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Specific Problems: Anemia - Aplastic Crisis and Other Causes PDF Print E-mail
Health Care Providers - Problem Oriented Clinical Guidelines

Anemia is lifelong, starting in the first year of life as the fetal hemoglobin level falls. The average red cell survival is reduced from a normal of 120 days down to an average of 10 to 20 days in sickle cell anemia. This produces anemia, a high reticulocyte count, and a striking proliferation of red cell precursors in the bone marrow to compensate for the hemolysis. Other problems related to the anemia are jaundice (elevated indirect bilirubin), changes in bone structure, and a high lactic dehydrogenase. Increase in the severity of anemia can be a sign of developing life-threatening complications such as aplastic crisis and splenic sequestration. Both of these important complications will be discussed in this chapter. Many infectious complications will cause partial suppression of erythrocyte production increasing the anemia in patients with sickle syndromes. Acute anemia can be caused by an aplastic episode, sequestration, G6PD, acute chest syndrome, an allo-antibody, renal failure, or folate deficiency

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

Almost all patients with significant hemoglobinopathies will be anemic. Hemoglobins as low as 6.0 gm% and hematocrits as low as 16% are not uncommon in asymptomatic patients. In hemoglobin SS disease, the white count is usually elevated in the range of 10,000 to 15,000 and the platelet count may be elevated to from 400,000 to 1,000,000. Evaluation and consideration for treatment depend more on changes in the hematologic levels from baseline and symptoms, rather than absolute values that are stable.

Increase in the severity of anemia can be a sign of developing life-threatening complications such as aplastic crisis and splenic sequestration. Both of these important complications will be discussed in this chapter. Many infectious complications will cause partial suppression of erythrocyte production increasing the anemia in patients with sickle syndromes.

General guidelines suggesting a need for evaluation include.

- A fall in the hemoglobin of greater than 1 gm% or hematocrit of greater than 3 vol% when compared to a stable baseline.

- A fall in the absolute reticulocyte count to less than 100,000 or to less than one half of the stable baseline with a falling hemoglobin.

- An MCV of greater than 105 or less than 85.

  • Significant increase in the size of the spleen or liver with falling hemoglobin levels.

Clinical Findings

Subjective Data

Present Illness. Patient may be asymptomatic or have symptoms of acute lethargy, loss of appetite, increased weakness, fatigue, or DOE. History of recent infections, change in jaundice, increased pallor, increase in abdominal girth, blood loss, bruising, petechiae, change in urine color, melena, hematemesis, dizziness, syncope, history of recent transfusion, and present medications. Review spleen stick (See splenic Sequestration,).

Review of symptoms. Specifically exclude symptoms of infection, left or right upper quadrant discomfort, early satiety, skin rash, gastrointestinal symptoms, symptoms of pregnancy such as missed menstrual period, morning sickness, breast tenderness. Do a detailed dietary and medication (NSAID use) history.

Past Medical History. Note previous episodes of severe anemia, transfusion history, history of splenomegaly and potential sources of blood loss such as ulcer disease.

Objective Data

Physical Exam

- Vital signs. Temperature, respiratory rate, supine/upright blood pressure and pulse.

- HEENT. Look for increased jaundice, retinal hemorrhages, and oral petechiae.

- Neck. Lymphadenopathy.

- Chest. Bibasilar rales, signs of consolidation.

- Heart. Neck veins, S3, increased murmur, pedal edema.

- Abdomen. Increase in size of liver or spleen, guaiac stool.

  • Extremities. Edema, ecchymosis, petechiae.
Laboratory

- Minimum Lab. CBC with differential, reticulocyte count & platelet count, and stool guaiac.

- Additional Lab. Bilirubin total and direct, LDH, AST, and ALT for increased jaundice, hepatomegaly, splenomegaly, or admission criteria. Urinalysis when dark urine is present. Ferritin for MCV of less than 85 if patient has not had one in past year and does not have documented sickle thalassemia. Serum folic acid and B12 indicated if MCV over 110. Antibody screen and direct Coomb’s if evidence of increased hemolysis and/or recent transfusion.

Assessment - Differential Diagnosis

- Aplastic Crisis. Hemoglobin drop of more than 1 gm% or absolute value of less than 5 gm% with an absolute reticulocyte count of less than 10,000. True aplastic crisis with very low reticulocyte count and only anemia is usually seen in children and associated with infection by the parvovirus B19. Relative aplastic crisis with falling hemoglobin, low reticulocyte count may be associated with viral or bacterial infection, pain episodes, or occur de novo. White count and platelet count are usually stable but may also be low.

  • Splenic or Liver Sequestration Crisis. Hemoglobin drop of more than 1 gm% or absolute value of less than 5 gm% with reticulocyte count of more than 100,000 with rapidly enlarging spleen and/or liver (See splenic Sequestration, Chapter 43). There is often increase in indirect bilirubin and LDH over baseline. In adults, there may be evidence of hepatic dysfunction, renal insufficiency, and rhabdomyolysis prompting a diagnosis of acute multiorgan failure. Splenic sequestration is more common in children less than three and a significant cause of morbidity and mortality. Splenic sequestration can be seen at any age in patients with Hb SC or Sthal. In adults with sickle cell anemia, hyperhemolytic crisis with rapid enlargement of the liver is more common.
  • Delayed Transfusion Reaction. History of transfusion 7 to 14 days before fall in hemoglobin and evidence of increased hemolysis with increased indirect bilirubin, LDH, AST, and no change in ALT suggest a delayed transfusion reaction. Patient may have new pain and fever. The diagnosis is establish by finding new antibodies with red cell antigen specificity.

- Iron Deficiency. Increasing anemia, falling reticulocyte count, and/or decreasing MCVsuggests iron deficiency which does occur in patients with sickle syndromes. A serum ferritin of less than 20 ng/ml is diagnostic of iron depletion.

- Folate Deficiency. Increasing anemia with increasing MCV, low reticulocyte count, and low serum or red cell folate supports the diagnosis of folate deficiency. It is wise to always exclude B12 deficiency if the MCV is elevated and the reticulocyte count is low. High reticulocyte counts may increase the MCV. The increased requirements for folic acid caused by the hemolytic anemia usually only cause a problem if the diet is poor in folic acid or there are other causes of deficiency.

- Bleeding. Hemoglobin drop with orthostatic hypotension, hematemesis, melena, or guaiac positive stool suggests acute bleeding as a cause of the more severe anemia.

- Anemia of Renal Failure. Increasing anemia is seen with an elevated serum creatinine or standard creatinine clearance of less than 50 ml/min/1.76m2. These tests underestimate the degree of renal dysfunction in sickle cell patients so erythropoietin determinations should be considered in older patients with falling hemoglobin levels. This problem is becoming more common as patients are living longer. The etiology may be a relative erythropoietin deficiency caused by the renal damage.

Plan -Treatment

- Aplastic Crisis or Sequestration Crisis both require immediate admission, preferably to an intensive care unit.

- Any patient with an unstable hemoglobin level of less than 6 gm% should be admitted.

- Almost all patients with drop in hemoglobin of over 1 gm% or hematocrit of 3 vol% and. heart failure, pain crisis, GI or GU bleeding, orthostatic drop in blood pressure (10 mm hg) or increase in pulse (20/min), or documented infection require admission to the hospital for evaluation and treatment.

- Aplastic Crisis. Transfusion support is indicated for the severe aplastic crisis seen in children secondary to parvo virus. Pregnant and immunocompromised individuals should not have direct contact with the child. The relative aplastic crisis seen commonly with infections and other complications can often be managed without transfusion. Very close observation is required with daily monitoring of hemoglobin and reticulocyte levels. When the anemia is stable and the reticulocyte count is at the patient’s normal level, discharge with less frequent monitoring is indicated.

- Splenic or Liver Sequestration Crisis(Also see splenic Sequestration, Chapter 43).. Admission to a unit with a high level of care is indicated for patients with these syndromes. Frequent monitoring of vital signs, spleen and liver size, hemoglobin, liver tests, clotting studies, and renal function are indicated in the severe episodes. These syndromes have a very high mortality if not managed aggressively. Immediate transfusion with packed red cells is almost always indicated to maintain a hemoglobin level of 9 to 10 gms%. Higher levels should be avoided because the hemoglobin may increase further as the episode resolves causing problems with viscosity if the percent of Hb A is less than 50%. This is the only specific treatment available for hyperhemolytic episodes where only the liver is involved. Other support measures including fluids, electrolytes, vitamin K, and antibiotics should be provided based on observed abnormalities.

- Splenic Sequestration - Children over Five and Adults. Many advocate splenectomy in children over five with one episode of sequestration because of a very high recurrence rate. Others will delay splenectomy until the second episode. Pneumococcal vaccine is given before surgery and prophylactic penicillin may be indicated after surgery. Individuals that do not have their spleens removed should be maintained on chronic transfusions for a presently unknown period of time.

  • Splenic Sequestration - Children under Five. Children under three are usually treated with chronic transfusion every 3 to 4 weeks to maintain the hemoglobin at about 11 gm%, the reticulocyte count at less than 4%, and the percent of Hb S at less than 30%. These are continued for two years and until the child is five. They are then stopped and splenectomy performed for recurrences after acute management. Children between three and five should probably be transfused until age five and have an elective splenectomy. Recurrences on transfusion or alloimmunization should prompt splenectomy in most cases. This area is controversial because of the desire to maximize immune function and avoid surgery without exposing the child to undo risk of death from recurrence and complications of transfusion.
  • Delayed Transfusion Reaction. Patient should be supported with hydration and transfusion as needed. All future transfusions should be monitored and done for clear indications. Transfusion of red cells that are extensively phenotypically matched is indicated to prevent further delayed transfusion reactions and autoimmune hemolytic anemia.

- Iron Deficiency. Without admission criteria start ferrous sulfate ( Children 10 mg/kg; Adults 300 mg) P.O. t.i.d. 30 minutes before meals. Iron may have to be given with meals if gastric upset occurs even though absorption is less. Recheck hemoglobin and reticulocyte count at one week and one month. If a response is observed, the patient should be treated for a period of 2 to 4 months then have ferritin drawn two weeks after stopping iron. A level of 100 ng/ml indicates normal stores. Serum iron may be helpful in documenting compliance in non-responders.

- Folate Deficiency. Without admission criteria start folic acid 1 mg P.O. daily. Recheck hemoglobin and reticulocyte count at one week and one month. If patient states the folic acid is being taken, check folic acid and B12 and increase the dose to 2 mg P.O. QD if levels are low and recheck as above.

- Renal Insufficiency. Without admission criteria, schedule for outpatient transfusions to maintain the hemoglobin at over 7 gm%. Administration of erythropoietin 10,000 units three times a week may benefit patients with significant decrease in hemoglobin and erythropoietin levels less than 200 u/ml. Baseline ferritin should be drawn and monitored once a year if patients are on regular transfusion..

Patient Education and Prevention

All patients and parents should be educated about the need for a high protein, balanced diet which provides appropriate numbers of calories. The need for fresh fruit and vegetables that are not over-cooked should be stressed. Careful dietary history should be assessed for adequacy of folates and vitamin therapy be given if there is any question of adequacy. Iron deficiency in an adult male or non-menstruating female should always prompt a work-up for occult blood loss usually including complete gastrointestinal evaluation.

Patients and parents must be taught the early detection of splenic sequestration at diagnosis. Signs and symptoms of increasing anemia or hemolysis must be delineated. Hemoglobin levels, reticulocyte counts, indirect bilirubin, and LDH should be determined on a regular basis during health maintenance to establish a baseline for each patient which will usually be relatively stable. Hemoglobin and reticulocyte levels must be checked when the patient presents with any complication.

Patients requiring chronic transfusion should have a red cell phenotype determined to characterize minor antigens. Phenotype specific blood should be given after the first alloantibody develops. Blood donation drives in the African American community are invaluable in providing phenotype specific blood to patients with sickle syndromes.

Education about diet, compliance with medications, and vitamins is important. The parents of infants need to be taught the signs of increasing anemia (pallor, lethargy, irritability, poor appetite, and increased jaundice). They need to learn how to assess spleen size and abdominal girth in an accurate way. Abdominal girth at the umbilicus can be measured and recorded with the parents at follow-up visits.

The use of a tongue blade as a spleen stick (See splenic Sequestration, ) provides an accurate way of assessing and recording spleen size at home and in the clinic.

References

Rabb et al. A trial of folate supplementation in children with homozygous sickle cell disease. Br. J. Hematol. 54:589, 1983.

Vichinsky E et al. The diagnosis of iron deficiency anemia in sickle cell disease. Blood 58:963, 1981

Pattison JR et al. Parvovirus infections and hypoplastic crisis in sickle cell anemia. Lancet 1:644, 1981.

Committee on Infectious Disease. Parvovirus, erythema infectiosum, and pregnancy. Pediatr. 85:131, 1990.

Rogers DW et al. Early deaths in Jamaican children with sickle cell disease. Br. J. Med. 1:1515, 1978.

Topley JM et al. Acute splenic sequestration crises in young children with sickle cell anemia. Arch. Dis. Child. 56:765, 1981.

Emond AM Acute splenic sequestration in homozygous sickle cell disease; natural history and management. J. Pediatr. 107.201, 1985.

Kinney TR et al. Long-term management of splenicsequestration in children with sickle cell disease. J. Pediatr. 117.194, 1990.

Grover R Wethers DL. Management of acute splenic sequestration crisis in sickle cell disease. J. Assoc. Acad. Minority Phys. 1.67, 1990.

Sheehy TW. Sickle cell hepatopathy. So. Med. J. 70.533, 1970.

Hatton CSR et al. Hepatic sequestration in sickle cell anaemia. Brit. Med J. 290.744, 1985.

Schubert TT. Hepatobiliary system in sickle cell disease. Gastroenterology 90.2013, 1986.

Ohene-Frempong K Steinberg MH. Clinical aspects of sickle cell anemia in adults and children. in Disorders of Hemoglobin: Genetics, Pathophysiology and Clinical Management. Steinberg MH, Forget BG, Higgs DR, Nagel RL. Cambridge University Press Cambridge UK 2001. pp. 624-628.

 

Last Updated on Monday, 14 June 2010 13:55
 
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