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Sickle Cell Disease

• Simple Facts about Sickle Cell
• Fever Management
• Chronic Problems
• Pregnancy
• Pain Management
• Acute Chest Syndrome
• Splenic Sequestration
• Stroke Intervention
• Aplastic Crisis & Intervention
• Hydroxyurea
• Transfusion Therapy
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Transfusion Therapy

Blood transfusions are used for management of acute conditions and prevention of complications associated with sickle cell disease.  Methods of transfusion depend upon the underlying goal of therapy.  The phenotypes most likely to need transfusion therapy at some time are homozygous sickle cell disease (Hb SS) and sickle beta zero thalassemia.

Simple transfusion involves transfusing PRBC without removing any of the patient’s blood volume.  Partial exchange transfusion refers to manually phlebotomizing a percentage of the patient’s whole blood prior to or concomitantly with PRBC transfusion.  Exchange transfusion involves removal and replacement of the patient’s blood volume by pheresis.  This is achieved by exchanging equal volumes of between 50-80cc/kg donor whole blood for the patient’s blood.  This method rapidly and substantially reduces the concentration of sickle cells without increasing the overall hematocrit or blood viscosity.  

 Blood viscosity is determined by the red cells themselves as well as the hematocrit.  Sickle cells are intrinsically more rigid and viscous.  Substantially raising the hematocrit without first reducing the proportion of sickle cells can lead to dangerous levels of blood viscosity.  For this reason, simple transfusions must be used with caution for patients with hematocrits >25 (NIH p.25).

NIH indications for transfusion in sickle cell disease:

• A need to increase oxygen carrying capacity via simple transfusion
• Acute anemia (aplastic crisis, sequestration, blood loss)
• Symptoms of high output cardiac failure, postural hypotension, angina, or cerebral dysfunction
• Symptoms of fatigue and dyspnea with a low hemoglobin (usually <5g/dl)

• A need to improve microvasculature perfusion and to decrease the proportion of Hb S via partial exchange or exchange transfusion therapy
• Acute, impending, or suspected cerebrovascular events (stroke, partial stroke, TIA)
• Arterial hypoxia (fat embolization) and progressive lung disease (acute chest syndrome)
• Unresponsive priapism
• Prior to surgery requiring general anesthesia
• Eye surgery (even when done under local anesthesia and in the nonanemic patient)
• Intractable acute events
• Before injection of contrast material

In the presence of certain chronic conditions, it is desirable to keep the proportion of Hb S below 30% v simple transfusions on a routine schedule.

• History of stroke
• Leg ulcers
• Pregnancy
• Chronic organ failure
• Interruption in activities of daily living due to extreme and frequent vaso-occlusive episodes

Transfusion therapy is usually not helpful or indicated for:

• Asymptomatic anemia
• Uncomplicated pain episodes
• Minor infections
• Minor surgery with brief anesthesia or conscious sedation
• Aseptic necrosis of the hip or shoulder

Blood products for patients with sickle cell disease:

• Must be screened for presence of Hb S (even trait) with a solubility test (Sickledex, turbidity test)
• Should be leukodepleted
• Patients who have been previously transfused should be checked for presence of alloantibodies
• Full  antigenic typing of the red cells should include at least: C, E, Kell, Duffy, Kidd, S.

Transfusion Administration
Simple transfusion usually consists of giving 10-15cc/kg of PRBC over about four hours.  A manual partial exchange transfusion usually involves pre-transfusion phlebotomy of about 5cc/kg whole blood followed by transfusion with 10-20cc/kg PRBC.  Another method is to remove whole blood from an IV in one arm while transfusing PRBCs into the other arm. In some cases, diuretics can be used to avoid overload with transfusion.

Rapid partial exchange technique
These formulas can be used to achieve Hb S concentrations below 30% whout increasing the hematocrit above 35 (assuming that PRBC units have a hematocrit of 80%, d whole blood units have a hematocrit of 40%).bsp; The total volume of blood to be infused is proportional to the patient’s weight and hematocrit.

For patients with hematocrit < 15:
Option 1: exchange equal volumes (50cc/kg) of donor whole blood for the patient’s blood.

Option 2: exchange equal volumes (30cc/kg) of packed red blood cells for the patient’s blood.

For patients with hematocrit between 16-30%:Otion 1:  exchange equal volumes (80cc/kg) of donor whole blood for patient’s blood.

Option 2: first exchange equal volumes of PRBC (10cc/kg) for patient’s blood; then exchange equal volumes (70cc/kg) of donor whole blood for patient’s blood.

In adults with hematocrits between 20-26% w are hemodynamically stable, an adequate exchange can be obtained by removing 1 unit of blood, infusing 500cc of saline, removing a second unit of blood, and then infusing 5 units of PRBC.

For patients with hematocrit >30% (sually patients with Hb SC or SB thal):

• First remove 10cc/kg of patient’s blood and replace with an equal volume of normal saline.
• Then exchange with equal volumes (90cc/kg) of donor whole blood for patient’s blood.  Avoid using packed red blood cells to avoid excessively raising the hematocrit.

Automated exchange transfusion:
Automated full red cell exchange uses continuous flow instrumentation to rapidly and effectively replace patient blood with donor packed red blood cells.

Chronic transfusion therapy:
Once a hemoglobin S% o<30% h been achieved as a therapeutic intervention, giving simple transfusions on a 2-4 week schedule can maintain the Hb S% aor below 30% tprevent further complications.

Complications of transfusion therapy:
Iron overload is generally defined as serum ferritin levels >2500.  When transfusions are required for patients with ferritins in this range, chelation therapy with deferoxamine (Desferal) is indicated.  This is expensive, cumbersome long term therapy for patients on chronic transfusions.  It requires long (10-12 hours) subcutaneous infusion usually 5-7 days (or nights) per week.  Untreated iron overload can result in cardiac disease/failure, hepatic disorders/failure, brain damage, and endocrine abnormalities.(Oski 743)

Alloimmunization to red cell antigens occurs in about 25% otransfused patients with sickle cell disease.  This is higher than in the general public, and results in difficulty in obtaining compatible blood and a high incidence of delayed (5-20 days post) hemolytic transfusion reactions.  The risk of alloimmunization can be significantly reduced by:

• Maintaining accurate transfusion and phenotyping records
• Limiting the number of transfusions given; giving transfusions for only clear-cut indications.
• Screening for newly acquired antibodies
• Typing the patient for antigens of the Rh and Kell blood groups and avoiding the transfusion of cells having these antigens (especially E, C, and Kell) if the patient lacks the antigen.
• Increasing the numbers of African American donors for more likely phenotypical matches.
• Provide frequently transfused patients with a card identifying their red cell phenotype and any identified antibodies.

Some highly alloimmunized patients can develop autoimmune hemolytic anemia after a transfusion.  Often, the Coomb’s test remains positive long after the transfused cells are gone.  This is attributed to the development of antibodies directed at self-antigens.  In this case, future transfusions will be with the least incompatible donor blood available.

Alloimmunization to antigens on donor white cells can be minimized by using a leukodepleting filter for transfusion.  Some patients also benefit from pre-treatment with anti-pyretics and anti-histamines to minimize reactions to donor cell proteins.

Transmission of hepatitis and HIV virus in transfused sickle cell patients is the same as in other multiply transfused patients.