Es confiable determinar el fibrinógeno como derivado del tiempo de protrombina? / Is fibrinogen determination by prothrombine time derived method confidant?

Los niveles elevados de fibrógeno (Fbg) plasmático son considerados como un factor de riesgo para eventos trombóticos y enfermedad cardiovascular. El Fbg se cuantifica habitualmente utilizando el método coagulable de Clauss y el de Fbg derivado del tiempo de protrombina. A pesar de ser éste último, simple y económico, ha sido cuestionado en distintos estudios porque sobrestimaría los valores de Fbg. Para evaluar la confiabilidad de éste método, se lo comparó respecto al valor obtenido por el método de Clauss. Se evaluó, además, el efecto de la heparina (0,2 y 0,6 UI/ml) sobre las determinaciones por el método de Fbg derivado. La equivalencia entre ambos métodos se estableció por el test de Bland y Altman y el test de la Mediana. El efecto de la heparina se evaluó por regresión lineal y correlación de Pearson. Se puede concluir que los valores de Fbg por el método de Fbg derivado dentro de los rangos normales correlacionan con los obtenidos con el método de Clauss. Cuando éstos valores superan los 400 mg/dl debería determinarse el Fbg por el método de Clauss u otra metodología. Los valores obtenidos mediante el método de Fbg derivado no se modifican en muestras que contienen heparina en el rango terapéutico

Factores de riesgo causales, condicionales y predisponentes en coronarios del sur argentino: asociación con la presencia y severidad de las lesiones demostradas por angiografía / Causal, conditional and predisposing risk factors in coronary subjects of south argentina: association with the presence and severity of the lesions demostrated by angiography

El objetivo de éste estudio fue determinar, en sujetos coronarios de ésta región, los factores de riesgo más frecuentes, categorizados en causales, condicionales y predisponentes, asociados con la presencia y severidad de enfermedad coronaria, demostrada por angiografía, y analizar la asociación del índice Apo B/C-HDL con la presencia y severidad de las lesiones. Se estudiaron 90 pacientes de 36 a 70 años de edad (64 varones y 26 mujeres) del Servicio de Hemodinamia del Hospital Privado del Sur a quienes se les realizó una cinecoronarioangiografía. Se obtuvieron datos clínicos y bioquímicos de cada paciente. Se analizaron dos grupos: controles (N=26), angiografías sin anormalidades o estenosis < 50 por ciento en un vaso, y coronarios (N=64), estenosis >= 50 por ciento y lesiones de distinta severidad en uno o varios vasos. Los factores de riesgo más frecuentes en coronarios vs. controles fueron: causales: hiperlipoproteinemias tratadas (P < 0,0007), diabetes mellitus Tipo 2 (P < 0,001), C-HDL < 35 mg/dl (P=0,016), hipertensión arterial o tratados (P < 0,02), ex-fumadores > 10/día (P < 0,04). Predisponentes: historia familiar (P < 0,0007), índice de conicidad > 1,24 (P < 0,005). Los índices, Apo B/C-HDL > 2,6, CT/C-HDL > 4,5, C-LDL/C-HDL > 3,0, P= 0,0049, P= 0,011 y P= 0,022, respectivamente. Los predictores de presencia de la enfermedad fueron (por análisis de regresión logística múltiple), hiperlipoproteinemias tratadas, Apo B/C-HDL > 2,6 o ambas, la historia familiar y el índice de conicidad. Los predictores de severidad fueron: la diabetes, hiperlipoproteinemias tratadas, Apo B/C-HDL > 2,6 o ambas, ex-fumadores > 10/día y la historia familiar...

Es confiable determinar el fibrinógeno como derivado del tiempo de protrombina? / Is fibrinogen determination by prothrombine time derived method confidant?

Los niveles elevados de fibrógeno (Fbg) plasmático son considerados como un factor de riesgo para eventos trombóticos y enfermedad cardiovascular. El Fbg se cuantifica habitualmente utilizando el método coagulable de Clauss y el de Fbg derivado del tiempo de protrombina. A pesar de ser éste último, simple y económico, ha sido cuestionado en distintos estudios porque sobrestimaría los valores de Fbg. Para evaluar la confiabilidad de éste método, se lo comparó respecto al valor obtenido por el método de Clauss. Se evaluó, además, el efecto de la heparina (0,2 y 0,6 UI/ml) sobre las determinaciones por el método de Fbg derivado. La equivalencia entre ambos métodos se estableció por el test de Bland y Altman y el test de la Mediana. El efecto de la heparina se evaluó por regresión lineal y correlación de Pearson. Se puede concluir que los valores de Fbg por el método de Fbg derivado dentro de los rangos normales correlacionan con los obtenidos con el método de Clauss. Cuando éstos valores superan los 400 mg/dl debería determinarse el Fbg por el método de Clauss u otra metodología. Los valores obtenidos mediante el método de Fbg derivado no se modifican en muestras que contienen heparina en el rango terapéutico (AU)

Factores de riesgo causales, condicionales y predisponentes en coronarios del sur argentino: asociación con la presencia y severidad de las lesiones demostradas por angiografía / Causal, conditional and predisposing risk factors in coronary subjects of south argentina: association with the presence and severity of the lesions demostrated by angiography

El objetivo de éste estudio fue determinar, en sujetos coronarios de ésta región, los factores de riesgo más frecuentes, categorizados en causales, condicionales y predisponentes, asociados con la presencia y severidad de enfermedad coronaria, demostrada por angiografía, y analizar la asociación del índice Apo B/C-HDL con la presencia y severidad de las lesiones. Se estudiaron 90 pacientes de 36 a 70 años de edad (64 varones y 26 mujeres) del Servicio de Hemodinamia del Hospital Privado del Sur a quienes se les realizó una cinecoronarioangiografía. Se obtuvieron datos clínicos y bioquímicos de cada paciente. Se analizaron dos grupos: controles (N=26), angiografías sin anormalidades o estenosis < 50 por ciento en un vaso, y coronarios (N=64), estenosis >= 50 por ciento y lesiones de distinta severidad en uno o varios vasos. Los factores de riesgo más frecuentes en coronarios vs. controles fueron: causales: hiperlipoproteinemias tratadas (P < 0,0007), diabetes mellitus Tipo 2 (P < 0,001), C-HDL < 35 mg/dl (P=0,016), hipertensión arterial o tratados (P < 0,02), ex-fumadores > 10/día (P < 0,04). Predisponentes: historia familiar (P < 0,0007), índice de conicidad > 1,24 (P < 0,005). Los índices, Apo B/C-HDL > 2,6, CT/C-HDL > 4,5, C-LDL/C-HDL > 3,0, P= 0,0049, P= 0,011 y P= 0,022, respectivamente. Los predictores de presencia de la enfermedad fueron (por análisis de regresión logística múltiple), hiperlipoproteinemias tratadas, Apo B/C-HDL > 2,6 o ambas, la historia familiar y el índice de conicidad. Los predictores de severidad fueron: la diabetes, hiperlipoproteinemias tratadas, Apo B/C-HDL > 2,6 o ambas, ex-fumadores > 10/día y la historia familiar...(AU)

Clinical significance of fibrinopeptide A in acute lymphocytic and non-lymphocytic leukaemia.

Fibrinopeptide A (FPA) was systematically investigated in 74 patients with acute leukaemia at different stages of the disease (50 with non-lymphocytic leukaemia, ANLL; 24 with lymphocytic leukaemia, ALL). At diagnosis, 75% of the cases had high FPA levels (86% in ANLL and 54% in ALL) with significantly higher levels in ANLL than in ALL (13.4 vs 4.4 ng/ml; p less than 0.001). Patients with DIC (20 cases in ANLL and 1 case in ALL) had significantly higher levels (p less than 0.001). FPA levels were neither correlated with fibrinogen or FDP levels nor with blast cell count. During chemotherapy, median FPA did not show significant changes whereas, at the end of therapy, a return toward normality was generally observed both in ALL and ANLL apart from the group of patients with acute promyelocytic leukaemia. Among the 24 patients who entered post-remission follow-up (13 ANLL and 11 ALL), 10 cases out of the 11 relapsing (6/6 with ANLL and 4/5 with ALL) had increased FPA 1 to 2 months before the ascertainment of the relapse. However, 16% and 9% of the samples obtained on different occasions, respectively from ANLL and ALL cases in maintained first remission, showed FPA above the normal limit. This study demonstrates that subclinical activation of blood coagulation, as indicated by high FPA level, is common both in lymphocytic and non-lymphocytic leukemia and suggests that this phenomenon is related to disease activity.

Influence of the red blood cell Ca2+-ion concentration on the erythrocyte aggregation in stasis.

Ca2+ ions were transported into the cell by incubation of the erythrocyte suspension with ionophore A23187, a lipophil electric neutral ion complexing substance. Erythrocyte aggregation could be increased twice, when doubling the intracellular Ca2+-ion concentration. Our measurements lead to the suggestion that an increase of the cytoplasmatic Ca2+ ion changes the physical and/or biochemical properties of the aggregation receptors on the membrane surface, i.e., cell-protein interactions are regulated by alteration of the intracellular Ca2+-ion concentration.

Acute phase response in horses: changes in plasma cation concentrations after localised tissue injury.

An acute phase reaction was elicited in four horses to which Freund's adjuvant was administered intramuscularly. The localised inflammation was accompanied by changes in the plasma concentrations of copper, iron and zinc. The plasma copper concentration, the plasma ceruloplasmin copper concentration and the ceruloplasmin oxidase activity in the plasma steadily increased to a maximum 24 days after the administration of the adjuvant. At this time, the plasma copper concentration was 2.2 micrograms/ml, a 90 per cent increase over the baseline concentration. The ratio of the concentration of plasma ceruloplasmin copper to plasma copper remained constant, indicating that the non-ceruloplasmin bound copper component of the plasma is also an acute phase reactant in the horse. The plasma zinc and iron concentrations decreased to 59 per cent and 30 per cent of their respective baseline concentrations and the severity of the inflammation appeared to influence the plasma concentrations of each metal. Weak correlations between the plasma fibrinogen concentration and the plasma copper and zinc concentrations of 25 horses with plasma fibrinogen concentrations of 5 g/litre or greater indicated that a single measurement of plasma copper concentration is not useful in the diagnosis of non-specific inflammatory disorders of the horse. However, the results suggest that the plasma copper concentrations in serial samples may be used to monitor the resolution of inflammatory disorders in the horse.

Fibrinopeptide A levels in maternal and newborn plasma.

Plasma fibrinopeptide A (FPA), a dynamic measure of intravascular coagulation, was determined in 70 healthy Chinese women during normal pregnancy, labour, delivery and the early puerperium and compared to a group of healthy non-pregnant adult controls. In the normal controls the plasma FPA level (mean +/- SD) was 1.43 +/- 0.46 ng/ml. During pregnancy and labour, the FPA levels were 3.05 +/- 0.98 ng/ml and 11.47 +/- 4.43 ng/ml, respectively, and it reached a peak of 32.95 +/- 11.66 ng/ml at parturition, then falling to 6.15 +/- 2.52 ng/ml in the early puerperium. All these levels were significantly higher (p less than 0.001) compared to controls. Fifteen of the 21 mothers with blood sampling during parturition also had umbilical cord blood taken for determination of FPA level. There was no significant difference between the maternal (34.07 +/- 10.12 ng/ml) and cord (31.06 +/- 12.67 ng/ml) plasma FPA levels. It is concluded that the hypercoagulable state in women during pregnancy and the puerperium is associated with increased intravascular coagulation activity, and that increased intravascular coagulation activity also occurs in the fetus during parturition. This observation may account for the increased risk of thrombotic disorders observed in pregnant and parturient women as well as in the newborn.

Enhancement of arterial thrombolysis with native tissue type plasminogen activator by pretreatment with heparin or batroxobin: an angioscopic study.

The enhancement of canine arterial thrombolysis with native tissue type plasminogen activator (nt-PA) obtained from human-derived normal cells by pretreatment with heparin or the defibrinogenating agent, batroxobin, was evaluated with angioscopy. The nt-PA, 0.25 mg/kg, was infused intravenously to lyse 1-hour-old thrombus (eight thrombosed arteries without medication, seven with nt-PA alone, seven with nt-PA and heparin, and seven with nt-PA plus batroxobin). Angioscopy provided a cross-sectional view of the vessel lumen with clear visualization of the thrombus. Thirty minutes after nt-PA infusion, the percent luminal obstruction decreased from 74 to 61 in nt-PA alone (p less than .025), from 77 to 37 in nt-PA plus heparin (p less than .005), and from 79 to 25 in nt-PA plus batroxobin (p less than .005). Fifteen minutes after drug infusion, plasma fibrinogen levels decreased to 89% of preinfusion value in nt-PA alone, to 84% in nt-PA plus heparin, and to less than 5% in nt-PA plus batroxobin. Thus rapid infusion of nt-PA alone provided slight thrombolytic effects. However, heparin and batroxobin showed marked enhancement of thrombolytic effects of nt-PA.

Two-year follow-up of changes in clinical chemistry in Singaporean Norplant-2 rod acceptors: haemostatic changes.

A longitudinal study of coagulation parameters was carried out on 100 Singaporean acceptors using Norplant-2 rods for contraceptive purposes. At the end of 2 years of use, results from this study show a return of platelet count to preinsertion level while platelet aggregation remained significantly enhanced. Thus the net effect of these two changes on an increased tendency for thrombosis needs further evaluation. The PT and APTT continued to remain persistently shortened during the period of use. There was also a general fall in fibrinogen and most other coagulation factors during the two years of use. Thus, again, the net effect of these two changes on the exposed potential for hypercoagulation at the end of the first year needs further evaluation throughout the five years of Norplant-2 use.

PIP: A longitudinal study of coagulation parameters was carried out on 100 Singaporean acceptors using Norplant-2 rods for contraceptive purposes. At the end of 2 years of use, results from this study show a return of platelet count to preinsertion level while platelet aggregation remained significantly enhanced. Thus the net effect of these 2 changes on an increased tendency for thrombosis needs further evaluation. The Prothrombin Time and Actived Partial Thromboplastin Time continued to remain persistently shortened during the period of use. There was also a general fall in fibrinogen and most other coagulation factors during the 2 years of use. Thus, again, the net effect of these 2 changes on the exposed potential for hypercoagulation at the end of the 1st year needs further evaluation throughout the 5 years of Norplant-2 use.

The effect of donor age on the packing susceptibility of erythrocytes.

The study of 411 healthy persons indicates that erythrocyte susceptibility to centrifugal packing at 200 g increases with age, evidencing an age-related decrease in red cell deformability. Positive correlations between donor age and blood plasma fibrinogen concentration and erythrocyte sedimentation rate were confirmed. The impairment of red cell deformability may affect the circulatory efficiency in the aged.

Spontaneous resolution of hypofibrinogenemia associated with death of a twin in utero: a case report.

Spontaneous resolution of hypofibrinogenemia after intrauterine death of one twin occurred and suggests that prophylactic heparin therapy in such cases is unnecessary.

Plasma fibronectin level in patients with connective tissue diseases.

The level of plasma fibronectin (Fn) was studied in 40 patients with connective tissue diseases. Fn concentration was found increased in patients with rheumatoid arthritis (mean +/- SE, 560 +/- 30 micrograms/ml, p less than 0.01) decreased in patients with mixed connective tissue disease (337 +/- 12 micrograms/ml, p less than 0.05) and was not significantly different from controls in systemic lupus erythematosus, scleroderma, polymyositis. The value of plasma Fn level was found increased in active diseases and decreased in the cases, with presence of cryoprecipitates. The factors which might influence the level of plasma Fn and the possibility of using the changes of Fn concentration in the estimation of the evolution of connective tissue diseases are discussed.

The German multicenter trial of anisoylated plasminogen streptokinase activator complex versus heparin for acute myocardial infarction.

A multicenter randomized trial of anisoylated plasminogen streptokinase activator complex (APSAC) versus heparin in patients with acute myocardial infarction of less than 4 hours' duration was undertaken in 19 hospitals. Of the 313 patients, 151 received heparin and 162 APSAC (30 U as intravenous injection). Within 28 days of hospital stay, 19 deaths (12.6%) occurred in the heparin group and 9 deaths (5.6%) in the APSAC group (p = 0.032). After 24 hours, patients in the APSAC group had a significantly lower incidence of cardiogenic shock (3.2 vs 9.5%, p = 0.031), asystole (3.8 vs 10.8%, p = 0.015) and need for resuscitation (5.1 vs 11.5%, p = 0.039). There was no difference in global and infarct-related ejection fraction between the 2 groups. Thus, APSAC favorably influences prognosis and clinical course in hospital.

Acute phase reactants in the elderly.

The erythrocyte sedimentation rate (ESR), plasma fibrinogen, serum orosomucoid, serum alpha 1-antitrypsin and serum haptoglobin were measured in 267 apparently healthy elderly subjects (median age 79 years, range 60-93), and compared to the values in 58 healthy younger subjects (median age 27 years, range 18-50). The acute phase reactants displayed no sex differences, but were significantly higher in elderly than in younger persons (mean +/- SD): ESR 13 +/- 10 mm/h vs 4 +/- 3 mm/h (p less than 0.001); fibrinogen 4.35 +/- 0.95 g/l vs 3.33 +/- 0.54 g/l (p less than 0.001); orosomucoid 0.68 +/- 0.20 g/l vs 0.60 +/- 0.16 g/l (p less than 0.01); alpha 1-antitrypsin 2.16 +/- 0.38 g/l vs 1.84 +/- 0.43 g/l (p less than 0.001); haptoglobin 1.30 +/- 0.50 g/l vs 1.00 +/- 0.30 g/l (p less than 0.001). Correlations existed between the acute phase reactants, being highest between ESR and fibrinogen (r = 0.53, p less than 0.001).

Hemorheologic variables in breast cancer patients at the time of diagnosis and during treatment.

The increased risk of thrombosis seen in patients with malignancy also was recently confirmed in breast cancer patients undergoing hormonal or chemotherapeutic treatment. Besides changes within the coagulation system, alterations of hemorheologic variables have been implicated in the genesis of thrombosis. We evaluated plasma viscosity, erythrocyte aggregation, fibrinogen level, sedimentation rate, hematocrit concentration, and protein concentration in patients with breast cancer at the time of primary diagnosis and during follow-up with or without treatment. We then compared the results to a control group without malignant or infectious disease. Plasma viscosity and erythrocyte aggregation were significantly higher in patients with malignant disease, with a further increase at the time of dissemination. Plasma fibrinogen level was significantly higher only at the time of dissemination. The influence of therapy on hemorheologic variables was minor. Tumor volume was the most important factor. As individual values vary considerably and form a continuous spectrum, no cutoff line between normal and pathologic values can be defined. However, high values should induce further measures to diagnose metastatic disease. Second, these factors could explain the relative inefficiency of thrombosis prophylaxis in this patient group and suggest the addition of rheologically active drugs to the treatment regimen.

Spontaneous intracerebral hemorrhage and liver dysfunction.

We evaluated liver function and coagulation parameters in 117 patients with spontaneous intracerebral hemorrhage (68 men and 49 women) admitted to our clinic within 24 hours after onset. Liver dysfunction was more common among men than women due to differences in alcohol consumption. Number of thrombocytes and fibrinogen concentrations were lower, especially among men with elevated concentrations of glutamic oxaloacetic transaminase or glutamic pyruvic transaminase and/or elevated gamma-globulin fraction. Five of the 78 patients undergoing stereotactic hematoma aspiration and one of the 39 treated nonsurgically rebled. All six of the patients who rebled were men, heavy alcohol consumers with liver dysfunction. Fibrinogen concentration was abnormally low in four of the six and at the lower end of the normal range in one. Two showed thrombocytopenia and one case showed prolonged prothrombin time. These facts suggest that liver disorders produce a state in which hemorrhage occurs more readily and that this hemorrhagic tendency may be one of the causal factors of spontaneous intracerebral hemorrhage.

Efficacy of antithrombin III in endotoxin-induced disseminated intravascular coagulation.

Antithrombin III (AT III) is a major modulator of the clotting cascade and is decreased in disseminated intravascular coagulation (DIC). AT III was given as a pretreatment to dogs with endotoxin-induced DIC. Significant improvement in clotting parameters (prothrombin time, fibrinogen, fibrin degradation products) was noted. There was no effect on platelets. Mean arterial blood pressure was improved, while there were no other significant changes in other measured hemodynamic, acid-base, or biochemical variables. It was concluded that AT III was effective in ameliorating endotoxin-induced changes in the clotting profile. AT III may prove to be a beneficial therapy in acquired DIC.

Prostaglandins E2 and F2 alpha are not involved in the monocytic-product (interleukin-1)-induced stimulation of hepatic fibrinogen synthesis in rats.

1. Monocytic products, especially interleukin-1 (IL-1), play an important role in the acute-phase response. Prostaglandins have been shown to act as second messengers in several physiological alterations of the acute-phase response, such as fever, muscle wasting and immunoregulation. The present study was undertaken to determine the role of prostaglandins in the monocytic-product-induced stimulation of the hepatic synthesis of fibrinogen, a well-known acute-phase protein. 2. Prostaglandin (PG) E2, PGF2 alpha and 16,16-dimethyl-PGE2 did not stimulate fibrinogen synthesis and fibrinogen polypeptide mRNA content when administered intraperitoneally to rats or when added to monolayer cultures of rat hepatocytes. 3. Cyclo-oxygenase inhibitors did not abolish the stimulation of fibrinogen synthesis and its mRNA content induced by monocytic products in vivo or in vitro. 4. These findings indicate that the enhanced synthesis of fibrinogen induced by monocytic products (including IL-1) during the acute-phase response is not mediated by prostaglandins or other products of the cyclo-oxygenase pathway of arachidonic acid.

Decrease in frequency of anginal episodes by control of thrombin generation with low-dose heparin: a controlled cross-over randomized study.

Increased thrombin generation is frequently associated with an increase in anginal activity. A cross-over, single-blind, completely randomized study was planned in order to evaluate whether the control of thrombin generation affected the increase in anginal activity. After discharge from the hospital, 24 patients (18 men and 6 women, aged 40 to 69 years) suffering from spontaneous angina were followed up to 12 months and were alternatively treated during two consecutive 6-month periods with calcium heparin, 12,500 IU by the subcutaneous route, or with placebo by the intramuscular route, in addition to the usual antianginal medications. Thrombin generation and clinical activity of angina were assessed every 15 days by measuring fibrinopeptide A (FPA) plasma levels and by grading in three classes (symptomless, mildly symptomatic, and severely symptomatic) the anginal activity on the basis of the number and the time concentration of the ischemic attacks and ECG changes. Low-dose heparin treatment significantly reduced both the FPA plasma level (from 4.1 +/- 3.7 to 2.3 +/- 1.8 ng/ml, p less than 0.001) and the clinical activity of angina. During heparin treatment, the frequency of the observations in the severely and mildly symptomatic classes decreased, respectively, by 53% and by 30%, whereas that in the symptomless class increased by 23% (p less than 0.001) in comparison with the period on placebo. Present results indicate that the control of thrombin generation obtained by low-dose heparin treatment favorably affects the degree of anginal activity in patients with spontaneous angina.