The above mentioned data were collected from patients who underwent surgery in the aorta. In our study,the incidence of HIT was 7.8%(16/204) for specific patients who underwent surgery under deep hypothermic circulatory arrest (DHCA), it’s really surprising. But for the patients undergoing cardiopulmonary bypass with heparin during the same period,the incidence of HIT was 1.2%(16/1364). Regarding thoracotomy, cardiopulmonary bypass is associated with the anticoagulation process of heparin. For this reason, patients with acute type A aortic dissection undergo a longer procedure and a short DHCA process during surgery. All patients in this series were exposed to a large dose of heparin, and postoperative PLTc reduction for unknown causes increases the risk for HIT development. HIT onset is not easy to perceive due to a lack of specificity in clinical manifestations, though a PLTc reduction 3 days after heparin administration is the most common. Occasionally, such a manifestation may be observed within 24 h or several months after the application of heparin [7].
The findings of the present study strengthen the awareness that HIT is a important complication worth causing our great attention after surgery for acute type A aortic dissection. Although the differences in preoperative data between the HIT group and the non-HIT group showed no statistical significance. Because of apparently longer extracorporeal circulation time and aortic cross-clamp time in the HIT group, the dose of heparin needs to be increased. In our study, the doses of heparin in both groups were not significantly different from each other (P > 0.05). The extension of the time of extracorporeal circulation may enable the body to be exposed to heparin for a longer time. Hence, achieving an appropriate ratio between heparin and PF-4 and produce pathogenic HIT antibodies becomes much more likely [8]. In this context, the time of extracorporeal circulation and aortic cross-clamp should be reduced to the greatest extent during surgery for acute type A aortic dissection. Thus, both the exposure dose of heparin and the time of exposure can be decreased. PLTc reduction induced by HIT after surgery for acute type A aortic dissection makes it more possible to administer renal replacement therapy after acute kidney injury. The pathogenesis might involve the influence of microvascular thrombosis development because microvascular thrombosis has the potential to reduce the volume of blood flow in the kidney, further lowering the glomerular filtration rate and finally leading to acute kidney injury [9]. Although HIT increases the rate of stroke incidence, both thromboembolism and microvascular blood flow disorder are the primary reasons why the risk of stroke increases in this group. Nonetheless, further investigations are warranted to identify the effects of PLTc reduction on AKI and stroke after cardiopulmonary bypass. Considering that a longer extracorporeal circulation time is also a critical cause of an increase in postoperative complications, corresponding causal relationships or interactions should be further explored and clarified as well. Both the duration of mechanic ventilation and length of ICU stay were apparently longer in the HIT group. Although the differences in the length of in-hospital were eventually found to be insignificant between the HIT and non-HIT groups and no statistical differences in in-hospital mortality rates were observed, the relevant treatment costs and risks increased. In contrast, HIT reduces the PLTc, but the 24 h postoperative volume of drainage fluid has not significant increase,and the probability of reoperation for bleeding does not increase at the same time, which may be related to the characteristics of HIT,that there are contradictions between PLTc reduction and thrombosis),conversely, the risk of hemorrhage does not increase.
HIT occurs along with arterial and venous thrombotic events; newly developed thromboembolism is the most serious clinical outcome of HIT, primarily including thrombosis in the lower limbs, pulmonary embolism, myocardial infarction, cerebral infarction, local necrosis in the heparin-injected site, gangrene, necrosis and hemorrhage in the adrenal gland [10]. Among the patients included in the present study, two patients had new-onset thromboembolism in both lower limbs, and three patients had postoperative cerebral infarction. The thromboembolism incidence rate reached 31.5%, greatly similar to the ratios (30–50%) reported in other countries [11]. If the PLTc decreases by over 50% or if thrombosis occurs, then suspected HIT is confirmed [12]. The 4Ts scoring system combines the following four characteristics: (1) amplitude of PLTc reduction, (2) duration of PLTc reduction after exposure to heparin, (3) presence of thrombosis,(4) absence of PLTc reduction due to other causes [13]. Such a system has been widely applied in the clinical setting. A score below four points indicates a high negative predictive value (97–100%), whereas that above six points suggests that the corresponding positive predictive value is low (40–82%) [14]. Clearly, the 4Ts scoring system has high sensitivity but low specificity, though it can be used as a preliminary screening method for exclusion of HIT in the clinical setting.
PLTc reduction is very common after surgery for acute type A aortic dissection, and true and false lumens are formed in the aorta after the onset of aortic dissection. Consequently, the blood flows through the intimal tear into the false lumen and thus comes into contact with the subendothelial tissues. In this way, coagulation and fibrinolysis systems are activated, leading to platelet activation and aggregation as well as the formation of blood clots [15]. In addition to extensive thrombosis in the false lumen, microthrombogenesis occurs in the whole body, causing the consumption of massive blood platelets and other blood coagulation factors. Therefore, both PLTc reduction and extensive thrombosis in the false lumen are closely related to platelet consumption [16]. The existing literature notes that expression of platelet-activating factor-4 is upregulated in the early stage of acute type A aortic dissection [17]. However, the correlation between platelet-activating factor-4 expression upregulation and HIT remains unclear. Regardless, there is no doubt that such upregulation increases the likelihood of binding after heparin exposure, which may be a reason for the occurrence of HIT. During extracorporeal circulation, the interaction of blood and the tube, together with the shear force of the loop, can lead to platelet activation. As a consequence, the blood constituents in peripheral circulation are consumed [18], though the platelet aggregation function may change after extracorporeal circulation. Accordingly, variations in surface marker expression, morphology and volume in blood platelets can be found [19]. Furthermore, PLTc reduction is associated with the administration of antiplatelet drugs, and 4Ts scores are therefore elevated. This may cause an increase in false-positive rates obtained through HIT diagnosis. Through 4Ts scoring, 38 patients in this study were suspected to have HIT, and these patients were divided into confirmed and suspected HIT groups based on laboratory testing of HIT antibodies. As shown in Table 4, the 4Ts scores of the confirmed HIT group showed no differences from those of the suspected HIT group. In terms of clinical manifestations, no significant differences in either absolute values of minimum PLT or PLT reduction were observed. Considering that the 4Ts scoring system has high sensitivity but low specificity [20], it should only be used as a preliminary screening method for preliminary exclusion of HIT in the clinical setting. Because of low specificity, HIT antibody detection needs to be further implemented to avoid overdiagnosis and incorrect treatment.
As seen from the trend illustrated in Fig. 1 and Fig. 2, the HIT antibody concentration in the HIT group reached its peak on the fifth day after surgery,when the platelet count reduced at its lowest. Furthermore, the concentration of HIT antibodies in the confirmed HIT group (2.7 ± 0.8 U/mL) was significantly higher than that of the Suspected HIT group (0.3 ± 0.2 U/mL), providing a valid basis for early diagnosis of HIT in the clinical setting. Currently, the corresponding diagnostic measures principally include specific anti-HIT-IgG antibody and anti-HIT antibody complexes (e.g., IgG, IgA and IgM) [3]. Enzyme-linked immunosorbent assays, particle immune approaches and colloidal gold immunochromatography are commonly used manual testing methods. In our study, immunonephelometry was used to achieve rapid detection with a fully automatic coagulometer (15 min) [21]. IF choose the appropriate cutoff value, The negative predictive value obtained through anti-PF4/H antibody is nearly 99% [5, 22]. Therefore, HIT antibody detection can be utilized as a method of differential diagnosis targeted at patients suspected of having HIT. Moreover, as the variations in HTI antibody concentration have a negative correlation with PLTc increase, this measure can be adopted as an index for predicting an improvement in the patient’s response to clinical treatment. But for intermediate value of 4Ts score and anti-PF4/H antibody,for example 4Ts score ≥ 4 points, and anti-PF4/H antibody ≤1.5 OD,these threshold values will be weakly negative or weakly positive [5] . which may be particularly dangerous in patients with HIT. 5-hydroxytryptamine release from activated platelet function tests was recommended for all intermediate probabilities, although it is seldom applied because of methodological defects [23].
Undoubtedly, there are certain limitations in the present study. As single-center observational research, laboratory tests were not conducted to determine HIT function.
