Prolonged Antithrombin Activity of Low-Molecular-Weight Heparins

Agnelli, Giancarlo; Iorio, Alfonso; Renga, Cinzia; Boschetti, Enrico; Nenci, Giuseppe G.; Ofosu, Frederick A.; Hirsh, Jack

doi:10.1161/01.cir.92.10.2819

Cited by 33 publications

(6 citation statements)

References 22 publications

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“…They compared the relative half-lives of prophylactic and therapeutic doses of LMWH by assessing both antiIIa and anti-Xa activity. In contrast to the other studies, which reported a low half-life of the anti-IIa activity, they found that a high and sustained plasma anti-IIa activity was achieved when LMWH were administered in therapeutic doses used in contempo rary trials with only a moderate prolongation of the APTT [27].…”

Section: Low Molecular Weight Heparins (Lmwh)contrasting

confidence: 81%

New developments in the treatment of deep venous thrombosis

Janssen¹,

Nováková²,

Verbruggen³

et al. 1997

The Netherlands Journal of Medicine

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An initial course of standard heparin (SH) or low-molecular-weight heparins (LMWH) is regarded as the treatment of choice for patients with deep venous thrombosis (DVT). LMWH have better bioavailability after subcutaneous administra tion, have a longer half-life, and show higher and more predictable anticoagulant activity. As a result they can be given subcutaneously and without laboratory control, using a dose that is determined by body weight. Because of these multiple advantages of LMWH they will replace SH in the future and subsequently home treatment with LMWH of selected patients seems feasible. The currently accepted approach is to start with SH or LMWH therapy combined with oral anticoagulant therapy (OAT) at the time of diagnosis. The course of SH or LMWH should continue for at least 5 days, provided that international normalized ratio (INR) is in the therapeutic range on 2 consecutive days. OAT should be continued for at least 3 months to prolong the prothrombin time to an INR of 2 -3 . When oral anticoagulants are either contraindicated or inconvenient, SH or LMWH can be used at the middosing interval. The role of anti-platelet treatment is not yet established 4 and should be compared with coumarin therapy in the future.

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Section: Low Molecular Weight Heparins (Lmwh)contrasting

confidence: 81%

New developments in the treatment of deep venous thrombosis

Janssen¹,

Nováková²,

Verbruggen³

et al. 1997

The Netherlands Journal of Medicine

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“…30 However, this assay still reflects only one part of a patient's coagulation system, more precisely one anticoagulant factor. Apart from factor Xa, proteins like antithrombin also inhibit other proteins of the coagulation system, such as thrombin, 31 factor VIIa, 32 factor IX, 33 and contact pathway factors. 34 Assays known to assess interactions in the coagulation system more holistically are viscoelastic whole blood tests, often used as point-of-care (POC) devices.…”

Section: Discussionmentioning

confidence: 99%

Low-Molecular-Weight Heparin Resistance and Its Viscoelastic Assessment in Critically Ill COVID-19 Patients

Bosch

Rugg

Schäfer

et al. 2022

Semin Thromb Hemost

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Critically ill COVID-19 patients present an inflammatory and procoagulant status with a high rate of relevant macro- and microvascular thrombosis. Furthermore, high rates of heparin resistance have been described; yet, individualized anticoagulation by drug monitoring has not been sufficiently researched. We analyzed data from critically ill COVID-19 patients treated at Innsbruck Medical University Hospital with routinely adapted low-molecular-weight heparin (LMWH) doses according to anti-Xa peak levels, and regularly performed ClotPro analyses (a viscoelastic hemostatic whole blood test). A total of 509 anti-Xa peak measurements in 91 patients were categorized as below (<0.008 IU/mL/mg), within (0.008–0–012 IU/mL/mg) or above (> 0.012 IU/mL/mg) expected ranges with respect to the administered LMWH doses. Besides intergroup comparisons, correlations between anti-Xa levels and ClotPro clotting times (CTs) were performed (226 time points in 84 patients). Anti-Xa peak levels remained below the expected range in the majority of performed measurements (63.7%). Corresponding patients presented with higher C-reactive protein and D-dimer but lower antithrombin levels when compared with patients achieving or exceeding the expected range. Consequently, higher enoxaparin doses were applied in the sub-expected anti-Xa range group. Importantly, 47 (51.6%) patients switched between groups during their intensive care unit (ICU) stay. Anti-Xa levels correlated weakly with IN test CT and moderately with Russell's viper venom (RVV) test CT. Critically ill COVID-19 patients present with a high rate of LMWH resistance but with a variable LMWH response during their ICU stay. Therefore, LMWH–anti-Xa monitoring seems inevitable to achieve adequate target ranges. Furthermore, we propose the use of ClotPro's RVV test to assess the coagulation status during LMWH administration, as it correlates well with anti-Xa levels but more holistically reflects the coagulation cascade than anti-Xa activity alone.

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“…Low-molecular-weight heparins offer high and sustained plasma antithrombin activity when administered in therapeutic doses, with only moderate prolongation of the activated partial thromboplastin time [21]. Low-molecular-weight heparins have pharmacokinetic advantages over unfractionated heparin [22], as detailed in table 4.…”

Section: Optimal Anticoagulant Regimenmentioning

confidence: 99%

Modern treatment of pulmonary embolism

Goldhaber¹

2002

Eur Respir J

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Modern treatment of acute pulmonary embolism requires rapid and accurate diagnosis followed by risk stratification to devise an optimal management strategy. Patients at low risk have good outcomes simply with intensive anticoagulation treatment. Higher-risk patients may require more aggressive intervention with thrombolysis or embolectomy.Clinical risk factors for an adverse outcome include increasing age, cancer, congestive heart failure, systemic arterial hypotension, chronic obstructive pulmonary disease and right ventricular dysfunction. A promising approach is the Geneva Prognostic Score, which is based upon a rapid clinical assessment.On physical examination, signs of right ventricular failure, including distended jugular veins and a right-sided S 3 gallop, should be looked for. The electrocardiogram may show evidence of right ventricular strain with a new right bundle branch block or T wave inversion in leads V1-V4. The troponin level may be elevated as a marker of cardiac injury and right ventricular microinfarction, even in the absence of coronary artery disease. The most useful imaging marker of high risk is the presence of moderate or severe right ventricular dilatation and hypokinesis on the echocardiogram, especially with progressively worsening right ventricular function despite intensive anticoagulation treatment.Patients at high risk should be considered for thrombolytic therapy or embolectomy rather than management with anticoagulation therapy alone. Special care must be taken to avoid thrombolytic therapy among patients who might be susceptible to intracranial haemorrhage. Intracranial haemorrhage reached a surprisingly high rate of 3.0% in the International Cooperative Pulmonary Embolism Registry of 2,454 prospectively evaluated acute pulmonary embolism patients at 52 hospitals in seven countries. An alternative approach to patients at high risk is a catheter-based or open surgical embolectomy. It is crucial to refer these patients as quickly as possible, rather than delaying intervention until cardiogenic shock has ensued. Fortunately the current tools for risk stratification provide an "early window" for prognostication and can help the coordination of a definitive treatment plan with optimal results.

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Prolonged Antithrombin Activity of Low-Molecular-Weight Heparins

Abstract: Our results provide an explanation for the effectiveness of LMWHs administered either once or twice daily. High and sustained plasma antithrombin activity is achieved when LMWHs are administered in therapeutic doses used in contemporary trials with only a moderate prolongation of the aPTT.

Cited by 33 publications

References 22 publications

New developments in the treatment of deep venous thrombosis

New developments in the treatment of deep venous thrombosis

Low-Molecular-Weight Heparin Resistance and Its Viscoelastic Assessment in Critically Ill COVID-19 Patients

Modern treatment of pulmonary embolism

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