Abstract
Introduction
Spontaneous bleeding into the soft tissues of the abdominal and thoracic wall is described as complication of anticoagulant therapy. Computed tomography (CT) allows to detect the presence of extravasation of the contrast agent into a hematoma, which is indicated as a sign of ongoing bleeding. Other specific CT signs of such coagulopathic bleeding have been described earlier.
Aim of the study
To evaluate the significance of specific coagulopathic CT signs for predicting the dynamics of spontaneous bleeding into soft tissues in patients with COVID-19.
Materials and methods
A retrospective study included 60 patients with COVID-19 with spontaneous bleeding into soft tissues and extravasation of a contrast agent on CT. In addition to extravasation, a “hematocrit effect” was detected in 43 patients on CT. Of these, 39 had extravasation in the form of a “signal flare.” All patients underwent transarterial catheter angiography (TCA). To assess the prognostic value of CT signs, the results of CT and TCA compared. The absence of extravasation on the TCA more often corresponded to stopped bleeding.
Results
Extravasation on TCA found in 27 (45%) patients. The presence of the “hematocrit effect” or the combination of this sign with the phenomenon of a “signal flare” on CT (n = 43) led to more frequent confirmation of extravasation on TCA than in their absence (n = 17): 23.5% vs. 53.4% (p = 0.028).
Conclusion
The presence of a fluid level and the phenomenon of a “signal flare” on CT in the structure of spontaneous hematomas of the soft tissues of the abdominal and thoracic wall in COVID-19 patients more often corresponded to ongoing bleeding on the TCA. The absence of coagulopathic CT signs more often corresponded to stopped bleeding.
Graphical abstract
Keywords: Spontaneous bleeding, Hematoma, CT, Extravasation, Ongoing bleeding, Embolization, COVID-19, Non-surgical treatment
Introduction
Spontaneous bleeding into the soft tissues of the abdominal wall and retroperitoneal space has become common due to an increased number of patients receiving anticoagulant therapy. More often than other localizations, hematomas formed in the rectus abdominal muscles and retroperitoneal space [1–4]. Due to the fascial spaces and muscles that limit these anatomical zones, bleeding is prone to self-tamponade and spontaneous hemostasis [5]. Therefore, non-surgical treatment is often used in stable patients [9]. However, with ongoing bleeding, especially in unstable patients, surgery is required. Transarterial catheter angiography successfully used to stop bleeding [5–8].
Computed tomography (CT) has optimal accuracy and allows determining the localization, the size, the structure of the hematoma, as well as the source of ongoing bleeding [9–11]. Extravasation of the contrast agent indicated as the main CT criteria for ongoing bleeding. The prognostic value of extravasation on CT as a sign of ongoing bleeding is confirmed by subsequent transarterial angiography in 70–90% of patients [5, 12–15].
In patients with COVID-19, the problem of spontaneous coagulopathic bleeding has become especially relevant against the background of anticoagulants, sepsis, and organ dysfunction [16–21]. However, surgery in patients with COVID-19 accompanied with high mortality [27], just as endovascular interventions also accompanied with complications [26]. In this regard, the accurate identification of patients in need of surgical treatment or non-surgical management is very important.
The “hematocrit effect,” described as a boundary between the accumulation of fluid of different densities and blood cells, indicated as a specific CT sign of coagulopathic bleeding into soft tissues [2, 8]. The contrast agent in these patients with extravasation often spreads on the line of demarcation between the layers of hematoma, which is described as a “signal flare” phenomenon [22]. However, the practical significance of these signs and their correlation with ongoing bleeding have not been investigated.
The aim of the study
To evaluate the significance of specific coagulopathic CT signs for the prognosis and dynamics of spontaneous bleeding into soft tissues in patients with COVID-19.
Materials and methods
A retrospective single-center cohort study was conducted. Specific CT signs of spontaneous bleeding into the soft tissues of the thoracic, abdominal wall, and retroperitoneal space were studied. 256 patients with COVID-19 and confirmed bleeding (hematomas) were examined for compliance with the inclusion criteria. The study dates are from 1/03/2020 to 1/03/2022.
- The inclusion criteria:
- Patients of both sexes;
- Over 18 years old;
- Receiving anticoagulants;
- Confirmed COVID-19 infection;
- The presence of spontaneous hematoma of the abdominal, thoracic wall, and retroperitoneal space;
- Confirmed extravasation on CT;
- Performed transarterial angiography.
Thus, 60 (23.4%) patients met the inclusion criteria.
- The exclusion criteria:
- Patients with traumatic or iatrogenic injury;
- intraperitoneal, intrapleural, or parenchymal bleeding.
All patients with suspected spontaneous soft tissue hematoma underwent four-phase 64-section CT, which included unenhanced CT, an arterial phase with bolus contrast, venous, and delayed phases.
The transarterial angiographies were performed on the Innova 530 Angiographic Complex (General Electric Medical Systems, USA). Depending on the location of the hematoma, selective catheterization of the “artery of interest” was performed. Indications for angiography were signs of extravasation on CT. When a hematoma was localized in the anterior abdominal wall (rectus abdominis muscle), the lower epigastric artery was catheterized selectively, when a hematoma was localized in the anterior thoracic wall (large and small pectoral muscles)—the thoracoacromial artery, lateral, and internal thoracic arteries were catheterized selectively. In case of a spontaneous hematoma in the retroperitoneal space (the iliopsoas muscle)—the iliolumbar artery, the deep circumflex iliac artery and lumbar arteries were catheterized. Upon confirmation of extravasation, the transcatheter arterial embolization was performed (n = 26). The empiric (preventive) embolization has performed in 15 patients without ongoing extravasation on angiography. Diagnostic catheters in modification C1-2, JR, and IM (Cordis, USA; Boston Scientific, USA) were used for selective catheterization; Omnipak-350 (General Electric Healthcare, USA) or Ultravist-370 (Bayer, USA) was used as a contrast agent.
At the first stage of the study, a retrospective analysis of the CT scans was carried out by an independent radiologist. The diagnostic task was to determine the fact of extravasation of the contrast agent, the “hematocrit effect” and the phenomenon of “signal flare.” The influence of time from the onset of bleeding on the development of structural changes in the hematoma on CT, the duration of previous intake of anticoagulants, the localization of the hematoma, and other factors were also investigated.
At the second stage, the results of transarterial angiography were retrospectively studied by an independent vascular interventional radiologist to confirm the ongoing bleeding (extravasation). Then the results of CT and angiography were compared with each other. The next CT signs of extravasation were studied: an isolated extravasation (the only sign), an extravasation, and the presence of fluid level in the hematoma (two signs), and combination of extravasation, hematoma with fluid level, and the phenomenon of “signal flare” (three signs) (Fig. 1).
Fig. 1.
Flowchart of the study. *In 3 patients, no extravasation on CT was detected in retrospective analysis
The coagulation system parameters were evaluated 1.8 ± 1.4 days after endovascular or spontaneous hemostasis (n = 51). The volume and structure of the hematomas were examined by ultrasound (n = 57) after 9.9 ± 8.6 h and by CT (n = 13) after 2.2 ± 1.3 days.
Statistical analysis was performed with software of IBM SPSS Statistics version 26 and Jamovi 1.6.23.0. Normality of data distribution was tested using the Kolmogorov–Smirnov and Shapiro–Wilk tests. In this article, the results are presented as mean values and standard deviations (SD) for continuous normally distributed variable, as a median (interquartile range (IQR)) for continuous non-normally distributed data, and as counts and percentages for categorical data. To identify statistically significant differences between groups, parametric and nonparametric statistical methods were used (Student's t test and Mann–Whitney U test for independent samples for quantitative data, F test for qualitative data). Statistically significant differences were taken at the level of p < 0.05.
Results
Characteristics of patients
The bleeding with hematoma formation was typical for elderly patients (73.5 ± 11.1 years), among them were 51 (85%) women, on 14.4 ± 4.8 days from the onset of the underlying condition (COVID-19) and 9.6 ± 5.3 days after the start of anticoagulant therapy. In general, according to standard laboratory tests, the normal coagulation status was recorded (INR: 1.1 [0.98; 1.19]; APTT: 31.05 [25.85; 38.37]). In the majority of patients, 41 (68.3%) hematomas localized in the anterior abdominal wall, in 9 (15%) cases—in the retroperitoneal space, in 10 (16.7%) cases—in the chest wall muscles.
Detection frequency of hematoma morphological signs
The presence of hematoma, both in the initial and retrospective assessment by an independent expert, was confirmed in all patients. The extravasation of the contrast agent on CT during primary evaluation established in 60 (100%). During comparative retrospective evaluation (by an expert)—in 57 (95%) patients, among them, there are patients in the arterial phase—in 39 (68.4%) patients, venous phase—17 (29.8%), and delayed phase—1 (1.8%).
On the unenhanced CT, in 43 (71.7%) patients, the hematoma had a fluid level (Fig. 2a), and in 17 (28.3%)—it was described as a homogeneous structure (Fig. 3). During intravenous phase, in 39 (90.7%) patients with a “fluid level,” the phenomenon of a “signal flare” was established, which was more often detected in the arterial phase—in 33 (84.6%) (Fig. 2b). It should be noted that in the initial description of CT, the “hematocrit effect” and the phenomenon of “signal flare” have not described in any case.
Fig. 2.
Abdominal CT scan. Hematoma of the rectus abdominis muscle with the level of cellular fluid in the native study (“hematocrit effect”) (a). Contrast agent at the boundary between liquid and cellular components (a fluid level in the context of the hematoma) during the delayed phase (“signal flare” phenomenon) (b)
Fig. 3.
Abdominal CT. The Hematoma of the rectus abdominis muscle without fluid level
To identify the development patterns of morphological signs, a comparative analysis between groups with and without fluid levels in the hematoma was performed (Table 1).
Table 1.
Comparison of patient groups by the presence/absence of a “fluid level” in the hematoma
| Parameters | Hematoma with fluid level (Group I) N = 43 |
Hematoma without fluid level (Group II) N = 17 |
p | |
|---|---|---|---|---|
| Only fluid level (n = 4) |
Fluid level+ «signal flare» (n = 39) |
|||
| Gender F/M, n (%) |
3 (75)/ 1 (25) |
35 (89.7)/ 4 (10.3) |
13 (76.5)/ 4 (23.5) |
0.390 |
| Age | 71.5 ± 10.5 | 75.7 ± 9.6 | 70.3 ± 13.5 | 0.251 |
| Days from the onset of the disease (COVID-19) to the appearance of a hematoma | 17.7 ± 2.9 | 13.5 ± 4.4 | 15.6 ± .5 | 0.104 |
| Days from the start of taking the anticoagulant until the appearance of a hematoma | 13 ± 7.2 | 8.2 ± 4.4 | 11.8 ± 5.4 | 0.059 |
| Anticoagulant therapy (n, %) | ||||
| Unfractionated heparin | 0 | 0 | 1 | 0.488 |
| Low molecular weight heparin | 4 | 36 | 14 | 0.682 |
| Novel Oral Anticoagulants (NOAC) | 0 | 0 | 1 | 0.687 |
| Combination | 0 | 3 | 1 | 0.297 |
| APTT at time of bleeding (s) | 30.5 ± 6.2 | 42.6 ± 42.3 | 33.5 ± 26.1 | 0.027 |
| INR at time of bleeding | 1.1 ± 0.2 | 1.2 ± 0.7 | 1.1 ± 0.2 | 0.550 |
| Hemoglobin (g/l) before detected hematoma | 88.5 ± 15.9 | 83.6 ± 26.4 | 79.6 ± 2.9 | 0.579 |
| Platelets (× 109/l) before detected hematoma | 136.7 ± 97.9 | 25.1 ± 115.4 | 233.8 ± 134.3 | 0.178 |
| Hematoma’s location, n (%) | ||||
| Anterior abdominal wall | 2 (50) | 29 (74.4) | 9 (52.9) | 0.232 |
| Anterior chest wall | 1 (25) | 5 (12.8) | 5 (29.4) | 0.332 |
| Retroperitoneal space | 1 (25) | 5 (12.8) | 3 (17.7) | 0.774 |
| Extravasation on CT n (%) | 4 (100) | 39 (100) | 14 (82.3) | 0.019 |
| Extravasation on CT (study phase), n (%) | ||||
| Arterial | 2 (50) | 33 (84.6) | 4 (23.5) | < 0.001 |
| Venous | 2 (50) | 6 (15.4) | 9 (5.9) | 0.011 |
| Delayed | 0 | 0 | 1 (5.9) | 0.277 |
| No | 0 | 0 | 3 (17.7) | 0.019 |
| Hematoma’s volume (ml) | 590 ± 341.4 | 1037.6 ± 669.6 | 1107.3 ± 618.8 | 0.427 |
There were no differences in gender and age, volume and localization of hematoma, and time from the onset of the disease. Most of the laboratory parameters did not differ with the exception of APTT, which was higher in patients with three CT signs (“extravasation,” “fluid level,” “signal flare”) (p = 0.027). This group of patients also has the shortest duration of anticoagulant therapy, although the differences are on the border of statistical significance (p = 0.059), At the same time, in patients with the “hematocrit effect,” extravasation on CT was more often detected in the arterial phase (p < 0.001), and vice versa, the extravasation into a hematoma without a fluid level was more often observed in the venous phase (p = 0.011).
The prognosis of bleeding on transarterial angiography
The extravasation on transarterial angiography was established in 27 (45%) patients, out of them, extravasation in the arterial phase of CT was shown in 19 cases, and in the venous phase (n = 17)—in 7 (41.2%) cases (p = 0.047). The rest did not have extravasation on angiography.
The relationship between extravasation on CT and transarterial angiography is presented in Table 2. The extravasation on angiography was detected only in patients with confirmed extravasation by CT in the arterial (n = 39) or venous phase (n = 17). In the remaining patients (n = 4), no extravasation was detected on angiography. Extravasation on angiography was more often detected in patients if extravasation was confirmed on CT in the arterial phase than in the venous phase: 20 (51.3%) vs. 7 (41.2%) patients (p = 0.047).
Table 2.
Correlation of morphological signs with the phase of contrast enhancement of CTa and extravasation on angiography after retrospective evaluation
| Morphological signs of hematoma and CT phase | Extravasation on angiography (n, %) | Total, (n, %) |
p value | |
|---|---|---|---|---|
| Morphological signs | CT phasea | |||
|
Extravasation (n = 17) (primary evaluation) |
Arterial (n = 4) | 1 (25) | 4 (23.5) | 0.031 |
| Venous (n = 9) | 3 (33.3) | |||
| Delayed (n = 1) | 0 | |||
| No extravasation (n = 3) | 0 | |||
| Extravasation + fluid level (n = 4) | Arterial (n = 2) | 1 | 23 (53.4) | |
| Venous (n = 2) | 0 | |||
| Extravasation + fluid level + «signal flare» (n = 39) | Arterial (n = 33) | 18 (54.5) | ||
| Venous (n = 6) | 4 (66.7) | |||
aThe only patient with extravasation in the delayed phase of CT had no extravasation on angiography
In the presence of a fluid level in the hematoma (n = 43) on CT, the extravasation on angiography was defined more often than in patients without a level (n = 17) (p = 0.031). In the presence of the “signal flare” phenomenon, extravasation on angiography was detected even more often than in the rest, 56.4% vs. 23.5% (p = 0.028).
Angiography revealed 2 (3.3%) complications—damage to the major vessels, which required the installation of a stent graft in one case.
Embolization of the target vessel performed in 41 (68.3%) patients (Table 3). Each patient underwent embolization of a single-target vessel.
Table 3.
Embolization in comparison groups
| Hematoma with fluid level (n = 43) | Hematoma without fluid level (n = 17) | p value | |
|---|---|---|---|
| Embolization as a therapeutic intervention, n (%)a | 22 (51.2) | 4 (23.5) | 0.05 |
| Empiric (preventive) embolization, n (%) | 9 (20.1) | 6 (35.3) | 0.247 |
| Embolization not done, n (%) | 12 (27.9) | 7 (41.1) | 0.37 |
| Total, n (%) | 31 (72.1) | 10 (58.8) | 0.319 |
aIn 1 case, the extravasation was not detected intraoperatively but was detected retrospectively. Embolization has not been performed
In case of a “fluid level” in the hematoma on CT, patients underwent therapeutic embolization more often on angiography (p = 0.05). The overall frequency of embolization in the groups did not differ.
Dynamics of structural changes in hematoma
Following 9.9 ± 8.6 h after angiography, in 57 (95%) patients, the hematoma dynamics assessment was performed by ultrasound. Further, ultrasound monitoring has scheduled every 6–12 h. Each patient underwent 4.3 ± 2.3 studies (Table 4). According to ultrasound data, the hematoma has enlarged in 6 patients, of which 5 (17.9%) after embolization and one patient (5.3%) without embolization. There were no differences in the frequency of hematoma enlargement in the groups (with or without a fluid level).
Table 4.
Dynamics of coagulation system parameters and structural changes of hematoma on ultrasound examination
| Hematoma with fluid level | Hematoma without fluid level | |||
|---|---|---|---|---|
| Embolization, (n = 28) | No embolization, (n = 12) | Embolization, (n = 10) | No embolization, (n = 7) | |
| Volume of the hematoma increased, n (%) | 3 (10.7)a | 0 | 2 (20) | 1 (14.3) |
Ultrasound control has not performed in three patients after embolization
aIn one patient, an increased hematoma's volume has not confirmed on a subsequent CT scan
In term of 2.2 ± 1.3 days after angiography, 13 (21.7%) patients, including patients with increased hematomas on ultrasound, underwent control CT (Table 5). CT showed an enlargement of the hematoma in 3 patients. In one case, an increased hematoma detected by ultrasound after embolization was excluded after CT. In addition, in 7 out of 8 patients, the fluid level in the hematoma’s structure disappeared. One patient had an arising “fluid level.” Extravasation on control CT was detected in a single case after embolization, but the fact of extravasation was not confirmed on control angiography.
Table 5.
Dynamics of structural changes of hematoma on control CT (n = 13)
| Hematoma with fluid level (n = 8) | Hematoma without fluid level (n = 5) | |||
|---|---|---|---|---|
| Embolization (n = 4) | No embolization (n = 4) |
Embolization (n = 2) | No embolization (n = 3) | |
| Structural changes of hematoma on control CT | ||||
| Appearance of the fluid level | – | – | – | 1 |
| Disappearance of the liquid level | 4 | 3 | – | – |
| Extravasation | 1 | – | – | – |
| Volume of the hematoma on the control CT increased, n (%) | 1 (12.5) | 0 | 1 (20) | 1 (20) |
Following 2.2 ± 1.3 days after angiography, the fluid level in the hematoma disappeared in 7 of 8 patients, and the only one patient had an extravasation. No extravasation was detected on repeated angiography.
In term of 1.8 ± 1.4 days after endovascular or spontaneous hemostasis, the APTT parameter was assessed (n = 51). In the group of patients with fluid level as a single sign (n = 4), it was 24.1 ± 2.5 s, in the group of patients with fluid level and the phenomenon of “signal flare”—28.3 ± 6.6 s, in the group without fluid level—22.8 ± 2.9 s.
Discussion
In this retrospective single-center study, the prognostic value of CT-detected coagulopathic structural changes in spontaneous soft tissue hematomas in patients with COVID-19 was studied.
The majority of our patients were senior women, although several studies have not shown sexual differences in spontaneous soft tissue bleeding. More often (67%) hematomas were localized in the anterior abdominal wall. In a recent study, retroperitoneal hematomas were more often detected [4], which in our study were found only in 15% of patients. We found hematomas in the chest wall in 18% of patients.
In all patients included into the study, CT revealed extravasation of the contrast agent into a hematoma. In addition, 43 (71.6%) patients showed specific laboratory coagulopathic signs of bleeding.
The «Hematocrit effect» was first described by researchers at the Mayo Clinic in 1984 [24] and established as a highly sensitive marker of coagulopathic bleeding in 87% of patients. The “fluid level” in the hematoma corresponds by the layering of heavier cellular elements located dependent on a liquid supernatant in hematoma with unclotted blood. In patients without hypocoagulation, the blood in the hematoma coagulates and looks like a heterogeneous structure [25], which we observed in about 30% of our patients. The phenomenon of “signal flare” was described by Ibukuro et al. in the experiment as a sign indicating ongoing bleeding [22]. The phenomenon develops due to the difference in the specific gravity of the blood cells, contrast agent, and plasma [22].
Bleeding was detected in patients 2–3 weeks after the onset of the disease (Covid-19), while in patients with a “signal flare” bleeding occurred 2–4 days earlier than in the rest, although the statistical significance of the differences was not confirmed (p = 0.104). Besides, in patients with a “signal flare,” the term from the start of anticoagulant therapy to the diagnosis of bleeding was 3–5 days shorter, but the statistical significance of the differences was also not achieved (p = 0.059). These differences in the groups could be related to the late diagnosis of spontaneous hematomas, which are often asymptomatic and are detected on CT or ultrasound when searching for the causes of anemia or even as an accidental finding [28]. The differences also could be related to unknown patterns of coagulopathic bleeding. Of the features established by us, it should be noted the regression of these signs in most patients. On a control CT scan performed 2.2 ± 1.3 days after angiography, we have not observed the phenomenon of a “signal flare,” and the “fluid level” disappeared in 7 out of 8 patients (a clot formed) and appeared only in one patient.
One of the interesting findings in patients with a “signal flare” was the identification of laboratory signs of coagulopathy as a significant increased APTT, the mechanism of which is not clear [29]. An increased APTT in patients with COVID-19 is considered as one of the predictors of an unfavorable outcome [30]. The increased APTT cannot be associated with anticoagulant therapy, since almost all patients received low-molecular-weight heparin. It should be noted that the regression of the “fluid level” and the formation of a clot in the hematoma on control CT coincided with the normalization of APTT. This fact needs additional study to substantiate a possible specific therapy.
CT showed high accuracy in the diagnosis of spontaneous hematomas [8, 23]. However, the assessment of ongoing bleeding based on CT and angiography results differed significantly. The extravasation detected on CT confirmed on angiography only in 47.3% patients. At the same time, in case of a “fluid level,” the extravasation on angiography was detected in 53.4% of patients, and in the absence of a fluid level, the extravasation was detected only in 23.5% of patients (p = 0.031). In the presence of the phenomenon of “signal flare,” the extravasation on angiography was determined in 56.4% of patients, which was higher than without this sign (p = 0.028). In the presence of a “fluid level” and a “signal flare,” patients were more often subjected to embolization (p = 0.05). In the absence of these signs in stable patients, nonoperative management may be justified, especially considering that angiography was accompanied by serious complications in two patients.
It should be noted that the frequency of detection of extravasation on angiography in our study was lower than in other studies dedicated to spontaneous soft tissue bleeding [5, 12–15]. We found a high frequency of extravasation (about 70%) during angiography only in retroperitoneal hematomas. In chest hematomas, extravasation detected only in 18.2% of patients. We performed embolization of the target vessels less often, but only in a single case a rising hematoma found by ultrasound or CT in a patient without embolization. Control angiography performed in a single patient, although a higher frequency of repeated embolizations is also reported [31].
The present study has a number of limitations. This is a single-center retrospective study with a small group of patients, so the results may have limited clinical significance. Our results apply only to patients with COVID-19 received therapeutic doses of anticoagulant therapy.
Conclusion
The presence of CT signs: fluid levels and the phenomenon of a “signal flare” in the structure of spontaneous soft tissue hematomas in patients with COVID-19 more often indicated ongoing bleeding and required endovascular intervention. In the absence of these signs, the probability of continued bleeding was significantly less. These data allow a more reasoned approach to the choice of surgical and non-surgical strategies for spontaneous soft tissue bleeding.
Author contributions
Conceptualization: AYP, AET; Methodology: AYP, AET, SVT; Formal analysis and investigation: VNV, AAP, EAS; Writing—original draft preparation: AYP, DYT; Writing—review and editing: MVB, EAS; Supervision: AVS. All authors read and approved the final manuscript.
Declarations
Conflict of interest
The authors have no relevant financial or non-financial interests to disclose.
Ethical approval
Institutional Review Board approval was not required because this research was retrospective and did not altered the treatment or the life of the patients in any way.
Informed consent
Written informed consent was not required for this study because this research was retrospective and did not altered the treatment or the life of the patients in any way.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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