Apparent Heparin Resistance From Elevated Factor Viii During Pregnancy

Raschke, Robert; Guidry, James R.; Foley, Michael R.

doi:10.1097/00006250-200011001-00001

Cited by 8 publications

(14 citation statements)

References 6 publications

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“…31,32 As discussed below, inadequate heparin dosing is associated with worse clinical outcomes, and the phenomenon of heparin resistance underscores the need for vigilant monitoring of anticoagulant effect in this high-risk group of patients. 34,35 In this situation, the subtherapeutic aPTT does not reflect the true degree of anticoagulation, which may be better assessed using an anti-factor Xa assay (along with demonstration of elevated factor VIII levels). 34,35 In this situation, the subtherapeutic aPTT does not reflect the true degree of anticoagulation, which may be better assessed using an anti-factor Xa assay (along with demonstration of elevated factor VIII levels).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

The Use and Limitations of Unfractionated Heparin

Krishnaswamy¹,

Lincoff²,

Cannon³

2010

Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine

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Despite the development of newer anticoagulants, unfractionated heparin remains an indispensible agent in the treatment of thrombotic disorders. Heparin exerts its major effect via antithrombin, converting antithrombin to a more efficient inhibitor of circulating thrombin (factor IIa), factor Xa, factor IXa, factor XIIa, and kallikrein. However, due to the multiple anticoagulant mechanisms of heparin, differential molecular weight-based clearance, issues of heparin resistance, and patient-specific characteristics (age, weight, gender, and tobacco), attaining therapeutic anticoagulation is complicated. As a result, a minority of patients in major clinical trials achieve an activated partial thromboplastin time within the target window in an appropriate time-frame despite the use of weight-based titration nomograms. The resultant under- or over-therapeutic anticoagulation is associated with increased risks of ischemic and bleeding complications, suggesting the importance of maintaining heparin anticoagulation within a relatively narrow therapeutic range. In this review we discuss the mechanisms of heparin action, clinical ramifications of incorrect dosing in major trials, and attempts to improve the achievement of therapeutic anticoagulation.

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Section: Mechanism Of Actionmentioning

confidence: 99%

The Use and Limitations of Unfractionated Heparin

Krishnaswamy¹,

Lincoff²,

Cannon³

2010

Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine

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“…Conversely, elevated FVIII activity without concomitant increase of CRP could underestimate heparin anticoagulant activity if only aPTT is used for heparin monitoring. This mechanism causes an apparent or pseudo heparin resistance and leads to heparin overdose and increase the risk of bleeding 8‐10 . Variability in CRP and FVIII levels could be responsible for aPTT/anti‐Xa discrepancy in heparin therapy monitoring, in addition to other previously described factors 11 .…”

Section: Discussionmentioning

confidence: 99%

C‐reactive protein‐induced activated partial thromboplastin time prolongation in heparinized samples is attenuated by elevated factor VIII

Kostousov

Devaraj

Bruzdoski

et al. 2020

Int J Lab Hematology

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Introduction Activated partial thromboplastin time (aPTT) and antifactor Xa (anti‐Xa) activity are used to monitor unfractionated heparin therapy in children on extracorporeal membrane oxygenation (ECMO). Elevated C‐reactive protein (CRP) can prolong aPTT and cause discrepancy between these two assays. We aimed to evaluate CRP effect on aPTT and anti‐Xa assays in the presence of heparin and to determine whether elevated CRP affects laboratory monitoring in pediatric ECMO patients. Materials and methods Citrated normal specimens were spiked with CRP, heparin, and recombinant factor VIII (FVIII) and followed by measurement of aPTT and anti‐Xa activity. Additionally, aPTT, anti‐Xa activity, FVIII, fibrinogen, and CRP were measured in 18 ECMO specimens. Results Elevated CRP prolonged aPTT in normal specimens with or without heparin, but did not affect anti‐Xa assay. In contrast, ECMO specimens showed similar aPTT and anti‐Xa values regardless of CRP level. Elevated CRP in specimens was accompanied by increased fibrinogen and FVIII activity. Additional in vitro experiments confirmed that FVIII spiked simultaneously with CRP attenuated CRP‐induced aPTT prolongation in heparinized specimens. Conclusion In vitro CRP‐induced aPTT prolongation is not observed in pediatric ECMO samples due to concomitant FVIII increase. Discordant changes of CRP and FVIII in plasma could contribute to aPTT/anti‐Xa discrepancies observed during heparin therapy in the pediatric population. The anti‐Xa assay is preferable for heparin monitoring in pediatric ECMO settings.

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“…Although there is blunting of the aPTT response in pregnancy, the heparin activity measured by anti-Xa assay is not affected. 6 We have observed clinically that paired aPTT and anti-Xa levels in this population can be discordant (e.g. for the same blood sample, aPTT can be lower than the therapeutic range whereas anti-Xa level is at target).…”

Section: Introductionmentioning

confidence: 91%

Using anti-Xa level for adjusting intravenous unfractionated heparin infusion in peripartum thromboembolic disease

et al. 2018

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Background Intravenous unfractionated heparin infusion is often used to minimize the duration of time without anticoagulation around delivery in pregnant patients with high thrombotic risk. Activated partial thromboplastin time is commonly used to monitor and adjust heparin dose. However, using activated partial thromboplastin time is problematic in pregnancy because activated partial thromboplastin time response to unfractionated heparin is attenuated due to elevated Factor VIII levels and may lead to incorrect dosing. Case We report a case of deep venous thrombosis occurring in a term pregnancy managed by intravenous unfractionated heparin adjusted using anti-Xa level around the time of delivery. We modified the intravenous unfractionated heparin nomogram by using anti-Xa levels instead of activated partial thromboplastin time and observed lower dosing of unfractionated heparin than otherwise required to achieve and maintain target levels. Conclusion This report demonstrates the feasibility and effectiveness of using anti-Xa level to monitor and adjust intravenous unfractionated heparin infusion in pregnancy.

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Apparent Heparin Resistance From Elevated Factor Viii During Pregnancy

Cited by 8 publications

References 6 publications

The Use and Limitations of Unfractionated Heparin

The Use and Limitations of Unfractionated Heparin

C‐reactive protein‐induced activated partial thromboplastin time prolongation in heparinized samples is attenuated by elevated factor VIII

Using anti-Xa level for adjusting intravenous unfractionated heparin infusion in peripartum thromboembolic disease

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