Sickle Cell Information Center Guidelines

Edited by James Eckman, M.D. and Allan Platt, PA-C

Transfusion Therapy by Beatrice Gee, MD

The treatment goals for transfusion are to relieve symptoms and to treat or prevent complications. Because of the risks of iron overload, exposure to hepatitis, HIV, and other infectious agents, alloimmunization, induction of hyperviscosity, and limits on the resource, transfusion therapy should be used judiciously.

Present Illness. Neurologic symptoms, acute lethargy, increased weakness, fatigue, or dyspnea on exertion, should be documented.

Review of symptoms. Specifically assess for symptoms of heart failure including edema, paroxysmal nocturnal dyspnea, orthopnea, and dyspnea with exertion.

Past Medical History. Note previous transfusions, reactions, history of alloantibodies, number of units, reasons for transfusions, and approximate dates, treatment for iron overload. Religious beliefs about transfusions and personal fears need to be explored.

Physical Examination

• Vital signs. Temperature, respiratory rate, blood pressure and pulse.
• Chest. Bibasilar rales.
• Heart. Neck veins, S3, increased murmur. Hyperdynamic precordium
• Abdomen. Increase in size of liver or spleen.
• Extremities. Edema.
• Neurologic. Document focal findings.

Minimum Lab tests. CBC with differential, reticulocyte & platelet count, screen for alloantibodies, type and cross match for the units required.

Additional Lab tests. Red cell minor antigen phenotype before first transfusion if possible. Direct and indirect Coomb’s, hepatitis profile, HIV, may be indicated if the patient has been previously transfused. Hemoglobin electrophoresis with quantitation of Hb ASC and ferritin may be done periodically to monitor therapy and iron overload with chronic transfusion.

Indications for Transfusion - The decision to transfuse a patient acutely or chronically must be based on the specifics of each individual case. The following are general, and likely controversial, recommendations for transfusion in patients with sickle syndromes.

Definite Indications for transfusion:

• Acute neurologic event.
• Splenic sequestration.
• Severe pneumonia or pulmonary infarction.
• Severe anemia with cardiac decompensation.
• Acute arterial hypoxia.
• Aplastic crisis with severe anemia.
• Hyperhemolytic crisis with enlarging liver/spleen.
• Ophthalmological surgery.

Relative Indications:

• Symptomatic anemia.
• Hepatic sequestration.
• Leg ulcers refractory to conservative therapy.
• Priapism resistant to acute treatment or recurrent.
• Severe or prolonged pain episodes.
• Frequent pain episodes.
• Chronic respiratory insufficiency.
• High dose intravascular contrast studies.
• Surgery with general anesthesia.
• Pregnancy.

Usually not indicated:

• Stable chronic anemia.
• Pain episodes without absolute or relative indications.
• Minor surgery under local or short general anesthesia.
• Uncomplicated infections.
• Chronic bone disease or organ failure without other indications.

Criteria for Admission for Transfusion

• All patients with absolute criteria for transfusion should be admitted to initiate transfusion therapy.
• All patients requiring acute, manual exchange.
• Patients with CHF or uncontrolled hypertension.

Criteria for Outpatient Transfusion

• Patients on stable chronic transfusion programs.
• Patients being initiated on transfusion therapy for symptoms of acute anemia, chronic stable complications, or pregnancy.
• Patients being prepared for elective surgery or intravascular contrast studies.

Transfusion of packed red cells is indicated in almost all situations. The volume of erythrocytes in packed cells is 60% of the volume of the unit when AdSol is used and 75% when CPD or ACD is used. All recommendations for replacement are based on the volume of the unit of packed cells assuming a hematocrit in the unit of 70%. Adjustments will be necessary for AdSol, washed or frozen deglycerated units. Fresh blood (less than 3 days old)should be used in exchange transfusions done to improve oxygen delivery because of hypoxia. Blood should be screened by hemoglobin electrophoresis if the level of Hb S is to be monitored after transfusion. Patients with a history of alloimmunization should be given as few transfusions as possible and phenotypically matched units if practical. These patients must carry a record of all documented alloantibodies and show it to any physician contemplating transfusion. Patients with a history of febrile transfusion reactions should be given leukocyte depleted units and may be pre-treated with acetaminophen and antihistamines if necessary.

Simple Transfusion. In general, simple transfusion is indicated for severe anemia, aplastic crisis, hyperhemolytic crisis, and in chronic transfusion programs. Simple transfusion should also be used in patients with a relative indication and a hematocrit of < 25? %.

With a relative indication for chronic transfusion, packed red cells should be given to raise the hematocrit to 30 vol.% (Hb 10 gm%) and then q week until the % S is < 50%. After the %S is < 50 the hematocrit can be increased to 35 vol.% (Hb 12 gm%). The patient should then be transfused every 3 to 4 weeks to keep the hematocrit 30-35vol.%, the percent S < 30 %.

Formulas of use in Blood Transfusion (Useful Approximations):

Total Blood Volume = 70 cc X Weight in kg.or 75 cc X Weight in Kg (With chronic anemia).

Red Cell Volume of Patient = Total Blood Volume X Hematocrit

Giving 3 cc/kg of packed red cells will raise the hemoglobin by 1 gm/dl

Giving 10 cc/kg of packed red cells will raise the hematocrit by 10 points (vol%) or hemoglobin by about 3 gm/dl

Transfusion volume = [Total Blood Volume X (Hcrit goal - Hcrit pre Tx)]/ Hcrit of Donor Unit

Example: For 50 kg person with pre-transfusion Hcrit 23%, goal Hcrit 30%, average PRBC unit Hcrit 70%,

[(75 cc/kg) (50 kg) (0.30 – 0.23)]/0.70 = 375 cc (or 7.5 cc/kg)

Hematocrit of donor unit average values in transfused units

Whole blood donor unit average Hematocrit = 35%

Packed red cell unit average Hematocrit = 70%

PRBC unit with AdSol averages Hematocrit = 60%

Those being treated for acute anemia, aplastic crisis, heart failure, splenic sequestration, and bleeding should be given packed cells to raise the hematocrit to 28 - 33 vol.%. Patients should receive further transfusions based on symptoms.

Exchange Transfusion. Exchange transfusions should be performed in patients with acute neurologic events, severe pneumonia or pulmonary infarction, acute arterial hypoxia, ophthalmological surgery, priapism, high dose intravascular contrast studies, and symptomatic anemia during pregnancy. This can be accomplished either manually or by apheresis. The volume of packed cells to be given must be based on the hematocrit of the packed cells, the red cell mass of the patient, and the desired percentage of Hb A. The desired final hemoglobin level, the initial patient hematocrit, and the blood volume will determine the volume of whole blood that needs to be removed. The general goal of the following approaches are to establish < 30% Hb S in the circulation with a hemoglobin of 10 gm%. Hemoglobin levels of greater than 12 gm% during exchange may be associated with increased whole blood viscosity and complications.

Estimation of exchange transfusion volume:

Single volume red cell exchange reduces %Hb S to approximately one-third (33%) of initial

PRBC volume = [Total blood volume (75 cc/kg) x goal Hcrit]/Hcrit of donor units

Example: 50 kg person, goal Hcrit 32, Hcrit of donor units 70%

PRBC volume = [(75 cc/kg)(50 kg)(0.32)]/0.70 = 1714 cc (or 34 cc/kg)

For patients under 25 kg having an automated exchange, an additional unit of blood is needed to prime the cytopheresis pump.

Automated Red Cell Exchange. Apheresis can be used to rapidly reduce the Hb S to less than 30% and giving extra packed cells to adjust the final hemoglobin using the formulas outlined above. This can only be accomplished if the red cell volume of the patient exceeds the minimums of the machine and venous access will allow two 16 gauge I.V. sites or a central pheresis catheter. A two red cell mass exchange should be performed and then the patient should be transfused up to a hemoglobin of 10 gm%. Hemoglobin electrophoresis with ASC quantitation should be obtained to assess the % Hb S.

Rapid Manual Partial Exchange Transfusion (Modified from Charache et al.1989).

Packed red cells are initially transfused while whole blood is removed to reduce the percentage of Hb S. Then whole blood or whole blood equivalent is transfused to increase the percentage of Hb S without further increasing the hemoglobin levels. This technique is applicable to adults and children and is based on the initial hematocrit and body weight in kg. The exchange can be done using one or two I.V. sites by removing and transfusing aliquots adjusted to the total blood volume (critical in children).

Hematocrit up to 19% (Hb > 6.5 gm%). Give packed cells equal to 30 cc/kg body weight while removing an equal volume of patient whole blood. Then give donor whole blood equivalents cc for cc while removing an additional 40 cc/kg of patient whole blood.

Hematocrit between 20 and 30% (Hb 6.6 - 10 gm%). Exchange 10 ml/kg body weight by giving packed cells while removing whole blood then exchange another 70 ml/kg body weight giving donor whole blood equivalent for patient whole blood volume removed.

Hematocrit > 30% (Hb > 10 gm%). Exchange whole blood removed with normal saline to 10 ml/kg body weight then exchange patient whole blood removed with donor whole blood equivalent (total volume??).

Whole blood equivalent is whole blood with a hematocrit of 40% or packed cells and saline or other plasma equivalents reconstituted to a hematocrit of 40%. Packed cells are assumed to have a hematocrit of 60% in AdSol. These are initial estimates of needs and need to be adjusted for the patients initial volume status and measured hemoglobin, hematocrit, and percent Hb S after the initial exchange. The protocol should give Hb S level of about 30% and a final hemoglobin been 10 and 12 gm%.

Elective Partial Exchange Transfusion. Patients can be prepared for elective procedures over days or weeks using the same general guidelines. The amount of blood transfused and removed can be optimized by measuring the hemoglobin before and the hemoglobin and percent of Hb S after each exchange. If this is done over several weeks the amount exchanged can be reduced by taking advantage of the differential survival of transfused erythrocytes and the suppression of erythropoiesis.

Chronic Transfusion. Regular transfusion is effective in maintaining low levels of Hb S if this is indicated by the clinical situation. Transfusion of 5 to 10 cc/kg of packed cells every 3 to 4 weeks is the usual dose. After the %S is < 50 the hematocrit can be increased to 30 vol.% (Hb 10 gm%). The patient should then be transfused every 3 to 4 weeks to keep the minimum hematocrit at 30 vol.%, the reticulocyte count at < 4%, and the percent S approximately 30%.

There are a number of important complications that may occur with transfusion. The most important include volume overload, alloimmunization, iron overload, and exposure to infectious agents. Volume overload is usually caused by too rapid administration of blood. Prevention includes reducing the rate of administration or concurrent administration of loop diuretics in patients with expanded blood volumes or limited cardiac reserve.

Alloimmunization is a common problem occurring in about one quarter of transfused sickle patients. Delayed transfusion reactions, difficulty obtaining blood, and development of autoantibodies are common sequelae. Factors such as racial differences in minor antigen frequency, amount of blood transfused, and previous alloantibodies all predispose to development of new antibodies. Prevention of alloimmunization and delayed transfusion reactions is facilitated by providing a record of previous transfusions, reactions, and alloantibodies to the parent and/or patient. Identification bracelets should provide alloantibodies and a number to obtain a transfusion history in sensitized individuals. Screening for alloantibodies six to eight weeks after transfusion will document new antibodies that may disappear if there is a prolonged interval without transfusion, but still cause delayed transfusion reactions if further transfusions are required.

Limiting the number of units transfused is also important. The antigenic mismatching can be reduced by using donors of the same ethnic background as the patient. Donor recruitment in churches and community groups may be required. Patients should have a phenotype determined for common hemolytic minor antigens before regular transfusion to assist in transfusion if multiple or autoantibodies develop. Phenotypically matched blood is indicated once an alloantibody develops. Some advocate matching for Kell, E, C, Kidd (Jkb), and Duffy (Fya) in all chronically transfused individuals. Most advocate limited phenotypic matching.

Leukocyte depletion prior to storage of red cells prevents febrile reactions.

Iron overload can only be effectively prevented by limiting the amount of red cells transfused. Guidelines for the prevention, diagnosis, and treatment of iron overload are presented in the Chelation chapter.

Testing for infectious agents markedly reduces but does not eliminate exposure to hepatitis, AIDS, and other viral diseases. All patients receiving transfusion from 1975 through 1985 should be offered counseling about testing for HIV infection. Others given screened blood should be tested for hepatitis or HIV on request or in clinical situations where infection is likely. Patients who are not immune to Hepatitis B should be immunized with the Hepatitis B vaccine.

Nursing Considerations:

Provide transfusion education to parent and patient about safety, the benefits, and risks involved in transfusions.

Consent must be obtained and the blood must be checked by appropriate personnel prior to each transfusion

Monitor vital signs for transfusion reactions.

Encourage hepatitis vaccination.

Patients/parents should maintain records of transfusions, reactions, and alloantibodies.

Counsel chronic transfusion patients regarding Partner’s for Life Program to reduce the exposure to alloimmunization and blood bourn infections

Patients and parents should be educated about the importance of carrying records of transfusions, reactions, and alloantibodies. These should be presented to any new physician and when transfusions are given. A running total of units transfused will facilitate estimation of iron overload.

The risks and benefits of transfusions should be explained before the transfusion is given. The indications and anticipated benefits need to be presented realistically. Risks such as volume and iron overload, alloimmunization, and exposure to infection need to be presented in understandable language. Often unrealistic fear of transfusions prevents beneficial treatment.

References

Charache S, Lubin B, Reid CD (eds.). Management and Therapy of Sickle Cell Disease NIH Pul. No. 89-2117, 1989, pp. 25-28.

Kernoff et al. Exchange transfusion in sickle cell disease using a continuous-flow cell separator. Transfusion 17:269, 1977.

Diamond et al. Delayed hemolytic transfusion reaction presenting as sickle-cell crisis. Ann. Intern. Med. 93:231, 1980.

Charache et al. Effects of blood transfusion on exercise capacity in patients with sickle-cell anemia. Amer.

Castro et al. Improved method for automated red cell exchange in sickle cell disease J. Clin. Apheresis 3:93, 1986.

Schmalzer EA et al. Viscosity of mixtures of sickle and normal red cells at varying hematocrit levels. Implications for transfusion. Transfusion 27:228,1987.

Reisner EG et al. Alloantibody responses in multiply transfused sickle cell patients. Tissue Antigens 30:161, 1987.

Ambruso DR et al. Experience with donors matched for minor blood group antigens in patients with sickle cell anemia who are receiving chronic transfusion therapy. Transfusion 27:94, 1987.

Vichinsky EP et al. Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood. New Engl. J. Med. 322:1617, 1990.

Rosse WF et al. Transfusion and alloimmunization in sickle cell disease. Blood 76:1431, 1990.

Treadwell MJ, Weissman L Improving adherence with deferoxamine regimens for patients receiving chronic transfusion therapy.Semin Hematol 2001 Jan;38(1 Suppl 1):77-84

Treadwell MJ, Weissman L. Improving adherence with deferoxamine regimens for patients receiving chronic transfusion therapy. Semin Hematol. 2001 Jan;38(1 Suppl 1):77-84.

Cohen AR, Martin MB. Iron chelation therapy in sickle cell disease. Semin Hematol. 2001 Jan;38(1 Suppl 1):69-72.

Porter JB. Deferoxamine pharmacokinetics. Semin Hematol. 2001 Jan;38(1 Suppl 1):63-8.

Olivieri NF. Progression of iron overload in sickle cell disease. Semin Hematol. 2001 Jan;38(1 Suppl 1):57-62.

Ohene-Frempong K. Indications for red cell transfusion in sickle cell disease.
Semin Hematol. 2001 Jan;38(1 Suppl 1):5-13.

Brittenham GM, Sheth S, Allen CJ, Farrell DE. Noninvasive methods for quantitative assessment of transfusional iron overload in sickle cell disease. Semin Hematol. 2001 Jan;38(1 Suppl 1):37-56.

Ballas SK. Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease. Semin Hematol. 2001 Jan;38(1 Suppl 1):30-6.

Eckman JR. Techniques for blood administration in sickle cell patients.
Semin Hematol. 2001 Jan;38(1 Suppl 1):23-9.

Vichinsky EP. Current issues with blood transfusions in sickle cell disease.
Semin Hematol. 2001 Jan;38(1 Suppl 1):14-22.