ABO Blood Groups Keep Emerging as a Cross-Disease Risk Marker
The ABO blood group system continues to sit at the intersection of transfusion medicine, vascular biology, oncology, and host defense. In this narrative review, ABO blood groups were examined as a potential marker of susceptibility and prognosis across cardiovascular disease, cancers, diabetes, malaria, COVID-19, and rheumatic diseases. The pattern that runs through these conditions is not a single disease-specific signal, but a recurring biological theme: blood group antigens appear to influence coagulation, endothelial behavior, immune recognition, and inflammatory signaling in ways that can alter clinical risk.
Non-O blood groups repeatedly carried higher risk across several disease categories.
Thrombosis and Vascular Risk Track Most Consistently With Non-O Blood Types
The clearest and most reproducible association in the review concerned cardiovascular disease, especially venous thromboembolism. Across epidemiological studies, non-O blood groups were linked to substantially higher vascular risk, with venous thromboembolism risk roughly two to four times higher than in type O. In practice, this finding aligns with long-recognized differences in hemostasis between blood groups, since ABO status is tied to circulating levels and glycosylation patterns of von Willebrand factor and factor VIII. Higher levels of these prothrombotic proteins can plausibly support clot formation, which helps explain why the association persists across observational cohorts.
The cardiovascular signal is important because it extends beyond an isolated laboratory curiosity. A blood group phenotype is fixed from birth, so any relationship with vascular events suggests an inherited biological substrate rather than a modifiable exposure. Even so, these data do not support using ABO status alone to make treatment decisions. The more realistic near-term role is as one piece of a broader risk profile, especially in settings where thrombosis prevention is already being considered.
Cancer Associations Appear Real, but They Vary by Tumor Type
ABO status also appeared to influence cancer susceptibility and prognosis, although the direction and magnitude of association differed across malignancies. Among the clearest examples in the review, type A was associated with increased gastric cancer risk, with a pooled odds ratio of about 1.2. This is a modest effect size rather than a dramatic one, but modest effects can still matter when they are biologically consistent and replicated across large cohorts. In cancer biology, blood group antigens may affect cell adhesion, membrane signaling, inflammatory tone, and interactions with host immunity. Those pathways are relevant to tumor initiation and spread, particularly in tissues where chronic inflammation and epithelial injury are already part of the carcinogenic process.
The review does not support a single uniform cancer rule for ABO. Instead, it suggests tumor-specific relationships that likely reflect a mix of host genetics, tissue environment, and population structure. Gastric cancer has been the most repeatedly discussed example, yet other cancers show different directions or weaker effects. The practical consequence is restraint: ABO typing may contribute to etiologic research, but it is not ready to function as a stand-alone cancer screening tool.
Infection Biology Explains the Malaria and COVID-19 Signals
In infectious disease, the review identified two particularly visible patterns. Type O individuals showed relative resistance to severe malaria caused by Plasmodium falciparum, a finding that fits long-standing work on rosetting, parasite binding, and microvascular obstruction. Severe malaria depends in part on the ability of infected erythrocytes to adhere and cluster within the microcirculation. ABO-linked differences in red cell surface antigens may alter those adhesive interactions, reducing the efficiency of sequestration in type O blood.
COVID-19 data were more heterogeneous, but the same general theme emerged: type A was associated with higher susceptibility and severity in several studies, while type O appeared mildly protective. The heterogeneity matters because it signals that host genetics did not act in isolation. Viral variants, vaccination status, prior infection, and differences in population structure likely all shaped the observed associations. Even with that variability, the mechanism remains biologically plausible. ABO antigens can influence endothelial interaction, inflammatory activation, and possibly the balance between coagulation and fibrinolysis, all of which are relevant in COVID-19, where thrombosis and systemic inflammation played a major role in severe outcomes.
Autoimmunity and Inflammation May Help Explain Rheumatic Disease Links
Rheumatic diseases were less uniformly studied, but the review identified ABO polymorphisms as possible modifiers of risk and phenotype in conditions such as systemic lupus erythematosus and rheumatoid arthritis. In this setting, the biologic logic is less about clotting and more about immune regulation. Blood group antigens are glycosylated structures, and glycosylation can shape how immune cells communicate, how antigens are recognized, and how inflammatory pathways are sustained. If ABO variation shifts those processes, it could influence who develops autoimmune disease and how aggressively it behaves.
The available evidence remains preliminary. Unlike the cardiovascular literature, where the thrombotic signal is relatively coherent, rheumatic disease associations are more fragmented and likely influenced by ethnicity, study design, and disease heterogeneity. Even so, the review places ABO biology within a broader framework of immune-mediated disease, which is clinically relevant given the central role of inflammation in rheumatology.
Diabetes and the Limits of Observational Genetic Associations
Diabetes was included among the disease categories assessed, but the review’s overall message was one of association rather than proof. ABO may modulate metabolic risk through inflammation, vascular dysfunction, or correlated genetic pathways, yet the evidence base is not strong enough to define a causal relationship from the review alone. The same caution applies across the full set of conditions examined. Observational studies can identify patterns, but they cannot fully separate a blood group effect from population structure, comorbidity, residual confounding, or publication bias.
This is the central limitation of the field. ABO status is biologically interesting and clinically familiar, but familiar does not mean actionable. The review makes a reasonable case for considering ABO as a candidate biomarker, not a clinical decision tool.
Multi-Ethnic Prospective Studies Will Be Needed Before ABO Can Guide Care
The review’s conclusion is measured and appropriate. ABO blood group status appears associated with susceptibility and outcomes across a wide range of diseases, but the findings remain hypothesis-generating. Large, multi-ethnic prospective studies will be needed to determine whether these associations persist after adjustment for confounding and whether they can be translated into risk stratification models. Future work will also need to clarify mechanism: whether the signal is driven mainly by coagulation biology, endothelial function, microbial binding, inflammatory regulation, or a combination of all four.
For now, ABO remains a useful biological clue rather than a bedside algorithm. The strongest evidence sits in thrombosis, while the cancer, infection, and rheumatic disease signals are more variable and context-dependent. The review makes clear that a blood group can be more than a transfusion label, but it does not justify treating ABO status as a deterministic forecast of disease.