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Heparin-induced thrombocytopenia (HIT)

American Society of Hematology 2018 guidelines for the management of venous thromboembolism: heparin-induced thrombocytopenia

Etiopathogenesis

• heparin-induced thrombocytopenia (HIT) represents one of the most serious complications of heparin therapy. Patients are at significantly increased risk of thromboembolism (30-50% of cases)
  • the incidence of HIT among these patients ranges from <0.1% to 7%, depending on the type of heparin (UFH > LMWH), duration of drug exposure, and patient population (e.g., surgical vs. medical)
• type I and II are distinguished (see table)
  • type I HIT – a non-immune mediated, probably caused by a direct effect of heparin on platelet activation; does not pose an increased risk to patients
  • type II HIT – an immune-mediated complication of heparin therapy
    • heparin interacts with platelets to release platelet factor 4 (PF4). A heparin/PF4 complex on the platelet surface may induce the production of specific antibodies (most often IgG, less commonly IgM and IgA). These antibodies activate platelets, leading to thrombocytopenia and a prothrombotic state.
      
    • rapid antibody production to PF4 occurs after heparin administration in previously sensitized patients
• patients with HIT develop thrombotic complications (HITTS – HIT with the Thrombotic Syndrome) – the so-called “white thrombus syndrome,” which is probably caused by in vivo platelet activation
  • the majority of thrombotic events occur in the venous system (DVT, PE), with a smaller proportion affecting the arteries (MI, stroke/TIA)

• keep heparin therapy as short as possible
• monitoring is not required if heparin is administered for < 4 days or in patients considered to have a low risk of HIT (<0.1%) (ASH guidelines 201)
  • low-risk patients:   medical and obstetric patients receiving LMWH, patients receiving LMWH after minor surgery or minor trauma, and any patients receiving fondaparinux
• otherwise, monitor platelet counts every 2-3 days if heparin administration lasts ≥ 4 days (until day 14 or until heparin is discontinued)
  
  • in high-risk patients (surgical and trauma patients receiving UFH), the ASH guideline panel suggests monitoring the platelet count at least every other day
• for patients who have received UFH/LMWH within the past 30 days, check the platelet count before UFH/LMWH administration and repeat 24 hours later
• in general, the risk is significantly lower with the use of LMWHs   [Walenga, 2004]

• thrombocytopenia, or a 30-50% decrease in platelet count from baseline values
  • commonly occurs between days 5-12 following initiation of heparin therapy; rarely, it may manifest several hours after the heparin administration
    
• hypercoagulable state
  • DVT, PE
  • cardioembolism, peripheral vascular occlusion
  • MI, stroke

Consider HIT in cases of unexplained thromboembolic events after heparin exposure. The platelet count must not drop below 100.000; a decrease of >50% from baseline is sufficient to diagnose HIT!

• immediately discontinue heparin (LMHW, UFH, including flushes from IV lines !)
• do not administer warfarin until the platelet count is normalized (≥ 150 x 10⁹/l)!
• consult a hematologist
• avoid administration of platelet concentrates!
  • consider only in acute bleeding or high-risk patients (e.g., after recent surgery) (ASH Guidelines 2018)
• start non-heparin anticoagulants at a therapeutic dose; continue until platelet counts normalize  (ASH guidelines 2018)
  • argatroban or bivalirudin are preferred for severe conditions thanks to their short half-lives
  • fondaparinux or DOACs are preferred in stable patients
  • use parenteral medication for pulmonary embolism
    
• consider IVIG in severe refractory cases
  • IVIG at a dose of 1g/kg for 2 days reduces platelet activation via the antibody pathway [Padmanabhan, 2017] [Warkentin, 2019]
  • ASH Guidelines 2018 do not mention IVIG use
• routine placement of an IVC (inferior vena cava) filter is not recommended   (ASH Guidelines 2018)