Mortality rate was 0%. Major bleeding occurred in 3 patients (1.1%), and the total rate of major complications was 1.5% (n = 4). One patient (10 kg), suspected of having an acute rejection after liver transplantation, experienced life-threatening hemorrhage localized to the biopsy site and developed a large (2×6 cm) intrahepatic hematoma. Hb dropped from 11.6 to 5.3 g/dL. A total of 100 IE/kg of LMWH had been administered the day before. The abdominal bleeding required surgical evacuation twice and the patient received several transfusions. He did not have any persisting consequences.
The second patient (25 kg), admitted due to liver failure of unknown origin, received prothrombin complex concentrate immediately before biopsy. Approximately 12 hours later, the patient's condition deteriorated and abdominal cavity hemorrhage was detected and evacuated surgically.
A patient (46 kg) with acute liver failure received a transfusion of platelets, fresh frozen plasma, prothrombin complex concentrate, and erythrocytes before liver biopsy. Twelve hours after the procedure, the patient experienced variceal bleeding and developed encephalopathy. He was stabilized with sclerotherapy and supportive therapy. Whether transfusion before the procedure or hemodynamic changes during and after the procedure could have triggered the variceal bleeding or if the timing was incidental was undetermined.
The fourth patient (17 kg) underwent 8 biopsies from a liver lesion and subsequently experienced abdominal pain, tachycardia, and metabolic acidosis. Ultrasound demonstrated fluid in the abdominal cavity; however, there was no significant drop in Hb (from 8.4–7.8 g/dL). He was transferred to the intensive care unit for blood transfusion and hemodynamic monitoring. The patient experienced no further complications and was transferred back to the ward within hours.
The overall minor complication rate was 25%, including minor sedation-related complications (described in Methods), abdominal pain, and minor bleeding. A total of 28 incidents of minor bleeding (10%), including fluid in the abdominal cavity or subcapsular hematoma detected with ultrasound, were recorded. None of these required any intervention. Patients with minor bleeding had a more pronounced (P = 0.0007) drop in Hb (0.78 ± 0.91) than those without bleeding (0.09 ± 1.00).
Abdominal pain requiring analgesic treatment was registered after 12% of the procedures (n = 32), and 8 of these procedures were associated with bleeding of some kind. An extra ultrasound control was performed after 21 procedures due to abdominal pain or vital changes indicative of blood loss. These controls revealed 11 cases of bleeding. Six of these bleeding incidents had not been visualized during the biopsy procedure. One was a major bleeding incident, described above.
Routine Postbiopsy Ultrasound
Routine control ultrasound was routinely performed the day after the biopsy and 266 (96.7%) radiological descriptions were available. Bleeding was visualized in 7.1% (19/266) of these controls. The bleeding had not been detected clinically or on previous ultrasound imaging in 2.6% (n = 7). Free abdominal fluid was detected in 4 and subcapsular hematoma in 3. None of these minor bleeding incidents required any intervention, changed therapy, or altered length of hospital stay.
Risk Factors for Complications
Focal Space Occupying Lesion/Tumor
A total of 25 of 275 biopsies were taken from a focal lesion such as hepatoblastoma (n = 6), hepatocellular carcinoma (n = 5), and other focal lesions (n = 14). Most procedures included additional biopsies of surrounding liver parenchyma, and samples were obtained with a 22-G fine needle in addition to the routinely used 18-G needle. Mean number of passes was 4.9 (range 1–8). One major bleeding incident, 5 minor bleeding incidents, and 5 other minor complications occurred. The total bleeding rate was significantly higher than in the rest of the population (odds ratio 2.84 [1.04–7.78]; P = 0.047) (Table 3). There was no difference in Hb drop between patients with focal lesions (0.21 ± 0.88) and those without (0.16 ± 1.05; P = 0.82).
The platelet count was <70 × 109 cells/L before 14 procedures. Platelet concentrates were transfused in 11, 4 received prothrombin complex concentrates, and 2 received plasma. There were 3 minor complications, but no bleeding was recorded. INR was ≥1.7 before 18 procedures. All of the patients with INR ≥1.7 received platelets (n = 9), fresh frozen plasma (n = 7), and/or prothrombin complex concentrate (n = 12) before procedure. One patient had a subcapsular hematoma not requiring any therapy, and 4 other minor complications occurred.
Acute Liver Failure
Of 275 biopsies, 12 were taken from patients with acute liver failure. One major and 1 minor bleeding and 3 other complications, including 1 major bleeding, occurred. Patients with acute liver failure had a significantly increased odds ratio for major complications: 26.1 (3.3–204.7; P = 0.01).
ASA treatment (3 mg/kg body weight, maximum 75 mg) had been given the last 5 days before 55 of the procedures. Five had also received LMWH the day before the procedure. Preprocedural treatment was given as platelets (n = 17), fresh frozen plasma (n = 4), and/or desmopressin and tranexamic acid (n = 1).
Six patients had minor bleeding incidents such as subcapsular hematoma or modest amounts of free abdominal fluid not requiring any therapy. No major bleeding occurred. Patients treated with ASA did not have significantly increased odds ratio for all bleeding 0.96 (0.37–2.26) or minor bleeding 1.10 (0.42–8.87) (Table 3). Mean drop in Hb (0.11 ± 0.82) was not significantly different from the mean decrease in the patients without ASA (0.18 ± 1.09) (P = 0.66).
Three of the 17 who had received platelets before the procedure and 3 of the 38 children who did not receive platelets before biopsy had minor bleeding (odds ratio 2.50 [0.45–13.9]; P = 0.36).
In 18 biopsies treatment with LMWH had been given the day before biopsy. One major and 3 minor bleeding and 2 other minor complications occurred. The odds ratio for all bleeding of 2.43 (0.75–7.93) was not significantly different from the rest of the population (P = 0.13). The mean decrease in Hb (0.54 ± 0.69) was not significantly different from those without LMWH (0.14 ± 1.05) (P = 0.11).
A total of 97 liver biopsies were performed in liver-transplanted children. A total of 50 of the 97 biopsies were performed within 4 months after liver transplantation. The most frequent indication for doing liver biopsy on transplanted livers was suspected rejection, followed by suspected posttransplantation lymphoproliferative disease or de novo autoimmune hepatitis (Figure 1). There were 7 minor hemorrhages and 10 other minor complications. Transplanted children did not have an increased risk for bleeding complications compared with the rest of the population. The odds ratio for all of the complications was significantly lower in the transplanted patients compared with the rest of the population 0.52 (0.29–0.96); P = 0.04.
Univariate regression with “all bleeding” (both major and minor bleedings) as the dependent factor demonstrated P < 0.1 for LMWH (P = 0.0997) and focal lesion (P = 0.035) (Table 4). These 2 were included in a multiple regression model (P = 0.02; R2 = 0.028). Although focal lesion (P = 0.024) made a significant contribution, LMWH (P = 0.066) was not significant.
Univariate regression with “major bleeding” as the dependent factor resulted in P < 0.10 for LMWH (P = 0.0498) and acute liver failure (P = 0.022). These 2 were included in a multiple regression model (P = 0.0050; R2 = 0.038). Both LMWH (P = 0.034) and acute liver failure (P = 0.009) made significant contributions.
Univariate regression with “minor bleeding” as the dependent factor resulted in P < 0.10 just for focal lesion (P = 0.089) and no multiple regression model was made.
We found that treatment with ASA 5 days before ultrasound-guided percutaneous liver biopsy in children did not increase the rate of bleeding complications. Routine postbiopsy ultrasound on the consecutive day detected previously unrecognized minor bleeding in 2.6% of the biopsy controls, but none of these required intervention and the findings did not change therapy or the length of hospital stay. The routine postbiopsy ultrasound increases the detection rate of bleeding and thus strengthens the finding that ASA does not increase the bleeding rate.
This is of practical importance because many patients who undergo liver transplants receive low-dose ASA to prevent thrombosis of the hepatic artery. The concern that treatment with ASA may increase the procedure-related bleeding risk may influence the decision whether to perform a liver biopsy or to treat on clinical suspicion. Our finding is in line with the report of Atwell et al (16), who did not find an increased risk of bleeding in 3195 patients taking aspirin within 10 days before percutaneous biopsies (including liver, kidney, lung, and pancreas biopsies). There are several differences in these studies in population (mean age was 5.8 and 56 years, respectively), type of biopsies studied, and methodology, but the conclusions are parallel.
The incidents of minor bleeding in the ASA-treated patients who received fresh platelets before biopsy was slightly higher than those in the patient group who had not. The number of patients treated with platelets was, however, too low to conclude whether pretreatment with fresh platelets is beneficial or adverse in low-dose ASA-treated children and remains to be investigated.
In contrast to the lack of bleeding risk in ASA-treated patients, LMWH treatment the day before the procedure significantly increased the risk of bleeding complications. Heparin administration on the day of biopsy has been demonstrated to be an independent risk factor for bleeding after liver biopsy in an adult population (17). Thus, extra care and surveillance should be provided to patients recently treated with LMWH when a percutaneous liver biopsy is indicated.
The risk of bleeding is greatest within the first 2 hours after the procedure (18), but delayed bleeding up to 18 days has been reported (19). Terjung et al (17) found that 70% of the major and 34% of the minor bleeding incidents were detected later than 24 hours in an adult population. Because that study did not routinely include postbiopsy ultrasound, the timing of the bleeding was unknown. In a prospective study of 40 adult patients, 23% had ultrasound-detected hematomas after percutaneous liver biopsy after 24 hours (20). In that study, a follow-up ultrasound at day 7 did not find new hematomas in a randomly selected subgroup (n = 10). In children, no previous studies have evaluated the value of doing postbiopsy ultrasound routinely. In the present study, routine postbiopsy ultrasound discovered minor bleeding in 7.1% of the cases, and in 2.6%, postbiopsy ultrasound revealed unsuspected bleeding, but none of these required intervention. The routine postbiopsy ultrasound was in addition to the frequent use of extra ultrasounds in the first hours after the procedure performed on clinical suspicion of bleeding. Postbiopsy ultrasound did not change therapy, length of hospital stay, or handling of the patients. The results of the present study question the value of doing postbiopsy routinely.
Although the value of doing postbiopsy ultrasound is debatable, more subclinical bleeding otherwise unrecognized is detected and affects the complication rate. In contrast to the higher rate of recorded minor complications, the incidence of major complications in the present study (1.5%) is low compared with other studies (2.4%–4.6%) (6,7). The recorded complication rate depends not only on the quality of the procedure but also on the definition of minor complications and how closely the patients are monitored and examined after the procedure.
The recorded rate of bleeding complications is affected by the performance or not of routine postbiopsy ultrasound and whether symptoms such as abdominal pain and Hb drop are regularly followed up with an extra ultrasound.
The frequency of complications also varies with the population studied. It has been proposed that infants are at higher risk for bleeding complications than older children (7,15). We found a significantly more pronounced drop in Hb in infants younger than 3 months compared with older children between 1 and 18 years old. Intravenous fluid is administered more frequently and during a prolonged period of time in the youngest population, and thus hemodilution may account for a part of the difference; however, children younger than 3 months had a higher frequency of minor bleeding compared with children older than 1 year.
All of the major complications in the present study were associated with risk factors such as acute liver failure, biopsy from a focal lesion, or LMWH the day before biopsy. Terjung et al (17), in an (mostly) adult population, found that 7 of 10 of the clinically overt bleeding incidents occurred in patients with an increased a priori bleeding risk, and they found an increased risk of bleeding after liver biopsy in patients with acute liver failure. In line with this, we found that acute liver failure was a significant risk factor for major complication.
Biopsies taken from a focal space-occupying lesion are at particular risk, with a 2.8 odds ratio for bleeding. Furthermore, focal lesion was identified as an independent risk factor for postbiopsy bleeding. Cohen et al (2) reported a 5-fold increase in transfusion rate in patients with cancer or bone marrow transplantation. One of the factors for the increased risk may be the increased number of passes.
Liver-transplanted children had a significantly reduced frequency of complications after percutaneous liver biopsy compared with the rest of the population. This may seem contradictory to the a priori risk with frequent use of medication of LMWH and ASA; however, the present study did not indicate an increased risk associated with ASA. Moreover, the liver-transplanted group included fewer patients with other risk factors such as focal lesions and acute liver failure. Our incidence of 1% of major complications in liver-transplanted children is comparable to the 1.7% of Sornsakrin et al (13).
Ultrasound-guided percutaneous liver biopsy in children has a low incidence of major complications. Minor bleeding is frequent and is detected both on extra ultrasounds indicated by symptoms and on routine postbiopsy ultrasound the day after the procedure. Routine postbiopsy ultrasound the day after the procedure did not reveal any unexpected major bleeding requiring therapy that had not been detected earlier with on-demand ultrasound. The results of the present study challenge the value of performing postbiopsy routinely on patients with normal a priori risk for bleeding; although the majority of these minor complications required no or minimal therapy, it is important to be aware that small bleeding occurs frequently and the avoidance of major bleeding requires awareness of risk factors.
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Keywords:Copyright 2012 by ESPGHAN and NASPGHAN
acetylsalicylic acid; children; complications; liver transplantation; percutaneous liver biopsy