acanthocytes_causes_etiology_clinical sognificance-future.pptx

Acanthocytes

1. Acanthocytosis Dr. E. Muralinath, Dr. C. Kalyan, Dr. K. Sravan Pragna & Dr. Bharat

2. Introduction The membrane of red blood cells (RBCs) can undergo a variety of changes resulting in morphologic alterations in these cells. When viewed under a freshly prepared peripheral blood smear (PBS), acanthocytes look like cells with a few spicules of different sizes, projecting from the surface of the RBC membrane at irregular intervals. They lead to alterations in membrane lipids and proteins and happen in patients with severe liver dysfunction, neuroacanthocytosis, abetalipoproteinemia, malnutrition, hypothyroidism, post-splenectomy, etc. The clinical significance of acanthocytes is related to their vulnerability to splenic trapping and destruction because of their morphology, which ultimately results in anemia. When remodeled by the spleen in liver disease patients, acanthocytes develop more blunt spicules and become relatively more spherocytic; these are termed as spheroacanthocytes or ‘spur cells.’

3. Issues of Concern It is important to differentiate acanthocytes from echinocytes, which have smaller and more uniform projections and observed in patients with end-stage renal disease, liver disease, pyruvate kinase deficiency, etc. The spiculated appearance of RBCs can also lead to an ethylene diamine tetra-acetic acid (EDTA) artifact after a delay of more than 6 hours between storage and smear preparation. Th at is why , for accuracy, it is critical to ensure that the peripheral blood smear is fresh when read. Spiculated RBCs from EDTA artifact exhibit more uniformly distributed spicules and influence almost all of the RBCs in the film. 4)Besides , the detection of spiculated red blood cells and hemolysis during the neonatal period shall result in the possibility of a hereditary disorder namely infantile pyknocytosis berfore considering an acquired causes of acanthocytosis.

4. Causes Common causes of acanthocytosis are listed here Severe liver dysfunction , Abetalipoproteinemia , McLeod syndrome and chorea-acanthocytosis syndrome , Post-splenectomy Hypothyroidism Myelodysplastic syndromes , Anorexia nervosa Medications

5. Clinicopathologic Correlations For maintenance of fluidity of RBC morphology, membrane fluidity plays an important role . This fluidity is, in turn, regulated by proportions of cholesterol, structural proteins, and phospholipids in the RBC membrane. Diseases namely abetalipoproteinemia, severe liver dysfunction, etc. and neuroacanthocytosis, etc. Influence the cholesterol and protein content of the RBC membrane, respectively. Subsequently, the RBC membrane fluidity shows alterations and the cells undergo morphologic changes resultinhg in the formation of acanthocytes or spur cells. These structural modifications make them susceptible to splenic trapping and destruction, ultimately leading to hemolytic anemia. Besides , there has been a different hypothesis suggesting that a component of the RBC membrane skeleton, band 3 plays an important role regarding acanthocyte formation.

6. Clinical Significance Clinical conditions associated with acanthocytosis: Severe liver dysfunction: Spur cell anemia (SCA) is a poorly studied clinical entity particularly in liver disease, and its clinical importance remains as yet undefined. It gets diagnosed with the following: Hb is less than10 mg/dl, hemolysis, over 5% spur cells on PBS, and the exclusion of other causes of anemia. Seen in severe liver disease patients regardless of the etiology, it is known to portend an unfavorable prognosis as a majority of patients die within months of diagnosis. SCA is characteristically not amenable to treatment particularly with blood transfusion, as transfused cells tend to undergo morphological alterations as well . It is important to note that SCA is readily reversible particularly after liver transplantation (LT). Although with limited success, there have been reports that have suggested various other modalities of treatment for SCA, namely plasmapheresis, transjugular intrahepatic portosystemic shunt, etc. These treatments may be helpful in patients awaiting LT or in those who are poor candidates for LT.

7. Abetalipoproteinemia: Also termed as Basseg-Kornzweig Syndrome, abetalipoproteinemia is a disease that presents in infants with failure to thrive, diarrhea, vomiting, and fat malabsorption. Acanthocytes are visible on PBS in a characteristical manner with associated hemolytic anemia, reticulocytosis, and raised bilirubin levels. Malabsorption of fat-soluble vitamins such as Vit A, D, E, and K leads to the majority of the clinical manifestations. Vit K deficiency may lead to a raised international normalized ratio in these patients and an increased risk of bleeding. Untreated individuals also possess a risk of development of progressive loss of night or color vision. Neuromuscular symptoms (Vit E deficiency) namely ataxia, muscle weakness, dysarthria, etc. usually manifest during the first or second decades of life. Although no formal clinical criteria exist, absent or extremely low LDL cholesterol, triglycerides, and apolipoprotein B levels are required to establish a diagnosis of abetalipoproteinemia. Molecular genetic testing may be beeded to identify and confirm mutations in the MTTP gene in these individuals. Appropriate intake of calories along with low-fat diet and supplementation of vitamins A, D, E, and K are required to treat manifestations of the disease. Long-term follow-up to monitor growth and potential complications are required . 10) Identification of genetic variants in genes namely MTTP may help guide the evaluation of relatives at risk and offer genetic counseling to prospective parents.

8. Neuroacanthocytosis: Two main neuroacanthocytosis syndromes are known: Chorea-acanthocytosis- Autosomal recessive McLeod syndrome- X-linked inheritance Clinically, the common characteristics of these two neurodegenerative disorders are as follow s Chore a, Dystonia , Peripheral neuropathy , Myopathy , Seizures and Psychiatric symptoms Hematologically, acanthocytosis is observed on PBS in these patients. The belief is that genetic mutations result in the absence of proteins namely XK protein in McLeod syndrome, which results in acanthocytosis and hemolytic anemia following splenic remodeling. Males with McLeod syndrome are more likely to exhibit acanthocytosis and hemolytic anemia compare to females. Enhanced degradation and phosphorylation of membrane proteins along with enhanced RBC sphingomyelin have implications in the causation of acanthocytosis in chorea-acanthocytosis patients. Overall, hemolytic anemia associated with acanthocytosis in neuroacanthocytosis syndromes is mild but may, on occasion, warrant blood transfusion. In patients, autologous blood transfusions may be required to inhibit immune-mediated blood transfusion reactions.

9. Others: Other clinical conditions associated with acanthocytosis are listed below- Post-splenectomy: Splenectomy results in several morphologic changes in RBCs, along with acanthocytosis. Hypothyroidism Mild acanthocytosis may present in about 20% of patients along with hypothyroidism. Thyroid function tests should merit consideration in patients with acanthocytosis particularly after the exclusion of all other causes. Hematologic abnormalities: Acanthocytosis may also lead to patients with myelodysplasia and some forms of hereditary spherocytosis. A proportion of patients with myelodysplasia may be referred to a hematologist along with acanthocytosis as the presenting finding. Anorexia nervosa: Some patients may also exhibit acanthocytosis along with anorexia nervosa. This condition may be because of changes in RBC membrane lipids or proteins and is reversible with treatment of anorexia. Drug-associated: Statins are one of the commonly prescribed drugs that have been found to be associated with acanthocytosis. This reversible change may lead to the reduction in serum lipids occurred by statins. Another drug that has implications in acanthocytosis is misoprostol.

10. Conclusions/Learning points: 1) Acanthocytes look like cells along with a few spicules of different sizes, projecting from the surface of the RBC membrane at irregular intervals. 2) They result from alterations in membrane lipids and proteins and happen in patients with severe liver dysfunction, neuroacanthocytosis, abetalipoproteinemia, hypothyroidism, post-splenectomy, etc. 3) The clinical significance of acanthocytes is related to their vulnerability to splenic trapping and destruction becvause of their morphology, which ultimately results in hemolytic anemia. For an accurate diagnosis of acanthocytes, it is essential to ensure that the peripheral blood smear is fresh when read.

11. References 1. Pacheco JM, Yilmaz M, Rice L. How low is too low: Statin induced hemolysis. Am J Hematol. 2016 Feb;91(2):267. [ PubMed ] 2. Privitera G, Meli G. An unusual cause of anemia in cirrhosis: spur cell anemia, a case report with review of literature. Gastroenterol Hepatol Bed Bench. 2016 Fall;9(4):335-339. [ PMC free article ] [ PubMed ] 3. Anoop P, Parker-Williams J. Morphological diagnosis of abetalipoproteinemia and the importance of a freshly prepared peripheral smear. Eur J Haematol. 2009 Dec 01;83(6):606. [ PubMed ] 4. El Nabouch M, Rakotoharinandrasana I, Ndayikeza A, Picard V, Kayemba-Kay's S. Infantile pyknocytosis, a rare cause of hemolytic anemia in newborns: report of two cases in twin girls and literature overview. Clin Case Rep. 2015 Jul;3(7):535-8. [ PMC free article ] [ PubMed ] 5. Wong P. A basis of the acanthocytosis in inherited and acquired disorders. Med Hypotheses. 2004;62(6):966-9. [ PubMed ] 6.

12. 6. Malik P, Bogetti D, Sileri P, Testa G, Blumenthal SA, Wiley TE, Layden TJ, Benedetti E. Spur cell anemia in alcoholic cirrhosis: cure by orthotopic liver transplantation and recurrence after liver graft failure. Int Surg. 2002 Oct-Dec;87(4):201-4. [ PubMed ] 7. Miki K, Maruki T, Imashuku S. Plasmapheresis for Spur Cell Anemia in a Patient with Alcoholic Liver Cirrhosis. Case Rep Hematol. 2018;2018:9513946. [ PMC free article ] [ PubMed ] 8. Chitale AA, Sterling RK, Post AB, Silver BJ, Mulligan DC, Schulak JA. Resolution of spur cell anemia with liver transplantation: a case report and review of the literature. Transplantation. 1998 Apr 15;65(7):993-5. [ PubMed ] 9. Burnett JR, Hooper AJ, Hegele RA. Abetalipoproteinemia. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews ® [Internet]. University of Washington, Seattle; Seattle (WA): Oct 25, 2018. [ PubMed ] 10. Di Filippo M, Créhalet H, Samson-Bouma ME, Bonnet V, Aggerbeck LP, Rabès JP, Gottrand F, Luc G, Bozon D, Sassolas A. Molecular and functional analysis of two new MTTP gene mutations in an atypical case of abetalipoproteinemia. J Lipid Res. 2012 Mar;53(3):548-555. [ PMC free article ] [ PubMed ]