HEPARIN-INDUCED THROMBOCYTOPENIA

Maria Helena L. Souza, CCP (Br)

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QUESTIONS

1. Heparin-Induced Thrombocytopenia (HIT) is a life-and-limb threatening condition that is associated with the development of antibodies that activate platelets and the coagulation system in the presence of unfractioned heparin or low molecular weight heparin.

true
false

2. Regarding HIT, all of the following are true, except:

A. HIT is a potentially lethal complication assiciated with exposure to exogenous heparin or heparin derivatives.
B. The binding of antibodies to heparin-PF4 complexes can activate platelets.
C. HIT is associated with severe bleeding diathesis.
D. The most common laboratory finding is the development of thrombocytopenia 5 or more days after beginning heparin treatment.
E. HIT can occurs in up to 1-5% of patients exposed to heparin, depending on type of heparin and indication for anticoagulation.

A
B
C
D
E

3. Answer the following question by using the key outlined below:

A. if 1,2, and 3 are correct
B. if 1 and 3 are correct
C. if only 4 is correct, and
D. if all four are correct

1. Regular heparin or low-molecular weight heparin, given in either therapeutic, prophylactic or trivial doses, binds to platelet factor-4 (PF-4) and causes a subtle conformational change in the protein.
2. The protein change, in some individuals, can lead to an immunological response and antibody formation.
3. The binding of antibody to the modified epitopes on PF-4 can cause the activation of platelets.
4. The platelet activation leads to aggregation, which in turnr leads to thrombocytopenia and widespread activation of coagulation.

A
B
C
D

4. In HIT clot formation can become clinically manifest in a very short period of time, both in the venous and arterial circulations.

true
false

5. All of the following statements regarding HIT are correct, except:

A. HIT in its most severe form can produce widespread venous thrombosis leading to phlegmasia cerulea dolens or venous limb gangrene.
B. HIT can also produce severe arterial thrombosis and occlusion which may produce ischemic gangrene.
C. With increased awareness of HIT and more frequent testing for HIT antibody, the number of patients diagnosed with HIT appears to be increasing
D. The incidence of severe HIT has approached 25% of patients exposed to beef lung heparin.

A
B
C
D

6. Answer the following question by using the key outlined below:

A. if 1,2, and 3 are correct
B. if 1 and 3 are correct
C. if only 4 is correct, and
D. if all four are correct

1. Aside from exposure to a heparin product, the clinical features that most commonly heralds the onset of HIT is thrombocytopenia.

2. Severe HIT may occur in the absence of specific antibodies.
3. Thrombocytopenia is usually defined as a fall in the platelet count of > 50% from the baseline value.
4. In patients exposed to heparin for the first time the platelet count do not usually decrease.

A
B
C
D

7. The most feared complication associated with HIT is:

vascular thrombosis
purpura
arterial hypotension
antibody formation
leucodepletion

8. All of the following statements regarding HIT are correct, except:

A. Not all patients who develop thrombocytopenia while receiving heparin have HIT.
B. All patients who receive UFH or LMWH should have their platelet count monitored closely.
C. Patients receiving heparin for the first time should be given platelets prophylatically.
D. If thrombocytopenia is noted, a repeat platelet count should be ordered to confirm the finding.

A
B
C
D

9. Circulating heparin or LMWH form complexes with PF-4 that is commonly found in the alpha-granules of platelets.

true
false

10. All of the following statements regarding HIT are true, except:

A. Tipically, heparin molecules with at least 12-14 saccharide units are needed in order to bind to PF-4 and induce a conformational change in this protein.
B. An immune response (IgG, IgA or IgM) develops to specific epitopes.
C. Antibody binding to these epitopes on PF-4 bound to platelets leads to platelet aggregation.
D. Platelet aggregation only occurs before the antibodies binding to fibrinogen molecules.

A
B
C
D

11. An immune response develops to specific epitopes. Antibody binding to these epitopes on PF-4 bound to platelets leads to platelet aggregation and clustering of FcgamaIIa receptors, which in turn leads to platelet activation. This leads to the release of NO from platelets, which perpetuates and amplifies the cycle.

true
false

12. All of the following statements regarding HIT are correct, except:

A. Any released PF-4 molecules typically bind to heparin-like molecules on the endothelial surface, resulting in local antibody binding, endothelial injury and release of tissue factor, which also activates coagulation.
B. Additionally, the activation of platelets generates membrane microparticles are thromboplastic and cause thrombin activation, resulting in clot formation.
C. Thrmobin binding to thrombomodulin leads to inhibition of protein C, which acts as a natural anticoagulant to dampen widespread thrombosis.
D. If warfarin is used as a substitute for heparin, initiation of treatment using this drug leads to an acute reduction in the levels of protein C, eliminating the anticoagulant effect and pardoxically, accelerating the development of thrombosis.
E. The released PF-4 binds and neutralises any free heparin, leading to a reduced anticoagulant effect of heparin.

A
B
C
D
E

13. All of the following are produced by activation of coagulation by HIT antibodies, except:

A. Low levels of thrombin-anti-thrombin complexes.
B. Low levels of anti-thrombin.
C. Low levels of protein C.
D. Low levels of protein S.
E. Elevated levels of D-dimer, a breakdown product of crosslinked fibrin.

A
B
C
D
E

14. All of the following are clinical manifestations of HIT, except:

heparin exposure
thrombocytopenia
acute thrombosis
onset 5-10 days after initial heparin exposure
hemolysis

15. Heparin continues to be the most common cause of drug-induced, antibody-mediated thrombocytopenia, and managing its thrombotic sequelase remais a difficult chalenge.

true
false

16. All of the following statements regarding HIT are correct, except:

A. HIT was first described in animals in 1942.
B. HIT is among the most serious potential complications of heparin use during CPB.
C. A transient non-immune-mediated type I HIT, causing moderate thrombocytopenia and without severe thromboembolic sequelae was first described in 1962.
D. HIT type I produces a mild decrease of platelets count (>100,000/mcL).
E. HIT type I occurs in more than 35% of patients exposed to heparin.

A
B
C
D
E

17. All of the following are true, except:

A. Heparin-induced thrombocytopenia and thrombosis (HITT) is an immunomediated disorder induceb by the administration of heparin for therapeutic purposes.
B. The incidence of HITT in cardiac surgical patients can be as high as 1.9%.
C. Late recognition with continued exposure to heparin can result in bleeding in 53% of patients.
D. Late recognition with contined exposure to heparin can result in thromboembolic complications in 44% of patients.
E. Late recognition with continued exposure to heparin can result in death in 5% of patients.

A
B
C
D
E

18. All of the following drugs can be used for the treatment of HIT, except:

warfarin
lepidurin
argatroban
desirudin
bivalirudin

19. Oral anticoagulants such as warfarin, phenprocoumon or acenocoumarol should never be used alone in the initial treatment of active HIT, as these drugs rapidly effect a significant inhibition of the synthesis of protein C shortly after starting warfarin and this effect is likely to accelerate the underlying active thrombotic process.

true
false

20. If surgery requiring the use of CPB is necessary in a patient with HIT, anticoagulation can be obtained with an infusion of lepidurin in a dosing protocol of:

0.016 - 0.035 mcg/kg/min
0.002 - 0.050 mcg/kg/min
0.01 - 0.05 mcg/kg/min
0.1 - 1.0 mcg/kg/min
1.0 - 5.0 mcg/kg/min

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