Let's HIT the topic Heparin-induced Thrombocytopenia (HIT)!

This #tweetorial is a deep dive into Episode 43 of Run the List (RTL) on Thrombocytopenia: https://bit.ly/32feVfQ 

Thanks @LeelaChock for covering this week’s topic!

Thrombocytopenia is a broad topic!

In Ep. 43 of RTL, Dr. Robert Stern, @NavinKumarMD, & @sonorato11 go over a general approach to thrombocytopenia

Broadly, there are THREE umbrellas:

1. destruction

2. Splenic sequestration

3. production

https://www.runthelistpodcast.com/s/RTL_Thrombocytopenia.pdf

HIT (Heparin-induced thrombocytopenia), is classified under “ destruction”

HIT in-depth:

It is *common*, occurring in 1 out of 5,000 hospitalized patients

It’s a can’t miss dx! 50% of patients w/ HIT who are not appropriately treated go on to develop a thrombosis

HIT risk factors?

duration/dose of heparin administration (can even happen w/ simple heparin flush!)

Type of heparin used: UFH > LMWH > fondaparinux

Surgical, trauma, cardiopulm bypass pts at risk (maybe 2/2 increased heparin use, but MoA unknown)

Patient sex (F>M)

HIT mechanism:

Heparin complexes w/ platelet factor 4 (PF-4), a protein released by platelets

B-cells make IgG antibodies (~5-7 days after heparin exposure) to the PF4-heparin complex

IgG then binds these heparin-PF4 complexes to platelets and then…

(HIT MoA cont.):

IgG-PF4-heparin complexes bind platelets causing BOTH:

Thrombocytopenia by marking the platelets for destruction via splenic macrophages (type II hypersensitivity rxn)

AND

Paradoxical PRO-thrombotic state by IgG Ab complexes activating platelets!

Sequelae include:

Thrombocytopenia to ~50-80k (usually >20K)

Paradoxical thrombosis (venous > arterial), despite thrombocytopenia!

(Rarely) anaphylaxis; HIT Ab may activate leukocytes

Skin necrosis at *heparin injection sites* (seen below) immediately suggests HIT!

Let’s review timing of HIT!

Suppose heparin is given on day 0:

d0-d1 = Rapid 50% drop (pt already has IgG Ab 2/2 heparin exposure w/i last 3 months)

d5-d7 = Rapid 50% drop (no prior heparin exposure)

d7-d14 after heparin withdrawal = Rapid drop ("delayed-onset HIT")

If suspecting HIT calculate a "4-T score"

The 4 T's are:

Thrombocytopenia

Timing of Onset

Thrombosis

oTher causes of Thrombocytopenia.

A LOW score (<4 points) has a very HIGH negative predictive value (NPV) of 97 to 99%, and essentially *rules out* HIT

The positive predictive value (PPV) of a 4-T score of 4-5 is 10-20%, but a score >=6 is 40-80%

A 4-T score >=4 requires:

Stopping all heparin products immediately !

An Anti–PF4–heparin ELISA test

Starting therapeutic NON-heparin anticoagulation (e.g. Argatroban )

Anti-PF4 test has high NPV (98-99%), but low PPV

a anti-PF4 result requires confirmation w/ *gold standard functional test*: serotonin release assay (SRA)

How does SRA work?

If pt's serum has active heparin-PF4 IgG Ab activate donor platelets releasing serotonin

All pts w/ suspected or confirmed HIT need therapeutic (non-heparin) anticoagulation (AC)!

Why?

HIT Abs activate plateletsclots despite thrombocytopenia

For HIT: continue AC until platelet count >150K

For HIT-related clot: continue AC for 3 months (like any provoked clot)

[on AC]

@ASH_hematology suggests the following tx as initial anticoagulants in acute HIT:

Argatroban, bivalirudin, fondiparinux, danaparoid, or a DOAC

Argatroban or bivalirudin = short half-lives (!)

Short half-lives = indicated for critically ill or bleeding risk pts

If pt is on warfarin, hold warfarin & reverse with IV Vitamin K

Seems strange right?

Warfarin has been shown to paradoxically WORSEN the hypercoagulable state in HIT

Once platelet count stabilizes, can re-start warfarin

in SUM:

1) HIT complexes both activate *and* deplete platelets (thrombocytopenia)

2) Use the 4-T score to assess for HIT

3) If >=4 heparin products, start non-heparin anticoagulation (not warfarin!), & send labs

4) Have a low threshold to look for thrombotic complications

REFs (1/2):

[1] https://theawkwardyeti.com/comic/blood-clot/
[2] https://www.runthelistpodcast.com/s/RTL_Thrombocytopenia.pdf
[3]
[4] https://www.aruplab.com/testing/HIT 
[5] http://www.nejm.org/doi/full/10.1056/nejmcp1411910#article_citing_articles
[6] https://www.semanticscholar.org/paper/Heparin-induced-thrombocytopenia-(HIT):-Review-of-Hogan-Berger/a1ab31b2e9ba719a81855a790145f86045842283/figure/0
[7] https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-heparin-induced-thrombocytopenia?search=HIT&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H19880151
[8] http://www.nejm.org/doi/full/10.1056/nejmcp1411910#article_citing_articles
[9] http://www.nejm.org/doi/full/10.1056/nejmcp1411910#article_citing_articles

REFs (2/2):

[11] https://www.slideshare.net/skyecreativeone/medical-sample-13
[12]
[13a] https://ashpublications.org/bloodadvances/article/2/22/3360/16129/American-Society-of-Hematology-2018-guidelines-for?searchresult=1&_ga=2.242345538.1943646382.1604025310-250888369.1604025310
[13b] https://www.jahjournal.org/viewimage.asp?img=JApplHematol_2015_6_4_141_171993_f1.jpg
[15] https://www.runthelistpodcast.com/s/RTL_Thrombocytopenia.pdf

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