-
BMJ Case Reports Mar 2017A young woman developed a line-associated deep vein thrombosis (DVT), which was treated with low molecular weight heparin (dalteparin). 8 days later, the DVT had...
A young woman developed a line-associated deep vein thrombosis (DVT), which was treated with low molecular weight heparin (dalteparin). 8 days later, the DVT had significantly extended-in spite of therapeutic heparin levels. A diagnosis of heparin-induced thrombocytopenia and thrombosis (HITT) was considered, but the platelet count had not dropped. Nevertheless, a HITT assay was carried out which came back positive, with a repeat assay confirming the result. Dalteparin was stopped and apixaban treatment started, with symptomatic recovery over the following days and weeks.
Topics: Adult; Anticoagulants; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Platelet Count; Pyrazoles; Pyridones; Thrombocytopenia; Thrombosis; Venous Thrombosis
PubMed: 28314810
DOI: 10.1136/bcr-2016-218919 -
Journal of Thrombosis and Haemostasis :... Nov 2014Low molecular weight heparins (LMWHs) constitute the mainstay of anticoagulant therapy for pediatric venous thromboembolism (VTE). The safety and effectiveness of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Low molecular weight heparins (LMWHs) constitute the mainstay of anticoagulant therapy for pediatric venous thromboembolism (VTE). The safety and effectiveness of dalteparin, an LMWH, has not been established in children, and pediatric data on dalteparin for VTE are limited to one single-center experience.
OBJECTIVE
To establish dose-finding (primary endpoint) and efficacy/safety outcomes (secondary endpoints) in children treated with dalteparin in a substudy of the Kids-DOTT trial.
PATIENTS AND METHODS
A prospective multicenter trial using dalteparin subcutaneously twice daily for acute VTE in children aged ≤ 21 years was conducted under an investigator-held Investigational New Drug application registered with the US Food and Drug Administration. Initial weight-based dosing per protocol was as follows: infants (< 12 months), 150 IU kg(-1) ; children (1-12 years), 125 IU kg(-1) ; and adolescents (13-18 years), 100 IU kg(-1) . Bleeding events were categorized according to ISTH criteria. Descriptive non-parametric statistics were employed for all analyses.
RESULTS
Eighteen patients (67% male) were enrolled from January 2010 to October 2013 across four centers. No supratherapeutic levels were observed. Median (range) therapeutic doses by age group were as follows: infants (n = 3), 180 IU kg(-1) (146-181 IU kg(-1) ); children (n = 7), 125 IU kg(-1) (101-175 IU kg(-1) ); and adolescents (n = 8), 100 IU kg(-1) (91-163 IU kg(-1) ). The median duration of dalteparin use was 48 days (range: 2-169 days), and the median follow-up was 10.5 months (range: 2-35 months). There were no related serious adverse events, no clinically relevant bleeding events, and no symptomatic recurrent VTEs.
CONCLUSION
Dalteparin successfully achieved targeted anti-factor Xa levels in 18 children and young adults with acute VTE with a standardized age-based dosing regimen, with a favorable safety and efficacy profile.
Topics: Acute Disease; Adolescent; Age Factors; Anticoagulants; Child; Child, Preschool; Dalteparin; Drug Administration Schedule; Female; Hemorrhage; Humans; Infant; Infant, Newborn; Injections, Subcutaneous; Male; Patient Safety; Pilot Projects; Prospective Studies; Recurrence; Risk Factors; Time Factors; Treatment Outcome; United States; Venous Thromboembolism
PubMed: 25182454
DOI: 10.1111/jth.12716 -
Journal of Thrombosis and Thrombolysis Jan 2020Cancer increases risk for venous thromboembolism. Incident thrombocytopenia increases hemorrhagic risk. Hospitalized adults with a cancer diagnosis who received... (Observational Study)
Observational Study
Cancer increases risk for venous thromboembolism. Incident thrombocytopenia increases hemorrhagic risk. Hospitalized adults with a cancer diagnosis who received subcutaneous dalteparin in doses adjusted according to platelet count were retrospectively evaluated. Outcomes of interest included nadir platelet counts, transfusions, thromboembolism, and hemorrhage. During a 2-year period of observation, 1854 cancer patients received individualized inpatient treatment with dalteparin. Transfusion was required in 38 of 77 (49.4%) patients with nadir platelet counts < 25 × 10 cells/L as compared with 16 of 75 (21.3%) patients whose nadir platelet counts were 25-50 × 10 cells/L [risk ratio (RR) 2.31; 95% CI 1.42 to 3.78, p < 0.001] and 45 of 1657 (2.7%) patients with platelet counts > 50 × 10 cells/L (RR - 8.07; 95% CI - 4.79 to - 13.59, p < 0.001). Transfusions were administered primarily as supportive therapy. Among transfusion recipients, new or recurrent venous thromboembolism was documented in 2.6%, 0%, and 2.2% of patients with nadir platelet counts of < 25, 25-50, or > 50 × 10 cells/L, respectively (p > 0.9 for all comparisons). Acute blood loss or major bleeding was documented in 10.5%, 12.5%, and 15.6% of patients with platelet counts of < 25, 25-50, or > 50 × 10 cells/L, respectively (p > 0.9 for all comparisons). Among hospitalized cancer patients who received individualized dalteparin treatment, transfusion requirements varied inversely with platelet count. Irrespective of platelet counts, occurrence rates for venous thromboembolism and acute hemorrhage were similar across all treatment groups. Individualized dalteparin treatment provided a consistent pattern of safety and effectiveness.
Topics: Adult; Aged; Blood Transfusion; Dalteparin; Female; Hospitalization; Humans; Incidence; Male; Middle Aged; Neoplasms; Platelet Count; Thrombocytopenia; Thromboembolism
PubMed: 31468319
DOI: 10.1007/s11239-019-01935-5 -
Acta Anaesthesiologica Scandinavica Apr 2021The aim of this study was to evaluate the utility of coagulation analyses to assess thromboprophylaxis with dalteparin in intensive care unit (ICU) patients.
BACKGROUND
The aim of this study was to evaluate the utility of coagulation analyses to assess thromboprophylaxis with dalteparin in intensive care unit (ICU) patients.
METHODS
Prospective observational study of ICU patients receiving dalteparin prophylaxis at Oslo University Hospital in Norway. Trough and peak antithrombin, protein C, anti-factor Xa activity (aFXa), d-dimer, thromboelastography, calibrated automated thrombogram and microparticles were analysed. Levels were compared in patients with and without venous thromboembolism (VTE), major bleeding, acute kidney injury (AKI) with use of renal replacement therapy (RRT) and variable dalteparin dose.
RESULTS
Among 50 included patients (76% male, mean age 62 years) five (10%) developed VTE and eight (16%) major bleeding. Median through aFXa level was 0.03 (0.02-0.05) IU/mL, and 48 (96%) of patients were within and two (4%) above target range. Peak aFXa level was 0.21 (0.13-0.29) IU/mL, the number of patients below, within and above prophylactic range were 21 (42%), 25 (50%) and four (8%). Peak aFXa levels were similar in patients with and without VTE (0.18 vs 0.21 IU/L, P = .72), major bleeding (0.22 vs 0.21 IU/mL, P = .38) and AKI with RRT (0.18 vs 0.24, P = .13), but lower in patients receiving dalteparin 5000 IU od compared to 7500 IU od (0.19 vs 0.30 IU/mL, P < .01).
CONCLUSIONS
Intensive care unit patients receiving dalteparin prophylaxis had half of patients within prophylactic peak aFXa target range. Peak aFXa levels was affected by administered dalteparin dose, but not presence of VTE, major bleeding or AKI with RRT.
PubMed: 33205407
DOI: 10.1111/aas.13748 -
The Netherlands Journal of Medicine Dec 2019Monitoring low-molecular-weight heparins is generally not required. However, guidelines advise to monitor anti-Xa levels in patients with renal insufficiency or a BMI...
BACKGROUND
Monitoring low-molecular-weight heparins is generally not required. However, guidelines advise to monitor anti-Xa levels in patients with renal insufficiency or a BMI above 50, and in pregnancy. Measuring anti-Xa levels is a complex challenge since sampling should be performed three to five hours after subcutaneous injection and after steady state concentrations have been reached. Strict compliance is pivotal for justified dose adjustments.
OBJECTIVES
We questioned compliance to our protocol and performed this study to explore that.
METHODS
This retrospective cohort study included patients ≥ 18 years receiving therapeutic dalteparin in a Dutch academic medical centre. Patients with a first anti-Xa level measured between February 23rd and December 30th, 2017 were selected. According to our local guideline, monitoring anti-Xa activity is indicated in patients on therapeutic doses of dalteparin who are pregnant, morbidly obese (BMI > 50), or have renal insufficiency (clearance < 60 ml/min). Accurate sampling was defined as measuring levels after at least three injections (after which a patient may reach steady state) and then four hours after the injection with dalteparin. The frequency of compliance to our protocol was assessed.
RESULTS
We included 158 patients with 396 anti-Xa levels, of which 41% (65/158) of all first anti-Xa levels were drawn without appropriate indication. Almost half, 48% (211/396), were sampled incorrectly and 25% of these (53/211) were followed by a dose adjustment. In total, 74% (293/396) of the samples were not indicated or were taken at the wrong time.
CONCLUSIONS
Monitoring anti-Xa levels is a complex clinical challenge. This study showed that non-compliance with recommendations for anti-Xa monitoring was high, often resulting in unjustified dose adjustments.
Topics: Academic Medical Centers; Adult; Anticoagulants; Dalteparin; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Male; Medication Adherence; Middle Aged; Netherlands; Retrospective Studies; Venous Thromboembolism; Young Adult
PubMed: 31880268
DOI: No ID Found -
Thrombosis and Haemostasis Jul 2024In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated noninferiority of apixaban to dalteparin for treatment of cancer-associated VTE without an increased risk of major bleeding. We compared the early time course of VTE recurrence and major bleeding events of apixaban compared with dalteparin at 7, 30, and 90 days of treatment in patients with cancer-associated VTE.
METHODS
The study design of the CARAVAGGIO trial has been described. Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed recurrent VTE. The primary safety outcome was major bleeding.
RESULTS
In 1,155 patients, recurrent VTE after 7, 30, and 90 days occurred in 6 (1%), 15 (2.6%), and 27 (4.7%) patients in the apixaban arm versus 5 (0.9%), 20 (3.5%), and 36 (6.2%) patients respectively in the dalteparin arm. By day 7, 30, and 90, major bleeding events had occurred in 3 (0.5%), 9 (1.6%), and 16 (2.8%) patients in the apixaban group versus 5 (0.9%), 11 (1.9%), and 17 (2.9%) patients in the dalteparin group.
CONCLUSION
The frequencies of recurrent VTE and major bleeding events at 7, 30, and 90 days of apixaban compared with dalteparin were similar in patients with cancer-associated VTE. This supports the use of apixaban for the initiation and early phase of anticoagulant therapy in cancer-associated VTE.
Topics: Humans; Pyridones; Pyrazoles; Dalteparin; Hemorrhage; Neoplasms; Female; Venous Thromboembolism; Male; Middle Aged; Aged; Recurrence; Anticoagulants; Time Factors; Factor Xa Inhibitors; Treatment Outcome; Adult
PubMed: 38196077
DOI: 10.1055/s-0043-1778642 -
The Netherlands Journal of Medicine Jul 2015Low-molecular-weight heparins (LMWHs) are increasingly used as anticoagulant during haemodialysis. The aim of this study is to establish the efficiency and duration of...
BACKGROUND
Low-molecular-weight heparins (LMWHs) are increasingly used as anticoagulant during haemodialysis. The aim of this study is to establish the efficiency and duration of anticoagulation with dalteparin and nadroparin administration in patients treated with nocturnal haemodialysis.
METHODS
All patients were treated with nocturnal in-centre haemodialysis, 3-4 times a week. Anticoagulation was obtained with dalteparin (n = 15) or nadroparin (n = 10). Anti-factor- Xa activity was measured during a midweek dialysis session at t = 0, 4 and 8 hours.
RESULTS
The LMWH dose necessary to prevent extracorporeal circuit clotting was higher for dalteparin than for nadroparin. In the dalteparin group, anti-Xa activity was almost negligible at the start of dialysis whereas most patients on nadroparin still had anti-Xa activity at the start of dialysis (0.08 (IQR 0.05-0.11) IU÷ml), reflecting the effect of previous LMWH administration. After eight hours of dialysis, median anti-factor-Xa activity was 0.49 (IQR 0.22-0.57) after dalteparin and 0.69 (IQR 0.55- .83) after nadroparin (p = 0.01). When a target range of 0.2-0.6 IU÷ml was applied, the present dosing method led to over-anticoagulation in more than half of the patients.
CONCLUSION
Administration of two doses of LMWH is an effective method of anticoagulation in nocturnal, eight-hour haemodialysis. With two doses of dalteparin, a larger proportion of patients reached but did not exceed target levels of anticoagulation, compared with two doses of nadroparin. Nadroparin caused prolonged anti-Xa activity with measurable anticoagulation up to the next dialysis session. The measurement of anti-Xa activity is advocated for dose assessment of LMWH, when LMWH is used as anticoagulant during nocturnal haemodialysis.
Topics: Anticoagulants; Blood Coagulation; Dalteparin; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nadroparin; Renal Dialysis; Treatment Outcome
PubMed: 26228191
DOI: No ID Found -
Low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease.The Cochrane Database of Systematic... Dec 2015Sickle cell disease is one of the most common and severe genetic disorders in the world. It can be broadly divided into two distinct clinical phenotypes characterized by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sickle cell disease is one of the most common and severe genetic disorders in the world. It can be broadly divided into two distinct clinical phenotypes characterized by either haemolysis or vaso-occlusion. Pain is the most prominent symptom of vaso-occlusion, and hypercoagulability is a well-established pathogenic phenomenon in people with sickle cell disease. Low-molecular-weight heparins might control this hypercoagulable state through their anticoagulant effect. This is an update of a previously published version of this review.
OBJECTIVES
To assess the effects of low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches. We also searched abstract books of conference proceedings and several online trials registries for ongoing trials.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 28 September 2015.
SELECTION CRITERIA
Randomised controlled clinical trials and controlled clinical trials that assessed the effects of low-molecular-weight heparins in the management of vaso-occlusive crises in people with sickle cell disease.
DATA COLLECTION AND ANALYSIS
Study selection, data extraction, assessment of risk of bias and analyses were carried out independently by the two review authors.
MAIN RESULTS
Two studies comprising 287 participants were included. One study (with an overall unclear to high risk of bias) involved 253 participants and the quality of the evidence for most outcomes was very low. This study, reported that pain severity at day two and day three was lower in the tinzaparin group than in the placebo group (P < 0.01, analysis of variance (ANOVA)) and additionally at day 4 (P < 0.05 (ANOVA)). Thus tinzaparin resulted in more rapid resolution of pain, as measured with a numerical pain scale. The mean difference in duration of painful crises was statistically significant at -1.78 days in favour of the tinzaparin group (95% confidence interval -1.94 to -1.62). Participants treated with tinzaparin had statistically significantly fewer hospitalisation days than participants in the group treated with placebo, with a mean difference of -4.98 days (95% confidence interval -5.48 to -4.48). Two minor bleeding events were reported as adverse events in the tinzaparin group, and none were reported in the placebo group. The second study (unclear risk of bias) including 34 participants and was a conference abstract with limited data and only addressed one of the predefined outcomes of the review; i.e. pain intensity. After one day pain intensity reduced more, as reported on a visual analogue scale, in the dalteparin group than in the placebo group, mean difference -1.30 (95% confidence interval -1.60 to -1.00), with the quality of evidence rated very low. The most important reasons for downgrading the quality of evidence were serious risk of bias and imprecision (due to low sample size or low occurrence of events).
AUTHORS' CONCLUSIONS
Based on the results of two studies, evidence is incomplete to support or refute the effectiveness of low-molecular-weight heparins in people with sickle cell disease. Vaso-occlusive crises are extremely debilitating for sufferers of sickle cell disease; therefore well-designed placebo-controlled studies with other types of low-molecular-weight heparins, and in participants with different genotypes of sickle cell disease, still need to be carried out to confirm or dismiss the results of this single study.
Topics: Anemia, Sickle Cell; Anticoagulants; Dalteparin; Heparin, Low-Molecular-Weight; Humans; Pain Measurement; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Tinzaparin
PubMed: 26684281
DOI: 10.1002/14651858.CD010155.pub3 -
The Journal of Pharmacology and... Apr 2020Bleeding resulting from the application of low-molecular-weight heparins (LMWHs) may be treated with protamine sulfate, but this treatment lacks efficiency; its action...
Bleeding resulting from the application of low-molecular-weight heparins (LMWHs) may be treated with protamine sulfate, but this treatment lacks efficiency; its action against antifactor Xa activity is limited to ∼60%. Moreover, protamine sulfate can cause life-threatening hypersensitivity reactions. We developed diblock heparin-binding copolymer (HBC), which can neutralize the anticoagulant activity of parenteral anticoagulants. In the present study, we explored the safety profile of HBC and its potential to reverse enoxaparin, nadroparin, dalteparin, and tinzaparin in human plasma and at in vivo conditions. HBC-LMWH complexes were characterized using zeta potential, isothermal titration calorimetry, and dynamic light scattering. The rat cardiomyocytes and human endothelial cells were used for the assessment of in vitro toxicity. Male Wistar rats were observed for up to 4 days after HBC administration for clinical evaluation, gross necropsy, and biochemistry and histopathological analysis. Rats were treated with LMWHs alone or followed by short-time intravenous infusion of HBC, and bleeding time and antifactor Xa activity were measured. HBC completely reversed antifactor Xa activity prolonged in vitro by all LMWHs with an optimal weight ratio of 2.5:1. The complexes of HBC-LMWHs were below 5 µm. We observed no effects on the viability of cardiovascular cells treated with HBC at concentrations up to 0.05 mg/ml. Single doses up to 20 mg/kg of HBC were well tolerated by rats. HBC completely reversed the effects of LMWHs on bleeding time and antifactor Xa activity in vivo after 20 minutes and retained ∼80% and ∼60% of reversal activity after 1 and 2 hours, respectively. Well-documented efficacy and safety of HBC both in vitro and in vivo make this polymer a promising candidate for LMWHs reversal. SIGNIFICANCE STATEMENT: Over the last decade, there has been significant progress in developing antidotes for the reversal of anticoagulants. Until now, there has been no effective and safe treatment for patients with severe bleeding under low-molecular-weight heparin therapy. Based on our in vitro and in vivo studies, heparin-binding copolymer seems to be a promising candidate for neutralizing all clinically relevant low-molecular-weight heparins.
Topics: Animals; Anticoagulants; Antidotes; Dose-Response Relationship, Drug; Factor Xa; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Human Umbilical Vein Endothelial Cells; Humans; Male; Protein Binding; Random Allocation; Rats; Rats, Wistar
PubMed: 31937564
DOI: 10.1124/jpet.119.262931 -
Journal of Medical Cases May 2022Homozygous factor V Leiden (FVL) is a rare condition, occurring in 0.2% of the white population. This disease's rarity and aggressive pathophysiology can represent a...
Homozygous factor V Leiden (FVL) is a rare condition, occurring in 0.2% of the white population. This disease's rarity and aggressive pathophysiology can represent a challenge even to the most experienced clinicians. We report a case of a 35-year-old white man, who presented to the emergency department with a 1-week history of bilateral thigh swelling and pain. His past medical history included homozygous FVL mutation complicated by multiple venous thromboembolic events in the last decade, recent inferior vena cava (IVC) filter placement, diabetes mellitus type 2, and hypertension. Despite being trialed for different anticoagulation therapies over 10 years, including warfarin (international normalized ratio (INR) goal 2 - 3), rivaroxaban, and dalteparin, he continued to thrombose. On admission, while on a therapeutic dose of dalteparin, he was diagnosed with extensive acute deep vein thrombosis involving the bilateral femoral and iliac veins, extending proximally to his IVC filter to the renal veins, and pulmonary embolisms in the bilateral lower lobes and right middle lobe. A heparin drip was initiated, and he developed progressive thrombocytopenia over 96 h. Heparin was discontinued, and he was switched to argatroban. He was diagnosed with heparin-induced thrombocytopenia (HIT) with positive anti-platelet factor 4 (PF4)/heparin antibodies and a serotonin release assay. His platelets trended up to normal levels 5 days after heparin discontinuation. He underwent multiple thrombectomies, thrombolysis, and angioplasty of the abdominal and lower extremity veins. The IVC filter was removed. Secondary thrombophilia workup was remarkable for a positive lupus anticoagulant, which had been negative in the past. The patient was bridged to warfarin, discharged with a higher INR goal of 3 - 3.5, and continuously monitored factor II activity (goal 15-30%). This case illustrates a patient with recurrent episodes of thromboembolic events because of homozygous FVL. This condition's pathophysiology and therapeutic approach has been well studied in heterozygous carriers; however, homozygous individuals represent <1% of cases. Given the rareness of the disease, there are no well-established therapeutic guidelines, and long-term anticoagulation remains the therapeutic cornerstone. This case emphasizes the challenges in managing patients with homozygous FVL and complications that can occur due to this gap in the literature. We suggest further case reports and research studies to shed light on this serious condition and its lifetime complications.
PubMed: 35655628
DOI: 10.14740/jmc3914