scholarly journals Cartridge-Based Thromboelastography Can Be Used to Monitor and Quantify the Activity of Unfractionated and Low-Molecular-Weight Heparins

TH Open ◽  
2019 ◽  
Vol 03 (03) ◽  
pp. e295-e305 ◽  
Author(s):  
João D. Dias ◽  
Carlos G. Lopez-Espina ◽  
Mauro Panigada ◽  
Heidi J. Dalton ◽  
Jan Hartmann ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Maximum Amplitude ◽  
Low Molecular Weight ◽  
Strongly Correlated ◽  
Mixed Effect ◽  
Blood Samples ◽  
Nonlinear Mixed Effect ◽  
Healthy Donors ◽  
Thrombotic Complications ◽  
Heparin Activity

AbstractThromboelastography is increasingly utilized in the management of bleeding and thrombotic complications where heparin management remains a cornerstone. This study assessed the feasibility of the cartridge-based TEG® 6s system (Haemonetics Corp., Braintree, Massachusetts, United States) to monitor and quantify the effect of unfractionated and low-molecular-weight heparin (UFH and LMWH). Blood samples from healthy donors were spiked with UFH (n = 23; 0–1.0 IU/mL) or LMWH (enoxaparin; n = 22; 0–1.5 IU/mL). Functional fibrinogen maximum amplitude (CFF.MA), RapidTEG activated clotting time (CRT.ACT), and kaolin and kaolin with heparinase reaction time (CK.R and CKH.R) were evaluated for their correlation with heparin concentrations, as well as the combination parameters ΔCK.R − CKH.R, ratio CK.R/CKH.R, and ratio CKH.R/CK.R. Nonlinear mixed-effect modelling was used to study the relationship between concentrations and parameters, and Bayesian classification modelling for the prediction of therapeutic ranges. CK.R and CRT.ACT strongly correlated with the activity of LMWH and UFH (p < 0.001). Using combination parameters, heparin activity could be accurately quantified in the range of 0.05 to 0.8 IU/mL for UFH and 0.1 to 1.5 IU/mL for LMWH. CRT.ACT was able to quantify heparin activity at higher concentrations but was only different from the reference range (p < 0.05) at >0.5 IU/mL for UFH and >1.5 IU/mL for LMWH. Combination parameters classified blood samples into subtherapeutic, therapeutic, and supratherapeutic heparin ranges, with an accuracy of >90% for UFH, and >78% for LMWH. This study suggests that TEG 6s can effectively monitor and quantify heparin activity for LMWH and UFH. Additionally, combination parameters can be used to classify blood samples into therapeutic ranges based on heparin activity.

Use of Low Molecular Weight Heparin in Pregnancy

1992 ◽  
Vol 68 (06) ◽  
pp. 652-656 ◽  
Author(s):  
Euthemia Melissari ◽  
Christopher J Parker ◽  
Noel V Wilson ◽  
Giovanni Monte ◽  
Chryso Kanthou ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Controlled Study ◽  
Low Molecular Weight ◽  
Placental Barrier ◽  
Fetal Blood ◽  
Blood Samples ◽  
Recurrent Miscarriages ◽  
Heparin Activity ◽  
First Time

SummaryIn a controlled study of 15 pregnant patients undergoing therapeutic termination of pregnancy, seven received subcutaneously 5,000 anti-FXa units of low molecular weight (LMW) heparin 15 and 3 h prior to the termination, and eight patients acted as controls. Paired maternal and fetal blood samples were taken (before or immediately after the termination) for assay of heparin activity by a chromogenic anti-FXa method sensitive to levels of 0.02 anti-FXa U/ml. LMW heparin was detected in all maternal samples of the test patients but was not detected in any of the fetal samples.The use of LMW heparin as a thromboprophylactic agent was then evaluated in 11 patients who were known to have a severe thromboembolic tendency, had suffered recurrent miscarriages and had responded poorly to conventional anticoagulation (oral anticoagulant, conventional heparin). All patients receiving LMW heparin in thromboprophylactic doses completed uneventful pregnancies and gave birth to healthy babies (three for the first time) without complication. Bone density scans performed in all patients shortly after the delivery showed normal mineral mass. We conclude that LMW heparin does not cross the placental barrier, and in addition offers satisfactory antithrombotic protection for both maternal and placental circulation. In addition, this study provides preliminary data from 11 patients suggesting LMWH may not give rise to maternal osteoporosis, a finding that now needs further investigation.

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.

Low- and Medium-molecular-weight Hydroxyethyl Starches

2000 ◽  
Vol 93 (5) ◽  
pp. 1231-1237 ◽  
Author(s):  
Marina Jamnicki ◽  
Thomas Bombeli ◽  
Burkhardt Seifert ◽  
Andreas Zollinger ◽  
Vladimir Camenzind ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Von Willebrand Factor ◽  
Partial Thromboplastin Time ◽  
Maximum Amplitude ◽  
Activated Partial Thromboplastin Time ◽  
Low Molecular Weight ◽  
Angle Alpha ◽  
Molar Substitution ◽  
Von Willebrand ◽  
Willebrand Factor

Background High-molecular-weight hydroxyethyl starch (HES) compromises blood coagulation more than medium-molecular-weight HES. The authors compared medium molecular weight HES (200 kd [HES200]) and low-molecular-weight HES (70 kd [HES70]). Methods In a prospective, double-blind, randomized-sequence crossover study, 22 male volunteers received 15 ml/kg HES200 and HES70. Blood samples were taken before and 5 min, 30 min, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion. The following parameters were analyzed at all time points: prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII, antigenetic and functional von Willebrand factor, platelets, Thrombelastograph analysis parameters (reaction time, coagulation time, maximum amplitude, angle alpha, and clot lysis 30 and 60 min after maximum amplitude), ionized calcium, hematocrit, HES plasma concentration, molecular weight (weight average and number average), molar substitution, and polydispersity (weight average/number average). Repeated-measures analysis of variance (P &lt; 0.05) was used to compare the response of the aforementioned parameters to the infusion of HES70 and HES200. Results Both HES solutions had a significant impact on all parameters. A slightly greater compromise with HES200 was found in activated partial thromboplastin time (P = 0.010), factor VIII (P = 0.009), antigenetic von Willebrand factor (P = 0.041), functional von Willebrand factor (P = 0.026), maximum amplitude (P = 0.008), and angle alpha (P = 0.003). No difference was established with the other parameters. HES concentration (P &lt; 0.001), weight average (P &lt; 0.001), number average (P &lt; 0.001), and polydispersity (P &lt; 0.001) were higher with HES200. There was no difference with molar substitution (P = 0.091). Conclusions Low-molecular-weight hydroxyethyl starch (70 kd) compromises blood coagulation slightly less than HES200, but it is unclear whether this is clinically relevant.

Treatment of Deep Vein Thrombosis with Enoxaparin in Pediatric Cancer Patients Receiving Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4065-4065 ◽  
Author(s):  
Kimo Stine ◽  
Robert Saylors ◽  
Suzanne Saccente ◽  
David Becton
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Adult Patients ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Children With Cancer ◽  
Factor V Leiden Mutation ◽  
Pediatric Cancer Patients ◽  
Thrombotic Complications ◽  
Deep Vein

Abstract Thrombosis is a known risk in pediatric patients with leukemia. This risk is increased when L-asparaginase is administered. However, children with cancer may have thrombotic complications similar to adults even in the absence of L-asparaginase. The risk may be related to the presence of central lines, surgery, immobilization, or inherited thrombophilia. Cancer in adult patients is also associated with an increased risk of thrombosis that may be related to the disease itself. Low molecular weight heparin such as enoxaparin has become widely used in adult patients with thrombosis. However, there is little data regarding the use of enoxaparin in children undergoing myelosuppressive therapy for malignancies. The purpose of this study was to review the utilization of low molecular weight heparin, enoxaparin (Lovenox), in children with cancer at our institution who had thrombosis while undergoing myelosuppressive chemotherapy. In particular we were interested in the efficacy of enoxaparin in these patients, and if these children were able to continue their chemotherapy without adjustment or interruption secondary to bleeding complications. We conducted a retrospective review from 1999 through April 1, 2004 which yielded seven patients with malignancies and a vascular thrombotic event. The age range was 4–17 years. Diagnosis include: B-precursor ALL (n=3), T-ALL, Hodgkin’s disease, Anaplastic large cell lymphoma, and rhabdomyosarcoma (n=1 each). Six patients developed a deep vein thrombus or clot of the vena cava. One of these 6 patients also had a pulmonary embolus. One patient presented with manifestations of a unilateral cerebral vascular accident without evidence of a DVT. U/S and CT/MRI were performed on patients when appropriate. All patients were screened for Protein C & S deficiency, ATIII deficiency, Factor V Leiden mutation, prothrombin 20210a mutation, and lupus anticoagulant. Treatment was enoxaparin, 1–1.5 mg/kg/dose twice daily to maintain a heparin anti-Xa level of 0.5-1.5 IU/mL. Once the clot had resolved, the enoxaparin was maintained daily for a total of 3–6 months of therapy. All patients had resolution of their thrombosis within 1–2 months of initiation of enoxaparin, and none required delays or dose-reduction of their chemotherapy regimens while on anti-coagulation. There were 10 documented occurences of thrombocytopenia (platelet count &lt; 50,000) in 2 patients without bleeding complications. There was a minimum of 50 days of documented thrombocytopenia while on enoxaparin. We conclude that enoxaparin is effective and safe treatment for thrombotic complications in children undergoing cancer chemotherapy.

scholarly journals Prevention and treatment of thrombosis in cancer and oncohematological patients

2021 ◽  
Vol 16 (4) ◽  
pp. 40-49
Author(s):  
O. V. Somonova ◽  
A. L. Elizarova ◽  
T. V. Davydova
Keyword(s):  
Molecular Weight ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Oncological Patient ◽  
Risk Of Death ◽  
Prevention And Treatment ◽  
Thrombotic Complications

The purpose of the review is to highlight the current possibilities for the prevention and treatment of venous thrombotic complications in patients with cancer.The data of 52 scientific sources published in the Russian and foreign press in 1997–2020 are considered.Cancer patients are at high risk of thrombotic complications, which worsen the outcome of anticancer treatment and are one of the leading causes of death. Thrombosis in an oncological patient increases the risk of death by 30 times, which is associated with fatal thromboembolism and a more aggressive course of the disease. The leading role in the pathogenesis of thrombotic complications is played by disorders in the hemostasis system caused both by the tumor itself and by therapy. Low molecular weight heparins are considered the basis for specific prophylaxis of thromboembolic complications in cancer patients. The use of low molecular weight heparins after surgery and during chemotherapy effectively reduces the incidence of venous thrombosis. Direct oral anticoagulants are promising drugs for oral administration and are indicated as one of the treatment options for patients with tumor-associated thrombosis with a low risk of bleeding and no drug interactions with ongoing systemic chemotherapy.

A Human Pharmacological Study Comparing Conventional Heparin and a Low Molecular Weight Heparin Fragment

1985 ◽  
Vol 53 (02) ◽  
pp. 208-211 ◽  
Author(s):  
G Bratt ◽  
E Törnebohm ◽  
D Lockner ◽  
G Bergströ
Keyword(s):  
Molecular Weight ◽  
Half Life ◽  
Low Molecular Weight Heparin ◽  
Pharmacological Study ◽  
Low Molecular Weight ◽  
Dose Dependency ◽  
First Order ◽  
First Order Kinetics ◽  
Heparin Activity ◽  
Different Doses

SummaryThe pharmacokinetics of a heparin fragment of low molecular weight (LMWH) of 4000-5000 D and unfractioned standard heparin (UFH) have been studied after i. v. injections of different doses and infusions in 8 humans.The heparin activity was significantly higher and the effect on APTT lower after LMWH fragment as compared to UFH in the same doses.The half-life of heparin activity was about 1 hr for UFH and about 2 hr for LMWH. LMWH was found to be eliminated according to first order kinetics and there were no signs of dose dependency.

Low Molecular Weight Heparin And Postoperative Deep Vein Thrombosis

1981 ◽  
Author(s):  
V V Kakkar ◽  
B Djazaeri ◽  
P Webb ◽  
M Scully ◽  
J Westwick ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Abdominal Surgery ◽  
Unfractionated Heparin ◽  
Lipoprotein Lipase ◽  
Major Abdominal Surgery ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Similar Response ◽  
Equivalent Amount ◽  
Blood Samples

Recent studies have indicated that commercially available heparin is a hetrogenous compound consisting of the molecules of diverse chain length and different molecular weights. Low molecular weight (LMW) heparin has been shown in vitro to possess unique properties which should not only improve its efficacy for preventing post-op DVT but also reduce or eliminate the risk of bleeding complications. The aim of this paper is to report the results of in vivo studies performed to test this hypothesis.Ten healthy volunteers received 5000 USP units of unfractionated heparin (mol. wt. 15,000 daltons) or equivalent amount of LMW heparin (mol. wt. 6000 daltons) subcutaneously. Blood samples were withdrawn 1/2 1, 3 and 5 hours later. These were analysed for anti-thrombotic effect using anti-factor Xa (anti Xa) assay and anticoagulant effect by estimating kaolin cephalin clotting time (KCCT) method. While both the preparations of heparin produced similar response in KCCT assay, LMW heparin was found to be 4 times more active in anti-Xa assay. 30 patients undergoing major abdominal surgery were randomly allocated to receive either 5000 units of unfractionated heparin or equivalent amount of LMW heparin every 12 hourly for 10 days. Blood samples were withdrawn before, during and immediately after surgery and every day during post-op period. These were analysed for anti-thrombin III and heparin concentrations, lipoprotein lipase, fibrinopeptide A, prekallikrein, TxB2 and 6-oxo-PGF1α to assess platelet effect. Significant differences were only observed in lipoprotein lipase and anti-thrombin III concentrations. In ongoing trial 43 patients undergoing major abdominal surgery have received 1500 units of LMW heparin every 12 hourly for 7 post-operative days. Only 1 patient has developed DVT and another wound haematoma. If these results are confirmed in a larger number of patient, then LMW heparin may be ideal drug for prophylaxis against DVT.

Mapping Low Molecular Weight Plasma Proteome of Chronic Lymphoblastic Leukemia Patients Using MALDI-TOF Mass Spectrometry.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1910-1910 ◽  
Author(s):  
Jianbiao Zhou ◽  
Zhinan Xia ◽  
Aihong Li ◽  
John G. Gribben
Keyword(s):  
Mass Spectrometry ◽  
Molecular Weight ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Peptide Sequence ◽  
Low Molecular Weight ◽  
Plasma Proteome ◽  
Maldi Tof ◽  
Apolipoprotein A ◽  
Healthy Donors

Abstract In the post-genomic era, even with advances in analytical separation methods, analysis of human serum or plasma remains complex. However differential serum protein and peptide profiles have already been identified in cancer, infectious disease, cardiovascular disease, AIDS and diabetes. Profiling all peptides in plasma is hindered by the abundant albumin, macroglobulin, which may account for more than 80% of total protein. It is estimated that there is at least 7–8 orders of magnitude difference between most abundant plasma peptides and lower abundant ones, although biomarkers are often among the low abundance proteins. Contamination of electrolytes and lipids further complicate analysis of plasma proteome by mass spectrometer because these contaminants inhibit the ionization of native peptide. Here we used a pre-fractionation and ultrafilitration column (molecular weight cutoff 30 KD) strategy to treat plasma samples, and then used matrix assisted laser desorption/ionization time of-flight (MALDI-TOF) to map low molecular weight peptides of CLL patients and healthy donors. Plasma was collected from 34 untreated patients with B-cell chronic lymphocytic leukemia (CLL) and 19 healthy donors. 25mM NH4HCO3, pH 8.2, 20% (v/v) acetonitrile was added to 5 mL of plasma, after vortexing to denature proteins. The mixture was applied onto an Amicon ultra-15 centrifugal filter unit (MWCO 30 KD), and centrifuged. The flow-through was then transferred to a centrifugal concentrator (MWCO 3 KD) until 90% of the volume had gone through the membrane and the volume further reduced. An aliquot was desalted, purified and then spotted on 96-well gold MALDI plates with sinapic acid matrix. Measurements were performed in linear mode with an Applied Biosystems Voyager System with acquisition mass range 3–10 KD. The next-well external calibration was used to calibrate each sample plate and sample preparation. SDS-PAGE analysis demonstrated significant depletion of large, abundant proteins, and enrichment of low molecular peptides in ultrafiltrate. Among the peptides identified in all 34 CLL patients that was absent in 19 healthy donor plasma was a m/z 4340.7 Da peptide. Sequence analysis of this peptide was performed by microcapillary reverse-phase HPLC nano-electrospray tandem mass spectrometry (μLC/MS/MS) and revealed that this peptide sequence is DEPPQSPWDRVKDLATVYVDVLKDSGRDYVSQFEGSALG derived from apolipoprotein A-I (amino acid 25–63 ). We performed ELISA to quantify apolipoprotein A-I in plasma. The mean value plasma apolipoprotein A-I of the 34 CLL patients was 20 mg/dL (range 6.6 to 51.7) compared to 10.4 mg/dL (range 2.2 to 16.9) in the 19 healthy donors (p-value < 0.002). Higher levels of apolipoprotein A-I did not appear to be associated with prognostic significance in the CLL patients in terms of predicting time from diagnosis to requirement for treatment. However, this study demonstrates the feasibility of mapping low molecular weight of plasma proteome by MALDI-TOF to discover novel biomarkers of disease. The identification and characterization of such disease-specific peptides and proteins in CLL patient plasma will help in diagnosis and understanding of CLL biology.

The Influence of Prior Oral Anticoagulation Therapy on the Anticoagulant Effect of Low Molecular Weight Heparin.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4080-4080
Author(s):  
Soumaya El Rouby ◽  
Urvashi Patel ◽  
Marsha Patsh ◽  
Marc Cohen ◽  
Marcia L. Zucker ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Oral Anticoagulation ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
Patient Specific ◽  
Low Molecular Weight ◽  
Oral Anticoagulation Therapy ◽  
Blood Samples ◽  
Peak Response

Abstract Low Molecular Weight Heparins (LMWHs) have been suggested by the ACCP as an alternative to UFH for the anticoagulation of patients on chronic oral anticoagulation therapy (OAT) with warfarin. However, the optimal way to manage these patients remains to be established particularly for high-risk patients who require any type of general surgery or urgent invasive PCI procedures. The purpose of this study is to evaluate the LMWH point-of-care (POC) HEMONOXTM assay (Edison, NJ) in patients on chronic OAT. This clot-based test uses rTF reagents and the Hemochron Jr. Signature+ system. The Hemonox clotting time (CT) was analyzed at baseline and at peak response post enoxaparin treatment. Following IRB approval, blood samples from patients on chronic OAT (5 to 20 years, n=13) were evaluated with the Hemonox assay within 12– 18 hours of their last warfarin dose, patients were evaluated weekly for 4 –12 consecutive weeks. In vitro enoxaparin dose response was evaluated by adding 1 U/ml to blood samples obtained from the OAT patients. In supplemental clinical evaluation, 2 PCI cases on OAT were performed at Newark Beth Israel Medical Center, Newark, NJ. Patients were anticoagulated during their PCI procedure with enoxaparin at a final IV dose of 0.5 mg/kg Hemonox CT baseline response was patient specific and the same response profile was obtained for each patient on OAT who underwent consecutive weekly testing. The majority of patients on OAT (9/13; 69%) exhibited elevated Hemonox baseline CT (150–350 secs) when compared to the previously reported range for PCI patients without prior OAT (baseline CT &lt; 100 secs in 100% of cases, Mean = 71.2 ± 9.0, n= 39). Three patients on OAT (23%) showed CT≤150 secs, and only one patient (8%) yielded a baseline &lt; 100 secs. When the blood of the patient with baseline &lt; 100 sec (baseline value = 70 secs) was spiked in vitro with 1 U/ml enoxaparin, the Hemonox CT was 339 secs which was comparable with the peak response (386 and 308 secs; anti-Xa activity = 0.70 ± 0.01 U/ml; concentration of enoxaparin in the circulation = 0.77± 0.13) observed in the PCI patients receiving enoxaparin (0.5 mg/kg IV) and with a prior OAT who showed similar baseline values. Spiked samples from clinic patients with Hemonox baseline &gt; 150 secs were &gt; 700 secs. Our results demonstrate that prior to administration of LMWH, baseline monitoring may be helpful in patients on OAT to alert clinicians to appropriate alterations of enoxaparin dosing and target anticoagulation times due to the influence of warfarin.

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