The use of rotational thromboelastometry parameters in understanding the coagulopathy following hump-nosed viper (Hypnale spp) bites: a preliminary study

This cohort’s epidemiological features were the same as those previously reported [1, 17,18,19]. The presence of more male victims is a reflection of the dominant workforce in farming communities. The majority of the patients were able to see a tertiary-level hospital facility that specializes in treating snakebites relatively quickly (median 12 h; IQR: 18 h) after being bitten, which was both interesting and reassuring. A study done in the Kurunegala district of Sri Lanka revealed a comparable, early health-seeking behavior, reporting a median time of 45 min (IQR 30–90 min) for a snake bite victim to arrive at a primary care hospital [20]. Additionally, they noted that 3.7% patients received indigenous care before visiting the hospital. Our study lacked data on, transfers from primary or secondary care facilities or indigenous treatments before patients presented to the hospital.

The above results indicate that ROTEM delta is more sensitive than WBCT20 and INR to identify coagulopathy. The single case of non-clotted WBCT20, despite normal ROTEM and INR without bleeding is unexpected. It may have been due to a deviation from the standard protocol as the WBCT20 is prone to false positive results even due to small preanalytical errors [9, 21]. The WBCT20 is still widely used as an indicator of envenoming, despite its reported low sensitivity of 40% [21, 22]. Its sensitivity can be improved to 80% when the test is performed under standardized conditions [23]. The need for an alternative bedside test which addresses its shortcomings has been highlighted [24]. We have previously demonstrated that EXTEM-CT in ROTEM has a 93% sensitivity and 92% accuracy in detecting Russell’s viper envenoming over WBCT20 [15].

The antivenom available in Sri Lanka is sourced from India and is effective in envenomation by Indian species of Naja naja, Bungarus caeruleus, Daboia russelii and Echis carinatus. The lack of efficacy of this polyvalent antivenom in HNV has been shown in many studies [6, 17, 24]. Despite this, many physicians use this antivenom in HNV bites [4]. This practice can be justified, as differentiating between the juvenile Russell’s viper and HNV can be challenging at times. Two patients in the present study were also treated with antivenom, although, one of them had normal WBCT20, INR and ROTEM results. The other had abnormal INR (1.79), EXTEM-CT (2285 s) and FIBTEM-MCF (3 mm) at presentation, prior to antivenom administration. Interestingly, the latter showed an improvement in the INR (0.67), EXTEM-CT (127 s) and FIBTEM-MCF (5 mm) within 24 h of receiving antivenom. Since the Indian Polyvalent antivenom has no benefit against Hypnale spp envenoming, the improvement may have been due to misidentification of the snake. On both occasions the culprit snake was not brought and was identified using the syndromic approach only.

Systemic effects of HNV bites are rare; coagulopathy has been described as the second commonest [8]. However, different studies have shown varying incidences of this complication. In a descriptive observational study involving 1543 HNV bite patients, only 59 (3.8%) were found to have coagulopathy by WBCT20, activated partial thromboplastin time (APTT) and PT/INR [4]. In another study, PT, APTT, Von Willebrand factor levels, clotting factor levels and D-dimers demonstrated a mild coagulopathy in all 80 patients evaluated, while WBCT20 was positive in only one patient [25]. It has also been reported that plasma containing Hypnale spp. venom cause weak, unstable and transient fibrin clots in thromboelastography [26]. Different frequencies of abnormal WBCT20 results were found in the three different sub species of HNV in Sri Lanka [27, 28]. This is also a possible contributor to the observed variation in coagulopathy among studies as the 3 species vary in their geographical distribution within the island [25, 29]. The results of these studies demonstrate that, mild HNV coagulopathy cannot be detected by WBCT20 possibly due to poor sensitivity and lack of standardization of the test. Furthermore, in patients presenting with clinically significant bleeding, understanding the exact coagulation derangement will be important in the management [8].

In contrast, when there is no clinically apparent bleeding despite abnormal coagulation, the need for a highly sensitive test to detect coagulopathy in HNV patients is obscure. ROTEM will be useful to understand the mechanism of bleeding in patients with VICC. In our study, this was seen in one patient who had hyperfibrinolysis on ROTEM, however, without apparent bleeding. (Fig. 2) Routine use of ROTEM in rural health care facilities in Sri Lanka is challenging due to high cost of the instrument (US$25,276) and high cost per test (approximately US$13) when compared to PT (US$2) and WBCT20 which only requires a borosilicate glass tube. However, this could be counterbalanced by applying ROTEM in other clinical settings such as obstetrical hemorrhage, liver transplantation, trauma and surgical bleeding [10].

Fig. 2figure 2

EXTEM of a 48-year-old male post HNV bite showing features of hyperfibrinolysis. ML = 45% (EXTEM, extrinsic pathway thromboelastometry; HNV, hump-nosed viper; ML, maximum lysis)

This study has several limitations. Firstly, in a majority of cases the snake was not available for the medical team to reliably identify the species. Species identification was done mainly using the syndromic approach and identifying the snake that was seen at the time of bite on a chart of photographs. It would have been ideal if the type and concentration of the specific venom could have been detected to identify the snake accurately. Secondly, although the time from bite to laboratory testing was available, information on any treatment such as “traditional or native” decoctions used prior to presenting to hospital was unavailable. Further, there were no records on patient transfers from primary care hospitals. Thirdly, this was a preliminary study with a small sample size which was not adequate to demonstrate a statistical significance.

One of the major limitations of this preliminary study was that the fibrinogen concentrations of the patients were not assessed. In VICC caused by Hypnale spp. venom, excessive fibrinogenolysis is a key feature which could be indicated by increased levels of fibrinogen degradation products and decreased levels of fibrinogen [25, 29]. However, the MCF of FIBTEM which is a measure of the fibrinogen generation of the clot was available in all patients. This parameter was normal in all 22 patients except the patient who had grossly abnormal coagulation parameters without clinical bleeding.

In this preliminary study including small sampling of patients with HNV bites, we have demonstrated that ROTEM parameters were more likely to pick up subtle changes in coagulation when compared to conventional tests of coagulation. The clinical utility of detecting these changes and their usefulness in managing snakebite should be further explored. It would be prudent to validate these preliminary findings in a prospective study that will address the shortcomings described above, and thereby establish a more useful and accurate bedside test to determine HNV coagulopathy.

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