Download Risk of HIT

Heparin-Induced
Thrombocytopenia
Farzaneh Dastan
Assistant Professor of Pharmacotherapy, Pharm D, BCPS
SBMU
Case
 A 64-year-old woman
 Hospitalized with endocarditis
 Condition is clinically stable while she is receiving
intravenous antibiotic agents
 Decrease in platelet count from 161,000 per cubic
millimeter on day 7 of hospitalization to 60,000 per
cubic millimeter on day
 Receiving low-molecular weight heparin at a dose
of 40 mg per day since admission.
 How should her case be further evaluated and
treated?
Epidemiology
 1 in 5000 hospitalized patients
 Incidence rates of 1 to 3%: reported after cardiac surgery.
 Thromboembolic complications: 50% of patients with
confirmed HIT.
 Most frequent complications: Venous thrombosis of the
large vessels of the lower limbs and pulmonary embolism
followed by peripheral arterial thrombosis and then stroke;
 Myocardial infarction: uncommon
 Thrombotic complications may also affect other vessels,
including the cerebral sinus or splanchnic veins.
Heparin-associated
Thrombocytopenia (HAT)
 Nonimmune heparin-associated thrombocytopenia
 Traditionally called type I HIT
 Mediated by direct interaction between heparin and
circulating platelets, causing platelet clumping or
sequestration.
 Self-limiting thrombocytopenia
 Affects 10% of patients receiving heparin
 Within the first 72 hours after heparin administration,
 Platelet counts do not drop below 100,000/mm
 Normalizes once the heparin is ceased
Heparin Induced
Thrombocytopenia
Immediate Onset
 who received within the previous 90 days
(especially, ≤30 days), persistent circulating (PF4)–
heparin antibodies
 start abruptly on reexposure to heparin (rapidonset HIT)
 anaphylactoid reaction within 30 minutes after a
heparin bolus
Delayed onset
 Develops or worsens after heparin has been
discontinued.
 These patients can present with thrombosis up to
3 weeks after heparin exposure
Spontaneous or
autoimmune HIT
 Rare but often catastrophic form of HIT
 Develops in the absence of heparin exposure
 Most often after major surgery (especially knee
replacement) or recent infection.
 In contrast to typical HIT, in which the platelet
count increases within 2 to 5 days after the start
of an alternative anticoagulant
 Autoimmune HIT may persist for weeks.
HIT
 Occurs 5–10 days after receiving heparin
 Median platelet count between 50 and 80*109 L
 Dropped by 50%
 Platelet count starts to rise 2–3 days after
discontinuing heparin
 Returns to normal within 4–10 days
 Antibody disappears within 2–3 months after
cessation of heparin therapy
HIT Criteria
 (a) thrombocytopenia (ie, a drop of the platelet
count to <100 109/L or a drop of >50% from the
patient’s baseline
 (b) exclusion of other causes of
thrombocytopenia (such as cancer, sepsis or
chemotherapy)
 (c) resolution of thrombocytopenia after
cessation of heparin
Strategies & Evidence
Risk of HIT:
Diagnosis
Treatment
 Key interventions:
 Prompt cessation of heparin (if still being
administered)
 Initiation of an alternative anticoagulant at a
therapeutic dose
Argatroban
 After discontinuation: aPTT returns to normal within 2
hours
 Standard starting dose is 2 microg/kg per minute by
continuous intravenous infusion
Aadjusted to maintain the aPTT at 1.5–3 times baseline
and not to exceed 100 seconds
 Metabolized by the liver
 Reduced dose and adjustment in; impaired liver
function, critically ill patients, or cardiac surgery.
 aPTT at 4-hour intervals after drug initiation or dose
change
 Dose adjustment is not required in the presence of
isolated renal impairment
Bivalirudin
 0.15–0.2 mg/kg per hour
 Adjusted to achieve an aPTT 1.5–2.5 times
 Doses of 0.14 mg/kg per hour in patients with
hepatic dysfunction
 0.03–0.05 mg/kg per hour in patients with renal or
combined hepatic and renal dysfunction
 doses of 0.04–0.03 mg/kg per hour in those
receiving continuous renal replacement therapy
Lepirudin and desirudin
 Lepirudin: approved for use in HIT
 Desirudin: Data limited
 dose of either 15 or 30 mg subcutaneously every
12 hours suggested
Danaparoid
 Analysis of outcomes:
 Rate of treatment success (platelet count recovery
without new thrombosis and absence of major adverse
events requiring drug cessation): higher than 90%.
 Renally metabolized
 Approved for treatment of HIT
 No longer marketed in the United
 Drug shortages have limited its availability
 Subcutaneously or intravenously
 Does not cross the placenta.
Fondaparinux
 Long half-life allows once-daily dosing
 Monitored by the use of anti-factor Xa assay
 In pregnant women with HIT
 It is worth noting that HIT developed in a few
cases with the use of fondaparinux
 Easier than argatroban to use outside the
intensive care unit.
 Exacerbations of HIT reported infrequently
 small percentage have true in vivo and in vitro
crossreactivity
 If manifestations of HIT worsen despite sufficient
levels of anti–factor Xa activity, treatment should
be switched (e.g., to argatroban)
Non-vitamin K Antagonist Oral
Anticoagulants (NOACs)
 Recommended by the European Society of Cardiology
 Orally using fixed dosing
 Need little attention regarding monitoring and drug–
drug interactions
 Well proven in the management of venous and arterial
thromboembolism
 Can be continued long term without conversion to
warfarin, which needs platelet count recovery
 Short course of parenteral argatroban followed by
NOACs for the treatment of patients with HIT is safe and
effective
NOACs
RENAL REPLACEMENT THERAPY
 Argatroban and danaparoid recommended for
patients with HIT who need renal replacement
therapy
 Use of regional citrate is suggested for patients
with a past history of HIT
PREGNANCY
 For pregnant women with acute or subacute HIT:
 Danaparoid has been suggested
 lepirudin or fondaparinux may be considered if
danaparoid not available
Warfarin
 Vitamin K antagonists (e.g., warfarin and
phenprocoumon) should not be given until HIT has
abated
 Platelet count has increased to >150,000 per cubic
millimeter at a stable plateau for 2 consecutive
days
 Increase the risk of venous limb gangrene and limb
loss by decreasing the level of protein C
 Overlap with an alternative anticoagulant is
needed
 Warfarin should be slowly introduced at a dose of
not more than 5 mg to avoid large loading doses.
SWITCHING TO AN ORAL
ANTICOAGULANT
 Avoidance of vitamin K antagonists (VKA) such as
warfarin
 Can induce skin necrosis owing to rapid depletion
of protein C
 Once HIT is confirmed, patient receiving VKA should
be held and (INR) should be reversed by vitamin K.
 Platelet recovery to normal level is a required to
initiate VKA
 Warfarin should be slowly introduced at a dose of
not more than 5 mg to avoid large loading doses.
DURATION OF
ANTICOAGULATION FOR HIT
 Continued for 4–6 weeks in patients with
confirmed isolated HIT
 For a minimum of 12 weeks in patients associated
with thromboembolic events.
IVIg
 High-dose intravenous immune globulin G
 Dose of 2 g per kilogram of body weight over a
2-day period
 By blocking platelet Fcγ receptors
 Limited data: may be an option (along with
anticoagulation) in patients at high risk for
thrombosis and bleeding (e.g., those who are
pregnant or have sinus-vein thrombosis
complicating HIT) or in patients who have
autoimmune HIT
In patients with a history of HIT who require cardiac
surgery:
 Postponing surgery until platelet-activating anti–
PF4–heparin antibodies disappear
 Using heparin intraoperatively
 Removal of platelet-activating anti–PF4–heparin
antibodies by plasmapheresis,
 Bivalirudin is a compatible anticoagulant for
cardiac surgery if platelet-activating anti–PF4–
heparin antibodies are present
 Prophylactic platelet transfusions avoided
 Risk of bleeding is very low
 Increase the risk of thrombosis
Guidelines
 ACCP and national European guidelines
recommend the use of a scoring system
 Need for therapeutic-dose anticoagulation in
cases of acute HIT
 ACCP: assessing patients at high risk (>1%) for HIT
every 2 to 3 days between day 4 and day 14
THANKS FOR YOUR
ATTENTION