Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 129
Filter
1.
JAMA Neurol ; 81(2): 118-125, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38190136

ABSTRACT

Importance: The effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown. Objective: To assess the efficacy of argatroban for END in AIS. Design, Setting, and Participants: This open-label, blinded-end point, randomized clinical trial was conducted from April 4, 2020, through July 31, 2022. The date of final follow-up was October 31, 2022. This was a multicenter trial. Eligible patients were adults with AIS who experienced END, which was defined as an increase of 2 or more points on the National Institutes of Health Stroke Scale within 48 hours from symptom onset. Patients who withdrew consent, experienced duplicate randomization, or were lost to follow-up were excluded from the study. Interventions: Patients were randomly assigned to the argatroban group and control group within 48 hours of symptom onset. Both groups received standard therapy based on guidelines, including oral mono or dual antiplatelet therapy. The argatroban group received intravenous argatroban for 7 days (continuous infusion at a dose of 60 mg per day for 2 days, followed by 20 mg per day for 5 days) in addition to standard therapy. Main Outcome and Measure: The primary end point was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3. Results: A total of 628 patients (mean [SD] age, 65 [11.9] years; 400 male [63.7%]) were included in this study (argatroban group, 314 [50%] and control group, 314 [50%]). Of these, 18 withdrew consent, 1 had duplicate randomization, and 8 were lost to follow-up. A total of 601 patients with stroke were included in the intention-to-treat analysis. Finally, 564 patients were included in the per-protocol analysis as 6 participants in the argatroban group and 31 participants in the control group did not follow the complete protocol. The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group (risk difference, 7.2%; 95% CI, 0.6%-14.0%; risk ratio, 1.10; 95% CI, 1.01-1.20; P = .04). The proportion of symptomatic intracranial hemorrhage was 3 of 317 (0.9%) in the argatroban group and 2 of 272 (0.7%) in the control group (P = .78). Conclusions and Relevance: Among patients with AIS with END, treatment with argatroban and antiplatelet therapy resulted in a better functional outcome at 90 days. This trial provided evidence to support the use of argatroban in reducing disability for patients with END. Trial Registration: ClinicalTrials.gov Identifier: NCT04275180.


Subject(s)
Arginine/analogs & derivatives , Ischemic Stroke , Stroke , Sulfonamides , Adult , Humans , Male , Aged , Ischemic Stroke/drug therapy , Stroke/complications , Stroke/drug therapy , Pipecolic Acids/therapeutic use , Pipecolic Acids/adverse effects , Anticoagulants/therapeutic use
2.
Crit Care ; 25(1): 160, 2021 04 29.
Article in English | MEDLINE | ID: mdl-33910609

ABSTRACT

BACKGROUND: During venovenous extracorporeal membrane oxygenation (vvECMO), direct thrombin inhibitors are considered by some potentially advantageous over unfractionated heparin (UFH). We tested the hypothesis that Argatroban is non-inferior to UFH regarding thrombosis and bleeding during vvECMO. METHODS: We conducted a propensity-score matched observational non-inferiority study of consecutive patients without heparin-induced-thrombocytopenia (HIT) on vvECMO, treated between January 2006 and March 2019 in the medical intensive care unit at the University Hospital Regensburg. Anticoagulation was realized with UFH until August 2017 and with Argatroban from September 2017 onwards. Target activated partial thromboplastin time was 50 ± 5seconds in both groups. Primary composite endpoint was major thrombosis and/or major bleeding. Major bleeding was defined as a drop in hemoglobin of ≥ 2 g/dl/day or in transfusion of ≥ 2 packed red cells/24 h, or retroperitoneal, cerebral, or pulmonary bleeding. Major thrombosis was defined as obstruction of > 50% of the vessel lumen diameter by means of duplex sonography. We also assessed technical complications such as oxygenator defects or pump head thrombosis, the time-course of platelets, and the cost of anticoagulation (including HIT-testing). RESULTS: Out of 465 patients receiving UFH, 78 were matched to 39 patients receiving Argatroban. The primary endpoint occurred in 79% of patients in the Argatroban group and in 83% in the UFH group (non-inferiority for Argatroban, p = 0.026). The occurrence of technical complications was equally distributed (Argatroban 49% vs. UFH 42%, p = 0.511). The number of platelets was similar in both groups before ECMO therapy but lower in the UFH group after end of ECMO support (median [IQR]: 141 [104;198]/nl vs. 107 [54;171]/nl, p = 0.010). Anticoagulation costs per day of ECMO were higher in the Argatroban group (€26 [13.8;53.0] vs. €0.9 [0.5;1.5], p < 0.001) but not after accounting for blood products and HIT-testing (€63 [42;171) vs. €40 [17;158], p = 0.074). CONCLUSION: In patients without HIT on vvECMO, Argatroban was non-inferior to UFH regarding bleeding and thrombosis. The occurrence of technical complications was similarly distributed. Argatroban may have less impact on platelet decrease during ECMO, but this finding needs further evaluation. Direct drug costs were higher for Argatroban but comparable to UFH after accounting for HIT-testing and transfusions.


Subject(s)
Arginine/analogs & derivatives , Extracorporeal Membrane Oxygenation/methods , Heparin/standards , Pipecolic Acids/standards , Sulfonamides/standards , Thrombocytopenia/prevention & control , Adult , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Antithrombins/adverse effects , Antithrombins/standards , Arginine/adverse effects , Arginine/standards , Equivalence Trials as Topic , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Germany , Heparin/adverse effects , Humans , Male , Middle Aged , Pipecolic Acids/adverse effects , Propensity Score , Prospective Studies , Registries/statistics & numerical data , Sulfonamides/adverse effects
3.
J Thromb Thrombolysis ; 51(3): 725-733, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33582956

ABSTRACT

Heparin-induced thrombocytopenia (HIT) is a highly thrombogenic condition. Cancer patients are already at high risk of thrombosis. The treatment and outcomes of HIT in cancer patients are not well established. We retrospectively identified patients with active cancer who were diagnosed with HIT at our institution. Only patients with a positive HIT assay and intermediate to high 4Ts score were included. We assessed patients for baseline characteristics, HIT characteristics, non-heparin agent usage, and outcomes (recurrent thrombosis, bleeding, and death) up to 180 days after diagnosis of HIT. Between November 1, 2006 and December 31, 2016, 39 patients with active cancer received a diagnosis of HIT. Of these, 35.9% had thrombotic complications at diagnosis. Gastrointestinal cancer was the most common solid organ malignancy while myeloproliferative neoplasm (MPN) was the most common hematological malignancy. Fondaparinux was the most often used parenteral agent at any point of follow-up (87.2%), followed by argatroban (41.0%). Less than half the patients transitioned to an oral agent. The recurrent thrombosis rate was 17.9%, the bleeding rate was 20.5%, the major bleeding rate was 10.3%, and the mortality rate was 15.4% in the entire cohort. HIT in cancer patients is associated with poor outcomes.


Subject(s)
Arginine/analogs & derivatives , Fondaparinux , Gastrointestinal Neoplasms/complications , Hematologic Neoplasms/complications , Heparin , Pipecolic Acids , Sulfonamides , Thrombocytopenia , Aged , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Arginine/administration & dosage , Arginine/adverse effects , Canada/epidemiology , Female , Fondaparinux/administration & dosage , Fondaparinux/adverse effects , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Hematologic Neoplasms/mortality , Hematologic Neoplasms/pathology , Hematologic Neoplasms/therapy , Hemorrhage/chemically induced , Heparin/administration & dosage , Heparin/adverse effects , Humans , Male , Patient Acuity , Pipecolic Acids/administration & dosage , Pipecolic Acids/adverse effects , Platelet Count/methods , Platelet Count/statistics & numerical data , Retrospective Studies , Risk Adjustment/methods , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombocytopenia/prevention & control
4.
Yakugaku Zasshi ; 140(11): 1373-1380, 2020.
Article in Japanese | MEDLINE | ID: mdl-33132273

ABSTRACT

The treatment of acute ischemic stroke usually involves argatroban administration by continuous infusion for 2 d and by intravenous infusion twice a day for 5 d after that. However, the appropriate dose of argatroban to be administered is not clear. Therefore, no studies have been reported a comparison of intravenous and continuous argatroban infusion after day 3 for acute ischemic stroke patients. We aimed to identify the connection between differences in argatroban administration and worsening of symptoms after day 3 in ischemic stroke patients. We retrospectively evaluated the data of 107 ischemic stroke patients who received treatment with argatroban. The study endpoint was defined as the worsening of symptoms from days 3 to 7. Logistic regression analysis was used to determine the risk factors that were significantly associated with worsening of symptoms. Patients were administered argatroban, with rates of 72.0%, and 28.0% for continuous, and intravenous infusion, respectively. A total of 10 (9.3%) patients experienced worsening of symptoms. In the single logistic regression analysis, carotid stenosis [non-adjusted odds ratio (OR) 5.775, 95% confidence interval (CI) 1.486-22.442, p=0.011] was only significantly associated with worsening of symptoms. Worsening of symptoms was not related to either intravenous or continuous infusion group (16.7% vs. 6.5%, p=0.104). Bleeding was also not associated with either group (6.7% vs. 3.9%, p=0.618). We suggest that the differences in the mode of argatroban administration were not related to the worsening of symptoms in ischemic stroke patients. We also found that safety was equivalent regardless of the administration route.


Subject(s)
Administration, Intravenous/methods , Pipecolic Acids/administration & dosage , Stroke/drug therapy , Symptom Flare Up , Aged , Aged, 80 and over , Arginine/analogs & derivatives , Drug Administration Routes , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Patient Outcome Assessment , Pipecolic Acids/adverse effects , Retrospective Studies , Safety , Sulfonamides
5.
Cardiovasc Ther ; 2020: 9783630, 2020.
Article in English | MEDLINE | ID: mdl-32405324

ABSTRACT

INTRODUCTION: Anticoagulants such as argatroban and heparins (low-molecular-weight and unfractionated) play an immense role in preventing thromboembolic complications in clinical practice. Nevertheless, they can also have a negative effect on the immune system. This study is aimed at investigating the influence of these substances on polymorphonuclear neutrophils (PMNs), whose nonspecific defense mechanisms can promote thrombogenesis. METHODS: Blood samples from 30 healthy volunteers were investigated, whereby PMNs were isolated by density gradient centrifugation and incubated with 0.8 µg/mL of argatroban, 1.0 U/mL of low-molecular-weight heparin (LMWH), 1.0 U/mL of unfractionated heparin (UFH), or without drug (control). A collagen-cell mixture was prepared and filled into 3D µ-slide chemotaxis chambers (IBIDI® GmbH, Germany). Stimulation was initiated by using a chemokine gradient of n-formyl-methionine-leucyl-phenylalanine (fMLP), and microscopic observation was conducted for 4.5 hours. The cells' track length and track straightness, as well as the number of attracted granulocytes, level of ROS (reactive oxygen species) production, and NET (neutrophil extracellular traps) formation, were analyzed and categorized into migration distances and time periods. RESULTS: All three anticoagulants led to significantly reduced PMN track lengths, with UFH having the biggest impact. The number of tracks observed in the UFH group were significantly reduced compared to the control group. Additionally, the UFH group demonstrated a significantly lower track straightness compared to the control. ROS production and NET formation were unaffected. CONCLUSION: Our data provide evidence that anticoagulants have an inhibitory effect on the extent of PMN migration and chemotactic migration efficiency, thus indicating their potential immune-modulatory and prothrombotic effects.


Subject(s)
Anticoagulants/adverse effects , Antithrombins/adverse effects , Chemotaxis, Leukocyte/drug effects , Enoxaparin/adverse effects , Granulocytes/drug effects , Pipecolic Acids/adverse effects , Adult , Arginine/analogs & derivatives , Extracellular Traps/metabolism , Female , Granulocytes/immunology , Granulocytes/metabolism , Humans , Male , Middle Aged , Reactive Oxygen Species/metabolism , Sulfonamides , Young Adult
6.
Clin Appl Thromb Hemost ; 26: 1076029620904131, 2020.
Article in English | MEDLINE | ID: mdl-32013541

ABSTRACT

There is a lack of studies on anticoagulant plus antiplatelet therapy for acute ischemic stroke. The present study made a pilot effort to investigate the efficacy and safety of argatroban plus dual antiplatelet therapy (DAPT) in patients with acute posterior circulation ischemic stroke (PCIS). We retrospectively collected patients diagnosed with acute PCIS according to inclusion/exclusion criteria. According to treatment drugs, patients were divided into an argatroban plus DAPT group and a DAPT group. The primary efficacy end point was the proportion of early neurological deterioration (END). The primary safety outcome was symptomatic intracranial hemorrhage. All outcomes were compared between the 2 groups before and after propensity score matching (PSM). A total of 502 patients were enrolled in the study, including 35 patients with argatroban plus DAPT and 467 patients with DAPT. There was a higher National Institutes of Health Stroke Scale (NIHSS) score in the argatroban plus DAPT group than the DAPT group before PSM (3 vs 2, P = .017). Compared with the DAPT group, the argatroban plus DAPT group had no END (before PSM: 0% vs 6.2%, P = .250; after PSM: 0% vs 5.9%, P = .298). Argatroban plus DAPT yielded a significant decrease in the NIHSS score from baseline to 7 days after hospitalization, compared with that of the DAPT group before PSM (P = .032), but not after PSM (P = .369). No symptomatic intracranial hemorrhage was found in any patient. A short-term combination of argatroban with DAPT appears safe in acute minor PCIS.


Subject(s)
Brain Ischemia/chemically induced , Pipecolic Acids/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Stroke/complications , Arginine/analogs & derivatives , Female , Humans , Male , Middle Aged , Pipecolic Acids/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Stroke/drug therapy , Sulfonamides , Treatment Outcome
7.
J Stroke Cerebrovasc Dis ; 27(12): 3647-3651, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30249518

ABSTRACT

BACKGROUND: A randomized trial of concurrent recombinant tissue-type plasminogen activator (r-tPA) + thrombin-inhibition with Argatroban in stroke patients recently demonstrated safety and signal of efficacy compared to r-tPA alone, but patients having endovascular therapy (EVT) were excluded. The current study intended to study feasibility and safety of concurrent r-tPA and Argatroban in patients undergoing EVT. METHODS: We conducted a single-arm, feasibility, and safety study of patients that received standard-dose r-tPA, had intracranial large vessel occlusions, and underwent EVT within 6 hours of stroke onset. During r-tPA, a 100 µg/kg Argatroban bolus, followed by 12-hour infusion, targeted an activated Partial Thromboplastin Time (aPTT) 2.25 timesbaseline. Feasibility was defined as ability to combine treatments without EVT time-metric delays, compared to cotemporaneous r-tPA + EVT treatments. Safety was incidence of symptomatic intracerebral hemorrhage (sICH), systemic hemorrhage, or EVT complications. RESULTS: All preplanned 10 patients were enrolled. Arterial occlusions were middle cerebral artery (n = 8), internal carotid artery (n = 1), and posterior cerebral artery (n = 1). All received Argatroban before EVT and completed infusions. There were no delays in time-metrics compared to nonstudy patients during the same period. Nine patients achieved excellent angiographic reperfusion (Thrombolysis In Cerebral Ischemia [TICI] ≥2b); with 7 complete (TICI = 3). There were no sICH, systemic hemorrhage, or EVT complications. At 90 days, 6 (60%) patients had a modified Rankin Scale of 0-2 and none died. CONCLUSIONS: In patients treated with r-tPA and EVT, concomitant Argatroban is feasible, does not delay EVT provision, produces high rates of recanalization, is probably safe, and warrants further study.


Subject(s)
Endovascular Procedures , Fibrinolytic Agents/therapeutic use , Pipecolic Acids/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Stroke/therapy , Tissue Plasminogen Activator/therapeutic use , Aged , Aged, 80 and over , Arginine/analogs & derivatives , Cerebral Hemorrhage/epidemiology , Combined Modality Therapy , Drug Therapy, Combination , Endovascular Procedures/adverse effects , Feasibility Studies , Fibrinolytic Agents/adverse effects , Humans , Incidence , Middle Aged , Pipecolic Acids/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Postoperative Complications/epidemiology , Stroke/epidemiology , Sulfonamides , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
8.
Ann Hematol ; 97(11): 2055-2059, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30003318

ABSTRACT

Heparin-induced thrombocytopenia (HIT) is a serious complication of the administration of heparin and its derivatives. Non-heparin anticoagulants such as argatroban and fondaparinux are widely used in the management of HIT to compare the effectiveness of argatroban and fondaparinux in the resolution of thrombocytopenia and to compare clinical outcomes in patients with isolated HIT. A retrospective cohort analysis was performed at King Abdulaziz Medical City (KAMC) on patients diagnosed with isolated HIT between 31 Jan, 2014 and 30 June, 2017. Demographics data, non-heparin anticoagulants, related laboratory results, and clinical outcomes were retrieved and analysed. The cohort comprised a total of 95 adult patients who received either argatroban (56 patients) or fondaparinux (39 patients) for isolated HIT. The median age and sex distribution were similar in both argatroban and fondaparinux groups. The mean (+ SD) time (in days) for the resolution of thrombocytopenia was 3.5 (± 1.8) for patients who received argatroban and 3.7 (± 1.7) for patients administered fondaparinux (p = 0.843). Thromboembolic events occurred in five patients (8.9%) administered argatroban and in three patients (7.7%) administered fondaparinux (p = 0.382). There was no significant difference in the rates of bleeding or death (p = 0.829); however, the small number of cases limits our ability to draw conclusions about these outcomes. In this retrospective study, fondaparinux and argatroban were similarly effective in resolving thrombocytopenia, preventing further thromboembolic events, and maintaining safety in patients with confirmed HIT. To confirm this observation, larger prospective studies are needed.


Subject(s)
Fondaparinux/administration & dosage , Heparin/adverse effects , Pipecolic Acids/administration & dosage , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy , Aged , Arginine/analogs & derivatives , Fondaparinux/adverse effects , Humans , Middle Aged , Pipecolic Acids/adverse effects , Retrospective Studies , Sulfonamides , Thrombocytopenia/pathology , Thromboembolism/chemically induced , Thromboembolism/pathology
9.
Thromb Haemost ; 118(5): 818-829, 2018 05.
Article in English | MEDLINE | ID: mdl-29614521

ABSTRACT

BACKGROUND: Staphylococcus aureus (S. aureus) bacteraemia is frequent and carries a high morbidity and mortality. Coagulases secreted by S. aureus initiate blood coagulation by directly activating prothrombin. This pathogen-activated coagulation is insensitive to most antithrombotic drugs, with the exception of small molecule direct thrombin inhibitors (DTIs). DTIs inhibit the coagulase-prothrombin complex, or staphylothrombin, and improve outcome in preclinical models of S. aureus infection. OBJECTIVE: A single-centre, randomized, controlled feasibility and safety trial of staphylothrombin inhibition with DTIs in patients with S. aureus bacteraemia. PATIENTS AND METHODS: Consecutive eligible adult patients with S. aureus positive blood cultures in the University Hospitals Leuven (Belgium) were randomized 1:1 to DTI (oral dabigatran 110 mg twice daily or intravenous argatroban according to activated partial thromboplastin time [aPTT]) for 7 to 10 days, or subcutaneous enoxaparin 40 mg once daily. Primary outcomes were feasibility and safety of DTI in patients with S. aureus bacteraemia. Secondary outcomes include D-dimer evolution (day 0-4) as marker of coagulation activation; inflammatory and microbiological parameters; and clinical outcomes including metastatic infections. RESULTS: Thirty-one percent (94/303) of screened patients were enrolled. Dabigatran plasma levels inhibited staphylothrombin. Clinically relevant bleeding (5/47 vs. 5/47) and thrombotic (7/47 vs. 7/47) complications were similar in both groups. Coagulase inhibition with DTIs was associated with a trend towards faster D-dimer decrease at day 4 (-662 ± 249 ng/mL vs. -40 ± 213 ng/mL for DTI-treated patients vs. control; p = 0.06) and a numerically lower number of persistently positive blood cultures. No differences in inflammatory parameters or other clinical outcomes were observed. CONCLUSION: Targeting staphylothrombin with DTIs is feasible in a subset of S. aureus bacteraemic patients, with comparable safety to standard thromboprophylaxis. In future studies of staphylothrombin inhibition, feasibility can be further improved by rapid diagnostics and by strategies without concomitant anticoagulant effect.


Subject(s)
Anticoagulants/administration & dosage , Antithrombins/administration & dosage , Bacteremia/drug therapy , Coagulase/antagonists & inhibitors , Dabigatran/administration & dosage , Enoxaparin/administration & dosage , Pipecolic Acids/administration & dosage , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Thrombin/antagonists & inhibitors , Thrombosis/prevention & control , Administration, Intravenous , Administration, Oral , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Antithrombins/adverse effects , Arginine/analogs & derivatives , Bacteremia/diagnosis , Bacteremia/microbiology , Belgium , Blood Coagulation/drug effects , Coagulase/metabolism , Dabigatran/adverse effects , Enoxaparin/adverse effects , Feasibility Studies , Female , Hemorrhage/chemically induced , Humans , Injections, Subcutaneous , Male , Middle Aged , Partial Thromboplastin Time , Pilot Projects , Pipecolic Acids/adverse effects , Prospective Studies , Staphylococcal Infections/diagnosis , Staphylococcal Infections/microbiology , Staphylococcus aureus/enzymology , Sulfonamides , Thrombin/metabolism , Thrombosis/blood , Thrombosis/diagnosis , Thrombosis/microbiology , Time Factors , Treatment Outcome
10.
Am J Perinatol ; 35(9): 898-903, 2018 07.
Article in English | MEDLINE | ID: mdl-29421832

ABSTRACT

INTRODUCTION: The rate of heparin-induced thrombocytopenia (HIT) on a population basis is unknown. The objective of this study was to characterize the risk for HIT during antepartum, delivery, and postpartum hospitalizations in the United States. MATERIALS AND METHODS: A large administrative database was used to determine the risk of HIT in hospitalized obstetric patients who received unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Patients were presumed to have HIT if they were exposed to UFH or LMWH, received a diagnosis of HIT, and were administered a medication for the treatment of HIT including bivalirudin, argatroban, fondaparinux, or lepirudin. We queried severe complications of HIT including arterial thrombosis, limb amputation, heart failure, and death. RESULTS: We identified 66,468 antepartum hospitalizations, 66,741 delivery hospitalizations, and 16,325 postpartum readmissions where women received pharmacologic prophylaxis. Of these, 10 antepartum admissions, 1 delivery admission, and 14 postpartum readmissions involved a diagnosis of HIT with treatment of bivalirudin, argatroban, fondaparinux, or lepirudin. There were no deaths and no diagnoses of arterial thrombosis, limb amputation, heart failure, and death. CONCLUSION: Risk for HIT among hospitalized obstetric patients is low. In this cohort, no cases of death or severe complications were noted in relation to the diagnosis.


Subject(s)
Delivery, Obstetric , Heparin/adverse effects , Hospitalization/statistics & numerical data , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Adolescent , Adult , Arginine/analogs & derivatives , Databases, Factual , Female , Fondaparinux/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Hirudins/adverse effects , Hospitalization/trends , Humans , Middle Aged , Peptide Fragments/adverse effects , Pipecolic Acids/adverse effects , Postpartum Period , Pregnancy , Recombinant Proteins/adverse effects , Risk Assessment , Sulfonamides , United States/epidemiology , Young Adult
11.
Int J Surg ; 44: 324-328, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28694001

ABSTRACT

BACKGROUND: To evaluate the safety and effectiveness of argatroban for the prevention of venous thromboembolism (VTE) after posterior lumbar decompressive surgery. METHODS: Included in this retrospective study were 556 patients who underwent posterior lumbar decompressive surgery for trauma and degenerative diseases. They were divided into two groups: argatroban group (n = 274), and low molecular weight heparin (LMWH) group (n = 282). The occurrence of postoperative venous thrombosis and complications including hemorrhage and allergic reaction was compared between the two groups. Neurological and clinical outcomes in terms of Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) were assessed before operation and at 6 and 12 months after operation. RESULTS: Postoperative venous thromboembolism (VTE) occurred in seven patient. No pulmonary embolism (PE) occurred in any patient. Thrombosis occurred in 3 cases (1.0%) and bleeding in 1 case (0.04%) in argatroban group vs. 4 (1.4%) and 4 (1.4%) in LMWH group, showing no significant between the two groups (P > 0.05). There was significant reduction in the severity of back and leg pain (VAS P < 0.05) and significant improvement in the patient quality of life (ODI, P < 0.05) 6 months and 1 year after operation, showing no significant difference between the two groups (P > 0.05). CONCLUSIONS: Argatroban proved to be equally effective as LWMH for anticoagulation therapy. Both drugs exhibited a similar preventive effect against postoperative VTE after posterior lumbar spine surgery, without increasing the risk of postoperative bleeding. The neurological and clinical outcomes are satisfactory and similar between the two pharmacological methods.


Subject(s)
Anticoagulants/therapeutic use , Decompression, Surgical , Heparin/therapeutic use , Lumbar Vertebrae/surgery , Pipecolic Acids/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Venous Thromboembolism/prevention & control , Adult , Aged , Anticoagulants/adverse effects , Arginine/analogs & derivatives , Female , Heparin/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Incidence , Male , Middle Aged , Pipecolic Acids/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Postoperative Complications/prevention & control , Quality of Life , Retrospective Studies , Sulfonamides , Venous Thromboembolism/etiology , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology
12.
Blood Cells Mol Dis ; 67: 48-53, 2017 09.
Article in English | MEDLINE | ID: mdl-28552476

ABSTRACT

Thrombotic complications are increasing at a steady and significant rate in children resulting in the more widespread use of anticoagulation in this population. Anticoagulant drugs in children can be divided into the standard agents (heparin, low molecular weight heparin, and vitamin K antagonists) and alternative agents (argatroban, bivalirudin, and fondaparinux). This review will compare and contrast the standard and alternative anticoagulants and suggest situations in which it may be appropriate to use argatroban, bivalirudin, and fondaparinux. Clearly, the standard anticoagulants all have significant shortcomings including variable pharmacokinetics, issues with therapeutic drug monitoring, frequency of administration, efficacy, and adverse effects. The alternative anticoagulants have properties which overcome these shortcomings and prospective clinical trial data are presented supporting the current and future use of these agents in place of the standard anticoagulants.


Subject(s)
Anticoagulants/therapeutic use , Heparin/therapeutic use , Peptide Fragments/therapeutic use , Pipecolic Acids/therapeutic use , Polysaccharides/therapeutic use , Thrombosis/drug therapy , Venous Thromboembolism/drug therapy , Warfarin/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Anticoagulants/pharmacokinetics , Arginine/analogs & derivatives , Blood Coagulation/drug effects , Child , Drug Monitoring , Fondaparinux , Heparin/administration & dosage , Heparin/adverse effects , Heparin/pharmacokinetics , Hirudins/administration & dosage , Hirudins/adverse effects , Hirudins/pharmacokinetics , Humans , Peptide Fragments/administration & dosage , Peptide Fragments/adverse effects , Peptide Fragments/pharmacokinetics , Pipecolic Acids/administration & dosage , Pipecolic Acids/adverse effects , Pipecolic Acids/pharmacokinetics , Polysaccharides/administration & dosage , Polysaccharides/adverse effects , Polysaccharides/pharmacokinetics , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/pharmacokinetics , Recombinant Proteins/therapeutic use , Sulfonamides , Thrombosis/blood , Venous Thromboembolism/blood , Warfarin/administration & dosage , Warfarin/adverse effects , Warfarin/pharmacokinetics
13.
Stroke ; 48(6): 1608-1616, 2017 06.
Article in English | MEDLINE | ID: mdl-28507269

ABSTRACT

BACKGROUND AND PURPOSE: We conducted a randomized exploratory study to assess safety and the probability of a favorable outcome with adjunctive argatroban, a direct thrombin-inhibitor, administered to recombinant tissue-type plasminogen activator (r-tPA)-treated ischemic stroke patients. METHODS: Patients treated with standard-dose r-tPA, not receiving endovascular therapy, were randomized to receive no argatroban or argatroban (100 µg/kg bolus) followed by infusion of either 1 (low dose) or 3 µg/kg per minute (high dose) for 48 hours. Safety was incidence of symptomatic intracerebral hemorrhage. Probability of clinical benefit (modified Rankin Scale score 0-1 at 90 days) was estimated using a conservative Bayesian Poisson model (neutral prior probability centered at relative risk, 1.0 and 95% prior intervals, 0.33-3.0). RESULTS: Ninety patients were randomized: 29 to r-tPA alone, 30 to r-tPA+low-dose argatroban, and 31 to r-tPA+high-dose argatroban. Rates of symptomatic intracerebral hemorrhage were similar among control, low-dose, and high-dose arms: 3/29 (10%), 4/30 (13%), and 2/31 (7%), respectively. At 90 days, 6 (21%) r-tPA alone, 9 (30%) low-dose, and 10 (32%) high-dose patients were with modified Rankin Scale score 0 to 1. The relative risks (95% credible interval) for modified Rankin Scale score 0 to 1 with low, high, and either low or high dose argatroban were 1.17 (0.57-2.37), 1.27 (0.63-2.53), and 1.34 (0.68-2.76), respectively. The probability that adjunctive argatroban was superior to r-tPA alone was 67%, 74%, and 79% for low, high, and low or high dose, respectively. CONCLUSIONS: In patients treated with r-tPA, adjunctive argatroban was not associated with increased risk of symptomatic intracerebral hemorrhage and provides evidence that a definitive effectiveness trial is indicated. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01464788.


Subject(s)
Antithrombins/pharmacokinetics , Brain Ischemia/drug therapy , Cerebral Hemorrhage/chemically induced , Fibrinolytic Agents/pharmacology , Outcome Assessment, Health Care , Pipecolic Acids/pharmacology , Severity of Illness Index , Stroke/drug therapy , Tissue Plasminogen Activator/pharmacology , Aged , Aged, 80 and over , Antithrombins/administration & dosage , Antithrombins/adverse effects , Arginine/analogs & derivatives , Drug Therapy, Combination , Female , Fibrinolytic Agents/administration & dosage , Humans , Male , Middle Aged , Outcome Assessment, Health Care/statistics & numerical data , Pipecolic Acids/administration & dosage , Pipecolic Acids/adverse effects , Sulfonamides , Tissue Plasminogen Activator/administration & dosage
14.
Med Klin Intensivmed Notfmed ; 112(4): 334-346, 2017 May.
Article in German | MEDLINE | ID: mdl-28005139

ABSTRACT

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.


Subject(s)
Heparin/adverse effects , Heparin/economics , Hospitalization/economics , Thrombocytopenia/chemically induced , Thrombocytopenia/economics , Thrombosis/economics , Thrombosis/prevention & control , Arginine/analogs & derivatives , Chondroitin Sulfates/adverse effects , Chondroitin Sulfates/therapeutic use , Costs and Cost Analysis , Dermatan Sulfate/adverse effects , Dermatan Sulfate/therapeutic use , Germany , Hemorrhage/blood , Hemorrhage/chemically induced , Hemorrhage/economics , Heparin/therapeutic use , Heparitin Sulfate/adverse effects , Heparitin Sulfate/therapeutic use , Humans , Pipecolic Acids/adverse effects , Pipecolic Acids/therapeutic use , Risk Factors , Sulfonamides , Thrombocytopenia/drug therapy , Thrombosis/blood , Treatment Outcome
16.
J Cardiothorac Surg ; 10: 19, 2015 Feb 07.
Article in English | MEDLINE | ID: mdl-25879883

ABSTRACT

BACKGROUND: Heparin-induced thrombocytopenia (HIT) causes thromboembolic complications which threaten life and limb. Heparin is administered to virtually every critically ill patient as a protective measure against thromboembolism. Argatroban is a promising alternative anticoagulant agent. However, a safe dose which still provides effective thromboembolic prophylaxis without major bleeding still needs to be identified. METHODS: Critically ill patients (n = 42) diagnosed with HIT at a tertiary medical center intensive care unit from 2005 to 2010 were included in this retrospective analysis. Patient records were perused for preexisting history of HIT, heparin dosage before HIT, argatroban dosage, number of transfusions required, thromboembolic complications and length of ICU stay (ICU LOS). Patients were allocated to Simplified Acute Physiology Scores above and below 30 (SAPS >30, SAPS <30), respectively. For calculations, patients (n = 19) without previous history of HIT were compared to patients (n = 23) with a history of HIT before initiation of argatroban. RESULTS: The mean initial argatroban dosage was below 0.4 mcg/kg/min regardless of SAPS score. Maintenance dosage had to be increased in patients with SAPS <30 to 0.54 ± 0.248 mcg/kg/min (p >0.05) to achieve effective anticoagulation. No thromboembolic complications were encountered. Argatroban had to be discontinued temporarily in 16 patients for a total of 57 times due to diagnostic or surgical procedures, supratherapeutic aPTT and bleeding without increasing the number of transfusions. A history of HIT was associated with a shorter ICU LOS and significantly reduced transfusion need when compared to patients with no history of HIT. Cost calculation favour argatroban due to increased transfusion needs during heparin administration and increase ICU LOS. CONCLUSION: Argatroban can be used at doses < 0.4 mcg/kg/min without an increase in transfusion requirements and at a reduced overall treatment cost compared to heparin.


Subject(s)
Anticoagulants/administration & dosage , Pipecolic Acids/administration & dosage , Thromboembolism/prevention & control , Adult , Aged , Anticoagulants/adverse effects , Anticoagulants/economics , Arginine/analogs & derivatives , Critical Illness/therapy , Dose-Response Relationship, Drug , Drug Costs/statistics & numerical data , Female , Germany , Health Care Costs/statistics & numerical data , Hemorrhage/chemically induced , Hemorrhage/economics , Hemorrhage/prevention & control , Heparin/adverse effects , Heparin/economics , Humans , Intensive Care Units/economics , Male , Middle Aged , Pipecolic Acids/adverse effects , Pipecolic Acids/economics , Retrospective Studies , Sulfonamides , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombocytopenia/economics , Thromboembolism/economics
17.
Arch Pathol Lab Med ; 138(9): 1229-32, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25171706

ABSTRACT

CONTEXT: Parenteral direct thrombin inhibitors (DTIs) may be used in pediatric patients with contraindications to heparin therapy, such as heparin-induced thrombocytopenia. Few data exist regarding the use of DTIs in pediatric patients. OBJECTIVE: To characterize the use of DTIs in pediatric patients, including monitoring strategies and bleeding complications. DESIGN: A retrospective descriptive study was designed and the Pediatric Health Information System database was queried from 2004 to 2011 for pediatric patients receiving a parenteral DTI. Patient demographic and hospital data, mortality, disease state, and procedure information (from International Classification of Diseases, Ninth Revision codes) were collected from the query. DTI monitoring information was also collected. Patients were divided into 2 time periods (2004-2007, 2008-2011) to evaluate trends. RESULTS: Two hundred eight patients met study criteria (50.9% male, 64.4% white), and children (2-12 years of age) represented 34.6% of the population. Congenital heart disease was present in 43.8% and cardiovascular surgical procedure occurred in 28.4%. Argatroban was most commonly used (73.1%) and bivalirudin use increased (P < .001). Bleeding complications were present in 37.9% of patients and mortality was 19.7%. Bleeding complications were associated with lepirudin (62.5%) and argatroban (41.7%) more often as compared with bivalirudin (18.8%) (P < .001). Activated partial thromboplastin time and prothrombin time were used more often in patients receiving argatroban and lepirudin in comparison with bivalirudin, and thrombin time was used more often in patients receiving lepirudin (P < .001). Activated clotting time use increased over time (5.1% versus 17.5%, P = .02). CONCLUSION: Pediatric use of DTIs is infrequent and occurs in patients with high morbidity and mortality.


Subject(s)
Antithrombins/administration & dosage , Antithrombins/therapeutic use , Databases, Factual/trends , Health Information Systems/statistics & numerical data , Infusions, Parenteral , Thrombocytopenia/drug therapy , Adolescent , Age Factors , Antithrombins/adverse effects , Arginine/analogs & derivatives , Child , Child, Preschool , Female , Hemorrhage/epidemiology , Hirudins/administration & dosage , Hirudins/adverse effects , Humans , Incidence , Infant , Infant, Newborn , Male , Peptide Fragments/administration & dosage , Peptide Fragments/adverse effects , Peptide Fragments/therapeutic use , Pipecolic Acids/administration & dosage , Pipecolic Acids/adverse effects , Pipecolic Acids/therapeutic use , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Retrospective Studies , Sulfonamides , Young Adult
18.
Eur Neurol ; 71(5-6): 319-25, 2014.
Article in English | MEDLINE | ID: mdl-24732894

ABSTRACT

BACKGROUND/AIMS: Restenosis following extracranial artery stenting is a limitation that affects long-term outcomes. Effective and satisfying pharmacological strategies in preventing restenosis have not been established. This study aimed to evaluate whether argatroban, a direct thrombin inhibitor, could reduce the risk of in-stent restenosis after extracranial artery stenting. METHODS: One hundred and fourteen patients hospitalized between August 2010 and August 2011 were enrolled. Patients were randomly assigned to argatroban (n = 58) and blank control groups (n = 56). The patients in the argatroban arm were treated with 10 mg of intravenous argatroban twice daily 2 days before and 3 days after the stenting procedures. Patients were followed for 12 months after the procedure. During follow-up, restenosis and target revascularization were analyzed. Recurrent cerebrovascular and cardiovascular events and deaths were also compared between the groups. RESULTS: One patient in the stenting group withdrew immediately after the procedure due to unsuccessful stenting. Restenosis occurred in 4 patients (7.4%) in the argatroban group and in 11 patients (21.6%) in the control group during the 6- to 9-month angiographic follow-up period (p = 0.032). Nine months after the procedures, argatroban-treated patients had a trend towards a lower incidence of target revascularization compared with the controls (5.4 vs. 13.7%, p = 0.188). No major bleeding events or other adverse events occurred in the argatroban group. CONCLUSION: This pilot clinical trial is the first that uses argatroban to prevent restenosis in ischemic cerebrovascular disease, and suggests that intravenous administration of argatroban is effective and safe in preventing restenosis after extracranial artery stenting. Larger randomized controlled clinical trials are warranted.


Subject(s)
Angioplasty , Carotid Stenosis/prevention & control , Carotid Stenosis/therapy , Pipecolic Acids/therapeutic use , Stents , Vertebrobasilar Insufficiency/prevention & control , Vertebrobasilar Insufficiency/therapy , Angiography, Digital Subtraction , Antithrombins/adverse effects , Antithrombins/therapeutic use , Arginine/analogs & derivatives , Carotid Stenosis/pathology , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Male , Middle Aged , Pilot Projects , Pipecolic Acids/adverse effects , Sulfonamides , Tomography, X-Ray Computed , Treatment Outcome , Vertebrobasilar Insufficiency/pathology
19.
J Thorac Cardiovasc Surg ; 147(6): 1918-24, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24485959

ABSTRACT

OBJECTIVES: Acute kidney injury requiring renal replacement therapy (RRT) is a common complication after cardiac surgery, complicated by suspected or proven heparin-induced thrombocytopenia (type II). The present study evaluated the use of argatroban as an anticoagulant during continuous RRT in the early period after cardiac surgery. Argatroban was compared with unfractionated heparin (UH) with respect to bleeding complications and the effectiveness of anticoagulation. METHODS: Patients requiring RRT after cardiac surgery from March 2007 to June 2009 were identified. The effectiveness of anticoagulation was measured indirectly by the duration of dialysis filter use. Bleeding was defined as clinical signs of blood loss or the need for transfusion. RESULTS: Of 94 patients, 41 received argatroban, 27 UH, and 26 required conversion from UH to argatroban. In all 3 subgroups, RRT was begun within a median postoperative period of 2.0 days. Similar levels of anticoagulation were achieved with the duration of the circuit and filter changed an average of 1.1 times daily during RRT. Liver function was comparable in all patients. Neither clinically relevant signs of bleeding nor significant differences in the hemoglobin levels or a requirement for transfusion were noted. However, the Simplified Acute Physiology Score II values during dialysis and mortality were significantly greater in the patients initially receiving argatroban compared with those who received UH alone (54 ± 2 vs 43 ± 3, P < .001; 71% vs 44%, P = .04). CONCLUSIONS: Argatroban can provide effective anticoagulation in postoperative cardiac patients receiving continuous RRT. Close monitoring and dose titration resulted in a comparable risk of bleeding for anticoagulation with both argatroban and heparin, regardless of the disease severity or impaired hepatic function.


Subject(s)
Acute Kidney Injury/therapy , Anticoagulants/therapeutic use , Cardiac Surgical Procedures/adverse effects , Pipecolic Acids/therapeutic use , Renal Dialysis , APACHE , Acute Kidney Injury/blood , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/mortality , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Arginine/analogs & derivatives , Biomarkers/blood , Blood Transfusion , Critical Illness , Drug Substitution , Female , Hemoglobins/metabolism , Heparin/therapeutic use , Hospital Mortality , Humans , Male , Middle Aged , Pipecolic Acids/adverse effects , Postoperative Hemorrhage/blood , Postoperative Hemorrhage/chemically induced , Postoperative Hemorrhage/therapy , Renal Dialysis/adverse effects , Renal Dialysis/mortality , Risk Factors , Sulfonamides , Time Factors , Treatment Outcome
20.
J Neurointerv Surg ; 6(8): 630-2, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24062254

ABSTRACT

BACKGROUND: Currently, heparin is used routinely for anticoagulation during cerebral angiography and neurointerventional procedures. In patients with heparin sensitivity, however, heparin cannot be used. Therefore, an alternative method of anticoagulation is necessary to prevent clot formation during such procedures. METHODS: Argatroban, a direct thrombin inhibitor, is used as an alternate to heparin for anticoagulation. It is indicated for treatment of heparin induced thrombocytopenia as well as for prophylaxis during percutaneous coronary intervention. There are no reports describing the protocols for its use during neurointerventional procedures. We report on a series of three patients where argatroban was used in a series of three patients who underwent endovascular interventional procedures. RESULTS: Argatroban was given in a loading dosage of 4 µg/kg/min for 10 min followed by an infusion of 1.0 µg/kg/min. During the procedure, no procedural complications were reported. Activated thrombin time was used to monitor anticoagulation. CONCLUSIONS: We describe here the use of argatroban as an alternate anticoagulant during such procedures, as well as outline our protocol for its administration.


Subject(s)
Antithrombins/pharmacology , Cerebral Angiography/standards , Cerebrovascular Disorders/therapy , Endovascular Procedures/standards , Pipecolic Acids/pharmacology , Anticoagulants/adverse effects , Antithrombins/administration & dosage , Antithrombins/adverse effects , Arginine/analogs & derivatives , Cerebrovascular Disorders/diagnosis , Cerebrovascular Disorders/drug therapy , Combined Modality Therapy , Heparin/adverse effects , Humans , Pipecolic Acids/administration & dosage , Pipecolic Acids/adverse effects , Sulfonamides , Thrombocytopenia/chemically induced
SELECTION OF CITATIONS
SEARCH DETAIL
...