Higher platelet counts are associated with migraine risk across three cohorts among more than 21,000 cases

Objective We assessed potential associations between migraine and complete blood cell count (CBC) data in three large population-based studies. Background Platelets are thought to be involved in migraine pathology through increased activation during an attack. Migraine attacks are often treated with NSAIDs that inhibit platelets, or triptans that target serotonin receptors, with serotonin being most highly expressed in circulation within platelet granules. However, the exact role of platelets in migraine remains unclear. Methods The UK BioBank (UKBB) has CBC data available from baseline blood samples and migraine diagnoses were obtained through self-report and electronic health records. CBC and migraine data from the 1999-2000, 2001-2002, and 2003-2004 National Health and Nutrition Examination Survey (NHANES) study were obtained during single exam visits. CBCs were obtained from Framingham Heart Study (FHS) participants. Migraine history was assessed through clinical diagnostic impressions. The UKBB sample (18,919 cases (4,580 incident); 448,339 controls) was the primary discovery cohort for CBCs, with replication meta-analysis done in NHANES (1,887 cases; 7,242 controls) and FHS (395 cases (229 incident); 3,172 controls). Our primary model adjusted for age and sex, with secondary analysis adjusting for additional factors. Sex-stratified, sex-interaction and ancestry-stratified (UKBB only) analyses were also performed. Results Migraine was associated with platelet count (PLT) in the UKBB (OR=1.058, 95% CI [1.043,1.073], p=2.09E-14) and was replicated in the NHANES-FHS meta-analysis (OR=1.074, 95% CI [1.025,1.126], p=0.003). PLT also drove multiple significant signals of PLT-involved CBC ratios. While neutrophil counts and hemoglobin were associated with migraine in UKBB, these did not replicate in FHS-NHANES meta-analysis. Conclusion Higher platelet count is associated with an increased likelihood of migraine. Further studies with longitudinal assessments of CBCs and migraine attacks are needed to further understand the role of platelets in the onset of migraine attacks.