Additional Treatment with Low-Molecular-Weight Heparin Provides a Better Patient Outcome for Neonatal Pulmonary Hemorrhage with Unfractionated 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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Markers of Hemostatic System Activation in Acute Deep Venous Thrombosis-Evolution during the First Days of Heparin Treatment

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649698 ◽

1993 ◽

Vol 70 (06) ◽

pp. 0909-0914 ◽

Cited By ~ 45

Author(s):

Keyword(s):

Molecular Weight ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Unfractionated Heparin ◽

Low Molecular Weight Heparin ◽

Factor Xa ◽

Low Molecular Weight ◽

Dose Adaptation ◽

Heparin Treatment ◽

Lung Scan

SummaryFibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly allocated into two treatment groups: 44 patients received adapted doses of continuous intravenous unfractionated heparin (UH) whereas 47 received 1 mg/kg every twelve hours of a low molecular weight heparin (enoxaparin) subcutaneously. A phlebography and a perfusion lung scan were performed before inclusion and on day 10. Failure of therapy (n = 9) was defined by venogram worsening or confirmed pulmonary embolism. Improvement (n = 44) or stationary state (n = 38) were defined by venogram evolution in the absence of new leg scan defects.At presentation, D-Di, F 1 + 2 and TAT were above cut-off values in 97, 66 and 89% of patients respectively. D-Di levels correlated with the extent of venous thrombosis whereas TAT and F 1 + 2 did not. Mean levels of D-Di decreased sharply during the first days of treatment but were still abnormal on day 10. A secondary increase of D-Di on days 6 or 10 by more than 3 μg/ml occurred in 4 of the 9 patients who developed a thromboembolic recurrence but in none of the 72 patients who had a more favorable outcome. F 1 + 2 and TAT time-courses were not related to clinical evolution. In the Enoxaparin group, there was no relationship between antifactor Xa activities and any biological markers. TAT and F 1 + 2 levels fell on day 2 and remained stable until day 10. In contrast, in the UH group, TAT and F 1 + 2 did not significantly decrease on day 2, probably due to a delay in dose adaptation, but they declined slowly until day 10.In conclusion, D-Di displays a higher sensitivity than F 1 + 2 or TAT for the diagnosis of D\T. D-Di, but not TAT or F 1 + 2, follow-up seems to be of potential value for early detection of recurrency. Hemostatic activation is controlled earlier by fixed doses of a low molecular weight heparin, irrespective of the plasma anti-factor Xa activities, than by unfractionated heparin at adapted doses.

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Comparison of effects of unfractionated heparin and low molecular weight heparin on skin wound healing of rats

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502012000900009 ◽

2012 ◽

Vol 27 (9) ◽

pp. 639-644 ◽

Cited By ~ 4

Author(s):

Can Engin Durmaz ◽

Aydin Ozkan ◽

Bugra Senel ◽

Hasan Alper Uyar

Keyword(s):

Molecular Weight ◽

Wound Healing ◽

Unfractionated Heparin ◽

Low Molecular Weight Heparin ◽

Skin Wound ◽

Control Group ◽

Low Molecular Weight ◽

Skin Wound Healing ◽

Significant Difference ◽

Experimental Group

PURPOSE: To compare the effects of unfractionated heparin (UH) and a low molecular weight heparin (LMWH) on skin wound healing of rats. METHODS: Forty eight male Sprague-Dawley rats underwent 8mm full thickness dorsal skin wounds and were randomly assigned to three equal groups. In experimental group A, heparin sodium was injected at a concentration of 1000U/kg. In experimental group B, enoxaparin was injected at a concentration of 1mg/kg. Physiologic saline (0.5ml) was administered to the control group. Injections were made subcutaneously, once daily, for seven days. At 7th and 10th days tissue samples were taken from all rats. Histologic examination of these tissues was made under light microscope and scored. RESULTS: Histological examination showed a significant difference between the 7th and 10th day groups in wound healing. It was observed that wound healing of LMWH injected group is better. This difference is statistically significant at 10th day. CONCLUSIONS: Daily administration of single doses of unfractionated heparin and a low molecular weight heparin improves wound healing positively. Low molecular weight heparin induces wound healing more than unfractionated heparin.

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Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648988 ◽

1994 ◽

Vol 72 (06) ◽

pp. 942-946 ◽

Cited By ~ 20

Author(s):

Raffaele Landolfi ◽

Erica De Candia ◽

Bianca Rocca ◽

Giovanni Ciabattoni ◽

Armando Antinori ◽

...

Keyword(s):

Molecular Weight ◽

Unfractionated Heparin ◽

Low Molecular Weight Heparin ◽

Primary Source ◽

In Vivo Studies ◽

Low Molecular Weight ◽

Heparin Administration ◽

To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

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Comparison of the Non-Specific Binding of Unfractionated Heparin and Low Molecular Weight Heparin (Enoxaparin) to Plasma Proteins

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649639 ◽

1993 ◽

Vol 70 (04) ◽

pp. 625-630 ◽

Cited By ~ 71

Author(s):

Edward Young ◽

Benilde Cosmi ◽

Jeffrey Weitz ◽

Jack Hirsh

Keyword(s):

Molecular Weight ◽

Unfractionated Heparin ◽

Plasma Proteins ◽

Low Molecular Weight Heparin ◽

Specific Binding ◽

Anticoagulant Activity ◽

Factor Xa ◽

Low Molecular Weight ◽

Heparin Binding ◽

Fixed Amount

SummaryThe non-specific binding of anticoagulantly-active heparin to plasma proteins may influence its anticoagulant effect. We used low affinity heparin (LAH) essentially devoid of anti-factor Xa activity to investigate the extent and possible mechanism of this non-specific binding. The addition of excess LAH to platelet-poor plasma containing a fixed amount of unfractionated heparin doubled the anti-factor Xa activity presumably because it displaces anticoagulantly-active heparin from plasma proteins. Although dextran sulfates of varying molecular weights also increased the anti-factor Xa activity, less sulfated heparin-like polysaccharides had no effect. These findings suggest that the ability to displace active heparin from plasma protein binding sites is related to charge and may be independent of molecular size. In contrast to its effect in plasma containing unfractionated heparin, there was little augmentation in anti-factor Xa activity when LAH was added to plasma containing low molecular weight heparin (LMWH), indicating that LMWH binds less to plasma proteins than unfractionated heparin. This concept is supported by studies comparing the anticoagulant activity of unfractionated heparin and LMWH in plasma with that in buffer containing antithrombin III. The anti-factor Xa activity of unfractionated heparin was 2-fold less in plasma than in the purified system. In contrast, LMWH had identical anti-factor Xa activity in both plasma and buffer, respectively. These findings may be clinically relevant because the recovered anti-factor Xa activity of unfractionated heparin was 33% lower in plasma from patients with suspected venous thrombosis than in plasma from healthy volunteers. The reduced heparin recovery in patient plasma reflects increased heparin binding to plasma proteins because the addition of LAH augmented the anti-factor Xa activity. In contrast to unfractionated heparin, there was complete recovery of LMWH added to patient plasma and little increase of anti-factor Xa activity after the addition of LAH. These findings may explain why LMWH gives a more predictable dose response than unfractionated heparin.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655907 ◽

1997 ◽

Vol 77 (01) ◽

pp. 057-061 ◽

Cited By ~ 7

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.

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