RESUMEN
Objectives: The objective is to evaluate whether danaparoid is effective in improving the live birth rate in patients with obstetric antiphospholipid syndrome (oAPS).Methods: This prospective study included 91 pregnancies of 60 patients with oAPS diagnosed according to criteria of the International Congress on APS. Live birth rates, adverse pregnancies and perinatal outcomes were compared among patients treated with danaparoid and low dose aspirin (danaparoid group, LDA), unfractionated heparin (UFH) and LDA (UFH group) and LDA and/or prednisolone (LDA group).Results: After excluding 11 miscarriages with abnormal embryonic chromosomes, one chemical pregnancy and one ectopic pregnancy, live birth rates were 87.5% (14/16) for the danaparoid group, 90.0% (36/40) for the UFH group and 63.6% (14/22) for the LDA group, respectively. The live birth rates of patients treated with danaparoid and UFH were similar and tended to be higher than that of patients treated with LDA, respectively (OR 4.0, 95% confidence interval 0.72-22.22 and 5.15, 1.33-20.00). No patient given danaparoid and one patient with UFH developed heparin-induced thrombocytopenia which resulted in a stillbirth. Another patient with UFH suffered a lumbar compression fracture.Conclusion: Danaparoid is effective for improving the live birth rate and is safe for patients with oAPS.
Asunto(s)
Síndrome Antifosfolípido/tratamiento farmacológico , Sulfatos de Condroitina/uso terapéutico , Dermatán Sulfato/uso terapéutico , Fibrinolíticos/uso terapéutico , Heparitina Sulfato/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológico , Adulto , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/administración & dosificación , Dermatán Sulfato/efectos adversos , Femenino , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Heparitina Sulfato/administración & dosificación , Heparitina Sulfato/efectos adversos , Humanos , Embarazo , Resultado del EmbarazoRESUMEN
BACKGROUND: Danaparoid sodium and synthetic protease inhibitors (SPIs) have been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan. OBJECTIVES: To compare the clinical results of the treatment of DIC with danaparoid or SPIs. METHODS: We retrospectively examined 188 patients with hematological malignancy-related DIC. RESULTS: DIC resolution rate in the danaparoid group was higher than that in the SPIs group (61.5 vs. 42.6%; p = 0.031) on day 7. Multivariate analysis identified the response to chemotherapy as independent predictive factor for DIC resolution on day 7 (odds ratio, OR, 2.28; 95% confidence interval, CI, 1.21-4.31; p = 0.011). While there was no significant difference in the DIC resolution rate on day 14 (75.0 vs. 62.4%; p = 0.117), in a subgroup analysis of patients who did not show an improvement in the underlying disease, the danaparoid group showed a significantly better DIC resolution rate (OR 3.89; 95% CI 1.15-13.2; p = 0.030). There was no difference in the rate of cumulative mortality from bleeding within 28 days between the 2 groups (6.6 vs. 3.3%; p = 0.278). CONCLUSIONS: Danaparoid may be associated with more frequent resolution of DIC in patients with refractory underlying disease.
Asunto(s)
Sulfatos de Condroitina/uso terapéutico , Dermatán Sulfato/uso terapéutico , Neoplasias Hematológicas/sangre , Heparitina Sulfato/uso terapéutico , Inhibidores de Proteasas/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Transfusión de Componentes Sanguíneos , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/efectos adversos , Coagulación Intravascular Diseminada/tratamiento farmacológico , Coagulación Intravascular Diseminada/terapia , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Neoplasias Hematológicas/tratamiento farmacológico , Hemorragia/etiología , Hemorragia/mortalidad , Heparitina Sulfato/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Plasma , Inhibidores de Proteasas/efectos adversos , Tiempo de Protrombina , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: In the context of inpatient and increasingly ambulatory thrombosis prophylaxis, heparins have been recognised as standard therapy for decades. In addition to the therapeutic benefit, therapy with heparins also entails the risk of undesirable side effects, such as bleeding and thrombocytopenia. Heparin-induced thrombocytopenia (HIT II) is deemed a serious side effect. AIM: In the following work, HIT II is subjected to a medico-economic consideration (treatment, pharmaceuticals, subsequent costs due to possible complications) and, with regard to a possible HIT II prophylaxis, aspects of increasingly respected patient safety are also considered. METHODS: In the context of a literature search the active ingredients argatroban and danaparoid, which are approved for HIT II treatment, were evaluated. RESULTS: HIT II - especially in combination with thromboembolic complications - represents a medical-economic burden for the hospital. Although this is only an orientation guide, it shows that HIT II syndrome is not adequately cost-covered by the GDRG system. An early thrombosis prophylaxis with argatroban/danaparoid for HIT II risk patients should therefore be taken into account for medical-related as well as patient safety-relevant aspects. According to experience, the pharmaceutical supply for these medically needed products (anticoagulants) should be ensured for reasons of patient safety. CONCLUSION: The risk of an immunological response to heparin therapy is known. Within the context of increased patient safety, thrombosis prophylaxis should be issued with a risk-adjusted prophylaxis.
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Heparina/efectos adversos , Heparina/economía , Hospitalización/economía , Trombocitopenia/inducido químicamente , Trombocitopenia/economía , Trombosis/economía , Trombosis/prevención & control , Arginina/análogos & derivados , Sulfatos de Condroitina/efectos adversos , Sulfatos de Condroitina/uso terapéutico , Costos y Análisis de Costo , Dermatán Sulfato/efectos adversos , Dermatán Sulfato/uso terapéutico , Alemania , Hemorragia/sangre , Hemorragia/inducido químicamente , Hemorragia/economía , Heparina/uso terapéutico , Heparitina Sulfato/efectos adversos , Heparitina Sulfato/uso terapéutico , Humanos , Ácidos Pipecólicos/efectos adversos , Ácidos Pipecólicos/uso terapéutico , Factores de Riesgo , Sulfonamidas , Trombocitopenia/tratamiento farmacológico , Trombosis/sangre , Resultado del TratamientoRESUMEN
In this issue of Blood, Brennan et al report that a noninfectious damage-associated molecular pattern (DAMP), heparan sulfate (HS),(1) aggravates graft-versus-host disease (GVHD) and that this enhanced severity can be dampened by administration of serine protease inhibitor α-1 antitrysin (AAT).(2)
Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/complicaciones , Heparitina Sulfato/efectos adversos , Trasplante de Células Madre/efectos adversos , Linfocitos T/efectos de los fármacos , Receptor Toll-Like 4/agonistas , Animales , Femenino , Humanos , MasculinoRESUMEN
Thromboembolism is an infrequent, yet serious cause of both maternal and fetal morbidity and death during pregnancy and the puerperium. Antithrombotic treatment and prophylaxis both before and during pregnancy are based on unfractionated heparin (UH), low-molecularweight heparin (LMWH), Warfarin and Aspirin. The prevalence and severity of thromboembolism during pregnancy and puerperium warrant special consideration of management and therapy. Such therapy includes the treatment of acute thrombotic events and prophylaxis for those at increased risk of thrombotic events. This paper assesses the safety and efficacy of antithrombotic therapy during pregnancy and the peripartum period. Its cardiovascular and obstetric indications, the evidence of association between thrombophilias and adverse pregnancy outcome, regimens and maternal and fetal side-effects are also discussed.
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Anticoagulantes/efectos adversos , Trombofilia/etiología , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Aspirina/efectos adversos , Aspirina/farmacología , Aspirina/uso terapéutico , Densidad Ósea/efectos de los fármacos , Lactancia Materna , Sulfatos de Condroitina/efectos adversos , Sulfatos de Condroitina/uso terapéutico , Dermatán Sulfato/efectos adversos , Dermatán Sulfato/uso terapéutico , Femenino , Fondaparinux , Heparina/efectos adversos , Heparina/farmacología , Heparina/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparitina Sulfato/efectos adversos , Heparitina Sulfato/uso terapéutico , Humanos , Recién Nacido , Polisacáridos/efectos adversos , Polisacáridos/uso terapéutico , Embarazo , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , Complicaciones Hematológicas del Embarazo/prevención & control , Tromboembolia/tratamiento farmacológico , Warfarina/efectos adversos , Warfarina/farmacología , Warfarina/uso terapéuticoRESUMEN
Graft-versus-host disease (GVHD) remains the most common cause of nonrelapse-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although T-cell depletion and intensive immunosuppression are effective in the control of GVHD, they are often associated with higher rates of infection and tumor recurrence. In this study, we showed that heparan sulfate (HS), an extracellular matrix component, can activate Toll-like receptor 4 on dendritic cells in vitro, leading to the enhancement of dendritic cell maturation and alloreactive T-cell responses. We further demonstrated in vivo that serum HS levels were acutely elevated at the onset of clinical GVHD in mice after allo-HSCT. Treatment with the serine protease inhibitor α1-antitrypsin decreased serum levels of HS, leading to a reduction in alloreactive T-cell responses and GVHD severity. Conversely, an HS mimetic that increased serum HS levels accelerated GVHD. In addition, in patients undergoing allo-HSCT for hematologic malignancies, serum HS levels were elevated and correlated with the severity of GVHD. These results identify a critical role for HS in promoting acute GVHD after allo-HSCT, and they suggest that modulation of HS release may have therapeutic potential for the control of clinical GVHD.
Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/complicaciones , Heparitina Sulfato/efectos adversos , Trasplante de Células Madre/efectos adversos , Linfocitos T/efectos de los fármacos , Receptor Toll-Like 4/agonistas , Animales , Proliferación Celular , Células Dendríticas , Femenino , Citometría de Flujo , Enfermedad Injerto contra Huésped/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Luciferasas/metabolismo , Depleción Linfocítica , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Persona de Mediana Edad , Tasa de Supervivencia , Linfocitos T/inmunología , Trasplante HomólogoRESUMEN
This article describes the pharmacology of approved parenteral anticoagulants. These include the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid, as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin, factor Xa, and other clotting enzymes. Heparin also binds to cells and plasma proteins other than antithrombin causing unpredictable pharmacokinetic and pharmacodynamic properties and triggering nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and plasma proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and are associated with a lower risk of nonhemorrhagic side effects. LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin. Therefore, fondaparinux-associated HIT or osteoporosis is unlikely to occur. Fondaparinux exhibits complete bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without coagulation monitoring. Three additional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in patients with HIT.
Asunto(s)
Medicina Basada en la Evidencia , Fibrinolíticos/administración & dosificación , Guías de Práctica Clínica como Asunto , Sociedades Médicas , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , Antitrombinas/agonistas , Arginina/análogos & derivados , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/administración & dosificación , Dermatán Sulfato/efectos adversos , Relación Dosis-Respuesta a Droga , Fondaparinux , Heparina/administración & dosificación , Heparina/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparitina Sulfato/administración & dosificación , Heparitina Sulfato/efectos adversos , Hirudinas/administración & dosificación , Hirudinas/efectos adversos , Humanos , Infusiones Intravenosas , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/efectos adversos , Ácidos Pipecólicos/administración & dosificación , Ácidos Pipecólicos/efectos adversos , Polisacáridos/administración & dosificación , Polisacáridos/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Sulfonamidas , Trombina/antagonistas & inhibidores , Trombosis/sangre , Estados UnidosRESUMEN
UNLABELLED: Danaparoid case reports of 91 pregnancies in 83 patients with a history of thrombophilia and/or intra-uterine growth retardation have been analysed. All had intolerance to the heparins including HIT and acute or past thromboses or a history of repeated pregnancy loss (RPL). Danaparoid was started in the first, second and third trimesters in 60.2%, 19.3% and 20.5% pregnancies respectively at a dosing intensity of 1000 to 7500 U/day. Subcutaneous and/or intravenous administration was continued for a median 105 days (range 1-252) during pregnancy and 7 days (range 2 to 56) post-partum. The live birth rate was 90.4% (75/81) and danaparoid was restarted after 37 deliveries. Maternal adverse events in 46.2% of the pregnancies included 2 post cesarean deaths (a failed post-operative resuscitation and a major bleed in a patient refusing transfusion), 3 non-fatal major bleeds (associated with cesarean section and faulty placental implantation), 3 thrombo-embolic events unresponsive to danaparoid dose increase and 10 recurrent rashes. Seven early miscarriages, 1 therapeutic termination and 1 neonatal death occurred. In 13 reports a maternal, but no fetal, adverse event was attributed to danaparoid. Anti-Xa activity levels in maternal plasma were between 0.1 and 1.2 U/mL, absent from 6 fetal cord blood samples and 0 - 0.07 U/mL in the 5 maternal breast milk samples tested. CONCLUSION: The successful birth rate and adverse event profile indicates that danaparoid can be an effective and safe alternative anti-thrombotic in pregnancies complicated by HIT or intolerance or resistance to (LMW)heparins.
Asunto(s)
Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/uso terapéutico , Dermatán Sulfato/administración & dosificación , Dermatán Sulfato/uso terapéutico , Heparina/efectos adversos , Heparitina Sulfato , Aborto Espontáneo/inducido químicamente , Aborto Espontáneo/tratamiento farmacológico , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/efectos adversos , Exantema/inducido químicamente , Exantema/tratamiento farmacológico , Femenino , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Heparina/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparitina Sulfato/administración & dosificación , Heparitina Sulfato/efectos adversos , Heparitina Sulfato/uso terapéutico , Humanos , Recién Nacido , Infusiones Intravenosas , Inyecciones Subcutáneas , Embarazo , Investigación , Trombosis/inducido químicamente , Trombosis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Thrombocytopenia following heparin administration can be associated with an immune reaction, now referred to as heparin-induced thrombocytopenia (HIT). HIT is essentially a prothrombotic disorder mediated by an IgG antiplatelet factor 4/heparin antibody, which induces platelet, endothelial cell, monocyte, and other cellular activation, leading to thrombin generation and thrombotic complications. Indeed, HIT can also be regarded as a serious adverse drug effect. Importantly, HIT can be a life-threatening and limb-threatening condition frequently associated with characteristically severe and extensive thromboembolism (both venous and arterial) rather than with bleeding. This article provides an overview of HIT, with an emphasis on the clinical diagnosis and management.
Asunto(s)
Anticoagulantes/efectos adversos , Heparina/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Trombocitopenia/inducido químicamente , Anticoagulantes/uso terapéutico , Arginina/análogos & derivados , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/administración & dosificación , Dermatán Sulfato/efectos adversos , Femenino , Heparina/uso terapéutico , Heparitina Sulfato/administración & dosificación , Heparitina Sulfato/efectos adversos , Hirudinas/administración & dosificación , Hirudinas/efectos adversos , Humanos , Masculino , Monitoreo Fisiológico , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/efectos adversos , Ácidos Pipecólicos , Inhibidores de Agregación Plaquetaria/efectos adversos , Recuento de Plaquetas , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Factores de Riesgo , Administración de la Seguridad , Índice de Severidad de la Enfermedad , Sulfonamidas , Tasa de Supervivencia , Trombocitopenia/diagnóstico , Trombocitopenia/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , Factores de TiempoRESUMEN
OBJECTIVE: Systemic inflammatory response syndrome (SIRS) is responsible for pancreatitis-associated mortality, but its initiating events are poorly understood. Possible candidates may be endogenous substances, which have previously been shown to mediate inflammatory responses. The aim of this study was to investigate whether SIRS could be exaggerated by heparan sulfate (HS) in acute pancreatitis (AP). MATERIAL AND METHODS: AP was induced in mice by cerulein injection and HS was administered one hour after the final cerulein injection. The severity of pancreatitis was assessed by serum amylase activity, pancreatic edema, and pancreatic myeloperoxidase (MPO) activity. Systemic inflammation was evaluated by assessing lung injury and by measuring serum levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. Cytokine levels were also measured in pancreas and lung tissues. RESULTS: HS did not worsen the pancreatic injury induced by cerulein. In contrast, HS exacerbated the systemic inflammation as measured by augmented lung MPO activity, increased lung TNF-alpha and IL-6 levels, and elevated serum IL-6 levels. CONCLUSIONS: Our results indicate a potential role for HS in propagating pancreatic inflammation from a local process to a systemic response and thus suggest the possibility that blockade of HS might improve the outcome of SIRS in AP.
Asunto(s)
Heparitina Sulfato/efectos adversos , Pancreatitis Aguda Necrotizante/tratamiento farmacológico , Pancreatitis Aguda Necrotizante/patología , Peroxidasa/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/patología , Animales , Biopsia con Aguja , Ceruletida/farmacología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Heparitina Sulfato/administración & dosificación , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Pruebas de Función Pancreática , Pancreatitis Aguda Necrotizante/mortalidad , Probabilidad , Distribución Aleatoria , Sensibilidad y Especificidad , Estadísticas no Paramétricas , Análisis de Supervivencia , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
A 54-year-old man had been admitted to Nara city hospital because of hematemesis and dyspnea caused by physical exertion, and was given a diagnosis of esophago-cardial varices and portal venous thrombosis. He was transferred to our hospital for further examinations and treatments. Ultrasonography (US) and computed tomography (CT) revealed the progression of portal venous thrombosis. Danaparoid sodium was administered to treat the portal vein thrombus. 5 days later, the patient was found to have hematemesis resulting from a cardial varices rupture. After endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS) was performed, danaparoid sodium was administered for 2 weeks. After the treatment, portal vein thrombus had almost disappeared. Due to an increased risk of bleeding, cases of esophago-cardial varices with portal venous thrombosis must be treated with care. This is the first report of upper gastrointestinal bleeding due to danaparoid sodium. Danaparoid sodium must be carefully administered when patients have portal venous thrombosis with delicate varices.
Asunto(s)
Anticoagulantes/efectos adversos , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/efectos adversos , Várices Esofágicas y Gástricas/inducido químicamente , Hemorragia Gastrointestinal/inducido químicamente , Heparitina Sulfato/efectos adversos , Vena Porta , Trombosis de la Vena/tratamiento farmacológico , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Hematemesis/etiología , Humanos , Cirrosis Hepática Alcohólica/complicaciones , Masculino , Persona de Mediana Edad , Escleroterapia , Trombosis de la Vena/etiologíaRESUMEN
Itching erythematous or eczematous plaques around injection sites are quite frequent side effects of heparin treatment and are clinical symptoms of a delayed-type hypersensitivity to heparins. In most cases, changing the subcutaneous therapy from unfractionated to low molecular weight heparin or treatment with heparinoids does not provide improvement, due to extensive cross-reactivity. Interestingly, it has been demonstrated that patients with delayed-type hypersensitivity to subcutaneously injected heparins tolerate intravenous application of heparin in controlled challenge tests. A patient with known delayed-type hypersensitivity to heparins received the heparinoid, danaparoid, subcutaneously for thrombosis prophylaxis after orthopedic surgery. After the first few injections, eczematous plaques developed; administration of the anticoagulant was continued and gradually resulted in generalized eczema despite treatment with topical and oral glucocorticoids. However, the patient required further anticoagulation. After discontinuation of subcutaneous injections and a switch to intravenous heparin, rapid improvement and clearing of skin lesions occurred. Therefore, in cases of delayed-type hypersensitivity to subcutaneously injected heparins, the switch from subcutaneous to intravenous heparin administration may be justified.
Asunto(s)
Anticoagulantes/uso terapéutico , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Eccema/inducido químicamente , Heparitina Sulfato/efectos adversos , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias/tratamiento farmacológico , Anciano , Anticoagulantes/administración & dosificación , Sulfatos de Condroitina/administración & dosificación , Dermatán Sulfato/administración & dosificación , Femenino , Heparina/administración & dosificación , Heparina/uso terapéutico , Heparitina Sulfato/administración & dosificación , Humanos , Inmovilización/efectos adversos , Infusiones Intravenosas , Inyecciones Subcutáneas , Trombofilia/tratamiento farmacológico , Trombofilia/etiología , Trombosis de la Vena/prevención & controlRESUMEN
The decision for an anticoagulant for renal replacement therapy (RRT) in patients with acute renal failure and heparin-induced thrombocytopenia (HIT) has to be made carefully. Based on results from the literature argatroban is favoured in patients without hepatic dysfunction, referring to its short halftime and easy feasable monitoring. In the case of coexsisting hepatic disorder, danaparoid provides a safe alternative therapy. However, long halftime and the difficult elimination of the substance are unfavourable. Lepirudin represents another possible anticoagulant therapy. Bleeding complications and monitoring of the ecarin clotting time imposes limitations. Experiences with bivalirudin, fondaparinux and prostaglandines are limited and future trials will have to determine the significance of their application in RRT in HIT patients. Furthermore it has to be proven whether the combination of alternative anticoagulants with citrate prolongates circuit halftime of CVVH.
Asunto(s)
Lesión Renal Aguda/terapia , Anticoagulantes/efectos adversos , Cuidados Críticos/métodos , Hemofiltración/métodos , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina/efectos adversos , Trombocitopenia/inducido químicamente , Anticoagulantes/administración & dosificación , Arginina/análogos & derivados , Pruebas de Coagulación Sanguínea , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/efectos adversos , Citratos/administración & dosificación , Citratos/efectos adversos , Dermatán Sulfato/administración & dosificación , Dermatán Sulfato/efectos adversos , Errores Diagnósticos , Relación Dosis-Respuesta a Droga , Epoprostenol/administración & dosificación , Epoprostenol/efectos adversos , Fondaparinux , Heparina/administración & dosificación , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparitina Sulfato/administración & dosificación , Heparitina Sulfato/efectos adversos , Hirudinas/administración & dosificación , Hirudinas/efectos adversos , Humanos , Iloprost/administración & dosificación , Iloprost/efectos adversos , Ácidos Pipecólicos/administración & dosificación , Ácidos Pipecólicos/efectos adversos , Polisacáridos/administración & dosificación , Polisacáridos/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Citrato de Sodio , Sulfonamidas , Trombocitopenia/diagnóstico , Trombosis/inducido químicamente , Trombosis/diagnósticoRESUMEN
Heparin induced thrombocytopenia (HIT) in addition to bleeding complications are the most serious and dangerous side effects of heparin treatment. HIT remains the most common antibody-mediated, drug-induced thrombocytopenic disorder and a leading cause of morbidity and mortality. Two types of HIT are described: Type I is a transitory, slight and asymptomatic reduction of platelet count occurring during 1-2 days of therapy. HIT type II, which has an immunologic origin, is characterized by a thrombocytopenia that generally onset after the fifth day of therapy. Despite thrombocytopenia, haemorrhagic complications are very rare and HIT type II is characterized by thromboembolic complications consisting in venous and arterial thrombosis. The aim of this paper is to review new aspects of epidemiology, pathophysiology, clinical features, diagnosis and therapy of HIT type II. There is increasing evidence that platelet factor 4 (PF4) displaced from endothelial cells, heparan sulphate or directly from the platelets, binds to heparin molecule to form an immunogenic complex. The anti-heparin/PF4 IgG immune-complexes activates platelets through binding with the Fcgamma RIIa (CD32) receptor inducing endothelial lesions with thrombocytopenia and thrombosis. Cytokines are generated during this process and inflammation could play an additional role in the pathogenesis of thromboembolic manifestations. The onset of HIT type II is independent from dosage, schedule, and route of administration of heparin. A platelet count must be carried out prior to heparin therapy. Starting from the fourth day, platelet count must be carried out daily or every two days for at least 20 days of any heparin therapy regardless of the route of the drug administration. Patients undergoing orthopaedic or cardiac surgery are at higher risk for HIT type II. The diagnosis of HIT type II should be formulated on basis of clinical criteria and confirmed by in vitro demonstration of heparin-dependent antibodies detected by functional and antigen methods. However, the introduction of sensitive ELISA tests to measure anti-heparin/PF4 antibodies has showed the immuno-conversion in an higher number of patients treated with heparin such as the incidence of anti-heparin/PF4 exceeds the incidence of the disease. If HIT type II is likely, heparin must be immediately discontinued, even in absence of certain diagnosis of HIT type II, and an alternative anticoagulant therapy must be started followed by oral dicumaroids, preferably after resolution of thrombocytopenia. Further studies are required in order to elucidate the pathogenetic mechanism of thrombosis and its relation with inflammation; on the other hand large clinical trials are needed to confirm the best therapeutic strategies for HIT Type II.
Asunto(s)
Anticoagulantes/efectos adversos , Heparina/efectos adversos , Trombocitopenia/inducido químicamente , Trombocitopenia/prevención & control , Trombocitopenia/terapia , Animales , Arginina/análogos & derivados , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/efectos adversos , Heparitina Sulfato/efectos adversos , Hirudinas/efectos adversos , Humanos , Fragmentos de Péptidos/efectos adversos , Ácidos Pipecólicos/efectos adversos , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/inducido químicamente , Proteínas Recombinantes/efectos adversos , Sulfonamidas , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologíaRESUMEN
Heparin-induced thrombocytopenia (HIT) and heparin induced thrombocytopenia with thrombosis (HITT) ar rare complications associated with use of unfractionate heparin (UFH) or low-molecular-weight heparin (LMWH) HIT is a benign clinical condition characterized by a mil drop in platelet count with no clinical significance. HIT is an immune-mediated reaction associated with a wide spread "hypercoagulable" state resulting in arterial an venous thrombosis. There is a higher incidence of HIT with UFH use than with LMWH use. Orthopedic surger patients are at higher risk for developing HITT than are patients who receive prophylactic heparin for cardiovascular surgery or medical reasons. Therapy for patients suspected of having HITT should begin with immedi ate discontinuation of heparin in any form followed by pharmacologic inhibition with thrombin (e.g., recombinant hirudin [lepirudin], argatroban, danaparoid sodium).
Asunto(s)
Anticoagulantes/efectos adversos , Heparina/efectos adversos , Trombocitopenia/inducido químicamente , Trombosis/inducido químicamente , Arginina/análogos & derivados , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/efectos adversos , Heparitina Sulfato/efectos adversos , Hirudinas/efectos adversos , Humanos , Ácidos Pipecólicos/efectos adversos , Proteínas Recombinantes/efectos adversos , Sulfonamidas , Trombocitopenia/diagnóstico , Trombosis/diagnósticoRESUMEN
La mucopolisacaridosis tipo I (MPS I) es una enfermedad lisosomal hereditaria producida por un déficit enzimático de a-Liduronidasa, que da lugar a una acumulación de los glucosaminglucanos (GAG) dermatán y heparán sulfato en los órganos y los tejidos, así como a un aumento de su excreción urinaria. Hay tres subtipos: la enfermedad de Hurler (MPS IH) es la más grave, la enfermedad de Scheie (MPS IS) es la más leve y la enfermedad de Hurler-Scheie (MPS IHS) es la forma intermedia. Es una enfermedad crónica y progresiva, con manifestaciones multisistémicas. La disminución de la capacidad pulmonar y los síntomas de obstrucción de las vías altas (síndrome apnea- hipopnea del sueño), la afectación cardiovascular y los problemas articulares son los que causan mayor morbimortalidad. El trasplante de médula ósea o de células madre hematopoyéticas, junto con el tratamiento enzimático sustitutivo, constituyen los principales pilares del tratamiento. Presentamos 2 casos de MPS I que han recibido tratamiento sustitutivo con enzima recombinante a-L-iduronidasa durante 30 meses y un tercer caso de un paciente que lo ha iniciado hace 3 meses. Ninguno ha presentado complicaciones atribuibles al tratamiento
Mucopolysaccharidosis type I is an inherited lysosomal storage disease caused by deficiency of the enzyme a-L-iduronidase that leads to a progressive accumulation of dermatan sulfate and heparan sulfato glycosaminoglycans in organs and tissues and to increased urinary excretion. There are three clinical syndromes in decreasing order of severity: Hurler (MPS IH), Hurler-Scheie (MPS IHS) and Scheie (MPS IS). Mucopolysaccharidosis I is a chronic, progressive, multisystemic disease. Respiratory insufficiency and sleep apnea- hypopnea syndrome, together with cardiovascular compromise and joint problems, are the main causes of morbidity and mortality. Bone marrow or hematopoietic stem cell transplantation and enzyme replacement therapy (ERT) are the mainstays of treatment of these patients. We report the clinical courses of two patients who have been treated with recombinant human a-L-iduronidase (laronidase) for 30 months and a third patient who began ERT 3 months ago. None of these patients has presented adverse events related to ERT
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Masculino , Femenino , Lactante , Niño , Adolescente , Humanos , Mucopolisacaridosis I/tratamiento farmacológico , Iduronidasa/farmacocinética , Glicosaminoglicanos/efectos adversos , Dermatán Sulfato/efectos adversos , Heparitina Sulfato/efectos adversos , Mucopolisacaridosis I/clasificación , Trasplante de Médula ÓseaAsunto(s)
Anticoagulantes/efectos adversos , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/efectos adversos , Erupciones por Medicamentos/diagnóstico , Heparitina Sulfato/efectos adversos , Hipersensibilidad Tardía/inducido químicamente , Pruebas Intradérmicas , Anticoagulantes/administración & dosificación , Sulfatos de Condroitina/administración & dosificación , Dermatán Sulfato/administración & dosificación , Heparitina Sulfato/administración & dosificación , Humanos , Hipersensibilidad Tardía/diagnóstico , Inyecciones Subcutáneas , Masculino , Trombosis/prevención & controlAsunto(s)
Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Procedimientos Quirúrgicos Cardíacos/métodos , Heparina/efectos adversos , Trombocitopenia/inducido químicamente , Ancrod/administración & dosificación , Ancrod/efectos adversos , Arginina/análogos & derivados , Puente Cardiopulmonar/métodos , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/administración & dosificación , Dermatán Sulfato/efectos adversos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparitina Sulfato/administración & dosificación , Heparitina Sulfato/efectos adversos , Hirudinas/administración & dosificación , Hirudinas/efectos adversos , Humanos , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/efectos adversos , Ácidos Pipecólicos/administración & dosificación , Ácidos Pipecólicos/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Sulfonamidas , Trombocitopenia/prevención & controlRESUMEN
Sulfated polyanions, including pentosan polysulfate (PPS) and heparan mimetics, number among the most effective drugs that have been used in experimental models of prion disease and are presumed to act in competition with endogenous heparan sulfate proteoglycans as co-receptors for prion protein (PrP) on the cell surface. PPS has been shown to prolong the survival of animals after intracerebral perfusion and is in limited use for the experimental treatment of human transmissible spongiform encephalopathies (TSEs). Here, PPS is compared with CR36, a new heparan mimetic. Ex vivo, CR36 was more efficient than PPS in reducing PrPres in scrapie-infected cell cultures and showed long-lasting activity. In vivo, CR36 showed none of the acute toxicity observed with PPS and reduced PrPres accumulation in spleens, but had only a marginal effect on the survival time of mice infected with bovine spongiform encephalopathy. In contrast, mice treated with PPS that survived the initial toxic mortality had no detectable PrPres in the spleens and lived 185 days longer than controls (+55%). These results show, once again, that anti-TSE drugs cannot be encouraged for human therapeutic trials solely on the basis of in vitro or ex vivo observations, but must first be subjected to in vivo animal studies.