A 59-year-old male with spherocytosis, splenectomy and chest pain: Does he have an increased risk of thrombosis?

Kam Newman, Junaid Mansuri, Salim Shackour, Shahriar Dadkhah

Department of Medicine, St Francis Hospital, Evanston, IL
St Francis Hospital
Evanston

Learning Objectives Discussion

 Recognizing the increased risk of thrombosis in
patients with hereditary spherocytosis.
 Understanding the pathophysiology of thrombosis
in spherocytosis.
Case
 A 59-year-old Caucasian male was admitted due to left-
sided chest pain, which woke the patient up. It was not
pleuritic or accompanied with dyspnea or palpitations. Past
medical history included hereditary spherocytosis (post
splenectomy), hypertension and hyperlipidemia. The
patient’s brother had spherocytosis too and died due to
pulmonary embolism. The patient’s EKG showed evidence
of ischemia in the lateral wall. Cardiac enzymes were not
elevated. His CBC showed Hb 13.2 g/dL, MCV 88 fL, PLT
337 k/mm3 and WBC 17.8 k/mm3. The patient had coronary
angiography, which showed a 95% lesion in the mid
circumflex artery, a 40% lesion in the proximal LAD and a
40% lesion in the ostial diagonal. He had PTCA and stent
for the circumflex lesion. The course of hospitalization was
uneventful. Before being discharged, the patient asked the
medical team if he had an increased risk for blood clots.
Mechanism
Defects in vertical
stabilization* of the
phospholipid bilayer of
the RBC membrane
cause separation of the
spectrin-phospholipid
bilayer.
Portions of the
phospholipid bilayer
form vesicles and are
lost from the RBC
surface resulting in
decreased surface area
and spherocytosis.
 Hereditary spherocytosis (HS) is the most common of the
hereditary hemolytic anemias in Northern Europeans with an
incidence of 1 in 5000 (1,2). Humans with heritable hemolytic
anemias suffer from a number of pathologic complications
including vaso-occlusion, thrombosis, and stroke. Thrombotic
events affect about 20% to 30% of patients with sickle cell disease
and 5% to 10% of patients with β-thalassemia (3,4). Disease severity
in human HS is variable; most patients exhibit only mild to
moderate anemia, mild jaundice and splenomegaly. Erythrocytes
have a membrane defect that makes them more rigid, yet fragile
and prone to premature destruction. The resultant loss of lipid
asymmetry is associated with increased procoagulant activity.
Nevertheless, both venous and arterial thrombosis, including stroke,
have been documented in patients with HS (5-8). Mice with
deficiencies in erythroid α-spectrin have the highest incidences of
thrombosis and stroke (62%-100% of adult mice). HS mice with β-
spectrin and ankyrin mutations have the lowest incidence (15% to
22%) (9-11). Pathophysiologies that contribute to hemostatic
changes and could predispose to thrombosis include
hyperbilirubinemia, hemosiderosis, and the increasing demand for
erythroid cells since the neonate doubles in size daily. These
pathologies may be preceded or accompanied by changes in blood
viscosity, in serum levels of free iron and homocysteine, or in the
"stickiness" of aberrant RBCs. All could exacerbate damage to
the endothelial vasculature. Normal RBCs could reverse some of
the adverse hemostatic changes or provide a hemostatic response
missing in the untreated mutant mice (9,12,13).
 Splenectomy for HS increases the risk of stroke and myocardial
infarction. After splenectomy Hb rises to a higher concentration
than found in non-affected family members. In the Framingham
study, the incidence of stroke was 2 times higher in patients with
“high” Hb compared with “not high” Hb. Also, after splenectomy,
the average PLT count remains above the normal average and in
HS cholesterol concentrations rise after splenectomy (14).
Acknowledgements
The authors wish to thank Dr. Gery Luger (Chairman, Department of Medicine), Dr.
Margaret Yungbluth (Histopathologist), Sheryl Bloom (Administrative Director of Medical
Education, Kathie Kafa (Coordinator of Internal Medicine Residency Program) for their
support.
Spherocytes on peripheral blood smear.
Splenectomy in a patient with HS shows splenomegaly.
Conclusion
 Hereditary spherocytosis (HS) is the most common of the hereditary
hemolytic anemias in Northern Europeans with an incidence of 1 in 5000.
 Patients with HS have an increased risk of thrombosis.
 Splenectomy for HS increases the risk of stroke and myocardial infarction.
References
3. Morton NE, MacKinney AA, Kosower N. Genetics of spherocytosis. Am J Hum Genet. 1962; 14: 170-184.
4. Smedley JC, Bellingham AJ. Current problems in Hematology 2: Hereditary spherocytosis. J Clin Pathol.
1991; 44: 441-444.
5. Tse WT, Lux SE. Red blood cell membrane disorders. Br J Haematol. 1999; 104: 2-13.
6. Palek J. Hereditary elliptocytosis, spherocytosis and related disorders: consequences of a deficiency or a
mutation of membrane skeletal proteins. Blood Rev. 1987; 1: 147-168.
7. Tokunaga Y, Ohga S, Suita S, Matsushima T, Hara T. Moyamoya syndrome with spherocytosis: effect of
splenectomy on strokes. Pediatr Neurol. 2001; 25: 75-77.
8. Schilling RF. Spherocytosis, splenectomy, strokes, and heat attacks. Lancet. 1997; 350: 1677-1678.
9. Hayag-Barin JE, Smith RE, Tucker FC Jr. Hereditary spherocytosis, thrombocytosis, and chronic pulmonary
emboli: a case report and review of the literature. Am J Hematol. 1998; 57: 82-84.
10. Nikol S, Huehns TY, Kiefmann R, Hofling B. Excessive arterial thrombus in spherocytosis: a case report.
Angiology. 1997; 48: 743-748.
11. Wandersee NJ, Roesch AN, Hamblen NR, et al. Defective spectrin integrity and neonatal thrombosis in the first
mouse model for severe hereditary elliptocytosis. Blood. 2001; 97: 543-550.
12. Kaysser TM, Wandersee NJ, Bronson RT, Barker JE. Thrombosis and secondary hemochromatosis play major
roles in the pathogenesis of jaundiced and spherocytic mice, murine models for hereditary spherocytosis. Blood.
1997; 90:4610-4619
13. Wandersee NJ, Lee JC, Kaysser TM, Bronson RT, Barker JE. Hematopoietic cells from alpha-spectrin
deficient mice are sufficient to induce thrombotic events in hematopoietically ablated recipients. Blood. 1998;
92:4856-4863.
14. Andrews DA, Low PS. Role of red cells in thrombosis. Curr Opin Hematol. 1999; 6:76-82.
15. Hillery CA, Du MC, Montgomery RR, Scott JP. Increased adhesion of erythrocytes to components of the
extracellular matrix: isolation and characterization of a red blood cell lipid that binds thrombospondin and
laminin. Blood. 1996; 87:4879-4886.
16. Schilling RF. Spherocytosis, splenectomy, strokes, and heat attacks.
Lancet. 1997; 350: 1677-1678.