RESUMO
Decreases in protein S levels have recently been reported in some human immunodeficiency virus (HIV)-infected patients. To examine predisposing factors, 25 men randomly selected from a long-term study of HIV-infected patients were studied. The minimum mean duration of HIV seropositivity in this group was 106.6 months (range 15 to 143 months). No patients were anticoagulated at the time of the study. Three of the 25 randomly selected patients gave a history of thrombosis, in each instance occurring after the onset of HIV positivity. Two of the 3 patients with thrombosis had more than one episode. Coagulation studies showed that 3 of 3 (100%) of the patients with thrombosis and 16 of 22 (72.7%) of those without previous thrombosis had decreased free protein S. Mean-free and total protein S levels were statistically lower for HIV-infected patients with and without previous thrombosis compared with healthy male controls. C4b-binding protein was not increased in study patients with decreased protein S levels. Decreases in protein S levels did not correlate with CD4+ cell levels, CDC class, p24 antigen positivity, zidovudine (AZT) use, or Pneumocystis carinii prophylaxis. The duration of disease statistically correlated with decreases in protein S levels (r = .37, P < .05). A linear correlation existed between increasing IgG anticardiolipin antibody levels and decreasing free protein S antigen (r = .67, P < .005). This study shows that protein S deficiency is common in long-term HIV-infected patients and is caused by a decrease in the free protein, rather than by changes in the bound complex. The data suggest that protein S deficiency is not correlated with HIV disease severity but may predispose patients to thromboembolic complications.
Assuntos
Infecções por HIV/sangue , Deficiência de Proteína S , Adulto , Anticorpos Anticardiolipina/sangue , Testes de Coagulação Sanguínea , Doença Crônica , Infecções por HIV/complicações , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Estudos Retrospectivos , Tromboembolia/sangue , Tromboembolia/complicaçõesRESUMO
Inherited deficiencies of protein S, an inhibitor of the coagulation system, are now recognized as occurring at least twice as frequently as antithrombin III deficiency in patients with venous thrombosis. Protein S is present in plasma in a complexed form, which is inactive, and in a free or functional form. Free protein S combines with activated protein C to inhibit factors V and VIII. This report describes the evaluation of a family with recurrent deep venous thrombosis and superficial thrombophlebitis. Levels of antithrombin III and protein C as well as plasminogen were normal. The levels of total protein S, which includes the value for the free and complexed forms of protein S, were also normal. However, the free protein S levels were greatly reduced in all symptomatic members who were studied. This report illustrates the importance of obtaining measurement of free protein S levels in patients who are suspected of having inherited venous thrombotic disorders.
Assuntos
Glicoproteínas/deficiência , Tromboflebite/genética , Adulto , Idoso , Antitrombina III/análise , Coagulação Sanguínea , Feminino , Glicoproteínas/genética , Humanos , Masculino , Linhagem , Proteína C/análise , Proteína S , Recidiva , Tromboflebite/sangueRESUMO
The cause of the thrombotic tendency in nephrotic patients is unknown. Recent reports of thrombotic complications in patients with deficiencies of protein C or protein S (natural inhibitors of coagulation) have raised the possibility that decreased levels of these proteins may play a role in the hypercoagulable state of nephrotic patients. We measured the levels of protein C, total protein S, and free protein S antigens in 42 patients (21 nephrotic and 21 non-nephrotic) with one of four types of glomerular pathology: diabetic nephropathy (DM), focal glomerular sclerosis (FGS), membranous glomerulonephritis (MGN), and chronic renal failure due to hypertension (CRF). Protein C and total protein S antigen levels were significantly higher in FGS and MGN than they were in DM or CRF. Free protein S levels were lower in DM than they were in MGN. Protein C, total protein S, and free protein S levels did not significantly correlate with either serum albumin or degree of proteinuria. The mean levels of the three proteins did not differ between nephrotic and non-nephrotic patients. Free protein S and protein C were, however, significantly correlated (P less than .005 and P less than .002, respectively) with the type of glomerular pathology, independent of differences in age, sex, serum albumin, or degree of proteinuria. These data suggest that abnormalities of free protein S and protein C are related to the nature of the underlying renal disease, rather than to the degree of proteinuria.
Assuntos
Glicoproteínas/sangue , Glomérulos Renais , Proteína C/sangue , Proteinúria/sangue , Humanos , Nefropatias/classificação , Nefropatias/complicações , Nefropatias/patologia , Glomérulos Renais/patologia , Proteína S , Proteinúria/etiologia , Proteinúria/patologia , Valores de ReferênciaRESUMO
Thrombin-induced clotting times were inversely proportional to fibrinogen concentrations within the range of 98 to 2900 nmol/L; these reciprocal velocity measurements had units of seconds per clot. By analogy with classical enzyme kinetics, we defined rectangular hyperbolic parameters where Km(clot) ranged from 0.14 to 0.56 mumol/L and kclot from 0.020 to 0.075 clot per second. Specificity ratios (kclot/Km(clot)) showed that reconstituted lyophilized human plasma is as good, if not better, a source of clottable fibrinogen as the purified protein itself. These ratios also showed that the presence of greater than 98% of the autoproteolytic forms (beta- and gamma-thrombins) of the human enzyme did not interfere with clotting activity attributable to alpha-thrombin. Contrary to simple enzyme kinetics, velocities (reciprocal clotting times) were rectangular hyperbolically related to clotting activities. Clotting times between 5 and 90 s/clot correlated (r greater than 0.999) with reciprocal alpha-thrombin concentrations, permitting standardization with lyophilized plasma (1000 U.S. "NIH" thrombin-clotting units/L corresponded to approximately 21 s/clot with these plasma). Lyophilized plasma re-examined after 15 months displayed no change in clottability.
Assuntos
Fibrinogênio/normas , Trombina/fisiologia , Adulto , Sangue , Feminino , Liofilização , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Trombina/normas , Tempo de TrombinaRESUMO
Antithrombin III (AT III) is the most potent physiologic inactivator of thrombin and other serine proteases in the blood clotting mechanism. Hereditary deficiency of this protein is associated with recurrent deep-vein thrombosis that begins in late adolescence. Untreated, this disease may lead to early death from recurrent and massive pulmonary emboli. Attempts to identify groups of patients who are the most likely to develop thromboembolic disease because of an acquired deficiency of AT III have been frustrated by the lack of standardization of the assays and the inability to compare results of the different AT III assays. The functional assays and immunoelectrophoretic determinations do not measure the same component. In order to compare the ability of current AT III procedures to determine levels of AT III in various disease states, we used immunoelectrophoretic, chromogenic, and clottable assays to measure the AT III of patients with congenital AT III deficiency and of patients with possible acquired AT III deficiency.
PIP: Antithrombin 3 (AT 3) is the most potent physiologic inactivator of thrombin and other serine proteases in the blood clotting mechanism. Hereditary deficiency of this protein is associated with recurrent deep vein thrombosis that begins in late adolescence. Untreated, this disease may lead to early death from recurrent and massive pulmonary emboli. Attempts to identify groups of patients most likely to develop thromboembolic disease because of an acquired deficiency of AT 3 have been frustrated by the lack of standardization of the assays and the inability to compare results of different AT 3 assays. The functional assays and immunoelectrophoretic determinations do not measure the same component. In order to compare the ability of current AT 3 procedures to determine levels of AT 3 in various disease states, we used immunoelectrophoretic, chromogenic, and clottable assays to measure AT 3 in patients with congenital AT 3 deficiency and with possible acquired AT 3 deficiency.
Assuntos
Antitrombina III/análise , Trombose/sangue , Antitrombina III/metabolismo , Testes de Coagulação Sanguínea , Compostos Cromogênicos , Anticoncepcionais Orais/efeitos adversos , Feminino , Humanos , Imunoeletroforese , Cirrose Hepática/sangue , Masculino , Trombose/induzido quimicamente , Trombose/genéticaRESUMO
Peritoneovenous shunting with the LeVeen valve is generally recognized as an effective procedure for the treatment of intractable ascites and renal failure associated with severe liver disease. We recently observed a generalized hemorrhagic diathesis in patients receiving these valves. To investigate the mechanism of this hemorrhagic complication, we prospectively performed kinetic studies with 51Cr-labelled platelets and 125I-labelled fibrinogen in ten patients. When results of studies before and after valve insertion were compared, the following reductions were noted: fibrinogen concentration, 55%; the fibrinogen survival, 49%; the platelet count, 55% and the platelet survival, 35%. No endotoxin was detectable in ascitic fluid preoperatively, and there was no apparent relationship between ascitic fluid cell counts and changes in fibrinogen and platelet survival. Until the component or components of ascitic fluid responsible for accelerated consumption can be identified and steps are taken to modify the rates of platelet and fibrinogen consumption, it would seem prudent to select patients for surgery conservatively.