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Hematology > Uncommon RBC Membrane Disorders
Pyropoikilocytosis, Hereditary
Article Last Updated: Jan 26, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Amanda D May, MD, Assistant Fellowship Director, Chief, Section of Hematology/Oncology, Augusta VAMC; Assistant Professor of Medicine, Department of Internal Medicine, Division of Hematology/Oncology, Medical College of Georgia
Amanda D May is a member of the following medical societies: American College of Physicians, American Medical Association, and Southern Medical Association
Coauthor(s):
Abdullah Kutlar, MD, Director of Sickle Cell Center, Fellowship Program Director, Professor, Department of Internal Medicine, Section of Hematology and Oncology, Medical College of Georgia
Editors: Karen Seiter, MD, Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Marcel E Conrad, MD, BS, (Retired) Distinguished Professor of Medicine, University of South Alabama; Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems; Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Author and Editor Disclosure
Synonyms and related keywords:
hereditary pyropoikilocytosis, congenital hemolytic anemia, homozygous hereditary elliptocytosis, partial spectrin deficiency, growth retardation, frontal bossing, gallbladder disease, irregular red blood cells, severe anemia, abnormal red blood cell morphology, splenectomy, low hemoglobin level, nonhemolytic hereditary elliptocytosis, spectrin deficiency, autosomal recessive gene
Background
Hereditary pyropoikilocytosis is a severe form of congenital hemolytic anemia. It is clinically similar to, and now considered a subtype of, homozygous hereditary elliptocytosis. Hereditary pyropoikilocytosis is an autosomal recessive disorder that produces a molecular defect in spectrin and a partial spectrin deficiency. It manifests as a severe hemolytic anemia with thermal instability of the red blood cells. Current understanding suggests that this phenotype results when one parent has hereditary elliptocytosis and the other parent carries a gene that causes a spectrin deficiency. Hereditary pyropoikilocytosis results when both of these conditions occur in an individual's genetic makeup.
Pathophysiology
The severe anemia can result in growth retardation and early gallbladder disease.
Frequency
United States
Hereditary pyropoikilocytosis is a rare disorder that is mostly observed in people of African descent.
International
As in the United States, this is a rare disorder that is mostly observed in people of African descent.
Mortality/Morbidity
Morbidity and mortality are related to the severity of the anemia and its effects on the developing child. These effects include growth retardation, frontal bossing, and gallbladder disease.
Race
This disorder is mostly observed in people of African descent, but it has been documented in people of European and Arab descent.
Sex
Hereditary pyropoikilocytosis does not predominate in either sex because it is inherited as an autosomal recessive gene.
Age
The disorder is usually discovered in infancy or early childhood.
History
An infant or young child presents with a transfusion-dependent hemolytic anemia that is moderately severe to severe. Family history most likely includes a parent or sibling with nonhemolytic hereditary elliptocytosis. The other parent likely has a previously undiagnosed spectrin deficiency.
Physical
Physical examination is remarkable for signs of anemia or, possibly, the effects of ongoing severe anemia, such as frontal bossing, growth retardation, or signs and symptoms of gallbladder disease. Splenomegaly may also be present.
Causes
Pyropoikilocytosis is a hereditary condition with an autosomal recessive mode of inheritance. One or both parents may exhibit nonhemolytic elliptocytosis. The red blood cells of patients with pyropoikilocytosis demonstrate thermal instability at temperatures as low as 45°C.
Hemolytic Anemia
Other Problems to be Considered
Homozygous hereditary elliptocytosis
Lab Studies
- A complete blood count and a peripheral blood smear are the most important studies to obtain when testing for hereditary pyropoikilocytosis (see Image 1). A reticulocyte count and, possibly, other markers of hemolysis may be of use in these cases. Reticulocytosis should occur, depending on how well the patient's bone marrow is able to respond. The mean corpuscular volume (MCV), reported in femtoliters, may be as low as 25-55 fL. The peripheral blood smear of a patient with hereditary pyropoikilocytosis demonstrates bizarre forms, anisocytosis, fragments, micropoikilocytosis, microspherocytosis, and budding red blood cells.
- Specialized hematology laboratories may also be able to perform both thermal sensitivity and osmotic fragility tests to confirm the diagnosis further. With this disorder, red blood cells should have thermal autohemolysis and increased osmotic fragility. Thermal sensitivity testing shows fragmentation of the red blood cells at temperatures as low as 45°C.
- Monitor iron stores periodically to determine if iron chelation is required to prevent irreversible end-organ damage and dysfunction.
Other Tests
- Evaluate the ratio of spectrin to band 3 to determine the spectrin level so that this entity can be differentiated from homozygous hemolytic elliptocytosis.
Medical Care
Treatment of hereditary pyropoikilocytosis includes transfusion of packed red blood cells and other supportive care. Supportive care encompasses intravenous fluids, oxygen, and monitoring in an acute care setting as determined by the needs of the individual patient. Further treatments such as medications or surgical procedures vary among patients, depending on their individual needs and other concurrent problems.
Surgical Care
Splenectomy has been shown to improve anemia but has no effect on abnormal red blood cell morphology.
Diet
No dietary restrictions are necessary for people with hereditary pyropoikilocytosis. However, at some point, hemolysis and increased erythrocyte production by the bone marrow may necessitate folic acid supplements.
Activity
Activity is limited only in relation to the severity of the anemia and its effects on other organ systems.
No specific medications are used to treat hereditary pyropoikilocytosis. Individual patients may require treatment with medications such as intravenous fluids or oxygen on a patient-specific basis. Other related conditions can arise that may require treatment with medications specific to the situation, but medications do not affect the underlying disorder. Folic acid is often used because of the relative or absolute folate deficiency that often occurs in patients with chronic hemolysis and increased erythropoiesis by the bone marrow.
Drug Category: Vitamins
A folate deficiency can develop because of the high turnover rate in the erythroid line and subsequent use of substrate. Replacement is often necessary. This is easily accomplished with an oral dose of 1 mg/d.
| Drug Name | Folate (Folvite) |
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| Description | Important cofactor for enzymes used in production of red blood cells. A folate deficiency can develop because of the high turnover rate in the erythroid line and subsequent use of substrate. |
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| Adult Dose | 1 mg/d PO/IM/SC |
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| Pediatric Dose | Administer as in adults |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Increase in seizure frequency and decrease in subtherapeutic levels of phenytoin reported when used concurrently |
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| Pregnancy | A - Safe in pregnancy
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| Precautions | Folate may cause anorexia, nausea, abdominal pain, flatulence, altered sleep patterns, irritability, overactivity, erythema, rash, or itching; benzyl alcohol may be contained in some products as a preservative (associated with a fatal gasping syndrome in premature infants); resistance to treatment may occur in patients with alcoholism and deficiencies of other vitamins |
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Further Inpatient Care
- Inpatient care of people with hereditary pyropoikilocytosis consists largely of transfusion requirements, care immediately after splenectomy, and treatment of illnesses that result from severe anemia or complications related to splenectomy.
Further Outpatient Care
- Provide routine outpatient care and monitor hemoglobin if symptoms occur.
- Maintain high suspicion for early involvement with gallbladder disease.
- Iron chelation therapy may be required to prevent irreversible end-organ damage due to transfusion-induced hemosiderosis. Monitor the number of transfusions performed and the iron status of the patient to determine if and when this therapy is needed.
- If a splenectomy has been performed, polyvalent pneumococcal polysaccharide vaccine (Pneumovax) therapy and prompt care of febrile illnesses is warranted.
In/Out Patient Meds
- No specific medications are used to treat people with hereditary pyropoikilocytosis. The need for treatment with medications is patient-specific and based on individual complications.
- Folic acid is often used to prevent folic acid deficiency that may occur as a result of increased erythropoiesis.
- Iron chelation therapy may be necessary in patients who develop significant iron overload from red blood cell transfusions.
Complications
- Most complications are related either to extended severe anemia with multiple resultant transfusions and iron toxicity to major organs or to infection with encapsulated organisms in patients who have undergone a splenectomy, although such infections are rare in patients who have been immunized against pneumococcus, Haemophilus influenzae, meningococcus, or a combination thereof.
Prognosis
- Prognosis is related to the number of transfusions needed to maintain adequate hemoglobin levels for a growing child and the ability to treat or to prevent life-threatening infections after splenectomy.
Patient Education
- Discuss with the patient's parents the possibility that they could bear another child with the same disease.
Medical/Legal Pitfalls
- Failure to diagnose hereditary pyropoikilocytosis properly
- Failure to counsel the patient's parents on the likelihood of bearing another child with the same disorder
- Failure to treat transfusion-induced hemosiderosis appropriately
Special Concerns
- Hereditary pyropoikilocytosis is a genetically linked disorder. Family pedigrees are helpful in determining who is at risk to have a child with this entity.
| Media file 1:
Peripheral smear that shows evidence of hereditary pyropoikilocytosis. |
 |  View Full Size Image | |
Media type: Image
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- Coetzer T, Palek J, Lawler J, et al. Structural and functional heterogeneity of alpha spectrin mutations involving the spectrin heterodimer self-association site: relationships to hematologic expression of homozygous hereditary elliptocytosis and hereditary pyropoikilocytosis. Blood. Jun 1 1990;75(11):2235-44. [Medline].
- Coetzer TL, Palek J. Partial spectrin deficiency in hereditary pyropoikilocytosis. Blood. Apr 1986;67(4):919-24. [Medline].
- Hoffman R, Benz EJ, Shattil SJ, eds. Hereditary pyropoikilocytosis. In: Hematology Basic Principles and Practice. New York, NY: Churchill Livingstone;2000:592.
- Lee GR, Foerster J, Lukens J, eds. Hereditary pyropoikilocytosis. In: Wintrobe's Clinical Hematology. Vol 1. Baltimore, Md: Williams & Wilkins;1999:1146-7.
- Stiene-Martin AE, Lotspeich-Steininger CA, Koepke JA, eds. Hereditary pyropoikilocytosis. In: Clinical Hematology: Principles, Procedures, Correlations. Lippincott Williams & Wilkins;1998:95, 257-8.
Pyropoikilocytosis, Hereditary excerpt Article Last Updated: Jan 26, 2007
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