Transcript Heparin-induced thrombocytopenia (HIT)

Anthony Worsham, MD
Friday, June 18, 2010
Hospital Medicine Best Practices Meeting
University of New Mexico
 Case vignette
 Background
 Pathophysiology
 Guidelines
 Action recommendations
 Discussion with Dr. Garcia
 44-year-old man
 HPI: ESRD secondary to DMII, CAD
 CC: sepsis/osteomyelitis
 Hospital course:
 osteomyelitis treated with piperacillin/tazobactam
 right subclavian catheter-associated DVT treated with
heparin drip
 Orthopedics consulted; BKA scheduled
 was switched to argatroban due to platelet drop
 morning prior to surgery, patient went into PEA arrest
and ACLS protocol initiated, but patient died.
platelets
300
250
241
227
200
207
193
192
180
161
158
150
120
111
100
94
50
50
0
2/6
2/7
2/8
2/9
2/10
2/11
2/12
2/13
2/14
2/15
2/16
2/17
73-year-old female
 transferred for workup of a possible left adnexal mass
 multiple abdominal surgeries at St. Vincent's
secondary to necrotizing fasciitis as well as multiple
abdominal abscesses
 several decubitus ulcers with wound VAC
 pulmonary embolism at outside hospital on a heparin
drip
 MDR UTI with Klebsiella, Pseudomonas, Candida and
VRE
 malnutrition
Platelet count x 109/L
400
364
350
342
307
300
303
282
258
250
230
265
218
200
184
150
100
50
0
183
138
132
100
98
60
55
50
36
34
 formerly known as HIT Type II
 thrombocytopenia
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absolute: <150,000/mL3
relative: 50 percent or more fall from baseline
surgical patients: baseline platelet count is post-surgical peak, not admission
Timing: classically
 incidence
 1% to 5% of postoperative patients
 0.5% to 1% of medical patients
 duration of heparin >1 wk v <1 day (OR ~20-100), type of heparin
(UFH>LMWH>fondaparinux) (OR~10-15), type of patient
(surgery>medical>pregnancy) OR ~3-4, higher risk in women (odds ratio, 1.5–
2.0)
 Timing: 5-10 days post heparin exposure
 Mechanism
 Platelet activation by binding of heparin-dependent IgG to platelet FcγIIa
receptors
 Venous thromboembolism
 DVT (50%) and pulmonary embolism (25%)
 Arterial thrombosis
 Limb artery thrombosis (10%–15), thrombotic stroke (5%–10%),
myocardial infarction (3%–5%), other (eg, mesenteric artery
thrombosis, spinal artery thrombosis)
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
Thrombotic stroke
Coumarin necrosis
Adrenal hemorrhage
Necrotizing skin lesions at heparin injection sites
Anaphylactoid reaction
DIC
 10%–20% of patients who have HIT have overt (decompensated) DIC
(eg, hypofibrinogenemia, increased INR, positive protamine sulfate
paracoagulation
Warkentin TE, Heparin-induced thrombocytopenia, Hematol Oncol Clin N Am 21
(2007) 589–607
Differential diagnosis
 Sepsis
 DIC
 TTP/HUS
 Drug-induced
 Antibiotics
 Heparin
 (see OSU website)
 ITP
2 points
1 point
0 points
Thrombocytopenia
>50% fall or nadir
20-100 x 109/L
30-50% fall or nadir
10-19 x 109/L
<30% fall or nadir
<10 x 109/L
Timing of platelet
count fall
Days 5-10 or <1 day if
heparin exposure
within past 30 days
>Day 10 or unclear
(but fits with HIT) or
<1 day if heparin
exposure within past
30-100 days
<1 day (no recent
heparin)
Thrombosis or other
sequelae
Proven thrombosis,
skin necrosis, or,
after heparin bolus,
acute systemic
reaction
Progressive,
recurrent, or silent
thrombosis;
erythematous skin
lesions
None
OTher cause for
thrombocytopenia
None evident
Possible
Definite
pretest probability of HIT by total points is as follows: 6 to 8=high (60-80%), 4 to
5=intermediate (10-30%); 0 to 3=low (<5%)
Lo GK, et al. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin- induced
thrombocytopenia in two clinical settings. J Thromb Haemost 2006; 4: 759–65.
 ISTH DIC score ≥ 5 sufficient to diagnose or rule out
DIC. (91% sensitivity, 97% specificity, 96% positive,
predictive value, 97% negative predictive value)
 functional assay: serotonin release assay (SRA)




gold standard
technically demanding, requires radiation
Send out lab
sensitive and specific (>95%)
 antigen immunoassays
 enzyme-linked immunosorbent assay [ELISA]
 high sensitivity, low specificity
 PIFA® (Particle ImmunoFiltration Assay)
 Platelet aggregation assay
 HIPA (heparin-induced platelet aggregation)
 Results not immediately available for any test
Warkentin TE, et al. Am J Med. 1996;101:502-507.
 Initial treatment decisions made on clinical grounds
 Confirm thrombocytopenia (repeat CBC)
 Test for DIC
 Test for HIT antibodies
 Assess for thromboses (eg, ultrasound for lower-limb DVT)
 Stop all heparin (including heparin “flushes” and, possibly,
use of heparin-coated intravascular catheters [catheters in
situ for several days may not have significant residual
heparin)
 Initiate alternative anticoagulation (options: argatroban,
lepirudin, bivalirudin, fondaparinux [?]) if HIT is strongly
suspected
Di Nisio M, et al. Direct thrombin inhibitors. NEJM 2005;353:1028-40.
Direct thrombin
inhibitors
Exosite 1 = dock for
substrates such as
fibrin
Exosite 2 = heparin
binding domain
 argatroban
 hepatically cleared
 lepirudin
 renally cleared
 ?higher risk of bleeds
 bivalirudin
 Mostly used during cardiac surgery
argatroban: thrombosis decreased to 13-19% vs 35% historical controls;
bleeding rate 6-11%
lepirudin: thrombosis decreased to 4% vs 15% historical controls;
bleeding rate 14%
bivalirudin: mostly used during PCI or cardiothoracic surgery
Di Nisio M, et al. Direct thrombin inhibitors. NEJM 2005;353:1028-40.
 postpone warfarin until platelet count > 150 × 109/L
 warfarin and DTI should overlap 4-5-days
 target INR for concomitant warfarin/argatroban 4.0
Warkentin T et al,Treatment and Prevention of Heparin-Induced Thrombocytopenia:
American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th
Edition) Chest June 2008 133:340S-380S
 When should hematology consult be obtained?
 Would placing a HIT protocol in CPOE be helpful?