Excessive bleeding is one of the most important complications of surgery. In case of neurosurgery or cardiac surgery, bleeding complications can lead to devastating consequences. Thus, it is very important to evaluate patient’s baseline bleeding tendency and to detect impaired hemostasis prior to invasive procedures such as surgery. In fact, it is common to have hemorrhagic complications that lead to a fatal outcome after surgery without proper evaluation of the hemostasis abnormalities. In order to identify patients with impaired hemostasis, it is necessary to assess bleeding history and family history and perform physical examination. In addition, various preoperative laboratory test parameters, including platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and bleeding time (BT), can be used to evaluate the risk of bleeding during surgery [1]. However, their role in assessing the risk of bleeding is still controversial and routine preoperative testing is not recommended in patients without a bleeding history [1,2].

Various coagulation screening tests, such as PT and aPTT, are used to identify defect of coagulation pathway. To evaluate the adequacy of platelet function, BT and platelet aggregation tests has been used for many years. However, the use of BT test is gradually decreasing due to several limitations: low sensitivity, high operator dependency, clinical usefulness, and invasiveness [3]. Platelet aggregation assessed by light transmission aggregometry or whole blood aggregometry is much more sensitive methods for detecting platelet dysfunction compared to BT test. However, these tests are relatively complicated, expensive, and time-consuming [4]. Recently, platelet function analyzer (PFA)-100 has been widely used as an alternative to overcome the limitations of prior tests [5-8]. The PFA-100 is a test device capable of measuring platelet adhesion and aggregation function under high shear-stress blood flow conditions comparable to those that occur in vivo [5]. Platelet adhesion and aggregation occur following exposure to platelet agonists, such as epinephrine (EPI)- or adenosine diphosphate (ADP)-coated membranes. As a result, the time until the membrane aperture occlusion (closure time) is measured by PFA-100. The recently introduced PFA-200 is an upgraded version of the PFA-100.

The most potent role of PFA-100/200 is that of a screening tool for detection of primary hemostasis abnormalities, such as von Willebrand disease (vWD) and various platelet disorders [9,10]. In addition, recent studies have shown its utility in monitoring antiplatelet therapy (including aspirin) and desmopressin therapy in both vWD and platelet disorders [5,11,12]. The use of PFA-100/200 test is increasing because it is easy to use and has a high sensitivity to detect hemostasis abnormalities [8]. However, its role as a preoperative screening tool to predict the risk of bleeding during invasive procedure, such as surgery, remains controversial. Some studies have reported that PFA-100/200 results were associated with perioperative bleeding risk, while other studies found no correlation between the calculated blood loss and either preoperative or postoperative PFA100 values [13-16]. Another problem of PFA test is that the closure time (CT) of PFA-100 is influenced by several other factors not actually related to bleeding. To date, blood group, time of blood collection, plasma vWF level, citrate concentration, low platelet count, and hematocrit have been reported to affect CT [8,17].

In this study, we aimed to identify the variables that affect the results of PFA-200 test. Furthermore, we estimated the usefulness of PFA-200 test as a preoperative test to predict the risk of bleeding in patients undergoing various types of surgery.

Unselected preoperative screening tests, such as PT, aPTT, and PFA-100/200, are generally not recommended for all patients without bleeding history because they may delay surgery inappropriately and cause unnecessary increases in medical costs [2,8]. However, unselected preoperative screening tests are widely used to identify the risk of intraoperative bleeding in real clinical practice. In this study, we aimed to clarify the role of a preoperative PFA-200 test in a relatively large cohort of patients who underwent various types of surgery. As a result, the preoperative CT prolongation revealed by COL/EPI test was associated with increased risk of intraoperative bleeding and postoperative RBC transfusion.

Preoperative screening tests to identify patients with primary or secondary hemostatic disorder is very important because intraoperative bleeding in these patients can cause fatal outcomes. However, until now, it is impossible to predict these diseases only by application of specific tests, so the bleeding history, family history, and physical examination should be performed. PFA-100 was first introduced in 1995 as a screening test for the diagnosis of vWD and platelet disorders [19]. In addition, the use of PFA-100 instead of BT to assess platelet function has also raised expectations for the role of PFA-100 as a preoperative screening test for primary hemostatic disorders. Koscielny et al. [13] reported in a large cohort study with preoperative questionnaire that the vast majority of patients with impaired hemostasis could be identified by PFA-100. The sensitivity of the PFA-100 COL/EPI CT was the highest (90.8%) in comparison with the other screening tests (BT, aPTT, PT, vWF:Ag). Fattorutto et al. [14] observed a weak correlation between preoperative COL/EPI CT and second-hour mediastinal blood loss in 70 patients with cardio-pulmonary bypass (r = 0.34, p = 0.01). However, Lasne et al. [15] and Cammerer et al. [16] reported no correlation between calculated blood loss and either preoperative or postoperative PFA-100 values. The worldwide prevalence of vWD is estimated to be 1%, but in Korea, the number of patients registered in the Korean Hemophilia Foundation by 2017 is only 130, which is much lower than prevalence of this disease in other countries. In case of platelet disorders, such as Bernard-Soulier syndrome and Glanzmann thrombasthenia, the prevalence is difficult to estimate, and only a few cases have been reported. Therefore, it is even more controversial to use PFA-100/200 as a preoperative screening tool for all unselected surgical patients to identify platelet disorders in Korea, where the prevalence of platelet disease is very low. This is consistent with the results of studies reported in Korea that preoperative PFA-100 screening test is less relevant to actual bleeding outcomes [20-22]. However, these studies had limitations to evaluate the role of PFA as a preoperative screening tool in unselected patients because the number of included patients was small and only specific operations were included.

The advantage of our study was that we included a relatively large number of patients and analyzed various types of surgery performed during the study period. Different surgeries may act as confounding factors for the amount of bleeding. However, the effect of variety of surgeries on the amount of blood loss was very small, because the proportion of patients according to the category of surgeries was not different between the two groups even though the category of operation was separately assessed. Another advantage of the present study is that various factors were identified to accurately assess perioperative bleeding. Because of the limitations of retrospective studies, it is difficult to accurately assess the amount of intraoperative bleeding and the amount of delayed blood loss after surgery. We reviewed both the intraoperative anesthesia notes recorded by the anesthesiologist and operation notes written by the surgeon, because surgeons tend to record less blood loss. In addition, the amount of blood transfusion during operation, the amount of transfusion within 72 hours after surgery, and the amount of Hb decrease within 72 hours after surgery were compared. In our study, PFA-200 prolongation was associated with the rate of intraoperative bleeding and RBC transfusion within 72 hours postoperatively. Although multivariate logistic analysis showed borderline significance, prolonged CT as revealed by COL/EPI was also associated with intraoperative blood loss (HR, 1.55; 95% CI, 0.97 to 2.47; p = 0.068). In addition, these results were more prominent in the subgroup analysis of patients without medication history in whom the bias related to antiplatelet drugs and NSAID use was excluded (HR, 1.16; 95% CI, 2.62 to 5.93; p = 0.021). These results suggest that preoperative PFA abnormality may increase the risk of perioperative bleeding regardless of the use of antiplatelet agents or NSAID. Therefore, in patients with these abnormalities, accurate history and physical examination and laboratory test findings should be checked to exclude primary hemostatic disorders.

It is widely known that the use of aspirin and NSAID can affect the results of PFA-100. In addition, it has been reported that the blood group, hematocrit, platelet count, and time of blood collection can affect the results of PFA-100 [8,23-25]. In our study, the use of aspirin and NSAID only affected the results of COL/EPI and did not affect the results of COL/ADP. Low Hb and hematocrit levels also affected the results of both COL/EPI and COL/ADP tests, which is consistent with the results of previous studies. Platelets count only affected the result of COL/ADP, which is difficult to interpret precisely because the number of patients with low platelet counts included in our study was too small. In particular, since our study was performed on patients who underwent surgery, most patients had platelets counts > 100 × 109/L and very few patients had platelet counts < 100 × 109/L. It has been reported that time of blood collection also affects the results of PFA-100 [17,24]. In accordance with the results of previous results, our study showed that the fast CT of COL/EPI occurred in the morning and the CT results became prolonged during the day. The results of COL/ADP showed a similar tendency, but without statistical significance, which is thought to be because of a diurnal variation in platelet function, which is more dependent on epinephrine than on ADP [26]. In addition, the increased platelet aggregation is estimated to be because of the higher in vivo epinephrine level in the morning, which induces platelet activation [27]. It was reported that the CT of PFA-100 was prolonged in the blood group O compared to other blood groups. Our study also showed that the PFA-200 results of group O were the most prolonged, but the statistical significance was not confirmed. Previous studies have shown that CT of PFA-100 is prolonged in the order of group AB, group B, group A, and group O, and our results are also exactly the same [25,28,29]. However, the association between blood group and PFA results did not have statistical significance, as the difference between the results of group A and group O was small. The prolongation of PFA in blood group O can be explained by the fact that the CT of PFA-100/200 is influenced by the plasma level of vWF and the vWF concentration, which is lower in blood group O.

In conclusion, preoperative PFA-200 test may be helpful in predicting the risk of bleeding in patients with surgery. However, the results of PFA-200 is influenced by various factors, such as use of aspirin and NSAID, blood group, hematocrit, and time of blood collection, the results of PFA-100/200 should be carefully interpreted after precluding the effects of these confounding factors.