Venous Thrombosis
Hau C. Kwaan, Meyer M. Samama in Clinical Thrombosis, 2019
The anticoagulant effect of heparin can be immediately neutralized by the intravenous injection of protamine sulfate. The appropriate neutralizing dose of protamine depends on the dose of heparin, its route of administration, and the time it was given. If protamine sulfate is used within minutes of an intravenous heparin injection, a full neutralizing dose (1 mg protamine sulfate per 100 U of heparin) should be given. An injection of protamine sulfate in a bolus of more than 50 mg is seldom required, since the plasma half-life of intravenous heparin is approximately 60 min. Protamine sulfate should be injected slowly over a 10- to 30-min period to avoid a hypotensive response. Treatment with protamine sulfate may need to be repeated because protamine is cleared from the blood more quickly than heparin. After a subcutaneous injection of heparin, repeated small doses of protamine may be required because of prolonged heparin absorption from the subcutaneous depot.
Endovascular repair of infrarenal abdominal aortic aneurysms
Sachinder Singh Hans, Alexander D Shepard, Mitchell R Weaver, Paul G Bove, Graham W Long in Endovascular and Open Vascular Reconstruction, 2017
A completion aortogram is performed with the pigtail catheter at the level of the RAs to confirm position, proximal seal, and RA patency (Figure8.7). Fluoroscopic imaging is prolonged to visualize any endoleaks. Commonly, the pigtail catheter is then drawn into the aortic graft for an additional injection to evaluate the iliac seal zones and IIA patency, and any evidence of type IB endoleaks. If there are concerns for a type I endoleak, additional angioplasty or aortic or iliac cuff placement may be necessary. Significant impingement on a RA can be addressed. If there is concern of kinking of iliac components as they transition into the iliac arteries, additional supportive stents, either covered or uncovered, may be necessary to treat any significant dissections in the iliac arteries. Once satisfactory insertion of the stent graft has been confirmed, the sheaths and catheters are removed. If an open surgical exposure was performed, the artery access sites are typically closed primarily with polypropylene suture in a transverse manner. More severely diseased atherosclerotic arteries may require endarterectomy and patch angioplasty. Percutaneous access is closed using the pre-close technique. For the percutaneous method of access, it is the author’s preference to address the main body delivery site first, and once successful the contralateral side. After ensuring satisfactory distal lower extremity arterial perfusion, protamine sulfate may be administered.
Pediatric vascular trauma
David E. Wesson, Bindi Naik-Mathuria in Pediatric Trauma, 2017
Unfractionated heparin and low-molecular-weight heparin are indirect thrombin inhibitors. Heparin is a mixture of sulfates mucopolysaccharides [29]. Heparin binds to antithrombin, resulting in a conformational change exposing its active site. This allows for more rapid interaction and subsequent inhibition of clotting factors, such as thrombin (IIa), IXa, and Xa. Unfractionated heparin is the first-line intervention to treat arterial and venous thrombosis in the pediatric population [31]. Age-dependent reference ranges are available for antithrombin, tissue factor pathways inhibitor, thrombin, and factor X to assist with monitoring heparin dosing. According to the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy, the plasma of neonates has decreased thrombin when compared with adults. Furthermore, the proportion of thrombin in the plasma of a neonate is similar to that of an anticoagulated adult. Over time the level of thrombin increases. Children, however, have 25% less thrombin than do adults [30]. Reported rate of bleeding from heparin use in the pediatric population is 1.5%. Only three cases of heparin-induced osteoporosis are reported in the literature. Therapeutic heparinization when indicated should be titrated to a target anti-Xa activity range of 0.35–0.70 units/mL [30]. Pediatric heparin-induced thrombocytopenia is also described. The anticoagulant action of heparin can be reversed by protamine sulfate, a basic peptide that combines with heparin and leaves it inactive [29]. One milligram of protamine sulfate is necessary for every 100 U of heparin remaining in the patient. The rate of infusion of protamine sulfate should not exceed 50 mg in 10 minutes.
The efficacy of anti-VEGF antibody-modified liposomes loaded with paeonol in the prevention and treatment of hypertrophic scars
Published in Drug Development and Industrial Pharmacy, 2019
Jun Shi, Yanting Wu, Siyi Guo, Huidi Zhang, Guitian Chen, Xiaoqi Xu
In the pretest and BBD experiment, the EE of PAE was used as the most important indicator to optimize the formulation. The commonly used methods for determining the EE include gel column chromatography, dialysis, protamine aggregation, and ultracentrifugation [53]. Protamine sulfate is a polycationic macromolecule composed of amino acids. It can be used to increase the density of liposomes by getting adsorbed on their surface through electrostatic interactions; hence, they can be separated rapidly, efficiently and easily from free drugs using a minimal centrifugal force. Since the separation is based on electrostatic attractions and independent of the encapsulated drug, this technique is pertinent for EE determination of nearly all drugs [54]. In this study, a large experimental validation showed that the protamine aggregation method could separate free PAE and liposomes effectively, and could determine EE accurately compared to other methods.
Perioperative management of anticoagulation
Published in Hospital Practice, 2020
Goutham Talari, Zachary D. Demertzis, Robert D. Summey, Baljinder Gill, Scott Kaatz
The reversal agent for all heparins is intravenous protamine sulfate, which may be administered as a fixed dose of 50 mg given over 10 min (to avoid hypotension) and repeated once if refractory bleeding continues, or as a calculated dose based on the time since last heparin dosing [33]. Protamine sulfate is derived from fish sperm and patients who have previously received NPH (Neutral Protamine Hagedorn) insulin, have fish allergies, or have undergone vasectomy are at increased risk for allergic reactions [33]. Notably, protamine will fully reverse UFH but only reverses approximately 60% of LMWH anti-Xa activity [34].
Heparin Induced Thrombocytopenia: A Novel Approach to Anticoagulation During Transcatheter Aortic Valve Replacement Utilizing Cangrelor
Published in Structural Heart, 2018
Daniel Walters, Mitul Patel, Eugene Golts, Swapnil Khoche, Ehtisham Mahmud, Ryan Reeves
Cangrelor is an ATP analog with very high receptor affinity and near immediate cessation of P2Y12/ADP- mediated platelet activation, resulting in greater than 80% inhibition in all patients at steady state infusion and 100% inhibition in nearly 90% of patients.3,4 The medication half-life is 3–5 minutes due to rapid dephosphorylation by serum esterases. Binding to the P2Y12 receptor is reversible, resulting in restoration of 60% of baseline platelet function within 1 hour of infusion cessation.3 Antithrombin-III activity is increased 1,000-fold after heparin binding, resulting in deactivation of thrombin and other proteases. Protamine sulfate binds directly to heparin creating a chemically inactive molecule and reversing the anticoagulant effect. HIT occurs when heparin binds to platelet factor 4 (PF4), causing the formation of IgG antibodies against the complex.5 This induces not only autoimmune-mediated platelet destruction but concurrent platelet activation via the FcγIIa receptor with a hyperthrombotic state. When manifestations of acute HIT are present, mortality rates have been reported between 14.5 and 25%.5 Here, cangrelor was used for potent platelet inhibition via ADP inactivation with the effect being more predictable and absolute than oral P2Y12 inhibitors. The ability of cangrelor to prevent platelet activation and PF4 release may result in less heparin-PF4 complex and antibody formation, as well as mitigate the arterial and venous thrombogenicity associated with HIT. Upon completion of the procedure, the heparin was rendered inert with protamine sulfate, eliminating both the anticoagulant effect and possible immune response, after which the cangrelor infusion was discontinued. This novel approach is the first reported of its kind in a percutaneous procedure.
Related Knowledge Centers
- Bradycardia
- Cardiac Surgery
- Childbirth
- Heparin
- Hypotension
- Vasectomy
- Anaphylaxis
- Allergy
- Low-Molecular-Weight Heparin
- Intravenous Therapy