Heparin-Induced Thrombocytopenia (HIT) Sunil Patel

1
Heparin-Induced Thrombocytopenia (HIT)Sunil
Patel
2
Why should I care about HIT?

• Because of common use of UFH or LMWH
• Limb and/or life threatening complication of HIT
• Availability of effective treatment
• Availability of diagnostic test
• If not treated right, can pose potential
  medicolegal risk
• STAY AWAKE!!!!

3
Causes of Thrombocytopenia

• Increased platelet destruction
• Non-immune
• Septicemia/Inflammation
• Disseminated intravascular coagulation
• Immune
• Autoimmune idiopathic or secondary immune
  thrombocytopenia
• Alloimmune post-transfusion purpura
• Drug-induced prothrombic (heparin),
  prohemorrhagic (quinine, quinidine, gold, sulfa
  antibiotics, rifampin, vancomycin, NSAIDs, many
  others)
• Thrombotic thrombocytopenic purpura

4
Causes of Thrombocytopenia (cont.)

• Decreased platelet production
• Alcohol, cytotoxic drugs
• Aplastic anemia
• Leukemia, myelodysplasia
• Metastatic invasion of marrow
• Infections
• Hypersplenism
• Hemodilution (infusion of blood products,
  colloids, or crystalloids)

5
Action of Heparin

• Primary action
• Binds to antithrombin (cofactor)
• After binding, increases antithrombins
  inhibition of thrombin (factor IIa) and factors
  IXa, Xa, XIa, XIIa, and kallikrein
• Limited anticoagulant action
• Prevents additional thrombus accretion
• Unable to dissolve an existing thrombus directly

6
Heparin mechanism of action
Heparin
Antithrombin III
Thrombin
7
Intrinsic Pathway
Extrinsic Pathway
Tissue Injury
Blood Vessel Injury
Tissue Factor
XIIa
XII
Thromboplastin
XIa
XI
IXa
IX
VIIa
VII
Xa
X
X
Prothrombin
Thrombin
Factors affected By Heparin
Fribrin monomer
Fibrinogen
Vit. K dependent Factors Affected by Oral
Anticoagulants
Fibrin polymer
XIII
8
Terminology Relating to HIT

• Heparin-induced thrombocytopenia (HIT) Type II
• Non-immune heparin-associated thrombocytopenia
  (non-immune HAT) Type I

9
Terminology Relating to HIT

• Heparin-induced thrombocytopenia (HIT)
• Also known as HIT type II, white clot syndrome
  (platelet rich thrombus), and Immune
  heparin-associated thrombocytopenia (HAT)
• Denotes demonstrable role of heparin in
  inducing thrombocytopenia (ie,
  heparin-dependent antibodies are detectable)
• Non-immune heparin-associated thrombocytopenia
  (non-immune HAT)
• Also known as HIT type I, HAT
• Denotes absence of heparin-dependent antibodies
  and the potential role for other factors in
  causing thrombocytopenia

10
Pathophysiology of HIT and Thrombosis

• Although HIT results from an immune response,
  heparin itself is not immunogenic.
• Rather heparin combines with a small platelet
  a-granular component called platelet factor 4
  (PF-4).
• Each heparin molecule bundles two or four PF-4
  molecules together, and this complex then binds
  to the platelet membrane

11
Pathophysiology of HIT and Thrombosis (cont.)
12
Pathophysiology of HIT and Thrombosis (cont.)

• Ab generated against Heparin/PF-4 complex binds
  to it through the Fab region.
• Then Fc portion of Ab occupies the Fc receptor on
  the platelets.
• Once this receptor has been occupied, platelets
  are activated and release microparticles which
  are responsible for platelet aggregation,
  endothelial damage and thrombi formation.
• Platelet microparticles bind to subendothelial
  matrix and can act as a substrate for further
  platelet binding. This interaction may play a
  significant role in platelet adhesion to the site
  of endothelial injury.
• Michael Merten,Platelet Microparticles Promote
  Platelet Interaction With Subendothelial Matrix
  in a Glycoprotein IIb/IIIaDependent Mechanism
  Circulation. 1999992577-2582

13
Pathophysiology of HIT and Thrombosis (cont.)
14
(No Transcript)
15
Case Summary

• A 61 YO WF with Raynauds phenomenon underwent
  mechanical aortic valve replacement for aortic
  insufficiency. Unfractinated heparin (UFH) was
  given until PO day 4, and warfarin(5,5 and 2.5)
  was given from days 2 to 4.On day 8,the patient
  developed ischaemic necrosis of multiple fingers
  and toes. The plt count dropped by 44 from
  221(day 4) to 124(day 8) and the INR was 4.3

16
When should HIT be suspected?

• For patient receiving heparin, OR who have
  received heparin within last 2 weeks,recommendatio
  n is to exclude HIT if the platelet counts falls
  by 50 and/or a thrombotic event occurs,between
  days 4 to 14 following initiation of heparin,even
  if the patient is no longer receiving heparin
  therapy when thrombosis or thrombocytopenia have
  occurred.
• Warkentin, Heparin-induced thrombocytopeniaRecog
  nition,Treatment,and Prevention.The seventh ACCP
  conference on Anthithrombotic and Thrombolytic
  Therapy, CHEST 2004126311s-337s.

17
Incidence of HIT and HIT Thrombosis Prospective
Studies of IV Therapeutic-Dose Heparin
No. of
Early (
4 days)
Late (
5 days)
?
?
Patients
Thrombosis
thrombo-
thrombo-
Arterial
Venous
cytopenia
cytopenia
Ansell, 1980
43
1
4
0
0
Ansell, 1985
104
5
5
0
0
Bailey, 1986
43
0
1
1
0
Ramirez-
Lassepas, 1984
211
2
9
2
1

Cipolle, 1983
Gallus, 1980
143
4
5
0
1
Green, 1984, 1986
89
0
2
1
1
Holm, 1980
90
0
1
0
0
Kakkasseril, 1985
142
--
9
2
2
Monreal, 1989
89
--
2
0
1
Nelson, 1978
37
6
3
0
0
Powers, 1979
120
2
2
1
1
Powers, 1984
131
2
3
0
0
Rao, 1989
94
3
3
0
0
Total
1,336
24 (1.8)
46 (3.4)
7
7
From Warkentin TE, Kelton JG. In Bounameaux H,
ed. Low-Molecular-Weight Heparins in Prophylaxis
and Therapy of Thromboembolic Diseases.
Fundamental and Clinical Cardiology. New York
Marcel Dekker, Inc 199475127. Some
information obtained by personal communication.
18
Differences Between HIT and Non-Immune HAT
Non-Immune HAT
HIT
Usually 514 days (may be
Onset
Within 4 days
sooner)
Platelet count
Typically 100,000150,000/
?
L
Typically 20,000150,000/
?
L
?

median nadir 50,000/
?
L in
most series rarely lt20,000/
?
L
?

sometimes falls gt30, but
remains gt150,000/
?
L
Complications
Thromboembolic lesions
None
530
1 at 1 week 3 at 2 weeks
Incidence
Recovery
13 days
57 days
Benign, tiny platelet
IgG-mediated strong platelet
Cause
aggregates
activation
19
Thromboembolic Disorders Associated With HIT
Consequences

• Venous thrombosis DVT(LEgtgtUE) venous limb
  gangrene pulmonary embolism (the most common
  life threatening event) cerebral sinus
  thrombosis
• Arterial thrombosis Limb gangrene
  cerebrovascular accident MI miscellaneous
  end-organ thromboses
• Other complications Adrenal hemorrhagic
  infarction heparin-induced skin lesions (at
  injection sites) acute systemic reactions (post
  IV heparin bolus) disseminated intravascular
  coagulation, global amnesia
• Because of many life threatening complication, it
  is absolutely necessary to suspect , diagnosis
  and treat HIT.

20
Incidence of Complications and Mortality of HIT
No. of
Age (year
Complications
Mortality
Year
Patients
range or SD)
n
()
n
()
M
F
1983
62
34
28
19-93
38 (61.0)
14 (23.0)
1986
169
97
72
2-94
38 (22.5)
20 (12.0)
1996
127
60
67
67.0 /- 11.4
99 (78.0)
26 (20.5)

1996
62
33
29
66.7 /- 12.3
32 (51.6)
13 (21.0)
Includes patients initially presenting with
thrombosis Subgroup of the 127 patients
presenting with thrombosis From Laster J, Cikrit
D, Walker N, Silver D. Surgery. 1987102763-770
and Warkentin TE, Kelton JG. Am J Med.
1996101502507.
21
Skin Necrosis

• Warkentin TE. Br J
  Haematol. 199692494497.

22
Skin Necrosis

• Affected areas are usually fat-rich, such as the
  abdomen, as in warfarin-induced necrosis
  however, the distal extremities and the nose can
  also be involved. The appearance of erythema is
  followed by purpura and hemorrhage leading to
  necrosis. Although the lesions appear similar to
  warfarin-induced skin necrosis(
  histopathologically different), deficiencies of
  the natural anticoagulants are not present.
  Affected patients develop heparin-dependent
  antibodies but most do not experience
  thrombocytopenia.

23
Pretest Probability of HIT, The 4 TsPretest
probability score 6-8 indicates high 4-5
intermediate and 0-3 low
24
Diagnosis of HIT

• Normal platelet count before commencement of
  heparin therapy
• Onset of thrombocytopenia typically 514 days
  after initiation of heparin therapy but can occur
  earlier
• Exclusion of other causes of thrombocytopenia
  (eg, sepsis)
• Occurrence of thromboembolic complications during
  heparin therapy

25
Diagnosis Platelet Aggregation Assay

• Measures platelet aggregation of IgG in serum or
  plasma of a HIT patient treated with heparin
• Donor platelets can be washed or suspended in
  citrated plasma
• Advantages
• Easily performed in most laboratories
• Specificity greater than 90
• Disadvantages
• Low sensitivity 3581 sensitivity higher
  using washed platelets
• Reactivity varies among donor platelets

26
Diagnosis Serotonin Release Assay

• Remains the gold standard among the diagnostic
  tests for HIT
• Measures the release of serotonin from aggregated
  platelets in serum of patient with HIT relies on
  platelet aggregation in the presence of heparin
• Platelets from normal donors are radiolabeled
  with 14C-serotonin. The platelets are then washed
  and patient serum is added along with either high
  or low heparin concentrations. A positive test is
  the release of 14C-serotonin when therapeutic
  (0.1 U/mL) concentrations of heparin are used,
  rather than high (100 U/mL) concentrations.
• Notify lab of any heparin use in last 24 hrs.
• Advantages
• High specificity and sensitivity
• Validated in blinded assessment of a clinical
  trial
• Disadvantages
• Technically demanding and time-consuming
• Requires the use of radioactive materials

27
Diagnosis Heparin/PF4 ELISA

• The solid phase immunoassay is different from the
  first two tests since it is not a functional
  assay. Heparin-PF4 complexes are coated on a
  microtiter plate and patient serum is added. If
  heparin-dependent antibodies are present in the
  serum sample, they will bind the complex, which
  can be identified by adding a second antibody.
  This is a very sensitive assay (91 percent), but
  its clinical utility remains to be determined,
  since many antibody-positive patients do not
  develop clinical HIT . The specificity of the
  test may be improved by assaying only for
  heparin-PF4-IgG antibodies .
• The test is best used along with one of the
  functional assays rather than as a single test,
  since up to 10 to 20 percent of sample results
  may be discordant between this assay and the
  others .
• Useful in patients who require UFH after HIT.

28
EIA-SRA (Enzyme Immunoassay Serotonin Release
Assay).

• Compared to 14-C Serotonin release assay, NO USE
  OF RADIOACTIVE MATERIAL (14-C Serotonin)
• Measures release of serotonin from donor platelet
  in the presence of Ab HIT and low concentration
  of heparin.
• The sensitivity and specificity of the EIA-SRA
  was 100 and 974 and of the 14C-SRA 100 and
  92.9 in HIT patients.
• No false-positive results were found in patients
  receiving heparin,in ,in patients with
  antiphospholipid antibody syndrome or in non-HIT
  patients with both assays.
• Harenberg, J., Huhle, G., Giese, CH., Wang,
  L. C., Feuring, M., Song, X. H. Hoffmann,
  U.Determination of serotonin release from
  platelets by enzyme immunoassay in the diagnosis
  of heparin-induced thrombocytopenia.British
  Journal of Haematology  109 (1), 182-186.doi
  10.1046/j.1365-2141.2000.01966.x

29
Treatment of Non-Immune HAT

• Heparin should be continued if still indicated
• Patients with non-immune HAT are asymptomatic
  platelet counts should return to normal during
  continuation of heparin therapy
• No additional risk of thrombosis

Note It may sometimes be difficult to
distinguish between immune HIT and non-immune HAT
on clinical grounds alone
30
Treatment of Suspected HIT

• Discontinue all heparin immediately, including
• Heparin flushes (also avoid LMWH)
• Heparin-coated pulmonary catheters
• Heparinized dialysate and any other medications
  or devices containing heparin
• Consider alternative anticoagulation ( DONOT
  START WARFARIN RIGHT AWAY )
• Confirm diagnosis of HIT with the appropriate
  laboratory test
• Monitor carefully for thrombosis ( routine Duplex
  scan for DVT in LE for patients with strongly
  suspected or confirmed HIT)
• Monitor platelet counts until recovery
• Avoid prophylactic platelet transfusions
• Warkentin, Heparin-induced thrombocytopeniaReco
  gnition,Treatment,and Prevention.The seventh ACCP
  conference on Anthithrombotic and Thrombolytic
  Therapy, CHEST 2004126311s-337s.

31
Fourteen-Year Study of HIT

• Study design Retrospective cohort study
• Population 127 patients with serologically
  confirmed HIT in one medical community
• Group I (n65) HIT diagnosed after appearance of
  new thrombosis
• Group II (n62) Initial diagnosis of isolated
  HIT (ie, no new thrombosis at time of diagnosis)
• Reason for hospitalizations
• Surgical approximately 2/3 (mostly orthopedic)
• Medical approximately 1/3 (DVT or PE)
• Warkentin TE, Kelton JG. Am J Med.
  1996101502507.

32
Fourteen-Year Study of HITGroup II Results
After Heparin Discontinuation
100 90 80 70 60 50 40 30 20 10 0
52.8
Cumulative Thrombotic Event Rate ()
0
2
4
6
10
12
14
16
8
18
22
26
28
30
24
20
Days After Isolated HIT Recognized
Adapted with permission from Warkentin TE, Kelton
JG. Am J Med. 1996101502507.
33
Fourteen-Year Study of HIT Summary

• Relatively conservative, conventional management
  of patients with isolated HIT (ie,
  discontinuation of heparin with or without
  substitution with warfarin)
• Conservative treatment approaches can result in
  unacceptably high rates (50) of subsequent
  thrombosis- Thats why heparin cessation alone is
  often not sufficient.
• Warkentin TE, Kelton JG. Am J Med.
  1996101502507.

34
Venous Limb Gangrene( with use of warfarin in
HIT)

Used with permission from Warkentin TE, Elavathil
LJ, Hayward CPM, Johnston MA, Russett JI, Kelton
JG. Ann Intern Med. 1997127804812.
35
Venous Limb Gangrene( with use of warfarin in
HIT)

• Patients with acute heparin-induced
  thrombocytopenia and deep venous thrombosis who
  are treated with warfarin seem to be at risk for
  developing venous limb gangrene.
• Laboratory studies suggest that this syndrome is
  related to a warfarin-induced failure of the
  protein C anticoagulant pathway to regulate the
  increased thrombin generation that occurs in
  patients with heparin-induced thrombocytopenia.

36
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37
Action of Thrombin
Releases from endothelium NO PGI2 t-PA
von Willebrand ADP
Factor V Va Factor VIII VIIIa
Prothrombin thrombin
Thrombin
Activation of platelets
Adapted with permission from Fuster V, Verstraete
M. In Braunwald E, ed. Heart Disease A Textbook
of Cardiovascular Medicine. Philadelphia WB
Saunders Company 199718091842.
38
Development of Lepirudin (rDNA) for Injection
(Refludan?)
Lepirudin (recombinant hirudin) approved for
anticoagulation in patients
1998 with heparin-induced
thrombocytopenia (HIT) and thromboembolic disease
in order to prevent further
thromboembolic complications



Lepirudin phase I-II trials (safety,
PK) 19901993
Potential indications






Clin-Pharm investigations of lepirudin
19871989




Lepirudin developed 19861987

Amino
acid sequence determined
19841985


LTYTDCTESGQNLCLCEGSNVCGQGNKCILGSDGEKNQCVTGEGTPKPQS
HNDGDFEEIPEEYLQ
Hirudin primary structure determined
1976


Hirudin defined as
thrombin inhibitor
19551957


Use of hirudin from H. medicinalis
19031904


Anticoagulant activity of
medicinal leech identified 1884
39
Hirudin Inhibition
Antithrombin
Endothelial Cells
Synthesis and release Prostacyclin EDRF,
t-PA Endothelin Tissue factor Activation Prote
in C ??PC a Thrombomodulin
Thrombin
HIRUDIN
Smooth Muscle
Contraction Mitogenesis
Adapted with permission from Markwardt F. Thromb
Res. 199474123.
40
Lepirudin (Refludan) is a recombinant hirudin

• Hirudin is an anticoagulant peptide that occurs
  naturally in the salivary glands of the medical
  leech Hirudo medicinalis
• Effective in preventing new thromboses in
  patients with isolated HIT and no clinically
  evident thromboembolic complications
• Dose- 0.1 to 0.4 mg/kg bolus followed by 0.1 to
  0.15 mg/kg per hour infusion
• Keep aPTT ratio between 1.5 and 2.5
• Caution should be used in patients with renal
  insufficiency, since the drug is cleared by the
  kidney and its anticoagulant effect is not easily
  reversed.
• The incidence of anaphylaxis in patients with HIT
  treated with lepirudin has been estimated to be
  0.015 percent on first exposure and 0.16 percent
  in reexposed patients

41
Lepirudin (Refludan)

• Lepirudin is a safe and effective anticoagulant
  that allows rapid recovery of platelet counts in
  patients with HIT
• Lepirudin does not cross-react with
  heparin-induced antibodies.
• Lepirudin substantially reduced the risk of
  serious complications associated with HIT
• Lepirudin is well-tolerated major bleeding was
  not significantly more common in the
  lepirudin-treated group
• Fatal anaphylaxis after IV bolus.

42
Development of Anti-Hirudin Antibodies

• Possible immunologic preselection as HIT patients
  already developed drug-induced antibodies
• Positive anti-hirudin antibodies (IgG) developed
  in 40 of pts
• No association of reduced hirudin plasma levels
  with formation of anti-hirudin antibodies
• No association between antibody levels and
  clinical endpoints (death, limb amputation, new
  thromboembolic complications, major bleedings,
  and allergic reactions)
• May increase anticoagulant effect of hirudin
  possibly due to delayed renal elimination of
  active lepirudin-antihirudin complex
• Because anti-hirudin antibodies can increase the
  anticoagulant effect of lepirudin, strict ongoing
  monitoring of aPTT is necessary even during
  prolonged therapy

43
Argatroban

• Direct thrombin inhibitor
• Short in vivo plasma half-life of 24 minutes
• Its effect is monitored by the aPTT. Steady-state
  anticoagulation is reached one to three hours
  after intravenous administration after
  discontinuation, the aPTT returns to normal
  within two hours
• In patients with normal hepatic function, the
  suggested starting dose is 2 µg/kg per minute by
  continuous intravenous infusion, adjusted to
  maintain the aPTT at 1.5 to 3 times baseline.
• Argatroban is mostly metabolized by the liver and
  excreted in bile a lower starting dosage (eg,
  0.5 µg/kg per minute) is suggested in patients
  with hepatic dysfunction. Dose adjustment is
  apparently not required in the presence of renal
  impairment .

44
Danaparoid Sodium - a LMW Heparinoid

• Mixture of anticoagulant glucosaminoglycans with
  a low degree of sulfation (50 fewer sulfate
  groups than heparin) .
• Although it is not FDA-approved for HIT, there is
  extensive experience using this agent in patients
  with HIT . It has also been given to patients
  with HIT or a history of HIT who require
  cardiopulmonary bypass surgery .

45
Danaparoid Sodium - a LMW Heparinoid

• There is a 10 percent crossreactivity between
  danaparoid and the antibody responsible for HIT
  in vitro, but the clinical significance of this
  is uncertain given the apparent therapeutic
  benefit in such patients.
• The disadvantages of using danaparoid are the
  need to measure anti-factor Xa levels to monitor
  its anticoagulant effect, its long half-life (25
  100 h) , and the absence of a reversing agent .
• As a result of shortage in drug substance in the
  United States, the manufacturer (Organon) has
  decided to discontinue providing this medication

46
Bivalirudin (Angiomax)

• Oligopeptide hirudin analogue
• Another promising agent for HIT (also used in
  cardiac pt undergoing PTCA)-Direct thrombin
  inhibitor
• Predominant nonrenal metabolism lack of
  immunogenicity (compared with lepirudin)
• Can cause minor prolongation of INR
• Francis JL Bivalirudin, a direct thrombin
  inhibitor,is a safe and effective treatment for
  HIT. Blood 2003102(suppl 1)164a.Abstract

47
Warfarin

• The use of warfarin in the absence of other
  anticoagulants should be avoided in patients with
  HIT until after the platelet count has
  substantially recovered. (to atleast 100,000/µL,
  and preferably,150,000 /µL)

48
Warfarin (cont.)

• The length of treatment is not well defined, but
  in view of the high risk of thrombosis within 30
  days of the diagnosis of HIT , warfarin
  anticoagulation should probably be continued for
  at least two to three months (without any
  documented DVT/PE)
• Start with low dose(Max.5mg)
• Use Vit K ( or FFP in case of protein C
  deficiency) for patient receiving warfarin at the
  time of diagnosis of HIT.

49
Fourteen-Year Study of HITGroup II Results
After Heparin Discontinuation
100 90 80 70 60 50 40 30 20 10 0
52.8
Cumulative Thrombotic Event Rate ()
0
2
4
6
10
12
14
16
8
18
22
26
28
30
24
20
Days After Isolated HIT Recognized
Adapted with permission from Warkentin TE, Kelton
JG. Am J Med. 1996101502507.
50
Prostacyclin Analogues

• Act as natural vasodilators
• Inhibit platelet aggregation
• Advantages
• Platelet activation blocked in patients with HIT
• Short half-life (1530 minutes) permits ease of
  control
• Disadvantage
• Adverse reactions, such as hypotension, may limit
  usefulness

51
Alternative Treatments of HIT

• IV immunoglobulin preparations of the IgG class
  success reported in a few cases
• Platelet transfusions usually unnecessary (low
  bleeding risk in HIT) may increase risk of new
  thromboembolic lesions
• Plasmapheresis anecdotal experience only

Note Consider alternative treatments only as
adjuncts to a major alternative anticoagulant
agent such as danaparoid sodium or recombinant
hirudin
52
Alternative Treatments of HIT

• A preliminary report of three patients suggests
  that a GLYCOPROTEIN IIb/IIIa INHIBITORS in
  combination with a direct thrombin inhibitor may
  be effective when a thrombin inhibitor alone
  fails to relieve acute thrombosis
• A pentasaccharide FONDAPARINUX (selectively
  binds antithrombin III ,selective factor Xa
  inhibitor) has a theoretical role in treatment
  and/or prevention of HIT, since the drug does not
  appear to interact with platelets or platelet
  factor 4. Although not yet formally approved for
  this indication, there are an increasing number
  of anecdotal reports of patients with HIT being
  successfully managed with fondaparinux in lieu of
  a direct thrombin inhibitor.

53
Conclusions
54
Special Patients Population with HIT
55
USE OF HEPARIN AFTER AN EPISODE OF HIT

• Patients with a history of HIT who require
  cardiopulmonary bypass (CPB) have been
  successfully anticoagulated with a brief course(3
  DAYS) of treatment unfractionated heparin without
  complications.
• This approach is based on the theory that a
  secondary immune response after reexposure to
  heparin should not occur until at least three
  days after exposure.
• Therefore, a brief exposure to heparin during
  CPB should not immediately elicit HIT antibodies.
  Further, since the heparin would be rapidly
  cleared after the procedure, even if antibodies
  appeared, they would not be thrombogenic in the
  absence of heparin.

56
USE OF HEPARIN AFTER AN EPISODE OF HIT

• This approach was tried in ten patients with a
  history of HIT who required CPB . At the time
  of surgery all patients were negative for HIT
  antibodies according to a PF4 solid phase assay.
• There were no complications of surgery, no
  prolonged thrombocytopenia, and no increase in
  the serum concentration of HIT antibodies during
  a 10-day post-operative period. Therefore, when
  managing such patients, the use of unfractionated
  heparin could be considered using the following
  guidelines
•      1.Consider if alternative anticoagulants
  are available
•     2. Prove, using a sensitive assay, that
  the HIT antibodies are no longer detectable
   3. Restrict the use of heparin to the operative
  procedure itself  4. Use alternative
  anticoagulants post-operatively if needed (eg,
  lepirudin, warfarin)Potzsch, B, Klovekorn, WP,
  Madlener, K. Use of heparin during
  cardiopulmonary bypass in patients with a history
  of heparin-induced thrombocytopenia letter. N
  Engl J Med 2000 343515.

57
Case Summary

• A 61 YO WF with Raynauds phenomenon underwent
  mechanical aortic valve replacement for aortic
  insufficiency. Unfractinated heparin (UFH)
  prophylaxis was given until PO day 4, and
  warfarin(5,5 and 2.5) was given from days 2 to
  4.On day 8,the patient developed ischaemic
  necrosis of multiple fingers and toes. The plt
  count dropped by 44 from 221(day 4) to 124(day
  8) and the INR was 4.3
• Stop UFH and warfarin
• Start nonheparin anticoagulant ( not only for HIT
  but also for mechanical aortic valve)
• Reverse INR with Vit K and FFP
• Watch Platelet count daily
• Confirm the diagnosis with Serotonin release
  essay

58
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. Suspect and treat.
• Treatment of HIT should be initiated before
  laboratory confirmation
• A new generation of drugs such as the thrombin
  inhibitors can provide important new options for
  the treatment and possible prevention of HIT

59
References

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Heparin-Induced Thrombocytopenia (HIT)THANK YOU