GROUP CASE STUDYDr. Nancy McQueenMICR 410 - Hematology

Spring, 2011Case # 2

Ruby KhanWilson Liu

Baron Morano

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: 10.8 g/dL

Hct: 0.29 L/L

Platelets: 504 x 109 /L

• Erythrocyte indices:

MCV = 72. 5

MCHC = 37.2

MCH = 27

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

Key Diagnostic Information•Age

•Right upper-quadrant pain

•Hemolytic anemia

•Aplastic Anemis

•Poikilocytosis

•Increased Osmotic fragility

•Abnormal red cell thermal sensitivity

Peripheral Blood smear

• Elliptocytes• Spherocytes• Teardrop cells• Micro - Spherocytes

Our Diagnosis

• Patient suffers from… • Acronym = H.P.P.• HEREDITARY PYROPOIKILOCYTOSIS• Hewlett Packard Pavilion• Honda Power Port• Hawaiian Paradise Park

**Main Defect: Spectrin!!!

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

Pathophysiology of HPPIn 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 HPPKEY 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

Therapy & Prognosis of HPPTreatment – 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 HPPSince 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 1933Source : M. Burleigh & W. Wippermann, The Racial State. Germany, 1933-1945, (Cambridge, 1991), pp.136-138.

Gene Therapy

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

References

1. Textbook – Clinical Hematology and Fundamentals of Hemostasis (Fifth edition) Denise M. Harmening

2. Medscape Online Reference - http://emedicine.medscape.com/article/205843-overview

3. National Insitute of Health; Office of Rare Diseases Research - http://rarediseases.info.nih.gov/GARD/Disease.aspx?PageID=4&diseaseID=4619

4. Wikipedia: The Free Encyclopedia - http://en.wikipedia.org/wiki/Hereditary_elliptocytosis ; http://en.wikipedia.org/wiki/Pyropoikilocytosis

5. Med India: Medical Lab Tests - http://en.wikipedia.org/wiki/Hereditary_elliptocytosis

6. University of Virginia: School of Medicine - http://www.med-ed.virginia.edu/courses/path/innes/rcd/membrane.cfm

7. eHow: Prevention of Hereditary Diseases - http://www.ehow.com/way_5188179_prevention-hereditary-diseases.html

8. Farlex Free Dictionary - http://acronyms.thefreedictionary.com/Hereditary+pyropoikilocytosis

9. History of The Holocaust.org - http://www.zupdom.com/icons-multimedia/ClientsArea/HoH/LIBARC/ARCHIVE/Chapters/Stabiliz/Racial/LawForPr.html

10. BMJ - http://www.bmj.com/content/314/7079/0.8.full

11. PubMed - http://www.ncbi.nlm.nih.gov/pubmed/12174674 ; http://www.ncbi.nlm.nih.gov/pubmed/21054813

12. PubMed Health - http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001597/

13. Check Orphan: Rare, Orphan, and Neglected Diseases - http://checkorphan.getreelhealth.com/index.php/research/view/pyropoikilocytosis/page/1

14. Inside Surgery - http://insidesurgery.com/tag/pyropoikilocytosis/