The initial search generated 1354 articles, five of which were identified as being strongly relevant following review of title and abstract. The detailed selection process is presented in Fig. 1 and a detailed review of coherent data is collected in Table 1. The included articles were studies about the association between PLA2 polymorphism and DVT, PE, or VTE.
The patient populations of the selected papers were from various nationalities.
All patients contributing in these studies were diagnosed with venous thrombotic events with or without PE. The patient populations ranged between 23 and 121 cases.
In all evaluated studies, PLA2 polymorphism was evaluated via restricted fragment length polymorphism (RFLP) PCR.
In all studies, DVT was diagnosed and confirmed using standard methods including ultrasonography, Doppler ultrasonography, d-dimer, and clinical symptoms. Various techniques were also used for PE diagnosis such as clinical presentation, chest X-ray, ventilation perfusion lung scan, electrocardiogram, determination of blood gases, and d-dimer test. PLA2 polymorphism prevalence was reported 13–42.9% in patients (mean = 27.95%).
The median age was within the range of 34–61 years. One of five papers compared age between cases with thrombosis risk concomitant with PLA2 allele and without it [15].
PLA2 polymorphism was associated with VTE in one study [14], but not in another one [15] (Table 1). One of the studies found no correlation between PLA2 polymorphism and thrombotic events in patients with age 60 years or older (P = 0.5) [15]. In two of the selected studies, the correlation between PE and PLA2 polymorphism was investigated; one of them showed no association [19], whereas the other one reported the correlation (P = 0.003) [20]. In the latter, the prevalence of PLA2 in patients with recurrent PE events was 37% (OR 3.52, CI 1.21–10.3) and one patient was homozygous genotype for this polymorphism.
The association between PLA2 polymorphism and DVT was reported in one of the articles. According to the findings, the frequency of PLA2 polymorphism was significantly higher in DVT, compared to control group (P < 0.001) [19]; however, no significant difference was found in the frequency of this polymorphism between PE/DVT or PE patients and control group.
One of the studies investigated the association between PLA2 polymorphism and thrombotic events in Behcet's disease [21]. In this study, the frequency of PLA2 polymorphism was compared between the Behcet patients with DVT and control group. No significant difference was observed between Behcet’s disease (BD) and control in the frequency of PLA2 polymorphism, but was found between these patients with DVT and control (OR 2, CI 1.1–3.7) (21). Carriage rate was also significantly higher in BD patients with DVT than control (P = 0.044, OR 2.2, CI 1.1–4.5).
The association between recurrent events and PLA2 polymorphism was found in another study [14]. Carriage of this polymorphism had more recurrent VTE events than other patients.
In one of the studies, the effect of aspirin consumption was studied on the association between PLA2 polymorphism and thrombosis. The exclusion of these patients from the cohort had no effect on final output [15].
The prognostic value of PLA2 polymorphism and its correlation with DVT, PE, or VTE has not been thoroughly evaluated. Nevertheless, the predictive value of this genetic marker has been mostly evaluated in cases with stroke or coronary thrombosis [12, 13, 22].
In 1996, Weiss et al. reported a relationship between the PLA2 allele and elevated risk of premature coronary thrombosis [12]. Some years later, in 1999, Feng et al. suggested that PLA2 allotype in GP IIb/IIIa could be a risk factor in patients with VTE. The PLA1/PLA2 polymorphism is characterized by increased affinity of the GP IIb/IIIa platelet receptor for fibrinogen and enhances platelet aggregation as a baseline for thrombosis [22]. Despite this, in 2008, Ivanov et al. declared no association between PLA2 polymorphism and risk of VTE, but it could be a potential risk factor for developing PE [20]. Their data showed comparable OR to other known thrombophilic mutations, FVL and FII G20210A. They reported that dual carriers of FVL/PLA2 along with early manifestation and unusual position of thrombosis had recurrent PE.
In another study in 2012, Pourgheysari et al. reported that PLA2 polymorphism is highly associated with VTE [14].This was the only inherited thrombophilic risk factor that was correlated with VTE among investigated polymorphisms, FVL, FIIG20210A and HTHFR. The PLA2 polymorphism also played a role in recurrent events in spite of the other polymorphisms. This finding demonstrated the importance of population-based studies.
According to the results of this systematic review, PLA2 polymorphism increased the thrombotic tendency, but no consistency was found between different studies. While Ivanove et al. demonstrated the association of the polymorphism with PE, Karimi et al. found no relationship. Instead, they found the association with DVT [20, 19].
A main limitation of the present review was the lack of enough comparable reports and paucity of research in this study. Due to the low number of publications, the study is not adequately powered to identify the importance of this polymorphism. Because of the limited accessibility of data, it was not possible to perform univariate or multivariate analyses of individual markers in all studies.
