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Beng H. Chong - One of the best experts on this subject based on the ideXlab platform.
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heparin induced thrombocytopenia and thrombosis syndrome in vivo cross reactivity with Danaparoid and successful treatment with r hirudin
British Journal of Haematology, 2001Co-Authors: Tee Beng Keng, Beng H. ChongAbstract:Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is an immune-mediated drug reaction that occurs 5-14 d after initiation of heparin therapy and is a potentially life-threatening thrombotic complication. The antibody-heparin-PF4 complexes cause platelet activation and generation of platelet microparticles. The need for anticoagulant treatment in asymptomatic thrombocytopenia is uncertain. However, treatment is warranted in HITTS, as illustrated in the case reported here. Danaparoid, r-Hirudin and argatroban are effective drugs. Danaparoid has a 10-50% in vitro cross-reactivity rate with the HIT antibodies, but has been proven to be clinically efficacious even in these cases. Here, we report a case of in vivo cross-reactivity with Danaparoid, the patient showed an excellent recovery with r-Hirudin.
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Prospective randomised open-label comparison of Danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study.
Thrombosis and haemostasis, 2001Co-Authors: Beng H. Chong, Alexander Gallus, John Cade, Harry N. Magnani, A Manoharan, M Oldmeadow, C. Arthur, K Rickard, J Gallo, J LloydAbstract:Aim: To compare clinical outcomes in a randomised comparison of treatment with Danaparoid sodium (a heparinoid), or dextran 70, for heparin-induced thrombocytopaenia (HIT) plus thrombosis. Methods: Forty-two patients with recent thrombosis and a clinical diagnosis of probable HIT who presented at ten Australian hospitals during a study period of six and one half years were randomly assigned to open-label treatment with intravenous Danaparoid or dextran 70, each combined with oral warfarin. Thirty-four patients (83%) had a positive platelet aggregation or 14C-serotonin release test for HIT antibody. Twenty-five received Danaparoid as a bolus injection of 2400 anti-Xa units followed by 400 units per hour for 2 h, 300 units per hour for 2 h, and then 200 units per hour for five days. Seventeen received 1000 mL dextran 70 on day one and then 500 mL on days 2-5. Patients were reviewed daily for clinical evidence of thrombus progression or resolution, fresh thrombosis or embolism, bleeding or other complications. The primary trial endpoint was the proportion of thromboembolic events with complete clinical resolution by the time of discharge from hospital. Results: With Danaparoid, there was complete clinical recovery from 56% of thromboembolic events compared to 14% after dextran 70 (Odds Ratio 10.53, 95% Confidence Interval 1.6-71.4; p = 0.02). Clinical recovery with Danaparoid was complete or partial in 86% of thromboembolic events compared with 53% after dextran 70 (Odds Ratio 4.55, 95% Confidence Interval 1.2-16.7; p = 0.03). Overall clinical effectiveness of Danaparoid was rated as high or moderate in 88% of patients compared with 47% for dextran 70 (p = 0.01). One patient given Danaparoid died of thrombosis compared with three patients given dextran 70. The platelet count returned to normal after a mean of 6.7 days with Danaparoid and 7.3 days with dextran 70. There was no major bleeding with either treatment. Conclusion: Danaparoid plus warfarin treatment for HIT with thrombosis is effective, safe, and superior to dextran 70 plus warfarin.
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Heparin‐induced thrombocytopenia and thrombosis syndrome: in vivo cross‐reactivity with Danaparoid and successful treatment with r‐Hirudin
British journal of haematology, 2001Co-Authors: Tee Beng Keng, Beng H. ChongAbstract:Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is an immune-mediated drug reaction that occurs 5-14 d after initiation of heparin therapy and is a potentially life-threatening thrombotic complication. The antibody-heparin-PF4 complexes cause platelet activation and generation of platelet microparticles. The need for anticoagulant treatment in asymptomatic thrombocytopenia is uncertain. However, treatment is warranted in HITTS, as illustrated in the case reported here. Danaparoid, r-Hirudin and argatroban are effective drugs. Danaparoid has a 10-50% in vitro cross-reactivity rate with the HIT antibodies, but has been proven to be clinically efficacious even in these cases. Here, we report a case of in vivo cross-reactivity with Danaparoid, the patient showed an excellent recovery with r-Hirudin.
Bernard Tardy - One of the best experts on this subject based on the ideXlab platform.
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Effects of argatroban, Danaparoid, and fondaparinux on trombin generation in heparin-induced thrombocytopenia.
Thrombosis and haemostasis, 2013Co-Authors: Brigitte Tardy-poncet, Marion Combe, Michèle Piot, Céline Chapelle, Majid Akrour, Bernard TardyAbstract:There is no in vitro data on the comparison of the effects of Danaparoid, argatroban and fondaparinux on thrombin generation in patients with heparin-induced thrombocytopenia. It was the study objective to compare the in vitro anticoagulant potential of argatroban, Danaparoid and fondaparinux using a thrombin generation assay TGA on a mixture of control platelet-rich plasma (PRP) and HIT patient platelet-poor plasma (PPP). The plasma of seven patients with a clear HIT diagnosed at our institution was selected. Mixtures of donor PRP and patient PPP were incubated with unfractionated heparin 0.2 U.mL⁻¹, argatroban at 600 ng.mL⁻¹, argatroban at 400 ng.mL⁻¹, Danaparoid at 0.65 IU.mL⁻¹ and fondaparinux at 1 μg.mL⁻¹. Thrombin generation was assessed by calibrated thrombinography. The percentage of inhibition of the endogenous thrombin potential observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with fondaparinux (median: 53.6% vs. 3.9%; p = 0.031) but not compared with argatroban at 400 ng.mL⁻¹ and Danaparoid. The percentage of inhibition of the thrombin peak observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with Danaparoid (median: 71.2 vs. 56.8; p = 0.031) and fondaparinux (mean: 71.2 vs. 30; p = 0.031) but not with argatroban at 400 ng.mL⁻¹. In conclusion, the in vitro effect of argatroban and Danaparoid on thrombin generation seems to corroborate the results of clinical studies of these drugs in the treatment of HIT in term of efficiency. Fondaparinux showed a very small effect on thrombin generation evaluated by calibrated thrombinography.
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Risk factors for unfavorable clinical outcome in patients with documented heparin-induced thrombocytopenia.
Thrombosis Research, 2009Co-Authors: Ismail Elalamy, Brigitte Tardy-poncet, Agnès Mulot, Emmanuel De Maistre, Claire Pouplard, Philippe Nguyen, Bénédicte Cleret, Yves Gruel, Thomas Lecompte, Bernard TardyAbstract:BACKGROUND: Prognostic factors for unfavorable clinical outcome in patients with heparin-induced thrombocytopenia (HIT) are largely unknown. DESIGN AND METHODS: In this multicenter, retrospective, case-control study, all HIT patients were treated with Danaparoid. Study cases were HIT patients with an unfavorable clinical outcome. Controls were HIT patients who were not study cases. Unfavorable clinical outcome was defined as the occurrence of at least one of the following clinical events: death within 60 days after HIT start date, or venous or arterial thromboembolism, amputation, major bleeding, or disseminated intra-vascular coagulation between 48 hours and 60 days after HIT start date. RESULTS: Compared with controls (n=65), thrombotic episodes within 48 hours of HIT start date were more frequent (59.2% versus 32.3%; p=0.004), the median time between HIT start date and initiation of Danaparoid infusion was longer (3.0 versus 1.0 days; p=0.001), and this treatment was more frequently underdosed (43.8% versus 18.8%; p=0.004) in study cases (n=49). Upon multivariate analysis, all these three parameters were significant predictive factors for unfavorable clinical outcome. The adjusted odds ratios [95% confidence interval] were 6.6 [2.5-17.3] for time between HIT start date and Danaparoid initiation over 48 hours, 4.3 [1.5-12.0] for Danaparoid underdosing, and 3.2 [1.3-8.0] for presence of a thromboembolic episode at HIT start date. CONCLUSIONS: This study supports the recommendations concerning the management of HIT patients, namely discontinuation of all heparin administration once the diagnosis is suspected and prompt initiation of an alternative anticoagulant drug with a strict adherence to doses specifically recommended for these patients.
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Danaparoid cross-reactivity with heparin-induced thrombocytopenia antibodies: report of 12 cases.
Intensive care medicine, 2009Co-Authors: Brigitte Tardy-poncet, Ismail Elalamy, M. Wolf, D. Lasne, A. Bauters, P. Ffrench, Bernard TardyAbstract:Purpose Danaparoid is a safe and effective drug for the treatment of heparin-induced thrombocytopenia (HIT). We describe an uncommon complication: Danaparoid cross-reactivity with HIT antibodies.
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Efficacy and safety of Danaparoid sodium (ORG 10172) in critically ill patients with heparin-associated thrombocytopenia
Chest, 1999Co-Authors: Brigitte Tardy-poncet, Bernard Tardy, Jacqueline Reynaud, Philippe Mahul, Patrick Mismetti, Eliane Mazet, Denis GuyotatAbstract:Objective To evaluate the effectiveness and the safety of Danaparoid sodium in the treatment of critically ill patients with standard unfractionated heparin-induced thrombocytopenia (HIT) or low-molecular-weight HIT. Setting University hospital. Patients and methods Retrospective analysis of 42 consecutive critically ill patients who were admitted for HIT between October 1992 and February 1997 and were treated either with therapeutic or prophylactic doses of Danaparoid sodium. Results Among the 26 patients treated with therapeutic doses, neither new thrombotic complications nor thrombosis extension was clinically suspected. Two deaths were directly related to lower limb acute arterial thrombosis associated with HIT. Two major hemorrhagic complications were observed when aspirin in addition to Danaparoid sodium was administered. When Danaparoid sodium was used in prophylactic doses (20 courses of treatment) to prevent either postsurgical or medical thrombotic complications, no thrombotic event was observed. No death related to HIT or Danaparoid sodium treatment was observed. One aggravation of a postsurgical cerebral lesion was observed. During Danaparoid sodium treatment, a persistence or a recurrence of thrombocytopenia was observed in 6.5% of patients without thrombotic complications. Conclusion Danaparoid sodium appears to be an efficient and safe treatment in critically ill patients with HIT. The concomitant use of aspirin in addition to Danaparoid sodium seems to represent an important additional hemorrhagic risk that should be avoided in patient management.
H.n. Magnani - One of the best experts on this subject based on the ideXlab platform.
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A review of 122 published outcomes of Danaparoid anticoagulation for intermittent haemodialysis.
Thrombosis research, 2009Co-Authors: H.n. MagnaniAbstract:Abstract One hundred and twenty-two case reports of treatment outcomes of Danaparoid use for intermittent haemodialysis (HD) in severely ill patients with heparin intolerance (including 97 HIT patients) have been analysed. HD sessions of 4 – 6 hours were successfully conducted daily to 3 times/week for periods of up to 4 years (median 7 sessions/patient (range 1 - > 650). In these patients Danaparoid use was relatively safe (4 unprovoked non-fatal major bleeds) and efficacious in protecting the circuit (95% no clotting problem) or patient (6 thromboses: 4 fatal or leading to Danaparoid discontinuation). HIT diagnosis was improved if recurrent platelet count reduction with each HD and circuit/AV graft clotting were included. Alternative reasons for and very low nadirs of the platelet count undermined the usefulness of the 4T pre-test HIT predictability scores, but a positive functional serological test confirmed HIT in most patients. Deaths (15.6%) and thrombosis only occurred in HIT cases. Possible reasons are discussed. Replacing the standard intermittent pre-HD dose regimen with the therapeutic infusion regimen to provide continuous daily systemic antithrombotic protection, should further improve efficacy. Conclusion Danaparoid appears to be a useful alternative antithrombotic for patients with heparin intolerance and renal failure requiring haemodialysis.
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An analysis of clinical outcomes of 91 pregnancies in 83 women treated with Danaparoid (Orgaran).
Thrombosis research, 2009Co-Authors: H.n. MagnaniAbstract:Abstract 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 caesarian deaths (a failed post-operative resuscitation and a major bleed in a patient refusing transfusion), 3 non-fatal major bleeds (associated with caesarian 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.
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Danaparoid in der Schwangerschaft bei Heparinunverträglichkeit - Einsatz in 59 Fällen
Hamostaseologie, 2007Co-Authors: Marc Schindewolf, H.n. Magnani, Edelgard Lindhoff-lastAbstract:Unter Therapie mit unfraktioniertem oder niedermolekularem Heparin treten haufig unerwunschte Arzneimittelwirkungen auf, die eine Fortsetzung der Therapie unmoglich machen. Insbesondere bei Schwangeren mit thromboembolischen Komplikationen kann es schwierig sein, ein geeignetes alternatives Antikoagulans zu finden, wenn zusatzlich eine Heparinunvertraglichkeit vorliegt. Fur den Einsatz von Danaparoid in der Schwangerschaft gibt es nur wenige Daten. Die Hauptgrunde in den untersuchten 59 Schwangerschaften fur eine Heparinunvertraglichkeit waren entweder eine HIT II bei 37/59 (62,7%) Schwangeren, oder eine kutane Nebenwirkung in 19/22 (86,4%) der nicht HIT-assoziierten Schwangerschaften (22/59, 37,3%). Ergebnisse: 40/59 Schwangerschaften konnten unter Danaparoid erfolgreich ausgetragen werden, bei 16/19 wurde die Therapie aufgrund unerwunschter Arzneimittelwirkungen beendet. Funf Patientinnen zeigten Blutungskomplikationen, die ebenso wenig Danaparoid-assoziiert waren wie die berichteten sechs Aborte und eine Abruptio. In 31/59 (52,5%) Schwangerschaften traten unerwunschte Arzneimittelwirkungen auf, 14/31 (45,2%) liesen sich auf Danaparoid zuruckfuhren. In funf Nabelschnurblut- und vier Brustmilchproben konnte keine Anti- Xa-Aktivitat gemessen werden. Schlussfolgerung: Danaparoid kann zur alternativen Antikoagulation bei Schwangeren mit hohem Thromboserisiko und Heparinunvertraglichkeit eingesetzt werden.
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Heparin-induced thrombocytopenia (HIT): A report of 1,478 clinical outcomes of patients treated with Danaparoid (Orgaran) from 1982 to mid-2004
Thrombosis and haemostasis, 2006Co-Authors: H.n. Magnani, Alexander GallusAbstract:Clinical outcomes of 1,478 Danaparoid treatment case reports for HIT (involving 1,418 patients) treated between 1982 and mid-2004 are analysed.Treatment in 1,291 episodes was for current HIT.Thromboembolism due to HIT was present in 39.4%. The patients include 33 children and 32 pregnancies. Two hundred twenty-six patients required extra-corporeal circuit use for renal failure, 241 patients had a concomitant thrombophilic disorder,and 351 major operations were performed.Clinical outcomes were assessed during Danaparoid treatment (range one day to 3.5 years) plus three months of follow-up. Of the Danaparoid-treated patients 83.8% survived; 63.7% had no or minor adverse events and 20.1% suffered serious non-fatal adverse events.New thromboses occurred during 9.7% of treatment episodes, and 16.4% of treatment episodes had an inadequate treatment response (i.e. developed one or more of the following: new/extended thrombosis, persistent/new platelet count reduction, unplanned amputation during treatment and follow-up). Major bleeding was reported in 8.1% of treatment episodes. Clinical cross-reactivity of Danaparoid (new/persistent platelet count reduction and/or new/extended thrombosis) was confirmed serologically in 23 of 36 patients with positive pretreatment serological Danaparoid cross-reactivity and in 22 of 32 additional patients tested at the time of the new event,i.e.a total of 45 patients (3.2%). Clinical outcomes of these case reports of patients given Danaparoid because of suspected or confirmed HIT appear to be comparable with those reported by others who used direct thrombin inhibitors, especially when a sufficient Danaparoid dosing intensity was used in patients with isolated HIT.Post-operative bleeding limits Danaparoid use for cardiopulmonary by-pass surgery. Routine clinical and platelet count monitoring are required to minimise adverse reactions due to cross-reactivity.
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Heparin-induced thrombocytopenia in paediatric patients--a review of the literature and a new case treated with Danaparoid sodium.
European Journal of Pediatrics, 1999Co-Authors: Oliver Ranze, H.n. Magnani, Petra Ranze, Andreas GreinacherAbstract:The immunological form of heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse reaction of heparin medication. It is mediated by multimolecular complexes consisting of platelet factor 4 (PF4)-heparin-IgG which bind to platelets via platelet Fcγ receptors. Cross-linking of multiple Fcγ receptors results in platelet activation, platelet aggregation and enhanced thrombin generation with a increasing risk of developing new thrombosis. In children, data on HIT are sparse. This review of the literature reports on 8 children aged 3 months to 15 years and 14 newborns suffering from HIT. Additionally, we report one new case treated with Danaparoid sodium. Thrombotic complications were venous (n = 12) and arterial (n = 15). The children received heparin either for a spontaneous thrombotic event, for severe cardiac diseases or to maintain patency of intravascular catheters which are used for nutrition, blood sampling, and for application of medication. After diagnosis of HIT they were further anticoagulated with aspirin, warfarin, Danaparoid sodium, lepirudin or low molecular weight heparin.
Brigitte Tardy-poncet - One of the best experts on this subject based on the ideXlab platform.
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Effects of argatroban, Danaparoid, and fondaparinux on trombin generation in heparin-induced thrombocytopenia.
Thrombosis and haemostasis, 2013Co-Authors: Brigitte Tardy-poncet, Marion Combe, Michèle Piot, Céline Chapelle, Majid Akrour, Bernard TardyAbstract:There is no in vitro data on the comparison of the effects of Danaparoid, argatroban and fondaparinux on thrombin generation in patients with heparin-induced thrombocytopenia. It was the study objective to compare the in vitro anticoagulant potential of argatroban, Danaparoid and fondaparinux using a thrombin generation assay TGA on a mixture of control platelet-rich plasma (PRP) and HIT patient platelet-poor plasma (PPP). The plasma of seven patients with a clear HIT diagnosed at our institution was selected. Mixtures of donor PRP and patient PPP were incubated with unfractionated heparin 0.2 U.mL⁻¹, argatroban at 600 ng.mL⁻¹, argatroban at 400 ng.mL⁻¹, Danaparoid at 0.65 IU.mL⁻¹ and fondaparinux at 1 μg.mL⁻¹. Thrombin generation was assessed by calibrated thrombinography. The percentage of inhibition of the endogenous thrombin potential observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with fondaparinux (median: 53.6% vs. 3.9%; p = 0.031) but not compared with argatroban at 400 ng.mL⁻¹ and Danaparoid. The percentage of inhibition of the thrombin peak observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with Danaparoid (median: 71.2 vs. 56.8; p = 0.031) and fondaparinux (mean: 71.2 vs. 30; p = 0.031) but not with argatroban at 400 ng.mL⁻¹. In conclusion, the in vitro effect of argatroban and Danaparoid on thrombin generation seems to corroborate the results of clinical studies of these drugs in the treatment of HIT in term of efficiency. Fondaparinux showed a very small effect on thrombin generation evaluated by calibrated thrombinography.
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Risk factors for unfavorable clinical outcome in patients with documented heparin-induced thrombocytopenia.
Thrombosis Research, 2009Co-Authors: Ismail Elalamy, Brigitte Tardy-poncet, Agnès Mulot, Emmanuel De Maistre, Claire Pouplard, Philippe Nguyen, Bénédicte Cleret, Yves Gruel, Thomas Lecompte, Bernard TardyAbstract:BACKGROUND: Prognostic factors for unfavorable clinical outcome in patients with heparin-induced thrombocytopenia (HIT) are largely unknown. DESIGN AND METHODS: In this multicenter, retrospective, case-control study, all HIT patients were treated with Danaparoid. Study cases were HIT patients with an unfavorable clinical outcome. Controls were HIT patients who were not study cases. Unfavorable clinical outcome was defined as the occurrence of at least one of the following clinical events: death within 60 days after HIT start date, or venous or arterial thromboembolism, amputation, major bleeding, or disseminated intra-vascular coagulation between 48 hours and 60 days after HIT start date. RESULTS: Compared with controls (n=65), thrombotic episodes within 48 hours of HIT start date were more frequent (59.2% versus 32.3%; p=0.004), the median time between HIT start date and initiation of Danaparoid infusion was longer (3.0 versus 1.0 days; p=0.001), and this treatment was more frequently underdosed (43.8% versus 18.8%; p=0.004) in study cases (n=49). Upon multivariate analysis, all these three parameters were significant predictive factors for unfavorable clinical outcome. The adjusted odds ratios [95% confidence interval] were 6.6 [2.5-17.3] for time between HIT start date and Danaparoid initiation over 48 hours, 4.3 [1.5-12.0] for Danaparoid underdosing, and 3.2 [1.3-8.0] for presence of a thromboembolic episode at HIT start date. CONCLUSIONS: This study supports the recommendations concerning the management of HIT patients, namely discontinuation of all heparin administration once the diagnosis is suspected and prompt initiation of an alternative anticoagulant drug with a strict adherence to doses specifically recommended for these patients.
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Danaparoid cross-reactivity with heparin-induced thrombocytopenia antibodies: report of 12 cases.
Intensive Care Med, 2009Co-Authors: Brigitte Tardy-poncet, Ismail Elalamy, M. Wolf, D. Lasne, A. Bauters, P. Ffrench, B. TardyAbstract:PURPOSE: Danaparoid is a safe and effective drug for the treatment of heparin-induced thrombocytopenia (HIT). We describe an uncommon complication: Danaparoid cross-reactivity with HIT antibodies. DESIGN AND SETTING: A retrospective observational multicenter study on HIT was conducted in France. In this study concerning HIT patients treated with lepirudin, 12 patients were treated with lepirudin because Danaparoid cross-reacted with the heparin-dependent antibodies. RESULTS: Three groups of situations can be separated. In a first group, four patients received a short course of Danaparoid until their initial functional HIT assay showed a cross-reactivity between Danaparoid and HIT antibodies. One patient presented a fatal thrombotic complication but the relationship between this thrombotic complication and Danaparoid cross-reactivity cannot be certain. In a second group, four patients received for 4 days at least a Danaparoid treatment while the initial functional test did not show any Danaparoid cross-reactivity. During Danaparoid treatment, no significant increase of platelet count was observed and two patients presented a fatal thrombotic complication. In a third group, cross-reactivity between Danaparoid and HIT antibodies was not checked before Danaparoid therapy. During Danaparoid treatment, no significant increase of platelet count was observed and the four patients developed a venous thromboembolic complication. CONCLUSION: Absence of any increase in platelet count after 3 to 5 days of Danaparoid therapy and/or the occurrence of a new thrombotic event should lead to Danaparoid cross-reactivity suspicion. However, before attributing thrombotic complications to Danaparoid cross-reactivity, it is crucial to verify that the patients received the recommended Danaparoid dosage regimen.
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Danaparoid cross-reactivity with heparin-induced thrombocytopenia antibodies: report of 12 cases.
Intensive care medicine, 2009Co-Authors: Brigitte Tardy-poncet, Ismail Elalamy, M. Wolf, D. Lasne, A. Bauters, P. Ffrench, Bernard TardyAbstract:Purpose Danaparoid is a safe and effective drug for the treatment of heparin-induced thrombocytopenia (HIT). We describe an uncommon complication: Danaparoid cross-reactivity with HIT antibodies.
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Predictive Factors for Poor Outcome in Danaparoid-Treated HIT-Patients: A French Multicentre Case-Control Study.
Blood, 2008Co-Authors: Ismail Elalamy, Brigitte Tardy-poncet, Agnès Mulot, Claire Pouplard, Philippe Nguyen, Bénédicte Cleret, E. Demaistre, M. Trossaert, Y. Blanloeil, Yves GruelAbstract:Objective: to identify predictive factors of complications and mortality in Danaparoid-treated HIT-patients. Patients and Methods: case-control study involving HIT-patients defined by a relative decrease in platelet count of over 40% with or without thrombosis at presentation and positive laboratory testing (functional assay +/− ELISA). A patient presenting a complication 48 hours after heparin replacement with Danaparoid (thrombosis, DIC, amputation, haemorrhage, death) was considered as a case. Results: 49 cases and 65 controls were included (mean age 67±14 y; 51% women), from cardiovascular (53%) or orthopaedic (5%) surgery, intensive care (6%) or medicine (8%) units. Mean duration to complication was 7 days (D): death (n=26); thromboses (n=23); DIC (n=6); amputations (n=4); and haemorrhages (n=8). In univaried analysis, compared to controls, cases presented: an earlier HIT (7.9±3.5 versus 10.1±7.1 D; p=0.03) a lower platelet nadir (53±37 versus 70±37 G/L ; p=0.01), a more frequent thrombosis at HIT diagnosis (59% versus 32%, p=0.004), a later heparin withdrawal after HIT diagnosis (2.8 versus 1.3 d; p=0.01), a delayed heparin replacement (3.7 versus 1.9 d ; (p=0.001), an inadequate dosage of replacement therapy (44% versus 19% ; p=0.004). In multivaried analysis, predictive factors leading for poor outcome were: an initial thrombosis at HIT diagnosis (OR=3.2 [1.3–8]), a delay greater than 48 h for replacement therapy with Danaparoid (OR=6.6 [2.5–17.3]), insufficient doses of Danaparoid (OR=4.3 [1.5–12]). Conclusion: this study confirms the mandatory need for a prompt replacement therapy and strict adherence to recommended doses for HIT-patients.
M J Kovacs - One of the best experts on this subject based on the ideXlab platform.
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Fondaparinux Versus Argatroban and Danaparoid for the Treatment of Suspected or Confirmed Heparin-Induced Thrombocytopenia: A Propensity Score Analysis.
Blood, 2012Co-Authors: Matthew Kang, M J Kovacs, Majed Alahmadi, Sonja Sawh, Alejandro Lazo-langnerAbstract:Abstract 2262 Background: Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy leading to platelet activation, thrombocytopenia and potentially thrombosis. Upon suspicion, current guidelines recommend heparin cessation and switching to a non-heparin anticoagulant such as argatroban or Danaparoid. Fondaparinux could be potentially effective but information supporting its use is limited. Methods: We retrospectively evaluated 239 patients admitted to London Health Sciences Centre from January 10, 2004 to June 21, 2011 receiving a non-heparin anticoagulant (133 fondaparinux, 59 Danaparoid, 47 argatroban) for suspected or confirmed HIT. Using logistic regression a propensity score was constructed based on age, gender, creatinine, 4T scores and comorbidities (assessed by the Charlson comorbidity index modified by Quan) and used to match 133 patients to 60 controls. Efficacy outcome was thrombosis or thrombosis-related death. Safety outcome was major bleeding. Group comparisons were done using χ2, Fisher9s exact or Mann-Whitney tests. Survival analysis was conducted using the Kaplan-Meier method. Analyses were conducted in SPSS 20.0 and R 2.12. Results: Population characteristics are shown in Table 1. Well-balanced groups were obtained after matching. There were no differences in the proportion of thrombotic or bleeding events between control and fondaparinux groups (Table 2). Subgroup analyses comparing fondaparinux versus argatroban or Danaparoid and unmatched analyses showed similar results. Sensitivity analysis stratified by propensity score quintiles showed no differences in either outcome. Survival analysis showed no differences in thrombosis or bleeding (Log-rank p = 0.415 and 0.779, respectively; Figure 1). Subgroup survival analysis for the 3 drugs independently found no difference in thrombotic events (Log-rank p=0.582) and a trend towards increased major bleeding in patients on argatroban (Log-rank p=0.068). In the fondaparinux group 60% of patients received prophylactic doses. Conclusion: Fondaparinux has similar effectiveness and safety as argatroban and Danaparoid in patients with suspected HIT. Prophylactic fondaparinux doses seem to be effective if no indication for full anticoagulation exists. Disclosures: Off Label Use: Fondaparinux as a treatment option in heparin-induced thrombocytopenia. Lazo-Langner:Pfizer: Honoraria; LeoPharma: Honoraria.
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Successful use of Danaparoid in treatment of heparin-induced thrombocytopenia during twin pregnancy.
Obstetrics and gynecology, 1997Co-Authors: J Gill, M J KovacsAbstract:The treatment of heparin-induced thrombocytopenia in pregnancy is uncertain. Warfarin is contraindicated and ancrod is of unknown safety. Low-molecular-weight heparin should not be used because of cross-reactivity with unfractionated heparin. We report a case of heparin-induced thrombocytopenia during pregnancy treated successfully with Danaparoid. A 25-year-old woman pregnant with twins developed heparin-induced thrombocytopenia after starting heparin therapy for a deep vein thrombosis. Treatment was initiated with Danaparoid by subcutaneous injection and was continued until the time of delivery. Treatment was completed with 6 weeks of warfarin therapy postpartum. No fetal or maternal ill effects were observed. Danaparoid, which has low cross-reactivity for heparin-dependent antibodies and no known fetopathic effects, was used successfully to treat our patient, who developed heparin-induced thrombocytopenia during pregnancy. Danaparoid may be the treatment of choice for this difficult clinical situation in which there are limited therapeutic options.
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Successful use of Danaparoid in treatment of heparin-induced thrombocytopenia during twin pregnancy.
Obstetrics & Gynecology, 1997Co-Authors: J Gill, M J KovacsAbstract:Background The treatment of heparin-induced thrombocytopenia in pregnancy is uncertain. Warfarin is contraindicated and ancrod is of unknown safety. Low-molecular-weight heparin should not be used because of crossreactivity with unfractionated heparin. We report a case of heparin-induced thrombocytopenia during pregnancy treated successfully with Danaparoid. Case A 25-year-old woman pregnant with twins developed heparin-induced thrombocytopenia after starting heparin therapy for a deep vein thrombosis. Treatment was initiated with Danaparoid by subcutaneous injection and was continued until the time of delivery. Treatment was completed with 6 weeks of warfarin therapy postpartum. No fetal or maternal ill effects were observed. Conclusion Danaparoid, which has low cross-reactivity for heparin-dependent antibodies and no known fetopathic effects, was used successfully to treat our patient, who developed heparin-induced thrombocytopenia during pregnancy. Danaparoid may be the treatment of choice for this difficult clinical situation in which there are limited therapeutic options.
