Introduction: Haptoglobin phenotype affects inflammation and may change rate of perihematoma edema formation (PHE) affecting outcomes. We reported better functional recovery in patients with intracranial hemorrhage (ICH) and the Haptoglobin 1-1 phenotype. This may be mediated through Haptoglobin 1-1 effects on PHE.
Hypothesis: The Haptoglobin 1-1 phenotype has a different rate of PHE compared to 2-1 and 2-2. Different PHE related to Haptoglobin phenotype affects clinical outcomes.
Methods: We determined Haptoglobin phenotype, ICH volume, and PHE in individuals identified prospectively from ICH cohorts, at Johns Hopkins University hospital (JHU) and the Massachusetts General Hospital (MGH) using established CT methodology. PHE were measured as differences in CT ICH edema volume divided by hours between scans. Associations of Haptoglobin phenotype (1-1 compared to 2-1, 2-2) and rate of PHE (cc/hr) using multivariate analysis adjusting for age, sex, race, diabetes (DM), hypertension (HTN), LDL cholesterol > 130 mm/dl (HDL), smoking, prior ICH, and use of antiplatelet or systemic anticoagulation were determined.
Results: 87 patients were included with the following characteristics: Mean age 61.6 (15), 44 (50%) females, 28 (32%) AA, 64 (74%) HTN, 17 (20%) HDL, 22 (25%) active smokers, 29 (33%) on some form of anticoagulation/antiplatelet and 9 (10%) with prior ICH. We included 57 JHU and 30 MGH participants with different baseline characteristics. There were 9 subjects with Haptoglobin genotype 1-1, 45 with 2-1 and 33 with 2-2, Mean PHE varied within each group. Fully adjusted estimated mean PHE for 1-1 haplotype was 1.84cc/hr (95%CI 0.87-2.28 cc/hr), which was significantly greater than Haplotype 2-1 at 0.29 cc/hr (-0.15-0.72 cc/hr) and Haplotype 2-2, at 0.44 cc/hr (-0.07-0.96 cc/hr).
Conclusion: In adjusted models, Haptoglobin 1-1 phenotype on average had a significantly increased rate of PHE in the early stages of ICH onset, opposite that predicted by our biological model. Our study suggests Haptoglobin haplotype is associated with PHE and may account for variability in disability and mortality in ICH. Our study is limited by insufficient power to determine haplotype effect on disability and mortality and larger prospective studies are warranted.