Anticoagulant
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they help keep the bite area unclotted long enough for the animal to obtain some blood. As a class of medications, anticoagulants are used in therapy for thr…
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What is the Normal PTT for heparin?
Abstract. Background: Unfractionated heparin therapy is care intensive because of dose-response variability, and because of the necessity of constant intravenous infusion and frequent monitoring. We sought to assess the real-world course of transition from heparin to warfarin in hospitalized patients undergoing anticoagulation therapy for acute venous or arterial …
What is the difference between LMWH and heparin?
Long-term follow-up results of unfractionated heparin infusion treatment for submassive pulmonary thromboembolism Our study suggests that unfractionated heparin is safe in the treatment of submassive pulmonary thromboembolism in terms of bleeding risk and reduces pulmonary artery pressure.
What is the difference between LMWH and UFH?
The current guidelines for percutaneous coronary intervention do not address the prolonged postprocedural use of unfractionated heparin (UFH) to prevent acute occlusion. However, recently published small studies have yielded mixed results, leaving the question unanswered.
Why is aPTT for heparin?
May 24, 2020 · Unfractionated heparin (UFH) binds to anti-thrombin III (AT-III), which enhances antithrombin's inhibition of several coagulation factors – especially factor Xa and factor IIa (thrombin). Low Molecular-Weight Heparin (LMWH) is a heterogeneous collection of heparin molecules with a lower average molecular weight compared to unfractionated heparin. Since …
What is the difference between fractionated and unfractionated heparin?
What is meant by unfractionated heparin?
How long does unfractionated heparin work?
What is the difference between heparin and unfractionated heparin?
What is the difference between UFH and LMWH?
Why is unfractionated heparin given?
What does a prolonged PTT mean?
What is the half life of unfractionated heparin?
| Unfractionated heparin | |
|---|---|
| Protein binding | Proteins in plasma and on endothelium |
| Bioavailability | Subcutaneous—10-30% at low doses, 90% at higher doses Intravenous—100% by definition |
| Effective half life | Subcutaneous—1.5 hours Intravenous—30 min |
What is a UFH level?
What is the meaning of unfractionated?
When is unfractionated heparin used?
What are the advantages of LMWH over UFH?
What is pseudo-heparin resistance?
Definition of pseudo-heparin resistance: elevation of factor VIII and/or fibrinogen decreases the PTT, making it difficult to achieve a target PTT ( Downie 2019 ). Elevated levels of factor VIII and/or fibrinogen are usually due to systemic inflammation.
What is a low molecule weight heparin?
Low Molecular-Weight Heparin (LMWH) is a heterogeneous collection of heparin molecules with a lower average molecular weight compared to unfractionated heparin.
How long does Argatroban stay in your system?
Argatroban is cleared by the liver with a ~45-minute half-life. In patients with normal hepatic function, coagulation will normalize about 2-4 hours after stopping the infusion. The half-life may extend to ~3 hours in patients with hepatic dysfunction. Argatroban may be used in patients with liver dysfunction, but lower doses should be used and it may be harder to rapidly discontinue anticoagulation.
Why is enoxaparin used in critically ill patients?
Increased dosing of enoxaparin may be beneficial for critically ill patients for several reasons:#N#i) Patients are generally at increased risk of DVT (compared to less ill patients).#N#ii) Inflammation triggers increased levels of acute-phase reactant proteins, which may reduce the effectiveness of heparin.
What is the goal PTT for titration?
Titration is based on the PTT value, with a goal PTT of ~1.5-2.5 times normal (table below).
What is UFH in biology?
UFH is a heterogeneous mixture of different length strands of heparin. It sticks to endothelial cells, macrophages, and various heparin-binding proteins. This makes its pharmacokinetics unpredictable, requiring monitoring.
How many units of XA is in 1 mg of dalteparin?
1 mg of dalteparin has 156 units of anti-factor Xa activity. Dalteparin is typically measured in terms of anti-Xa units, rather than in milligrams.
What is heparin used for?
Heparin is a natural agent used to prevent clot formation in the vessels . Two types of heparins are widely used, unfractionated heparin (UFH) and low molecular weight heparin (LMWH). Heparin‐induced thrombocytopenia (HIT) is an adverse reaction that can occur during treatment with heparin. It is common in practice and its most important consequence is a paradoxical increase in the risk of clotting (thromboembolic) complications. A number of factors are thought to influence its frequency, including the type of heparin and the type of patient, with patients who have had a surgery at higher risk. We compared the risk of HIT in people who had had surgery and had been exposed to UFH or LMWH. A better understanding of this problem will allow safer management of postoperative patients who need thromboprophylaxis with heparin.
What is heparin induced thrombocytopenia?
Heparin‐induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody‐mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin‐exposed patient population, with the postoperative patient population at higher risk.
What is the objective of a review of heparin-induced thrombocytopenia?
The objective of this review was to compare the incidence of heparin‐induced thrombocytopenia (HIT) and HIT complicated by venous thromboembolism in postoperative patients exposed to unfractionated heparin (UFH) versus low molecular weight heparin (LMWH).
Is heparin a thromboembolic drug?
Heparin is a commonly used medication worldwide since it is essential in the treatment and prophylaxis of thromboembolic disorders. There are two types of heparin drugs comprising unfractionated heparin (UFH), also known as standard heparin, and low molecular weight heparin (LMWH). LMWH is constituted by a group of several drugs (for example, enoxaparin, dalteparin, nadroparin, tinzaparin, certoparin) (Hirsh 2004). LMWH has been largely replacing UFH as front‐line therapy as it is judged to be at least as efficacious in preventing thromboembolic complications and in inducing fewer bleeding adverse outcomes (Alikhan 2014; Barrera 2013; Falck‐Ytter 2012; Gould 2012; Kahn 2012; Schulman 2008). However, similar efficacy and risks have been described (Akl 2014; Handoll 2002; Wille‐Jørgensen 2003), as well as insufficient and low‐quality evidence (Bain 2014; Barrera 2013). Inadequate assessment of adverse effects is also demonstrated even in the most recent evidence (Di Nisio 2016).
What is delayed onset?
delayed‐onset is when HIT is diagnosed after the discontinuation of heparin.
Is LMWH the same as UFH?
Although LMWH has largely replaced UFH as a front‐line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by harmful effects such as HIT. We therefore sought to determine the relative impact of UFH and LMWH on HIT in postoperative patients receiving thromboembolism prophylaxis. This is an update of a review first published in 2012.
Is heparin induced thrombocytopenia a complication of heparin
Although haemorrhagic events are the main recognised risk of heparin use, heparin‐induced thrombocytopenia (HIT) is a potentially severe, morbid complication of heparin therapy. HIT is a prothrombotic disorder defined as a relative reduction in platelet count of about 50% (even if the platelet count at its lowest remains greater than 150 x 109/L) occurring within five to 14 days after the start of heparin therapy (Warkentin 2003; Warkentin 2003a; Warkentin 2006). People re‐exposed after a recent treatment may develop a rapid onset of HIT within 24 hours of heparin administration (Warkentin 2009). Also, a less frequent delayed onset of HIT, when it occurs after discontinuation of heparin, has been described (Smythe 2005; Warkentin 2001). Formerly designated as white clot syndrome or HIT type II, it is considered an acquired hypercoagulability syndrome caused by an immune‐mediated reaction which is commonly followed by venous or arterial thrombosis (Greinacher 1995; Hong 2003; Walenga 2000; Warkentin 1995).
What is the focus of unfractionated heparin therapy?
The focus of clinicians who manage unfractionated heparin therapy should be to ensure that an adequate starting dose of unfractionated heparin is used and that the aPTT method is standardized.
What is the best way to measure unfractionated heparin?
Laboratory monitoring is widely recommended to measure the anticoagulant effect of unfractionated heparin and to adjust the dose to maintain levels in the target therapeutic range. The most widely used laboratory assay for monitoring unfractionated heparin therapy is the activated partial thromboplastin time (aPTT). A fixed therapeutic range for the aPTT of 1.5 to 2.5 times the control value has become widely accepted, but the evidence supporting this range is weak and the clinical validity of using the aPTT for predicting thrombotic or bleeding events is questionable. The aPTT test is also affected by numerous preanalytic and analytic variables that are unrelated to the anticoagulant effect of unfractionated heparin, further eroding its potential value for monitoring unfractionated heparin treatment. Unfractionated heparin dose appears to be more important than the aPTT in predicting clinical efficacy. Despite serious limitations, the reliance on the aPTT is likely to continue because of its ready availability and familiarity of clinicians with the test. The focus of clinicians who manage unfractionated heparin therapy should be to ensure that an adequate starting dose of unfractionated heparin is used and that the aPTT method is standardized. Future research efforts should be directed towards developing methods to improve standardization of the aPTT assay for monitoring unfractionated heparin. Direct measures of the concentration of unfractionated heparin in the blood are attractive because these assays are not affected by many of the biologic variables that interfere with the aPTT and may be suitable for automation. However, currently available unfractionated heparin assays are much more expensive than the aPTT, are not widely available, and their validity has not been adequately assessed in clinical outcome studies.
Why are direct measures of the concentration of unfractionated heparin in the blood attractive?
Direct measures of the concentration of unfractionated heparin in the blood are attractive because these assays are not affected by many of the biologic variables that interfere with the aPTT and may be suitable for automation.
Is unfractionated heparin more important than aPTT?
Unfractionated heparin dose appears to be more important than the aPTT in predicting clinical efficacy. Despite serious limitations, the reliance on the aPTT is likely to continue because of its ready availability and familiarity of clinicians with the test.
When is the data cutoff date for UFH?
Patient data including demographics, reason for admission, location (ward vs intensive care unit [ICU]), laboratory values, indication for UFH infusion, duration of UFH infusion, and bleeding events were obtained by manual review of the EMR with a data cutoff date of May 31, 2020. When the indication for anticoagulation was deep vein thrombosis (DVT) or pulmonary embolism (PE), we recorded whether the diagnosis was empiric or supported by radiographic confirmation.
What is the goal aPTT for UFH?
UFH infusions were predominantly high intensity (91.8% of patients who were COVID‐19 positive and 77.8% of patients who were COVID‐19 negative), with a goal aPTT of 60 to 80 seconds. When ordered, low‐therapeutic‐intensity infusions were more commonly observed in patients who were COVID‐19 negative. Treatment of confirmed or suspected DVT/PE was a common indication for UFH infusion but a significantly higher proportion of patients who were COVID‐19 positive were treated for this indication (51.5% vs 37.2%; P < .0001). Both acute and chronic DVT/PE were managed (COVID‐19 positive, 47 acute and 3 chronic; and COVID‐19 negative, 68 acute and 29 chronic). Atrial fibrillation or atrial flutter was the second most common indication, and there was no significant difference in the proportion of patients who were COVID‐19 positive and patients who were COVID‐19 negative using UFH for this indication.
Does UFH cause bleeding complications?
Our data indicate a higher incidence of bleeding complications in patients with COVID‐19 receiving weight‐based nursing‐nomogram titrated UFH infusions despite a higher prevalence of subtherapeutic aPTTs in this population. These data underscore the need for prospective studies aimed at improving the quality and safety of therapeutic anticoagulation in patients with COVID‐19.
What is the therapeutic range of heparin?
The CAP suggests the one-time establishment of a heparin concentration-derived aPTT therapeutic range. The cumulative summation method is suggested for range re-evaluation following reagent/instrument change. When anti-Xa monitoring is used, a therapeutic target of 0.3–0.7 units/mL is suggested.
How often should heparin be monitored?
We suggest using anti-Xa level monitoring in patients with heparin resistance, a prolonged baseline aPTT or altered heparin responsiveness. We suggest the aPTT or anti-Xa level be checked every 6 h until two consecutive therapeutic results are obtained, after which the frequency of monitoring can be extended to once daily.
How much heparin should I infuse for VTE?
In 1993, Raschke et al. compared weight based heparin dosing (80 units/kg followed by 18 units/kg/h) to a standard regimen (5000 units followed by 1000 units/h) in 115 patients with venous or arterial thrombosis [6]. A five-fold reduction in recurrent VTE was observed with weight-based dosing (95 % CI 1.1–21.9). Nevertheless, most VTE treatment trials incorporated a fixed dose initial heparin infusion regimen of 5000 unit bolus followed by infusion of approximately 1300 units /h [7]. In 1992, the ACCP VTE treatment guidelines suggested a 5000–10,000 unit bolus followed by a fixed heparin infusion of 1300 units/h (31,200 units/day) and in 1995 and 2004 they endorsed either a fixed regimen or the Raschke weight based regimen [8–10]. For a 70 kg patient, the Raschke regimen translates into a heparin bolus of 5600 units followed by infusion of 1260 units/h. The 2012 version of the guidelines do not address UFH dosing in the VTE treatment chapter [11]. However, in the chapter on parenteral anticoagulants, UFH dosing recommendations are similar to those in 1995 and include either a weight based regimen (Raschke regimen) or a fixed regimen of 5000 unit bolus followed by a continuous infusion of at least 32,000 units/day [12].
Is heparin anti-XA better than aPTT?
A recent review identified the potential advantages of the heparin anti-Xa level over the aPTT for heparin monitoring. Advantages included fewer monitoring tests, fewer dose changes and a shorter time to obtain therapeutic anticoagulation [20]. Large VTE trials evaluating patient outcomes with heparin anti-Xa level monitoring are not available. Although both the aPTT and the anti-Xa level can be used to monitor heparin, paired results within individual patients are often discordant [21]. In a recent trial in which clinical outcomes of aPTT versus anti-Xa monitoring were evaluated, a disproportionate prolongation of the aPTT relative to the anti-Xa level was the most common discordant pattern [22]. Patients with relatively high aPTT to anti-Xa levels had higher rates of major bleeding and death compared to patients with concordant paired test results. National guidelines for heparin monitoring recognize the limitations of both approaches without recommending a preferred approach [23].
Is heparin used for venous thromboembolism?
Heparin has been a component of the initial treatment of venous thromboembolism (VTE) for decades. Despite its long history, various aspects of the practical use of unfractionated heparin (UFH), whether delivered intravenously (IV) or subcutaneously (SC), continue to challenge clinicians. In 1998, the US FDA approved the low molecular weight heparin (LWMH) enoxaparin (Lovenox) for VTE treatment, followed by approval of the synthetic heparin-like compound fondaparinux (Arixtra) in 2004. In 2007, the LMWH dalteparin (Fragmin) was approved for VTE treatment in patients with cancer. These agents, intended for subcutaneous administration, offer practical advantages over unfractionated heparin, yet present their own challenges, particularly in special populations. This chapter will address the practical use and management of the parenteral heparin anticoagulants available in the US when used in the treatment of VTE.
Is anti-XA level monitored with heparin?
Direct anti-Xa level monitoring is recommended in those with heparin resistance (see subsequent section), baseline aPTT elevation from a lupus anticoagulant or contact factor deficiency or those with markedly elevated levels of fibrinogen or factor VIII [24].
