scholarly journals Low Molecular Weight Heparin Protects Lung, Renal and Microcirculation Function in Patients with Covid-19 Pneumonia

2020 ◽  
Author(s):  
Li Ma ◽  
Yigang Zeng ◽  
Bing Zhao ◽  
LiLi Xu ◽  
Jian Li ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Renal Function ◽  
Lactic Acid ◽  
Acid Content ◽  
Low Molecular Weight Heparin ◽  
Arterial Oxygen ◽  
Control Group ◽  
Low Molecular Weight ◽  
Arterial Blood ◽  
Lactic Acid Content

Abstract BackgroundCoronavirus disease 2019 (Covid-19) remains a serious health threat worldwide. It is crucial to explore effective treatment measures that reduce mortality. Our aim was to investigate whether low molecular weight heparin (LMWH) can reduce organ injury in patients with Covid-19 pneumonia.MethodsA retrospective study was conducted at the Shanghai Public Health Clinical Center. We initiated a LMWH protocol from January 18th 2020. LMWH was injected subcutaneously at 4100U per day until the D-dimer(DD) level returned to normal, or 5-7 days after admission, whichever occurred first. Admitted patients who received LMWH between January 18th and February 17th 2020 were assigned to the LMWH group. Patients admitted between January 18th and February 17th who did not receive LMWH anticoagulant therapy were the control group. All patients in both groups were aged >18 years, were not pregnant, had no tumors and were in accordance with the following inclusion criteria: 1) DD increased on admission; 2) Body mass index(BMI) >30; 3) History of diabetes. The exclusion criteria were: 1) Platelets <30x109/L or fibrinogen <150 mg/dL; 2) Pregnancy and lactation; 3) Presence of blood system diseases; 4) Immunosuppression; 5) Diseases with a potential risk of bleeding; 6) Receiving anticoagulant drugs or antiplatelet drugs during treatment. General clinical information, indicators for renal function, arterial blood gas analyses and blood lactic acid content were recorded in the two groups 0 (Day 0), 3 (Day 3), 7 (Day 7), and 11 (Day 11) and 15 (Day 15) days after admission.ResultsThere were 48 patients in the LMWH group and 74 patients in the control group. General information, including age, gender, co-existing diseases and onset-to-admission time in both groups was similar. Compared to the control group, LMWH treatment improved the estimated glomerular filtration rate (eGFR) reduced the serum creatinine level (Scr), blood urea nitrogen (BUN)，arterial blood carbon dioxide partial pressure (PaCO2) and arterial blood lactic acid content. However, LMWH treatment reduced arterial oxygen partial pressure (PaO2) and arterial oxygen saturation (SaO2).ConclusionLMWH might be beneficial to improve renal function, CO2 discharge and microcirculation during the early phase of Covid-19 patients . Further randomized controlled trials(RCTs) are warranted in order to further investigate this issue.Trial registrationChiCTR, ChiCTR2000034796. Registered 19 July 2020 - Retrospectively registered, http:// www. chictr.org.cn/listbycreater.aspx.

Systemic Thrombin Generation and Activity Resistant to Low Molecular Weight Heparin Administered Prior to Streptokinase in Patients with Acute Myocardial Infarction

1997 ◽  
Vol 77 (01) ◽  
pp. 057-061 ◽  
Author(s):  
Dennis W T Nilsen ◽  
Lasse Gøransson ◽  
Alf-Inge Larsen ◽  
Øyvind Hetland ◽  
Peter Kierulf
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Molecular Weight ◽  
Body Weight ◽  
Low Molecular Weight Heparin ◽  
Troponin T ◽  
Bleeding Complications ◽  
Control Group ◽  
Low Molecular Weight ◽  
Creatine Kinase Mb

SummaryOne hundred patients were included in a randomized open trial to assess the systemic factor Xa (FXa) and thrombin inhibitory effect as well as the safety profile of low molecular weight heparin (LMWH) given subcutaneously in conjunction with streptokinase (SK) in patients with acute myocardial infarction (MI). The treatment was initiated prior to SK, followed by repeated injections every 12 h for 7 days, using a dose of 150 anti-Xa units per kg body weight. The control group received unfractionated heparin (UFH) 12,500 IU subcutaneously every 12 h for 7 days, initiated 4 h after start of SK infusion. All patients received acetylsalicylic acid (ASA) initiated prior to SK.Serial blood samples were collected prior to and during the first 24 h after initiation of SK infusion for determination of prothrombin fragment 1+2 (Fl+2), thrombin-antithrombin III (TAT) complexes, fibrinopeptide A (FPA) and cardiac enzymes. Bleeding complications and adverse events were carefully accounted for.Infarct characteristics, as judged by creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT), were similar in both groups of patients.A comparable transient increase in Fl+2, TAT and FPA was noted irrespective of heparin regimen. Increased anti-Xa activity in patients given LMWH prior to thrombolytic treatment had no impact on indices of systemic thrombin activation.The incidence of major bleedings was significantly higher in patients receiving LMWH as compared to patients receiving UFH. However, the occurrence of bleedings was modified after reduction of the initial LMWH dose to 100 anti-Xa units per kg body weight.In conclusion, systemic FXa- and thrombin activity following SK-infusion in patients with acute MI was uninfluenced by conjunctive LMWH treatment.

The Use of Low Molecular Weight Heparins for Post-Surgical Deep Vein Thrombosis Prevention in Orthopaedic Patients

1988 ◽  
Vol 16 (5) ◽  
pp. 359-366 ◽  
Author(s):  
E. Chiapuzzo ◽  
G. B. Orengo ◽  
G. Ottria ◽  
A. Chiapuzzo ◽  
E. Palazzini ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Deep Vein Thrombosis ◽  
Low Molecular Weight Heparin ◽  
Control Group ◽  
Low Molecular Weight ◽  
Factor X ◽  
Vein Thrombosis ◽  
Orthopaedic Patients ◽  
Antithrombotic Efficacy ◽  
Deep Vein

The prophylactic antithrombotic efficacy of a low molecular weight heparin was compared with a traditional unfractionated calcium heparin after orthopaedic surgery in 140 patients. Deep vein thromboses were detected in legs either by Doppler sonography or [125I]fibrinogen uptake tests in five (7.1%) and seven (10%) patients, respectively. The capacity of both drugs to prevent deep vein thrombosis was demonstrated. Compared with the control group, those who used low molecular weight heparin showed a significant increase of activated factor X inhibition and smaller increases in activated partial thromboplastin times. Tolerability of both drugs was good, with a low incidence of local side-effects.

Use of Therapeutic Dose Low Molecular Weight Heparin in Patients with Renal Insufficiency: Analysis of Anti-Xa Levels and Creatinine Clearance.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 884-884
Author(s):  
Wendy Lim ◽  
Manasa Sridhara ◽  
Luqi Wang ◽  
Krystyna Kinnon ◽  
James Douketis ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Creatinine Clearance ◽  
Therapeutic Dose ◽  
Low Molecular Weight Heparin ◽  
Dose Adjustment ◽  
Low Molecular Weight ◽  
Recurrent Vte ◽  
Dependent Patient

Abstract Low molecular weight heparin (LMWH) is predominantly eliminated by the kidneys. In patients with severe renal impairment, use of therapeutic dose LMWH may be associated with accumulation and a resultant bleeding risk. Tinzaparin may be less dependent on renal clearance due to its higher molecular mass and greater negative charge compared to other LMWHs. The objective of this prospective cohort study was to serially measure the anti-Xa anticoagulant effect of therapeutic dose tinzaparin over 5–7 days, used for the initial treatment of venous thromboembolism (VTE) in patients with varying degrees of renal insufficiency. We present the anti-Xa results from the first 78 patients enrolled in the study, correlated with renal function. In this study, consecutive in- and outpatients with objectively confirmed VTE requiring anticoagulation were enrolled and stratified into 4 groups based on the calculated Cockcroft-Gault creatinine clearance (CrCl): &gt; 60 mL/min, 30–60 mL/min, ≤ 30 mL/min and hemodialysis-dependent. Tinzaparin 175 IU/kg was administered subcutaneously once daily for 5–7 days or until the INR ≥ 2.0 with warfarin therapy. Trough anti-Xa levels were measured prior to the 3rd, 5th and/or 7th tinzaparin doses. Patients with anti-Xa level &gt; 0.5 IU/mL received tinzaparin dose adjustment using a standardized nomogram. Bleeding and recurrent VTE events were recorded. The relationship between anti-Xa levels and CrCl is shown in Figure 1. Based on our predefined anti-Xa threshold of 0.5 IU/mL, 5 of 78 patients (6.4%) required dose adjustment; 1 hemodialysis dependent patient, 2 patients with CrCl &lt; 30 mL/min, 1 patient each with CrCl 30–60 and &gt; 60 mL/min, respectively. None of these patients developed bleeding or recurrent VTE. Among all 78 patients, 1 hemodialysis-dependent patient developed a hematoma following a traumatic line insertion, and no patients developed recurrent VTE. In conclusion, in a cohort of 78 patients with differing degrees of renal function including patients requiring hemodialysis, use of therapeutic-dose tinzaparin for the initial treatment of VTE resulted in accumulation (defined by trough anti-Xa &gt; 0.5 IU/mL) in 6% of patients. There appears to be a weak inverse relationship between renal function and trough anti-Xa levels, but does not result in clinically significant accumulation when tinzaparin is used for up to 7 days. Further evaluation of tinzaparin in patients with severe renal insufficiency is required. Figure Figure

Preeclampsia and pregnancy loss in women with a history of venous thromboembolism and prophylactic low-molecular-weight heparin (LMWH) during pregnancy

2006 ◽  
Vol 96 (09) ◽  
pp. 285-289 ◽  
Author(s):  
Guelay Alguel ◽  
Rainer Vormittag ◽  
Ralph Simanek ◽  
Paul Kyrle ◽  
Peter Quehenberger ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pregnancy Outcome ◽  
Low Molecular Weight Heparin ◽  
Post Partum ◽  
Control Group ◽  
Low Molecular Weight ◽  
Limited Data ◽  
Vein Thrombosis ◽  
History Of ◽  
Risk Of Preeclampsia

SummaryLimited data are available regarding complications of pregnancy and pregnancy outcome under prophylaxis with low-molecular-weight heparin (LMWH) in women with a history of thromboembolism (TE).We retrospectively evaluated pregnancy complications ina cohort of 80 women. All hada history of TE (76 venous, two arterial and two venous and arterial) and received prophylactic LMWH during 86 pregnancies. The rate of preeclampsia and stillbirth in these women was compared to that of a control group of 313 women without a history of TE and LMWH. Prophylaxis was started at a median of 10 weeks of gestation and usually continued until six weeks post partum. In 94% of the cases the outcome of pregnancy was favourable with a live birth. Four pregnancies (4.7%) ended in miscarriage. Two (2.3%) pregnancies were complicated bya thromboembolic event (one deep leg vein thrombosis and PRIND, respectively). One patient developed HELLP-syndrome. Severe preeclampsia occurred in three (3.8%) and stillbirth in one (1.3%) of the patients (n=80), whereas this was the case in four (1.3%, odds ratio 3.01; 95% confidence interval (CI) 0.66–13.73, p=0.15) and 10 (3.2%, OR=0.38; 95% CI 0.05–3.04, p=0.72) control women. Mean birth weight and standard deviation of infants was 3,160± 930 g in patients and 3,300 ± 540 g in controls (p=0.11).We conclude that a favourable pregnancy outcome in women with a history of thromboembolism who use prophylactic LMWH during pregnancy can be expected. There was a trend towardsa higher risk of preeclampsia, and these women should be carefully monitored for this complication.

Novel subcutaneous low-molecular-weight heparin injection technique to reduce post-injection bruising

2018 ◽  
Vol 34 (6) ◽  
pp. 399-405 ◽  
Author(s):  
Sommapun Jueakaew ◽  
Rattana Piancharoensin ◽  
Natchayakorn Pinkesorn ◽  
Sarunya Thippayarom ◽  
Nuttawut Sermsathanasawadi
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Controlled Trial ◽  
Standard Technique ◽  
Control Group ◽  
Injection Technique ◽  
Low Molecular Weight ◽  
Study Group ◽  
Vein Thrombosis ◽  
Deep Vein

Objective To investigate the efficacy of a novel low-molecular-weight heparin injection technique compared to the standard technique relative to bruising incidence, bruise size, and pain. Methods A randomized controlled trial was conducted in 44 patients with acute deep vein thrombosis. Patients who were randomized into the control group received a 10-s duration injection with immediate needle withdrawal, whereas study group patients received a 30-s duration injection with a 10-s pause before needle withdrawal. Two injection sites were assessed for pain and bruising between 48 and 60 h after injection. Results Bruises occurred in 50.0% and 18.2% of control and study group patients, respectively ( p = 0.03). Mean bruise size between 48 and 60 h after injection was 172.73 ± 372.60 mm2 and 28.18 ± 70.01 mm2 in the control group and study group, respectively ( p = 0.026). Pain scores were comparable between groups. Conclusion A 30-s duration injection with a 10-s pause before needle withdrawal resulted in significantly fewer and smaller bruises.

Randomized Trial of the Effect of the Low Molecular Weight Heparin Nadroparin on Survival in Patients With Cancer

2011 ◽  
Vol 29 (15) ◽  
pp. 2071-2076 ◽  
Author(s):  
Frederiek F. van Doormaal ◽  
Marcello Di Nisio ◽  
Hans-Martin Otten ◽  
Dick J. Richel ◽  
Martin Prins ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Weight ◽  
Therapeutic Dose ◽  
Low Molecular Weight Heparin ◽  
Locally Advanced ◽  
Control Group ◽  
Low Molecular Weight ◽  
Cancer Type ◽  
Time To Progression ◽  
Patients With Cancer

Purpose Earlier studies showed that low molecular weight heparin significantly prolongs the survival of a wide variety of patients with cancer without venous thromboembolism. This study was designed to confirm these findings in a more homogeneous group of patients with cancer. Patients and Methods In this multicenter, randomized, open-label study, patients with non–small-cell lung cancer (stage IIIB), hormone-refractory prostate cancer, or locally advanced pancreatic cancer were randomly assigned to nadroparin or to no nadroparin in addition to their standard anticancer treatment. In the nadroparin arm, subcutaneous nadroparin was administered for 6 weeks (2 weeks at therapeutic dose, and 4 weeks at half therapeutic dose). The patients were eligible to receive additional cycles of nadroparin (2 weeks at therapeutic dose, and 4 weeks of washout period). Outcomes were overall survival, time to progression, and major bleeding. All study outcomes were adjudicated by an independent, blinded committee. Results A total of 244 patients were allocated to nadroparin, and 259 were allocated to the control group. A median survival of 13.1 months was observed in the nadroparin recipients compared with 11.9 months in the no-treatment arm (hazard ratio, 0.94; 95% CI, 0.75 to 1.18, adjusted for cancer type). No difference in time to progression was observed. The number of major bleedings was comparable at 4.1% in the nadroparin set and 3.5% in the control set. Conclusion This study did not show a survival benefit of nadroparin in patients with advanced prostate, lung, or pancreatic cancer. Given the ongoing studies in this area and the previous data, the role of low molecular weight heparins in cancer survival remains undefined.

scholarly journals Early Effects of Low Molecular Weight Heparin Therapy with Soft-Mist Inhaler for COVID-19-Induced Hypoxemia: A Phase IIb Trial

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1768
Author(s):  
Mustafa Erelel ◽  
Mert Kaskal ◽  
Ozlem Akbal-Dagistan ◽  
Halim Issever ◽  
Ahmet Serhan Dagistanli ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Day Treatment ◽  
Heparin Therapy ◽  
Control Group ◽  
Low Molecular Weight ◽  
Open Label ◽  
Peripheral Oxygen Saturation ◽  
Open Label Phase ◽  
Early Effects

In COVID-19-induced acute respiratory distress syndrome, the lungs are incapable of filling with sufficient air, leading to hypoxemia that results in high mortality among hospitalized patients. In clinical trials, low-molecular-weight heparin was administered via a specially designed soft-mist inhaler device in an investigator initiated, single-center, open-label, phase-IIb clinical trial. Patients with evidently worse clinical presentations were classed as the “Device Group”; 40 patients were given low-molecular-weight heparin via a soft mist inhaler at a dose of 4000 IU per administration, twice a day. The Control Group, also made up of 40 patients, received the standard therapy. The predetermined severity of hypoxemia and the peripheral oxygen saturation of patients were measured on the 1st and 10th days of treatment. The improvement was particularly striking in cases of severe hypoxemia. In the 10-day treatment, low-molecular-weight heparin was shown to significantly improve breathing capability when delivered via a soft-mist inhaler.

scholarly journals The potential of low molecular weight heparin to mitigate cytokine storm in severe COVID-19 patients: a retrospective clinical study

2020 ◽  
Author(s):  
Chen Shi ◽  
Cong Wang ◽  
Hanxiang Wang ◽  
Chao Yang ◽  
Fei Cai ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Complete Blood Count ◽  
World Health ◽  
Therapeutic Drug ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Low Molecular Weight ◽  
Retrospective Clinical Study ◽  
Before And After

SummaryBackgroundOn March 11, 2020, the World Health Organization declared its assessment of COVID-19 as a global pandemic. However, specific antiviral drugs are still unavailable, and pateints are managed by multiple complementary treatments.MethodsThe electronic medical records of COVID-19 patients where basic information, complete blood count, coagulation profile, inflammatory cytokines and serum biochemical indicators in 42 patients with COVID-19 (21 of whom were treated with low molecular weight heparin (LMWH), and 21 without LMWH) that were retrospectively analyzed to compare and evaluate the effect of LMWH treatment on disease progression.Findings42 patients with COVID-19 treated at the hospital between February 1 and March 15, 2020, were selected for the study, of which 21 underwent LMWH treatment (LMWH group), and 21 did not (Control), during hospitalization. Changes in the percentage of lymphocytes in the LMWH group before and after LMWH treatment were significantly different from those in the control group (11·10±9·50 vs. 3·08±9·66, p=0·011, respectively). Changes in the levels of D-dimer and fibrinogen degradation products (FDP) in the LMWH group before and after LMWH treatment were significantly different from those in the control group (-2·85±3·90, -0·05±0.85, p=0·002; -9·05±13·14, -1·78±3·15, p=0·035). Strikingly, in the LMWH group, IL-6 levels were significantly reduced after LMWH treatment (47·47±58·86, 15·76±25·71, p=0·006). Besides, the changes in IL-6 levels in the LMWH group before and after LMWH treatment were significantly different from those in the control group (-32·46±65·97, 14·96±151·09, p=0·031).InterpretationLMWH improves the coagulation dysfunction of COVID-19 patients and exerts anti-inflammatory effects by reducing IL-6 and increasing lymphocyte %. It appears that LMWH can be used as a potential therapeutic drug for the treatment of COVID-19, paving the way for a subsequent well-controlled clinical trial.FundingNational Natural Science Foundation of China (No. 81603037 to SC) and the National Key Research and Development Plan of China(2017YFC0909900).

scholarly journals Additional Treatment with Low-Molecular-Weight Heparin Provides a Better Patient Outcome for Neonatal Pulmonary Hemorrhage with Unfractionated Heparin Treatment

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Youmin Zheng ◽  
Lingling Chen ◽  
Lingzi Zhang ◽  
Yongxia Liu
Keyword(s):  
Molecular Weight ◽  
Pulmonary Function ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Pulmonary Hemorrhage ◽  
Control Group ◽  
Low Molecular Weight ◽  
Coagulation Function ◽  
Intravenous Drip ◽  
Heparin Treatment

Pulmonary hemorrhage occurring in preterm newborns is a catastrophic event and is significantly associated with neonatal deaths. Low-weight-molecular heparin is a medical agent usually used as anticoagulants during pregnancy and has the advantages of good absorption, long half-life, and high bioavailability. This study evaluated the pulmonary function and coagulation function in neonates with pulmonary hemorrhage following intravenous drip of low-molecular-weight heparin and the effects of low-molecular-weight heparin on serum prealbumin and retinol-binding protein levels. A total of 96 neonates with pulmonary hemorrhage were included as study subjects and arranged into the control group and the observation group, 48 per group, based on intravenous drip of unfractionated heparin with or without low-molecular-weight heparin. The neonates receiving intravenous drip of unfractionated heparin and low-molecular-weight heparin exhibited elevated partial pressure of oxygen (PaO2) concomitant with declined partial pressure of carbon (PaCO2) compared to those receiving unfractionated heparin treatment alone. With regard to pulmonary function, neonates receiving combined treatment of unfractionated heparin and low-molecular-weight heparin displayed increased forced expiratory volume in the first second (FEV1), FEV1/forced expiratory vital capacity (FVC), and peak expiratory flow (PEF) ( P < 0.05 ) when comparable to neonates receiving unfractionated heparin treatment alone. As for coagulation function, neonates with pulmonary hemorrhage had decreased activated partial thromboplastin time (APTT), prothrombin time (PT), thromboplastin time (TT), and fibrinogen (FIB) after treatment. Expectedly, these decreases were more significantly in neonates undergoing unfractionated heparin coupled with low-molecular-weight heparin ( P < 0.05 ). The control group was given unfractionated heparin, and the observation group was given unfractionated heparin coupled with low-molecular-weight heparin. In addition to pulmonary function and coagulation function, it was also observed that neonates undergoing unfractionated heparin coupled with low-molecular-weight heparin exhibited higher serum levels of serum prealbumin and retinol-binding protein than those treated with unfractionated heparin alone. Finally, higher recovery rate and lower incidence rate of complications, such as pulmonary infection, intracranial hemorrhage, and respiratory distress, were found in the observation group than the control group ( P < 0.05 ). In conclusion, additional treatment with low-molecular-weight heparin could provide a better patient outcome for neonatal pulmonary hemorrhage with unfractionated heparin treatment, as it could notably improve pulmonary function and coagulation function and reduce the incidence of complications.

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