Nadroparina em pacientes com tromboembolia pulmonar de repetição / Nadroparin in patients with recurrent pulmonary thromboembolism

O objetivo é analisar as evidências científicas disponíveis atualmente sobre a eficácia e a segurança da nadroparina em pacientes com tromboembolia pulmonar de repetição, visando à redução da reincidência dos eventos tromboembólicos, sangramentos e demais eventos adversos. A tromboembolia pulmonar (TEP) e a trombose venosa profunda (TVP) constituem o tromboembolismo venoso (TEV), doença silenciosa potencialmente fatal. Ambas constituem processos patológicos freqüentes que podem afetar tanto pessoas sãs quanto aquelas que se submeteram a processos cirúrgicos ou médicos invasivos. Podem se manifestar de modo isolado ou em conjunto e, em regra, os sintomas são inespecíficos; muitas vezes, a primeira manifestação já leva ao óbito. Ou então, manifestam-se de forma aguda fazendo com que o doente procure atenção médica. A embolia pulmonar comumente tem início súbito, apresentando-se com dispnéia, dor pleural, tosse, hemoptise ou choque, na ausência de outras causas. Em regra, os sintomas ocorrem de forma aguda e levam o paciente a procurar atendimento médico. Podem ser classificados em três grupos: dispnéia isolada; dor pleurítica e hemoptise; e colapso circulatório. A gravidade depende da magnitude da embolia e da condição cardiorrespiratória prévia. Nadroparina é uma heparina de baixo peso molecular com propriedades anticoagulantes, registrada na Agência Nacional de Vigilância Sanitária (ANVISA) com o nome comercial de Fraxiparina®, na forma farmacêutica de solução injetável para uso subcutâneo e com apresentação de seringas preenchidas com 0,3 mL de solução equivalente a 2850 UI anti-Xa em cartuchos contendo 10 seringas ou 0,6 mL de solução equivalente a 5700 UI anti-Xa em cartuchos contendo 5 seringas.A Fraxiparina® é indicada para profilaxia de doenças tromboembólicas, tais como \r\naquelas associadas à cirurgia em geral ou ortopédica e em pacientes clínicos de alto risco (insuficiência respiratória e/ou infecção respiratória e/ou insuficiência cardíaca) hospitalizados em unidade de tratamento intensivo; tratamento de doenças tromboembólicas; prevenção de coagulação durante a hemodiálise; \r\ntratamento de angina instável e infarto do miocárdio não-Q. O presente relatório demonstrou que não existem evidências científicas robustas a respeito da tecnologia avaliada para o tratamento de TEP. Uma parcela da \r\nliteratura sobre a condição clínica traz os resultados das HBPM de forma agrupada, nesses casos, em regra, o comparador é HNF. Os membros da CONITEC presentes na 19ª reunião do plenário realizada nos dias 04/09/2013 e 05/09/2013 apreciaram a proposta de incorporação da nadroparina em pacientes com\r\ntromboembolia pulmonar de repetição e, decidiram, por unanimidade, pela não incorporação do medicamento.

Nadroparina cálcica: una revisión de su farmacología básica y clínica / Nadroparin calcium: a review of its basic and clinical pharmacology

Objetivo. Evaluar críticamente la información sobre la farmacología básica y clínica de la nadroparina cálcica. Fuente de datos. Se hizo una búsqueda en la literatura científica de octubre de 1985 a septiembre de 2010, en las bases de datos electrónicas: Pubmed, Cochrane, MDConsult,Scielo y Medscape, y en el Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA).Selección de estudios. Se incluyeron los estudios publicados en inglés, español o francés, realizados en humanos y animales de experimentación, en los que se revisarala farmacología básica y clínica de la nadroparina cálcica. Extracción y síntesis de datos. Se revisaron 792 resúmenes y se seleccionaron 60artículos que cumplieron los criterios de inclusión, de acuerdo con un método se resolvieron todas las discrepancias por discusión y consenso.Conclusión. En algunos estudios la nadroparina cálcica ha mostrado una eficacia igual o superior a la de la heparina no fraccionada y la de un placebo. Sin embargo, la información evaluada no es lo suficientemente sólida para considerar superior lanadroparina frente a las otras heparinas de bajo peso molecular. La literatura científica muestra que, en general, el tratamiento con estas últimas es más seguro y costo-efectivo que con heparina no fraccionada. No existen pruebas suficientes, fuertes y concluyentes para calificar la nadroparina cálcica como superior aotras heparinas de bajo peso molecular en el tratamiento antitrombótico. Las de bajo peso molecular han demostrado una reducción significativaen la angiogénesis tumoral y un aumento en la supervivencia de pacientes con enfermedades oncológicas. Sin embargo, se requieren más investigaciones para caracterizar y comprender mejor este nuevo hallazgo...

Objective: To evaluate critically the evidence on the basic and clinical pharmacology of nadroparin calcium.Data source: We conducted a literature review from October 1985 to September 2010 in the electronic databases: Pubmed, Cochrane,MD Cosult, Medscape, Scielo and Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA).Study selection: Studies published in English, Spanish or French made in humans and animals for experimentation which reviewed the basic and clinical pharmacology of nadroparin calcium wereincluded. Data extraction and synthesis: 792 abstracts were reviewed by authors and 60 papers were selected that met inclusion criteria according to a standardized method All discrepancies were resolved by discussion and consensus. Conclusion: Some studies have shown that the efficacy of nadroparin calcium is equal or superior to unfractionated heparin (UFH) and placebo, however, the strength of assessed evidencehas been insufficient for considering nadroparin calcium superior to other low molecular weight heparins (LMWH). Literature shows that LMWHstherapy is more cost-effective and safer than UFH therapy in general. It does not exist enough, strong and conclusive evidence for considering antithrombotic nadroparin calcium therapy greater to other LMWHs. LMWHs have shown a significantreduction in tumor angiogenesis and increased survival in oncology patients. To conduct further research is necessary to characterize and understand better this new finding...

Clinical application of low-molecular-weight heparin (Fraxiparine) in rescuing venous crisis of island skin flap / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of low molecular weight heparin (Fraxiparine) in rescuing venous crisis of island skin flap.</p><p><b>METHODS</b>Of the 73 patients with venous crisis of island skin flap, 47 received subcutaneous injection of low-molecular-weight heparin (group I) and 26 were treated with phlebotomy, local compression and topical application of unfractionated heparin solution gauze (group II).</p><p><b>RESULTS</b>The flap survival ratio was (88.46∓8.64)% in group I and (38.37∓6.53)% in group II (P<0.001). At 0, 2, and 4 h after injection of low-molecular-weight heparin, the activated partial thromboplastin time (APTT) was obviously delayed (24.28∓6.71, 41.35∓7.64 and 32.34∓6.35, respectively, P<0.01), FXa:C level was significantly decreased (152.4∓30.7, 65.8∓24.4 and 83.4∓18.4, respectively, P<0.01), while FIIa:C level underwent no obvious alterations (155.70∓31.61, 143.20∓24.75, and 143.4∓23.35, respectively, P=NS).</p><p><b>CONCLUSION</b>Fraxiparine has good antithrombotic efficacy in rescuing venous crisis of island skin flap without adverse effect on systemic coagulation.</p>

Bleeding Complications Associated With the Use of Low Molecular Weight Heparin According to the Degree of Renal Impairment / 대한신장학회지

PURPOSE: Low molecular weight heparin (LMWH) is safe and effective in the treatment of acute coronary syndrome (ACS) and venous thromboembolism. Compared with unfractionated heparin (UFH), it is known to have less bleeding tendency in the general population. However, it is not certain whether bleeding complications are decreased by LMWH in patients with renal failure. We postulated that the use of LMWH may lead to increase in bleeding tendency in patients with renal dysfunction. METHODS: We conducted a retrospective study in 486 hospitalized patients who were diagnosed as cerebral infarction or ACS, and treated with enoxaparin or nadroparin from January 2008 to December 2009. Bleeding complications were compared in 3 groups according to estimated glomerular filtration rate (GFR> or =60, 30-59, and <30 mL/min/1.73m2). Age, hypertension (HTN), diabetes mellitus (DM), smoking and usage of antithrombotics were examined and the relationship of these variables with bleeding tendency was analyzed. RESULTS: Compared with group I, the frequency of total bleeding complications increased in patients with group II (p=0.002) and III (p=0.005) regardless of adequate dose reduction. Multiple logistic regression analysis after adjustment for age, HTN, DM, and usage of antithrombotics revealed that decreased GFR groups [odds ratio (OR) of group II was 5.79 (95% confidence interval (CI), 1.23-29.97; p=0.042), OR of group III 5.92 (95% CI, 1.22-27.61; p=0.029)] and DM [OR of DM 7.88 (95% CI; 1.46-46.32, p=0.026)] were two independent factors which affect major bleeding. CONCLUSION: These findings suggest that renal insufficiency, even if it is mild, could affect major bleeding complications in the use of LMWH.

Comparison of safety and efficacy between fondaparinux and nadroparin in non-ST elevation acute coronary syndromes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) guidelines gave fondaparinux a class I recommendation for use in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) undergoing invasive or conservative strategy. Nadroparin is one of the common anticoagulants used in NSTE-ACS in China. Accordingly, this study compared the safety and efficacy between fondaparinux and nadroparin in patients with NSTE-ACS.</p><p><b>METHODS</b>In this prospective, randomized, open-label, and single center study, a total of 300 patients with NSTE-ACS were randomized to receive either fondaparinux (group F, n = 150, 2.5 mg/d) or nadroparin (group N, n = 150, 0.1 ml/10 kg q12 h) for a mean of 4 days. The primary safety endpoint was the incidence of major or minor bleeding at 9 days that was not related to coronary artery bypass grafting (CABG). The primary efficacy endpoints included death, myocardial infarction, or recurrent ischemia at 9 days. All patients underwent a 180-day follow-up.</p><p><b>RESULTS</b>Baseline characteristics were well matched between the two groups. There was a non-significant 28% relative risk reduction in the primary safety endpoint in group F compared with group N (4.7% vs. 6.7%, HR 0.72, 95%CI 0.42-1.65, P = 0.38). The primary efficacy endpoint was 8.0% in group F and 10.0% in group N (HR, 0.82, 95%CI 0.54-1.71, P = 0.49). The composite of the safety and efficacy endpoints at 9 days (10.0% vs. 16.0%, HR 0.61, 95%CI 0.31-1.10, P = 0.10), 30 days (14.0% vs. 17.9%, HR 0.72, 95%CI 0.47-1.16, P = 0.21), or 180 days (18.7% vs. 27.3%, HR 0.65, 95%CI 0.38-1.11, P = 0.11) showed a non-significant trend toward a lower value in group F.</p><p><b>CONCLUSION</b>Fondaparinux resulted in a nonsignificant risk reduction in patients with NSTE-ACS in both bleeding and ischaemic events during short- and long-term follow-up compared with nadroparin.</p>

In vitro anticoagulation monitoring of low-molecular-weight heparin / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxaparin, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time.</p><p><b>METHODS</b>A total of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied.</p><p><b>RESULTS</b>The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r = 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU, diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant.</p><p><b>CONCLUSIONS</b>The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin. The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-IIa activities.</p>

Efficacy comparison with low and high dose nadroparin for patients with acute coronary syndrome underwent percutaneous coronary intervention / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the safety and optimal prior percutaneous coronary intervention (PCI) nadroparin dose in patients with acute coronary syndrome (ACS).</p><p><b>METHODS</b>A total of 236 ACS patients were randomly treated with subcutaneously nadroparin 0.075 ml/10 kg (group I, n = 120) and 0.1 ml/10 kg (group II, n = 116) respectively (bid for 48 hours). PCI was the performed 1 h after final nadroparin injection. No additional nadroparin was applied during PCI. Plasmic anti-Xa level was assayed before and at 1, 2, 4 and 8 hours after final nadroparin administration. Adverse clinical events (death, myocardial infarction, need for revascularization) and bleeding events were recorded up to 30 days post PCI.</p><p><b>RESULTS</b>Baseline clinical characteristics as well as the MACE and severe bleeding events between the two groups were similar (all P > 0.05). Plasmic anti-Xa level of group II was significantly higher than that of group I post nadroparin application (P < 0.01).</p><p><b>CONCLUSION</b>Anticoagulation effects and MACE as well as severe bleeding events up to 30 days post PCI were similar with either 0.075 ml/10 kg or 0.1 ml/10 kg nadroparin dose in ACS patients.</p>

Low Molecular Weight Heparin Treatment in Pregnant Women with a Mechanical Heart Valve Prosthesis

No definitive recommendation is available concerning optimal antithrombotic therapy in pregnant women with a mechanical heart valve. The purpose of the current study was to evaluate the clinical results of nadroparin treatment with respect to pregnancy outcome and maternal complications. From 1997 to 2005, 31 pregnancies were reviewed in 25 women. Nadroparin (7,500 U, twice daily) was used in 23 pregnancies between 6 and 12 weeks of gestation and close-to-term only, and coumarin derivatives were used with aspirin at other times. Eight pregnant women treated with coumarin derivatives throughout pregnancy were compared to evaluate the safety and efficacy of nadroparin. No maternal death or bleeding complication occurred in either of the two groups, and frequencies of maternal thromboembolism including valve thrombosis (8.7% vs. 12.5%, p>0.05) were similar. However, the frequencies of live born (91.3% vs. 50%, p=0.01) and healthy babies (90.4% vs. 25%, p<0.01) were significantly higher, and the fetal loss rate was significantly lower (8.7% vs. 50%, p=0.01) in the nadroparin-treated group. Regarding the efficacy and safety of antithrombotic treatment in pregnant women with prosthetic heart valves, nadroparin treatment during the first trimester is an acceptable regimen and produces better results than coumarin derivatives.

Effectiveness and safety of nadroparin in acute coronary syndrome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the effectiveness and safety of subcutaneous low molecular weight heparin (LMWH) used in acute management of patients with non-ST segment elevation acute coronary syndrome (ACS).</p><p><b>METHODS</b>A total of 102 patients with non-ST segment elevation ACS were treated for at least 48 hours ( > or =5 times) with subcutaneous nadroparin (1 mg/kg each 12 hours). All 102 patients underwent coronary angiographies (CAG) within 8 hours after LMWH injection, followed by immediate percutaneous coronary intervention (PCI).</p><p><b>RESULTS</b>Anti-Xa activity at the time of catheterization was (0.62 +/- 0.18) IU/ml, and 90% of the patients had anti-Xa activity > 0.5 IU/ml. No death, myocardial infarction relapse or emergent revascularization occurred after PCI. Thrombosis and/or embolism occurred in 2 patients (3.5%) during PCI. Mild hemorrhage was observed in 4 patients (3.9%) of PCI group and in 2 patients (4.4%) in CAG group. No major hemorrhage occurred.</p><p><b>CONCLUSION</b>PCI within 8-12 hours of the last dose after > or =48 hours nadroparin subcutaneous injection seems to be effective and safe.</p>

Nadroparina cálcica vs. heparina sódica en el síndrome coronario agudo. Unidad de Cuidados Coronarios del hospital Luis Vernaza / Nadroparine calcium vs. sodic heparine in the acute coronary syndrome. Coronary Unit Care of Luis Vernaza hospital

Tipo de estudio: ensayo clínico, unicéntrico, prospectivo, doble longitudinal, descriptivo, analítico, realizado en la Unidad de Cuidados Coronarios del hospital “Luis Vernaza” de Guayaquil, en pacientes con síndrome coronario agudo. Objetivo: determinar cual de las dos heparinas es superior, tanto en mejoría clínica como en costos y efectos secundarios. Resultados: se estudió un total de 34 pacientes; 14 con heparina sódica (grupo A) y 14 con nadroparina cálcica (grupo B), aparte de la aspirina y demás medicación antianginosa a criterio médico. La edad de presentación más frecuente en varones fue entre los 50 y 59 años, y en mujeres entre los 70 y 79 años; el grupo A tuvo una estancia hospitalaria de 29,35 días (ET 4,39) y en el grupo B de 21,24 días (ET 3,53) p= 0,160; los gastos en el grupo B fueron el doble que en el grupo A; el grupo A tuvo sangrados leves en un 2,9%, anginas recurrentes 11,76%, infarto recurrente 2,9%, trombocitopenia 2,9%. El grupo B tuvo sangrados leves en el 8,8%, infarto recurrente en el 2,9% y angina recurrente en el 14,7%. Conclusiones: absoluta paridad entre las dos estrategias terapéuticas; la única diferencia radica en los costos.

Type of study: clinic test, unicentric, prospective, double longitudinal, analytic and descriptive, performed in the Coronary Unit Care of Luis Vernaza Hospital of Guayaquil, with patient with acute coronary syndrome. Objective: To establish which of two heparin is superior, as much in clinic provement as in fees and secondary effects. Results: In the study was with 34 patients; 14 with sodic heparine (group A) and 14 with nadroparine calcium (group B), besides aspirin and any antiangina drugs of medical criteria. The age more frequently in men was between 50 to 59 years, and women between 70 to 79 years; Group A had a hospital stay of 29,35 days (ET 4,39) and group B de 21,24 days (ET 3,53) p= 0,160; the expenses in the group B was double than group A; Group A had mild bleeding in 2,9 %, recurrent angina 11,76%, recurrent heart attack 2,9 %, thrombocytopenia 2,9%. Group B had mild bleeding in 8,8%, recurrent heart attack in 2,9% and recurrent angina in 14,7%. Conclusion: Absolute similarity between two therapeutic strategies; the only difference is in fees.

Comparison of the antithrombotlic effect and safety between intravenous nadroparin and unfractionated heparin in patients undergoing percutaneous coronary intervention / 中华心血管病杂志

<p><b>OBJECTIVE</b>The study was designed to compare the antithrombotic property and safety between nadroparin and unfractionated heparin during percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>A prospective, single blind, randomized study was performed. A total of 98 patients (aged 65.1 +/- 8.6 years, female, 28.6%, diabetes, 7.1%) undergoing selective PCI were randomized to be administered intravenously either nadroparin (0.075 ml/10 kg) or unfractionated heparin (100U/kg) for procedural anticoagulation, in whom stable angina was 42.9%, unstable angina, 27.6%, myocardial infarction, 29.6%, two or three-vessel disease, 23.5%, stent, 100%. Blood samples for anti-Xa level were assayed in the first 22 patients of the nadroparin group before and after administration at the following intervals: 8 min, 1 h, 2 h and 4 h. Bleeding complications were classified according to Thrombolysis In Myocardial Infarction (TIMI) criteria. The bleeding index (change in hemoglobin) was calculated. All patients were monitored for adverse clinical events (i.e. death, myocardial infarction, need for revascularization) during the period of 30 days after PCI.</p><p><b>RESULTS</b>(1) There were no significant differences in baseline characteristics between the two randomized groups. (2) Plasma anti-Xa activities were 0.10 +/- 0.00 IU/ml at the time just before the administration of nadroparin, 1.89 +/- 0.24 IU/ml, 0.96 +/- 0.24 IU/ml, 0.47 +/- 0.13 IU/ml, and 0.30 +/- 0.12 IU/ml at the time of 8 min, 1 h, 2 h and 4 h after the use of nadroparin (and the rate of > 0.5 IU/ml were 100%, 100%, 45% and 9% patients), respectively. (3) There were no significant differences in the mean bleeding index, post-PCI hemoglobin and hematocrit between nadroparin and unfractionated heparin group [(1.16 +/- 5.80) g/L vs (0.90 +/- 6.50) g/L, P = 0.858; (129.5 +/- 13.6) g/L vs (125.5 +/- 14.9) g/L, P = 0.175; (39.0 +/- 3.9)% vs (37.9 +/- 4.6)%, P = 0.205]. (4) None of the patients in two randomized groups were observed hemorrhagic events, which including TIMI major or minor bleeding complications, gross or microscopic hematuria, melena, positive stool occult blood. There were no blood transfusions and no hematoma at the vascular access site in either of the group. (5) No death, no recurrent angina pectoris, and no urgent revascularization occurred within 30 days in both groups. One patient in nadroparin group was observed "no reflow" phenomenon that was accompanied with an elevated ST segment and a risen serum level of cTnI. This patient was diagnosed as non-Q-wave myocardial infarction. Though no myocardial infarction was found in unfractionated heparin group, there was no significant difference in the rate of myocardial infarction between the two groups of the study (P = 0.970).</p><p><b>CONCLUSIONS</b>The administration of nadroparin before PCI seems effective and safe. Compared with unfractionated heparin, nadroparin was associated with neither an excess of bleeding nor an increase of clinical complications in this study.</p>

Nadroparin plus aspirin versus aspirin alone in the treatment of acute ischemic stroke.

Low-molecular-weight-heparin (LMWH) has been widely used in the treatment of acute ischemic stroke but controlled trials are few. In this study, 40 patients with acute ischemic stroke of less than 24 hours duration were randomized to receive either aspirin (325 mg/day) alone or aspirin (325 mg/day) plus subcutaneous nadroparin 4100 units/day. At the end of 4 weeks, the morbidity and mortality were significantly less in the nadroparin group as compared to the aspirin group. There was no increased risk of clinically significant intracranial hemorrhage in either group. The combination of aspirin and LMWH deserves to be tested in larger studies.

Seguridad de una heparina de bajo peso molecular en tromboprofiláxis de cirugía de cadera / Security of to heparin of under molecular weight in tromboprofilaxis of hip surgery

Objetivo: Determinar la seguridad de una Heparina de Bajo Peso Molecular (HBPM) Nadroparina Cálcica en Cirugía Ortopédica Mayhor, mediante un estudio clínico experimental con 70 pacientes hosp;italizados para cirugía de cadera en el Servicio de Ortopedia y Traumatología del Hospital Nacional Guillermo Almenara Irigoyen -IPSS, entre mayo y setiembre de 1996. Pacientes: Se asignaron al azar en el grupo/profilaxis 35 pacientes que recibieron Nadroparina Cálcica 03 ml desde 2 horas antes de la operación y 35 pacientes en el grupo-control que siguieron el esquema convencional sin usar anticoagulantes. Resultados: El volumen de sangrado intra y post-operatorio, sangrado mayhor operatorio no mostraron diferencias estadísticamente significativas entre los 2 grupos, tampoco se presentó sangrado extra-operatorio, ni reacciones adversar al fármaco. El porcentaje de fallecimiento en el grupo control fue de 8.6 por ciento y cero en el grupo p;rofilaxis. Conclusión: La profilaxis del Tromboedmbolismo Venoso en Cirugía Cadera con Nadroparina Cálcica, mostró seguridad, tolerancia y facilidad de manejo sin necesidad de monitoreo laboratorial

Prophylaxis of Postoperative Deep Vein Thrombosis and Thromboembolism with Low Molecular Weight Heparin ( Nadroparin Calcium ) after Hip Arthroplasty: Comparison with Warfarin and Low Molecular Weight Dextran / 대한정형외과학회잡지

PURPOSE: To evaluate the preventive effect of deep vein thrombosis (DVT) by low molecular weight heparin (LMWH) after hip arthroplasty. MATERIALS AND METHODS: We analyzed 98 consecutive patients (107 cases) who were older than forty years of age and were scheduled to have elective primary or revision hip arthroplasty from August 1996 to March 1998. All of them received prophylactic LMWH, Nadroparin calcium (Fraxi-parine, Sanofi France). The effectiveness and safety of LMWH were evaluated in a prospective randomized trial. LMWH was injected subcutaneously once daily, from twelve hours before the operation to the tenth postoperative day with fixed dosage according to patient s body weight. For the detection of DVT after hip arthroplasty, patients were evaluated with color doppler image (CDI) preoperatively, postoperatively 7-10 days and six weeks consecutively. RESULTS: DVT was detected in six patients (5.61%) and no symptomatic pulmonary embolism occurred. Asymptomatic isolated calf vein thrombosis was identified in four patients, they had no therapeutic treatment for the thrombosis but the thrombi were resolved spontaneously without any proximal propagation. Proximal vein DVT was identified in two patients and the thrombi were resolved within 6 weeks with additional treatment using Nadroparin calciurn administration. In three cases, late developing thrombi was detected at follow-up CDI carried out at the sixth postoperative week. There were three cases of bleeding complications. CONCLUSIONS: Compared to our previous report of the incidence of DVT using low molecular weight dextran (12.2%) and warfarin (16.6%) with the incidence of DVT using low molecular weight heparin (5.61%), we considered that prophylaxis with LMWH is more effective in preventing DVT after hip arthroplasty. We also found that asymptomatic isolated calf vein thrombosis is resolved spontaneously. For the detection of late developing thrombosis, we recommend consecutive follow-up CDI.

Clinical and Angiographic Outcomes: Subcutaneous Nadroparin versus Ticlopidine after Coronary Stenting

BACKGROUNG AND OBJECTIVES: It was reported that low molecular weight heparin (LMWH) was more effective than unfractionated heparin in patients with acute coronary syndrome. Recent studies have shown that the pathophysiology of restenosis in stented lesions was different from those of nonstented lesions. Treatment strategies designed to limit cellular proliferation that were ineffective in nonstented lesions may be efficacious in reducing in-stent restenosis. This study was aimed to compare the clinical and angiographic results of LMWH (nadroparin) after coronary stenting with those of conventional ticlopidine regimen. MATERIALS AND METHODS: Patients were eligible for inclusion if they had angina and/or objective evidence of myocardial ischemia, and a significant (>50%) stenosis that was documented on a recent coronary angiogram. After stenting, prospective randomized comparison study was performed. Patients were randomly assigned to either nadroparin (200 IU/kg, sc, bid) or ticlopidine (250 mg bid) plus aspirin (200 mg qd) treatment groups. Repeat coronary angiography (KERN=*)was performed at 236+/-90days after stenting, and quantitative coronary angiographic analysis (QCA) was done. RESULTS: Intracoronary stent implantation was performed in eighty five lesions in eighty one patients (ticlopidine:40, nadroparin:41). There was no significant difference in any baseline clinical/angiographic variables between the two treatment groups. There were no subacute stent thrombosis, infarction and death in both groups. Six-month event-free survival was 36 (90%) in the ticlopidine group and 35 (85.4%) in the nadroparin group. Follow-up quantitative angiographic data such as late loss (1.35+/-0.70 vs 1.32+/-0.69), loss index (0.53+/-0.70 vs 0.56+/-0.23) and restenosis rate (36% vs 25.8%) were not different between ticlopidine and nadroparin groups. CONCLUSION: Effects of nadroparin were not different from those with ticlopidine therapy in the prevention of restenosis and subacute stent thorombosis after coronary stenting. Clinical outcomes between two strategies were similar. Low molecular weight heparin may be an alternative to ticlopidine in patients that ticlopidine cannot be administered because of severe adverse effects.

Thrombolysis for Prosthetic Mitral Valve Thrombosis: 3 cases report / 대한흉부외과학회지

Thrombosis in valve or left atrium after mechanical mitral valve replacement causes prosthetic valve dysfunction or thromboembolism. Early and adequate therapy is very important but clinically not easy. Thrombolysis can avoid reoperation-related risks and act as an optimal therapy for prosthetic valve thrombosis. This report describes three patients who were treated by using low molecular weight heparin (LMWH) and wafarin. Two patients, including one pregnant woman, had prosthetic valve thrombosis and immobility of valve leaflets, and one patient with recent cerebral infarction due to thromboembolism had thrombus in left atrium. Fraxiparine 0.3 cc (7,500 ICU AXa) was administrated subcutaneously twice or triple daily. At discharge, thrombosis in valve and left atrium were completely or near totally lysed and valve leaflets were normally mobile. During the period of thrombolysis and follow up, there were no complications in all patients.

Tromboprofilaxis en cirugía de cadera con nadroparina cálcica / Thromboprophylaxis vith calcium nadroparine in hip surgery

Objetivo.- Determinar la seguridad de una heparina de bajo peso molecular (HBPM) nadroparina cálcica en Cirugía Ortopédica Mayor, mediante un estudio clínico experimental aleotorizado con 70 paciedntes hospitalizados para cirugía de cadera en el Servicio de Ortopedia y Traumatología del Hospital Nacional Guillermo Almenara Irigoyen, IPSS, entred diciembdrfe 1996 y marzo de 1997. Pacientes.- Se asignaron en el grupo-p;rofilaxis 35 pacientes que recivbierffon 0.3 ml de nadroparina cálcica desde 12 horas antes de la operación y 35 pacientes en el grupo control que siguieron el esquema convencional sin usar anticoagulantes. Resultados.- El volumen de sangrado intra y p;ost operatorio, así como el sangrado mayor operatorio no mostgraron diferencias estadísticamente significativas entre los dos grupos, tampoco se presentó sangrado extra operatorio, ni reacciones adversas al fármaco. El porcentaje de fallecidos en el grupo control fue de 8.6 por ciento y cero en el grupo profilaxis. Conclusión.- La profilaxis de tromboembolismo venoso (TEV) en Cirugía de Cadera con nadroparina cálcica, mostró seguridad, tolerancia y facilidad de manejo sin necesidad de monitoreo laboratorial

Embolectomy of Arteries of Extremities: Clinical analysis of 26 cases / 대한흉부외과학회지

We present a retrospective analysis of arterial embolectomies performed at the Inje University Seoul Paik Hospital. During the period of March 1987 - Feburary 1996 twenty-six patients underwent embolectomies, eighteen patients were male and eight patients were female, mean age of patients was 56.8 years. Rest pain was the chief complaint in 24 patients, the remaining two patients complained of long term history of claudication after recovery of acute symtoms. But only 10 patients had sensory/motor symtoms. Heart was the most common source of embolization and frequent predisposing factor of embolism was ischemic heart disease in 8 cases and valvular heart disease in 11 cases. The sites of embolization were upper extremities artery in 6 cases, saddle embolism in 2 cases, lower extremities artery in 18 cases and the most common site of embolism was femoral artery in 11 cases. Preoperative angiography was taken in the diagnosis and planning of the embolectomy in 13 patients while in the other patient preoperative angiography was not taken. Only two cases were operated within the golden period of 6 hours and other cases were operated in more than 6 hours after embolization. In all patients, the Fogarty embolectomy catheter was used without bypass surgery via bachial ateriotomy in the embolism of upper extremities artery, bilateral groin approaches in the saddle embolism and transfemoral approach in the embolism of lower extremities artery. However 3 patients were re-operated via transpopliteal approach in the distal poplitiotibial embolism. Eighteen patients received perioperative anticoagulation therapy by heparin or fraxiparine and wafarin was used in 17 patients at the time of discharge and the indication of anticogulation was patients of valvular heat disease and/or atrial fibrillation, peripheral artery atherosclerosis and recurrent embolism. Postoperative results of the embolectomy were as follows: fouteen pateints had excellent results, five cases had symtom improvement after re-operation, B.K. amputation in 1 case who had sever atherosclerosis of lower extremities, recurrent embolism in 1 case and death in 2 cases the cause of death were acute renal failure and cerebral artery embolism, respectively. The complications of the embolectomy were reperfusion syndrome, pseudoaneurysm and intimal dissection in one case each. Conclusively the problems of embolism is delayed diagnosis and increasing number of old aged patient who had suffered ischemic heart diease. Preoperative angiography was not always needed for embolectomy. Selective anticoagulation therapy can decrease incidence of re-embolism. In the distal poplitiotibial embolism, seletive embolectomy of tibial artery was difficult.

Embolectomy of Arteries of Extremities: Clinical analysis of 26 cases / 대한흉부외과학회지

We present a retrospective analysis of arterial embolectomies performed at the Inje University Seoul Paik Hospital. During the period of March 1987 - Feburary 1996 twenty-six patients underwent embolectomies, eighteen patients were male and eight patients were female, mean age of patients was 56.8 years. Rest pain was the chief complaint in 24 patients, the remaining two patients complained of long term history of claudication after recovery of acute symtoms. But only 10 patients had sensory/motor symtoms. Heart was the most common source of embolization and frequent predisposing factor of embolism was ischemic heart disease in 8 cases and valvular heart disease in 11 cases. The sites of embolization were upper extremities artery in 6 cases, saddle embolism in 2 cases, lower extremities artery in 18 cases and the most common site of embolism was femoral artery in 11 cases. Preoperative angiography was taken in the diagnosis and planning of the embolectomy in 13 patients while in the other patient preoperative angiography was not taken. Only two cases were operated within the golden period of 6 hours and other cases were operated in more than 6 hours after embolization. In all patients, the Fogarty embolectomy catheter was used without bypass surgery via bachial ateriotomy in the embolism of upper extremities artery, bilateral groin approaches in the saddle embolism and transfemoral approach in the embolism of lower extremities artery. However 3 patients were re-operated via transpopliteal approach in the distal poplitiotibial embolism. Eighteen patients received perioperative anticoagulation therapy by heparin or fraxiparine and wafarin was used in 17 patients at the time of discharge and the indication of anticogulation was patients of valvular heat disease and/or atrial fibrillation, peripheral artery atherosclerosis and recurrent embolism. Postoperative results of the embolectomy were as follows: fouteen pateints had excellent results, five cases had symtom improvement after re-operation, B.K. amputation in 1 case who had sever atherosclerosis of lower extremities, recurrent embolism in 1 case and death in 2 cases the cause of death were acute renal failure and cerebral artery embolism, respectively. The complications of the embolectomy were reperfusion syndrome, pseudoaneurysm and intimal dissection in one case each. Conclusively the problems of embolism is delayed diagnosis and increasing number of old aged patient who had suffered ischemic heart diease. Preoperative angiography was not always needed for embolectomy. Selective anticoagulation therapy can decrease incidence of re-embolism. In the distal poplitiotibial embolism, seletive embolectomy of tibial artery was difficult.