HIT definition, diagnosis, and treatment. summery

1. Heparin induced thrombocytopenia
By: Boushra Al Saoor, PharmD intern, Al Maarefa college
20 May 2015

2. Definition:
• Heparin-induced thrombocytopenia (HIT) is a life-threatening
complication of exposure to heparin (ie, unfractionated heparin,
low molecular weight [LMW] heparin) that occurs in up to 5
percent of patients exposed, regardless of the dose, schedule, or
route of administration.

3. Types of HIT:
HIT type I (HIT I): is a mild, transient drop in platelet count that
typically occurs within the first two days of heparin exposure.
The platelet count typically returns to normal with continued heparin
administration.
Direct effect of heparin on platelets by non-immune-mediated
platelet aggregation.
Not clinically significant.

4. Types of HIT:
• HIT type II (HIT II) an immune-mediated disorder that
typically occurs 4-10 days after exposure to heparin and has life-
and limb-threatening thrombotic complications.
In general medical practice, the term HIT refers to type 2 HIT

5. Mortality/Morbidity
• 20-50% risk of developing new thromboembolic events.
• 10% of patients require amputations or suffer other major
morbidity.
• The mortality rate is approximately 20%.

6. Pathophysiology(mechanism of HIT) :
Courtesy of Laura Ibsen, MD.

7. RISK FACTORS
1. Unfractionated versus LMW heparin
• UH >LMW in surgical patients.
2. Heparin dose:
• Therapeutic doses > prophylactic doses>very high doses.
3. Sex:
• female=2×male taking UH .
4. Surgery
• Surgical patients >medical patients (possibly due to the
vascular trauma of surgery).

8. Complications:
1. Deep venous thrombosis
2. Pulmonary embolism
3. Myocardial infarction
4. Occlusion of limb arteries (possibly resulting in amputation)
5. Transient ischemic attack and stroke
6. Skin necrosis
7. End-organ damage (eg, adrenal, bowel, spleen, gallbladder, or
hepatic infarction; renal failure)
8. Bleeding (rare)
9. Death

9. Diagnosis:
• Quick presumptive judgment using 4 Ts.
• Definitive diagnosis by clinical features supported by laboratory
testing.

10. HIT suspicion:
• It must be suspected when a patient who is receiving heparin has
a decrease in the platelet count, particularly if the fall is over 50%
of the baseline count, even if the platelet count nadir remains
above 150 x 109/L.

11. Evaluation: 4Ts
Feature Score
2 points 1 point 0 points
Thrombocytopenia >50% fall
and
platelet nadir 20-100 × 109/L
30%-50% fall
or
platelet nadir 10-19× 109/L
>30% fall
or
platelet nadir < 10× 109/L
Timing of platelet count fall Clear onset on day 5-10, or =1 d if
heparin exposure within past 30 d
Consistent with day 5-10 fall, but not
clear (eg, missing platelet counts); onset
after day 10; or fall = 1 day if heparin
exposure 30-100 days ago
Platelet count fall =4 d without recent
heparin exposure
Thrombosis or other sequelae New thrombosis (confirmed); skin
necrosis; acute systemic reaction
after IV UHF bolus
Progressive or recurrent thrombosis;
erythematous skin lesions; thrombosis
suspected but not proven
None
Other causes of
thrombocytopenia
None apparent Possible Definite
www.hematology.org/Practice/Guidelines/11747.aspx (Accessed on January 07, 2014

12. Evaluation: 4Ts
Total scores and corresponding probability of HIT are as follows:
0-3: Low probability
4-5: Intermediate probability
6-8: High probability

13. Diagnosis, Laboratory tests:
The two types of HIT antibody tests are:
1- Immunoassays [ELISAs], which detect the presence of a HIT
antibody in patient serum.
2- Functional assays, which measure the ability of a HIT antibody
from patient serum to activate test platelets.

14. Management of HIT
Suspected HIT
Discontinue all forms of
heparin
Start Warfarin
if thrombocytopenia
resolves
Notification
Start non-heparin
anticoagulant
Lab test:
ELISA
HIPA
Re -evaluate for
other cause
-ve+ ve HIP AB

15. Rational for anticoagulant use:
1. The condition for which heparin was administered originally .
2. The risk of thrombosis associated with HIT.
40 to 61 % of the thrombotic events occurring more than 24 hours
after cessation of heparin.
Subsequent 30-day thrombosis risk is 53 %.

16. * Important massage:
Use non heparin anticoagulant with HIT regardless of the dose of
heparin used.
One exception: if patient has bleeding or at high risk.

17. Choice of non-heparin anticoagulant
Bivalirudin
Argatroban
Fondaparinux
Danaparoid
Use any of the alternative
anticoagulants.
Argatroban –Bivaluridin in reduced
dose.
Danaparoid,or fondaparinux at
therapeutic doses.
Argatroban or bivalirudin at reduced
doses.

18. General rule of anticoagulant dose and duration:
• Therapeutic dose should be used, with the exception of patients
with combined renal and hepatic impairment.
• Anticoagulant should be used for at least 2 to 3 months, and for at
least 3 to 6 months if a thrombotic event has occurred.

19. 1- Bivalirudin
• Bivalirudin is parenteral hirudin analog.
• It is a competitive, direct inhibitor of thrombin that inhibits both free and
clot-bound thrombin and thrombin-induced platelet aggregation.
• Approved for use in patients who are undergoing PCI and have, or are at risk
for HIT.
• Its effect is monitored by the aPTT.
• Bivalirudin is hemodialyzable.
The recommended initial dose of bivalirudin for HIT:
Normal patient: 0.15 mg/kg /hr.
Hepatic dysfunction: of 0.14 mg/kg /hr.
Renal or combined hepatic and renal dysfunction : 0.03 to 0.05 mg/kg/hr.
Receiving continuous renal replacement therapy: 0.03 to 0.04 mg/kg /hr.

20. 2- Argatroban
• Argatroban is a DTI; it inhibits fibrin formation, platelet aggregation, and
activation of coagulation factors V, VIII, XIII, and protein C.
• Metabolized hepaticlly .
• Not excreted by kidney(Ideal alternative if patient receiving dialysis).
• Its effect is monitored by the aPTT, and also has dose-dependent increases in
the PT.
• Steady-state anticoagulation is reached 1 to 3 hrs after IV administration.

21. Argatroban dose:
Standard starting dose:
Normal hepatic function:
2 mcg/kg/min by continuous IV infusion, adjusted to maintain the aPTT at 1.5
to 3 times baseline, not to exceed 100 seconds.
Hepatic dysfunction, combined hepatic/renal dysfunction, heart
failure, severe anasarca, or who are post cardiac surgery:
0.5 to 1.2mcg/kg per minute. Check the aPTT at four-hour intervals after drug
initiation or dose change.
Critically ill patients with multiple organ dysfunction syndrome
and HIT:
0.5 mcg/kg per minute .

22. 3- Fondaparinox:
• A synthetic anticoagulant that works by inhibiting factor Xa.
• It provides a highly predictable response.
• Bioavailability is 100%, has a rapid onset of action, and a half-life of 14-
16 h, allowing for sustained antithrombotic activity over 24-h period.
• It does not affect PT or aPTT, nor does it affect platelet function or
aggregation.
• Administered SC.
• Patients taking it for prolonged periods should have periodic monitoring
of renal function.
• Use full therapeutic dose of fondaparinux ( 5 to 10 mg/day).

23. 4- Danaparoid:
Heparan derivative that consists predominantly of dermatan sulfate
and low-sulfated heparan sulfate; it is devoid of heparin.
• SC or IV
• Monitored by anti-factor Xa activity (four hours after injection if
administered subcutaneously).

24. The recommended therapeutic dose of danaparoid in HIT:
• Doses are adjusted to achieve anti-factor Xa levels of 0.5 to 0.8
anti-Xa units/mL.
IV) bolus of
2250 units-
IV infusion
400 units/hour
IV infusion
300 units/hr
IV infusion
200 units/hr
4 hrs 4hrs

25. Warfarin:
• For long term oral treatment.
Warfarin should be started in a patient with HIT only when both of
the following have been accomplished:
1. The patient has been stably anticoagulated with an alternative
anticoagulant.
2. The platelet count has increased to at least 150,000/microL.

26. Warfarin, cont:
• Overlap between warfarin and other anticoagulant for at least 5
days.
• Use low starting dose (5mg or less) and adjust dose according to
INR.

27. Managing complication: Bleeding(rare):
• Rare (platelet in HIT >20,000/microL).
• Manage by platelet transfusion.

28. References:
• Steven coutre. Clinical presentation and diagnosis of heparin-
induced thrombocytopenia. Up to date. April 2015.
• Steven coutre. Management of heparin-induced thrombocytopenia.
Up to date. April 2015.
• Sancar Eke,Emmanuel C Besa. Heparin-Induced Thrombocytopenia.
Medscape. Aug 2014

29. THANK YOU