Postpartum Superior Mesenteric Vein Thrombosis and Heparin-Induced Thrombocytopenia: Clinical Insights

Introduction

Cardiovascular disease is the leading cause of maternal death in developed countries, responsible for over one-third of pregnancy-related fatalities, with venous thromboembolism (VTE) as a major contributor [1]. Hormonal changes, an enlarged uterus compressing abdominal veins, decreased physical activity, and vascular trauma from childbirth or surgery predispose pregnant and postpartum women to the Virchow triad: hyper-coagulability, venous stasis, and vascular injury [2]. Pregnant women have a 4- to 5-fold increased risk of VTE, compared with non-pregnant women, with the highest risk occurring in the first postpartum week [2–5].

VTE most commonly affects the lower limb veins, and its occurrence in the mesenteric veins is sporadic. Mesenteric vein thrombosis (MVT) is a rare and potentially life-threatening thrombotic condition, with an incidence of 2 to 2.7 per 10 000 cases, primarily affecting the superior mesenteric vein [6]. Superior mesenteric vein thrombosis (SMVT) can lead to intestinal ischemia, sepsis, septic shock, multiple organ failure, and other complications in severe cases [7]. Additionally, its symptoms are nonspecific, and delayed or missed diagnosis can result in mortality rates as high as 60% to 80% [6].

Heparin-induced thrombocytopenia (HIT) is a rare, serious immune complication triggered by antibodies to platelet factor 4-heparin in patients on heparin therapy. It rarely occurs in pregnancy (<1%) [2] and primarily presents with thrombocytopenia, arteriovenous thrombosis, and, in severe cases, bleeding [8]. HIT is rare, occurring in approximately 1 in 5000 hospitalized patients. HIT has an insidious onset, and if not detected and treated promptly, can result in amputation or death in 20% to 30% of cases [8].

Here we report a case of a 30-year-old female patient who, following the birth of her second child, experienced 2 consecutive episodes of severe VTE due to distinct causes. SMVT occurred as a result of pregnancy and childbirth, followed by HIT, due to anticoagulation therapy. These less common thrombotic events warrant attention, given their unique diagnostic and therapeutic complexities during pregnancy and puerperium. With this report of the first case of SMVT combined with HIT, clinicians can enhance their recognition of such diseases, thereby facilitating earlier diagnosis and treatment, and reducing the occurrence of adverse outcomes.

Case Report

STAGE I:

Upon admission, the patient received heparin anticoagulant therapy (nadroparin calcium 0.6 mL every 12 h). This was followed by mesenteric angiography and catheter-directed thrombolysis of the superior mesenteric vein, successfully clearing the main trunk. On day 2 after the interventional operation, the patient’s abdominal pain still existed, and she developed symptoms of hematocheia and peritonitis. The ECG monitor showed a blood pressure of 108/67 mmHg, heart rate of 78 beats per min, and respiratory rate of 30 breaths per min. An urgent follow-up abdominal CT revealed new perihepatic and perisplenic effusions, a small intestinal air-fluid level, worsened jejunal wall edema, and increased mesenteric exudate (Figure 2). A multidisciplinary team convened urgently, including Interventional Radiology, Obstetrics and Gynecology, Imaging, Intensive Care, and General Surgery departments. Taking into account the radiological changes in the patient’s abdominal CT, the presence of peritonitis signs, and symptoms of septic shock, the multidisciplinary team strongly suspected that the patient had developed intestinal necrosis and decided to proceed with an exploratory laparotomy. During the operation, about 200 mL of bloody ascites was found in the abdominal cavity, 20 cm away from the Treitz ligament, and approximately 100 cm of small intestine already had ischemic necrosis, which was characterized by edema of the bowel wall, no blood supply, and no peristalsis to the intestine. A partial small bowel resection with anastomosis was performed. During dissection, multiple thrombi were also observed in the mesenteric vessels (Figure 2). After surgery, the patient was transferred to the Intensive Care Unit for intensive perioperative management.

STAGE II:

Following anti-shock and anti-infection treatment, the patient’s abdominal symptoms improved, and heparin anticoagulation therapy was continued for SMVT. However, on postoperative day 3, new thrombosis developed in the femoral and popliteal veins of the patient’s right lower extremity. Given the patient’s high thrombosis risk factors, we initially suspected thrombophilia. Observing decreased D-dimer levels and improved abdominal symptoms, we deemed the treatment effective and continued heparin anticoagulation. Unfortunately, the thrombosis did not improve as expected. On postoperative day 7, an ultrasound revealed thrombosis in the intermuscular vein of the right lower extremity, and enhanced CT of the chest and abdomen showed thrombosis in the main trunk of the superior mesenteric artery, root, and left internal branch of the portal vein, superior mesenteric vein, inferior vena cava, and inferior branches of both pulmonary arteries (Figure 3). These findings indicated exacerbation of the thrombosis. The multidisciplinary team reconvened to explore potential systemic illnesses, including autoimmune disorders. We conducted tests for lupus anticoagulant, antiphospholipid antibodies, vasculitis antibodies, 6-item vasculitis panel, 16-item ENA profile, and complement levels, all of which were normal, ruling out some connective tissue diseases. The patient denied any history of heparin exposure. Given the patient’s deteriorating condition after heparin, such as thrombocytopenia, with an initial platelet count of 207×109/L that decreased to 74×109/L by day 10 of heparin therapy (Figure 4), and developing extensive thrombosis in the portal vein, superior mesenteric artery and vein, inferior vena cava, and pulmonary artery, we strongly suspected HIT. In addition, the patient had a 4Ts score (Thrombocytopenia, Timing, Thrombosis, absence of oTher explanations) of 8 out of 8, supporting the HIT diagnosis. Our hospital was not equipped to perform HIT antibody testing; therefore, a definitive diagnosis of HIT could not be established. Treatment adjustments included discontinuing heparin, initiating argatroban anticoagulants, and adding glucocorticoids and intravenous immunoglobulin (IVIG) as adjunctive therapy, while surgical intervention was deemed unnecessary at this stage. The use of IVIG and glucocorticoids can suppress autoimmune responses and modulate immune function, mitigating the impact of HIT.

STAGE III:

Following consultations, we transitioned from nadroparin to argatroban (60 mg daily), adding methylprednisolone sodium succinate (80 mg daily) and IVIG (20 g daily). On postoperative day 14, CT angiography showed no new thrombosis. Additionally, superior mesenteric vein thrombus and bilateral pulmonary artery branch thrombus had significantly reduced, while thrombi in the portal vein, inferior vena cava, and superior mesenteric artery were completely resolved (Figure 5). The patient’s platelet count returned to normal (Figure 4), and she was discharged 20 days after surgery. After being discharged, she continued to take rivaroxaban (20 mg daily). One month later, repeat contrast-enhanced CT of the chest and abdomen and lower extremity venous ultrasonography showed only a small thrombus remained in the right popliteal vein, with no thrombi in other regions. The patient reported positive recovery and satisfaction with treatment. The patient was followed up 3 years after discharge, and there was no recurrence of thrombosis.

Discussion

VTE is a serious complication in pregnant and postpartum women and one of the leading causes of maternal death in developed countries, accounting for 9% of cases in the United States, France, and United Kingdom [9]. Compared with non-pregnant women, pregnant women have a markedly higher risk of venous thrombosis, with an incidence of about 1.2 per 10 000 [2]. Studies indicate that a personal or family history of VTE, advanced maternal age (>35 years), obesity, smoking, multiple pregnancies, cesarean section, and varicose veins are additional risk factors for venous thrombosis in pregnant women [4,10,11]. Furthermore, studies suggest a dose-dependent relationship between obesity and VTE [12], as obesity can lead to venous stasis, hypercoagulability, impaired fibrinolysis, and increased risk of venous thrombosis. Although this patient had no history of hormone use or varicose veins, the first postpartum week was a high-risk period for thrombosis, especially given her body mass index of 32, indicating obesity. Therefore, pregnancy, childbirth, and obesity were critical factors in the patient’s SMVT.

MVT is a rare form of intestinal ischemia resulting from embolism in the mesenteric vein, primarily affecting middle-aged and elderly individuals. MVT has a subtle clinical onset, with abdominal pain as the primary symptom, sometimes accompanied by nausea, vomiting, hematochezia, and abdominal distension. Due to its nonspecific symptoms, MVT is often mis-diagnosed or overlooked. MVT has a mortality rate of up to 25%, with disease severity ranging from mild local ischemia to severe intestinal necrosis, peritonitis, shock, and death [6,7]. Studies indicate that deep vein thrombosis and pulmonary embolism are the most common types of venous thrombosis in pregnant women, with a small number occurring in the intracranial venous sinuses or ovarian veins. However, SMVT in pregnant and postpartum women is exceedingly rare, with only about 20 cases reported worldwide [13]. In this case, the patient presented solely with superior mesenteric VTE and obstructive symptoms, indicating a highly unusual presentation. For pregnant women and puerperal patients experiencing abdominal pain, when clinicians are in pursuit of the etiological factors, they are highly inclined to take into account diseases associated with pregnancy or childbirth and are apt to overlook diseases of other systems.

Prompt anticoagulation therapy is essential upon diagnosing SMVT. If no intestinal necrosis is present, and the patient remains stable, catheter-directed thrombolysis and thrombectomy are the preferred initial treatments. However, signs of peritonitis, CT findings of intestinal necrosis or perforation, or worsening symptoms necessitate urgent surgical resection or open thrombectomy [6,14]. In the present case, systemic heparin was started immediately, followed by percutaneous venography and thrombolytic therapy, to restore mesenteric vein patency. Abdominal CT re-evaluation revealed worsening air-fluid levels, severe jejunal edema, and increased mesenteric exudate, alongside peritonitis and signs of infectious shock. Immediate surgical exploration confirmed necrotic small bowel requiring resection. In acute mesenteric ischemia, neither anticoagulation nor interventional techniques can fully assess ischemic bowel necrosis; only surgery can verify bowel viability. Precise timing is critical, as delayed or premature surgery can cause irreversible damage. A multidisciplinary team approach supports surgeons in diagnosis and treatment decisions [6]. Surgeons should initially evaluate the intestinal condition through laparoscopic exploration. For ischemic bowel that has not yet become necrotic, interventionalists may attempt thrombolysis, thrombectomy, stent implantation, or angioplasty. If the bowel is necrotic, surgeons should perform bowel resection to preserve as much bowel as possible and minimize intra-abdominal infection [14].

HIT, as a potential complication of heparin anticoagulation therapy, is a rare condition with an incidence of 0.2%. It has a high rate of disability and mortality, with approximately 10% of patients with HIT dying in the hospital [15,16]. HIT is an immune thrombotic disorder resulting from the formation of immunoglobulin G antibodies against ultra-large complexes of heparin and platelet factor 4. This condition can arise during heparin use in clinical settings and is characterized by transient or persistent thrombocytopenia, with or without pathological thrombosis, and can lead to severe bleeding in some cases [16,17]. The diagnosis of HIT primarily relies on the 4Ts score and dynamic monitoring of platelet levels, combined with HIT antibody detection and/or platelet function tests to confirm or exclude the diagnosis [18,19]. In suspected HIT cases, heparin should be stopped immediately and replaced with non-heparin anticoagulants, such as factor Xa inhibitors (fondaparinux, apixaban, rivaroxaban) or thrombin inhibitors (argatroban, bivalirudin, dabigatran). IVIG is beneficial as adjunctive therapy for patients with HIT, and plasma exchange is an effective adjunctive therapy [15,17,20,21]. In the present case, the patient’s 4Ts score was 8 (out of 8), with a platelet level of 207×109/L upon admission, which decreased to 74×109/L on day 10 of heparin anticoagulation. The patient exhibited severe systemic thrombosis, including thrombosis in the portal vein, superior mesenteric artery, superior mesenteric vein, inferior vena cava, and pulmonary artery, confirming the diagnosis of HIT. Furthermore, after discontinuing heparin and switching to argatroban for anticoagulation, the platelet level gradually returned to within the reference range. CT and ultrasound results indicated improvement in the patient’s thrombosis, suggesting that the treatment was effective and further corroborating the diagnosis of HIT. Regrettably, we did not conduct the HIT antibody test, as our hospital does not have this testing item available. Additionally, it is important to consider differential diagnoses, such as thrombophilia, thrombotic thrombocytopenic purpura, immune thrombocytopenic purpura, and other conditions, when encountering thrombosis and thrombocytopenia in clinical practice. If there is a high suspicion of HIT, but the diagnosis cannot be confirmed, discontinuing heparin immediately and switching to other anticoagulants is also a good option.

Conclusions

Overall, this report presents the first documented case of HIT secondary to heparin anticoagulation following surgery for SMVT, underscoring the significant challenges in treating SMVT and the complexities of diagnosing HIT. Furthermore, SMVT is a serious condition that necessitates a multidisciplinary approach to diagnosis and treatment as early as possible. Excessive conservative treatment can potentially delay or exacerbate the condition, and accurately determining the timing of surgery is the key to treatment. Additionally, HIT is a severe and rare complication of heparin administration that necessitates prompt diagnosis and treatment. For patients exposed to heparin, if there is unexplained thrombocytopenia (sometimes accompanied by thrombosis), the possibility of HIT should be considered. It is necessary to conduct the 4Ts score and test for HIT antibody.