Sickle Cell Disease: Overview and Transfusion Support AABB - PowerPoint PPT Presentation

Sickle Cell Disease Overview/Transfusion Support Wednesday, August 29, 2012 2:00 p.m. – 3:30 p.m. (ET) / 6:00p.m.-7:30 p.m. (GMT) When this file is opened, Acrobat Reader will, by default, display the slides including the Acrobat reader controls. To return to full screen mode, hit Ctrl-L on your computer keyboard or use your mouse to click View>Full Screen on the menu bar of the Acrobat Reader program. To take the slides out of full screen mode and display the Acrobat Reader controls, simply hit the Esc key on your computer keyboard. To advance slides during the program, use the Enter, Page Down, down arrow or right arrow on your computer keyboard. To back up slides during the program, use the Page Up, up arrow of left arrow on your computer keyboard. Please remember to logon to the Live Learning Center using your email address and session number to complete an evaluation of the program and speakers. At this time, advance to the next slide and wait for the audioconference to begin. A 2012 Audioconference presented to you by AABB

Sickle Cell Disease: Overview and Transfusion Support AABB Audioconference August 29, 2012 Jeanne Hendrickson, MD

Objectives  To define sickle cell disease and determine what population is affected  To assess the indications for transfusion of sickle cell patients  To review potential adverse outcomes of transfusion in sickle cell patients (eg RBC alloimmunization and delayed hemolytic transfusion reactions)

Objectives  To define sickle cell disease and determine what population is affected  To assess the indications for transfusion of sickle cell patients  To review potential adverse outcomes of transfusion in sickle cell patients (eg RBC alloimmunization and delayed hemolytic transfusion reactions)

Sickle Cell Disease: 5000 Affected Babies Born Each Year in the U.S.  Hb SS: 65%  Hb SC: 25%  Hb S β + thalassemia: 8%  Hb S β ° thalassemia: 2%

Sickle Cell Trait  8 ‐ 10% of African Americans in the U.S. have sickle cell trait (Hb AS)  2.5 million people  Sickle Dex or sickle prep is positive

Hemoglobin S  Glutamine to Valine substitution in the 6 th codon of the Beta globin gene cluster on chromosome 11  Leads to polymerization (and sickling) when deoxygenated  Membrane changes lead to increased adherence to the vascular endothelium

Newborn Screen **Hemoglobin presented in quantitative order**  Hb FA = normal (80% F, 20% A)  Hb FS = sickle cell disease  Most likely to be Hb SS, but could be Hb S β ° thalassemia  Hb FSA = sickle cell disease  Hb S β + thalassemia  Hb FAS = sickle cell trait  Hb FSC = SC disease  Hb FA with Bart’s = alpha thalassemia variant  Hb F = beta thalassemia major

Sickle Cell Disease: Manifestations  Head/ENT  Chest  Abdomen  GU  Skeletal  Other

Objectives  To define sickle cell disease and determine what population is affected  To assess the indications for transfusion of sickle cell patients  To review potential adverse outcomes of transfusion in sickle cell patients (eg RBC alloimmunization and delayed hemolytic transfusion reactions)

Risk/Benefit Ratio of RBC Transfusion in Sickle Cell Disease  Benefit of increasing oxygen carrying capacity must be balanced by the risk of serious hazards of transfusion

“ in spite of the documented clinical data supporting transfusion therapy, the physiologic and rheologic aspects of this treatment approach are not fully understood ” Alexy et al, Transfusion 2006

Transfusion Options  One time vs chronic  Simple vs exchange

Potential Transfusion Indications To Be Further Discussed:  Acute chest syndrome  Splenic sequestration  Priapism  Pre ‐ operative transfusion  CVA  Others

Acute Chest Syndrome  Defined as a new infiltrate in a patient with sickle cell disease  May be accompanied by chest pain, fever, tachypnea, wheezing, or cough  A leading cause of death

Acute Chest Syndrome Has Many Causes Vichinsky et al, NEJM 2000

Transfusion Improves Oxygenation  670 episodes of ACS  68% of patients received simple transfusion  pAO2 improved from 63 mm Hg to 71 mm Hg with transfusion  O2 saturations increased from 91% to 94% with transfusion  Similar increases with simple versus exchange transfusion  Length of hospital stay decreased with transfusion Vichinsky et al, NEJM 2000

Is Simple or Exchange Transfusion Best for ACS?  Not known  No adequately powered, randomized trials have examined this question

Historic Data Suggests Dramatic Response to Exchange  32/35 patients with severe ACS “responded dramatically” to exchange transfusion  Many patients initially received a simple transfusion without improvement Nathan et al, Blood 1993

No difference in outcome with simple versus exchange transfusion seen in a recent retrospective study  Similar baseline characteristics between patient groups with a few exceptions:  Higher admission Hb levels in exchange group  Higher post ‐ transfusion Hb in exchange group  4 times more blood exposure in exchange group  10.3 versus 2.4 units Turner et al, Transfusion 2009

Turner et al, Transfusion 2009

Short Term Chronic Transfusion Therapy May Decrease ACS Incidence  27 patients with recurrent or unusually severe ACS were treated with chronic transfusion therapy  Incidence of ACS decreased from 1.3 episodes/pt year to 0.1 episodes/pt year  No obvious difference in severity of ACS in patients on chronic transfusion therapy  Chronic lung damage may be minimized Hankins et al, JPHO 2005

Chronic Transfusion Arm of STOP with Less ACS Miller et al, J Pediatr 2001

Splenic Sequestration  Collection of sickled RBCs in splenic sinusoids  Often quite acute; “minor” episodes also occur  Precipitating events unclear  Peak age 6 months ‐ 2 years  Occurs at an earlier age in children with low fetal Hb levels  Tends to recur  Historically a leading cause of death in infants with Hb SS disease

Splenic Sequestration Treatment  Transfusion of small aliquots (5 cc/kg) of RBCs slowly is advocated for acute splenic sequestration  Beware of autotransfusion  Splenectomy is a potential treatment for patients with recurrent sequestration  Often done after 2 years of age  Chronic transfusion therapy may bridge gap until splenectomy can be done  Limited efficacy data

“Reverse Sequestration” in a patient with sickle cell disease Lee et al, Postgrad Med J 1996

Priapism  Results from vaso ‐ occlusion of venous penile drainage

Transfusion For Priapism  Review of existing case reports (n=42) shows no decrease in “time to detumescence” with conventional therapy (8 days, n=16) versus transfusion therapy (10.8 days, n=26) Merritt et al, CJEM 2006

ASPEN (association of sickle cell disease, priapism, exchange transfusion, and neurologic events)  Has been reported in a total of 9 patients  May present immediately or within a week following transfusion  Etiology unclear  Hyperviscosity  Release of activated clotting factors, activated platelets, and cytokines from sludge like blood in corpora cavernosa  Sickle patients have increased vWF and fibrinogen at baseline, with decreased protein S

ASPEN May Occur in Cases with High Post ‐ Exchange Hb Levels Rackoff et al, J Peds 1992

Pre ‐ Operative Transfusion  High rates of post ‐ operative complications have been reported in patients with sickle cell disease  Including VOC, ACS, other  Does pre ‐ op transfusion decrease this risk?  How low does the %S have to be?

Pre ‐ Operative Transfusion: NIH Guidelines  Recommend preoperative simple transfusions to maintain (and not to exceed) a Hgb of 10 g/dL

Pre ‐ Operative Transfusion  Preoperative Transfusion in Sickle Cell Disease Study:  551 patients with Hgb SS disease  Randomized to 2 transfusion arms:  Aggressive (Hb of 10 g/dL and Hb S <30%)  Conservative (Hb of 10 g/dL regardless of percent S)

Similar Non ‐ transfusion Complication Rates in Each Arm Vichinsky et al, NEJM 1995

50% Fewer Transfusion Related Complications in Conservative Arm Vichinsky et al, NEJM 1995

Randomized Trial in Cholecystectomy Patients Haberkern et al, Blood 1997

May Consider RBC Exchange Prior to “High Risk” Surgeries:  Abdominal procedures  Orthopedic procedures  Cardiac surgery  Retinal surgery

CVA  At least 10% of patients with HbSS disease will have a clinical stroke by 20 yo  A higher percentage will have a silent stroke

Most CVAs <20 yo and >30 yo are Ischemic Ohene-Frempong et al, Blood 1998

Silent Cerebral Infarcts Have a High Prevalence (yet are not obviously associated with abnormal TCDs) DeBaun MR et al, Blood 2012

Wechsler FSIQ Scores are Significantly Lower in Patients with Infarcts (Silent or Overt) DeBaun et al, Blood 2012

Treatment of Acute Ischemic Events  Case reports of exchange transfusion reversing TIAs Russell et al, JAMA 1979

Prevention of Stroke  Stroke Prevention Trial in Sickle Cell Anemia (STOP):  Randomized “at risk” children with MCA velocity >200 cm/sec by TCD to standard therapy or chronic transfusion therapy (keeping %S <30) Adams et al, NEJM 1998