Heparin-induced thrombocytopenia: Difference between revisions

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==Background==
==Background==
*Despite low plt count pt is actually hypercoagulable
*Pathologic activation / consumption of platelets due to antibodies against heparin-platelet complex
*Pathophysiology
*Can be caused by [[unfractionated heparin]] or [[LMWH]] (10 times more common in unfractionated)
**Pathologic activation / consumption of platelets due to Ab against heparin-plt complex
*Occurs in 0.5-5% of patients treated with heparin<ref name="Lovecchio"> Lovecchio F. Heparin-induced thrombocytopenia. Clin Toxicol (Phila). 2014 Jul;52(6):579-83</ref>
**Activated platelets then cause blood clot formation
*Thrombosis occurs in 35-75% of patients ; 20-30% die within 1 month<ref name="Lovecchio"></ref>
***Platelet count falls b/c plts are bound in clots
*HYPER-coagulable, ''despite'' low platelet count
**Can be caused by unfrationated or LMWH (much more common in the former)
**activated platelets bound in clot, thus low platelet count
***Occurs in 0.5-5% of pts tx'd w/ heparin
**bleeding is unusual
*Thrombosis occurs in 35-75% of pts; 20-30% die w/in 1 month
 
===Type 1 HIT===
*Onset within 48h of initiating heparin
*Drop in platelet count due to platelet activation by heparin
*Platelet count usually normalizes in a few days with continued heparin treatment<ref name="guidelines hit">Warkentin T. et al. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):311S-337S</ref>
===Type 2 HIT===
*Immune-mediated process
*Onset typically 5-10 days after exposure to heparin
*Complicated by thrombosis<ref name="guidelines hit"></ref>


==Clinical Features==
==Clinical Features==
*Typical
[[File:PMC1865550 1752-1947-1-13-1.png|thumb|Gangrenous right hand and left foot in a patient with antibody-confirmed HIT.]]
**Symptoms begin 5-15d after initiation of heparin
[[File:PMC4763479 cvja-26-e13-g003.png|thumb|Ischaemic changes in the right hand (A), right foot (B), and left food (C) from HIT.]]
***>50% decrease in plt count
[[File:PMC3555208 hr-2012-4-e20-g002.png|thumb|Lower extremity gangrene secondary to both arterial and venous thrombosis.]]
***DVT or PE
*The 4 T's: (formal scoring system below)
***Cerebral vein or adrenal vein thrombosis
**[[Thrombocytopenia|Thrombocytopenia]]
***Limb arterial occlusion
**Timing (5-14d)
***CVA
**[[thromboembolism|Thrombosis]]
***MI
**No oTher cause
***Skin lesions at injection sites
 
*Rapid onset
===Immediate Symptoms===
**Symptoms begin within hours of initiation of heparin
*Flushing
***Due to preexisting circulating antibody from sensitization several weeks earlier
*[[Tachycardia]]
***Sudden drop in plt count
*[[Hypotension]]
***Thrombosis
*[[Dyspnea]]
***Flushing
 
***Tachycardia
===Delayed Symptoms===
***Hypotension
*>50% decrease in platelet count (median nadir is ~60K; rarely <20K)
***Dyspnea
*[[DVT]] or [[PE]]
*Delayed onset
*Cerebral vein or adrenal vein thrombosis
**Symptoms begin several days after heparin stopped
*[[Acute arterial ischemia|Limb arterial occlusion]]
**Severe thromboses
*[[CVA]]
*[[MI]]
*Skin necrosis
 
==Differential Diagnosis==
{{Thrombocytopenia}}
{{Hemolytic anemia DDX}}
 
==Evaluation==
*Serotonin release assay (SRA) = gold standard
*Anti-PF4 plus SRA has combined sensitivity of 99% <ref>Warkentin TE, et al. Chest. 2008;133(6 Suppl):340S-380S.</ref>
*Positivity determined by optical density (OD) reported with assay (same concept as a titer)
**OD <1 = <5% chance of HIT
**OD 1.4 = 50% chance of HIT
**OD >2 = 90% chance of HIT
 
===Pre-test Probability Scoring (The 4 T Score)<ref>Janz TG, Hamilton GC: Disorders of Hemostasis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 120: p 1578-1589.</ref>===
*Thrombocytopenia
**2 points: platelets > 50% fall AND nadir > 20k
**1 points: patient 30-50% fall OR nadir 10-19k
*Timing
**2 points: clear onset 5-10 days OR platelet fall < 1 day with prior heparin exposure within 30 days
**1 point: likely onset 5-10 days OR fall < 1 day with prior heparin exposure 30-100 days
*Thrombosis
**2 points: new thrombosis or skin necrosis at injection sites
**1 point: suspected thrombosis or progressive/recurrent thrombosis
*Likelihood of other causes
**2 points: none apparent
**1 point: possible
*Scoring
**≤3 is low risk and do not require further testing or heparin discontinuation
**≥4 should have serologic testing performed, heparin discontinued, and alternative anticoagulation started
 
==Management==
*Discontinue all [[heparin]] products <ref>Cuker A, Arepally GM, Chong BH, Cines DB, Greinacher A, Gruel Y, Linkins LA, Rodner SB, Selleng S, Warkentin TE, Wex A, Mustafa RA, Morgan RL, Santesso N. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018 Nov 27;2(22):3360-3392. doi: 10.1182/bloodadvances.2018024489. PMID: 30482768; PMCID: PMC6258919.</ref>
*Do not give [[platelets]] (may precipitate thrombosis)
*Start anticoagulation with no heparin based compound such as a direct thrombin inhibitor: [lepirudin (unless renal failure), [[argatroban]] (unless hepatobiliary disease), [[bivalirudin]]] or direct Xa inhibitor ([[fondaparinux]], danaparoid)
**4T Score ≥4 with/without thrombosis and average bleeding risk should receive therapeutic dose
**4T Score ≥4 with/without thrombosis and high bleeding risk should receive prophylactic dose
*''Avoid [[warfarin]] until platelets >100K-150K''
**Those already on warfarin should receive vitamin K to restore protein C & S levels
 
==Disposition==
*Admit (with hematology consult)


==Treatment==
== Calculators ==
#Discontinue all heparin products
{{HIT_4Ts_Calculator}}
#Start anticoagulation
##Consider lepirudin, argatroban, or danaparoid
##Avoid warfarin


==Dispostion==
==See Also==
*Admit
*[[Unfractionated heparin]]
*[[Low molecular weight heparin]]
*[[Coagulopathy (main)]]
*[[Hirudins]]


==Source==
==References==
Tintinalli
<references/>


[[Category:Heme/Onc]]
[[Category:Heme/Onc]]

Latest revision as of 09:34, 22 March 2026

Background

  • Pathologic activation / consumption of platelets due to antibodies against heparin-platelet complex
  • Can be caused by unfractionated heparin or LMWH (10 times more common in unfractionated)
  • Occurs in 0.5-5% of patients treated with heparin[1]
  • Thrombosis occurs in 35-75% of patients ; 20-30% die within 1 month[1]
  • HYPER-coagulable, despite low platelet count
    • activated platelets bound in clot, thus low platelet count
    • bleeding is unusual

Type 1 HIT

  • Onset within 48h of initiating heparin
  • Drop in platelet count due to platelet activation by heparin
  • Platelet count usually normalizes in a few days with continued heparin treatment[2]

Type 2 HIT

  • Immune-mediated process
  • Onset typically 5-10 days after exposure to heparin
  • Complicated by thrombosis[2]

Clinical Features

Gangrenous right hand and left foot in a patient with antibody-confirmed HIT.
Ischaemic changes in the right hand (A), right foot (B), and left food (C) from HIT.
Lower extremity gangrene secondary to both arterial and venous thrombosis.

Immediate Symptoms

Delayed Symptoms

Differential Diagnosis

Thrombocytopenia

Decreased production

Increased platelet destruction or use

Drug Induced

Comparison by Etiology

ITP TTP HUS HIT DIC
↓ PLT Yes Yes Yes Yes Yes
↑PT/INR No No No +/- Yes
MAHA No Yes Yes No Yes
↓ Fibrinogen No No No No Yes
Ok to give PLT Yes No No No Yes

Microangiopathic Hemolytic Anemia (MAHA)

Evaluation

  • Serotonin release assay (SRA) = gold standard
  • Anti-PF4 plus SRA has combined sensitivity of 99% [3]
  • Positivity determined by optical density (OD) reported with assay (same concept as a titer)
    • OD <1 = <5% chance of HIT
    • OD 1.4 = 50% chance of HIT
    • OD >2 = 90% chance of HIT

Pre-test Probability Scoring (The 4 T Score)[4]

  • Thrombocytopenia
    • 2 points: platelets > 50% fall AND nadir > 20k
    • 1 points: patient 30-50% fall OR nadir 10-19k
  • Timing
    • 2 points: clear onset 5-10 days OR platelet fall < 1 day with prior heparin exposure within 30 days
    • 1 point: likely onset 5-10 days OR fall < 1 day with prior heparin exposure 30-100 days
  • Thrombosis
    • 2 points: new thrombosis or skin necrosis at injection sites
    • 1 point: suspected thrombosis or progressive/recurrent thrombosis
  • Likelihood of other causes
    • 2 points: none apparent
    • 1 point: possible
  • Scoring
    • ≤3 is low risk and do not require further testing or heparin discontinuation
    • ≥4 should have serologic testing performed, heparin discontinued, and alternative anticoagulation started

Management

  • Discontinue all heparin products [5]
  • Do not give platelets (may precipitate thrombosis)
  • Start anticoagulation with no heparin based compound such as a direct thrombin inhibitor: [lepirudin (unless renal failure), argatroban (unless hepatobiliary disease), bivalirudin] or direct Xa inhibitor (fondaparinux, danaparoid)
    • 4T Score ≥4 with/without thrombosis and average bleeding risk should receive therapeutic dose
    • 4T Score ≥4 with/without thrombosis and high bleeding risk should receive prophylactic dose
  • Avoid warfarin until platelets >100K-150K
    • Those already on warfarin should receive vitamin K to restore protein C & S levels

Disposition

  • Admit (with hematology consult)

Calculators

4Ts Score for HIT

4Ts Score for Heparin-Induced Thrombocytopenia
Criteria 0 Points 1 Point 2 Points
Thrombocytopenia 1 <30% fall or nadir <10 30–50% fall or nadir 10–19 >50% fall and nadir ≥20
Timing of platelet fall 1 <4 days without recent heparin Consistent but unclear; or fall after day 10 5–10 days; or ≤1 day if recent heparin
Thrombosis or other sequelae 1 None Progressive/recurrent or suspected Confirmed new thrombosis or skin necrosis
Other causes for thrombocytopenia 1 Definite other cause present Possible other cause No other cause apparent
4Ts Score / 8
Interpretation — Pretest Probability for HIT
0–3 Low probability (~5% risk of HIT). HIT antibody testing usually not needed.
4–5 Intermediate probability (~14% risk). Send HIT antibody; consider alternative anticoagulation.
6–8 High probability (~64% risk). Start alternative anticoagulant; send confirmatory testing.
References
  • Lo GK, et al. Evaluation of pretest clinical score (4 Ts) for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost. 2006;4(4):759-765. PMID 16634744.

See Also

References

  1. ↑ 1.0 1.1 Lovecchio F. Heparin-induced thrombocytopenia. Clin Toxicol (Phila). 2014 Jul;52(6):579-83
  2. ↑ 2.0 2.1 Warkentin T. et al. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):311S-337S
  3. ↑ Warkentin TE, et al. Chest. 2008;133(6 Suppl):340S-380S.
  4. ↑ Janz TG, Hamilton GC: Disorders of Hemostasis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 7. St. Louis, Mosby, Inc., 2010, (Ch) 120: p 1578-1589.
  5. ↑ Cuker A, Arepally GM, Chong BH, Cines DB, Greinacher A, Gruel Y, Linkins LA, Rodner SB, Selleng S, Warkentin TE, Wex A, Mustafa RA, Morgan RL, Santesso N. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018 Nov 27;2(22):3360-3392. doi: 10.1182/bloodadvances.2018024489. PMID: 30482768; PMCID: PMC6258919.
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