Heparin and Its Derivatives

• Learn the mechanisms of Herapin, an anticoagulant commonly administered through IV infusion and other subcutaneous methods. 
• Understand the pharmacotherapeutics of Herapin, such as it drug interactions, availability, and administration to patients.
• Review the nursing process when using Heparin, such as key diagnostic criteria, and educational resources nurses can provide to patients. 

Heparin is an antithrombotic drug prepared from animal tissues, used to prevent clot formation. It does not affect the synthesis of clotting factors. Therefore can not dissolve the already-formed clots because  

As a nurse, it may be easy to confuse Heparin with Hespan, a hetastarch. Make sure to check the drug twice before administration.  

Low-molecular-weight heparins, such as dalteparin sodium and enoxaparin sodium, are heparin derivatives made by decomposing unfractionated heparin into similar compounds. They were used to prevent deep vein thrombosis events.  

However, now they are more commonly used because of the advantage that they can be given subcutaneously and don’t require as much monitoring as unfractionated heparin. Another advantage is that they have longer half-lives compared to unfractionated heparin. Therefore, they need to be administered once or twice daily subcutaneously.  

Heparin and its derivatives are not well absorbed through the gastrointestinal tract. They are given parenterally. Unfractionated heparin is administered by continuous IV infusions.  

Heparin and its compounds aren’t given intramuscularly because of the risk of bleeding at the local injection site. It is metabolized in the liver, and metabolites are excreted through urine and not removed by hemodialysis. The half-life of heparin is 1 to 6 hours.  

Mechanisms of Heparin 

Heparin and its derivatives work by preventing the formation of new thrombi. Here is how they work: 

• By activating antithrombin III, heparin inhibits the formation of thrombin and fibrin.  
• Antithrombin III then inactivates factors IXa, Xa, XIa, and XIIa in the intrinsic and common pathways that eventually prevent the formation of a stable fibrin clot.  
• In low doses, heparin increases the activity of antithrombin III against factor Xa and thrombin and inhibits clot formation. To inhibit fibrin formation after a clot has formed, large doses of heparin are needed. This relationship between dose and effect is the rationale for using low-dose heparin to prevent clotting. 
• With heparin therapy, whole blood clotting time, thrombin time, and partial thromboplastin time (PTT) are prolonged. However, these changes may be only slightly prolonged with low or ultra-low preventive dosages.  

Pharmacotherapeutics 

Heparin is used in clinical conditions to prevent clot formation and extension of existing clots, in conditions, such as: 

• For the prevention or treatment of venous thromboembolism– characterized by inappropriate or excessive intravascular activation of blood clotting with extending embolisms.  
• Treatment of disseminated intravascular coagulation- a complication in which coagulation is increased.  
• Treating arterial clotting  
• Prophylaxis and treatment of thromboembolic disorders and thromboembolic complications associated with atrial fibrillation 
• Acute myocardial infarction prevents thrombus formation and promotes cardiac circulation by preventing clot formation at the already formed site.  
• Prevents clotting in arterial and cardiac surgery 

Off-label use of heparin is in STEMI, non-STEMI, unstable angina, and as an anticoagulant during percutaneous coronary intervention. 

Heparin is also used to prevent clot formation when the patient’s blood circulates out of their body, such as in: 

• cardiopulmonary bypass machine  
• hemodialysis machine 
• extracorporeal circulation 
• blood transfusions 

Heparin is also used to prevent clot formation during intra-abdominal or orthopedic surgery because in these surgeries, often, the clotting cascade is activated excessively. In fact, heparin is the drug of choice for orthopedic surgery. 

Low molecular weight heparins are also used to prevent deep vein thrombosis.  

Drug Interactions

With heparin or its derivatives, following drug interactions can occur. 

• When given concomitantly with oral anticoagulants, the clotting time can be increased more than desired. Keep an eye on the international normalized ratio (INR), and prothrombin time( PT) as it may be prolonged.  
• The risk of bleeding increases when the patient takes other drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), iron dextran, clopidogrel, cilostazol, or an antiplatelet drug, such as aspirin, ticlopidine, or dipyridamole.  
• Drugs that can inactivate the actions of heparin or its derivatives are antihistamines, digoxin, penicillins, cephalosporins, nitroglycerin, nicotine, phenothiazines, tetracycline hydrochloride, quinidine, neomycin sulfate, and IV penicillin. Therefore, when these drugs are being given concomitantly with heparin, monitor INR and prothrombin time.  
• Nicotine intake can inactivate the actions of heparin or its derivatives. If your patient smokes cigarettes, it can interact with the anticoagulant action of heparin.  
• Nitroglycerin can inhibit the effects of heparin or its derivatives.  
• Administration of protamine sulfate and fresh frozen plasma counteract the effects of heparin and heparin derivatives. 
• Herbs with anticoagulant and antiplatelet properties, such as garlic, ginger, and ginkgo biloba, may increase the risk of bleeding.  

In lab tests, heparin may cause an increase in free fatty acids, serum ALT, AST; aPTT and may decrease serum cholesterol. 

Cautions

Exercise precaution in the following conditions with heparin therapy: 

• In patients allergic to pork  
• Patients at risk for bleeding, such as those having congenital or acquired bleeding disorders, active GI ulcerative disease, hemophilia, concomitant platelet inhibitors 
• Severe hypertension 
• Menstruation  
• Recent lumbar puncture or spinal anesthesia 
• Recent major surgery or trauma 
• The use of preservative-free heparin is recommended in neonates, infants, and pregnant or nursing mothers. 

Contraindications

Heparin and its derivatives use are contraindicated in the following conditions: 

• Patients hypersensitive to heparin 
• Severe thrombocytopenia 
• Uncontrolled active bleeding (unless secondary to disseminated intravascular coagulation DIC) 
• History of heparin-induced thrombocytopenia (HIT) 
• Heparin-induced thrombocytopenia with thrombosis (HITT) 
• Patients who test positive for HIT antibody 

Lifespan Considerations

• For pregnant women in the last trimester, use heparin with caution, especially in the postpartum period, because of the increased risk of maternal hemorrhage. Heparin does not cross the placenta and is not distributed in breast milk.  
• In infants, benzoyl peroxide may cause gasping syndrome.  
• The elderly are more susceptible to hemorrhage, and age-related renal impairment that can increase the risk of bleeding with heparin therapy.  

Availability

In the form of an injection solution, heparin is available as: 

• 10 units/mL, 100 units/ mL, 1,000 units/mL, 5,000 units/mL, 10,000 units/mL, 20,000 units/mL 

As a premix solution for infusion, it is available as: 

• 25,000 units/250 mL infusion, 25,000 units/500 mL infusion 

Administration and Handling

When injecting, be mindful of following things with its administration and handling.  

• Do not give by IM injection as it poses a risk of pain, hematoma, ulceration, and erythema at the injection site.  
• For intravenous routes, Use in full-dose therapy. 
• Intermittent IV dosage produces a higher incidence of bleeding abnormalities. Therefore, a continuous IV route is preferred. 
• Premix solution needs no reconstitution. Infuse and 
• Titrate per protocol using an infusion pump. 

For subcutaneous administration: 

• It is used in low-dose therapy. 
• After withdrawl from the vial, change the needle before injection as it prevents leakage along the needle track.  
• Inject above the iliac crest or in the abdominal fat layer. 
• Do not inject within 2 inches of the umbilicus or any scar tissue.  
• Withdraw the needle rapidly and apply prolonged pressure at the injection site.  
• Do not massage or apply heat or cold to the injection site.  
• Rotate injection sites. 

IV Incompatibilities

Heparin is incompatible with the following drugs: 

• Amiodarone (Cordarone) 
• Amphotericin B complex (Abelcet, AmBisome, Amphotec), 
• Ciprofloxacin (Cipro) 
• Dacarbazine (DTIC) 
• Diazepam (Valium) 
• Dobutamine (Dobutrex) 
• Doxorubicin (Adriamycin) 
• Filgrastim (Neupogen) 
• Gentamicin (Garamycin) 
• Haloperidol (Haldol) 
• Idarubicin (Idamycin) 
• Labetalol (Trandate) 
• Nicardipine (Cardene) 
• Phenytoin (Dilantin) 
• Quinidine (Cardioquin) 
• Tobramycin (Nebcin) 
• Vancomycin (Vancocin) 

IV Compatibilities

Heparin and its derivatives are compatible with the following drugs: 

• Ampicillin/sulbactam (Unasyn) 
• Aztreonam (Azactam) 
• Calcium gluconate, 
• Cefazolin (Ancef) 
• Ceftazidime (Fortaz) 
• Ceftriaxone (Rocephin) 
• Dexmedetomidine (Precedex) 
• Digoxin (Lanoxin) 
• Diltiazem (Cardizem) 
• Dopamine (Intropin) 
• Enalapril (Vasotec) 
• Famotidine (Pepcid) 
• Fentanyl (Sublimaze) 
• Furosemide (Lasix) 
• Hydromorphone (Dilaudid) 
• Insulin 
• Lidocaine 
• Lorazepam (Ativan) 
• Magnesium sulfate 
• Methylprednisolone (SoluMedrol) 
• Midazolam (Versed) 
• Milrinone (Primacor) 
• Morphine 
• Nitroglycerin 
• Norepinephrine (Levophed) 
• Oxytocin (Pitocin) 
• Piperacillin/tazobactam (Zosyn) 
• Procainamide (Pronestyl) 
• Propofol (Diprivan) 

Adverse Reactions

An advantage of heparin therapy is that it produces relatively few adverse effects, which can usually be prevented if the patient’s PTT is maintained within the therapeutic range, like one and a half or two times the control. 

The most common adverse effect of heparin therapy is bleeding. However, to reverse that, you can administer protamine sulfate that binds with the heparin and forms a stable salt.  

Other adverse effects of heparin and its derivatives are: 

• Bruising 
• Hematoma formation 
• Necrosis of the skin or other tissue 
• Thrombocytopenia 

Nursing Processes 

For a patient taking heparin or its derivatives, the following nursing processes should be followed. 

Assessment  

• Assess the patient for adverse drug reactions and bleeding.  
• Before starting the therapy, assess the patient’s underlying condition.  
• Before starting the therapy, and with it, monitor the patient’s vital signs, hemoglobin level, hematocrit, platelet count, PT, INR, and PTT. And assess the urine, stool, and emesis for blood. 

Key Nursing Diagnoses 

• Ineffective protection related to the drug’s effects on the body’s normal clotting and bleeding mechanisms 
• Risk for deficient fluid volume related to bleeding 
• Deficient knowledge related to drug therapy 

Planning Outcome Goals 

• The patient’s clotting time will be appropriate according to the drug therapy.  
• The patient will maintain adequate fluid volume, as evidenced by vital signs and laboratory studies. 
• The patient and their family members will have an understanding of the drug therapy.  

Baseline Assessment  

• Before starting heparin therapy, make sure you have obtained the patient’s CBC, PT/INR, and aPTT.  
• Cross-check dose with a co-worker to avoid errors. 
• Assess the patient for bleeding risk. Question them about the history of recent trauma, head injuries, and GI/GU bleeding. Ensure that the patient has not received spinal anesthesia, and spinal procedures recently.   

Implementation 

With heparin and its derivatives therapy, follow these nursing implementations.  

• Monitor CBC, and PT/INR daily. Obtain aPTT 6 hours after starting the drug or any change in dosage until a maintenance dose is established, then check aPTT every 24 hours or per clinical standards. In long-term therapy, monitor 1 to 2 times monthly. Diligently assess the patient for external or internal bleeding. If the platelet count decreases more than 50% from baseline, obtain a stat HIT antibody test. If HIT antibodies are positive, discontinue heparin and consider treatment with a direct thrombin inhibitor, such as argatroban. Moreover, avoid all heparin products and place heparin allergy on the chart. Monitor urine and stool for occult blood. Assess for the decrease in blood pressure, increase in pulse rate, abdominal or back pain, and severe or pulsating headache that can indicate hemorrhage.  
• For female patients, ask them if they have an increase in discharge during menses.  
• Assess peripheral pulses and skin for ecchymosis, and petechiae.  
• Check the patient’s body for excessive bleeding from minor cuts and scratches. Assess gums for erythema, gingival bleeding, and urine output for hematuria. 
• When shifting to warfarin (Coumadin) therapy, monitor PT/INR results that will be 10%–20% higher while heparin is given concurrently. 
• Keep a keen eye on the patient’s prothrombin time. Anticoagulant effects are obtained when the patient has one and a half to two times the control values.  
• Avoid intramuscular injections of anticoagulant drugs if possible. However, do not administer heparin through the intramuscular route.  
• Keep protamine sulfate handy to prevent bleeding because of heparin or its derivatives.  
• If the patient has serious adverse reactions, inform the physician soon.  
• To minimize the risk of hematoma, avoid intramuscular administration of other drugs.  
• Maintain bleeding precautions throughout therapy. 
• Administer IV solutions using an infusion pump, as appropriate. 

Patient Teaching  

Heparin can cause bleeding. When teaching the patient and their family members about heparin therapy, the following points can be helpful: 

• Instead of using a sharp razor, use an electric razor. 
• Use a soft toothbrush to prevent bleeding. 
• Report immediately if you notice red or dark urine, black or red stool, coffee-ground vomitus, blood-tinged mucus from cough, signs of stroke, nosebleeds, or increased menstruation. 
• Do not use any OTC medication without the approval of your physician, as it may interfere with platelet aggregation.  
• While on heparin therapy, you should wear or carry an identification that notes anticoagulant therapy.  
• Inform the dentist and other physicians that you receive heparin therapy.  
• Make sure to limit alcohol with heparin therapy, as their combination can lead to liver damage and increased adverse effects.  

Route, Dosage, and Indications of Heparin 

• For line flushing in children, adults, and the elderly, given through an intravenous route: 100 units as needed. However, for infants less than 10 kgs, the dose is 10 units as needed.  
• For acute coronary syndrome, in adults and the elderly, IV infusion: 60 units per kg bolus (Maximum: 4,000 units), then 12 units/kg/hr (Maximum: 1,000 units per hour as a continuous infusion). 
• For cardiothoracic surgery in adults and elderly, given intravenously: Initially, 300 to 400 units/kg before arterial or venous cannulation. Titrate according to the activated clotting time. Bypass initiated once activated clotting time is at least 400 seconds. 
• For the treatment of deep vein thrombosis and pulmonary embolism, in adults and the elderly, given as IV infusion: 80 units/ kg bolus (Maximum: 5,000 units), then 18 units/kg/hr adjusted according to aPTT. 
• The usual pediatric or neonatal dose is given intravenously: 75 units/kg bolus over 10 min, then an initial maintenance dose of 28 units/ kg/hr. Adjust dose according to aPTT per protocol. 
• For thromboembolic prophylaxis, in adults and the elderly, given subcutaneously: 5000 units every 8 to 12 hours.  

Antidote For Heparin Toxicity  

The antidote for heparin toxicity is Protamine sulfate, given 1 to 1.5 mg IV for every 100 units of heparin SQ within 30 min of overdose, 0.5 to 0.75 mg for every 100 units heparin SQ if within 30 to 60 min of overdose, 0.25 to 0.375 mg for every 100 units heparin SQ if 2 hours have elapsed since overdose, 25 to 50 mg if heparin was given by IV infusions. 

The Bottom Line

Heparin is an essential drug in preventing blood clots. However, at the same time, it poses a risk of bleeding. Monitor PT and INR closely with heparin therapy. Ask the patient to report to you soon if they notice blood in their bodily secretions.  

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