HEPARIN INDUCED THROMBOCYTOPENIA (HIT)

Abscess of pharyngomaxillary or lateral pharyngeal space is also known as parapharyngeal abscess.

Infection can come to this space from acute or chronic infections of tonsils and adenoids, bursting of peritonsillar abscess, dental infection of lower third molar teeth, Bezold’s abscess, petrositis, infections of parotid, retropharyngeal, and submaxillary spaces, injuries of neck etc.

Fever, odynophagia, sore throat, torticoilis and signs of toxemia may develop.

Dabigatran etexilate is an oral thrombin inhibitor and rivaroxaban is an oral factor Xa inhibitor.

Dabigatran etexilate is used as an alternative to warfarin for stroke prevention in patients with atrial fibrillation.

Argatroban is a parenteral direct thrombin inhibitor. Alfimeprase is a fibrinolytic agent.

HIT results from antibody formation to a complex of the platelet specific protein platelet factor 4 and heparin.

Rivaroxaban is the first orally active Factor Xa inhibitor. Useful in Heparin induced thrombocytopenia and thrombosis syndrome.

Ans. is ‘b’ i.e., Lepirudin

Heparin induced thrombocytopenia (HIT)

o Heparin induced thrombocytopenia is an important adverse effect of heparin administration, usually caused by unfractionated heparin, but may also be seen with the use of low molecular weight heparin (LMWH).

o HIT may be of two types :

Type 1 (Non-immune mediated) :- It is mild and heparin may be continued.

Type 2 (Immune mediated) :- It is due to formation of antibodies against platelets. Paradoxical thrombosis can occur. Heparin must be discontinued immediately.

Warfarin and LMW are contraindicated. Lepirudin (a direct thrombin inhibitor) is anticoagulant of choice. Alternatives are danaparoid, hirudin and Argatroban.

Ans. is ‘c’ i.e., More common with fractionated heparin

Features of Heparin Induced Thrombocytopenia

o Platelet count £ 100,000/µL or decreased by 350%.

o Starts 5-10 days after starting heparin.

o More common with unfractionated heparin than LMW heparin.

o Venous thrombosis is more common than arterial.

Ans. is ‘d’ i.e., Heparin should be replaced with Warfarin

Warfarin and LMW Heparin are contraindicated in HIT.

Ans. is ‘c’ i.e., Argatroban

Answer is B (Lepirudin)

Lepirudin (direct thrombin inhibitor) is a recommended agent for Heparin induced thrombocytopenia and thrombosis.

Currently Recommended Agents for Heparin Induced Thrombocytopenia

• Lepirudin (Direct Thrombin Inhibitor)
• Argatroban (Direct Thrombin Inhibitor)
• Danaparoid (Mixture of Non Heparin Glycosaminoglycans)
• Bivalirudin (Direct thrombin inhibitor) is under evaluation for HIT
• Heparin Induced Thrombocytopenia (HIT)
• Heparin Induced Thrombocytopenia is an important complication / adverse effect of Heparin administration that necessitates use of alternative agents to treat or prevent thrombus formation

HIT is usually seen as a complication of the use of unfractionated heparin but may also be seen with the use of LMWH HIT may be non immune mediated (Type I, Mild) or immune mediated due to development of antibodies (Type 2/ Significant)

Type I

• Non immune mediated
• Benign
• Mild Thrombocytopenia
• Heparin Therapy may be continued

Type II

• Immune mediated
• Severe
• Significant thrombocytopenia
• Heparin must be discontinued immediately
• Heparin Induced thrombocytopenia Type II is a serious form of HIT that can result in serious complications
• The diagnosis of Immune mediated HIT depends on clinical criteria with confirmation by specific laboratory tests

Clinical Criteria for Immune Mediated (Type II) HIT

• Thrombocytopenia < 150, 000/111 or a 50% decrease from pretreatment values
• Thrombocytopenia follows heparin exposure by at least 5 days (Time taken to form antibodies)
• Reasonable exclusion of other clinical causes of thrombocytopenia
• Onset of new thrombotic event or extension of previous thrombosis

Management of HIT (Immune mediated)

• Direct Thrombin Inhibitors

Lepirudin and Argobatran along with Danaparoid are the recommended alternative anticoagulants for patients with Heparin Induced thrombocytopenia.

Direct thrombin inhibitors (Lepirudin and Argobatram) are usually preferred but all three drugs are effective anticoagulants and the choice of drug depends on personal experience and patient characteristics like hepatic or renal insufficiency and desired route of administration

• Heparin administration should be stopped immediately.
• Low Molecular Weight Heparin (LMWH) should not be substituted because it may cross react with and-heparin antibodies
• Warfarin should not be used until the thrombocytopenia is resolved and the patient is adequately anticoagulated with another agent. Warfarin may precipitate venous limb gangrene or multicentric skin necrosis in patients with HIT

All three drugs are anticoagulant in patients with heparin-induced thrombocytopenia. The choice of drug depends on personal experience and patient characteristics such as renal or hepatic insufficiency, desired route of administration.

Ans. is ‘a’ i.e., Lepirudin

Heparin induced thrombocytopenia (HIT)

• Heparin induced thrombocytopenia is an important adverse effect of heparin administration, usually caused by unfractionated heparin, but may also be seen with the use of low molecular weight heparin (LMWH).
• HIT may be of two types :

1. Type 1 (Non-immune mediated) :- It is mild and heparin may be continued.
2. Type 2 (Immune mediated) :- It is due to formation of antibodies against platelets. Paradoxical thrombosis can occur. Heparin must be discontinued immediately. Warfarin and LMW are contraindicated. Lepirudin (a direct thrombin inhibitor) is anticoagulant of choice. Alternatives are danaparoid, hirudin and Argatroban.

Ans. is ‘a’ i.e., Argatroban

Direct thrombin inhibitors (DTIs)

• This is a class of medications that act as anticoagulants by directly inhibiting the thrombin (unlike heparin which inhibits thrombin indirectly through antithrombin → so, heparin is an indirect thrombin inhibitor).

Ans. is ‘c’ i.e., Argatroban 

Ans. is ‘c’ i.e., Rivaroxaban 

• Rivaroxaban – it is an orally active direct inhibitor of activated factor Xa which has become available for prophylaxis and treatment of DVT.
• Alteplase – given by i.v. infusion due to short half life of 4 – 8 min and often requires heparin coadministration.
• Argatroban – direct thrombin inhibitor; given by i.v. infusion; used in place of lepirudin for short term indications in patients with heparin induced thrombocytopenia.
• Fondaparinux – 100% bioavailability with subcutaneous injection