The initial electronic database search yielded 729 studies; 71 met our inclusion criteria, and 21 were eligible after the full-text screening. A total of 45 studies were excluded by full-text screening, according to the PRISMA flow chart (Fig. 1). A manual search yielded three additional studies. As a result, only 24 studies were included in our review. Additionally, a detailed illustration of the results of each database is provided in (Supplementary Table 3).

PRISMA flow diagram of included studies

Out of 24 included articles, 10 received good scores, 11 got fair and 3 self-controlled case series (SCCS) received no quality assessment. The score of each article is shown in Supplementary Tables (4, 5, 6, 7 and 8). We have included 1 RCT study with a good score. Out of 11 case report studies, 4 received a good score, and 7 received a fair score. Two Cohorts and 2 case controls received a good score. Of 5 cross sectional studies, 1 received a good score and other 4 got a fair score.

Eleven case series that comprised 13 patients were identified and described [10,11,12,13,14,15,16,17,18,19,20]. The mean age was 52.9 years (3–88), and 53.8% of patients were male. The most prevalent geographic location where thrombocytopenia was reported following influenza vaccination was Japan (6, 46%). Several patients presented with chronic diseases prior to receiving the influenza vaccine, including hypertension (2, 15%), primary biliary cirrhosis (1, 8%), and hepatitis C (1, 8%).

All patients had received an influenza vaccination; however, only 4 case series reported the name of the vaccine. Of these 4, 2 received Vaxigrip, and 1 received Fluarix, and 1 patient received Kitaken. Only 2 patients were co-administered with the influenza vaccination and other vaccines, including DTP/Polio/Hib, Hepatitis B, and pneumococcal conjugate vaccine. The ITP occurred following 1 dose of the influenza vaccine in 3 patients (23%), following three doses in 2 patients (15%), and following 2 doses in 1 patient (8%). The remaining 7 case reports did not present data on how many vaccine doses the patients received when ITP occurred (Table 1).

All patients identified and included in this SR presented with ITP, diagnosed after examining their platelet count. Table 2 describes the platelet count before and after vaccination for each patient, with a substantial decrease being observed in all patients. The period between vaccination and the occurrence of ITP differed greatly between patients, ranging between 2 and 35 days. The mean duration was 13.5 days. Bone marrow biopsy findings were described in 8 cases, with hypercellularity observed in 5 cases (38%) (Table 2). Purpura or a bleeding event was described in 12 cases (92.3%), including purpuric rashes, epistaxis and petechiae, haemoptysis, bruising, buccal haematoma, bleeding gums, petechial lesions to the sclera, nasal bleeding, gross haematuria, cutaneous and mucosal bleeding, genital bleeding, and bleeding blisters.

A total of 13 studies [4, 13, 19, 21,22,23,24,25,26,27,28,29,30] reported the occurrence of ITP after influenza vaccination. Five [5, 27,28,29, 31]studies were surveillance representing 38.4% of included studies, while self-controlled case series were presented in 3 [13, 19, 25]studies. Cohort [24, 30]and case-control [4, 22] studies were conducted in 2 studies, while only 1 [23] study was a randomized controlled trial. More details regarding the country and type of influenza vaccine are provided in (Table 3).

Only 4 [24, 25, 27, 30] studies were included in the analysis of the incidence rate ratio (IRR) of ITP occurrence 42 days after receiving influenza vaccination. Generally, the analysis showed a positive statistically significant IRR = 1.85, 95% CI [1.03–3.32]. However, heterogeneity was statistically significant with I2 = 0.66% and a p-value < 0.01. Thus, a subgroup analysis according to the age of patients was performed, and it was only applicable in 3 studies [24, 25, 30]for the age group above 65 years. This yielded a statistically insignificant positive IRR = 2.13, 95% CI [0.71–6.43] with I2 = 83% and p-value < 0.01 (Fig. 2).

Meta-analysis of incidence rate ratio (IRR) of ITP after 42 days of influenza vaccine administration