A Comprehensive Nurses’ Guide to Heparin Drips

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Introduction   

Heparin is the most widely used antithrombotic and anticoagulant therapy today. It became widely used in 1916 and is still a first line of defense for many conditions being treated today. Not only is it an effective antithrombotic and anticoagulant, but it also has antitumor, antiviral, and anti-inflammatory properties, furthering its extensive use. Heparin administration is most commonly used for cardiovascular and cerebrovascular disease management [1]. 

Unlike many other drugs, heparin is still in use after its initial inception over a century ago. Medical advancements have been made in improving heparin, but in addition to its being a long-used therapy, it is also inexpensive, has a quick onset when given intravenously, and can easily be reversed [1]. 

Heparin is used in a variety of clinical settings and can be administered both intravenously and subcutaneously. As will be discussed further in the course, heparin administration should be closely monitored to prevent adverse events and promote patient safety. 

Mechanism of Action 

Heparin is a naturally occurring anticoagulant that prevents blood clot formation. It works primarily by enhancing the activity of antithrombin III (ATIII), a protein that inactivates several key enzymes involved in blood clotting.  

Antithrombin III is a naturally occurring protein in the blood that inhibits several key clotting factors. The most important of these is Thrombin (Factor IIa): Thrombin converts fibrinogen to fibrin, the protein that forms the mesh of a clot. Factor Xa is crucial in the common pathway of coagulation, where it activates thrombin (Factor II) from prothrombin. 

Without antithrombin, these enzymes would be more active, leading to excessive clotting. Heparin works by binding to antithrombin III and increasing its ability to inhibit thrombin and Factor Xa. 

Medical advances in the 1980s gave way to Low Molecular Weight Heparin (LMWH), changing and improving some of the initial properties of unfractionated heparin (UFH). The full-length heparin molecule binds to ATIII, and the complex can inhibit both thrombin (Factor IIa) and Factor Xa effectively. However, the heparin molecule is large, limiting its ability to directly inhibit thrombin in certain conditions. However, it is fast-acting, wears off quickly, and requires extensive lab assessment [1]. 

LMWH is derived from heparin but has smaller molecules. It still binds to ATIII but primarily inhibits Factor Xa, which has less effect on thrombin. This is why LMWH can be used as a subcutaneous injection in outpatient settings: It has a more predictable dose response and longer half-life compared to unfractionated heparin. Examples include Lovenox and Enoxaparin injections [1]. 

Indications for Heparin Use 

As stated above, heparin is widely used to treat many conditions and diseases. In the emergency department, heparin drips are commonly used to treat myocardial infarction with S-T elevation (STEMI). Often, patients with STEMI have unstable plaque due to coronary atherosclerosis. Thrombosis can become an issue and impede blood flow to coronary arteries, causing ischemia in the heart [1,2].  

When this occurs, the main goal (before cardiac catheterization) is to restore reperfusion as quickly as possible. Heparin is beneficial as it prevents further thrombus formation, supports blood flow through the coronary artery, and increases the patency of the damaged artery, allowing oxygen to return to the ischemic cardiac tissue [2].  

Furthermore, heparin benefits STEMI patients as it reduces the risk of further thrombolytic events. It can lower the likelihood of continued myocardial ischemia or subsequent STEMIs [2].  

If the patient is continuing from the emergency department for cardiac catheterization, “pretreatment with unfractionated heparin (UFH) before arrival at the coronary catheterization laboratory is often administered to improve spontaneous reperfusion rates and reduce clot burden [3]. 

Patients receiving emergency care for STEMI often immediately undergo a percutaneous coronary intervention (PCI), which involves balloon and stent placement. A cardiologist will identify the blockage, widen the vessel with a balloon, and then place a stent to minimize stenosis and blockage [4].  

Depending on the medical indication, subcutaneous heparin or heparin drips are also utilized to “bridge the gap” until long-term anticoagulant therapy, such as warfarin, coumadin, or Eliquis, can be achieved. The American College of Chest Physicians also recommends heparin use during cardioversion to correct atrial fibrillation, systemic emboli, or venous thrombosis [5]. 

Radiofrequency catheter ablation is employed to correct atrial fibrillation and improve symptoms such as syncope, palpitations, and shortness of breath in patients with the condition. Unfortunately, there is a risk of peri-procedure thromboembolism, making an anticoagulant a necessary line of defense. Studies have shown that heparin infusions during the procedure greatly reduce the risk of blood clots [6]. 

Heparin Drips and Dosing 

If a patient’s condition warrants a heparin drip, the dose will depend on the provider’s orders and hospital policy. Heparin drips are most often weight-based, and nurses should work closely with the pharmacy and the provider to ensure safe and therapeutic dosing. The University of Washington School of Medicine has provided general guidelines on dosing for different conditions [7]. 

Lab Monitoring 

Lab monitoring during intravenous heparin administration is critical, not only for patient safety but also to ensure that therapeutic levels are achieved. To determine therapeutic levels for heparin administration, both activated partial thromboplastin time (aPTT) and activated clotting time (ACT) must be monitored. aPTT and ACT measure clotting time, which is extended by heparin. 

“Activated partial thromboplastin time is performed at baseline and every 6 hours until two or more therapeutic values are obtained, then aPTT can be assessed every 24 hours” [5]. Monitoring aPTT is not only crucial to ensure therapeutic levels but also to guide heparin drip titration to maintain them. 

aPTT is deemed at a therapeutic level when it is 1.5 to 2 times a control, which is facility-dependent (the goal being prolonged clotting time). It should be noted that aPTT is a more reliable marker when measuring clotting time. It is far more sensitive to clotting abnormalities than ACT. “ACT will only detect abnormalities when there is a 95% abnormality rate in the factors, whereas aPTT can detect when there is a 70% abnormality” [5]. 

ACT is, however, a point-of-care test, meaning it can be done at the bedside, making it much easier for patients, and it also offers quick results. ACT monitoring will often be employed during cardiopulmonary bypass, ECMO, and PCI to monitor real-time heparin infusion effectiveness [5].  

Adverse Effects 

The healthcare team should closely monitor heparin use and administration. Although heparin is relatively safe, it can cause patient complications such as excessive bleeding and alopecia. Patients may experience blood in the stool or urine, new-onset bruising, petechia, or nosebleeds. Any of these symptoms should be immediately reported to the provider [5].  

Heparin can cause mild to severe bleeding events, such as intracranial hemorrhage. Research has shown that excessive bleeding from heparin can cause paralysis when a hematoma occurs at the site of epidural anesthesia or a spinal cord puncture.  Heparin can also bind to bone, resulting in loss of bone mass and causing long-term osteoporosis [15].  

Thrombocytopenia can also occur when the body does not make enough platelets, the blood cells responsible for clotting. Thrombocytopenia can occur in up to 30% of patients receiving heparin therapy. Usually, this does not cause adverse outcomes, but it can be reversed by stopping heparin use. However, there is a more serious form called heparin-induced thrombocytopenia (HIT) [5].  

HIT is an immune response and can have severe patient outcomes. “This complex alerts the immune system and causes an immune-mediated reaction with platelets. Clot formation activates and consumes platelets by providing a pro-thrombotic environment with a low platelet count” [5]. Thrombosis can occur, causing serious complications such as deep vein thrombosis, myocardial infarction, pulmonary embolus, and stroke. Thrombosis in major arteries supporting vital organs can occur, leading to amputation or even death [5]. 

HIT is usually identified in patients approximately five days into heparin therapy. The first course of action is to stop using all heparin infusions or subcutaneous injections immediately. Other non-heparin anti-coagulants will need to be introduced, such as bivalirudin, to prevent and treat HIT-related thrombosis [8].  

Nurses and healthcare providers should monitor their patients closely for bleeding complications and review labs accordingly when considering HIT as a diagnosis. The “4 Ts” should be considered: timing, thrombocytopenia, thrombosis, and any other possible causes of thrombocytopenia [9]. 

To confirm the presence of HIT, lab results need to be looked at as a whole. Platelet counts are crucial to monitor. If there is a significant decrease from the baseline, HIT should be considered. Immunoassays, or the ELISA test, detect antibodies against the heparin-platelet factor 4 (PF4) complex, which is commonly present in patients with HIT. A positive test indicates the diagnosis of HIT, although it’s not wholly diagnostic by itself [9]. 

Functional assays are also used to diagnose HIT. This included a serotonin release assay (SRA) or a heparin-induced platelet activation (HIPA) test. These tests measure the functional activity of the HIT antibodies and are more specific for diagnosing HIT. They are often used when the clinical suspicion for HIT is high, but the immunoassay is negative or unclear [9].  

Nurses should also monitor vital signs closely and be especially aware of hypotension. If the nurse identifies hypotension or a decrease in hemoglobin and/or hematocrit, evaluation for hemorrhage from heparin toxicity should be considered, and the provider should be immediately made aware [5].  

If patients are experiencing heparin toxicity, protamine sulfate is indicated as the reversal agent. Protamine binds to heparin, making it ineffective and restoring its coagulation properties. No more than 50 mg of protamine should be administered intravenously, slowly over 10 minutes. Every 1mg of protamine neutralizes 100 units of heparin, and heparin neutralization should occur within 5 minutes [5].  

Protamine pushed too rapidly can cause severe side effects, including hypotension, pulmonary edema, pulmonary vasoconstriction, pulmonary hypertension, and anaphylaxis. 

Nursing Considerations 

Nurses need to exercise great responsibility when administering heparin. “According to ISMP (Institute for Safe Medication Practices), heparin is in the high-risk medication classification that correlates with a multitude of patient safety errors and has the potential to cause significant harm” [5]. A nurse needs to be aware of the high risk for errors during heparin administration. Nurses need to be acutely aware of dosing, route of administration, the weight of the patient, lab monitoring, and heparin toxicity [5].  

Nurses should follow hospital policy when beginning a heparin infusion and use the two-nurse method to verify the right dose and the right route. 

Heparin is most often administered by weight, which can increase the margin of administration error. Doses can vary from unit/kilogram/hour to unit/hour or milliliters/hour, and administration is also based on indication. The variation in dosing and indication warrants careful consideration and multi-discipline checks for safety and accuracy. Studies have shown that patient safety is enhanced when pharmacists are involved in heparin administration and provide safe dosing support [5].  

Nurses need to have a thorough understanding of aPTT monitoring as therapeutic levels guide heparin titration. APTTs should be monitored every 4-6 hours based on facility protocol. Facility protocols then guide the titration based on the results, leaving the nurse responsible for titrating heparin accordingly [5].  

Nurses need to clearly understand titration principles and the different dosing methods such as unit/kilogram/hour, etc. Attention to detail during titration is paramount, and the nurses should work with another nurse to verify dosing. Labs should be closely evaluated along with patient response to therapy [5]. 

Again, safe heparin drip administration requires a multidisciplinary effort involving the provider, pharmacy, and nursing to maximize patient safety. Heparin is a high-risk medication, and safety precautions should be implemented for each bolus, at the start of the continuous drip, during titration, and throughout the patient’s treatment [5].  

Nursing assessment of patients receiving heparin or about to receive heparin should be thorough. Patients should be screened for heparin allergy or allergies to anticoagulants, and the nurse should ensure labs such as CBC, PT/INR, aPTT, and ACT are being monitored. Nurses should also screen for hematuria, skin bruising, gingival bleeding, or skin discoloration that could indicate excessive bleeding [10].  

Nurses should also continuously assess patients for severe abdominal and back pain or headaches, as these can be signs of heparin toxicity. Nurses should also be aware of excessive bleeding during invasive procedures such as lab draws and IV starts. Extra pressure and gauze will be needed to inhibit bleeding. Nurses should also continuously check any IV sites or surgical incisions for abnormal bleeding [10]. 

Patient contraindications to heparin infusion should also be closely evaluated before administration. The nurse should be aware of the following and hold heparin for any of the following [5]: 

• Patients unable to receive continuous lab monitoring 
• Previous heparin-induced thrombocytopenia 
• Platelet count of > 100,000 
• Patients with an uncontrolled bleed 
•  

Heparin Use in Pregnancy & Postpartum 

Pregnant women are at increased risk of blood clots due to hormonal changes and decreased blood flow to the legs later in pregnancy, making them at higher risk for DVT or PE. Women who give birth by C-section are also at increased risk of blood clots due to decreased mobility. Heparin therapy is a first-choice treatment for DVT during pregnancy as it doesn’t cross the placenta [11]. 

Heparin also has no known teratogen effects on the fetus, unlike vitamin K agonists such as warfarin. Studies have also denoted that HIT is very rare in pregnant women, further making it the therapy of choice for pregnant women with suspected or confirmed PE [11].  

Heparin dosing during pregnancy follows the same guidelines as non-pregnant people and should be weight-based. Currently, LMWH is most often used during pregnancy, given the subcutaneous route. However, the LMWH is usually transitioned to UFH infusion (as discussed above, it is fast-acting and wears off quickly) at approximately 36 hours before delivery. At approximately four to six hours before delivery, the heparin infusion should be paused [11].  

Depending on facility protocol and the provider, LMWH may be reintroduced after delivery. The route of administration and type of heparin should be determined based on thrombosis risk and the patient’s health profile [11]. 

Heparin Use in the Pediatric Population 

Heparin is an advantageous choice for anticoagulant therapy in both the adult and pediatric patient populations. Heparin is widely used in the management of venous thromboembolism, congenital heart defects, and pulmonary embolus, amongst other conditions in infants and children. Like adults, dosing is based on indication, patient weight, and facility policy. 

According to the University of Wisconsin Medical School, guidelines for pediatric heparin dosing are as follows [12]: 

Like adults, heparin infusion titration is based on lab monitoring and clotting factors. aPTT, ACT, or anti-Xa levels (depending on facility policy) should be monitored just before initiation of infusion and then 6 hours after any titrations [12]. 

It should be noted that heparin therapy can be challenging to manage in children. Even though heparin is most often weight-based, neonates require the highest dosages to reach therapeutic levels due to their low antithrombin levels and fast clearance.  

Antithrombin levels can also be very low in critically ill children and neonates, giving way to heparin resistance. In addition, “heparin monitoring is challenging as measurement of anti-Xa levels and activated partial thromboplastin time (aPTT) require intravenous access, which can be very problematic for children” [12].  

Patient Education 

Nurses are integral to patient and family teaching and should provide comprehensive education during heparin administration. Nurses should include the following key teaching points when discussing heparin [10]:  

• Instruct your patient to use a soft bristle toothbrush during therapy to decrease bleeding in their gums. 
• Advise patients to use an electric razor to avoid cuts, reducing the opportunity for excessive bleeding. 
• Patients should be instructed to report any nosebleeds, hematuria, blood in their stool (black stool), unusual bruising, or skin discoloration to their nurse or healthcare provider immediately.  
• Alcohol can increase the risk of bleeding. 
• Patients should report severe headaches, abdominal pain, or back pain to their nurse or healthcare provider immediately, as these may be signs of excessive bleeding and heparin toxicity. 
• Patients should be encouraged to report any signs or symptoms they deem unusual after heparin therapy is started, especially if they experience fatigue, hypotension, or dizziness.   
• Non-steroidal anti-inflammatories can increase the risk of bleeding, so patients should be aware not to take any medications their nurse and providers are not aware of.  

Emerging Trends 

Since the initial use of heparin in the early 1900s, advances and changes in heparin derivatives have continued to emerge. New heparin-based biomolecules and conjugates are developing. Heparin is widely used as an anticoagulant, but it’s also being trialed to treat inflammation. Studies using heparin to treat conditions such as arthritis, inflammatory bowel disease, and bronchial asthma are proving very productive [13].  

In the case of sepsis, LMWH is now found to be a key supportive therapy. It decreases the risk of multiple organ dysfunction syndrome and reduces mortality rates. “The interactions of heparin with pro-inflammatory factors and involvement in procoagulant cascades hold promise in mitigating the inflammation and coagulopathy associated with sepsis” [13].  

Studies also reveal that heparin not only provides anticoagulation properties for cancer patients but also inhibits metastasis. Heparin interferes with tumor cells and the endothelial cells of blood vessels, slowing or halting cancer progression. Heparin use in oncology patients is continuously being researched with promising results [14]. 

Heparin use is also showing promising results in combatting malaria. Vaccine research has been stagnant, making the need for new treatments crucial. The structural makeup of heparin and its ability to bind to packed red blood cells give it anti-malarial properties. Heparin increases bleeding, which could increase the risk of infection in malaria treatment, making heparin on its own not a viable malaria treatment. However, its anti-malarial properties are promising for further research to find treatment.  

As discussed above, HIT can also have severe outcomes. HIT can cause skin damage or skin necrosis at the injection site. Heparin can also bind to bone, resulting in loss of bone mass and causing long-term osteoporosis. Heparin should be used judiciously, and nurses should closely monitor patients on heparin therapy [15]. 

Conclusion

Heparin has long been used for its anticoagulant properties. Advances to its structure have been made, producing low molecular weight heparin, which can be used as an outpatient due to its predictable dosing and longer half-life. Heparin infusions, however, are a valuable treatment for patients in the hospital who have had a STEMI, are going for PCI, radio frequency catheter ablation for AFIB, or to bridge the gap to oral or subcutaneous therapy. 

Labs are to be monitored regularly for patient safety and to titrate heparin infusions. Labs most commonly checked are aPTT, ACT along with PT/INR, platelets, hemoglobin, and hematocrit. Nurses should assess their patients regularly, watching for any signs of heparin-induced thrombocytopenia, such as hypotension. ELISA and or a HIPA test. 

Heparin is a high-alert medication, and nurses should employ multidisciplinary verification when infusing heparin. Another nurse should always verify the right dose and right route and make sure there are no contraindications to the patient starting heparin therapy. Patients should be thoroughly educated on signs and symptoms associated with excessive bleeding, and the nurse should assess for skin discoloration, hematuria, hypotension, bruising, and bleeding from IV or surgical sites.  

Heparin use continues to grow and expand, with trials being researched for its anti-inflammatory and anti-malarial properties. Heparin is being used to help treat sepsis, along with new uses in cancer treatment. Although it is a high-risk medication and should be used with extreme caution, it’s also the most widely used anti-coagulant with a relatively safe safety profile. It shows great promise in the treatment of many conditions. 

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