Heparin was discovered in 1916 by a medical student named Jay McLean while working with Dr. William Howell at Johns Hopkins University. The name "Heparin" comes from the Greek word hepar, meaning liver, as it was first isolated from liver tissue.

Although discovered early, heparin was not used clinically until the late 1930s and early 1940s, after being purified and proven safe for human use. It became the first anticoagulant used in medicine to prevent and treat blood clots.

In the 1970s and 1980s, new forms called Low Molecular Weight Heparins (LMWH) were developed, offering more predictable effects and easier administration.                   

Heparin exerts its anticoagulant effect through an antithrombin (AT)-dependent mechanism, by inhibiting both factor Xa and thrombin (factor IIa). This occurs when heparin binds to AT via a high-affinity pentasaccharide sequence, which is present in approximately one-third of heparin molecules.

In order to inhibit thrombin, heparin must simultaneously bind to both AT and thrombin, which requires a chain length of at least 18 saccharide units. In contrast, inhibition of factor Xa only requires heparin to bind to AT, and even shorter heparin fragments containing the pentasaccharide can achieve this.

By inactivating thrombin, heparin not only prevents fibrin formation but also limits thrombin-induced activation of platelets and coagulation factors V and VIII. 

Indications of Unfractionated Heparin (UFH):

Unfractionated heparin is widely used for both prophylactic and therapeutic purposes in various clinical settings. Its main indications include:

1. Venous Thromboembolism (VTE):

Prophylaxis and treatment of venous thrombosis and its extension.

Prevention of postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE).

2.Cardiovascular Surgery and Procedures:

Prevention of clot formation during arterial and cardiac surgeries.

Prevention of coagulation during dialysis and surgical procedures.

3.Cardiology:

Prevention of embolic events in patients with atrial fibrillation.

Adjunct antithrombin therapy in patients with unstable angina or non-Q wave myocardial infarction (i.e., non-ST elevated acute coronary syndrome), particularly those receiving platelet glycoprotein IIb/IIIa receptor inhibitors.

4. Maintenance of Vascular Access Devices:

Maintaining the patency of intravenous (IV) injection devices (e.g. catheters).

5.Laboratory and Blood Handling:

Prevention of in vitro coagulation in blood samples drawn for laboratory testing. 

Prevention of clotting during blood transfusions. 

Heparin sodium must be used with caution due to its potential for serious and sometimes fatal complications. Key precautions include:

Risk of Fatal Hemorrhage:

Fatal bleeding events have occurred due to medication errors (e.g., using high-dose heparin as catheter flush).

Heparin should not be used in the presence of active major bleeding unless benefits outweigh risks.

Bleeding can occur at any site (e.g., adrenal, ovarian, retroperitoneal), and is more common in females over 60 years.

Conditions Requiring Caution:

Cardiovascular: Subacute bacterial endocarditis, severe hypertension.

Surgical: During or immediately after spinal tap, spinal anesthesia, or major surgery involving the brain, spinal cord, or eye.

Gastrointestinal: Ulcerative lesions, gastrointestinal tube drainage.

Hematologic: Hemophilia, thrombocytopenia, vascular purpura.

Other: Menstruation, liver disease with impaired coagulation.

Antithrombin III Deficiency:

Concomitant use with antithrombin III increases bleeding risk; heparin dose should be reduced.

Hypersensitivity:

Use only in life-threatening situations for patients with known hypersensitivity. Monitor for allergic reactions due to its animal origin.

Monitoring Requirements:

Frequent coagulation testing (e.g., APTT) is essential during full-dose therapy.

Monitor hematocrit and platelet count periodically.

Discontinue heparin immediately if hemorrhage or prolonged clotting time occurs. 

primarily involve bleeding risks, as it reduces blood clotting. Common side effects include:

• Easy bruising and prolonged bleeding

• Bleeding at injection sites causing pain, redness, or sores

• Allergic reactions such as rash, itching, and hives

• Severe bleeding internally or externally, which can be life-threatening (e.g., blood in urine, stools, or vomit)

• Heparin-induced thrombocytopenia (HIT), a serious immune reaction causing low platelet counts and increased                  clotting risk

• Elevated liver enzymes

• Osteoporosis with long-term use

• Other symptoms like chest pain, dizziness, and unusual tiredness may occur and require urgent medical                                attention

Heparin is contraindicated in the following conditions:

• Active major bleeding or uncontrollable bleeding states (except in disseminated intravascular coagulation) due                   to the risk of worsening hemorrhage.

• History of heparin-induced thrombocytopenia (HIT) or immune-mediated HIT within the past 100 days or                                  presence of circulating HIT antibodies, as heparin can cause severe thrombocytopenia and thrombosis.

• Known hypersensitivity or allergy to heparin, pork products, or benzyl alcohol (in multi-dose formulations),                            which can cause allergic or anaphylactic reactions.

• Conditions with high risk of bleeding such as hemophilia, active peptic ulcer, acute bacterial endocarditis,                               severe hypertension, and postoperative neurosurgery or ophthalmic surgery.

• Severe thrombocytopenia or inability to monitor coagulation parameters properly.

• Pregnancy near term due to risk of hemorrhage during delivery (contraindicated at the end of pregnancy).

Additional precautions include caution in elderly patients and those with hepatic or renal failure.

In summary, heparin should be avoided in patients with active bleeding, HIT history, hypersensitivity to heparin or related substances, and bleeding-prone conditions to prevent serious adverse effects like hemorrhage and thrombocytopenia.

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antithrombin%20(AT)%2Ddependent%20mechanism.

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6-https://www.leading-medicine-guide.com/en/medical-specialty/surgery/heart-surgery

7- https://www.osmosis.org/video/Antithrombin_III_deficiency

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9-http://egyptiandrugstore.com/index.php?route=product/product&product_id=3576

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