Heparin Induced Thrombocytopenia (HIT)

HEPARIN INDUCED THROMBOCYTOPENIA (HIT)

Q. 1

A 40-year-old woman had lower third molar extracted due to dental caries. Then she developed high fever and pain. On examination, tonsil deviated medially and there was swelling in upper one-third of sternocleidomastoid muscle, Most likely diagnosis is:

 A

Hematoma

 B

Retropharyngeal abscess

 C

Parapharyngeal abscess    

 D

Ludwig’s angina

Q. 1

A 40-year-old woman had lower third molar extracted due to dental caries. Then she developed high fever and pain. On examination, tonsil deviated medially and there was swelling in upper one-third of sternocleidomastoid muscle, Most likely diagnosis is:

 A

Hematoma

 B

Retropharyngeal abscess

 C

Parapharyngeal abscess    

 D

Ludwig’s angina

Ans. C

Explanation:

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.


Q. 2

Which of the following drugs is recommended for the treatment of Heparin Induced thrombocytopenia?

 A

Abciximab

 B

Lepirudin

 C

Warfarin

 D

Alteplase

Q. 2

Which of the following drugs is recommended for the treatment of Heparin Induced thrombocytopenia?

 A

Abciximab

 B

Lepirudin

 C

Warfarin

 D

Alteplase

Ans. B

Explanation:

Lepirudinis a recombinant preparation of hirudin which acts by inhibiting thrombin directly.
It is the recommended drug for treatment of heparin induced thrombocytopenia.
Ref: Goodman And Gillman’s Manual of Pharmacology, 2007, Page 955; Clinical Hematology & Oncology By Bruce Furie, 2003, Page 488.

Q. 3

Which of the following is an oral thrombin inhibitor?

 A

Rivaroxaban

 B

Dabigatran

 C

Argatroban

 D

Alfimeprase

Q. 3

Which of the following is an oral thrombin inhibitor?

 A

Rivaroxaban

 B

Dabigatran

 C

Argatroban

 D

Alfimeprase

Ans. B

Explanation:

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.

Ref: Harrisons principles of internal medicine, 18th edition, Chapter: 118

Quiz In Between


Q. 4

The antibody responsible for heparin induced thrombocytopenia is:

 A

Antiheparin / PF4 antibody

 B

Antiheparin / PF2 antibody

 C

Antiheparin / GP IIb/IIIa antibody

 D

Antiheparin GP Ib/IX antibody

Q. 4

The antibody responsible for heparin induced thrombocytopenia is:

 A

Antiheparin / PF4 antibody

 B

Antiheparin / PF2 antibody

 C

Antiheparin / GP IIb/IIIa antibody

 D

Antiheparin GP Ib/IX antibody

Ans. A

Explanation:

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

Ref: Harrisons principles of internal medicine, Edition -18, Page – 967.

Q. 5

The mechanism of action of Rivaroxaban, used in the treatment of heparin induced thrombocytopenia and thrombosis syndrome is:

 A

Direct factor Xa inhibitor

 B

Activated factor VIIa

 C

Vitamin K antagonist

 D

None of the above

Q. 5

The mechanism of action of Rivaroxaban, used in the treatment of heparin induced thrombocytopenia and thrombosis syndrome is:

 A

Direct factor Xa inhibitor

 B

Activated factor VIIa

 C

Vitamin K antagonist

 D

None of the above

Ans. A

Explanation:

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

 

Ref: Harrisons principles of internal medicine, 18th edition, Page 2737

Q. 6

Which of the following drugs is recommended for the treatment of heparin induced thrombocytopenia­ –

 A

Abciximab

 B

Lepirudin

 C

Warfarin

 D

Alteplase

Q. 6

Which of the following drugs is recommended for the treatment of heparin induced thrombocytopenia­ –

 A

Abciximab

 B

Lepirudin

 C

Warfarin

 D

Alteplase

Ans. B

Explanation:

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.

Quiz In Between


Q. 7

True about HIT syndrome are all Except‑

 A

LMWH shouldn’t be used for treatment

 B

It causes both arterial and venous thrombosis

 C

More common with fractionated heparin

 D

Occurs commonly in about a week of heparin therapy

Q. 7

True about HIT syndrome are all Except‑

 A

LMWH shouldn’t be used for treatment

 B

It causes both arterial and venous thrombosis

 C

More common with fractionated heparin

 D

Occurs commonly in about a week of heparin therapy

Ans. C

Explanation:

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.


Q. 8

Which one of the following statement is incorrect regarding Heparin induced thrombocytopenia

 A

Heparin should be discontinued immediately

 B

Alternative anticoagulant such as lepirudin should be administered

 C

Low molecular weight heparins should be avoided

 D

Heparin should be replaced with Warfarin

Q. 8

Which one of the following statement is incorrect regarding Heparin induced thrombocytopenia

 A

Heparin should be discontinued immediately

 B

Alternative anticoagulant such as lepirudin should be administered

 C

Low molecular weight heparins should be avoided

 D

Heparin should be replaced with Warfarin

Ans. D

Explanation:

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

Warfarin and LMW Heparin are contraindicated in HIT.


Q. 9

Parenteral direct thrombin inhibitor‑

 A

Ximelagatran

 B

Dabigatran

 C

Argatroban

 D

Heparin

Q. 9

Parenteral direct thrombin inhibitor‑

 A

Ximelagatran

 B

Dabigatran

 C

Argatroban

 D

Heparin

Ans. C

Explanation:

Ans. is ‘c’ i.e., Argatroban

Quiz In Between


Q. 10

Which of the following drugs is recommended for the treatment of Heparin Induced thrombocytopenia

 A

Abciximab

 B

Lepirudin

 C

Warfarin

 D

Alteplase

Q. 10

Which of the following drugs is recommended for the treatment of Heparin Induced thrombocytopenia

 A

Abciximab

 B

Lepirudin

 C

Warfarin

 D

Alteplase

Ans. B

Explanation:

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

Comparison of Danaproid, Lepirudin, and Argatroban for the treatment of Heparin induced Thrombocytopenia    

 

Danaproid

Lepirudin

Aragtroban

Mechanism of action

Primarily inhibits Xa in a complex

with Antithrombin III

Directly inhibits thrombin

Directly inhibits

thrombin

Administration

IV or SC

IV

IV

Half-life

24 hours

13 hours

30 minutes

Reversible

No

No

No

Monitoring

Anti-Xa activity using a danaproid

standard

aPTT

aPTT

Use in pregnancy

Several reported cases

No reported experience

.No reported experience

Dose adjustment for

renal failure

Yes, monitor Xa activity dosely in

patients with renal insufficiency

Yes, monitor Xa activity closely in

patients with renal insufficiency

No

Special considerations

Cross- reacts with heparin-induced

antibodies in some cases

Antibodies may develop to

lepirudin and prolong the half –life

 

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.


Q. 11

Agent used for treatment of heparin induced thrombocytopenia ‑

 A

Lepirudin

 B

Abciximab

 C

Warfarin

 D

Alteplase

Q. 11

Agent used for treatment of heparin induced thrombocytopenia ‑

 A

Lepirudin

 B

Abciximab

 C

Warfarin

 D

Alteplase

Ans. A

Explanation:

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.

Q. 12

Which of the following is a univalent direct thrombin inhibitor?

 A

Argatroban

 B

Hirudin

 C

Bivalirudin

 D

Lepirudin

Q. 12

Which of the following is a univalent direct thrombin inhibitor?

 A

Argatroban

 B

Hirudin

 C

Bivalirudin

 D

Lepirudin

Ans. A

Explanation:

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).

Quiz In Between


Q. 13

Parenteral direct thrombin inhibitor

 A

Ximelagatran

 B

Dabigatran

 C

Argatroban

 D

Heparin

Q. 13

Parenteral direct thrombin inhibitor

 A

Ximelagatran

 B

Dabigatran

 C

Argatroban

 D

Heparin

Ans. C

Explanation:

Ans. is ‘c’ i.e., Argatroban 

 

Parentral direct thrombin inhibitors

  • Argatroban      Bivalirudin
  • Hirudin           Lepirudino Melagatran
  • Desirudin

Oral Direct thrombin inhibitors

  • Dabigatran (recent)
  • Ximelagatran (withdrawn)

 


Q. 14

Which of the following is given orally 

 A

Argatraban

 B

Alteplase

 C

Rivaroxaban

 D

Fondaparinux

Q. 14

Which of the following is given orally 

 A

Argatraban

 B

Alteplase

 C

Rivaroxaban

 D

Fondaparinux

Ans. C

Explanation:

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

Quiz In Between



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