Although its cause is poorly understood, situs ambiguus has been linked to family history of malformations<ref>{{cite journal |author=Martínez-Frías ML |title=Heterotaxia as an outcome of maternal diabetes: an epidemiological study |journal=American Journal of Medical Genetics |volume=99 |issue=2 |pages=142–6 |date=March 2001 |pmid=11241474 |doi=10.1002/1096-8628(2000)9999:999<00::AID-AJMG1139>3.0.CO;2-Z |url=}}</ref><ref>{{cite journal |vauthors=Maeyama K, Kosaki R, Yoshihashi H, Casey B, Kosaki K |title=Mutation analysis of left-right axis determining genes in NOD and ICR, strains susceptible to maternal diabetes |journal=Teratology |volume=63 |issue=3 |pages=119–26 |date=March 2001 |pmid=11283968 |doi=10.1002/tera.1022 |url=}}</ref> and maternal [[cocaine]] use,<ref>{{cite journal |vauthors=Kuehl KS, Loffredo C |title=Risk factors for heart disease associated with abnormal sidedness |journal=Teratology |volume=66 |issue=5 |pages=242–8 |date=November 2002 |pmid=12397632 |doi=10.1002/tera.10099 |url=}}</ref> suggesting both genetic and environmental factors play a role.<ref>{{cite journal |vauthors=Kuehl KS, Loffredo CA |title=Population-based study of l-transposition of the great arteries: possible associations with environmental factors |journal=Birth Defects Research. Part A, Clinical and Molecular Teratology |volume=67 |issue=3 |pages=162–7 |date=March 2003 |pmid=12797457 |doi=10.1002/bdra.10015 |url=}}</ref> Several genes in the [[Transforming growth factor beta|TGF-beta pathway]], which controls left-right patterning of visceral organs across the body axis, have been indicated in sporadic and familial cases of atrial isomerism. Disrupted mitochondria function has also been recently linked to heterotaxy. <ref>{{cite journal |author=Burkhalter MD, Sridhar A, Sampaio P, Jacinto R, Burczyk MS, Donow C, Angenendt M, Competence Network for Congenital Heart Defects Investigators, Hempel M, Walther P, Pennekamp P, Omran H, Lopes SS, Ware SM, Philipp M |title= Imbalanced mitochondrial function provokes heterotaxy via aberrant ciliogenesis |journal= J Clin Invest |volume=129 |issue=7 |pages=2841-28552841–2855 |date=2019 |pmid=31094706 |pmc= 6597216 |doi= 10.1172/JCI98890|url=}}</ref>

[[Functional asplenia|Functionally asplenic]] patients have an elevated lifetime risk of [[sepsis]], as they have no functional [[spleen]] for fighting [[infection]]. For this reason, asplenic patients are under constant observation for any signs of [[fever]] or infection. In the case of infection, patients are placed on controlled [[Empiric therapy|empiric antibiotic therapy]] to avoid development of [[Antimicrobial resistance|antibiotic resistance]].<ref>{{Cite web|url = http://www.uptodate.com/contents/clinical-features-and-management-of-sepsis-in-the-asplenic-patient?source=see_link&sectionName=MANAGEMENT&anchor=H14#H14|title = Clinical features and management of sepsis in the asplenic patient.|date = December 11, 2014|accessdate = December 10, 2015|website = UpToDate|last = Pasternack|first = Mark S;|display-authors=etal}}</ref> This therapy battles infection by both [[Gram-positive bacteria|gram-positive]] and [[Gram-negative bacteria|gram-negative]] bacteria.