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{{Heparin-induced thrombocytopenia}}
{{Heparin-induced thrombocytopenia}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}, Aric C. Hall, M.D., [mailto:achall@bidmc.harvard.edu]
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}, Aric C. Hall, M.D., [mailto:achall@bidmc.harvard.edu] {{shyam}}
 
==Overview==
==Overview==
[[Heparin-induced thrombocytopenia]] is diagnosed when the [[platelet]] count falls by > 50% typically after 5-10 days of [[heparin]] therapy. The four commonest diagnostic tests used for heparin-induced thrombocytopenia (HIT) are Serotonin release assay, heparin-induced platelet aggregation assay, solid phase immunoassay (enzyme-linked immunosorbent assay), and particle gel immunoassay.
A variety of laboratory tests can be used to aid in the diagnosis of HIT. A [[complete blood count]] is always necessary and will show low [[Platelet count|platelet coun]]<nowiki/>t. A high value of the PF4 IgG optical density can suggest HIT. Confirmatory testing is done with the serotonin release assay (SRA), heparin-induced platelet aggregation (HIPA) assay, or other functional assay. These confirmatory tests have high specificity.


==Lab tests==
==Lab tests==
The most sensitive lab tests are:
* [[Complete blood count]] (CBC): This will show a low [[platelet]] count, (also known as [[thrombocytopenia]]). There is no specific threshold below which HIT is diagnosed, but the typical standard is a decrease in platelet count by approximately 50% or more.
* Anti-heparin-PF4 IgG: This is a test that employs enzyme-linked immunosorbent assay (ELISA) to detect antibodies against the heparin-PF4 complex. The higher the optical density (OD), the stronger the antibody titer and the higher the likelihood of HIT.
The most specific tests are:  
The most specific tests are:  
* The serotonin release assay (SRA)
* Serotonin release assay (SRA)
* The heparin induce platelet aggregation (HIPA) assays and
* Heparin induce platelet aggregation (HIPA) assays  
* Sthe solid-phase immunoassay (SPI) (H-PF4 enzyme-linked immunosorbent assay [ELISA]), and
* Solid-phase immunoassay (SPI) (H-PF4 enzyme-linked immunosorbent assay [ELISA])
* Particle gel immunoassay (PIFA)
* Particle gel immunoassay (PIFA)
* The sensitivity of these tests is 94% at best.
 
===The serotonin release assay (SRA)===   
These specific tests are used for confirmatory testing for HIT after the initial PF4-IgG test is found to be high. The sensitivity of these confirmatory tests, however, is 94% at best.
* The gold standard is the serotonin release assay (SRA) where antibodies from the patient’s serum result in release of radiolabeled serotonin attached to platelets from a normal patient.  
 
===The heparin induce platelet aggregation (HIPA) assays===
===Serotonin release assay (SRA)===   
* The HIPA looks for platelet aggregation that is present with heparin, platelets and patient serum but does not occur in the absence of heparin.
* The gold standard is the serotonin release assay (SRA) where antibodies from the patient’s serum result in release of carbon-14 radiolabeled serotonin attached to [[Platelet|platelets]] from a normal patient.
 
===Heparin-induced platelet aggregation (HIPA) assay===
* The HIPA assay is done via a light transmission aggregometer.<ref name="pmid21740405">{{cite journal| author=Harenberg J, Marx S, Krejczy M, Wehling M| title=New anticoagulants - promising and failed developments. | journal=Br J Pharmacol | year= 2012 | volume= 165 | issue= 2 | pages= 363-72 | pmid=21740405 | doi=10.1111/j.1476-5381.2011.01578.x | pmc=3268190 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21740405  }} </ref> It is performed by mixing platelet-poor plasma from a patient with suspected HIT with platelet-rich plasma from donors.  
* It has a >90% specificity but is limited by low sensitivity.  
* It has a >90% specificity but is limited by low sensitivity.  
===The solid-phase immunoassay (SPI)===  
 
* The SPI is an enzyme-linked immunosorbent assay (ELISA) that tests for the presence or absence of heparin-PF4 complexes.
===Solid-phase immunoassay (SPI)===  
* The SPI is an [[Enzyme linked immunosorbent assay (ELISA)|enzyme-linked immunosorbent assay]] (ELISA) that tests for the presence or absence of heparin-PF4 complexes.
* As it does not determine whether the antibodies are functionally significant, it is best used in conjunction with one of the two prior tests. <ref>{{cite journal |author=Harenberg J, Huhle G, Giese C, Wang L, Feuring M, Song X, Hoffmann U |title=Determination of serotonin release from platelets by enzyme immunoassay in the diagnosis of heparin-induced thrombocytopenia |journal=Br J Haematol |volume=109 |issue=1 |pages=182-6 |year=2000 |pmid=10848798}}.</ref> <ref>Hirsh J, Dalen JE, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1992; 102:337S-351S. PMID 1327666</ref> <ref>Walenga JM, Bick RL. Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other side effects of heparin therapy. Med Clin North Am 1998; 82:635-58. PMID 9646784</ref> <ref>Fabris F, Luzzatto G, Stefani PM, Girolami B, Cella G, Girolami A. Heparin-induced thrombocytopenia. Haematologica 2000 Jan; 85:72-81. PMID 10629596</ref>
* As it does not determine whether the antibodies are functionally significant, it is best used in conjunction with one of the two prior tests. <ref>{{cite journal |author=Harenberg J, Huhle G, Giese C, Wang L, Feuring M, Song X, Hoffmann U |title=Determination of serotonin release from platelets by enzyme immunoassay in the diagnosis of heparin-induced thrombocytopenia |journal=Br J Haematol |volume=109 |issue=1 |pages=182-6 |year=2000 |pmid=10848798}}.</ref> <ref>Hirsh J, Dalen JE, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1992; 102:337S-351S. PMID 1327666</ref> <ref>Walenga JM, Bick RL. Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other side effects of heparin therapy. Med Clin North Am 1998; 82:635-58. PMID 9646784</ref> <ref>Fabris F, Luzzatto G, Stefani PM, Girolami B, Cella G, Girolami A. Heparin-induced thrombocytopenia. Haematologica 2000 Jan; 85:72-81. PMID 10629596</ref>


If HIT is suspected it may take hours to days to obtain the laboratory back.
If HIT is suspected it may take hours to days to obtain the laboratory back.
In the meantime it may simply be a safer approach to substitute another agent (eg agatroban) for heparin. If there is a major diagnostic doubt then there is a "4T" system for identifying patients at risk for HIT.  It is defined as follows;
In the meantime it may simply be a safer approach to substitute another agent (eg agatroban) for heparin.
0-3 points; low probability
4-5 points; intermediate probability
6-8 points; high probability
If the probability is high then discontinue the heparin and begin an alternative anticoagulant; some references recommend the same for those of intermediate risk too. 


1) Thrombocytopenia;
==Reference==
* 0 points for <30% fall or a nadir <10,000
{{Reflist|2}}
* 1 point for a 30-50% fall or a nadir of 10-19,000
* 2 points for a >50% fall or a nadir greater than or equal to 20,000
2) Timing of the decrease in platelet count;
* 0 points for less than a day
* 1 point for greater than day 10 or timing unclear or less than day 1 if heparin exposure was within the past 30-100 days.
* 2 points for day 5-10 or less than or equal to day 1 with recent heparin use (past 30 days)
3) Thrombosis or other sequelae;
* 0 points for no thrombosis
* 1 point for progressive, recurrent or silent thrombosis; erythematous skin lesions.
* 2 points for a proven thrombosis, skin necrosis or acute systemic reaction after heparin bolus. 
4) Other causes of thrombocytopenia;
* 0 points if a definitive concurrent cause.
* 1 point if there is a possible other  reason for thrombocytopenia. 
* 2 points if there are no other possible reasons for thrombocytopenia. 


Isolated HIT: 
This entity occurs when there is a decreased platelet count but without evidence of thrombosis.  It is recommended to stop the heparin and use alternative anticoagulation.  It is also recommended to screen for subclinical deep venous thrombosis with a compression ultrasound (~50% of patients show a DVT with this check).
==References==
{{Reflist|2}}
[[Category:Drugs]]
[[Category:Hematology]]
[[Category:Hematology]]
[[Category:Up-To-Date]]


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Latest revision as of 19:07, 18 August 2017

Heparin-induced thrombocytopenia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2], Aric C. Hall, M.D., [3] Shyam Patel [4]

Overview

A variety of laboratory tests can be used to aid in the diagnosis of HIT. A complete blood count is always necessary and will show low platelet count. A high value of the PF4 IgG optical density can suggest HIT. Confirmatory testing is done with the serotonin release assay (SRA), heparin-induced platelet aggregation (HIPA) assay, or other functional assay. These confirmatory tests have high specificity.

Lab tests

The most sensitive lab tests are:

  • Complete blood count (CBC): This will show a low platelet count, (also known as thrombocytopenia). There is no specific threshold below which HIT is diagnosed, but the typical standard is a decrease in platelet count by approximately 50% or more.
  • Anti-heparin-PF4 IgG: This is a test that employs enzyme-linked immunosorbent assay (ELISA) to detect antibodies against the heparin-PF4 complex. The higher the optical density (OD), the stronger the antibody titer and the higher the likelihood of HIT.

The most specific tests are:

  • Serotonin release assay (SRA)
  • Heparin induce platelet aggregation (HIPA) assays
  • Solid-phase immunoassay (SPI) (H-PF4 enzyme-linked immunosorbent assay [ELISA])
  • Particle gel immunoassay (PIFA)

These specific tests are used for confirmatory testing for HIT after the initial PF4-IgG test is found to be high. The sensitivity of these confirmatory tests, however, is 94% at best.

Serotonin release assay (SRA)

  • The gold standard is the serotonin release assay (SRA) where antibodies from the patient’s serum result in release of carbon-14 radiolabeled serotonin attached to platelets from a normal patient.

Heparin-induced platelet aggregation (HIPA) assay

  • The HIPA assay is done via a light transmission aggregometer.[1] It is performed by mixing platelet-poor plasma from a patient with suspected HIT with platelet-rich plasma from donors.
  • It has a >90% specificity but is limited by low sensitivity.

Solid-phase immunoassay (SPI)

  • The SPI is an enzyme-linked immunosorbent assay (ELISA) that tests for the presence or absence of heparin-PF4 complexes.
  • As it does not determine whether the antibodies are functionally significant, it is best used in conjunction with one of the two prior tests. [2] [3] [4] [5]

If HIT is suspected it may take hours to days to obtain the laboratory back. In the meantime it may simply be a safer approach to substitute another agent (eg agatroban) for heparin.

Reference

  1. ↑ Harenberg J, Marx S, Krejczy M, Wehling M (2012). "New anticoagulants - promising and failed developments". Br J Pharmacol. 165 (2): 363–72. doi:10.1111/j.1476-5381.2011.01578.x. PMC 3268190. PMID 21740405.
  2. ↑ Harenberg J, Huhle G, Giese C, Wang L, Feuring M, Song X, Hoffmann U (2000). "Determination of serotonin release from platelets by enzyme immunoassay in the diagnosis of heparin-induced thrombocytopenia". Br J Haematol. 109 (1): 182–6. PMID 10848798..
  3. ↑ Hirsh J, Dalen JE, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1992; 102:337S-351S. PMID 1327666
  4. ↑ Walenga JM, Bick RL. Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other side effects of heparin therapy. Med Clin North Am 1998; 82:635-58. PMID 9646784
  5. ↑ Fabris F, Luzzatto G, Stefani PM, Girolami B, Cella G, Girolami A. Heparin-induced thrombocytopenia. Haematologica 2000 Jan; 85:72-81. PMID 10629596

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