Early Vascular Complications

This chapter treats early vascular complications after pediatric liver transplantation (PLT), which herein will be defined as complications that occur during the first 4 weeks after liver transplantation (LT).

General Considerations

PLT is characterized by coagulation disorders. Preoperatively, routine coagulation tests fail to detect the subtle interactions between a developing coagulation balance, the various etiologies of chronic liver disease, and acute liver failure. Post-operatively, hemostasis is in a complex, not perfectly understood balance, and hemorrhage or thrombosis may endanger the child and his or her liver graft. In general, during the first 4 weeks following PLT, thrombotic complications occur more frequently than hemorrhage. Early vascular complications, thrombosis in particular, have been reported to occur as much as in a fifth (21%) of patients after PLT, whereas hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) are by far the most common ( Fig. 20.1 ). Overall, complications associated with the portal vein and hepatic veins are less common than those arising from the hepatic artery.

Fig. 20.1

(A) Hepatic artery thrombosis management. (B) Portal vein thrombosis management.

The small-diameter vessels, vessel size discrepancy, and recipient’s weight are the most often incriminated reasons for these complications; however, they obviously are nonmodifiable. Any underlying disease contributing to the need for patients requiring LT is also a nonamendable factor, but it is important to know that children with fulminant hepatic failure are more at risk for developing early vascular complications; a reason might be the more liberal use of oversized grafts related to the superemergency in these circumstances and the associated lack of time to wait for a smaller graft. This shows that modifiable factors involved in the development of early vascular complications are also thought to be donor related: large-for-size grafts should be avoided. Furthermore it is well known that the surgeon plays an important role in preventing vascular complications. He or she must always aim for a most meticulous and scrupulous technique and must, during closure of the abdomen, prevent compression of the graft; the abdomen thus might be left open, or only the skin will be closed. During the LT and post-operative care, hypovolemia, associated with a high hematocrit and hemoglobin higher than 10 g/dL, must be avoided, and coagulation overcorrection must be averted.

Intraoperative Doppler ultrasound (US) can spot vascular problems that can already be solved perioperatively and is thus strongly recommended to be performed preferably before closure of the abdomen as well as immediately after closure. Thereafter, a twice-a-day Doppler US follow-up is optimal in the first week to promptly detect vascular complications and to allow for swift treatment. Daily Doppler US during the second week to confirm patency is paramount, if available. Afterward, a twice-a-week Doppler US is performed for the following 2 weeks if the patient is still hospitalized. Whenever thrombosis is suspected, computed tomography (CT) angiography must confirm the diagnosis and detailed anatomy. Of interest, implantable Doppler probes were also reported to be used for a continuous follow-up of the vascular inflow; we speculate that their actual low sensitivity precluded its spread.

In general, patient and graft survival are significantly lowered by all types of early vascular complications ; notably, if thrombectomy and revascularization are unsuccessful, death might ensue if the patient cannot be retransplanted in time (see Chapter 22 . Early post-operative complications. General aspects). It is thus of utmost importance to know the different types of early vascular complications as well as their treatment modalities. In the following sections, the early arterial and venous complications will be described.

Early Hepatic Artery Complications

The hepatic artery can present with four different types of complications: (1) thrombosis, (2) stenosis, and, much more rarely, (3) pseudoaneurysm and (4) artery steal syndrome.

Early Hepatic Artery Thrombosis

Early HAT is defined as thromboembolic occlusion of the hepatic artery within the first 4 weeks after LT. Table 20.1 summarizes studies that have investigated the incidence of early HAT. The median time to the detection of early HAT is 7 days; the median incidence of early HAT in PLT is 8%, but reports range from 2% to as high as 14% in recent series. During the post-operative period, whenever a low or weak arterial flow is detected on US (see Chapter 29 ), suspicion of HAT must be raised and confirmation sought by CT scan, which will confirm the diagnosis of HAT or show indirect signs of hepatic artery stenosis.

Table 20.1

Overview of Articles Looking at Early Hepatic Artery Thrombosis

Article No. of patients Donor Graft Incidence of early HAT
Someda et al. 1995 46 46 LDLT 16 Left lobe
29 Left lateral segment
1 Right lobe
Sheiner et al. 1997 78 NA NA 7.7%
Sieders et al. 2000 120 NA 67 Whole liver
11 Right lobe
35 Left lobe
23 Left segmental
13% overall 10%
Wagner et al. 2000 12 12 LDLT 12 Left lateral segment 8.3%
Stringer et al. 2001 400 NA NA 5.5%
Nishida et al. 2002 139 129 DDLT
107 Whole liver
22 Reduced size
Broniszczak et al. 2006 71 71 LDLT NA 5.6%
Yilmaz et al. 2007 69 33 DDLT
30 Whole liver
3 Split liver
Bekker et al. 2009 Systematic review Systematic review Systematic review 8.3%
Ooi et al. 2009 97 NA NA 3.4%
Uchida et al. 2009 382 403 LDLT 3 Right lobe
41 Left lobe
426 Left lateral segment
33 Monosegment
Backes et al. 2010 437 NA NA 6.8%
McLin et al. 2010 103 NA NA 1.9%
Warnaar et al. 2010 232 232 DDLT NA 13.7%
Sevmis et al. 2011 119 122 LDLT NA 8.1%
Ackermann et al. 2012 516 NA NA 7.6%
Seda-Neto et al. 2016 656 656 LDLT 554 Left lateral segment
79 Left lobe
9 Right lobe
8 Left lobe and segment 1
6 Monosegment
Ziaziaris et al. 2017 275 298 DDLT
88 Whole liver
116 Split liver
94 Reduced liver
5.7% overall 8.5%
Zuo et al. 2018 73 73 LDLT 56 Left lateral segment
8 Left lobe
7 Right lobe
2 NS
Astarcioglu et al. 2019 61 NA NA 4.9%
Kutluturk et al. 2019 175 175 LDLT 17 Reduced left lateral segment
99 Left lateral segment
46 Left lobe
9 Right lobe

DDLT , Deceased donor liver transplant, HAT , hepatic artery thrombosis; LDLT, living donor liver transplantation; NA, not available

Risk Factors for Early Hepatic Artery Thrombosis

The high incidence of HAT in children is multifactorial, and recipient- as well as donor- and graft-related factors play a role, as do peri- and post-operative aspects; they are summarized in Table 20.2 .

Table 20.2

Risk Factors Associated With Early Hepatic Artery Thrombosis

  • 1.

    Recipient factors

Small hepatic artery (≤ 3mm)
Female sex
Primary sclerosing cholangitis

  • 2.

    Donor factors

Small donors
Donor age
CMV-positive donor and CMV-negative recipient

  • 3.

    Graft factors

High vascular resistance
Graft size (too small, too large)

  • 4.

    Perioperative factors

Prolonged cold and warm ischemia time
Surgical technique
Surgical time
Intraoperative hepatic artery thrombosis

  • 5.

    Post-operative factors

Decreased arterial perfusion pressure
Increased intraabdominal pressure

Recipient factors for early HAT in children after PLT have been reported to include small diameter of the hepatic artery (≤ 3 mm), vasospasm, primary sclerosing cholangitis, and, surprisingly, female sex. Re-LT is also a risk factor for developing early HAT. Graft-related factors have been reported to lead to an increased intravascular resistance within the graft for several reasons, such as ischemia-reperfusion lesions, early rejection, outflow obstruction, as well as intravascular volume overload. In addition, graft size has an impact on the development of HAT; high graft-to-recipient weight ratio (GRWR) is a risk factor for HAT. This goes together with the fact that the higher the donor-to-recipient weight ratio in reduced-size grafts, the higher the potential for vascular complications. In contrast, small donors, with GRWRs of 1.1% or less, also have been reported to be associated with higher HAT rates. In summary, a graft-to-recipient mismatch represents a risk factor for early HAT. But even when no mismatch is present, too small a graft is a risk factor; it is said that if the cumulated donor and recipient’s weight is less than 20 kilograms, the risk for HAT is too significant and the donor should be declined if not emergently needed. Also, age seems to play a role: in PLT complicated by HAT, the donor-to-recipient age ratio was significantly lower ; in other words, the younger the donor, compared with the recipient, the higher the risk for HAT. Further, a factor both incriminated for early and late HAT is the cytomegalovirus (CMV)-positive status of a donor in a CMV-negative recipient.

Is there a difference in HAT incidence between living donor and deceased donor LT? A systematic adult and pediatric review did not find a difference in HAT rates between living donor and deceased donor LT. Also in regards to graft type, data on HAT rates in split/reduced and whole liver grafts are not conclusive. This might be because the child often gets the entire arterial axis from the aorta to the hepatic artery, even in partial grafts, a universal rule in the procurement technique.

Perioperative risk factors for early HAT include longer surgical time and prolonged ischemia time : a median warm ischemia time of 45 minutes was found in a group of patients with early HAT versus 38 minutes in the group without early HAT, a difference found to be statistically significant in an adult population ; a median cold ischemia time of 14.3 hours was found in the group with early HAT versus 11.7 hours in the group without, which is statistically significant. But probably most importantly, technical aspects play a critical role in the development of HAT, and it has been reported that up to 20% of early HAT cases develop because of surgical technique failure. Steady improvement of technique must be sought. Microsurgical techniques, for example, have been reported to diminish the HAT rate. Yet loupe magnification yields the same HAT rates as operative microscopy and possibly is the least intricate and most simple assistance a surgeon can get to perform a proper anastomosis. Interrupted sutures might lead to lower HAT rates than running continuous sutures, yet they are only described in the adult literature. Nonetheless, it seems that back-table reconstruction of the hepatic artery was not found to be a risk factor. Also, grafts supplied by multiple arteries do not seem to have an increased HAT rate in a small series ; and of interest, even a trend for less HAT was reported in the presence of two arterial anastomoses! As for arterial interposition grafts between the aorta and the donor hepatic artery, there are controversies regarding their associated risks for HAT: some proved that arterial grafts increase the risk of HAT, whereas others found the contrary, advocating the liberal use of interposition grafts in cases of small-caliber arteries. A combined adult and pediatric meta-analysis identified arterial grafts as risk factors for early vascular complications. However, confounding factors might be also the prolonged operative time and the presence of extra anastomoses. Even if the literature is discordant in general, it has been reported that in recipients with Alagille syndrome, the aortic conduit reconstruction was proved to lead to fewer HAT cases than standard arterial anastomosis. Another subgroup of patients that may benefit from the use of interposition grafts are patients with metabolic disease, known to have higher rates of hepatic artery complications; the use of interposition grafts was advocated in pediatric living donor LT to reduce the hepatic artery complication rates. Last but not least, and quite obvious, intraoperative HAT was also found to be associated with early post-operative HAT.

Post-operatively, decreased arterial perfusion pressure and increased intra-abdominal pressure also seem to promote HAT. Therefore, post-operative hemodynamic management is of utmost importance, and hypovolemia must be avoided. And, as for other thrombotic complications, if abdominal closure seems difficult perioperatively, the use of absorbable meshes to hold the muscular wall together should be advised to decrease the intraabdominal pressure.

Consequences and Management of Early Hepatic Artery Thrombosis

Acute liver failure is the most severe complication of early HAT, needing emergent re-LT. Secondly, and much more frequently, HAT can lead to the following ischemic biliary complications: (1) early bile leak with possibly subsequent biliary stenosis, or (2) late multiple intrahepatic biliary strictures, that is, ischemic cholangiopathy, which later mostly need re-LT. Both types of presentations might also be associated with severe sepsis and can thus be life threatening.

Consequently, early HAT detection followed by rapid management and graft salvage is of utmost importance. The first-line treatment in early HAT is urgent graft revascularization ( Figure 20.1A ). Classically, in the first 10 days, it is surgical, with revision of the anastomosis, possibly donor interposition jump graft, and, if deemed beneficial, associated with urokinase and low-molecular-weight heparin. Failure of revascularization might lead to the need for re-LT.

During the surgical revision, if an anastomotic stricture or kinking is found, this needs a local revision associated with thrombectomy using a Fogarty catheter followed by thorough ante- and retrograde injection of a heparin solution. A local vasodilator (papaverine) locally applied with a swab might also improve the blood flow. If thrombectomy does not lead to recovery of arterial flow, local thrombolysis with urokinase (100,000 IU–250,000 IU) might be attempted if the patient does not show hemorrhagic complications. If no anatomic anomaly of the standard anastomosis is found in the first few days after LT, an aortohepatic reconstruction with the donor iliac conduit might be performed. All types of surgeries are post-operatively managed with intravenous anticoagulation. Additionally, local or systemic recombinant tissue plasminogen activator (1–3 mg) might be used after surgical thrombectomy. The choice and dosage of urokinase and/or recombinant tissue plasminogen activator vary according to center policies.

Overall, surgical revascularization success rates are around 50% ; revascularization leading to graft salvage has been shown to be more frequently successful in asymptomatic (82%) than in symptomatic patients (40%).

Endovascular interventions have also been reported for the treatment of early HAT; transcatheter arterial thrombolysis alone or associated with intraluminal stent placement has been reported with high long-term patency rates of 90% if successful and a graft salvage rate of 50%. The timing after PLT, when these procedures might be attempted, is controversial, given the risk of hemorrhage, but sporadic reports have been received about doing this procedure as soon as 4 days after LT. Risks and benefits must be carefully considered, and interventional radiologists must be experienced if early endovascular intervention is dared.

If HAT occurs later than 10 days and in the absence of hepatic failure, conservative treatment with therapeutically dosed low-molecular-weight heparin can be an option, with HAT resolution reported.

Re-LT has been reported to be needed in as many as 62% of the patients with HAT. Of note, 30% of all early re-LT are caused by HAT. Mortality in HAT, stated to be as high as 33%, is mainly caused by the inability to supply a new graft.

In summary, HAT leads to increased graft loss (as high as 70%) but does not significantly impact patient survival, probably because re-LT is successful in most patients. Graft survival rates are higher after revascularization and especially if revascularization is performed early in asymptomatic patients. Even if reoperated, HAT patients have higher biliary complication rates. Surgery is the milestone of the treatment of HAT.

Early Hepatic Artery Stenosis

The incidence of early hepatic artery stenosis has been reported at 7.2%, with two-thirds of the stenosis occurring at the anastomotic site. Hepatic artery stenosis can lead to HAT, typically in the immediate post-operative period, when hemostasis is still unbalanced and the procoagulation status is still predominant. Etiologies of hepatic artery stenosis are summarized in Table 20.3 .

Feb 23, 2021 | Posted by in HEPATOPANCREATOBILIARY | Comments Off on Early Vascular Complications

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