Complement Inhibition Using Eculizumab to Overcome Platelet Transfusion Refractoriness in Patients With Severe Thrombocytopenia
Condition: Thrombocytopenia; Alloimmune Platelet Refractoriness
MeSH terms: Thrombocytopenia
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      - Platelets are tiny cells in the blood that help stop bleeding. Thrombocytopenia happens
      when people do not have enough normal platelets. Getting a transfusion of another person s
      platelets can help stop too much bleeding. But because these cells are from other people, the
      body may reject them,putting them at risk for serious bleeding complications. This conditions
      is called alloimmune platelet refractoriness . There are evidence that in many patients,
      platelet counts fail to increase after a platelet transfusion because the transfused
      platelets are destroyed by the body s defence soldier, called complement . Researchers want
      to see if a drug, that inhibits complement, can help increase platelet levels and reduce
      bleeding

      Objectives:

      - To see if eculizumab increases platelet levels more after a transfusion. To see if it
      reduces the chance of bleeding too much.

      Eligibility:

      - Adults 18-75 years old who have thrombocytopenia and alloimmune platelet refractoriness.

      Design:

        -  Participants will be screened with medical history, physical exam, and blood tests.

        -  Participants will have the procedures listed below. They can have them while they are in
           the hospital. Or they can go to the outpatient clinic for them. Each visit may take up
           to 3 hours.

        -  Participants will get a meningitis vaccine if needed. Then they will get the study drug
           as an infusion.

        -  Participants will have a platelet transfusion. Their blood will be drawn every 24 hours
           until the platelet count is less than 10,000 per 1 microliter of blood.

        -  They will take antibiotics for 14 days.

        -  Participants will have a checkup and blood drawn twice a week for 2 weeks. They will get
           more transfusions if needed.
    

Detailed description: 
      Platelet transfusion can be a life-saving procedure in preventing or treating serious
      bleeding in patients who have low and/or dysfunctional platelets. Treatment of blood cancer
      and other blood diseases as well as bone marrow transplantation is not possible without
      platelet transfusion support. Unfortunately, 20-60% of chronically transfused patients will
      stop responding to these transfusions putting them at risk for serious bleeding
      complications. Data support the concept that in many patients, platelet counts fail to
      increase after a platelet transfusion because the transfused platelets are destroyed by the
      body s complement. In order to overcome this problem, we will inhibit complement activity
      with the medication eculizumab that specifically binds and suppresses complement. We
      hypothesize that when we treat patients who have platelet refractoriness with eculizumab, the
      platelet counts will increase to higher numbers after platelet transfusions, decreasing the
      risk of bleeding complications associated with having a low platelet count.
    

Intervention name(s): Eculizumab
Intervention type(s): Drug
Intervention description(s): 300 mg single-use vials
Intervention MeSH terms: Eculizumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Complement Inhibition; Platelet Refractoriness; Eculizumab