https://imcjms.com Ibrahim Medical College Journal of Medical Science https://imcjms.com/registration/journal_full_text/541 Sun, 07 Jul 2024 11:01:42 +0000 Abstract Background and objectives: Asymptomatic thrombocytopenia, characterized by a reduced platelet count without bleeding symptoms, is notably prevalent in certain regions of India and Bangladesh, presenting a diagnostic challenge. A significant portion of healthy blood donors from Bangladesh and various parts of India, particularly West Bengal, exhibit this condition, termed Harris platelet syndrome (HPS). This review explores the potential correlation between mustard oil consumption, a common dietary staple in these regions, and the incidence of HPS. Methods: A comprehensive narrative review was conducted using systematic search strategies across databases such as Google Scholar, MEDLINE, PubMed, and Scopus. Keywords included "Harris platelet syndrome," "mustard oil consumption," "thrombocytopenia," and "erucic acid." Studies were selected based on relevance and quality, focusing on the epidemiology of HPS, dietary habits, and the thrombocytopenic effects of erucic acid. Results: HPS shows a significant geographical prevalence in the Indian subcontinent, notably in regions like West Bengal, Kashmir, and Assam. The review identifies a higher prevalence of thrombocytopenia in areas with predominant mustard oil usage. Studies highlight the association between dietary erucic acid from mustard oil and thrombocytopenia, with notable effects observed in patients treated with Lorenzo’s Oil, which contains erucic acid. Conclusions: The review highlights a significant association between mustard oil consumption and asymptomatic thrombocytopenia in the Indian subcontinent. The similarity in hematological profiles between HPS and erucic acid-induced thrombocytopenia underscores the need for further research. This includes measuring erucic acid levels in patients, conducting controlled dietary interventions, and genetic analyses to differentiate between genetic and environmental factors. July 2024; Vol. 18(2):009. DOI:https://doi.org/10.55010/imcjms.18.021 *Correspondence: Wasim Md MohosinUl Haque, Department of Nephrology, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), 122 Kazi Nazrul Islam Avenue, Dhaka-1000, Bangladesh. Email: wmmhaque@live.com   Introduction Asymptomatic thrombocytopenia, characterized by a reduced platelet count without bleeding symptoms, is prevalent in certain regions of India and Bangladesh. This poses a diagnostic challenge for clinicians encountering patients with unexplained low platelet counts during routine checkups. Although comprehensive epidemiological data for Bangladesh are sparse, a pivotal study conducted at Christian Medical College revealed that 8.5% of healthy blood donors from Bangladesh exhibited asymptomatic thrombocytopenia, which was arbitrarily diagnosed as Harris platelet syndrome (HPS) [1]. HPS, originally termed asymptomatic constitutional macrothrombocytopaenia (ACMT), was first identified in blood donors from West Bengal​​ [2]. It was later renamed Harris platelet syndrome (HPS) to avoid confusion with congenital amegakaryocytic thrombocytopenia [1]. HPS is defined by the presence of thrombocytopenia and giant platelets without bleeding symptoms or MYH9 mutations. The disorder appears to be inherited in an autosomal dominant manner, although the specific genes responsible for HPS remain unidentified​​ [1]. The geographic prevalence of HPS in the Indian subcontinent, particularly in regions such as West Bengal, Kashmir, and Assam, suggests a regional pattern influenced by genetic and environmental factors. One intriguing hypothesis is the potential link between dietary habits, specifically mustard oil consumption, and the prevalence of thrombocytopenia [3]. Mustard oil, rich in erucic acid, is a staple in many parts of Northern and Eastern India and neighbouring countries​​ [4]. The potential thrombocytopenic effects of erucic acid, evidenced in conditions like adrenoleukodystrophy (ALD) treated with Lorenzo's Oil, further underscore the need to investigate this association [5-7]. This review aims to explore the epidemiology of HPS in the Indian subcontinent, its potential correlation with mustard oil consumption, and the underlying pathophysiology of erucic acid-induced thrombocytopenia.   Materials and methods This narrative review synthesizes insights from a comprehensive examination of scientific journals and authoritative sources, focusing on the epidemiology of HPS in the Indian subcontinent, its associations with mustard oil consumption, and the underlying pathophysiology of mustard oil-induced thrombocytopenia. To gather relevant data, a systematic search strategy was employed using keywords such as "constitutional asymptomatic macrothrombocytopenia," "Harris platelet syndrome," "mustard oil consumption," "epidemiology," "Indian subcontinent," and "erucic acid." Various databases, including Google Scholar, MEDLINE, PubMed, and Scopus, were utilized, with no restrictions on the search scope. Exclusion criteria were applied to non-English articles. Researcher independently conducted article searches and evaluated the quality of each study. The inclusion of studies in the review was based on a thorough examination of the full text, ensuring the relevance and reliability of the data presented.   Results Regional prevalence and characteristics HPS exhibits a distinct geographic distribution, with significant prevalence in the Indian subcontinent, particularly in northern and eastern regions such as Kashmir, West Bengal, and Assam, with potential extensions to Bangladesh, Nepal, and Bhutan (Figure-1, Table-1). A study at Christian Medical College, Vellore, screened 10,200 blood donors and found that prevalence rates are highest in Eastern India (35%), followed by Northern India (18%), Western India (8.5%), Southern India (4.5%), and neighbouring countries (8.5%) [1].     Figure-1: The geographic distribution of HPS. The dotted area indicates distribution of HPS cases [1].  Table-1:Geographical distribution of Harris platelet syndrome [1]     Summary of studies on macrothrombocytopenia in different regions of India is presented in Table-2. Key findings indicate significant regional variations in the prevalence of macrothrombocytopenia, with higher rates among people of north and eastern regions compared to other areas. Diagnostic advancements, such as the use of automated complete blood count (CBC) data and platelet histograms have been proven effective in identifying this condition. Genetic studies highlight the heterogeneity of macrothrombocytopenia. Clinical characteristics often include lower platelet counts and increased mean platelet volume, with no significant bleeding symptoms in most cases.   Table-2: Summary of studies on macrothrombocytopenia in different regions of India     Thrombocytopenia and mustard oil consumption The geographical distribution of HPS closely aligns with regions in the Indian subcontinent where mustard oil is commonly used as the primary cooking oil [1,4]. In contrast, regions where mustard oil is less popular, such as the southern and western parts of India, exhibit lower instances of thrombocytopenia. A study conducted in southern India highlights this disparity, revealing a significant difference in the prevalence of thrombocytopenia between immigrants from northern and north-eastern India (4.3%) and the local southern Indian population (0.66%) [8]. Similarly, asymptomatic thrombocytopenia is relatively uncommon in western India, with a study in Surat reporting its prevalence of only 1.95% among healthy college students [14]. These observations suggest a potential correlation between dietary habits, specifically mustard oil consumption, and thrombocytopenia prevalence. A case-control study in the Bangladeshi population found a significant link between mustard oil use and thrombocytopenia, with 83.3% of thrombocytopenia cases reporting mustard oil consumption compared to 28.3% of controls [3].   Erucic acid: the main contributor to mustard oil-associated thrombocytopenia Mustard oil, commonly used in Eastern and Northern India, contains high levels of erucic acid. Commercial varieties have 41.8% erucic acid, while traditional Ghani mustard oil contains about 51.98% [18]. Erucic acid, a monounsaturated omega-9 fatty acid also found in rapeseed oil, has been linked to thrombocytopenia in animal studies and in patients treated with Lorenzo's oil, a therapeutic agent containing 20% erucic acid [5-7,19]. Several studies have explored the impact of erucic acid on platelet count and morphology. A study on 46 ALD patients treated with Lorenzo's Oil observed significant thrombocytopenia in 19 patients, with platelet counts inversely correlated with erucic acid levels and platelet size. Thrombocytopenia resolved within 2 to 3 months after discontinuing erucic acid [6]. Another study reported decreased platelet counts in five patients with X-linked ALD upon erucic acid administration, with marked thrombocytopenia in three patients. Thrombocytopenia was fully reversible after discontinuing erucic acid [5]. A study by Johns Hopkins University found a significant decrease in mean platelet count over six months in ALD patients treated with Lorenzo's Oil, with alterations in platelet size and structure but no consistent abnormalities in platelet function tests [7]. Historical data also support the thrombocytopenic effects of erucic acid, as seen with rapeseed oil [20]. Additionally, a case report of a 73-year-old man with ALD who developed thrombocytopenia after using mustard oil further supports this association [21]. Key findings of the studies on the haematological effects of erucic acid in ALD patients are summarize in Table-3.   Table-3: Key Findings of the studies on the haematological effects of Lorenzo's Oil/erucic acid in ALD patients     Discussion The findings from this review highlight a significant geographical overlap between the prevalence of HPS and regions with high mustard oil consumption. The shared hematological profile between HPS and erucic acid-related thrombocytopenia, including thrombocytopenia with giant platelets and normal platelet function tests, suggests potential common underlying mechanisms. Despite significant reductions in platelet counts, the absence of bleeding symptoms indicates intact platelet functionality, a crucial clinical observation. The stable, non-progressive nature of HPS and the reversibility of erucic acid-related thrombocytopenia upon discontinuation of erucic acid intake highlight the potential influence of environmental factors, particularly dietary habits, in its aetiology. The exclusion of MYH9 mutations and other systemic issues reinforces the hypothesis of a dietary link with the condition. Given the high prevalence of mustard oil use in regions with notable HPS cases, dietary erucic acid could be a significant environmental contributor to thrombocytopenia. This correlation calls for more focused research to distinguish between the genetic basis of HPS and the environmental impacts of mustard oil consumption. Studies involving direct measurement of erucic acid levels in patients with HPS, alongside controlled dietary interventions and genetic analyses, are essential to elucidate the precise relationship between mustard oil and thrombocytopenia. Further research should explore the potential health implications for populations with high dietary intake of erucic acid. Understanding these correlations could lead to better management and prevention strategies for thrombocytopenia cases in affected regions. In conclusion, this review highlights the significant association between mustard oil consumption and asymptomatic thrombocytopenia in the Indian subcontinent. By drawing attention to the similarities between HPS and erucic acid-related thrombocytopenia, it provides a compelling case for further investigation into dietary influences on platelet biology. Enhanced understanding of these relationships could lead to improved diagnostic, therapeutic, and preventive strategies, ultimately benefiting the population at risk.   References 1.     Naina HVK, Nair SC, Harris S, Woodfield G, Rees MI. Harris syndrome - a geographic perspective. J Thromb Haemost. 2005; 3(11): 2581-2582. doi: 10.1111/j.1538-7836.2005.01601.x 2.     Naina HV, Nair SC, Daniel D, George B, Chandy M. Asymptomatic constitutional macrothrombocytopenia among West Bengal blood donors. Am J Med. 2002; 112(9):742-743. doi: 10.1016/s0002-9343(02)01114-2. 3.     Haque WMMUH, Alam M, Ahmed AS, Mahmud A. Association between mustard oil consumption and thrombocytopenia: a case-control study in Bangladesh. IMC J Med Sci. 2024; 18(2). doi: 10.55010/imcjms.18.017. 4.     Yadav P, Alivelu K, Kumar GDS, Sujatah M. Survey of per capita consumption of vegetable oil in India. Curr Sci. 2022; 123(9): 1159-1164.doi: 10.18520/cs/v123/i9/1159-1164 5.     Zierz S, Schröder R, Unkrig CJ. Thrombocytopenia induced by erucic acid therapy in patients with X-linked adrenoleukodystrophy. Clin Investig. 1993; 71(10): 802-805. doi: 10.1007/bf00190322. 6.     Zinkham WH, Kickler T, Borel J, Moser HW. Lorenzo’s oil and thrombocytopenia in patients with adrenoleukodystrophy. N Engl J Med. 1993; 328(15): 1126-1127. doi: 10.1056/NEJM199304153281513. 7.     Kickler TS, Zinkham WH, Moser A, Shankroff J, Borel J, Moser H. Effect of erucic acid on platelets in patients with adrenoleukodystrophy. Biochem Mol Med. 1996; 57(2): 125-133. doi: 10.1006/bmme.1996.0018. 8.     Edupuganti HS, Krishnamurthy V. Prevalence of constitutional macrothrombocytopenia in the immigrants of Northern and Eastern states of India. Indian J Pathol Microbiol. 2020; 63(4): 593-596. doi: 10.4103/IJPM.IJPM_20_20. 9.     Bhola A, Garg R, Sharma A, Gupta N, Kakkar N. Macrothrombocytopenia: Role of automated platelet data in diagnosis. Indian J Hematol Blood Transfus. 2023; 39(2): 284-293. doi: 10.1007/s12288-022-01590-6. 10.  Ali S, Ghosh K, Daly ME, Hampshire DJ, Makris M, Ghosh M, et al. Congenital macrothrombocytopenia is a heterogeneous disorder in India. Haemophilia. 2016; 22(4): 570-582. doi:10.1111/hae.12917. 11.  Naina HVK, Harris S. Platelet and red blood cell indices in Harris platelet syndrome. Platelets. 2010; 21(4): 303-306. doi: 10.3109/09537101003615402. 12.  Naina HVK, Nair SC, Daniel D, George B, Chandy M. Asymptomatic constitutional macrothrombocytopenia among West Bengal blood donors. Am J Med. 2002; 112(9): 742-743. doi: 10.1016/s0002-9343(02)01114-2. 13.  Kakkar N, John MJ, Mathew A. Macrothrombocytopenia in north India: role of automated platelet data in the detection of an under diagnosed entity. Indian J Hematol Blood Transfus. 2015; 31(1): 61-67. doi: 10.1007/s12288-014-0367-3. 14.  Patel P, Shah A, Mishra K, Ghosh K. Prevalence of macrothrombocytopenia in healthy college students in western India. Indian J Hematol Blood Transfus. 2019; 35(1): 144-148. doi: 10.1007/s12288-018-0970-9. 15.  Ali S, Ghosh K, Shetty S. Differential expression of genes involved in Bengal macrothrombocytopenia (BMTCP). Blood Cells Mol Dis. 2015; 55(4): 410-414. doi: 10.1016/j.bcmd.2015.09.005. 16.  Lorenzo FR, Tashi T, Koul P, Camp NJ, Thiagarajan P, Prchal JT. Inherited giant platelet disorder, Kashmiri thrombocytopenia, a common syndrome found in Srinagar, India. Blood. 2014; 124(21): 4211-4211. doi: 10.1182/blood.v124.21.4211.4211. 17.  Sultan N, Sharma SK. Prevalence of low platelet count and identification of associating determinants and genetic polymorphism in healthy individuals of upper Assam, India. Indian J Hematol Blood Transfus. 2019; 35(2): 332-338. doi: 10.1007/s12288-018-1007-0. 18.  Sarwar MT, Rahman MH, Raza MS, Rouf S, Rahman MN. Determination of erucic acid content in traditional and commercial mustard oils of Bangladesh by gas-liquid chromatography. Advances in Biochemistry. 2014; 2(1): 9-13. 19.  Kramer JKG, Sauer FD, Farnworth ER, Stevenson D, Rock GA. Hematological and lipid changes in newborn piglets fed milk‐replacer diets containing erucic acid. Lipids. 1998; 33(1): 1-10. doi: 10.1007/s11745-998-0174-1. 20.  Kramer JKG, Sauer FD, Pigden WJ. High and Low Erucic Acid Rapeseed Oils : Production, Usage, Chemistry, and Toxicological Evaluation. New York: Academic Press, 1983. 21.  Shin DS, Perlman S, Rosove MH. Romiplostim mitigates dose-limiting thrombocytopenia of erucic acid for adrenomyeloneuropathy. Br J Haematol. 2015; 171(5): 879-881. doi: 10.1111/bjh.13440. 22.  Aubourg P, Adamsbaum C, Lavallard-Rousseau MC, Rocchiccioli F, Cartier N, Jambaqué I, et al. A two-year trial of oleic and erucic acids (‘Lorenzo’s oil’) as treatment for adrenomyeloneuropathy. N Engl J Med. 1993; 329(11): 745-752. doi: 10.1056/NEJM199309093291101. 23.  Konijnenberg A, van Geel BM, Sturk A, Schaap MC, von dem Borne AE, de Bruijne-Admiraal LG, et al. Lorenzo’s oil and platelet activation in adrenomyeloneuropathy and asymptomatic X-linked adrenoleukodystrophy. Platelets. 1998; 9(1): 41-48. doi: 10.1080/09537109876997. 24.  van Geel BM, Assies J, Haverkort EB, Koelman JH, Verbeeten B, Jr., Wanders RJ, et al. Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with ‘Lorenzo’s oil’. J Neurol Neurosurg Psychiatry. 1999; 67(3): 290-299. doi: 10.1136/jnnp.67.3.290. 25.  Chai BC, Siminoski K. Thrombocytopenia associated with use of Lorenzo’s oil. Am J Hematol. 1993; 44(4): 290-291. doi: 10.1002/ajh.2830440417. 26.  Crowther MA, Barr RD, Kelton J, Whelan D, Greenwald M. Profound thrombocytopenia complicating dietary erucic acid therapy for adrenoleukodystrophy. Am J Hematol. 1995; 48(2): 132-133. doi: 10.1002/ajh.2830480217.       Cite this article as: Haque WMM. Mustard oil consumption and Harris platelet syndrome: unveiling a dietary link to thrombocytopenia in the Indian subcontinent. IMC J Med Sci. 2024; 18(2):009. DOI:https://doi.org/10.55010/imcjms.18.021 2026 Ibrahim Medical College. All rights reserved.