Heparin

How Heparin Works?

Heparin is the first choice anticoagulant in the treatment of Venous Thromboembolism because its onset of action is immediate. It is a heterogeneous mixture of branched glucosaminoglycans. It is produced naturally inside the human body by white blood cells and mast cells. Heparin combines at Arginine Reactive Centre of Anti-thrombin III (AT), a plasma cofactor, to form Heparin-Antithrombin complex. The Heparin-Antithrombin complex produces a conformational change in AT. AT then binds with the active serine centre of thrombin, a clotting enzyme, to inhibit its coagulation activity. Thus, Heparin works by converting AT from slow thrombin inhibitor to the rapid inhibitor.


Fig: action of Heparin to inactivate the clotting enzymes. Heparin reacts with slow inhibitor ATIII and converts it to active inhibitor by binding at its high affinity arginine reactive centre. Activated ATIII binds covalently to the clotting enzyme and inhibits the clotting of blood.

Heparin Administration

Treatment of VTE with Heparin is based on body weight, and the dosage is calculated based on Partial Thromboplastin Time (PTT) test. PTT test measures the time for anticoagulation (Guyton, & Hall, p. 464, 467). The normal range of PTT value is 60-80 seconds. If the PTT value is less than the normal range, Heparin dose is increased and vice versa. VTE patients are usually given 5,000 units/ml or less of low dose Heparin subcutaneously as a prevention. A 5-7 day course of low dose therapy is considered effective. It is also given in bolus (50-100 Units/kg) and infusion (15-25 Units/kg/hr) as high dose treatment for acute VTE. Application of Heparin is immediately stopped on the detection of any kind of bleeding, if severe Protamine sulfate is given to neutralize its anticoagulant effect.
Institute for safe medication practices has enlisted Heparin a high alert drug. It comes in different concentration and there are chances of wrong concentration being used in wrong patient.In order to reduce the risk s of Heparin, U.S Food and Drug Administration has changed the standard of Heparin. It will be 10% less potent than its normal dose.

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm184504.htm


Read the story( Actor Dennis Quaid’s newborn twins were given 1000 times greater dose of heparin)
http://www.kcby.com/news/entertainment/11697086.html

Is Heparin really safe?

There are several complications that can arise with the long term use of Heparin even if the drug dose is controlled. The U.S Food and Drug Administration released a warning regarding the use of this drug in 2008.

Heparin is a high risk drug which interacts with other drugs and further increases the complication. Aspirin, alcohol, and antibiotics increase the risk of bleeding with Heparin. Risks of hemorrhage, hypersensitivity, osteoporosis, alopecia are few of the side effects of using Heparin. It has been found that up to 10% of patients can develop major/minor bleeding which requires quick assessment of the patient and the contact with the physician. Bleeding due to injury or fall, bleeding from brain (hemorrhage), and any undiagnosed bleeding in digestive system are the side effects of Heparin.

HIT

Another major complication of Heparin is Heparin Induced Thrombocytopenia (HIT). About 3-30% of patients on Heparin Therapy have tendency to develop HIT after 3-4 days of medication. It is characterized when platelet count is less than 150 x 109/L or by 30% to 50% during treatment. It can result from any type of Heparin exposure, by any route of administration and from very tiny dose. Its detection is characterized by the formation of new emboli. Cessation of Heparin must be done after diagnosing HIT; however, it is not sufficient because it leaves patients in a hypercoagulable state. Therefore, anticoagulants argatroban and lepirudin are being used in the medical management of HIT. The best approach to prevent HIT is the regular monitoring of platelet count. Because HIT patients develop new clot rather than bleeding, platelet transfusion should not be done at once. It might increase the risk of bleeding.



Case study of HIT

Postoperative Stroke in a Young Man:

“A healthy 43 year old man underwent lumbar laminectomy and received postoperative prophylactic unfractionated heparin, 5,000 U subcutaneously every 8 hours. On the seventh postoperative day, he became hemiparetic and aphasic. On the 10th postoperative day, he was unresponsive. An angiogram showed left common and internal carotid occlusion. Postoperative blood work revealed that the platelet count, which had been normal preoperatively, was 32 × 109 cells/L. The vascular surgeon retrieved a “white clot” from the carotid artery as heparin and platelet transfusions were given during the patch angioplasty, and vascular catheters continued to be flushed with heparin postoperatively. The next morning, the platelet level remained at 45 × 109 cells/L, and the left leg was cold and pulse less. An emergency thrombectomy saved the leg. The hematology department was consulted, HIT was immediately diagnosed, and all heparin exposures stopped. A test for heparin-induced platelet antibodies was strongly positive (by an aggregation test). The platelet count normalized in few days. After 2 months in the hospital, the patient was transferred to a long-term care facility in a vegetative state” (Lawrence Rice).
Comment: The drop in the platelet count of the young man in this case indicates the development of HIT. The continuation of Heparin medication and platelet transfusion after the development of HIT increased the complication by forming more clots.

Contraindication in Heparin

Use of Heparin is risky for the patients with severe renal failure. Heparin can have teratogenic effect if taken during pregnancy. Similarly, heparin is contraindicated in patients with leukemia, gastrointestinal obstruction, serious inflammation, infection, recent surgery.

http://chestjournal.chestpubs.org/content/119/1_suppl/64S.full?ijkey=8afa523e49a5e53d211e584523e56396161df903&keytype2=tf_ipsecsha#sec-4

http://chestjournal.chestpubs.org/content/127/2_suppl/21S.full?sid=073d5472-76b2-4967-9a30-f2821dcda11d

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm184504.htm