Heparin; Uses, Dosage, Side Effects, Drug Interactions

Heparin also is known as unfractionated heparin (UFH), is medication which is used as an anticoagulant (blood thinner). Specifically, it is used to treat and prevent deep vein thrombosis?, pulmonary embolism?, and arterial thromboembolism. It is also used in the treatment of heart attacks and unstable angina. It is given by injection into a vein. Other uses include inside test tubes and kidney dialysis machines. Heparin is obtained from liver, lung, mast cells, and other cells of vertebrates.

Mechanism of Action of Heparin

Under normal circumstances, antithrombin III (ATIII) inactivates thrombin (factor IIa) and factor Xa. This process occurs at a slow rate. Administered heparin binds reversibly to ATIII and leads to almost instantaneous inactivation of factors IIa and Xa The heparin-ATIII complex can also inactivate factors IX, XI, XII, and plasmin. The mechanism of action of heparin is ATIII-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin is not thrombolytic or fibrinolytic. It prevents the progression of existing clots by inhibiting further clotting. The lysis of existing clots relies on endogenous thrombolytics.

Indications of Heparin

• Angina
• Antiphospholipid syndrome
• Deep vein thrombosis, 
• Heart attack
• Pulmonary embolism?
• Unstable angina 
• Venous thromboembolism
• Acute? coronary syndrome,
• Atrial fibrillation
• Deep-vein thrombosis and pulmonary embolism?
• Cardiopulmonary bypass for heart surgery
• ECMO circuit for extracorporeal life support
• Hemofiltration
• Indwelling central or peripheral venous catheters
• Anticoagulation during pregnancy
• Thrombotic/thromboembolic disorder
• Clotting
• Consumption coagulopathy
• Disseminated Intravascular coagulation
• Interstitial cystitis
• ST elevation myocardial infarction? thromboembolism
• Thrombosis?, venous
• Embolization
• Peripheral arterial embolism?

Contra-Indications of Heparin

• Brain operation
• Spinal tap
• Operation on the spine
• Eye surgery
• Hemophilia
• Deficiency of anti-clotting agents
• Decreased platelets due to the medication heparin
• Decreased blood platelets
• Severely decreased platelets
• Patient with a catheter in the vascular system
• Severe uncontrolled high blood pressure
• Subacute infection? of the heart valve
• Hemorrhage in the brain
• Bulge and tear of the aorta blood vessel wall
• Acute? hemorrhage
• Stomach or intestinal ulcer?
• Ulcerated colon
• Diverticulitis
• severe liver disease
• Biliary and gallbladder problem
• The possibility of having a miscarriage
• Osteoporosis
• Chronic? kidney disease stage 4 (severe)
• Chronic? kidney disease stage 5 (failure)
• Kidney disease with likely reduction in kidney function

Dosage? of Heparin

Strengths: 2500 units/mL; 1000 units/mL; 20000 units/mL; 5000 units/0.5 mL; 5000 units/mL; 7500 units/mL ;beef lung 10000 units/mL

Deep Vein Thrombosis

The manufacturer provides the following dosing guidelines based on clinical experience:

Continuous IV infusion

• Initial dose: 5000 units by IV injection
• Maintenance dose: 20,000 to 40,000 units per 24 hours by continuous IV infusion

Intermittent IV injection

• Initial dose: 10,000 units IV
• Maintenance dose: 5000 to 10,000 units IV every 4 to 6 hours

Deep subcutaneous (intrafat) injection

• 333 units/kg subcutaneously followed by 250 units/kg subcutaneously every 12 hours; the following dosage? regimen has also been recommended
• 5000 units by IV injection followed by 10,000 to 20,000 units subcutaneously, and then 8000 to 10,000 units subcutaneously every 8 hours or 15,000 to 20,000 units subcutaneously every 12 hours.

Pulmonary Embolism?

The manufacturer provides the following dosing guidelines based on clinical experience

Continuous IV infusion

• Initial dose: 5000 units by IV injection
• Maintenance dose: 20,000 to 40,000 units per 24 hours by continuous IV infusion

Intermittent IV injection

• Initial dose: 10,000 units IV
• Maintenance dose: 5000 to 10,000 units IV every 4 to 6 hours

Deep subcutaneous (intrafat) injection

• 333 units/kg subcutaneously followed by 250 units/kg subcutaneously every 12 hours; the following dosage? regimen has also been recommended
• 5000 units by IV injection followed by 10,000 to 20,000 units subcutaneously, and then 8000 to 10,000 units subcutaneously every 8 hours or 15,000 to 20,000 units subcutaneously every 12 hours.

Intravascular Coagulation

The manufacturer provides the following dosing guidelines based on clinical experience:

Continuous IV infusion

• Initial dose: 5000 units by IV injection
• Maintenance dose: 20,000 to 40,000 units per 24 hours by continuous IV infusion

Intermittent IV injection

• Initial dose: 10,000 units IV
• Maintenance dose: 5000 to 10,000 units IV every 4 to 6 hours

Deep subcutaneous (intrafat) injection

• 333 units/kg subcutaneously followed by 250 units/kg subcutaneously every 12 hours; the following dosage? regimen has also been recommended:
• 5000 units by IV injection followed by 10,000 to 20,000 units subcutaneously, and then 8000 to 10,000 units subcutaneously every 8 hours or 15,000 to 20,000 units subcutaneously every 12 hours.

Thromboembolism in Atrial Fibrillation

The manufacturer provides the following dosing guidelines based on clinical experience:

Continuous IV infusion

• Initial dose: 5000 units by IV injection
• Maintenance dose: 20,000 to 40,000 units per 24 hours by continuous IV infusion

Intermittent IV injection

• Initial dose: 10,000 units IV
• Maintenance dose: 5000 to 10,000 units IV every 4 to 6 hours

Deep subcutaneous (intrafat) injection

• 333 units/kg subcutaneously followed by 250 units/kg subcutaneously every 12 hours; the following dosage? regimen has also been recommended:
• 5000 units by IV injection followed by 10,000 to 20,000 units subcutaneously, and then 8000 to 10,000 units subcutaneously every 8 hours or 15,000 to 20,000 units subcutaneously every 12 hours.

Side effects of Heparin

The most common

• Bleeding gums
• blood in the urine
• bloody stools
• blurred vision
• constipation
• muscle aches
• Nausea and vomiting
• Severe stomach ache
• diarrhoea,
• anorexia,
• headache,
• dizziness,
• joint pain

Common

• nusual bruising,
• unexplainable bruises
• bruises that grow in size
• nosebleeds
• bleeding gums
• bleeding from cuts that takes a long time to stop
• heavier than normal menstrual or vaginal bleeding
• pink or brown urine
• red or black stools
• coughing up blood
• vomiting blood

Less common

• Bleeding gums
• blood in the urine
• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• chest pain or discomfort
• confusion
• coughing up blood
• the difficulty with breathing or swallowing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• excessive bruising
• a headache
• increased menstrual flow or vaginal bleeding
• nosebleeds
• paralysis
• peeling of the skin
• prolonged bleeding from cuts
• red or black, tarry stools

Drug Interactions of Heparin

Warfarin may interact with following drugs, supplements & may change the efficacy of the drug

• alcohol
• angiotensin receptor blockers (ARBs; e.g., irbesartan, losartan)
• anticancer medications (e.g., carboplatin, cyclophosphamide, fluorouracil)
• azathioprine
• “azole” antifungals (e.g., fluconazole, ketoconazole, voriconazole)
• barbiturates (e.g., phenobarbita, secobarbital)
• carbamazepine
• cephalosporins (e.g., cefazolin, cefoperazone, cefotetan, cefoxitin)
• chloral hydrate
• chloramphenicol
• chlorpropamide
• clopidogrel
• coenzyme Q10
• corticosteroids (e.g., hydrocortisone, prednisone)
• COX-II inhibitors (celecoxib, rofecoxib)
• ethacrynic acid
• estrogen-containing medications (e.g., birth control pills)
• glucagon
• glucosamine
• griseofulvin
• heparin
• macrolide antibiotics (e.g., azithromycin, clarithromycin,
• methyl salicylate
• methyldopa
• metronidazole
• mirtazapine
• multivitamins
• nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., diclofenac, ibuprofen,naproxen)
• omega-3 fatty acids orlistat
• penicillins (e.g., ampicillin, cloxacillin, penicillin G, piperacillin, ticarcillin)
• pentoxifylline
• phenobarbital
• phenytoin
• proton pump inhibitors (e.g., lansoprazole, omeprazole)
• quinolone antibiotics (e.g., ciprofloxacin, norfloxacin, ofloxacin)
• ranitidine
• selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
• “statins” (e.g., fluvastatin, lovastatin, simvastatin)
• testosterone
• tetracyclines (e.g., doxycycline, minocycline, tetracycline)
• tolterodine
• tramadol
• tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
• vitamin A
• vitamin E
• vitamin K (phytonadione)
• zafirlukast

Pregnancy & Lactation of Heparin

FDA Pregnancy Category C

Pregnancy

Maternal and fetal outcomes associated with this drug during pregnancy have been investigated in numerous studies, which generally reported normal deliveries with no maternal or fetal bleeding and no other complications. However, increased incidence of human fetal loss and prematurity associated with hemorrhage have been reported. Before using heparin must consult with doctor or pharmacist

Lactations

Benefit should outweigh risk; if used during lactation, preservative-free formulations are recommended. Excreted into human milk. The effects in the nursing infant are unknown.

References