GROUP CASE STUDY
Dr. Nancy McQueen
MICR 410 - Hematology
Spring, 2011
Case # 2
Ruby Khan
Wilson Liu
Baron Morano
Case Summary
• 12-year-old male with right upper-quadrant pain and history of
hemolytic and aplastic crises.
• Lab results:
WBC:
RBC:
Hgb:
Hct:
Platelets:
• Erythrocyte indices:
8.0 x 109/L
MCV = 72. 5
4.0 x 1012 /L
MCHC = 37.2
10.8 g/dL
MCH = 27
0.29 L/L
504 x 109 /L
Case Summary
• Based on the indices, the patient’s red blood cells are…
Microcytic - Normochromic
• Osmotic fragility test:
– Initial hemolysis
– Complete hemolysis
patient
0.65% NaCl
0.40% NaCl
control
0.45% NaCl
0.30% NaCl
• Thermal Sensitivity Test:
Erythrocytes fragmented at 46.0 Degrees Celcius
Key Diagnostic Information
•Age
 Young!
•Right upper-quadrant pain
 Gallbladder – Cholecystitis
•Hemolytic anemia
 Premature RBC Death
•Aplastic Anemis
 Reticulocytopenia
•Poikilocytosis
•Increased Osmotic fragility
•Abnormal red cell thermal sensitivity
Peripheral Blood smear
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Elliptocytes
Spherocytes
Teardrop cells
Micro - Spherocytes
Our Diagnosis
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Patient suffers from…
Acronym = H.P.P.
HEREDITARY PYROPOIKILOCYTOSIS
Hewlett Packard Pavilion
Honda Power Port
Hawaiian Paradise Park
**Main Defect: Spectrin!!!
Pathophysiology of HPP
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HPP is an autosomal recessive disorder
Patients with HPP are compound heterozygotes &
exhibit 2 genetic defects:
(1) A mutant α or β spectrin that causes severe
impairment of spectrin dimer self-association
(2) A partial spectrin deficiency, resulting from
decreased synthesis of α spectrin, which causes
Microspherocytosis
Current understanding suggests HPP results when 1
parent has Hereditary Elliptocytosis (HE) & the other
parent carries a gene that causes a spectrin deficiency
HPP involves a spectrin dimer-dimer association
problem
Defective spectrin dimer self-association or protein 4.1
deficiency weakens the RBC skeleton, and under sheer
stress in the circulation, the cells become distorted and
lose their ability to regain their original disc shape
 Resulting in Elliptocytes & Poikilocytes
Pathophysiology of HPP
In HPP, the clinical severity & morphology are thought to result from
a combination of Horizontal & Vertical Defects
Horizontal Defect – Spectrin self-association is severely impaired,
which decreases the strength & stability of the skeleton, resulting in
Poikilocytes & Fragmentation.
 Vertical Defect - Spectrin deficiency impairs the vertical interaction
of the skeleton with the lipid bilayer, which causes Microsphereocytes.
HPP manifests as a severe hemolytic anemia with thermal instability
of the RBCs.
The severe anemia can result in growth retardation & early
gallbladder disease (upper right quadrant pain).
Hemolysis can lead to rapid sequestration
& destruction of RBCs.
Testing for HPP
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KEY TESTS
Peripheral Blood Smear
RBC Indices
Osmotic Fragility
Thermal Sensitivity
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ADDITIONAL
Coomb’s Test
Vitamin B12 : Folate
Bilirubin levels
Ham’s Test
Autohemolysis Test
Acidified Glycerol Test
FUTURE???
• SDS-PAGE = Gel Electrophoresis
• Eosin-5-maleimide (EMA)-binding test
Therapy & Prognosis of HPP
Treatment – Transfusion of packed red blood cells.
Supportive Care – Intravenous fluids, Oxygen, & Monitoring
HPP patient in an acute care setting as determined by the needs
of the individual patient.
Surgical Procedures – Splenectomy
Treatment of Individual Symptoms
No Specific Medications for HPP
Therapy & Prognosis of HPP
Vitamins – Folic Acid often recommended due to Folate
Deficiency that often occurs in patients with chronic hemolysis
& increased erythropoiesis by the bone marrow.
 Recommended Oral Dose of 1 mg/day
Prognosis - Related to the number of transfusions needed to
maintain adequate hemoglobin levels for a growing child & the
ability to treat or to prevent life-threatening infections after
splenectomy
Preventing HPP
Since HPP is a genetic disease, there is not much that can be done to prevent it, aside
from...
Genetic Counseling
From the Law for the Prevention of Progeny with Hereditary Diseases
of 14 July 1933
Source : M. Burleigh & W. Wippermann, The Racial State. Germany, 19331945, (Cambridge, 1991), pp.136-138.
Gene Therapy
Take Home Message
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The diagnosis:
– Hereditary Pyropoikilocytosis
Typical symptoms
– Moderate to Severe Hemolytic Anemia
– Gallbladder Disease and Splenomegaly
– A Parent or Sibling With Hereditary Elliptocytosis
The cause of the disease:
– Spectrin Defect
Diagnostic tests include:
– CBC
– Peripheral Blood Smear
– Osmotic Fragility Test
– Thermal Sensitivity Test
Treatment:
– Splenectomy
Prognosis:
– Variable
Prevention:
– Genetic Counseling
– Gene Therapy
References
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Textbook – Clinical Hematology and Fundamentals of Hemostasis (Fifth edition) Denise M. Harmening
Medscape Online Reference - http://emedicine.medscape.com/article/205843-overview
National Insitute of Health; Office of Rare Diseases Research http://rarediseases.info.nih.gov/GARD/Disease.aspx?PageID=4&diseaseID=4619
Wikipedia: The Free Encyclopedia - http://en.wikipedia.org/wiki/Hereditary_elliptocytosis ;
http://en.wikipedia.org/wiki/Pyropoikilocytosis
Med India: Medical Lab Tests - http://en.wikipedia.org/wiki/Hereditary_elliptocytosis
University of Virginia: School of Medicine - http://www.med-ed.virginia.edu/courses/path/innes/rcd/membrane.cfm
eHow: Prevention of Hereditary Diseases - http://www.ehow.com/way_5188179_prevention-hereditary-diseases.html
Farlex Free Dictionary - http://acronyms.thefreedictionary.com/Hereditary+pyropoikilocytosis
History of The Holocaust.org - http://www.zupdom.com/iconsmultimedia/ClientsArea/HoH/LIBARC/ARCHIVE/Chapters/Stabiliz/Racial/LawForPr.html
BMJ - http://www.bmj.com/content/314/7079/0.8.full
PubMed - http://www.ncbi.nlm.nih.gov/pubmed/12174674 ; http://www.ncbi.nlm.nih.gov/pubmed/21054813
PubMed Health - http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001597/
Check Orphan: Rare, Orphan, and Neglected Diseases http://checkorphan.getreelhealth.com/index.php/research/view/pyropoikilocytosis/page/1
Inside Surgery - http://insidesurgery.com/tag/pyropoikilocytosis/