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THROMBOCYTOPENIA
By
SESHU
INTRODUCTION
• Heparin-induced
thrombocytopenia (HIT) without or
with thrombosis (HITT) is the
development of thrombocytopenia
(low platelet counts) due to the
administration of the
anticoagulant (blood clotting
inhibitor) heparin, either in its
"unfractionated" or "low molecular
weight" form.
• It predisposes to thrombosis, the
INTRODUCTION Contd…
• If someone receiving heparin develops
new or worsening thrombosis, or if the
platelet count falls, HIT can be confirmed
with specific blood tests.
• The treatment of HIT requires both
protection from thrombosis and choice of
an agent that will not reduce the platelet
count further.
• Several agents exist for this purpose,
mainly lepirudin and argatroban.
• While heparin was discovered in the
1930s, HIT was not reported until the
1960s and 1970s.
Thrombocytopenia and Heparin
• Heparin - • Heparin -
associated induced
Thrombocytopenia Thrombocytopenia
(HAT) (HIT)
– Non-immune – Immune-mediated
mediated – Moderate/severe
– Slight/moderate decrease in
decrease in platelet count
platelet count – Occurs 5-10 days
– Occurs 1-4 days after
after start of start of heparin
heparin
– Frequency ~ 1-3%
CLASSIFICATION
• Types of HIT
– Isolate HIT (thrombocytopenia
only)
– HIT with thrombosis syndrome
(HITTS)
Heparin-Induced Thrombocytopenia
(HIT): Pathophysiology
IgG antibody
PF4 Heparin
Formation of
immune complexes
(PF4-heparin-IgG)
Formation of
PF4-heparin
complexes
Microparticle
release
EC injury
Platelet PF4
release
Platelet
activation*
Heparin-like
Fc receptor molecules
Blood vessel
Pathophysiology of HIT and
Thrombosis
7
4
6
3
1 5
2
Platelets
7
4
6
3
1 5
Platelets
7
4
6
3
1 5
Platelets
6
3
1 5
2
Platelets
• Pathological
– Heparin-dependent, platelet-activating
IgG antibodies
Heparin-induced thrombocytopenia (HIT)
Possible
Thrombocytopenia (> 50% decrease) +
Thrombosis +
Unusual thromboembolism;
skín lesions; anaphylaxis +
Strongly Suspected
Platelet Activation
Coagulation
Death
PF4 /HIT-IgG Release PF4 /HIT-IgG
Coagulation
“Iceberg model” of HIT
HIT and associated thrombosis occurs in the
subset of patients with platelet-activating
anti-PF4/H antibodies
Thrombosis
HIT
Thrombocytopenia
syndrome Positive
washed
platelet Positive
activation PF4
assay antigen
assay
Numbers of Patients
Differential diagnosis
• Hemodilution post-surgery
• Severe pulmonary embolism
• Sepsis
• DIC (multiple causes besides HIT)
• Cancer-associated DIC
• Antiphospholipid syndrome
• Thrombolytic therapy
• EDTA-induced pseudothrombocytopenia
• GP IIb/IIIa inhibitor-induced
thrombocytopenia
• Drug-induced thrombocytopenia (other
than heparin)
• Post-transfusion purpura
• Thrombotic thrombocytopenic purpura
• Non-immune heparin-associated
Diagnosis - pretest probability : the 4 T’s
Points: Score 0, 1 or 2 for each of 4 2 1 0
categories:
• Score 4 - 5:
a minority have HIT (10-30%)
• Score 6 – 8:
20 to >80% have HIT, depending on the
clinical setting and scorer´s experience :
these patients usually require an alternative,
non-heparin anticoagulant in therapeutic doses
Management of HIT – treatment
When HIT is strongly-suspected:
• Stop heparin (UFH/LMWH), even in
patients without thrombosis
• Initiate alternative non-heparin
anticoagulant because of high risk
of symptomatic thrombosis
• Test for HIT antibodies
• Duplex ultrasonography for lower-
limb DVT
Alternative Anticoagulants
Drug Indications
Argatroban FDA-approved for HIT
[also for Percutaneous
Coronary Intervention
Lepirudin (PCI)]
FDA-approved for HIT
(FDA-Food and drug
Bivalirudin administration)
PCI (including HIT patients)