LOW MOLECULAR WEIGHT HEPARIN(LMWH) INJECTIONS IN UNSTABLE ANGINA

Low-molecular-weight heparin (LMWH) is a newer form of the blood thinner heparin with some advantages over standard heparin. You do not need regular blood tests to measure the time it takes for your blood to clot, and LMWH does not appear to carry an increased risk of osteoporosis with long-term use.

LMWH is given through an intravenous (IV) line in the arm or injected under the skin.

LMWHs are closely related to heparin, which is one of the oldest blood thinners available. These drugs have an advantage over heparin in that they have longer duration in the body, more predictable effects after a given dose, require less blood tests to check for their effectiveness and side effects, and do not have to be given in the hospital setting only. LMWHs have been found to be safe and effective in blood clot prevention after general surgery, orthopedic surgery, neurosurgery, multiple trauma, hip fracture, certain types of stroke, unstable angina, heart attack and treatment DVT and PE. These drugs are usually given with warfarin (Coumadin) for treatment of blood clots and with aspirin for prevention of complications after heart attack or angina attack. 

Low molecular weight heparins are smaller pieces of the heparin molecule that inhibit clotting factor Xa more than factor IIa (thrombin). These drugs are given subcutaneously and can usually be administered in a weight-based dose without subsequent monitoring or dose-adjustment. At a higher dose these drugs are used to treat active thrombotic disease and at lower dose to prevent thrombosis.

Uses of LMWH to treat unstable angina

LMW-heparins have proven to be at least as effective as intravenous unfractionated heparin in the treatment of unstable angina. Cost-analysis of LMW-heparin treatment of unstable angina indicate that when total costs are considered, LMW-heparin incurs no more expense than unfractionated-heparin. Dalteparin and enoxaparin are both approved for treatment of unstable angina. Enoxaparin or dalteparin can be given safely to any patient who is a candidate for unfractionated heparin. The major contraindications are active internal bleeding and heparin-induced thrombocytopenia (HIT).

Guidelines for LMWH treatment for unstable angina.

• Obtain baseline ECG, cardiac enzymes, troponin, APTT, PT, and CBC
• Determine need for thrombolytic therapy
• Start aspirin, ß-adrenergic blocker and nitrates
• Check for contraindications to LMW-heparin
• Start enoxaparin* or dalteparin* subcutaneously q 12 hr without monitoring or dose-adjustment.
• Determine need for long-term anticoagulants (warfarin)

Dosage and administration

Unstable Angina and Non-Q-Wave Myocardial Infarction;

In patients with unstable angina or non-Q-wave myocardial infarction, the recommended dose of Lovenox is 1 mg/kg administered SC every 12 hours in conjunction with oral aspirin therapy (100 to 325 mg once daily). Treatment with Lovenox should be prescribed for a minimum of 2 days and continued until clinical stabilization. The usual duration of treatment is 2 to 8 days; up to 12.5 days of Lovenox has been administered in clinical trials.

Treatment of acute ST-segment Elevation Myocardial Infarction: 

In patients with acute ST-segment Elevation Myocardial Infarction, the recommended dose of Lovenox is a single IV bolus of 30 mg plus a 1 mg/kg SC dose followed by 1 mg/kg administered SC every 12 hours (maximum 100 mg for the first two doses only, followed by 1 mg/kg dosing for the remaining doses). Dosage adjustments are recommended in patients >75 years of age.

When administered in conjunction with a thrombolytic (fibrin-specific or non-fibrin specific), Lovenox should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. All patients should receive acetylsalicylic acid (ASA) as soon as they are identified as having STEMI and maintained with 75 to 325 mg once daily unless contraindicated. In the pivotal clinical study, the Lovenox treatment duration was 8 days or until hospital discharge, whichever came first. An optimal duration of treatment is not known, but it is likely to be longer than 8 days.

For patients managed with Percutaneous Coronary Intervention (PCI): 

If the last Lovenox SC administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last Lovenox SC administration was given more than 8 hours before balloon inflation, an IV bolus of 0.3 mg/kg of Lovenox should be administered.

Precautions

The use of LMWHs should be avoided in persons undergoing any procedure involving spinal puncture or anesthesia. Using these medicines before these procedures has caused severe bruising and bleeding into the spine and can lead to paralysis.
The use of these medicines should be avoided in patients with allergies to LMWHs, heparin, or pork products, allergies to sulfites or benzyl alcohol, people with active major bleeding, and people with a history of heparin-induced low blood platelet count (also known as heparin-induced thrombocytopenia or HIT).
LMWHs should be used with caution in the following persons:

• people with bleeding disorders
• people with a history of recent stomach ulcers
• people who recently had brain, spine, or eye surgery
• people on other blood thinners (such as warfarin, aspirin, ibuprofen, naproxen) because of increased risk of bleeding
• people with kidney or liver disease (the dose of LMWHs may need to be decreased)
• breast-feeding mothers (it is not known if these medicines cross into breast milk)
• women who are pregnant, unless benefits to the mother outweigh the risks to the baby

A doctor should be contacted immediately if any of these symptoms develop:

• tingling, weakness, numbness or pain
• blood in the urine or stool
• itching, swelling, skin rash, trouble breathing
• unusual bleeding or bruising

A physician may perform blood tests during therapy with LMWHs to prevent side effects. Blood tests to check for effectiveness of these medicines are usually not needed, except in children, people with kidney disease, and overweight persons.

Side Effects

The most common side effects of LMWHs include irritation and pain at the injection site, easy bruising and bleeding, fever, increase in liver enzyme tests usually without symptoms, and allergic reactions. Severe painful erection sometimes requiring surgery has been reported with tinzaparin in some patients. LMWHs can lower platelet counts, which may necessitate discontinuation.

Interactions

LMWHs should be used with caution in people on other oral blood thinners (aspirin, non-steroidal anti-inflammatory drugs, warfarin, and ticlopidine) because of increased risk of bleeding. If using both drugs together is necessary, the patients must be closely monitored.