Why We Should Not Talk About hit it is rare and over publicized

Why We Should Not Talk About HIT

• It is rare and over publicized

• Not every hospitalized patient get heparin…

• No unifying clinical picture and the serology is “poor”..

• How can we justify anticoagulating a thrombocytopenic patient using medications that do not have antidotes?

• Most hospitalized patients with thrombocytopenia have multifactorial etiology..

Is it a rare and over publicized disease

Confusing Terminology

• Also known as: HIT type II, white clot syndrome
• Heparin-dependent antibodies are usually detectable
• Also known as HIT type I, HAT
• Denotes absence of heparin-dependent antibodies and the potential role for other factors in causing thrombocytopenia

Immune- vs Non Immune-Mediated HIT

Factors Influencing the Frequency of HIT

No unifying clinical picture DIFFERENTIATE CLASSICAL HIT FROM ATYPICAL FORMS

Variable Frequency of Reported HIT

• Technical Explanations

• Variable definition of thrombocytopenia used
• Differing baseline platelet counts permitted for inclusion
• Requirement to repeat platelet count testing to confirm thrombocytopenia
• Variable intensity of platelet count surveillance
• Variable intensity of surveillance for thrombotic events
• Failure to exclude nonimmune heparin-associated thrombocytopenia

Classical HIT: Thrombocytopenia Criteria

• <150,000

• or a 50% drop in platelet count from baseline (even if nadir remains > 150,000)

• or >30-50% decrease with documented thrombosis

“Classical” HIT Criteria: Thrombocytopenia Tips and Clues

• Relative, rather than absolute, thrombocytopenia

• Platelet count may be normal when patient presents with thrombosis (Delayed onset HIT)

• In skin necrosis the drop in platelets is small but it may predict arterial thrombosis when it occurs

• Platelets recovers after heparin withdrawal (Median=4 days)

• HIT is unlikely when platelets recover despite ongoing heparin therapy

Delayed-Onset HIT: Similar Pthophysiology

Remember Special Cases

Are There Other Forms of Atypical HIT?

Thrombocytopenia in most hospitalized patients is multifactorial in etiology

Non Drug-Induced Thrombocytopenia

HIT is a Thrombotic Storm!

HIT = Thrombin Generation The Actions of Thrombin

Cumulative Frequency of Thrombosis in Isolated HIT w/o effective anticoagulation

Just hold Heparin and It will Go Away! How can we justify anticoagulating thrombocytopenic patients with medications that do not have antidotes?

• A transient increase in risks of new thrombosis is observed once heparin is stopped w/o an alternative AC (Greinacher Blood 2000)

• Patients with the lowest platelet counts are most likely to experience devastating thrombosis and are in greatest need of alternative anticoagulation (Rice, Arch Intern Med 2004)

• 10 of HIT pts have platelets 10,000-20,000. Bleeding is rare even when fully anticoagulated. (Rice, Arch Intern Med 2004)

1 week later, L foot

Just Switch to LMWH

• HIT incidence in pts receiving LMWH 0.5%

• Once HIT diagnosed, all heparinoids are contraindicated

• The vast majority of HIT antibodies cross react with PF-4/ LMWH complex

• May give unusual skin necrotic lesions distal to injection sites

Skin Necrosis at UFH injection Sites (Prophylactic dose)

• Warkentin TE. Br J Haematol. 1996;92:494–497.

This can’t be HIT because the platelet count is not low, (or too low)

Distribution of Platelet Count in HIT

Well, what about “good ol’ Coumadin”? Let’s get a therapeutic INR, quickly..

Serologic Tests: A Quick Overview

Laboratory Tests for HIT

Laboratory Testing for HIT

• Test Advantages Disadvantages

Now…… Which Serologic Markers are Required to Establish the Diagnosis of HIT?

Serologic Markers and the Diagnosis of HIT

• • Serologic markers (SRA, HIPA, PF4) are helpful, BUT:

• • They must be interpreted within the CLINICAL context, AND:

• • They are NOT required as part of the diagnostic criteria

Principles of Management of HIT

Treatment of Suspected HIT

• Discontinue ALL heparin immediately

• Initiate alternative anticoagulation

• Monitor carefully for thrombosis

• Avoid prophylactic platelet transfusions

• Document HIT in medical records

• Laboratory evaluation

• Monitor platelet counts recovery

• Medi-alert bracelets, heparin “allergy” education

Discontinue ALL Heparin Exposure

• Heparin gtt, SQ, line flushes

• LMWH SQ therapeutic and prophylactic doses

• Heparin-coated catheters

• Hemodialysis

• TPN preparations

• Other sources of potential; heparin exposure include: ECMO, CPB, Cardiac cath/endovascular intervention procedures

Direct Thrombin Inhibitors in HIT

Anticoagulants Not Indicated for HIT

Lepirudin

Argatroban

Thrombin Inhibitors: Recommended Dosing

• 2 µg/kg/min
• Check aPTT after 2 hrs
• adjustment should be made as clinically indicated (not to exceed 10 µg/kg/min)
• Do not use if aPTT > 100 sec at baseline

Clinical Studies of Argatroban

Clinical Trials of Lepirudin: HAT-1 and HAT-2 Studies on HIT

• Prospective, historically controlled trials

• Primary objective: treatment of HIT with lepirudin increases platelet counts or maintains normal baseline values while providing effective anticoagulation (prolongation of aPTT to 1.5 to 3 times baseline value)

• Secondary objective: Evaluate incidences of new arterial or venous thromboembolic complications, major bleeding complications, surgical interventions/limb amputations, and deaths

Efficacy Results for Argatroban Composite Endpoint

Efficacy Reslts for Argatroban Individual Components of Composite Endpoint*† (Study 1)

Independent Efficacy Outcomes

Argatroban in Patients With HIT-T

Results of HAT-1 and HAT-2: Cumulative Risk of Death, Limb Amputation, or Thromboembolic Complications

Argatroban Impact on Anticoagulation

Bleeding in HIT

Safety Results for Argatroban Major Hemorrhagic Events*

Results of HAT-2: Platelet Count Recovery Profile

Guidelines for Conversion to Oral Anticoagulant Therapy

Impact of HIT Therapy: Complication Development

Impact of HIT Therapy: Total Attributed Therapy Days

Conclusions

• Heparin, although an important anticoagulant, has several drawbacks, most notably its ability to cause HIT

• HIT can lead to severe and even life-threatening thromboembolic disorders

• Treatment of HIT should be initiated before laboratory confirmation

• A new generation of drugs such as the thrombin inhibitors, including the hirudins, may provide important new options for the treatment and possible prevention of HIT