Danaparoid Anticoagulant Drug

INTRODUCTION

Danaparoid sodium (Orgaran) is an anticoagulant[1] that works by inhibiting activated factor X (factor Xa).

Danaparoid is a heparinoid but considered to be a low molecular weight heparin by some sources. However it is chemically distinct from heparin, has different protein binding properties and thus has little cross-reactivity in heparin-intolerant patients.

It consists of a mixture of heparan sulfate, dermatan sulfate, and chondroitin sulfate

THERAPEUTIC USES:

It is used to prevent deep venous clots, particularly in situations with a high risk of clot formation, such as after hip surgery.

It is also used as a heparinoid substitute in heparin-induced thrombocytopenia[3][4] (HIT) which may otherwise cause paradoxical thrombosis. Danaparoid is used for thrombosis prophylaxis and treatment in heparin-induced thrombocytopenia patients, although cross-reactivity with heparin-induced antibodies can occur in 10–20% of the patients (ESRA). It has been proposed for use in Kasabach-Merritt syndrome

SIDE EFFECT

• Bleeding (solely restricted to patients undergoing cardio-pulmonary surgery with by pass).

• Low platelets, due to a low level of structural similarity between danaparoid and heparin, i.e. only in some patients sensitive to heparin or a LMWH but to date never developed spontaneously.

• Possibly Asthma exacerbations, due to allergies to sulfites contained within the medicine (no case has been reported to date).

• There is a risk of bleeding in the spinal or epidural space, possibly resulting in paralysis, when danaparoid is used along with spinal or epidural anesthesia or spinal puncture. This risk may be increased by the use of indwelling epidural catheters or by the concomitant use of drugs that affect blood clotting.

Less common: 

• Bleeding gums,coughing up blood,difficulty in breathing or swallowing

• Dizziness,headache,increased menstrual flow or vaginal bleeding

• nosebleeds,paralysis,prolonged bleeding from cuts 

• red or black, tarry stools,red or dark brown urine

• shortness of breath,unexplained pain, swelling, or discomfort, especially in the chest, abdomen, joints, or muscles

• unusual bruising ,vomiting of blood or coffee ground–like material; weakness

Rare: 

• Back pain

• burning, pricking, tickling, or tingling sensation

• leg weakness

• numbness

• problems with bowel or bladder function

PRECAUTIONS:

You should not use danaparoid if you

• have a very low level of platelets in your blood,

• have uncontrolled active bleeding,

• have an allergy to pork products, or

• cannot have accurate blood testing done prior to and during dosing.

Before using danaparoid, tell your doctor if you

• have bacterial endocarditis,

• have high blood pressure that is not being controlled,

• need to have surgery or another invasive procedure,

• have hemophilia or another blood disorder,

• have a stomach ulcer,

• have liver disease, or

• have kidney disease.

PHARMACOKINETICS

Danaparoid is a low molecular weight heparinoid derived from porcine gut mucosa. Its active components consist of heparan sulfate, dermatan sulfate and chondroitin sulfate. The major difference between danaparoid and other low molecular weight heparins (LMWH) is that danaparoid is devoid of heparin or heparin fragments. However, similar to LMWHs, it exerts its antithrombotic effect principally through anti-thrombin III-mediated inhibition of factor Xa and, to a much lesser extent, thrombin.1,2

Danaparoid is primarily eliminated via the kidneys. The elimination half-life based on anti-Xa activity ranges from 17-28 hours (mean 25 hours).

PHARMACODYNAMICS

Danaparoid sodium (Orgaran, Organon) is a heparinoid glycosamino-glycuronan antithrombotic agent approved for the prophylaxis of post-operative deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing elective hip replacement surgery. Danaparoid is a low molecular weight heparinoid consisting of a mixture of heparan sulphate (84%), dermatan sulphate (12%) and small amounts of chondroitin sulphate (4%), whose antithrombotic activity has been well established. Its pharmacological effect is exerted primarily by inhibiting Factors Xa (FXa) and IIa (FIIa) at a ratio greater than heparin, with a minimal effect on platelet function. Danaparoid exhibits low cross-reactivity with heparin-induced antibodies when compared with heparin or low molecular weight heparins (LMWH), thereby making it an excellent choice for the management of heparin-induced thrombocytopenia (HIT)

MECHANISM OF ACTION:

Its pharmacological effect is exerted primarily by inhibiting Factors Xa (FXa) and IIa (FIIa) at a ratio greater than heparin, with a minimal effect on platelet function. Danaparoid exhibits low cross-reactivity with heparin-induced antibodies when compared with heparin or low molecular weight heparins (LMWH), thereby making it an excellent choice for the management of heparin-induced thrombocytopenia (HIT).

Therefore, Danaparoid is used to prevent deep venous thrombosis, a condition in which harmful blood clots form in the blood vessels of the legs. These blood clots can travel to the lungs and can become lodged in the blood vessels of the lungs, causing a condition called pulmonary embolism. Danaparoid is used for several days after hip replacement surgery, while you are unable to walk. It is during this time that blood clots are most likely to form

DRUG-DRUG INTERACTIONS:

• Abciximab +danaparoid = may increase the risk of bleeding, including severe and sometimes fatal hemorrhage

• Drug+ ibuprofen=bruising, swelling, vomiting, blood in your urine or stools, headache, dizziness, or weakness.

• Danaparoid+ urokinase =may increase the risk of bleeding, including severe and sometimes fatal hemorrhage

• Alteplase +danaparoid =may increase the risk of bleeding, including severe and sometimes fatal hemorrhage

• Danaparoid +aspirin= Combining these medications can increase the risk of bleeding complications

REFERENCE: Triapthi K.D; "Essentials of medical pharmacology"; Page no- 617,620