Comparison of Two Methods of Transfusion for Stroke Prevention in Sickle Cell
Condition: Anemia, Sickle Cell; Sickling Disorder Due to Hemoglobin S
MeSH terms: Anemia, Sickle Cell
Study type: Observational

Summary: 
      Chronic blood transfusions are essential supportive care for sickle cell patients at high
      risk for morbidity and mortality due to stroke. These patients, however, are at risk for iron
      overload. In the investigator's comprehensive sickle cell center, the investigators support
      chronic transfusion with rapid manual partial exchange transfusions (RMPET) using a single
      access central line port. The investigators do not have a comprehensive adult sickle cell
      program but upon transition of patients the patients would be provided simple transfusion
      (ST) in an adult ambulatory infusion setting due to nursing acuity needed for RMPET. The
      investigators plan to study the institution's participants currently on chronic transfusion
      support and compare different transfusion modalities to better understand the effects from
      switching from RMPET to ST. To date, there are no such comparisons within and between sickle
      cell patients in the literature.
    

Detailed description: 
      II. Objective. Compare differences in RMPET versus ST.

      III. Specific Aims:

        1. To compare key predictive hematologic factors (hematocrit, hemoglobin, hemoglobin S
           quantification, blood volume and alloantibodies) for relative risk of stroke utilizing
           two methods of blood transfusion therapy.

        2. To determine the nursing time to administer straight versus manual exchange transfusion
           therapy.

        3. To survey patient satisfaction for both procedures.

      IV: Background/Significance:

      Stroke occurs in 10% of Sickle Cell Disease (SCD) patients before the age of 20 Years.
      Current standard of care for secondary overt stroke prevention in patients with SCD is
      chronic red blood cell (RBC) transfusions. Stroke recurs in ~ 60% of patients without chronic
      RBC therapy and in ~ 20% of patients with chronic transfusion while maintaining a hemoglobin
      S percentage of less than 30%. Indefinite transfusion therapy is practiced as discontinuation
      after short-term or long-term prophylactic transfusions leads to recurrent overt strokes and
      more ensuing CNS damage, even with transition to hydroxyurea. Chronic transfusions also
      prevent initial stroke in high-risk patients identified by transcranial Doppler (TCD)
      ultrasound. The Stroke Prevention Study in Sickle Cell Disease (STOP) demonstrated a 92%
      stroke risk reduction among 63 of 130 children with abnormal TCD results. Rates of stroke
      declined significantly since implementing routine TCD screening and primary prophylactic
      transfusion therapy. The subsequent STOP 2 trial supports the use of chronic transfusion
      indefinitely because discontinuation resulted in an increased rate of abnormal TCD conversion
      and development of overt stroke. Discontinuing transfusions on the STOP 2 trial was also
      associated with a higher occurrence of silent cerebral infarcts, documented in 3 of 37
      patients (8.1%) in the continued-transfusion group compared with 11 of 40 (27.5%) in the
      transfusion-halted group. More recent studies demonstrate that SCD patients are also at risk
      for silent cerebral infarcts. An association between worsening vasculopathy shown by magnetic
      resonance angiography and progressive overt and silent infarcts on magnetic resonance imaging
      has been found. More aggressive magnetic resonance imaging screening may be indicated and
      this could result in more patients with SCD treated with chronic transfusion.

      Common chronic transfusion modalities include ST or RMPET. The goal of therapy is to reduce
      the hemoglobin S level either by diluting the blood (ST) or by removing and replacing the
      blood with non-sickle hemoglobin (RMPET). To prevent further brain injury, the goal of
      transfusion therapy is to lower the hemoglobin S quantification to less than 30% on a routine
      basis, usually monthly transfusion procedure. There are many large centers that utilize
      erythrocytapheresis which is considered the preferable method if available.

      The investigator's study will focus on the types of RBC exchange therapy currently utilized
      in the investigator's Infusion Clinic at T.C. Thompson Children's Hospital. The investigators
      will determine which transfusion method is best for each participant for achieving the
      hematologic parameters of lower hemoglobin S quantification.The investigators will also
      measure the amount of nursing time for each procedure and which method is preferred by
      participants. The investigators will share the institutional observations with other
      institutions who may intend to switch between RMPET and ST.

      V. Methods:

      Study Design: Prospective observational cohort study

      The investigators will utilize the institution's current population of 8 eligible chronically
      exchanged transfused participants at the T.C. Thompson Children's Infusion Clinic. The
      eligible participants will be invited to participate in a cross over design study so that
      each participant serves as its own control. Eight participants will be randomly assigned
      (blinded envelope) whereby four participants will start with rapid manual partial exchange
      transfusion: 3 months will be spent in a wash out period, then 3 months of data collection
      for RMPET. This group will then be switched to simple transfusion with a wash out period of
      three months, then data collection for three months. The second group of four participants
      will start with simple transfusion and have an identical study design over 12 months (3
      months of collected data during simple transfusion, a 3 month wash out period, switch to
      rapid manual partial exchange transfusion for three months, then 3 months of data collection
      for RMPET).

      The investigators will optimize all therapy to achieve the post transfusion goal of <30%
      hemoglobin S and post transfusion Hb <12g/DL.with each transfusion performed for best
      practice in avoiding sickle cell complications.
    

Intervention name(s): Rapid manual partial exchange transfusion; Simple Transfusion
Intervention type(s): Other; Other
Intervention description(s): The first four participants will receive peripheral red blood cells via rapid manual partial exchange transfusions every month for 6 months. There is a pre-study washout for 3 months then there is a 3 month test period (data collection) before the participant is transferred to ST treatment.; The second group of four participants will receive peripheral red blood cells via simple transfusion every month for 6 months. There is a pre-study washout period for 3 months then there is a 3 month test period (data collection) before the participant is transferred to RMPET treatment.
Observational model: Case-Crossover
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        8 chronically exchanged transfused participants at T.C. Thompson Children's Infusion Clinic
        with sickle cell disease (Hemoglobin SS or SBeta thalassemia) currently receiving rapid
        manual partial exchange transfusion.