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Understanding Heparin-Induced Thrombocytopenia (HIT): Historical and Clinical Perspectives

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Diovision of Cardiology Beth Israel Deaconess Medical Center Boston Heparin-Induced Thrombocytopenia Heparin as a Cause of Thrombosis and The HIT Syndromes – PowerPoint PPT presentation

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Title: Understanding Heparin-Induced Thrombocytopenia (HIT): Historical and Clinical Perspectives


1
Amjad AlMahameed, MD, MPH Diovision
of Cardiology Beth Israel Deaconess Medical
Center Boston
Heparin-Induced Thrombocytopenia Heparin as a
Cause of Thrombosis and The HIT Syndromes
2
Why We Should Not Talk About HIT
  • It is rare and over publicized
  • Not every hospitalized patient get heparin
  • No unifying clinical picture and the serology is
    poor..
  • How can we justify anticoagulating a
    thrombocytopenic patient using medications that
    do not have antidotes?
  • Most hospitalized patients with thrombocytopenia
    have multifactorial etiology..
  • Just stop haparin and it will go away.
  • Or start a LMWH and dont worry about it any more
  • Or, start warfarin and it will take care of the
    problem
  • This is DIC, not HIT.. You must continue
    heparin
  • It is a disease born in the industry

3
Not every hospitalized patient get heparin
Ubiquity of Heparin Heparin-based Therapies
Increasing indications
12 million patients are exposed to heparin
per year
One of the most commonly used parenteral Rx in
the hospital setting
Is heparin use Always Documented In the Chart?
Side Effects BOAT
1000,000,000,000 Units used per year in the US
essential medication essential
medication
Fahey. J Vasc Nurs 199513112-116. Kelton
Warkentin. Current Therapy in Hematology-Oncology,
1995149-152
4
Is it a rare and over publicized disease
LETS DO THE MATH
12 million patients exposed annually
Up to 5 incidence of HIT
Up to 600,000 cases every year
x

How many cases are recognized and treated
properly?
18,000 !!!
5
Confusing Terminology
  • Also known as HIT type II, white clot syndrome
  • Heparin-dependent antibodies are usually
    detectable
  • Also known as HIT type I, HAT
  • Denotes absence of heparin-dependent antibodies
    and the potential role for other factors in
    causing thrombocytopenia

Immune HIT/HIT-T
Non-Immune HAT
6
Immune- vs Non Immune-Mediated HIT
Parameter Type I HIT (non-immune mediated) Type II HIT (immune mediated)
Epidemiology 10-30 of UFH treated patients 1-5 of UFH-treated patients Less common with LMWH
Temporal pattern Between days 1-4 of initiating UFH Between days 4-16 of initiating UFH/LMWH
Severity of thrombocytopenia Mild, usually platelet counts remain gt 100,000 Moderate to severe, mean platelet count 60,000
Antibody-mediated No Yes
Thrombosis common No yes
Management Observe Discontinue heparin/LMWH and start treatment with DTI
Outcome Self-limited Death, arterial and venous thromb-osis are potential complications
UFH unfractionated heparin, LMWH low-molecular
weight heparin, DTI direct thrombin inhibitor
7
Pathogenesis of Immune-Mediated HIT
Caiola E, Cleve Clin J Med 2000
67621-624 Bartholomew JR et al 2005
72(S1)S32-S36
8
THROMBOSIS
THROMBOCYTOPENIA
ACTIVATION ASSAY
ANTIGEN ASSAY
9
Endothelial cell activation by HIT Ab, DIC w
natural Anticoagulant, Alternative
platelet-activating IgG
Multiple Thrombosis
Thrombosis
Concomitant factors - ASO -
Vascular trauma (catheters) - Post-op
immobility
0.2 1.0
Thrombocytopenia
- Clinical Setting (OHS, Orthopedic pts) -
Heparin Dose - Platelet FC receptor Number or
genotype - Definition of thrombocytopenia used -
Inflammatory response
1 - 3
Antibody Formation
Frequency of HIT Ab formation depends on
Heparin chain length and degree of
sulfation Clinical setting (OHS, orthopedic
pts) Perioperative PF4 levels Nonimmune platelet
activation
3 - 60
10
Factors Influencing the Frequency of HIT
Type of heparin Bovine lunggtporcine intestinalgtLMWH
Patient population Post- surgerygtmedicalgtobstetrical
Duration of heparin Each day of heparin beyond day 5 and to day 14 increases the risk
Dose of heparin Change from prophylactic dose to therapeutic dose can cause abrupt platelet count fall in patient with HIT antibodies
Sex Female gt male
Definition of thrombocytopenia used Proportional platelet count fall (gt50) is more sensitive than an absolute count (of 100,000 150,000)
11
No unifying clinical pictureDIFFERENTIATE
CLASSICAL HIT FROM ATYPICAL FORMS
12
Variable Frequency of Reported HIT
  • Technical Explanations
  • Variable definition of thrombocytopenia used
  • Differing baseline platelet counts permitted for
    inclusion
  • Requirement to repeat platelet count testing to
    confirm thrombocytopenia
  • Variable intensity of platelet count surveillance
  • Variable intensity of surveillance for thrombotic
    events
  • Failure to exclude nonimmune heparin-associated
    thrombocytopenia

Lee and Warkentin. Heparin-Induced
Thrombocytopenia. New York Marcel Dekker
200081112.
13
Clinically When Should You Consider HIT?
Start with a high index of suspicion increased
awareness and vigilance are required
HIT
14
Classical HIT Thrombocytopenia Criteria
Degree of thrombocytopenia
Timing of thrombocytopenia
  • lt150,000
  • or a 50 drop in platelet count from baseline
    (even if nadir remains gt 150,000)
  • or gt30-50 decrease with documented thrombosis
  • Usually occurs within
  • 514 days of exposure
  • ? Within hours to days if recent heparin exposure
    (past 100days)
  • ? After hospital discharge (9-30 days) with
    delayed onset HIT

15
Classical HIT Criteria ThrombocytopeniaTips
and Clues
  • Relative, rather than absolute, thrombocytopenia
  • Platelet count may be normal when patient
    presents with thrombosis (Delayed onset HIT)
  • In skin necrosis the drop in platelets is small
    but it may predict arterial thrombosis when it
    occurs
  • Platelets recovers after heparin withdrawal
    (Median4 days)
  • HIT is unlikely when platelets recover despite
    ongoing heparin therapy

16
Different Temporal Patterns of Thrombocytopenia
in HIT
Heparin (re) Exposure
Delayed HIT
Early HIT
Day 1
Day 4
Day 16
Week 4
THROMBOCYTOPENIA (/- THROMBOSIS)
17
Delayed-Onset HIT Similar Pthophysiology
Very high titers of IgG super antibodies to
Heparin
Ab
Ab
PLATELET
PF4
Ab
Ab
18
Remember Special Cases
Early-Onset HIT vs. Type I
HIT Non-immune mediated HIT, usually
associated with using large doses of Heparin,
moderate thrombocytopenia usually gt 100,000,
benign course, and platelets recover despite
ongoing heparin Rx
HIT with Normal Platelet Counts Seen in
patients with HIT- associated skin necrosis
Acute Adrenal Insufficiency (secondary to adrenal
vein thrombosis and subsequent adrenal
hemorrhagic infarction)
19
Are There Other Forms of Atypical HIT?
TYPE III
?
TYPE IV
Reaction of antibodies (seropositivity)
without thrombocytopenia
Reaction of antibodies (seropositivity) With
systemic allergic reaction
20
Thrombocytopenia in most hospitalized patients is
multifactorial in etiology
21
Non Drug-Induced Thrombocytopenia
Pseudothrombo- cytopenia
Decreased Platelet Production
Increased Platelet Destruction
Dilutional Thrombocytopenia
DIC
Autoimmune (ITP)
Viruses
Dec Folate
Marrow Replace- ment
Alloimmune (PTP)
Hypersplenism
Dec B12
Dec Fe
22
Just hold Heparin and It will Go Away!How can we
justify anticoagulating thrombocytopenic patients
with medications that do not have antidotes?
23
HIT is a Thrombotic Storm!
Thrombosis Begets Thrombosis!
24
HIT Thrombin GenerationThe Actions of Thrombin
Releases from endothelium NO PGI2 t-PA
von Willebrand ADP
Factor V Va Factor VIII VIIIa
Prothrombin thrombin
Thrombin
Activation of platelets
Fuster V, Verstraete M. In Braunwald E, ed.
Heart Disease A Textbook of Cardiovascular
Medicine. Philadelphia WB Saunders Company
199718091842.
25
Cumulative Frequency of Thrombosis in Isolated
HIT w/o effective anticoagulation
100
90
80
70
52.8
60
Cumulative frequency of thrombosis ()
50
40
30
N62
20
10
0
0
4
6
10
12
14
16
8
18
22
26
28
30
24
20
2
Days after isolated HIT recognized
Warkentin and Kelton. Am J Med. 1996101502-507.
26
Just hold Heparin and It will Go Away!How can we
justify anticoagulating thrombocytopenic patients
with medications that do not have antidotes?
  • A transient increase in risks of new thrombosis
    is observed once heparin is stopped w/o an
    alternative AC (Greinacher Blood 2000)
  • Patients with the lowest platelet counts are most
    likely to experience devastating thrombosis and
    are in greatest need of alternative
    anticoagulation (Rice, Arch Intern Med 2004)
  • 10 of HIT pts have platelets 10,000-20,000.
    Bleeding is rare even when fully anticoagulated.
    (Rice, Arch Intern Med 2004)
  • 6 per day incidence of new thrombosis while
    awaiting serologic confirmation w/o DTI Rx. This
    was decreased to 1.3 per day after Refludan Rx
    (Greinacher et al Blood 2000)
  • Therapeutic dose Argatroban lowered new
    thrombosis from 23 to 6-8 (P lt 0.001) and
    lowered the frequency of composite end point of
    new thrombosis, all cause mortality, and limb
    amputation from 39 to 26-28 (P 0.04) (Lewis
    BE. Circulation 2001 and Arch Intern Med 2003)

27
Could not start DTI due to recurrent GI bleed
28
1 week later
29
1 week later, L foot
30
2 weeks later L arm
31
(No Transcript)
32
Decision making when confronting possible HIT
DEGREE OF ACTION
Very High
Moderate
Very Low
Continue heparin
Start Direct Thrombin Inhibitor
  • Platelet fall lt 30
  • Platelet nadir lt 10,000
  • Platelet fall too early
  • w/o previous exposure
  • No thrombosis
  • - Other cause present
  • gt 50 platelet fall
  • Platelet nadir 20-100 x 109/L
  • Onset between day 5-10 of exposure
  • Onset lt 1 day w prior exposure- 100 d
  • New thrombosis
  • Skin necrosis
  • Systemic reaction
  • No other cause identified

Rice L, Arch. Intern Med Vol 164, Oct 11 2004,
British of Haematology. 123(2)374-375, Oct 2003
33
Just Switch to LMWH
  • HIT incidence in pts receiving LMWH 0.5
  • Once HIT diagnosed, all heparinoids are
    contraindicated
  • The vast majority of HIT antibodies cross react
    with PF-4/ LMWH complex
  • May give unusual skin necrotic lesions distal to
    injection sites

34
Necrotic lesion in HIT patient receiving LMWH
injections
35
Skin Necrosis at UFH injection Sites
(Prophylactic dose)
  • Warkentin TE. Br J Haematol. 199692494497.

36
Necrotic lesions in HIT patient receiving LMWH
injections
37
L arm
Necrotic lesion in HIT patient receiving LMWH
injections
38
This cant be HIT because the platelet count is
not low, (or too low)
39
Distribution of Platelet Count in HIT
Median nadir59 ? 109/L
40
30
Number of patients with HIT
20
10
0
3
5
10
30
100
1000
20
50
15
70
200
300
500
Platelet count nadir ? 109/L
Warkentin. Semin Hematol. 199835(suppl 5)9-16.
40
Thrombotic Complications of HIT 50 of untreated
HIT patients with isolated thrombocytopenia
progress to thrombosis
41 Incidence Ratio Venous to Arterial
ARTERIAL
VENOUS
  • Deep vein thrombosis
  • Pulmonary embolism
  • Cerebral dural sinus
  • thrombosis
  • Adrenal hemorrhagic
  • infarction
  • Aortic occlusion
  • Acute thrombotic stroke
  • MI
  • Intracardiac thrombosis
  • Peripheral arterial
  • thrombosis (limbs,
  • mesenteric, renal
  • and spinal arteries)

Warkentin Kelton. A 14-year study on HIT. Am J
Med 1996 101502-507.
41
Well, what about good ol Coumadin?Lets get a
therapeutic INR, quickly..
42
(No Transcript)
43
Serologic Tests A Quick Overview
44
Laboratory Tests for HIT
Functional (activation)
Antigen
Washed Platelets
Citrated Plasma
Serum or Plasma
  • Serotonin release
  • HIPA
  • ATP release
  • Flow cytometry
  • Platelet aggregation
  • Flow cytometry
  • Heparin-PF4 ELISA
  • Other IA

Citrated plasma is not recommended because of
low sensitivity and low specificity
45
Laboratory Testing for HIT
  • Test Advantages Disadvantages

SRA Sensitivity high Technically
demanding Specificity high (radioisotopes)
(false positives rare) Not readily
available Platelet (HIPA) Specificity high
Sensitivity low aggregation Technique-dependen
t Immunoassay Sensitivity high Specificity
low (false (ELISA) Technically easy positives
common for Rapid turnaround time some
populations)
Fabris et al. Arch Pathol Lab Med.
20001241657-1666 Kelton. Semin Hematol.
199936(suppl 1)17-21.
46
NowWhich Serologic Markers areRequired to
Establish the Diagnosis of HIT?
47
HIT is a CLINICAL DIAGNOSIS HIT is a CLINICAL
DIAGNOSIS HIT is a CLINICAL DIAGNOSIS HIT is a
CLINICAL DIAGNOSIS HIT is a CLINICAL
DIAGNOSIS HIT is a CLINICAL DIAGNOSIS HIT is a
CLINICAL DIAGNOSIS HIT is a CLINICAL
DIAGNOSIS HIT is a CLINICAL DIAGNOSIS HIT is a
CLINICAL DIAGNOSIS HIT is a CLINICAL
DIAGNOSIS HIT is a CLINICAL DIAGNOSIS HIT is a
CLINICAL DIAGNOSIS HIT is a CLINICAL
DIAGNOSIS HIT is a CLINICAL DIAGNOSIS HIT is a
CLINICAL DIAGNOSIS
48
Serologic Markers and the Diagnosis of HIT
  • Serologic markers (SRA, HIPA, PF4) are helpful,
    BUT
  • They must be interpreted within the CLINICAL
    context, AND
  • They are NOT required as part of the
    diagnostic criteria

49
Principles of Management of HIT
50
Treatment of Suspected HIT
  • Discontinue ALL heparin immediately
  • Initiate alternative anticoagulation
  • Monitor carefully for thrombosis
  • Avoid prophylactic platelet transfusions
  • Document HIT in medical records
  • Laboratory evaluation
  • Monitor platelet counts recovery
  • Medi-alert bracelets, heparin allergy education

51
Discontinue ALL Heparin Exposure
  • Heparin gtt, SQ, line flushes
  • LMWH SQ therapeutic and prophylactic doses
  • Heparin-coated catheters
  • Hemodialysis
  • TPN preparations
  • Other sources of potential heparin exposure
    include ECMO, CPB, Cardiac cath/endovascular
    intervention procedures

52
Direct Thrombin Inhibitors in HIT
Argatroban
Lepirudin
Anticoagulant for prophylaxis or treatment of
thrombosis in patients with HIT and in patients
with or at risk of HIT undergoing PCI
Indication
Anticoagulant in patients with HIT and associated
thromboembolic disease in order to prevent
further thromboembolic complications
1.3 h Renal
Elimination Half-life Major Route of Elimination
40-50 min Hepatic
Dosing
HIT 0.4-mg/kg bolus Slowly, intravenously
followed by 0.15 mg/kg/h IV as a continuous
infusion for 2-10 days if clinically
needed PCI NOT INDICATED
HIT 2 mcg/kg/min - Adjustments should be made as
clinically indicated (not to exceed 10
mcg/kg/min) PCI Start infusion at 25 mcg/kg/min
a bolus of 350 mcg/kg administered over 3-5
minutes, check ACT 5-10 min after bolus dose is
complete, therapeutic ACT values are usually
attained within 10-15 min after initiating the
bolus (See full prescribing information)
Antidote
None
None
Formation ofantibodies
No
40 (anti-hirudin)
In healthy subjects Body weight up to 110
kgaPTT, activated partial thromboplastin time.
Refludan lepirudin (rDNA) for Injection
prescribing information Berlex Laboratories
October 2002. Argatroban Injection prescribing
information. GlaxoSmithKline 2003.
53
Anticoagulants Not Indicated for HIT
Drug Name
HITIndication
Type
Limitations
Requires dose adjustment for patients with renal
impairment. Limited data in HIT. Not approved for
HIT.
No
DTI
Bivalirudin
Angiomax
LMWH
Enoxaparin
No
Nearly 100 risk of cross-reactivity with HIT
antibodies contraindicated for patients with HIT.
Lovenox
Fondaparinuxsodium
No
ActivatedFactor X (Xa) Inhibitor
Contraindicated in patients with thrombocytopenia
associated with a positive in vitro test for
antiplatelet antibodies in the presence of
fondaparinux sodium half-life 17 to 21 hours.
Arixtra
Warfarin Coumadin
No
Vitamin Kantagonist
Initiation during acute HIT may lead to venous
limb gangrene due to initial reduction in protein
C levels.

DTIdirect thrombin inhibitor LMWHlow molecular
weight heparin PCIpercutaneous coronary
interventions. Angiomax (bivalirudin) for
Injection prescribing information. The
Medicines Company 2004. Lovenox (enoxaparin
sodium injection) prescribing information.
Aventis Pharmaceuticals Inc. 2004. Arixtra
(fondaparinux sodium) injection prescribing
information. GlaxoSmithKline 2004. Coumadin
(Warfarin Sodium for Injection, USP) prescribing
information. Bristol-Myers Squibb Company 2002.
54
Amjad AlMahameed, M.D. Associate
Staff Section of Vascular Medicine Department of
Cardiovascular Medicine Cleveland Clinic
Foundation
Heparin as a Cause of Thrombosis Heparin-Induced
Thrombocytopenia and The HIT Syndromes
55
Lepirudin
Lepirudin (recombinant herudin) is indicated for
anticoagulation in patients with HIT and
associated thromboembolic disease in order to
prevent further thromboembolic complications
56
Argatroban
Argatroban is indicated as an anticoagulant for
prophylaxis or treatment of thrombosis in
patients with heparin-induced thrombocytopenia
57
Thrombin InhibitorsRecommended Dosing
Argatroban Lepirudin
  • 2 µg/kg/min
  • Check aPTT after 2 hrs
  • adjustment should be made as clinically
    indicated (not to exceed 10 µg/kg/min)
  • Do not use if aPTT gt 100 sec at baseline
  • Bolus 0.4 mg/kg (up to 110 kg)
  • Then 0.15 mg/kg gtt for as long as clinically
    needed
  • Check renal function should be considered prior
    to administration
  • Do not use if aPTT ratio gt 2.5

58
Clinical Studies of Argatroban
The safety and efficacy of Argatroban as
anticoagulant therapy were demonstrated in two
(ARG-911 and ARG-915) multicenter, prospective,
open-label clinical trials in 568 patients with
HIT
59
Clinical Trials of Lepirudin HAT-1 and HAT-2
Studies on HIT
  • Prospective, historically controlled trials
  • Primary objective treatment of HIT with
    lepirudin increases platelet counts or maintains
    normal baseline values while providing effective
    anticoagulation (prolongation of aPTT to 1.5 to 3
    times baseline value)
  • Secondary objective Evaluate incidences of new
    arterial or venous thromboembolic complications,
    major bleeding complications, surgical
    interventions/limb amputations, and deaths

60
Efficacy Results for ArgatrobanComposite Endpoint
21 reduction in death, amputation, new
thrombosis
80
70
60
43 83/193
50
Percent of Patients
34 104/304
34 89/264
40
30
20
10
0
Historical Control
Study 1
Study 2
p lt 0.05 vs historical controls
61
Efficacy Reslts for ArgatrobanIndividual
Components of Composite Endpoint (Study 1)
60
Historical Controls
Argatroban
50
40
Percent of Patients
30
23 45/193
17 53/304
16 31/193
20
11 32/304
6 19/304
4 7/193
10
0
All-Cause Death
All-Cause Amputation
New Thrombosis
Ranked by severity (deathgtamputationgtnew
thrombosis) p NS
62
Independent Efficacy Outcomes
Control
Initial Group
P0.23
30 25 20 15 10 5 0
Plt0.001
P0.07
Outcome ()
Plt0.001
Death
Death Caused by Thrombosis
Amputation
New Thrombosis
Lewis et al. Circulation 2001 Lewis et al. Annual
American Society of Hematology Meeting Dec 2000
Abstract 216. Argatroban injection product
information. Philadelphia, PA GlaxoSmithKline
August 2000.
63
Argatroban in Patients With HIT-T
1
0.8
0.6
Proportion Events-Free
0.4
0.2
P0.014, Hazard ratio0.57, 95 CI0.360.90
0
0
10
20
30
40
Study Day
Lewis et al. Circulation 2001
64
Results of HAT-1 and HAT-2 Cumulative Risk of
Death, Limb Amputation, or Thromboembolic
Complications
Lepirudin
10255
9238
7628
2720
912
611
36
Historical control
80
70
60
P 0.004, log-rank test
50
Cumulative Risk ()
40
30
20
10
0
0
7
14
21
28
35
42
49
Days After Start of Treatment
Lepirudin (n 113, censored 88) Historical
control (n 75, censored 45)
Number at risk Censored observations
65
Argatroban Impact on Anticoagulation
100 80 60 40 20 10 0
Mean (SD) aPTT, seconds
Time after initiation of argatroban, hours
Initial group N250536
Lewis et al. Circulation 2001 in press. Lewis et
al. Annual American Society of Hematology
Meeting Dec 2000 Abstract 216. Argatroban
injection product information. Philadelphia, PA
GlaxoSmithKline August 2000.
66
Bleeding in HIT
Rate of Major Bleeding ()


Lepirudin study
Lepirudin study
Argatroban study
Greinacher. Circulation 1999100587.
Greinacher. Circulation 19999973. Lewis et
al. Circulation 2001 in press.
67
Safety Results for ArgatrobanMajor Hemorrhagic
Events

Argatroban Historical Control

(n568) (n193) Overall
Bleeding 5.3 6.7 GI 2.3 1.6 GU
hematuria 0.9 0.5 ? Hgb Hct 0.7 0
Multisystem Bleed DIC 0.5 1
Limb BKA 0.5 0 ICH 0 0.5
Patients may have experienced more than one
adverse event Defined as overt with a
hemoglobin decrease ?2 g/dL, that led to a
transfusion of ?2 units, or that was
intracranial, retroperitoneal, or into a major
prosthetic joint. Other overt bleeding was
considered minor Typical therapy for patients in
the historical control group was heparin
discontinuation and/or warfarin
68
Results of HAT-2 Platelet Count Recovery Profile
Platelets x 109/L
n 60 63 62 60 57 60 54
57 58 51 51 51 37
500- 400- 300- 200- 100- 0-
Nadir
Before heparin
Before lepirudin
2
4
5
6
7
3
8
9
10
11
Day
Day 1 Start of infusion of lepirudin
69
Guidelines for Conversion to Oral Anticoagulant
Therapy
4 days overlap (Warfarin Argatroban) Use
expected Warfarin dose (no loading dose) Reduce
Argatroban dose to 2 ?g/kg/min 4-6 hours prior to
measuring INR
Measure INR daily
INR gt4.0, stop argatroban infusion
INR ?4.0,continue concomitant Rx
Repeat INR 46 hours later
INR sub therapeutic for warfarin alone, resume
argatroban therapy
INR therapeutic on warfarin alone, continue
warfarin monotherapy
70
Impact of HIT Therapy Complication Development
14 12 10 8 6 4 2 0
No complications
Complications
Number of patients
Delayed Anticoagulant
No Delay in Anticoagulant
P0.034 Fishers exact test
Gene G. Gibson, PharmD, University of
Pennsylvania Medical Center
71
Impact of HIT Therapy Overall Costs of Therapy
25,000 20,000 15,000 10,000 5,000 0
Complications/Length of Stay
Drugs
Ancillary/Lab
No Delay in Anticoagulant
Delayed Anticoagulant
Overall Mean Cost of Therapy9,131 (SD 11.702)
Courtesy of Gene G. Gibson, PharmD, University of
Pennsylvania Medical Center
72
Impact of HIT Therapy Total Attributed Therapy
Days
11.5
12 10 8 6 4 2 0
Days
6.56
No Delay in Anticoagulant
Delayed Anticoagulant
P0.0043, Wilcoxon Rank-Sum a significant
difference existed between groups with respect to
total potential therapy days.
Gene G. Gibson, PharmD, University of
Pennsylvania Medical Center
73
Conclusions
  • Heparin, although an important anticoagulant, has
    several drawbacks, most notably its ability to
    cause HIT
  • HIT can lead to severe and even life-threatening
    thromboembolic disorders
  • Treatment of HIT should be initiated before
    laboratory confirmation
  • A new generation of drugs such as the thrombin
    inhibitors, including the hirudins, may provide
    important new options for the treatment and
    possible prevention of HIT

74
Interpretation of Laboratory Testing for HIT in
Postoperative Cardiac and Orthopedic Surgical
Patients with Late-Onset thrombocytopenia
Antigen Assay (Anti PF4-H ELISA) Activation Assay (SRA or HIPA) Posttest Posttest Prob. Prob. Post-op Pretest If Result is If Result Patient Prob. Population for HIT Sensitivity Specificity Pos Neg Sensitivity Specificity Pos Neg Antigen Assay (Anti PF4-H ELISA) Activation Assay (SRA or HIPA) Posttest Posttest Prob. Prob. Post-op Pretest If Result is If Result Patient Prob. Population for HIT Sensitivity Specificity Pos Neg Sensitivity Specificity Pos Neg
CARDIAC 0.5 (mod) 0.95 0.50 0.66 0.09 0.95 0.80 0.83 0.06
CARDIAC 0.90 (high) 0.94 0.47 0.98 0.36
ORTHO-PEDIC 0.50 (mod) 0.95 0.92 0.92 0.05 0.95 0.97 0.97 0.05 0.90 (high) 0.99 0.33 0.997 0.32
Greinacher et al. 1994a Visentin et al 1996,
Bauer et al 1997, Warkentin et al 2000,
Warkentin and Greinacher 2001.
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