scholarly journals Heparin and SARS-CoV-2: Multiple Pathophysiological Links

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2486
Author(s):  
Pierpaolo Di Micco ◽  
Egidio Imbalzano ◽  
Vincenzo Russo ◽  
Emilio Attena ◽  
Vincenzo Mandaliti ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Low Molecular Weight Heparin ◽  
Anticoagulant Activity ◽  
The Other ◽  
Low Molecular Weight ◽  
Pharmacological Properties ◽  
Prolonged Administration ◽  
Pass Through ◽  
Therapeutic Doses ◽  
Underlying Diseases

Low molecular weight heparin, enoxaparin, has been one of most used drugs to fight the SARS-CoV-2 pandemic. Pharmacological properties of heparin recognize its specific ability, as with other oligosaccharides and glycosaminoglycan, to bind several types of viruses during their pass through the extracellular matrix of the respiratory tract, as well as its anticoagulant activity to prevent venous thromboembolism. Antithrombotic actions of enoxaparin have been testified both for inpatients with COVID-19 in regular ward and for inpatients in Intensive Care Units (ICUs). Prophylactic doses seem to be able to prevent venous thromboembolism (VTE) in inpatients in the regular ward, while intermediate or therapeutic doses have been frequently adopted for inpatients with COVID-19 in ICU. On the other hand, although we reported several useful actions of heparin for inpatients with COVID-19, an increased rate of bleeding has been recorded, and it may be related to several conditions such as underlying diseases with increased risks of bleeding, increased doses or prolonged administration of heparin, personal trend to bleed, and so on.

scholarly journals New anticoagulant therapy aspects to the COVID-19 patients: From prophylaxis to complications treatment therapy

2021 ◽  
Vol 26 (81) ◽  
pp. 33-51
Author(s):  
Aleksandar Đenić
Keyword(s):  
Molecular Weight ◽  
Body Weight ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Bleeding Events ◽  
Risk Of Bleeding ◽  
Therapeutic Doses ◽  
D Dimer

COVID-19 patients have a high risk of thrombosis of the arterial and venous systems due to extensive systemic inflammation, platelet activation, endothelial dysfunction, and stasis. D-dimer is an important prognostic marker of mortality caused by COVID-19 patients and its increased values indicate tissue damage and inflammation. The incidence of venous thromboembolism (VTe) is between 16 and 49% as a complication of more severe forms of COVID-19 infection in patients hospitalized in intensive care units. Prophylactic doses of low molecular weight heparin (lMWH) should be given to all hospitalized patients with COVID-19 infection in the absence of active bleeding. The safest way is to adjust the low molecular weight heparin (lMWH) dose according to body weight, especially in obese patients. Unfractionated heparin (UFH) is used in patients with a creatinine clearance of less than 30 ml/min. The therapeutic dose of anticoagulation should be discontinued if the platelet count is <50 × 109 /l or fibrinogen <1.0 g/l. Clinically significant bleeding events are higher in those who received therapeutic doses compared to those with standard thromboprophylaxis doses. Thrombolytic therapy is recommended in patients with proven pulmonary embolism (Pe) and hemodynamic instability or signs of cardiogenic shock, who are not at high risk of bleeding. In hospitalized COVID-19 patients with a high clinical risk of developing venous thromboembolism (VTe) and D-dimer values greater than 2600 ng/ml, the use of therapeutic doses of lMWH in doses adjusted to the patient's body weight should be considered, in the absence of a higher risk of bleeding.

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

1993 ◽  
Vol 70 (04) ◽  
pp. 625-630 ◽  
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.

scholarly journals Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
N Hussain ◽  
S Adeel Hassan ◽  
S Mandava ◽  
F Yasmin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Efficacy And Safety ◽  
Dichotomous Data ◽  
Significant Difference

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and  DOACs in the management of malignancy induced  VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November  28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p &lt; 0.05.  Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs  (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p &gt; 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events

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