Heparin-Induced Thrombocytopenia Lawrence Rice, md

Heparin-Induced Thrombocytopenia

• Lawrence Rice, MD

• Chief, Division of Hematology

• Clinical Chief, Hem/Onc Service

• The Methodist Hospital

• Weill Cornell Medical College

• Houston, Texas

DVT in a Breast Cancer Patient

• 69-year-old woman, first Dx Breast Ca in 2002, on and off chemotherapy last 2 years for recurrent pleural metastases

• First left leg DVT in March ‘06

• July ’06 Admitted for progressive leg pain and swelling, worse DVT, despite outpatient warfarin Rx IV heparin, IVC filter (platelets 350K)

• Two weeks later: Discharged on warfarin (platelets 81K; had been ~80K last several days)

Some Lessons from this Case

• HIT is a common problem

• HIT engenders an extreme risk for serious thrombotic complications

• Unopposed warfarin increases this risk

• IVC filters should be avoided

• Alternative anticoagulants should be started expeditiously

• Therefore, clinicians must be highly informed and remain vigilant for HIT

Frequency of HIT Perspectives

• More than 1 trillion units heparin used yearly in US; 1/3 of hospitalized exposed (12 million)

• Unfractionated heparin – 3 - 5% incidence; Heart surgery 2.5% incidence

• LMWHeparin, Catheter-flushes -- ~0.5%

• Warkentin, NEJM ’95, 11/332 SQ heparin v. 0/333 LMWH developed HIT

• Laster, 1988, 10/2,000 (0.5%) HIT exposed only to coated vascular catheter

• Frequency of thromboemboli – 30-75%

Some Paradoxes of HIT

• Heparin, the most powerful anticoagulant of the twentieth Century, saving uncountable lives and limbs, also produces the most extreme hypercoagulable disorder, costing thousands yearly their lives and limbs.

• HIT, an immune reaction to an anticoagulant that lowers platelet count, rarely causes bleeding,

• it causes thromboses,(and platelet transfusions are contraindicated).

• Health professionals should be knowledgeable about a reaction that is common, often catastrophic, preventable, treatable, iatrogenic, and a major source of litigation,yet textbooks and medical curriculae pay little attention,

• and prevailing lack of awareness is shocking.

Heparin-Induced Thrombocytopenia (HIT): Pathophysiology1

Heparin-Induced Thrombocytopenia (HIT): Clinical Consequences if Untreated

• Sequelae Incidence

• New thromboses ~50%

• (arterial or venous)

• Amputation ~21%

• Death ~30%

Risk of Thrombosis with HIT After Heparin is Stopped (if an effective alternative is not begun)

HIT is a Clinico-Pathologic Syndrome

• Fall in platelet counts (generally >50%)

• Appropriate time after heparin initiation (5-12 days)

• Extreme risk for venous or arterial thromboembolic complications

• Eventually:

• Serologic confirmation of platelet-activating heparin-PF4 antibodies

Clinical Suspicion for HIT The 4 T’s (Warkentin, 2003)

• Thrombocytopenia

• Timing

• Thrombosis

• oTher causes for low platelets

• award 0–2 points for how typical for HIT

• high prob 6–8 pts; intermed 4-5; low 0-3

• The 5th T: The Test

Distribution of Platelet Count

Laboratory Tests for Heparin-PF4 Antibodies

• Commercially available ELISAs Highly sensitive (95-99%); High “false positive” rates; titer important

• Serotonin-release assays Technically demanding; variation lab- to-lab; limited availability

• Platelet aggregation assays Poor reproducibility

• Multiple others Flow cytometry or fluorescence-based Rapid bedside immunoassays

• Newer tests in development

ACCP Antithrombotic Guidelines Chest supplement, Sept. 2004, Chapter on HIT: Monitoring, Dx and Rx

• Examples of Evidence-Based Recommendations:

• “postoperative prophylaxis with UFheparin (HIT risk > 1%), at least every other day platelet count monitoring between post-op days 4-14 or until UFH is stopped (2C)”

• “postoperative prophylaxis with LMWheparin (HIT risk 0.1-1%), platelet count monitoring every 2 to 3 days between days 4-14 (2C)”

Treatment of Other Drug-Induced Thrombocytopenias

• Stop the drug

• Consider platelet transfusions

• Consider other measures to reduce bleeding risk

• Once platelets rise, the reaction is over

• Stop all heparin exposures

• Initiate an alternative anticoagulant on suspicion

• Do NOT transfuse platelets; initiate warfarin early

• Risk of thrombosis extends weeks after platelet recovery

Alternative Anticoagulants

The Key to Avoiding Catastrophes from HIT is Awareness, Vigilance, High Degree of Suspicion

HIT Summary

• A distinct clinico-pathologic syndrome

• Common—among most common causes of thrombocytopenia in hospital

• Serious, always potentially catastrophic

• Unique pathophysiology and testing

• Unique complication profile: Thromboemboli

• Unique management: alternative anticoagulants

Proposed ICD-9 CM

• New Code

• 289.84 Heparin-induced thrombocytopenia (HIT)

• A new 5 digit subclassification code as follows:

• 287 Purpura and other hemorrhagic conditions
• 287.4 Secondary thrombocytopenia
• Post-transfusion purpura
• Thrombocytopenia (due to):
• Dilutional
• Drugs
• Extracorporeal circulation of blood
• Platelet alloimmunization
• Use addition E code to identify cause
• Add Excludes: Heparin-induced thrombocytopenia (289.84)

Proposed ICD-9 CM

• A new 5 digit subclassification code as follows:

• 289 Other diseases of blood and blood-forming organs
• 289.8 other specified diseases of blood and blood-forming organs
• 289.81 Primary hypercoagulable state
• 289.82 Secondary hypercoagulable state
• Add Excludes: Heparin-induced thrombocytopenia (289.84)
• 289.83 Myleofibrosis
• New Code
• 289.84 Heparin-induced thrombocytopenia (HIT)