1. GROUP CASE STUDY Dr. Nancy McQueen MICR 410 - Hematology Spring, 2011
Ruby Khan
Wilson Liu
Baron Morano
TO DO!!! Incorporate Ruby’s slides…send Wilson the answers to the case study form, print out forms, re-arrange order of presentation, edit content, practice

2. Case Summary
12-year-old male with right upper-quadrant pain and history of hemolytic and aplastic crises.
Lab results:
WBC: 8.0 x 109/L
RBC: 4.0 x 1012 /L
Hgb: g/dL
Hct: L/L
Platelets: 504 x 109 /L
Erythrocyte indices:
MCV =
MCHC = 37.2
MCH = 27

3. Case Summary Based on the indices, the patient’s red blood cells are…
Microcytic - Normochromic
Osmotic fragility test:
patient control
Initial hemolysis 0.65% NaCl 0.45% NaCl
Complete hemolysis 0.40% NaCl 0.30% NaCl
Thermal Sensitivity Test: Erythrocytes fragmented at 46.0 Degrees Celcius

4. Key Diagnostic Information
Age
Right upper-quadrant pain
Hemolytic anemia
Aplastic Anemis
Poikilocytosis
Increased Osmotic fragility
Abnormal red cell thermal sensitivity
 Young!
 Gallbladder – Cholecystitis
 Premature RBC Death
 Reticulocytopenia

5. Peripheral Blood smear
Elliptocytes
Spherocytes
Teardrop cells
Micro - Spherocytes

6. Our Diagnosis Patient suffers from… Acronym = H.P.P.
HEREDITARY PYROPOIKILOCYTOSIS
Hewlett Packard Pavilion
Honda Power Port
Hawaiian Paradise Park
**Main Defect: Spectrin!!!

7. Pathophysiology of HPP
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

8. Hemolysis can lead to rapid sequestration
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.

9. Testing for HPP KEY TESTS Peripheral Blood Smear RBC Indices
Osmotic Fragility
Thermal Sensitivity
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

10. 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

11. 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

12. 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, , (Cambridge, 1991), pp
Gene Therapy

13. Take Home Message 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

14. References
Textbook – Clinical Hematology and Fundamentals of Hemostasis (Fifth edition) Denise M. Harmening
Medscape Online Reference -
National Insitute of Health; Office of Rare Diseases Research -
Wikipedia: The Free Encyclopedia - ;
Med India: Medical Lab Tests -
University of Virginia: School of Medicine -
eHow: Prevention of Hereditary Diseases -
Farlex Free Dictionary -
History of The Holocaust.org -
BMJ -
PubMed - ;
PubMed Health -
Check Orphan: Rare, Orphan, and Neglected Diseases -
Inside Surgery -