[Cost-effectiveness analysis of enoxaparin for the prophylaxis of venous thromboembolism in major orthopedic surgery patients]. / Análisis coste-efectividad de enoxaparina en la proxilaxis de la enfermedad tromboembólica venosa en pacientes sometidos a cirugía mayor ortopédica.

OBJECTIVES AND METHODS: A retrospective, modeled, cost-effectiveness analysis was conducted with enoxaparin versus non-prophylaxis, tinzaparin, and unfractionated heparin for venous thromboembolic disease in Spanish patients undergoing major orthopedic surgery from the standpoint of the Spanish national health system. Episodes avoided and life-years gained with each treatment were estimated by a meta-analysis of clinical trials. RESULTS: With enoxaparin fewer thromboembolic episodes and deaths occurred, when compared to the available alternative options. Enoxaparin was the dominant option (lower total cost and equal or greater effectiveness than any alternative option) in comparison with non-prophylaxis, tinzaparin, and unfractionated heparin. A sensitivity analysis confirmed the stability of these results. CONCLUSION: The administration of enoxaparin as a prophylactic treatment for venous thromboembolic disease in patients undergoing hip or knee surgery is a cost-effective intervention in every case, and less expensive than the alternative options used in Spain.

Análisis coste-efectividad de enoxaparina en la profilaxis de laenfermedad tromboembólica venosa en pacientes sometidos acirugía mayor ortopédica / Cost-effectiveness analysis of enoxaparin for the prophylaxis of venous thromboembolism in major orthopedic surgery patients

Objetivos y métodos: Se hizo un análisis coste-efectividad, retrospectivo y modelizado, de enoxaparina frente a la no profilaxis, tinzaparina y heparina no fraccionada de la enfermedad tromboembólica venosa, en pacientes españoles sometidos a cirugía mayor ortopédica, desde la perspectiva del Sistema Nacional de Salud. Los episodios evitados y años de vida ganados con cada tratamiento se estimaron mediante un metaanálisis de ensayos clínicos. Resultados: Con enoxaparina hubo un menor número de episodios tromboembólicos y muertes que con las opciones alternativas. Enoxaparina fue la opción dominante (costes totales menores y efectividad igual o mayor que la opción alternativa) en comparación con la no profilaxis, tinzaparina y las heparinas no fraccionadas. El análisis de sensibilidad confirmó la estabilidad de estos resultados. Conclusión: La administración de enoxaparina como profilaxis de la enfermedad tromboembólica venosa, en la cirugía de cadera o rodilla, es una intervención coste-efectiva en todos los casos, suponiendo un ahorro respecto a opciones alternativas utilizadas en nuestro país. (AU)

Comparative study of a portable prothrombin time monitor employing three different systems in oral anticoagulant units.

The aim of this study was to evaluate the accuracy of the portable coagulometer CoaguChek (Roche Diagnostics) as a prothrombin time (PT) monitor, and to correlate capillary blood results with those of three different routine methods used for monitoring oral anticoagulant therapy (OAT): capillary, plasma and whole blood samples. Three hospitals participated in the study with a total of 235 patients on OAT. The international normalized ratio (INR) results obtained with CoaguChek were compared with those obtained using each of the routine methods. The study presents a good correlation between the PT monitor and the three methods studied: r = 0.9745 (hospital A), r = 0.9283 (hospital B), r = 0.9136 (hospital C). A simplified concordance test of the methods results in a nine-field comparison table showing concordances of 87.2, 85.7 and 68.4%, respectively. The absolute difference (mean +/- SD) between laboratory A and CoaguChek INRs was 0.0571 +/- 0.2042, with values of 0.04286 +/- 0.3906 for laboratory B and 0.6986 +/- 0.6170 for laboratory C. These results confirm that CoaguChek could be used as a new method for oral anticoagulant monitoring, and is in best agreement with the capillary blood PT system.

Platelet ultrastructural morphometry for diagnosis of partial delta-storage pool disease in patients with mild platelet dysfunction and/or thrombocytopenia of unknown origin. A study of 24 cases.

BACKGROUND AND OBJECTIVE: Exact diagnosis is sometimes difficult in patients presenting with a slight bleeding diathesis, prolonged bleeding times, non-specific aggregometric abnormalities, and/or mild thrombocytopenia. The objective of this study was to evaluate the use of platelet ultrastructural morphometry in detecting a partial d-storage pool disease in such patients. DESIGN AND METHODS: Platelets from 52 patients and 15 controls were fixed immediately in glutaraldehyde in White's saline without anticoagulant and processed for transmission electron microscopy. Using computer-assisted morphometry, the size and shape of the platelets were measured, as were the size and number per platelet of the dense- and a-granules. Ultrastructural morphology of the above and other intraplatelet structures was observed. RESULTS: Twenty-four cases were diagnosed as having a partial d-storage pool disease. Mean platelet area (2.28 microm(2)) and maximum diameter (2.58 microm) were significantly greater in patients than in control subjects (1.64 microm(2) and 2. 25 microm, respectively) but discoid shape was preserved. Mean dense-granule number was decreased, both per platelet and per microm(2) of platelet area (patients 0.22 and 0.09; controls 0.42 and 0.24). Seven patients also had a marked decrease in a-granules, resulting in a significantly lower mean number of granules per microm(2 )(patients 2.43; controls 3.15). Additionally, the patients' platelets had significant increases in both lipid droplets and surface-connected canalicular system. INTERPRETATION AND CONCLUSIONS: A partial dense-granule deficiency, sometimes associated with partial a-granule deficiency, should be borne in mind faced with patients who have a slight bleeding diathesis, non-specific platelet dysfunction tests and/or mild thrombocytopenia of unknown origin. Platelet ultrastructural morphometry is useful in diagnosing this condition.

¿La eficacia y seguridad de las heparinas de bajo peso molecular (HBPM) dependen de la actividad anti-FXa y anti-FIIa? Otras actividades antitrombóticas de las HBPM / Do the efficacy and safety of low molecular weight heparins (LMWH) depend on the anti-Fxa and anti-FIIa activity? Other antithombotic activities of the LMWH

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The prophylactic effect of aprotinin on intraoperative bleeding in liver transplantation: a randomized clinical study.

Fibrinolysis has been recognized as an important cause of intraoperative bleeding during orthotopic liver transplantation (OLT). Several investigators have used prophylactic administration of aprotinin in patients to inhibit fibrinolysis and to decrease transfusion requirements, morbidity, and mortality. Nevertheless, the role of aprotinin in this situation is not yet clear. The goal of this study was to determine the effects of prophylactic administration of aprotinin on intraoperative bleeding and blood requirements, and on hemostatic changes during OLT. Eighty consecutive patients were included in a double-blind, prospective study and were randomized in two groups. In group A (n = 39), an initial dose of 2 x 10(6) kallikrein inactivator units (KIU) of aprotinin was administered in the induction of anesthesia followed by infusion of 5 x 10(5) KIU/h until the end of the procedure. The control group (n = 41) received an identical volume of saline solution. The majority of the operations were performed with vena cava preservation (piggy-back technique) without venovenous bypass. During the anhepatic phase, a significant increase in levels of tissue plasminogen activator, thrombin-antithrombin complexes (TAT) and D-dimers (DD) was noted in both groups. A significant increment of TAT was observed in group A during reperfusion. The remaining hemostatic parameters were similar in both groups. Intraoperative requirements of packed red cells, fresh-frozen plasma (FFP), platelets, and cryoprecipitate were similar in the two groups. Our results suggest that prophylactic administration of aprotinin is not useful in reducing bleeding and blood product requirements during OLT.

Increased prothrombin fragment 1 + 2 and D-dimer in first-degree relatives of type 2 diabetic patients. Prethrombotic state in relatives of type 2 diabetic patients.

To evaluate whether or not activated coagulation is present in the preclinical phases of type 2 diabetes mellitus, we studied 46 non-diabetic first-degree relatives of type 2 diabetic patients and 21 matched controls with no family history of diabetes. We determined the plasma levels of prothrombin fragment 1 + 2, D-dimer, fibrinogen, plasminogen activator inhibitor type 1, tissue plasminogen activator, von Willebrand factor and coagulation factors VII and VIII. Glucose tolerance, beta-cell function and insulin sensitivity were assessed in all subjects by a continuous glucose infusion of 5 mg.kg ideal body weight-1.min-1 for 60 min with model assessment of glucose, insulin and C-peptide values. Plasma levels of prothrombin fragment 1 + 2 (median 1.24 vs 0.68 nmol.l-1; P = 0.0001) and D-dimer (331 vs 254 micrograms.l-1 UEF; P = 0.018) were higher in relatives, without significant differences in the other haemostatic variables. Relatives showed higher fasting (5.5 vs 4.9 mmol.l-1, P = 0.004) and post-infusion (9.3 vs 8.3 mmol.l-1, P = 0.02) serum glucose, no differences in insulin or C-peptide levels, lower beta-cell function (122% vs 147%; P = 0.02) and no significant differences in insulin sensitivity. Fifteen relatives were glucose-intolerant and had lower beta-cell function and insulin sensitivity than glucose-tolerant relatives. Both subsets of relatives exhibited higher levels of prothrombin fragment 1 + 2 and D-dimer than control subjects. Thus, first-degree relatives of type 2 diabetic patients present an activated coagulation, even in the absence of minor degrees of glucose intolerance. These abnormalities can play a role in the pathogenesis of cardiovascular diseases frequently seen at diagnosis of type 2 diabetes.

[Standardization Committee for Haematology. External Quality Assurance Program for General Hematology. Evaluation of the 1994 results]. / Comité de Estandardización en Hematología. Programa de Evaluación Externa de la Calidad en Hematología General. Valoración de los resultados correspondientes a 1994.

UNLABELLED: Since 1994, the Standardisation Committee for Haematology publishes yearly the results of its external quality assurance programme (EQAPH), after it has been improved and even integrated in the Health Services of some autonomous communities. METHODS: Four hundred and seventy-three laboratories take part in EQAPH. The evaluation of the haematological records is carried out every year from the results of two whole blood samples. Two samples of lyophillised plasma are sent every month to participant laboratories in order to assess prothrombin time (PT), partial thromboplastin time (PTT) and fibrinogen. Samples are sent every three months for antithrombin III (AT-III) determination. According to the types of autoanalysers used, 9 groups have been established: Group I (Technicon H* and H-6000), group II (Technicon H*2 and H*3), group III (Coulter MaxM, STKS, Cobas Argos and Cell-Dyn 3000/3500), group IV (Coulter STKR), group V (Coulter JS/JT), group VI (Coulter S/T, Cobas Helios/Minos), group VII (Sysmex E/NE), group VIII (Sysmex K-1000), and group IX (other semi-automated counters). Three groups are established for general coagulation tests and two others for AT-III. The value of the mean of all results (consensus mean) and of each particular group (group mean) are used as statistical methods. The results are expressed as: (1) coefficient of variation, % (CV); (2) deviation index (DI); DI values attained with respect to the same group (or method) or all groups (or methods) allowed us to classify the results in four categories: excellent (0 < DI < 0.5), good (0.5 < DI < 1.0), satisfactory (1.0 < DI < 2.0), and out of acceptable limits (ID > 2.0); (3) Youden graphs or graphic representations of DI calculated from the analysis of the control specimens. RESULTS: Group I yielded lesser values for leucocyte count (0.221) and higher for MCH (0.833). Group II showed high DI values for PCV (0.933) and MCV (1.146). Group III had lower values for red cell count (0.097), haemoglobin concentration (0.133) and MCH (0.91). Group IV showed lower platelet count. Group V had higher haemoglobin concentration values. Group VI yielded higher DI in the platelet count and group VII in the white cell count. Group VII showed the lowest DI for MCV and MHC. Group IX had high values for red cell count and MCH. In the coagulation field, group I had higher values for PT and AT-III. Group II showed higher DI values for PTT and fibrinogen. The highest CV values were seen in groups VIII and IX. The lowest values were present in group II for haemoglobin, IV for MCH, in V for PCV and MCV, in VII for red cell count and MCH, in VII for white cell count and in VII for platelet count. The coagulation tests showed lower CV values than cytometry, the lowest being for PT in group I and PTT and fibrinogenein group II. With regard to the influence of acceptable results on adverse ones within this group, the percentage of laboratories with mean DI over 2 were calculated. Thus, the laboratories achieved 43.5% of values within acceptable limits for platelet count and 56.7% for white cell count. Regarding the PCV, out of 47.9% of the laboratories, only 1.0% showed high deviation of some results. In the coagulation parameters, of the 37.2 in this group for AT-III, 32.4% showed a mean DI over 2. CONCLUSIONS: Participation in External Quality Assurance programmes contributes to the comparability of the results provided by different laboratories, thus increasing their accuracy and improving the quality of patient care.

Characteristics and performance of the external quality assessment scheme (EQAS) for haematology in Spain. Ten years of experience.

The external quality assessment scheme for haematology (EQAS-H) in Spain started in 1984 with 56 laboratories, being 473 in 1994. Participants come from public health services (70%) and from private laboratories (30%). Surveys are performed monthly or quarterly depending on the tests and on each occasion the following samples are prepared and sent by the professional organizing team: human (HIV/HBsAg free) or equine whole blood for cell counts (erythrocytes and leucocyte), platelet suspensions for platelet counts, lyophilized plasmas for prothrombin time (PT), partial thromboplastin time (APTT), fibrinogen (F) and antithrombin III (ATIII), and blood films for cell morphology and reticulocyte counts. In 1992 a new scheme on oral anticoagulant treatment control (OATC) has been established jointly by the Spanish Haematology Association (AEHH) and the Spanish Society of Thrombosis and Haemostasis (SETH). After preparation, the control material is sent to participants in the scheme where the requested tests are performed and the results reported back to the organizer (Haematology Laboratory Department of Hospital Clínic i Provincial) for statistical analysis. For evaluating the results, laboratories are divided into four to eight groups depending on the methodologies used. Individual results are assessed against a consensus value (mean) and a deviation index (DI) from the mean, and the coefficient of variation (CV), Youden plots and other statistical information are provided for all results and groups of each parameter. More than 80% of laboratories responded regularly (up to 6 trials) for blood counts and haemoglobin and compared to the previous year (1984), the values of CV(%) improved significantly for RBC count (from 3.3 to 2.2%), haemoglobin (from 2.7 to 2.1%) and platelet count (from 22.6 to 16.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparative multicenter study of a rabbit high-sensitivity thromboplastin and a recombinant thromboplastin with synthetic phospholipids]. / Estudio multicéntrico comparativo entre una tromboplastina de conejo de alta sensibilidad y una tromboplastina recombinante con fosfolípidos sintéticos.

PURPOSE: The purpose of the present study was to compare the results obtained with a human recombinant thromboplastin (Innovin, Baxter) (IN) and a high-sensitivity rabbit brain reagent (Thromboplastin IS, Baxter) (IS), on the performance of prothrombin time (PT) test and the functional assay of factors included in the extrinsic coagulation system, in order to establish possible differences on imprecision, diagnostic accuracy and sensitivity to the oral anticoagulant defect, between the two products. MATERIAL AND METHODS: Six Spanish hospital took part in the study. Plasma samples from 221 healthy subjects, 100 patients with severe liver disease, 27 with dysfibrinogenaemia, 10 with lupus anticoagulant and from 13 individuals propositus and their relatives with congenital deficiencies of the extrinsic coagulation pathway, and their relatives were studied; 188 patients stabilized on oral anticoagulant therapy and 82 on heparin therapy were also included. The in vitro effect of heparin was tested by addition of increasing amounts of heparin (0.3 to 10.0 IU/mL) to aliquots of normal plasma. RESULTS: Both in the intra-assay and in the inter-assay imprecision study, a better coefficient of variation was obtained with IN when the PT was performed on abnormal samples. Prothrombin time ratio from patients with liver disease had significantly higher values with IS. On the contrary, IN had a higher sensitivity in samples from patients with dysfibrinogenaemia or from those stabilized on oral anticoagulant therapy. In showed a very low sensitivity to heparin at concentrations corresponding to the therapeutic range. CONCLUSIONS: The results of this field study indicate that IN, compared with a high-sensitivity rabbit brain thromboplastin, is a suitable reagent for PT determination in normal subjects, patients with liver disease or with congenital deficiencies of clotting factors. It shows a higher sensitivity in cases of dysfibrinogenaemia and in patients on oral anticoagulant therapy. In addition, the recombinant reagent had better reproducibility when the PT was performed on abnormal samples, and it was hardly affected by heparin within the therapeutic range.

[Thrombosis and thrombocytopenia associated with the use of unfractionated heparin in a female patient with unstable angina]. / Trombosis y trombocitopenia asociadas al uso de heparina no fraccionada en una paciente con angina inestable.

A case of heparin-induced platelet activation with thrombocytopenia and several arterial emboli in a 60-year-old woman suffering unstable angina is presented. The early recognition of the syndrome, with cessation of heparin and the use of unfractionated heparin, led to an immediate remission of the thrombocytopenia and thromboembolic complications.

[Shock. Antioxidant immunologico-therapeutic replacement]. / Consideraciones acerca del shock. Substitución inmunológica-terapéutica antioxidante.

Shock is a specific reaction to a non specific severe injury. The organic reaction is a biphasic (excitation/depression) threefold response: haemodynamic, hemostatic and immunologic. The physiopathology is related with changes produced by injury on macrophages, neutrophils, platelets and endothelial cells. The release of enzymes and certain vasoactive compounds enhance activation of neutrophils, which produce great amounts of free oxygen radicals. Therapy must be basically substitutive, including immunologic substitution. Therapeutic trends are based on the use of substances which can avoid the overproduction or nocive effects of free oxygen radicals.