Whiteboard Animation Video

Transcript/Show Notes

• Let’s review some key takeaways from the episode on heparin induced thrombocytopenia:
  • Pathophysiology and incidence
  • The 4T score
  • Testing
  • Treatment
• So what is heparin induced thrombocytopenia, HIT? Its s an antibody-mediated activation of platelets caused by heparin exposure, which leads to thrombocytopenia.
• Left untreated, HIT carries about a 6% daily risk of thrombosis, amputation, and/or death. 
  • So it can be devastating to miss.
• What causes this profoundly hypercoagulable state?
  • The culprit is an immune complex made of 3 “HIT antibodies”:
    • Heparin, which binds to platelet factor 4, which in turn gets coated by an antibody which is usually IgG. Together, this complex activates platelets
    • Once activated, platelets change shape and release prothrombotic granules that recruit more platelets and create a positive feedback loop. 
    • And then the consumption of platelets occurs at the site of thrombosis as well as being removed from the spleen.
    • Generally, after new heparin exposure, it takes 5-10 days for these antibodies to be produced and circulate.
    • Rarely, if patients also received heparin in the last 30-100 days, they may have antibodies against platelet factor 4, leading to rapid-onset HIT with 24 hours after repeat heparin exposure…a 2-HIT hypothesis, if you will 😀
• Risks of HIT
  • This all sounds pretty scary! But remember that overall incidence of HIT is low, ranging from 0.1 to 5%, and clinical context matters a lot: surgical patients are more at risk than medical patients, and unfractionated heparin gives a higher risk than low molecular weight heparin because heparin has larger strands.
• Differential Diagnosis for Thrombocytopenia 
  • So how do you distinguish HIT from thrombocytopenia from other reasons? 
  • Getting the diagnose right is important because HIT is treated differently. HIT is the unique because it increases risk of clotting, BUT not bleeding
• Let’s use a systematic approach to think through your patient with low platelets:
  • Our first bucket could be labeled: “Is this real?” Pseudothrombocytopenia is platelet clumping due to the way the blood is processed, not a pathologic condition. If a patient has a history of fluctuating low platelets, be sure to rule out pseudothrombocytopenia 
  • Onto the second bucket: “Did we cause this?” Many meds cause thrombocytopenia but not HIT – so a thorough med rec going back up to 1-2 weeks prior, not just 1-2 days, prior is key!
  • The third bucket: is this from decreased production? Includes liver disease, ineffective erythropoiesis (megaloblastic anemia, myelodysplastic syndrome), and bone marrow hypoplasia (drugs, bugs, pregnancy), or infiltration (cancer, infection, myelofibrosis)
  • The fourth and final bucket, is this from increased destruction? This includes hypersplenism, ITP, and some can’t miss diagnoses like DIC, thrombotic microangiopathies, and HIT
• So that differential is important to keep in mind with the 4T score. (as transition slides)
  • What is the 4T score?
    • It helps you calculates likelihood of HIT based on
      • (1) degree of thrombocytopenia,
      • (2) timing,
      • (3) is there presence of thrombosis, and
      • (4) possible other thrombocytopenia etiologies – this last category is the trickiest call  to make
• When you calculate the 4T score, it will put your patient into 3 categories, low, intermediate and high
  • The tricky part is if your patient falls in the intermediate risk 4T score
• Don’t forget the two main lab tests for HIT before you consult heme: anti-PF4 antibody, and the serotonin release assay
  • The anti-PF4 antibody test result looks for presence of an antibody. Thus, it is very sensitive and great for ruling out HIT if negative. Anti-PF4 is  not very specific which means it won’t be as helpful when positive. 
    • The test is also called optical density (hence its reported as OD), Technically, OD > 0.6 is considered the cutoff for “positive” by most labs, of course, more positive the OD, the more our suspicion for HIT goes up
  • The serotonin release assay checks whether the anti-PF4 antibodies are actually causing platelet activation
    • It is highly specific – a positive result confirms HIT. But, it can take up to a week to result, so keep in mind it wont be available right away
    • So to recap, if the anti-PF4 is negative, you we can rule out HIT but if the anti-PF4 is positive, then we have to wait the confirmatory serotonin release assay
• Generally, if you’re concerned enough to send the two tests we just discussed, you should also be considering empiric treatment. But remember – stopping the heparin is not enough! Because thrombotic risk is so high, you need to treat HIT with anticoagulation.
• The exact type of anticoagulation depends multiple factors. 
  • If you need something quick on and quick off: go with argatroban (though avoid this in liver dysfunction)  and bivalirudin
  • If the patient is stable and ready for discharge and needs something longer-acting: consider fondaparinux, apixaban, and rivaroxaban
  • In general, avoid warfarin until platelets recover to 150k, since warfarin inhibits protein C and inhibition of protein C on top low platelets worsen thrombotic risk in patients with HIT
• To recap, recall that:
  • HIT is a rare condition with a very high thrombotic risk. Surgical patients on unfractionated heparin are most susceptible.
  • If you’re worried about HIT in a patient, calculate the 4T score and consider our systemic approach to the different buckets of alternative thrombocytopenia etiologies (and ask yourself…. Is this real? Did we cause this? Is there decreased production? Is there increased destruction?)
  • If the 4T score comes back at intermediate risk or above, send off that anti platelet 4 antibody test and serotonin release assay – but be aware that the anti-platelet 4 antibody is sensitive so good to rule out HIT and serotonin release assay is more specific so good to confirm diagnosis but may take a while to come back.
  • Treatment for suspected or confirmed HIT depends on whether the patient needs quick on, quick off anticoagulation or can tolerate a longer-action option. But whatever you do, don’t give warfarin until their platelets recover fully!

That’s all for now! We hope this review was useful, and join us next time for another rapid review of our five pearls series! Thanks for joining us in this rapid review of heparin induced thrombocytopenia.