Revisiting the Pharmacology of Unfractionated Heparin

Derbalah, Abdallah; Duffull, Stephen B.; Newall, Fiona; Moynihan, Katie; Al‐Sallami, Hesham S.

doi:10.1007/s40262-019-00751-7

Cited by 12 publications

(17 citation statements)

References 92 publications

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“…Table 2 shows the results of the associations between each covariate and heparin infusion rate upon achieving the target APTTs. We additionally assessed the associations of antithrombin III level as a continuous variable, given that this variable is well known to be involved in heparin’s mechanism of action and was important in the pediatric ECMO study 19 , 20 , which resulted in finding no significant association (P = 0.32). The infusion rates of heparin drip by type of surgical procedure are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Factors/parameters from current practice which contributed to heparin dosing included the type of surgery in the main analysis, and age and the type of surgery in subgroup analysis. A similar study investigating variability in heparin dose response in the pediatric patients on ECMO was conducted using this approach by Moynihan et al They showed that less than 50% of the variability was explained using a model incorporating age and antithrombin activity 19 , 20 . Other studies that assessed interindividual variability of other than heparin dose response were regarding capacity for motor recovery after ischemic stroke or sleeping metabolic rate.…”

Section: Discussionmentioning

confidence: 99%

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Individual variation in unfractionated heparin dosing after pediatric cardiac surgery

Hikino

Koido

Ide

et al. 2020

Sci Rep

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We aimed to identify attributing factors to the interindividual variabilities of the infusion rates in unfractionated heparin therapy. We included patients who required unfractionated heparin therapy to achieve the target APTT after cardiac surgery between May 2014 and February 2018. Fifty-nine patients were included, of whom 8 underwent Blalock-Taussig shunt; 27, Glenn procedure; 19, Fontan procedure; 3, mechanical valve replacement; and 2, Rastelli procedure. Previously reported variables that influenced the response to unfractionated heparin treatment were initially compared, which included age; weight; sex; type of surgery; platelet count; fibrinogen, antithrombin III, total protein, albumin, alanine transaminase, and creatinine levels; and use of fresh frozen plasma. The type of surgical procedure was found to be significantly associated with the differences in heparin infusion rate (P = 0.00073). Subsequently, the variance explained by these factors was estimated through a selection based on the minimum Akaike information criterion value; models constructed by various combinations of the surgery types were compared. The model including the Blalock-Taussig shunt, Glenn procedure, and mechanical valve replacement showed the highest summed variance explained (29.1%). More than 70% of the interindividual variability in initial heparin maintenance dosing was unexplained.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Individual variation in unfractionated heparin dosing after pediatric cardiac surgery

Hikino

Koido

Ide

et al. 2020

Sci Rep

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“…The most common anticoagulant during HD is systemic UFH. UFH is a heterogeneous mixture of negatively charged mucopolysaccharide molecules that bind antithrombin III (at lower doses) and heparin cofactor II (at higher doses), and increases tissue factor inhibitor in order to produce an anticoagulant effect 22,23 . UFH is affordable and considered safe for repeated use.…”

Section: Clotting Preventionmentioning

confidence: 99%

“…UFH is predominantly cleared by hepatic and vascular endothelial heparinases, though non‐specific binding to plasma proteins and leukocytes has been reported to influence half‐life 25 . Due to these pharmacokinetic properties, UFH is known to have heterogeneous effects and an unpredictable dose–response relationship that can complicate clinical application 22 …”

Section: Clotting Preventionmentioning

confidence: 99%

“…UFH is a heterogeneous mixture of negatively charged mucopolysaccharide molecules that bind antithrombin III (at lower doses) and heparin cofactor II (at higher doses), and increases tissue factor inhibitor in order to produce an anticoagulant effect. 22,23 UFH is affordable and considered safe for repeated use. The rapid onset of action (3-5 minutes) and short half-life (approximately 1 hour) also favor its use.…”

Section: Unfractionated Heparinmentioning

confidence: 99%

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Anticoagulation in hemodialysis: A narrative review

Claudel

Miles

Murea

2020

Seminars in Dialysis

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Systemic anticoagulation in maintenance hemodialysis (HD) has historically been considered necessary to maintain the extracorporeal circuit (ECC) and preserve dialysis efficiency. Unfractionated heparin (UFH) is the most commonly used anticoagulant due to low cost and staff familiarity. Despite widespread use, there is little standardization of heparin dosing protocols in the United States. Although the complication rates with UFH are low for the general population, certain contraindications have led to exploration in alternative anticoagulants in patients with end‐stage kidney disease (ESKD). Here we review the current evidence regarding heparin dosing protocols, complications associated with heparin use, and discuss alternatives to UFH including anticoagulant‐free routine HD.

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Synthesis, Biological Evaluation and Reversal of Sulfonated Di‐ and Triblock Copolymers as Novel Parenteral Anticoagulants

Swieton,

Miklosz,

Bielicka

et al. 2024

Adv Healthcare Materials

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Despite targeting different coagulation cascade sites, all Food and Drug Administration‐approved anticoagulants present an elevated risk of bleeding, including potentially life‐threatening intracranial hemorrhage. Existing studies have not thoroughly investigated the efficacy and safety of sulfonate polymers in animal models and fully elucidate the precise mechanisms by which these polymers act. The activity and safety of sulfonated di‐ and triblock copolymers containing poly(sodium styrenesulfonate) (PSSS), poly(sodium 2‐acrylamido‐2‐methylpropanesulfonate) (PAMPS), poly(ethylene glycol) (PEG), poly(sodium methacrylate) (PMAAS), poly(acrylic acid) (PAA), and poly(sodium 11‐acrylamidoundecanoate) (PAaU) blocks are synthesized and assessed. PSSS‐based copolymers exhibit greater anticoagulant activity than PAMPS‐based ones. Their activity is mainly affected by the total concentration of sulfonate groups and molecular weight. PEG‐containing copolymers demonstrate a better safety profile than PAA‐containing ones. The selected copolymer PEG47‐PSSS32 exhibits potent anticoagulant activity in rodents after subcutaneous and intravenous administration. Heparin Binding Copolymer (HBC) completely reverses the anticoagulant activity of polymer in rat and human plasma. No interaction with platelets is observed. Selected copolymer targets mainly factor XII and fibrinogen, and to a lesser extent factors X, IX, VIII, and II, suggesting potential application in blood‐contacting biomaterials for anticoagulation purposes. Further studies are needed to explore its therapeutic applications fully.

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Revisiting the Pharmacology of Unfractionated Heparin

Cited by 12 publications

References 92 publications

Individual variation in unfractionated heparin dosing after pediatric cardiac surgery

Individual variation in unfractionated heparin dosing after pediatric cardiac surgery

Anticoagulation in hemodialysis: A narrative review

Synthesis, Biological Evaluation and Reversal of Sulfonated Di‐ and Triblock Copolymers as Novel Parenteral Anticoagulants

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