Coagulopatía, tratamiento anticoagulante en COVID-19 y trombosis posvacunación / Coagulopathy, anticoagulant treatment in COVID-19 and thrombosis postvaccine

Resumen La coagulopatía y la trombosis son situaciones graves que afectan a los pacientes con enfermedad por coronavirus 2019 (COVID-19) que requieren hospitalización. En estos pacientes se alteran mecanismos procoagulantes y fibrinolíticos que condicionan un estado procoagulante progresivo y grave. La anticoagulación oportuna en estos pacientes es importante, pero han surgido preguntas sobre el tipo, la dosis y el momento adecuado de la anticoagulación. Las directrices y documentos de consenso existentes ofrecen sugerencias generales sobre la dosis de heparinas de bajo peso molecular en función de la gravedad de la enfermedad y el riesgo de trombosis, pero todavía falta una relación entre los marcadores de coagulación y el régimen de anticoagulación. Se están llevando a cabo muchos ensayos clínicos que abordan estas cuestiones; se alienta la participación en estos ensayos para determinar las mejores estrategias de tratamiento para los pacientes de COVID-19. Es necesario aumentar los conocimientos con un rápido intercambio para atender adecuadamente a los pacientes en esta pandemia.

Abstract Coagulopathy and thrombosis are serious situations that COVID-19 patients require hospitalization. In these patients, procoagulant and fibrinolytic mechanisms are altered that condition a progressive and severe procoagulant state. Timely anticoagulation in these patients is important, but questions have been raised about the type, dose, and timing of anticoagulation. The guidelines and consensus documents offer general suggestions on the dose of LMWH based on the severity of the disease and the risk of thrombosis, but a relationship between coagulation markers and anticoagulation regimen is still lacking. Many clinical trials are underway that address these issues; Participation in these trials to determine the best treatment strategies for COVID-19 patients is encouraged. Increasing knowledge with rapid exchange is necessary to adequately care for patients in this pandemic.

Progress of recurrence of venous thromboembolism in cancer patients / 肿瘤研究与临床

Cancer patients complicated with venous thromboembolism (VTE) face treatment problems, very high recurrence rate and bleeding rate. Cancer itself and the antitumor treatment plan are the important factors causing the recurrence. After the relapse, the prognosis of the patients is extremely bad, and more than 50% of the patients died within 1 year. Until now, there is no unified effective treatment plan for the relapse. This paper reviews the recurrence of VTE and the related research progress.

Rationality Analysis of the Utilization of Anticoagulant Drugs in the Inpatients of Our Hospital during 2013-2015 / 中国药房

OBJECTIVE:To provide reference for rational use of anticoagulant drugs in the clinic. METHODS:Medical or-ders of anticoagulant drugs were collected from hospital information system of our hospital during 2013-2015. Those medical orders were analyzed in respects of consumption sum,DDDs,DDC and drug utilization. RESULTS:During 2013-2015,the sum tatio of Low-molecular-weight heparins calcium injection(6000 AXaIU),Enoxaparin sodium injection(6000 AXaIU),Dalteparin sodium injection(5000 IU) and Rivaroxaban tablets(10 mg)were on the rise,while those of Nadroparin calcium infection(6150,4100 AXaIU)and Fondaparinux sodium injection(2.5 mg)were in the decline. DDDs of Nadroparin calcium injection(4100 AXaIU), Dalteparin sodium injection(5000 IU)and Enoxaparin sodium injection(6000 AXaIU)took up the first 3 places. DDC of Rivar-oxaban tablets was the highest,being 167.60-180.25 yuan. The utilization of Nadroparin calcium injection(6150,4100 AXaIU), Low-molecular-weight heparins calcium injection (6000 AXaIU),Fondaparinux sodium injection(2.5 mg) and Warfarin sodium tablets(3 mg)showed good synchronization within 3 years,and the values of B/A ranged 0.50-1.50. Both consumption sum and utili-zation rate of rivaroxaban took up the first place in vascular surgery department. CONCLUSIONS:Based on the spectrum of diseases, the features of drugs and ADR,the utilization of anticoagulant drugs in our hospital is rational during recent 3 years. However,the uti-lization of anticoagulant drugs should be still used as routine pharmaceutical monitoring content.

Technical analysis of low molecule weight heparins patents and R&D suggestions / 中国药科大学学报

@#An analysis of low molecule weight heparins(LMWH)patents throughout China and aroud the world is made. The suggestion, in terms of patent technical solution, is given to the R&D of LMWH, especially the enoxaparin, dalteprin and nadroparin.

Clinical efficacy analysis on treatment of unstable angina pectoris with low-molecular-weight heparins calcium / 重庆医学

Objective To investigate the clinical efficacy and safety on treatment of unstable angina pectoris (UAP) with low-molecular-weight heparins calcium .Methods 64 cases in our hospital from February 2012 to January 2013 with UAP were random-ly divided into treatment group and control group ,and 32 cases in each group .The control group was treated with routine drugs such as aspirin ,and the treatment group was treated with low-molecular-weight heparins calcium on the basis of routine therapy . The clinical efficacy and safety were evaluated by the frequency and duration of angina attacks ,the improvement of electrocardio-gram(ECG) and adverse reactions .Results The frequency and duration of angina attacks of the two groups were significantly re-duced and the performances of ECG were improved .The clinical improvement and performance of ECG were better in treatment group than those in the control group(P<0 .05) .And the total efficiency of the treatment group and control group were 93 .8%(30/32) and 84 .4% (27/32) ,respectively ,the difference had statistically significant (P<0 .05) .There was no serious adverse reac-tion in the two groups .Conclusion Low-molecular-weight heparins calcium can effectively control the frequency and duration of UAP and has less adverse reaction in treatment of UAP .It is worthy to be recommended in clinical .

Tromboprofilaxis en pacientes no quirúrgicos internados en un hospital general / Venous thromboembolism prevention in non-surgical adult patients admitted in a general hospital

Los pacientes adultos internados por una enfermedad no quirúrgica tienen un riesgo alto de padecer una tromboembolia venosa y pueden desarrollar alguna forma de esta enfermedad cuando no reciben un tratamiento preventivo adecuado. Los objetivos de este estudio prospectivo, analítico, observacional y transversal, fueron: 1) determinar cuál es el porcentaje de pacientes adultos internados por una enfermedad aguda no quirúrgica en el Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, que tienen indicación de tromboprofilaxis, 2) establecer cuántos de ellos reciben un tratamiento preventivo para la tromboembolia venosa, y 3) comprobar cuántos estaban medicados con alguna forma de tromboprofilaxis sin tener causas que justificaran este tratamiento. Se estudiaron 93 pacientes durante un lapso de 72 horas consecutivas. Se encontró que el 90.3% de ellos necesitaba un tratamiento preventivo para la tromboembolia venosa y el 76.2% de estos enfermos recibían tromboprofilaxis farmacológica. Un 33.3% de los pacientes internados tenía indicado un tratamiento farmacológico preventivo sin tener una causa que justificara esta prescripción. El porcentaje encontrado de pacientes tratados con tromboprofilaxis es más alto que el comunicado en otros estudios observacionales.

Adult patients hospitalized for a non-surgical condition, usually have a high risk of venous thromboembolism and may develop some form of this disease when they do not receive appropriate preventive treatment. The objectives of this prospective, analytical, observational and cross-sectional study were: 1) to determine what percentage of adult patients hospitalized for a non-surgical acute condition at the Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, had indication for preventive thromboprophylaxis, 2) to establish how many of them had been prescribed a preventive treatment of venous thromboembolism, 3) to establish how many of them had been prescribed a preventive treatment of venous thromboembolism without having reasons to justify the treatment. The study was performed on 93 patients for 72 consecutive hours. It resulted in 90.3% in need of preventive treatment for venous thromboembolism and 76.2% of these patients had received pharmacological thromboprophylaxis. A 33.3% of the studied patients had received preventive pharmacological treatment without having a proper indication. In this study, the percentage of patients treated is higher than in those reported in other published observational studies.

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 Danhong injection combined with low-tnoiecular-weight heparins in treatment of unstable angina pectoris / 中国综合临床

Objective To observe the efficacy of Danhong injection combined with low-molecularweight heparins in treating unstable angina pectoris.Methods One hundred and three cases of unstable ansina pectoris were enrolled and divided into group A and B,Group A were given Danhong injection and lowmolecular-weight hepafins,Group B were given routine treatment.Results The overall response rate of group A was 90.7％ and it was 74.0％ for group B.The difference was significant (x2 =4.90,P＜0.05).Conclusion Treatment with Danhong combined with low-molecular-weight heparins produced a good outcome in the patients with unstable angina pectoris.

Application of low molecular weight heparins in myeloproliferative neoplasms / 白血病·淋巴瘤

Myeloproliferative neoplasms (MPN) are a group of diseases with malignant cloning in hematopoietic stem / progenitor cells. The main clinical feature is excessive proliferation of one or more lineage of myeloid cells, which cause increasing count of erythrocytes, granulocytes and platelets in peripheral blood.Arterio-venous thrombosis and complications are responsible for the mortality of MPN. Low molecular weight heparin (LMWH) is a kind of anticoagulant that commonly used for its safety and validity. It can improve the hyperviscosity of blood , affect platelets, and interact with leukocytes and endothelial cells, by which can reduce cells aggregation. LMWH can effectively play an active role of anticoagulant in high-platelet plasma. All of these provides a theoretical basis to its availability in MPN.

Influence of different anticoagulants on coagulation state in hemodialysis / 中华肾脏病杂志

Objective To investigate the characteristics and proper use of anticoagulants in hemodialysis (HD). Methods Thirty-one HD patients were enrolled in the study. Unfractionated heparins (UFH), dalteparin sodium or argatroban were used for HD anticoagulation respectively. Blood specimens were taken from the arterial line at the beginning (0 h) and at the end of HD (4 h), and from the arterial (2a) and the venous (2v) line respectively at 2 h of the HD session. Glass bead activated clotting time (gbACT), clot rate (CR) and platelet function (PF) were examined by Sonoclot analyzer. Prothrombin fragment 1+2 (PF1+2) and granule membrane protein-140 (GMP-140) were assayed by ELISA. Meanwhile, blood was taken from 8 healthy volunteers to examine the above parameters as control. Results (1) Compared with the control group, CR, PF1+2, PF, GMP-140 were increased significantly in all the patients (P<0.05). (2) UFH group:Compared with the 0 h point, gbACT of other time points increased significantly (P<0.05), CR, PF, and PF1+2 decreased significantly (P<0.05). Compared with the control group, gbACT increased (P<0.05) and CR decreased (P<0.05) significantly at the end of the sessions. (3) Daheparin sodium group: Compared with the 0 h point, gbACT of 2a point increased significantly (P<0.05), CR and PF1+2 of 2a, 2v and 4 h points decreased significantly (P<0.05), meanwhile, the extents of increased gbACT and decreased CR from the arterial line were greater than those from the venous line. Compared with the control group, gbACT increased significantly at the end of HD session (P<0.05), but CR was not significantly different. (4) Argatroban group: There were no significant differences of gbACT between 0 h and other time points. CR of 2a, 2v points decreased obviously than that of 0 h point, and CR of 2v decreased more significantly. CR of 2a point was not different from the control group, while CR of 4 h point was greater as compared to control group. During the monitoring, PF1 +2 tended to increase. Conclusions With intensive anticoagulant effect, UFH may induce the risk of hemorrhage not only during but also after the dialysis sessions. Dalteparin sodium, a good anticoagulant, is stir related with the risk of hemorrhage during HD. Argatroban is an ideal anticoagulant for patients with the risk of hemorrhage.

Biological potency evaluation and physicochemical characterization of unfractionated heparins

Unfractionated heparins are used clinically as anticoagulants. The biological potency of thirteen samples of raw material and pharmaceutical formulations were assessed utilizing the 5th International Standard of heparin using the sheep plasma coagulation inhibition assay, activated partial thromboplastin time, anti-factor Xa assay, and anti-factor IIa assay, resulting in mean potencies of 101.15 percent, 96.15 percent, 98.15 percent and 99.37 percent, respectively. The samples were also evaluated by the protamine neutralization test giving results within the range of 92 - 138 IU/mg. The anti-factor IIa assay was performed showing reproducibility and significant correlation with the pharmacopoeial assays, thus demonstrating it to be a feasible alternative to the sheep plasma coagulation inhibition assay. Moreover, an analysis by nuclear magnetic resonance and capillary electrophoresis showed some peaks attributable to oversulfated chondroitin sulfate. The results show that batch-to-batch variations and the quality of samples contributed to improvements in the quality control of pharmaceutical products and to assure the safe use and clinical efficacy of this biological medicine.

As heparinas não fracionadas são utilizadas clinicamente como anticoagulantes. A potência biológica de 13 amostras de matérias-primas e produtos farmacêuticos foram avaliadas em relação ao 5ª Padrão Internacional de heparina pelos ensaios da inibição da coagulação do plasma ovino, tempo de tromboplastina parcial ativada, anti-fator Xa e anti-fator IIa, que forneceram potências médias de 101,15 por cento, 96,15 por cento, 98,15 por cento e 99,37 por cento, respectivamente. As amostras foram também submetidas ao teste de neutralização pela protamina que apresentou resultados entre 92-138 UI/mg. Demonstrou-se reprodutibilidade e correlação significativa do ensaio do anti-fator IIa com os farmacopeicos, constituindo-se em alternativa ao ensaio da inibição da coagulação do plasma ovino. Além disso, as análises realizadas por ressonância magnética nuclear e eletroforese capilar mostraram picos correspondentesà condroitina supersulfatada. Os resultados mostraram variações lote-a-lote e a qualidade das amostras contribuindo para aprimorar o controle de qualidade dos produtos farmacêuticos e garantir a segurança e eficácia terapêutica desses produtos biológicos.

Inhibition of low molecular weight heparin on the growth and metastasis of human hepatocarcinoma implanted in nude mice / 中国普通外科杂志

Objective To study the effect of low molecular weight heparin on the growth and metastasis of hepatocarcinoma in vivo Methods Metastatic model simulating human hepatocarcinoma was established by orthotopic implantation of the tumor tissue into nude mice Animals were randomly divided and submitted to different treatment groups: control group treated with nornal saline, chemotherapy group with 5 FU and CDDP i p , Fragmin group (low molecular heparin), combination group After 5 weeks of treatment, tumor volume、 microvessel density (MVD)、 VEGF smoothmuscle actin (SMA) and metastasis in Fragmin group significantly decreased and tumor inhibitive rate increased ( P

Clinical study of low molecular weight heparins in treatment of chronic pulmonary heart diseases / 中国临床药理学与治疗学

AIM: To investigate the effects and safe of low molecular weight heparins (LMWH) in the treatment of patients with chronic pulmonary heart diseases (CPHD) at hypercoagulability state. METHODS: 65 patients were randomly assigned to treatment group (n=33) and control group (n=32). All patients were given routine treatments. The patients of treatment group were hypodermically injected with 4 100～6 150 U of LMWH per day for 7 days as a course. RESULTS: After 7 days of the treatments, the patients of treatment group showed better curative effect and significantly increase in PaO_2 and AT-III and decrease in PaCO_2 and FIB in comparison with the patients in control group (P