de los fármacos , Heparina/química , Caolín/química , Aprotinina/uso terapéutico , Puente Cardiopulmonar , Tierra de Diatomeas/química , Interacciones Farmacológicas , HumanosRESUMEN
OBJECTIVE: Patients with hyperleukocytic leukaemia were graded according to the severity of symptoms possibly caused by leukostasis to evaluate the effectiveness of therapy and to test the relative contribution of blast type and count of blasts and promyelocytes in the development of leukostasis syndrome. METHODS: Ninety-five patients (59 male, 36 female, median age 52 yr) with hyperleukocytic leukaemia [leukocytes above 50 x 10(9)/L, 48 acute myeloid leukaemia (AML), 31 chronic myeloid leukaemia (CML), 13 acute lymphoblastic leukaemia (ALL), three chronic myelomonocytic leukaemia (CMML)] were grouped according to the presence or absence and severity of neurologic, pulmonary and other symptoms into four categories (no, possible, probable and highly probable leukostasis syndrome). Age, white blood count (WBC), haemoglobin, blast count and total of blasts plus promyelocytes of these groups were compared by Mann-Whitney U-test. RESULTS: Patients with myeloid leukaemia (AML M1/M2, CML) which scored as highly probable leukostasis showed significantly higher WBC (P = 0.011), lower haemoglobin (P = 0.004), higher peripheral blast counts (P = 0.004) and higher total of peripheral blasts plus promyelocytes (P < 0.001) compared with the lower probability groups. In leukaemia involving the monocytic lineage (AML M4/M5, CMML) no significant differences were found in any of these factors between patients with highly probable leukostasis and the other patients. CONCLUSIONS: Our results show that a four-stage clinical grading scale is a valuable tool for analysing hyperleukocytic patient populations and evaluate the effectiveness of therapy more precisely. We further demonstrate that the mechanisms of leukostasis are different in myeloid leukaemia as compared with leukaemia with involvement of the monocytic lineage.