Effectiveness of a diagnostic algorithm combining clinical probability, D-dimer testing, and computed tomography in patients with suspected pulmonary embolism in an emergency department.

OBJECTIVE: The aim of our study was to assess the clinical effectiveness of a simplified algorithm using the Wells clinical decision rule, D-dimer testing, and computed tomography (CT) in patients with suspected pulmonary embolism (PE) in an Emergency Department (ED). METHODS: Patients with clinically suspected PE from the Emergency Department were included from May 2007 through December 2008. Clinical probability was assessed using the Wells clinical decision rule and a VIDAS D-dimer assay was used to measure D-dimer concentration. Patients were categorized as "pulmonary embolism unlikely" or "pulmonary embolism likely" using the dichotomized version of the Wells clinical decision rule. Pulmonary embolism was considered excluded in patients with unlikely probability and normal D-dimer test (< 500 ng/ml). All other patients underwent CT, and pulmonary embolism was considered present or excluded based on the results. Anticoagulants were withheld from patients classified as excluded, and all patients were followed up for 3 months. RESULTS: 241 patients were included in the study. The prevalence of PE in the entire population was 23.6%. The combination of unlikely probability using the dichotomized Wells clinical decision rule and a normal D-dimer level occurred in 23.6%, thus making CT unnecessary. During the followup period, no thromboembolic events were recorded and there were no deaths related to venous thromboembolic disease (3-month thromboembolic risk 0% [95% CI, 0%-8%]). CONCLUSIONS: In this study we have confirmed the effectiveness of a diagnostic management strategy using a simple clinical decision rule, D-dimer testing, and CT in the evaluation and management of patients with clinically suspected pulmonary embolism.

[Cerebral venous thrombosis: when etiology makes the difference]. / Trombosis venosa cerebral: cuando la etiología marca la diferencia.

OBJECTIVES: To make a retrospective study of the clinical, etiological, diagnostic and prognostic features of cerebral vein and sinus thrombosis (CVST) diagnosed at our University Hospital. METHODS: We performed a systematic research of the clinical records of our University Hospital's electronic database (1977-2009) using the key words <>. RESULTS: Ninety-five possible cases were found, and 16 were excluded due to alternative or uncertain diagnosis. Seventy-nine patients (43 females), median age of 46 years (2-82), were studied. Hereditary or acquired thrombophilia was detected in 22 patients (27.8%): prothrombin G20210A mutation (10), factor V Leyden (3), protein C deficiency (2), homozygous MTHFR C677T mutation (1), antiphospholipid syndrome (7) and hematological conditions (3). CVST was associated with infection in 17 cases, intracranial neoplasm in 9, malignancy in 13, treatment with prothrombotic drugs in 20 (including substitutive/antineoplastic hormones and oral contraceptives) and other causes in 8. Thirteen cases were idiopathic. Clinical presentation was intracranial hypertension in 83.5%, focal deficits in 45.6% and seizures in 12.6 %. Transverse (57%) and superior sagittal sinus (49.4%) were the most commonly involved. Seizures occurred in 25.3%, venous infarction in 41% and severe intracranial hypertension in 22.8 %. Up to 31.6 % required surgical drainage, decompressive craniectomy or ventricular drainage. Nine cases associated peripheral venous thromboembolism and 4 CVST recurred. Evolution was favorable (modified Rankin scale 0-2 at 3 months) in 74.7%. Mortality rate was 13.9% (11 patients). Neoplastic and infectious origin was significantly associated with mortality and disability. CONCLUSION: We describe a large retrospective series of CVST where infectious and neoplastic etiologies were linked to an unfavorable outcome.

Trombosis venosa cerebral: cuando la etiología marca la diferencia / Cerebral venous thrombosis: when etiology makes the difference

Objetivos. Estudio retrospectivo de aspectos clínicos, etiológicos, diagnósticos y pronósticos de las trombosis venosas cerebrales y de senos durales (TVCSD) diagnosticadas en nuestro centro. Métodos. Revisión sistemática de historias clínicas de la base de datos de nuestro hospital universitario (1977-2009) con los términos de búsqueda «trombosis venosa o tromboflebitis de senos cerebrales». Resultados. Se encontraron 95 posibles casos, de los que 16 se excluyeron por diagnóstico incierto o alternativo. Se analizaron 79 TVCSD (43 mujeres), con edad mediana de 46 años (2-82). Se encontró trombofilia hereditaria o adquirida en 22 casos (27,8%): mutación G20210A de protrombina (10), factor V Leyden (3), deficiencia de proteína C (2), mutación homocigótica MTHFR C677T (1), síndrome antifosfolípido (7) y trastornos hematológicos (3). La TVCSD se asoció a infección en 17 casos, a neoplasia intracraneal en 9, a neoplasia sistémica en 13, a fármacos protrombóticos en 20 (hormonales, antineoplásicos, anovulatorios) y a otras causas en 8. Trece casos (16,5%) fueron idiopáticos. La TVCSD se presentó con hipertensión intracraneal en el 83,5%, déficit focal en el 45,6% y crisis comiciales en el 12,6 %. El seno transverso (57%) y el sagital superior (49,4%) fueron los más afectados. Como complicaciones se encontraron crisis (25,3%), infarto venoso (41%) e hipertensión intracraneal grave (22,8%). El 31,6% precisó drenaje quirúrgico, craniectomía o derivación ventricular. Hubo enfermedad tromboembólica periférica en 9 casos y 4 recurrencias de TVCSD. El 74,7% tuvo una evolución favorable (escala de Rankin modificada [ERm] 0-2) a los 3 meses. La mortalidad fue del 13,9% (11 pacientes). El origen infeccioso y neoplásico se asoció significativamente a mayor mortalidad y dependencia. Conclusión. Describimos una extensa serie de TVCSD en que las etiologías infecciosa y neoplásica constituyen factores pronósticos desfavorables (AU)

Eficacia diagnóstica de los complejos trombina-antitrombina III y dímero D ELISA rápido en el embolismo pulmonar: efecto de la anticoagulación con heparina / Diagnostic and capacity of the thrombin-antithrombin III and rapid D dimer ELISA in pulmonary embolism: effect of anticoagulation with heparina

Hemos evaluado la eficacia de los complejos trombina-antitrombina III por ELISA (TAT) y dímero D ELISA rápido (DD-VIDAS) en el diagnóstico del embolismo pulmonar (EP). También se analizó el efecto que sobre la eficacia diagnóstica de TAT y DD-VIDAS puede tener el inicio del tratamiento con heparina previo a la toma de la muestra. El estudio incluye a 52 pacientes consecutivos con sospecha clínica de EP. El diagnóstico de confirmación de EP o exclusión de EP se realizó según la impresión clínica y resultados de la gammagrafía pulmonar, estudio de miembros inferiores y arteriografía pulmonar. En todos los pacientes, antes de transcurridas 24 horas desde la sospecha de EP, se obtuvo una muestra de plasma para determinar TAT y DD-VIDAS. En cada caso se registró el inicio o no del tratamiento anticoagulante con heparina previo a la toma de la muestra. En 24 pacientes se confirmó EP (46%) y en 28 se excluyó (54%). Con un punto de corte de 500 ng/ml el DD-VIDAS mostró una sensibilidad del 96%, especificidad del 53%, valor predictivo positivo del 63% y valor predictivo negativo del 93%, observándose un solo falso negativo. Para los TAT con un nivel de corte de 4 ng/ml la sensibilidad fue del 79%, la especificidad del 50%, el valor predictivo positivo del 57% y el valor predictivo negativo del 73%, presentando 5 falsos negativos. La anticoagulación previa a la toma de la muestra estaba presente en 4 de los 5 falsos negativos observados para los TAT y en el único caso falso negativo para el DD-VIDAS. En conclusión, de las dos técnicas estudiadas, DD-VIDAS y TAT, el DD-VIDAS con un punto de corte de 500 ng/ml parece potencialmente útil para excluir EP en nuestro medio, aunque es necesario ampliar la serie para confirmar estos resultados. Los TAT mostraron escasa utilidad en el diagnóstico de exclusión de EP. El inicio de la anticoagulación con heparina previo a la toma de la muestra parece un factor decisivo que puede afectar a los resultados obtenidos con los TAT (AU)

We have evaluated the efficacy of the thrombin-antithrombin III complexes by ELISA (TAT) and rapid D dimer (VIDASDD) in the diagnoses of pulmonary embolism (PD). The effect that the initiation of treatment with Heparin before the sample is obtained has on diagnostic efficacy of TAT and DD-VIDAS was also analyzed. The study includes 52 consecutive patients with clinical suspicion of PD. The confirmation diagnoses of PD or exclusion of PD was made according to a clinical impression and results on the pulmonary scintigraphy, study of the lower limbs and pulmonary arteriography. A sample of plasma was obtained in all of the patients within 24 hours from the suspicion of PD to determine TAT and VIDAS-DD. In every case, the initiation or not initiation of anticoagulant treatment with heparin prior to obtaining the sample was recorded. In 24 patients, PD (46%) was confirmed and it was excluded in 28 (54%). Using a cut off of 500 ng/ml, the VIDAS-DD showed a sensitivity of 96%, specificity of 53% and negative predictive value of 93%, only one false-negative being found. For the TAT with a cutoff of 4 ng/ml, sensitivity was 79%, specificity 50%, positive predictive value 57% and negative predictive value 73%, there being five false negatives. Anticoagulation prior to obtaining the sample was present in 4 of the 5 false negatives observed for TAT and in the only case of false-negative for VIDAS- DD. In conclusion, of the two techniques studied, VIDAS-DD and TAT, VIDAS-DD with a cutoff of 500 ng/ml seems to be potentially useful to exclude PD in our setting, although this series must be extended to confirm these results. The TAT showed little utility in the exclusion diagnosis of PD. Initiation of anticoagulation with heparin before the sample is obtained seems to be a decisive factor that may affect the results obtained with TAT (AU)

Coagulative system activation and fibrinolytic system inhibition activities arise from tumoral draining vein in colon carcinoma.

UNLABELLED: Hypercoagulability and activation/inhibition of the fibrinolytic system have been observed in abdominal cancer surgery. Because surgery itself and also neoplastic diseases are associated with these situations, a method for separating the origin of these two processes was designed. Eighteen patients with colon cancer who underwent a surgical procedure were studied: Immediately before surgery blood was taken from a peripheral vein. During the surgical procedure, before the exclusion of tumoral tissue from general circulation and at the same time of a second peripheral vein blood sample, a blood sample was taken from the main tumoral draining vein. Platelet-poor plasma samples were aliquoted and stored at -72 degrees C, ready for analytical procedures. RESULTS: A moderate activation of the fibrinolytic system during surgery was observed, expressed by elevation of tissue plasminogen activator (t-PA) (P<.05) and D-dimer (DD) (P<.05) levels, without changes in fibrinogen (FG), plasminogen (PG) or antiplasmin (AP) levels. There were no modifications in antithrombin III (AT-III) and protein C (PC) levels. In the tumoral draining vein samples, there was a high elevation of levels of thrombin-antithrombin III complexes (TAT) (P<.001) and PAI-1 (P<.01), compared with the second sample peripheral vein. There was no difference between peripheral and tumoral vein sample levels of AT-III, PC, FG, DD, PG and AP. CONCLUSIONS: The tumour itself is the origin of hypercoagulability (TAT) and fibrinolytic system inhibition (PAI-1); the surgical procedure elicits an evident though moderate activation of the fibrinolytic system (t-PA and DD elevation).

Improvement in lipid and haemostasis patterns after Helicobacter pylori infection eradication in type 1 diabetic patients.

Helicobacter pylori has been implicated in the cardiovascular risk of diabetic patients. The aim of our study was to investigate whether the Helicobacter pylori infection plays a role in the lipid and haemostasis patterns of type 1 diabetic patients. Twenty nine patients with type 1 diabetes mellitus and H. pylori infection were enrolled (Chlamydia pneumoniae negative). The H. pylori infection status was assessed by serology and urease breath test. In all patients levels of total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, lipoprotein (a) (Lpa) C reactive protein (CRP), fibrinogen, thrombin/antithrombin III complex (TAT), plasminogen activator inhibitor type 1(PAI-1), tissue plasminogen activator (t-PA) and von Willebrand antigen were measured. All patients were evaluated before and after H. pylori eradicating treatment with amoxicillin, clarithromycin and omeprazole. Twenty two patients were eradicated and seven remained infected. In H. pylori eradicated patients, HDL cholesterol increased (59.7+/-18.9 mg/dl vs 65.2+/-15. 9 mg/dl, P << 0.05), after treatment. After H. pylori eradication, the levels of CRP and TAT decreased (48+/-0.7 ng/l vs 3.3+/-0.4 ng/l;P << 0.05), (27.7+/-44.7 microg/ml vs 2.1+/-1.4 microg/ml, P << 0.05), respectively. The decrease in TAT was higher in the group of H. pylori (+) patients with higher levels of TAT (TAT >> 20 ng/ml, 92.8+/-41.6 ng/ml vs 1.9+/-2.0 ng/ml, P << 0.005; TAT 4Eth 20 ng/ml; 10.1+/-5.2 ng/ml vs 2.2+/-0.6 ng/ml, P << 0.05). These changes did not occur in patients without H. pylori eradication. Eradication of H. pylori infection in type 1 diabetic patients modifies some parameters of lipid and haemostasis patterns, (increase of HDL-cholesterol, reduction of Lpa and decrease of CRP and TAT) and so contributes to improvement of cardiovascular risk factors in these patients.

Degree of hypercoagulability and hyperfibrinolysis is related to organ failure and prognosis after burn trauma.

Severely burned patients often present a hypercoagulability situation. However, its magnitude, time course, and relationship with organ failure and outcome remains to be established. Forty-three patients were studied on the first and seventh day after burn for hypercoagulability and fibrinolysis parameters. A hypercoagulability and hyperfibrinolysis state was found the first day after burn demonstrated by high levels of activated factor VII (VIIa, p<0.01), thrombin-antithrombin III complex (TAT, p<0.01), tissue plasminogen activator (t-PA, p<0.001) and D dimer (DD, p<0.01) and low levels of antithrombin III (ATIII, p<0.01), protein C (PC, p<0.01), plasminogen (PG, p<0.001) and alpha2 antiplasmin (AP, p<0.001). A paradoxical coexisting hypofibrinolysis was found as suggested by a low global fibrinolytic activity in the euglobulin plasma fraction fibrin plate assay (FA, p<0.01) and high levels of tissue plasminogen activator inhibitor type 1 (PAI-1, p<0.01). On day 7, a less marked hypercoagulability situation was found, with low ATIII (p<0.01) and PC (p<0.01), persisting the hypofibrinolytic situation observed on the first day. Non-survivors (NS) showed higher levels of VIIa (p<0.01), TAT (p<0.05) and t-PA (p<0.05), and lower levels of ATIII (p<0.05), PC (p<0.05) and AP (p<0.001) than survivors (S) on the first day. Also, there was a positive correlation of Marshall organ failure score with ATIII, (r2=0.49, p<0.001), PC, (r2=0.14, p<0.045) and PG levels, (r2=0.41, p<0.0003). Severely burned patients show a state of transient disseminated intravascular coagulation, related to the development of organ failure and outcome.

Subcutaneous versus intravenous low-dose IL-2 therapy after autologous transplantation: results of a prospective, non-randomized study.

Use of IL-2 therapy after autologous transplantation is currently being explored to reduce relapse rate. Low doses of the cytokine induce significant immunomodulation avoiding the severe side-effects associated with high-dose IL-2 therapy. However, low-dose IL-2 is usually given by continuous infusion through central venous lines with the consequent risks of thrombosis and infections. Twenty-six consecutive patients who received autologous transplants received low-dose IL-2 after stable engraftment had been achieved. The first 13 patients (group A) were scheduled to receive 400,000/IU/m2/day for 3 months by continuous intravenous infusion. Ten of these patients suffered infectious episodes, mainly bacteriemias that often necessitated delaying IL-2 therapy (median delivered dose: 32% of planned). The next 13 patients were then assigned to receive IL-2 (800,000-1,000,000 IU/m2/day for 3 months) subcutaneously (group B). For group B patients, median dose intensity was 84% (P = 0.01 when compared with group A patients). Only one severe infectious episode was observed in these patients. Clinical toxicity in group B patients consisted mainly of s.c. nodules. Immunomodulation, measured as an increase in the absolute number of CD56+ cells and CD56+(bright) cells, was higher in patients who received the cytokine by the subcutaneous route (median peak increase of CD56+ cells: 160 and 220% for group A and B patients respectively; median peak increase of CD56+(bright) cells: 210% and 310% for group A and B respectively, P < 0.05 between groups A and B). No statistically significant increment of T lymphocytes was observed in any group. No hematologic toxicity was observed apart from eosinophilia, which was very marked in group B (P < 0.01). Our results show that low-dose s.c. IL-2 therapy is associated with low clinical and hematologic toxicity after autologous transplantation. The immunomodulation achieved is no less than that achieved with the i.v. approach.

Increased levels of plasma von Willebrand factor in migraine crisis.

INTRODUCTION: To evaluate the participation of the vessel wall in the pathogenesis of migraine attack, we measured the plasma levels of von Willebrand factor (vWF), a protein secreted from the endothelial cells. MATERIAL & METHODS: 17 patients suffering from migraine without aura and 25 healthy volunteers were studied. von Willebrand factor and platelet aggregation tests were studied by conventional methods. RESULTS: The levels of vWF:antigen increased from 72.4 +/- 29 U/dl in the intercrisis to 130.2 +/- 75 U/dl during the attack (p < 0.01). We did not detect difference in the platelet aggregability in both phases. Plasma vWF activity measured as ristocetin cofactor (vWF:RCo) was similar in intercrisis and crisis (100.6 +/- 31 U/dl vs 94.5 +/- 44 U/dl). CONCLUSIONS: There is a plasma release of vWF molecules during the migraine crisis. This feature is not platelet dependent and is probably a consequence of endothelial stress.

Efficacy of D-dimer and total fibrin degradation products evaluation in suspected pulmonary embolism.

Three different assays for fibrin/fibrinogen degradation products (FDP) were evaluated in patients with suspected pulmonary embolism (PE) as rapid screening tests with the aim of evaluating whether they could be used either as a substitute of ventilation/perfusion lung scanning or to supplement scintigraphy in patients in whom the scan was inconclusive (low or intermediate probability). D-Dimer by enzyme-linked immunosorbent assay (ELISA) and latex and total FDP by ELISA were measured prospectively in 85 consecutive patients with suspected PE. With a cutoff of 500 ng/ml, D-dimer by ELISA presented a 96% sensitivity and a 42% specificity, with positive and negative predictive values of 49 and 96%, respectively. D-Dimer by latex, also with a cutoff of 500 ng/ml showed a 93% sensitivity and 29% specificity, with positive and negative predictive values of 43 and 89%. For total FDP, with a cutoff of 900 ng/ml, the sensitivity and specificity were 96 and 26% respectively, with positive and negative predictive values of 42 and 93%. A normal assay may have reduced the necessity of a ventilation/perfusion only in 28% patients with D-dimer ELISA, 21% with D-dimer latex and 17% with total FDP ELISA and with a possible error of 4, 11 and 7%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

High plasma levels of plasminogen activator inhibitor 1 (PAI-1) in polycythemia vera and essential thrombocythemia are associated with thrombosis.

We attempted to determine if a hypercoagulability state exists in patients with polycythemia vera (PV) and essential thrombocythemia (ET). We studied the hematocrit level, platelet count, use of any antiaggregant drugs, thrombotic or bleeding accidents and plasma levels of antithrombin III, protein C, total protein S, free protein S, vWF:Ag (Von Willebrand's factor related antigen), thrombin-antithrombin complexes, D-dimer, fibrinolytic activity, tissue plasminogen activator, plasminogen and PAI-1 in 33 patients (19 with ET and 14 with PV). PAI-1 plasma concentration was significantly higher in, both ET and PV patients than in the control group, and were higher in those patients with previous thrombotic episodes than in asymptomatic patients or with previous bleeding episodes. Increasing age was associated to more thrombotic episodes while younger patients presented with more hemorrhagic complications. A linear correlation between platelet count and PAI-1 levels in PV patients (r = 0.44, p < 0.05) and ET patients (r = 0.30, p < 0.05) was found. Fibrinolytic activity in patients with ET was significantly decreased when compared to the control group. A hypofibrinolytic state could be an additional factor which could be used as a predictive index of the thrombotic or bleeding tendency in each patient.

[Pentoxifylline is not useful in the prevention of toxicity associated with bone marrow transplantation]. / La pentoxifilina no es útil en la prevención de la toxicidad asociada al trasplante de médula ósea.

BACKGROUND: To evaluate the possible beneficial effect of pentoxifylline (PTX) on both the decrease of toxicity related to bone marrow transplantation (BMT) and the acceleration of the hematopoietic graft. METHODS: Twenty consecutive patients treated with BMT received pentoxifylline (400 mg/6 hours, orally) up to day +50 to prevent toxicity derived from BMT. A previous group of 29 consecutive patients transplanted in the same center were used as controls. The different clinical toxicities (mucositis, kidney failure, hepatic venocclusive disease, graft versus host disease, number of days with fever, day of hospital discharge and survival at day +50), the time elapsed until the hematopoietic graft and the levels of tumoral necrosis factor alpha were evaluated. RESULTS: No significant differences were observed in any of the parameters studied in the two groups of patients. CONCLUSIONS: Treatment with pentoxifylline does not prevent the toxicity derived from BMT or accelerate the hematopoietic grafting.

Von Willebrand factor availability in platelet concentrates stored for 5 days.

Von Willebrand factor (vWF) availability was assessed in platelet concentrates (PCs). After 5 days of storage, 82 +/- 9% of basal levels of ristocetin cofactor activity (vWF:RCo) remained in PCs. vWF antigen (vWF:Ag) increased up to 166 +/- 38% (P < 0.05) in the same period. Autoradiograph pattern of vW:Ag showed an increase in low molecular weight multimers, and fast migrating multimeric forms were visualized by crossed immunoelectrophoresis on day 5. Studies carried out in platelet free plasma stored as PCs showed similar changes in vWF:RCo but increments in vWF:Ag were not detected. These data indicate that PCs maintain vWF:RCo levels of clinical value even after 5 days of storage and suggest that vWF comes out from platelets to plasma during storage.

High F1.2 fragment of prothrombin, thrombin-antithrombin III complex (TAT) and soluble fibrin plasma levels demonstrate hypercoagulability induced during loco-regional thrombolytic therapy with rt-PA.

In order to investigate the coagulation and fibrinolysis state in arterial peripheral thrombosis and thrombolysis, we studied 33 consecutive patients (mean age = 65, range: 28-88), 25 males and 8 females diagnosed of acute or subacute lower limb arterial thrombosis, treated with an intrathrombus infusion of rt-PA (0.1 mg/Kg/h) for three hours. Plasma levels of antithrombin III (AT-III), protein C (PC), plasminogen (Pg) and alpha 2-antiplasmin (AP), total and free protein S (PS), thrombin-antithrombin III complex (TAT), F1.2 fragment of prothrombin (F1.2), fibrinogen (Fg), soluble fibrin monomers (FM), tissue-plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), total fibrinogen/fibrin degradation products (TDP) and D dimer (DD) were determined prior to the therapeutic regime, at the end of the treatment, and 24 hours later. Levels of AT-III and protein C were somewhat low during the complete study. There was an increase in t-PA, TDP and D Dimer and a decrease of fibrinogen, alpha 2-antiplasmin and plasminogen at 3 hours. An elevation of TAT, fibrin monomers and F1.2 levels was found at three hours. A positive correlation between TAT and F1.2 was observed (r = 0.57, p < 0.05). There was also a positive correlation between soluble fibrin and TAT (r = 0.59, p < 0.05) and with F1.2 (r = 0.56. p < 0.05). These latter facts reflect an hypercoagulable situation induced during loco-regional thrombolytic therapy.

[Current status of thrombolysis. The need for coadjuvant antithrombotic therapy]. / Estado actual de la trombolisis. Necesidad de la terapéutica antitrombótica coadyuvante.

Thrombolytic therapy yields a 80% repermeabilitation in the acute myocardium infarct if applied soon. In other thrombotic sites such as deep venous thrombosis, pulmonary thromboembolism and peripheral arterial thrombosis, with no large cooperative randomized clinical trials, its usefulness is clear, tough selectively. The high rethrombosis frequency is the major drawback of this therapy. The concomitant use of an anti-thrombotic and/or anti-aggregant agent, even tough the possible higher risks of hemorrhages, seems a key element to improve the results obtained with thrombolysis.

Time course of hemostatic abnormalities in sepsis and its relation to outcome.

OBJECTIVES: To investigate the time course and the relation to prognosis of coagulation and fibrinolytic abnormalities in patients with septic shock. PATIENTS AND METHODS: Forty-eight consecutive patients admitted to the medical ICU with the diagnosis of septic shock (diagnosed by defined criteria) were studied. Mortality was 25 of 48. Mean age was 57 +/- 7.3 years. Blood samples were obtained on days 1, 4, and 7 after hospital admission to measure tissue-type plasminogen activator antigen (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor antigen (PAI-1), plasminogen, alpha 2-antiplasmin, fibrinogen, antithrombin III, protein C, protein S, thrombin-antithrombin complexes (TAT), D-dimer, and von Willebrand factor-related antigen (vWF:Ag). RESULTS: All patients showed marked abnormalities in both the coagulation and fibrinolytic systems. There were signs of coagulation activation and elevation of both activators and inhibitors of fibrinolysis. Nonsurvivors showed lower levels of protein C and antithrombin III and higher concentration of TAT than survivors. While both t-PA and PAI-1 concentrations were high in survivors and nonsurvivors, only survivors showed a progressive normalization of both parameters during the study period. Low plasminogen levels and plasminogen/alpha 2-antiplasmin ratio were found in both groups, presenting a trend toward normalization only in survivors. The differences reported were not apparent at the time of hospital admission. CONCLUSIONS: Septic shock is characterized by coagulation activation and fibrinolysis activation and inhibition. Nonsurvivors present a particular hemostatic profile characterized by a more marked activation of coagulation and a more intense inhibition of fibrinolysis. None of the abnormalities studied was significantly different between survivors and nonsurvivors at the time of hospital admission. In the presence of fibrin formation, nonsurvivors present a maintained imbalance in the fibrinolytic response determined by higher PAI-1 plasma concentration, probably contributing to their poor outcome.