scholarly journals Comparison of Low Molecular Weight Heparin Activity Assays with and without Addition of Exogenous Antithrombin in a Pediatric and Young Adult Leukemia Cohort

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4915-4915
Author(s):  
Beverly Schaefer ◽  
Adriane Hausfeld ◽  
Paul Steele ◽  
Jan Martin ◽  
Sandra Brannon ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Research Funding ◽  
Low Molecular Weight Heparin ◽  
Lymphoblastic Leukemia ◽  
Clinical Care ◽  
Low Molecular Weight ◽  
Plasma Samples ◽  
History Of ◽  
Heparin Activity ◽  
Adult Leukemia

Introduction: Enoxaparin (low molecular weight heparin, LMWH) is the most commonly prescribed anticoagulant for pediatric patients with venous thromboembolism (VTE) (Goldenberg et al. 2015). The gold-standard LMWH activity (anti-Xa activity) assays differ in whether they add exogenous antithrombin (AT) or dextran sulfate (Ignjatovic et al. 2007). Adding AT would "standardize" results in patients with low antithrombin, such as infants and asparaginase-treated patients (Mitchell et al 2010); however, questions remain about which assay best reflects the patient's anticoagulation effect and the degree of discrepancy between assays. We assessed LMWH activity in residual plasma samples from a cohort of anticoagulated pediatric acute lymphoblastic leukemia and lymphoma (ALL) patients, with history of VTE and variable AT levels, on four platforms (two instruments and their kits +/- exogenous AT). Methods: We analyzed 60 de-identified residual plasma samples from 12 anticoagulated ALL patients (2-19 years. Mean 13.75 yr) who had AT levels obtained for clinical care. All consented to the IRB-approved Oncology Tissue Repository. LMWH activity was assessed on Siemens and Stago instruments using their recommended kits that did or did not contain exogenous AT (Table 1), according to manufacturer recommendations, by experienced laboratorians. Results: Results were interpretable on 236/240 with 4 rejected for lipemia. Mean AT activity was 80 (42-138 ng/ml, lab normal >81%). Correlation was acceptable for the published kit ranges of LMWH activity when comparing kits +AT (Berichrom® to Stachrom®, r=0.82, p<0.0001), -AT (Innovance® to STA®-Liquid Anti-Xa: r=0.93, p<0.0001), and within the same manufacturer (Berichrom® to Innovance®, r=0.92, p<0.0001, Stachrom® to STA®-Liquid Anti-Xa r=0.98, p<0.0001) (Table 2, Figure 1, Figure 2). Comparing +AT or not by manufacturer, there was a nonsignificant trend to higher LMWH activity result with +AT kits. When AT levels were <70 ng/ml (n=19, mean 56 ng/dl) there was a trend to underestimate LMWH activity when AT was not added; this reached significance when the Stago methods were compared (Table 2.) Conclusions: There is acceptable correlation of LMWH activity using kits with or without exogenous AT in anticoagulated pediatric plasma samples; however, in low AT samples, LMWH activity trends lower in platforms without exogenous AT. Use of residual samples precluded conclusions about the clinical impact of this difference; however, there were a few instances where subtherapeutic activity in the -AT assay was in the therapeutic range (0.5-1 activity units) in the +AT assay. Clinicians should know whether exogenous AT is used in their own laboratory's assay and understand that added AT could overestimate the LMWH effect in patients with low AT levels. Disclosures Schaefer: Stago: Research Funding; Siemens: Research Funding.

Venous Thromboembolism Prophylaxis with Low-Molecular-Weight Heparin in Primary Central Nervous System Lymphoma

2020 ◽  
pp. 1-6
Author(s):  
Stav Gazal ◽  
Eyal Lebel ◽  
Yosef Kalish ◽  
Chen Makranz ◽  
Moshe E. Gatt ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Central Nervous System ◽  
Nervous System ◽  
Venous Thromboembolism ◽  
Low Molecular Weight Heparin ◽  
Bleeding Event ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Low Molecular Weight ◽  
History Of

<b><i>Background:</i></b> Venous thromboembolism (VTE) is a frequent, potentially lethal complication in individuals with cancer. Patients with brain tumors are at particularly high risk for VTE. Primary central nervous system lymphoma (PCNSL) is a rare subtype of diffuse large B cell lymphoma, involving the craniospinal axis. The incidence of VTE in patients with PCNSL was reported as very high, occurring mostly in the early period of therapy. <b><i>Objectives:</i></b> We aimed to evaluate the efficacy and safety of prophylactic low-molecular-weight heparin (LMWH) throughout the treatment of PCNSL. <b><i>Patients:</i></b> All patients &#x3e;18 years of age diagnosed and treated for PCNSL at our institution in 2005–2017 were included. <b><i>Results:</i></b> There were 44 patients; mean age at diagnosis was 61.5 years. Three patients (6.8%) had a personal history of thrombosis, 11 (25%) had a history of diabetes or smoking, and 32 (72%) had an Eastern Cooperative Oncology Group performance status of 0–1 at diagnosis. During treatment with LMWH, no VTE events were recorded; 2 (4.5%) patients experienced a minor bleeding event and 1 (2.3%) a major bleeding event. <b><i>Conclusions:</i></b> Among our 44 patients with PCNSL treated with prophylactic LMWH, no VTE events were recorded, and only 1 (asymptomatic) intracranial bleed was recorded. Within the limitations of a retrospective nonrandomized study, our findings suggest that VTE prophylaxis may be beneficial for individuals with PCNSL.

In Vivo Studies On The Inhibition Of Coagulation By Fractionated Heparin

1981 ◽  
Author(s):  
U Schmitz-Huebner ◽  
L Balleisen ◽  
F Asbeck ◽  
J van de Loo
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Gel Filtration ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Chromogenic Substrate ◽  
Serotonin Content ◽  
Heparin Activity ◽  
Heparin Fractions

Recent investigations suggest that low molecular weight heparin may have advantages over conventional heparin with regard to the prevention of venous thrombosis and haemorrhagic side effects.High (HMW) and low (LMW) molecular weight heparin fractions with mean MWs of 16,000 and 8,800 respectively, obtained by gel filtration chromatography of sodium mucosal heparin (B. Braun Melsungen), were injected subcutaneously into six volunteers and compared with the unfractionated substance in a cross-over trial. Doses of 5,000 U were administered twice daily over a period of three days and heparin activity was controlled before injection and 2,4,8 hours afterwards by means of the APTT, the anti-Xa clotting test and a chromogenic substrate assay. In addition, the in vivo effect of fractionated heparin on platelet function was examined. The results show that the LMW fraction induced markedly higher anti-Xa activity than the other preparations. At the same time, APTT results did not significantly differ. Unfractionated heparin and the HMW fraction enhanced ADP-induced platelet aggregation and collagen-mediated MDA-production, while the LMW fraction hardly affected these assays, but potently inhibited thrombin-induced MDA production. All heparin preparations stimulated the release of PF IV, whereas the serotonin content of platelets determined at the same time increased.It is concluded that s.c. injections of LMW heparin induce relatively high levels of anti-Xa activity without leading to sensitive platelet activation or to major effects on overall clotting tests.

Spontaneous spinal subdural hematoma associated with low-molecular-weight heparin

2005 ◽  
Vol 2 (5) ◽  
pp. 612-613 ◽  
Author(s):  
Yoon-Hee Cha ◽  
John H. Chi ◽  
Nicholas M. Barbaro
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Spinal Instrumentation ◽  
Cord Compression ◽  
Low Molecular Weight ◽  
Content Type ◽  
First Case ◽  
Spinal Subdural Hematoma ◽  
History Of ◽  
Fine Print

✓ Spinal subdural hematomas (SDHs) are a rare cause of cord compression and typically occur in the setting of spinal instrumentation or coagulopathy. The authors report the first case of a spontaneous spinal SDH occurring in conjunction with low-molecular-weight heparin use in a patient with a history of spinal radiotherapy.

Differential inhibition of thrombin generation by vitamin K antagonists alone and associated with low-molecular-weight heparin

2009 ◽  
Vol 102 (07) ◽  
pp. 42-48 ◽  
Author(s):  
Grigoris T. Gerotziafas ◽  
Charlotte Dupont ◽  
Alex C. Spyropoulos ◽  
Mohamed Hatmi ◽  
Meyer M. Samama ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Vitamin K ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Vitamin K Antagonists ◽  
Low Molecular Weight ◽  
Plasma Samples ◽  
Thrombin Generation Assay ◽  
International Normalised Ratio ◽  
Inhibition Of Thrombin

SummaryVitamin K antagonists (VKA) treatment starts with co-administration of low-molecular-weight heparin (LMWH). The anticoagulation induced by the two drugs is still not well determined. In the present study we used thrombin generation assay to evaluate the hypo-coagulation induced by treatment with VKA and by the combination of VKA with LMWH. Tissue factor triggered thrombin generation in platelet-poor plasma was assessed in samples from 15 healthy volunteers, 97 samples from patients treated with VKA and 41 samples from patients receiving enoxaparin and VKA. Patients were classified according to international normalised ratio (INR) level (<2, 2–3 and >3).In plasma samples from patients treated with VKA having INR 2–3 the inhibition of thrombin generation reached 50% compared to controls. In samples with INR>3 this inhibition was 80%. In samples from patients receiving both LMWH and VKA, thrombin generation was significantly decreased compared to the controls and VKA group. In samples with an INR 2–3 obtained from patients treated with LMWH and VKA, the inhibition of thrombin generation was similar to that observed in samples with an INR>3 obtained from VKA treated patients. Thrombin generation assay is sensitive to detect the global the anticoagulant effect produced by the association of LMWH and VKA. For equal INR dual anticoagulant treatment induces significantly more profound inhibition of thrombin generation compared to treatment with VKA alone. The clinical relevance of this observation merits to be studied in prospective studies in patients with defined indications of anticoagulant therapy.

Low Molecular Weight Heparin to Achieve Live Birth Following Unexplained Pregnancy Loss: A Meta-Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 489-489
Author(s):  
Simon Mantha ◽  
Kenneth A. Bauer ◽  
Jeffrey I Zwicker
Keyword(s):  
Molecular Weight ◽  
Board Of Directors ◽  
Low Molecular Weight Heparin ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Meta Analysis ◽  
Fetal Loss ◽  
Low Molecular Weight ◽  
Advisory Committees ◽  
History Of

Abstract 489 The management of recurrent pregnancy loss is uncertain. Some cohort studies have identified an association between inherited thrombophilias and recurrent or late-nonrecurrent pregnancy loss which has prompted investigators to evaluate the benefit of low molecular weight heparin to achieve live birth. A similar benefit for low molecular weight heparin has also been proposed independent of thrombophilia status. A recent Cochrane Review on this topic included the results of a single randomized trial in their analysis. As there are several recent randomized trials using low molecular weight heparin in women with recurrent pregnancy loss published in the obstetrical literature, we performed a meta-analysis to evaluate the benefit of low molecular weight heparin in women who experienced unexplained recurrent or late-nonrecurrent pregnancy loss. Methods: We conducted a meta-analysis of randomized controlled trials investigating the benefit of low molecular weight heparin versus a non-anticoagulant control arm in women with a history of ≥2 early pregnancy losses or ≥1 late pregnancy loss; we excluded women with antiphospholipid antibodies and those with an underlying cause of recurrent fetal loss, except for the hereditary thrombophilias. We planned to use random-effects analysis as the primary summary model due to the anticipated variations in enrollment criteria and interventions between the studies. Results: A total of 757 women were enrolled in five studies that satisfied the eligibility criteria. Using the random effects model, the risk ratio of fetal loss for low molecular weight heparin versus control was 0.49 (0.25-0.97 95% CI, P=0.04). There was significant heterogeneity observed between studies (Q-value was 15.59, P=0.004, and I2=74.33%). A priori, we identified the presence or absence of a hereditary thrombophilia as a potential source of heterogeneity. However, subgroup analysis of the studies according to the inclusion or exclusion of women with hereditary thrombophilia did not resolve the observed heterogeneity between studies. Exclusion of the only trial that enrolled women following a non-recurrent pregnancy loss improved the observed heterogeneity but diminished the apparent benefit of low molecular weight heparin (0.63, 95% CI 0.34-1.16, P=0.14). In this trial, the observed birth rate in the control arm was significantly lower than in the other two trials included in this meta-analysis with aspirin-only controls (29% versus 84% or 87% in aspirin-only arms, P<0.001). Conclusion: There is a trend for increased live births when using low molecular weight heparin for the prevention of recurrent pregnancy loss. However, considering the observed heterogeneity across studies, there is insufficient evidence to support the routine use of low molecular weight heparin to improve pregnancy outcomes in women with a history of pregnancy loss. Disclosures: Off Label Use: low molecular weight heparin to prevent pregnancy loss. Bauer:Bayer Healthcare: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Speakers Bureau; GTC Biotherapeutics: Membership on an entity's Board of Directors or advisory committees. Zwicker:Sanofi-Aventis: Research Funding.

Treatment of antiphospholipid syndrome in pregnancy

Lupus ◽  
1998 ◽  
Vol 7 (2_suppl) ◽  
pp. 95-97 ◽  
Author(s):  
S Cowchock
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Term Treatment ◽  
Medical Complication ◽  
Low Molecular Weight ◽  
Appropriate Treatment ◽  
Long Term Treatment ◽  
History Of ◽  
Early Onset Preeclampsia ◽  
Prophylactic Anticoagulation

Women with antiphospholipid antibodies (aPL = IgG anticardiolipin and/or lupus anticoagulants) and a history of either prior thrombotic events or pregnancy loss are at high risk during pregnancy for either another fetal death or thrombosis. The treatment of choice is anticoagulation with heparin. Both standard unfractionated heparin and low-molecular-weight heparin are used for prophylactic anticoagulation during pregnancy. The half-lives of either standard heparin, or low-molecular-weight heparin, and the peak values for each after subcutaneous injection, are lower than those in nonpregnant patients. Doses and injection intervals need to be adjusted when treating a pregnant woman. Clotting tests such as the activated partial thromboplastin time (aPTT) vary greatly during pregnancy, and the aPTT is often not even prolonged when antithrombotic levels of heparin are achieved. The aPTT is not a useful test when the patient has a lupus anticoagulant. Levels of plasma heparin are therefore needed to best care for pregnant women who need anticoagulation—even for prophylaxis. Low-dose aspirin is often added empirically to heparin for treatment of aPL during pregnancy, but its efficacy has not been evaluated. Intravenous infusions of gamma globulins (IVGG) have been used as additional therapy when prior treatment with heparin during pregnancy failed to save the fetus, when severe and early onset preeclampsia has complicated a prior pregnancy (in such cases efficacy is unproven), or when there is an additional medical complication (such as immune thrombocytopenia) for which IVGG is an appropriate treatment. There are some situations in which treatment with corticosteroids is the best, or the only choice. However, corticosteroids should not be combined with heparin for long-term treatment during pregnancy because the risk for vertebral fracture is so high.

Sign in / Sign up

Export Citation Format

Share Document