Acute Mesenteric Ischemia Secondary to Protein C Deficiency: A Case Report

ABSTRACT

A 43‐year‐old hypertensive male presented with severe abdominal pain, nausea, and constipation due to Protein C deficiency with lupus anticoagulant. CT angiography revealed thrombotic occlusion of mesenteric arteries with collateral circulation. Conservative management with dual anticoagulation and parenteral nutrition achieved clinical improvement without surgery, highlighting thrombophilia's role in mesenteric ischemia.

Key Clinical Message

Mesenteric ischemia should be considered in young patients presenting with severe abdominal pain, as early CT angiography and prompt anticoagulation can prevent bowel infarction and avoid surgical intervention, even in extensive arterial thrombosis secondary to Protein C deficiency.

1. Introduction

Acute mesenteric ischemia (AMI) is a surgical emergency resulting from abrupt interruption of intestinal blood supply, which can rapidly progress to bowel ischemia and necrosis if left untreated. Early recognition and intervention are essential to reduce morbidity and mortality [1]. Approximately 0.1% of hospital admissions are attributed to mesenteric ischemia, with reported mortality ranging from 24% to 94% [2]. Depending on the underlying mechanism, AMI may result from arterial embolism, arterial thrombosis, mesenteric venous thrombosis, or non‐occlusive mesenteric ischemia [3]. Acute mesenteric arterial thrombosis accounts for approximately 30% of cases and most commonly involves the proximal superior mesenteric artery, resulting in extensive bowel ischemia [1, 4].

Diagnosis is often challenging because the presenting symptoms are non‐specific, with acute abdominal pain being the most common presenting complaint in emergency settings [1, 4]. Other symptoms such as nausea, vomiting, constipation, diarrhea, and rectal bleeding may also occur [5].

Acute mesenteric ischemia secondary to arterial thrombosis associated with Protein C deficiency is an uncommon clinical presentation that has been reported in isolated case reports [6, 7]. Protein C is a natural anticoagulant that inactivates factors Va and VIIIa, thereby regulating the coagulation cascade. Protein C deficiency may be inherited or acquired and predisposes affected individuals to thrombotic events [7].

Prompt diagnosis is essential in the management of mesenteric arterial thrombosis. In patients with high clinical suspicion, CT angiography is recommended by the World Society of Emergency Surgery, with a reported sensitivity of 96% and specificity of 94% [3]. Management depends on bowel viability, the nature of the occlusive lesion, the patient's clinical condition, and the presence or absence of peritonitis [3].

This case highlights an uncommon presentation of acute mesenteric ischemia secondary to arterial thrombosis associated with Protein C deficiency. Early diagnosis, prompt imaging, and timely initiation of appropriate management, including anticoagulation when indicated, may reduce the risk of disease progression and facilitate timely surgical or endovascular intervention when required.

2. Case Presentation

2.1. History and Examination

A 43‐year‐old hypertensive male presented with a 2‐week history of severe cramping abdominal pain, aggravated by food intake and associated with nausea and constipation. He initially received symptomatic management at a local hospital; however, his symptoms progressed, prompting referral to a tertiary care center.

On examination, the patient appeared uncomfortable, with a soft but mildly distended abdomen and generalized tenderness. Vital signs were within normal limits.

The patient had no prior history of venous or arterial thromboembolic events. There was no history of recent COVID‐19 infection, malignancy, prolonged immobilization, recent surgery, hormonal therapy, or smoking. Family history was negative for inherited thrombophilia or premature thromboembolic disease.

2.2. Investigations and Management

Contrast‐enhanced computed tomography (CECT) of the abdomen revealed a hypertrophied inferior mesenteric artery (IMA) with acute thrombotic occlusion of its branches, complete occlusion of the superior mesenteric artery (SMA), and celiac axis, and the presence of multiple collateral vessels.

There was no family history of vascular or thrombotic disorders. Based on clinical and radiologic findings, a provisional diagnosis of acute mesenteric ischemia was made. Laboratory investigations (Table 1) and a thrombophilia panel demonstrated Protein C deficiency.

TABLE 1.

Laboratory panel.

Test names	Patient value	Reference values
Protein C‐plasma	43%	70%–140%
Activated Protein C resistance, plasma (normalized ratio)	0.86	0.86–1.10
Protein S‐plasma	90%	56%–121%
Lupus anticoagulant LA screen	50.4 s	31–44 s
LA confirmatory	40.7 s	30–38 s
LA ratio	1.2 ratio	0.8–1.1
Serum anti‐cardiolipin IgG	2.7	< 10 GPL/mL
Serum anti‐cardiolipin IgM	2.12	< 5 MPL/mL
Homocysteine	9.58	5–12 μmol/L
Serum P‐ANCA	< 1	< 9.6 U/mL
Serum C‐ANCA	0.8	< 1.7 U/mL
ESR	80	< 10
Hemoglobin	11.8	13–18 g/dL
WBC count	7.3	4–11 × 103/μL
Platelet count	323	150–400 × 109/L
D‐dimers	1153 ng/mL	< 500 ng/mL
Coagulation profile (PT/INR, APTT)	PT = 13	PT = 11–14
	INR = 0.9	INR = 0–1.3
	APTT = 29	APTT = 26–32

The patient was admitted under the gastroenterology service. The case was discussed in a multidisciplinary meeting involving vascular surgery and gastroenterology; conservative management was selected because the patient remained clinically stable without evidence of bowel infarction or peritonitis. The presence of well‐developed collateral circulation suggested preserved bowel perfusion, allowing close observation with systemic anticoagulation and serial clinical assessment. The patient was admitted under the gastroenterology service. Management included keeping the patient NPO, starting total parenteral nutrition, and initiating treatment with anticoagulant agents. Therapeutic anticoagulation was initiated with low‐molecular‐weight heparin (LMWH) (enoxaparin 1 mg/kg subcutaneously every 12 h). Following clinical stabilization, the patient was bridged to oral warfarin with INR‐guided dose adjustment. As symptoms improved, oral intake was gradually reintroduced, progressing from liquids to semi‐solid meals. Considering the confirmed diagnosis of Protein C deficiency and the occurrence of acute mesenteric arterial thrombosis, long‐term oral anticoagulation was planned, with regular INR monitoring and follow‐up.

2.3. Outcome and Follow Up

He was discharged in stable condition with resolution of abdominal symptoms and scheduled for regular outpatient follow‐up in the gastroenterology clinic.

3. Discussion

Acute mesenteric ischemia may result from arterial embolism, arterial thrombosis, mesenteric venous thrombosis, or non‐occlusive mesenteric ischemia. Mesenteric arterial thrombosis is one of the major causes of acute mesenteric ischemia and accounts for approximately 20%–35% of cases [3]. In certain patients, arterial obstruction occurs secondary to an underlying hypercoagulable state; therefore, selected patients should undergo evaluation for inherited and acquired thrombophilic disorders, including Protein C and S deficiencies, Antithrombin III deficiency, anti‐cardiolipin antibodies, lupus anticoagulants, and homocysteine levels [1]. In our case, investigations demonstrated reduced Protein C levels (43%) and the presence of lupus anticoagulants, reinforcing their strong association with thromboembolic events.

Once Protein C deficiency is detected, clinicians must determine whether the cause is genetic or acquired. Acquired causes may include liver disease, vitamin K deficiency, renal disease, and disseminated intravascular coagulation among others [7]. Severe (homozygous or compound heterozygous) variants are extremely rare, estimated at roughly 1 per 500,000 people, while heterozygous cases occur in approximately 1 per 500 births [8]. However, in our case, genetic testing could not be pursued due to financial limitations.

Diagnostic delay is common because acute mesenteric thrombosis often presents with vague and non‐specific symptoms, making early recognition critical in preventing fatal outcomes. Our patient presented with severe acute abdominal pain and constipation, which are among the most commonly reported symptoms [1]. If no physical findings suggest peritonitis, the next step is usually urgent imaging. In most cases, a CT scan is initially performed to exclude other causes of acute abdominal pain. CT angiography has largely replaced conventional angiography because of its wide availability, high diagnostic accuracy, and non‐invasive nature [1]. CT features such as pneumatosis intestinalis and pneumoperitoneum can provide valuable guidance in selecting appropriate management strategies. In this case, no such findings were noted on CT angiography. The presence of extensive collateral circulation and hypertrophy of the inferior mesenteric artery may indicate pre‐existing chronic mesenteric arterial insufficiency with acute thrombotic occlusion superimposed. However, the absence of a history of postprandial abdominal pain, food fear, or weight loss makes chronic mesenteric ischemia difficult to confirm in the present case.

Management relies on rapid recognition, supportive measures, and attempts to reestablish perfusion through endovascular or surgical intervention, along with exploration and resection of any gangrenous bowel if present [9]. As our patient showed no evidence of peritonitis, exploratory Laprotomy was not undertaken. Although revascularization was attempted, it was unsuccessful; the patient demonstrated notable improvement with dual anticoagulation therapy.

Protein C deficiency has also been associated with other arterial thrombotic events, including ischemic stroke [10], myocardial infarction [11], and rarely, aortic thrombosis [12]. These reports further support evaluation for inherited thrombophilic disorders in patients presenting with unexplained arterial thrombosis. In our case, neither the patient nor family members underwent genetic workup because of financial constraints.

In contrast to many previously reported cases where delayed diagnosis resulted in bowel infarction and surgical intervention, our patient was successfully managed without operative intervention. This favorable outcome was likely related to early diagnosis, preserved collateral circulation, the absence of peritonitis, and prompt initiation of anticoagulation, highlighting the importance of individualized management based on the patient's clinical and radiological findings.

4. Conclusions

This case highlights the importance of maintaining suspicion for mesenteric ischemia in young patients with acute abdominal pain, especially in the context of thrombophilic disorders. Early CT angiography and timely initiation of anticoagulation can improve outcomes and may avoid operative intervention, even in extensive arterial occlusion.

5. Limitations

The original CT angiographic images were not available for inclusion in the manuscript, which limited the ability to provide representative imaging figures.

Author Contributions

Asad Ullah Khan: conceptualization, writing – original draft. Ahmed Ayyan: validation, visualization, writing – review and editing. Moeez Ahmad Saeed: writing – review and editing, writing – original draft. Muhammad Usman Mehmood: conceptualization, writing – original draft, writing – review and editing. Ali Gohar: validation, visualization. Wasfa Shafiq: conceptualization, writing – original draft, writing – review and editing. Muhammad Husnain Ahmad: writing – review and editing, writing – original draft. Hashim Mohamed Siraj: conceptualization, writing – review and editing. Aniqa Iqbal: writing – original draft.

Funding

The authors have nothing to report.

Consent

A written informed consent was obtained from the patient based on the journal's policies. No identifying patient information is included in this report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.