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Last month¶s Case Study featured a 61-year-old male who was diagnosed in November 2006
with myasthenia gravis. He received IGIV for limited maintenance, and subsequently sustained a
12-day hospitalization after the IGIV was discontinued. The patient¶s hospitalization included 8
days in ICU, multiple consults, treatment for myasthenia gravis crisis including plasmapheresis,
and a diagnostic angiogram and stress test. The patient also had a descending platelet count
during his hospitalization, as evidenced by his lab work: 4/12/07 platelets 181,000/mcL; 4/14/07
platelets 130,000/mcL; 4/20/07 platelets 99,000/mcL. Three days after discharge, the patient was
again in crisis, but this time it was a different crisis.

$   - The patient notices numbness in his left leg which got persistently worse until
his appointment with his PCP on May 1.

  - The patient¶s PCP notes that the patient is experiencing numbness in his left leg,
which worsens and is associated with pain when walking. He speculates that the patient may
have a pinched nerve. That evening, the patient notices while bathing that the left foot is darker
than the right foot, and his toenails are dark blue. He immediately returns to the emergency
room.
Upon presentation to the ER, the patient is found to have a deep vein thrombosis in the popliteal
artery. There is no palpable pulse in the left foot, confirmed through Doppler. The patient is
admitted to the ICU and placed on a heparin drip.

  - The patient¶s cardiologist completes a threaded tPA drip through the artery of the
left leg behind the knee. The blockage is successfully eliminated from the popliteal artery, and
circulation is restored to the left foot. The heparin drip is continued prophylactically based on the
DVT diagnosis.

&  - The patient experiences major chest pain and a CT scan reveals fluid on the
gallbladder and infarctions in the spleen. Clots are identified in both arms and in the chest cavity.
Platelet count reveals that the patient is in heparin-induced thrombocytopenia. After further
clinical and laboratory assessment, the patient is diagnosed with HIT, a serious side effect of
heparin use. The patient receives a platelet transfusion and the heparin is immediately
discontinued. Anticoagulation with lepirudin, a nonheparin, alternative anticoagulant is
administered.

Heparin-induced thrombocytopenia, or HIT, usually develops after a patient has been on

heparin for 5 days or more. Heparin binds to platelet factor 4 (PF4), forming a highly reactive
antigenic complex on the surface of platelets and on endothelial cell surfaces, thereby increasing
the number of targets for heparin-dependent antibodies. Susceptible patients then develop an
antibody (IgG) to the heparin-PF4 antigenic complex. Once produced, immunoglobulins, usually
IgG, bind to the heparin-PF4 immune complex on the platelet surface. The Fc portion of the IgG
then activates the platelets by binding to platelet Fc receptors. Thromboembolic complications
can occur in 50% - 65% of patients with HIT, including those with and without thrombosis at
diagnosis, and thrombotic complications of HIT can be catastrophic. Approximately 20% of
patients with thrombotic complications lose a limb, and about 30% die without appropriate
nonheparin therapy.

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  - The patient¶s platelet counts, PTT and INR are continuously
monitored to achieve acceptable ranges. The patient¶s lower limbs are assessed for presence of
DVT. The goal is to switch the patient to oral warfarin once the platelet counts have normalized.

  ± The patient is discharged on warfarin and instructed to follow up with his
physician. Monitoring of the INR and platelets continue.

Post Script:
June 1, 2007 -- The costs for the first hospitalization (Case Study Part 1) exceeded $225,000.
Costs for the second hospitalization, totaling 16 days, have not yet been determined. The
arbitration on the original maintenance treatment with IGIV is still under review by the health
plan.

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