Remember the different types of HIT:

Pathophysiology:

1. Autoantibodies (IgG) are formed to platelet factor 4 (PF4) complexed with heparin
2. Platelet Fc receptors bind the antibody-heparin-PF4 immune complex

• Thrombocytopenia occurs by two mechanisms:

1) Platelet removal by splenic macrophages
2) Platelet consumption due to thrombus formation

Clinical Variability:

• 10 times higher incidence with UFH compared with LMWH
• A metaanalysis of 15 studies (>7000 patients) that evaluated the risk of HIT with prophylactic UFH vs LWM found the following absolute risks of developing HIT
• UFH – 2.6% (95% CI 1.5 – 3.8%)
• LMH – 0.2 % (95% CI 0.1 – 0.4%)
• Surgical > Medical patients; Incidence is particularly high after orthopedic surgery

Risk Factors:

• There is no dose of heparin that is too low to cause HIT! Patients have developed HIT after exposure to as little as 250 U flush.
• Female sex appears to be at a higher risk for unclear reasons – this was based on 7 trials comparing UFH vs LWH found approximately twice the risk.

Clinical Manifestations:

• Thrombocytopenia (<150,000/microL ~ 85-90%)
• Platelet drop of >50% is typical with mean nadir of 60,000/microL and RARELY <20,000/microL
• Typical onset is 4-10 days after heparin therapy
• Patients with exposure to heparin in the previous 100 days can develop a early onset (<24 hours) HIT
• Thrombosis occurs in up to 50% of HIT patients (venous > arterial); presenting finding in up to 25%
• Thrombotic sequelae – skin necrosis, limb gangrene, organ ischemia/infarction

4T Score:

• A total score <4 points has a very high negative predictive value (97-99%); additional testing is not necessary

Assuming an intermediate/high risk score – what other labs can aid in the diagnosis:

• Anti-PF4 heparin antibodies – excellent NPV (98-99%), but low PPV due to presence of clinically insignificant antibodies (IgM, IgA)
• Our lab restricts the antibodies to only IgG – which increases the specificity
• Also provides an optical density (magnitude of anti-PF4-heparin reactivity) ~ greater activity (>2.0) correlates to a greater likelihood of HIT
• Serotonin-release assay – functional assay that measures heparin-dependent platelet activation; a negative result rules out HIT

Treatment:

Step 1: Immediate cessation of heparin

Step 2: : Initiation of an alternative anticoagulant at a therapeutic dose.

• Vitamin K antagonists should NOT be given until HIT has resolved (i.e. platelets > 150,000 for >2 days) because they increase the risk of venous limb gangrene/limb loss by decreasing levels of protein C.
• Argatroban (direct thrombin inhibitor) is the only currently FDA approved medication in the US.  Danaparoid (anti-factor Xa) is approved in Canada, EU, and Australia.  Other options include: Lepirudin and Bivalrudin.