Assuntos
Hemorragia Cerebral/etiologia , Hemofilia A/complicações , Hemorragia Cerebral/diagnóstico , Diagnóstico Diferencial , Fator XII/administração & dosagem , Seguimentos , Hemofilia A/sangue , Hemofilia A/diagnóstico , Humanos , Recém-Nascido , Infusões Intravenosas , Masculino , Tempo de Tromboplastina Parcial , Proteínas Recombinantes , Ultrassonografia Doppler TranscranianaRESUMO
Patients with haemophilia A have seriously impaired thrombin generation due to an inherited deficiency of factor (F)VIII, making them form unstable fibrin clots that are unable to maintain haemostasis. Data on fibrin structure in haemophilia patients remain limited. Fibrin permeability, assessed by a flow measurement technique, was investigated in plasma from 20 patients with severe haemophilia A treated on demand, before and 30 minutes after FVIII injection. The results were correlated with concentrations of fibrinogen, FVIII and thrombin-activatable fibrinolysis inhibitor (TAFI), and global haemostatic markers: endogenous thrombin potential (ETP) and overall haemostatic potential (OHP). Fibrin structure was visualised using scanning electron microscopy (SEM). The permeability coefficient Ks decreased significantly after FVIII treatment. Ks correlated significantly with FVIII levels and dosage, and with ETP, OHP and levels of TAFI. SEM images revealed irregular, porous fibrin clots composed of thick and short fibers before FVIII treatment. The clots had recovered after FVIII replacement almost to levels in control samples, revealing compact fibrin with smaller intrinsic pores. To the best of our knowledge, this is the first description of fibrin porosity and structure before and after FVIII treatment of selected haemophilia patients. It seems that thrombin generation is the main determinant of fibrin structure in haemophilic plasma.
Assuntos
Fator XII/administração & dosagem , Fibrina/metabolismo , Hemofilia A/tratamento farmacológico , Adolescente , Adulto , Idoso , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/genética , Carboxipeptidase B2/metabolismo , Fator XII/genética , Fibrina/ultraestrutura , Fibrinogênio/metabolismo , Hemofilia A/sangue , Hemostasia/genética , Humanos , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Estrutura Molecular , Porosidade , Adulto JovemRESUMO
We studied the hemodynamic responses to the administration of 20 ml of three protein solutions having different prekallikrein activator (PKA) activities in patients undergoing cardiac operation. PKA levels of the two plasma protein fraction (PPF) solutions studied were 193% and 60%, respectively, while that of the albumin solution was less than or equal to 3%. A significant correlation was found between the PKA activity of the test solutions and the decrease in systemic vascular resistance produced by the solutions during cardiopulmonary bypass and in the postoperative period. Vasodilatation was considerably more marked in the postoperative phase than during cardiopulmonary bypass. Since cardiac output increased simultaneously with the decrease in vascular resistance in the postoperative period, the hypotension observed did not fully reflect the degree of vasodilatation. In some patients, substantial vasodilatation was observed also after the administration of albumin solution with low PKA level. We conclude that although the PPF-induced vasodilatation correlates with the PKA activity of the solution, occasional hypotensive reactions are probably due to mechanisms other than those linked with increased PKA level.