Early catheter-directed portal vein thrombolysis in myeloproliferative disorder-related diffuse mesenteric venous ischemia: A case report

Abstract

BACKGROUND

Portal vein thrombosis (PVT) is a rare condition and is often associated with cirrhosis, malignancy, or prothrombotic states. Currently, systemic anticoagulation is the standard to treat PVT. The role of alternative treatments are currently under investigation. In particular direct thrombolysis for the treatment of nonmalignant PVT is controversial due to the risk of bleeding. Here we have reported a case highlighting therapeutic considerations and outcomes of direct thrombolysis.

CASE SUMMARY

A 67-year-old male without a prior history of cirrhosis or malignancy presented with acute abdominal pain and peritonitis. Contrast-enhanced computed tomography revealed complete thrombosis of the portal vein with extension into the superior mesenteric vein. These findings were consistent with impending mesenteric ischemia. Despite systemic anticoagulation the patient’s symptoms progressed. Urgent catheter-directed thrombolysis via a transhepatic approach was initiated using continuous urokinase infusion. We observed substantial thrombus regression and resolution of ischemic symptoms, thereby avoiding surgical intervention. Subsequent hematologic evaluation revealed a JAK2 V617F mutation-associated polycythemia vera as the underlying prothrombotic disorder.

CONCLUSION

Early low-dose catheter-directed thrombolysis provided a safe and effective treatment for a patient with noncirrhotic, nonmalignant PVT associated with mesenteric ischemia, demonstrating the utility of an alternative treatment for PVT.

Key Words: Portal vein thrombosis; Myeloproliferative disorder; Catheter-directed thrombolysis; Transhepatic thrombolysis; Transjugular thrombolysis; Case report

Core Tip: Systemic anticoagulation is currently the first-line treatment for noncirrhotic portal vein thrombosis, and endovascular therapy typically reserved as a rescue option. Early direct thrombolysis with lower doses achieved good recanalization and a low risk of bleeding for our patient. However, the optimal therapeutic dose range requires further investigation.

INTRODUCTION

The portal vein collects venous return from all digestive organs and supplies 75% of the blood flow to the liver[1]. Portal vein thrombosis (PVT) is a rare condition with an incidence of 0.7-3.79 per 100000. Patients with noncirrhotic, nonmalignant PVT are often (21%-32% of the time) associated with myeloproliferative neoplasms[2]. Extension of the thrombus into mesenteric vessels increases the risk of intestinal infarction with mortality rates up to 60%[2].

Anticoagulation is the first-line therapy recommended for recent thrombi (i.e., those having presented within 6 months)[3]. Anticoagulation achieves recanalization in 30% of patients. Unfractionated heparin or low-molecular-weight heparin is initially prescribed, followed by vitamin K antagonist or direct oral anticoagulants, which have been shown to increase recanalization rates[4,5]. Alternative interventional therapies, including thrombus aspiration, catheter-direct thrombolysis (CDT), or transjugular intrahepatic portosystemic shunt, have been reported in selected patients with noncirrhotic PVT. Currently, the evidence for the success of these therapies remains limited, and comparative outcomes are unclear.

We presented a case in this report in which CDT was initiated within 1 day of PVT diagnosis. The patient made a complete recovery within 2 weeks, emphasizing the potential benefit of timely interventional therapy. We also performed a literature search of the terms “recent noncirrhotic portal vein thrombosis”, “direct thrombolysis”, and “endovascular treatment” to summarize the safety and efficacy of direct thrombolysis.

CASE PRESENTATION

Chief complaints

A 67-year-old male from Taiwan, who was an active smoker, presented to the emergency department with persistent right upper quadrant abdominal pain that had persisted for 3 days.

History of present illness

The patient denied experiencing nausea or vomiting. He reported normal bowel movements with smooth defecation noted the day before admission.

History of past illness

The patient had a history of coronary artery disease. He had undergone coronary artery stenting in 2016 but was lost to follow-up for 5 years. At the time of admission, he was not taking any medication. He had no history of hepatic disease or malignancy.

Personal and family history

The patient’s family history was unremarkable.

Physical examination

The patient weighed 86 kg. Upon presentation his vital signs were as follows: Temperature: 36.6 °C; blood pressure: 156/116 mmHg; heart rate: 102 beats/minute; and respiratory rate: 18 breaths/minute. Abdominal examination revealed diffuse tenderness that was greatest in the right upper quadrant. This tenderness improved after administering analgesia. No rebound tenderness or muscle guarding was detected. Bowel sounds were decreased, and the liver and spleen were not palpable.

Laboratory examinations

Serology revealed hyperbilirubinemia [total bilirubin concentration: 2.3 mg/dL (normal range: 0.3-1.0 mg/dL)] and leukocytosis [white blood cell: 14560/μL (normal range: 4500-11000 μL); neutrophil count: 78.5% (normal range: 40.0%-74.0%)]. Fibrinogen levels were elevated to 501.6 mg/dL (normal range: 200.0-400.0 mg/dL), and D-dimer levels were markedly increased [> 100000 ng/mL (normal range: < 0.5 ng/mL)]. Creatine kinase and lactate levels were within normal limits. The prothrombin time and partial thromboplastin time were normal. The patient’s procalcitonin level was mildly elevated [0.63 ng/mL (normal range: < 0.05 ng/mL)].

Imaging examinations

Contrast-enhanced abdominal computed tomography (CT) demonstrated a completely occlusive PVT extending into the superior mesenteric vein without evidence of cavernous transformation. Segmental small bowel wall thickening with fatty stranding, suggestive of an ischemic process, was observed (Figure 1).

Figure 1 Contrast-enhanced abdominal computed tomography images of portal and superior mesenteric vein thrombosis. A: Portal vein occlusion (arrow) upon admission; B: Mesenteric fat stranding with bowel wall thickening (circle), consistent with early mesenteric ischemia.

MULTIDISCIPLINARY EXPERT CONSULTATION

A multidisciplinary discussion was conducted involving the general surgery, radiology, and hematology teams. The radiology team recommended and performed CDT. They also provided serial venography during hospitalization to evaluate the therapeutic response and guide the duration of the infusion. The hematology team was consulted for diagnosis and management of the underlying myeloproliferative disorder. The coordinated input from these specialty teams optimized the patient’s treatment strategy while monitoring potential complications.

FINAL DIAGNOSIS

The patient was diagnosed with PVT and imminent ischemic bowel secondary to JAK2 V617F mutation-related polycythemia vera after a comprehensive hypercoagulability survey.

TREATMENT

Systemic anticoagulation with unfractionated heparin was initiated immediately, targeting an activated partial thromboplastin time of 50-70 seconds. Due to persistent symptoms, interventional radiology was consulted the day after admission. The general surgeon recommended CDT and discussion with the radiologist led to the latter performing placement of a 4.0 Fr Fountain catheter in the superior mesenteric vein using a transhepatic approach. A continuous urokinase infusion was initiated at a rate of 12000 U/hour. Fibrinogen levels were closely monitored to assess the bleeding risk and were maintained above 100 mg/dL. Follow-up venography was conducted 1 week after CDT was initiated. Venography demonstrated partial recanalization of the portal vein. CDT was continued for a total of 14 days with a cumulative urokinase dosage of approximately 2880000 U (10000-16000 U/hour). Overlapping systemic anticoagulation with heparin was continued for 5 days. Then the patient was transitioned to apixaban (a direct oral anticoagulant). Detailed laboratory results and medication records are presented in Table 1.

Table 1 Laboratory parameters and medications during hospitalization.

Parameter	Time to treatment initiation (days)
	D - 0	D + 1	D + 2	D + 3	D + 4	D + 5	D + 6	D + 7	D + 8	D + 13	D + 15
CDT with urokinase (U/hour)		12000	12000	12000	14000	16000	16000	16000	12000	10000	Off
Systemic anticoagulant
Heparin pump (U/hour)	440	440	320	320	200	Off
Oral apixaban						2.5 mg twice/day
Fibrinogen (mg/dL)		684	501	624	624	551			342	460	668
APTT (second)	32.8	44.9	38.2	35.9	39.6	41.5	41.3	36.0	45.5		39.8
Lactate (mmol/L)	2.2	2.5	1.6	1.0	0.7	0.9
CK (U/L)	57		47	220	195				76	48
WBC (103/μL)	12480	14180	12030	10830	10720	8980			11110	9140	8570
Hemoglobin (g/dL)	18.8	17.0	13.7	13.5	13.4	12.4			13.7	11.1	11.4
CRP (mg/dL)	11.10		10.58		1.77	3.85	4.30
Imaging				Abdominal CT					Venography		Venography

D - 0 indicates the day of presentation to the Department of Emergency and the initiation of treatment; D + indicates the number of days after initiation of treatment. APTT: Activated partial thromboplastin time; CDT: Catheter-direct thrombolysis; CK: Creatine kinase; CRP: C-reactive protein; WBC: White blood cell.

OUTCOME AND FOLLOW-UP

The patient experienced a self-limited episode of melena, resolving after urokinase tapering. His abdominal pain also subsided. The fibrinogen concentration decreased steadily throughout the course of treatment but remained above 100 mg/dL. A follow-up portal vein venography demonstrated portal vein patency with residual filling defects in the superior mesenteric vein branches, indicating partial thrombus resolution (Figure 2). After completing 14 days of CDT, the patient tolerated a soft diet and resumed normal bowel function. He was discharged on a therapeutic regimen of clopidogrel and apixaban.

Figure 2 Contrast abdominal computed tomography after 7 days demonstrated partial resolution of portal vein thrombosis. A: Partial recanalization of the portal vein (arrow); B: Persistent thrombus in the superior mesenteric vein (arrow).

Hematological evaluation confirmed a JAK2 V617F mutation, establishing polycythemia vera as the underlying prothrombotic condition. The patient was referred to the Department of Hematology for long-term management, which included cytoreductive therapy and anticoagulation therapy. At the 3-month follow-up, the patient remained asymptomatic with no abdominal pain or gastrointestinal complaints. Another contrast-enhanced CT will be performed at the 6-month follow-up.

DISCUSSION

Noncirrhotic, nonmalignant PVT tends to present as a more acute course compared with cirrhotic PVT. Acquired hematological disorders account for up to 32% of extrahepatic PVT cases in Western and Asian populations[6]. Among these disorders myeloproliferative neoplasms with JAK2 V617F mutations are the most significant risk factors. Screening for this mutation is recommended for all adult patients who present with splanchnic vein thrombosis[1].

Although systemic anticoagulation is the standard first-line therapy for acute noncirrhotic PVT, patients with signs of impending bowel ischemia require advanced interventions such as CDT or thrombectomy[2]. Surgical resection of necrotic bowel is necessary after failure to achieve timely reperfusion. Complete recanalization is achieved in 30% of patients with acute PVT after treatment with systemic anticoagulation[2]. Factors associated with treatment failure include the onset of thrombosis, the presence of ascites, splenic vein involvement, and underlying prothrombotic disorders[4]. Endovascular therapy is typically a rescue option after anticoagulation fails, but the risk of bleeding complications remains the primary concern[2].

Recent studies have reported improved safety of endovascular therapy due to refined techniques and the adoption of lower-dose thrombolysis regimens. Our literature search identified six relevant studies: Five retrospective series and one prospective study (Table 2)[7-12]. Although endovascular therapy achieved higher complete recanalization rates (48%-70%) than anticoagulation alone (particularly when performed within 10 days of diagnosis), this benefit was offset by a significant risk of major bleeding. The thrombolytic regimens varied across the studies [urokinase: 20000-100000 IU/hour; recombinant tissue plasminogen activator (rtPA): 0.5-1.0 mg/hour; duration 2-14 days]. Complications have been reported in 19.1%-37.5% of patients, especially with higher-dose rtPA regimens. In response to this risk, lower-dose thrombolytic protocols have been developed and appear safer. One study used a sequential protocol of urokinase (20000 IU/hour, first day) followed by rtPA (0.5 mg/hour) and reported a 52% recanalization rate. Similarly, three additional studies[7,8,10] reported that low-dose urokinase regimens were associated with fewer complications[13] while maintaining acceptable efficacy (Table 2).

Table 2 Clinical and therapeutic parameters of portal vein thrombolysis, including the catheter access method, recanalization, and complication rate.

Ref.	Case	MPD (%)	Total occlusive PVT	CDT timing (day)	CDT		Complete recanalization rate, AC/CDT (%)	Failure rate, AC/CDT (%)	Bleeding complications[13]
					Transhepatic approach	TIPS			Grade 1/2, AC/CDT (%)	Grade 3/4, AC/CDT (%)	Death, AC/CDT (%)
Rössle et al[7], 2020	65	23	52	8.9		35	30.0/54.0	15.0/14.3	0/22.5	0/2.5	0/0
Benmassaoud et al[8], 2019	22	22.7	17	4		11	13.7/70.0	63.6/9.1	Total 318	0/18.1	0/0
Wu et al[9], 2025	25	12	18	6		25	-/48	-/16	-/16	0/0	0/0
Klinger et al[10], 2017	29	20.7	16	7		17	-/52.9	-/11.8	-/5.9	-/0	-/0
Mansour et al[11], 2022	21	14.3	14	13	9	12	-/35.0	9.5	-/23.8	-/19.0	-/1.0
Gerwing et al[12], 2019	8	0	5	0	6	2	-/62.5	-/12.5	-/12.5	-/37.5	-/1.0

AC: Anticoagulation; CDT: Catheter-direct thrombolysis; MPD: Mesenteric/portal vein thrombosis; PVT: Portal vein thrombosis; TIPS: Transjugular intrahepatic portosystemic shunt.

In our case, several factors contributed to the successful outcome. First, CDT was initiated immediately upon recognition of PVT and clinical signs suggesting early bowel ischemia rather than waiting until systemic anticoagulation failed. Most published studies reported CDT as a rescue intervention after deterioration or nonresponse to anticoagulation, a scenario in which bowel ischemia can already be advanced and higher-dose thrombolytic regimens are required. Early intervention before irreversible mesenteric injury occurred allowed the use of a relatively low-dose thrombolytic protocol while still achieving effective reperfusion in our patient. This approach likely reduced the bleeding risk commonly associated with aggressive CDT regimens and may partially explain the favorable vascular response and complete bowel salvage observed in our patient.

Two studies identified in our literature search specifically compared percutaneous and transjugular approaches for CDT in acute noncirrhotic PVT[11,12]. The transjugular intrahepatic portosystemic shunt approach demonstrated higher rates of complete recanalization and fewer severe adverse events. However, differences in major bleeding did not reach statistical significance. There may be a safety and efficacy advantage of the transjugular approach, but current evidence remains limited and heterogeneous. Further comparative studies are needed to clarify the optimal access strategies and patient selection criteria for CDT.

Although our patient had a favorable outcome, this case highlighted the significant challenges that remain in managing acute noncirrhotic PVT. The choice of a low-dose urokinase regimen and a transhepatic approach was guided by institutional experience and the limited current evidence from small, retrospective studies. Further large-scale, multicenter prospective trials are urgently needed to establish optimal treatment strategies, including ideal thrombolysis dosages and intervention timing.

CONCLUSION

Early transhepatic CDT with low-dose urokinase infusion can be an effective and safe intervention for completely occlusive PVT with impending bowel ischemia, potentially avoiding extensive bowel resection. However, further prospective studies are urgently needed to determine the optimal dosage and timing for this intervention.