Rapid-Onset Venous Thrombosis After Tibia Fracture: A Case Report

Introduction

Systematic evidence demonstrates a 20% incidence of deep vein thrombosis (DVT) following lower-extremity fractures, with established risk factors including prior venous thromboembolism (VTE), advanced age (≥60 years), prolonged immobilization (>72 hours), decompensated heart failure (NYHA class III–IV), and morbid obesity (BMI ≥35 kg/m2) [1]. While conventional clinical paradigms maintain that thrombogenesis typically occurs 48–72 hours after injury [2], the present case shows that venous thrombosis occurred within 7.5 hours after a proximal tibia fracture, which is the fastest onset reported in the orthopedic literature, suggesting that the window for thromboprophylaxis needs to be significantly shortened.

Case Report

A 43-year-old man developed acute-onset persistent dizziness accompanied by visual disturbances (blurred vision), inability to work at a computer, and Chinese pinyin typing impairment at 17: 00 on May 22, 2024. The patient did not seek medical attention despite these neurological symptoms. Upon awakening at 07: 00 on May 23, 2024, all the symptoms persisted unchanged. At 08: 30 the same day, while riding an electric bicycle, he collided with a roadside barrier, sustaining right lower-extremity trauma manifesting as significant mobility restriction. He was subsequently transported to our ED, arriving at 13: 53 on May 23, 2024 with significant cognitive impairment: incoherent verbal responses and impaired attention and concentration. Lower-extremity CT imaging demonstrated a complete, closed, proximal tibia intra-articular fracture, classified as AO/OTA type B (Figure 1A, 1B). Brain magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) sequences demonstrated multiple acute ischemic stroke (Figure 2A–2C) involving in the left occipital cortex and periventricular white matter adjacent to the body of the left lateral ventricle. An emergency diagnostic workup revealed a coagulation profile showing markedly elevated D-dimer at 9.39 mg/L (reference: <0.24 mg/L) (a 39.1-fold increase) and normal coagulation parameters, including PT, aPTT, fibrinogen, and platelet count. Additional laboratory workup involved complete blood count, cardiac biomarkers (Troponin I and CK-MB) and renal function, all within normal limits. In the ED, bilateral lower-extremity venous ultrasound (Figure 3A) showed no deep or superficial venous thrombosis, preserved venous compressibility, normal phasic flow in all segments, and no evidence of venous reflux.

During the admission physical examination, the vital signs were: temperature 37.1°C (98.8°F), pulse 94 beats per minute, respiratory rate 19 breaths per minute, blood pressure 130 over 82 mmHg, and oxygen saturation 97% on room air. Mental status was recovered (GCS 15). Visual field testing showed right homonymous hemianopia. Musculoskeletal examination of the right lower extremity revealed marked periarticular swelling of the knee and diffuse edema extending to the distal leg. The left lower extremity had a normal sensory examination result, with intact light touch and pinprick sensations bilaterally. The deep-tendon reflexes were 2+ bilaterally (normal) and showed no pathological reflexes (Babinski-negative). The patient had type 2 diabetes mellitus, suboptimally controlled due to intermittent adherence to metformin therapy. There were no known diabetic complications. He denied any history of tobacco use (he was a never-smoker) and denied any history of alcohol consumption, and had no family history of thromboembolic disorders or premature cardiovascular disease.

Due to progressive right-calf swelling, repeat lower-extremity venous duplex ultrasonography was performed at 16: 04 on May 23, revealing right soleal vein dilatation (maximum diameter: 0.5 cm), hypoechoic intraluminal thrombus (length: 3.0 cm), non-compressible venous segment, and absent color Doppler flow (Figure 3B), which indicates the formation of a right soleal vein thrombosis. A spiral computed tomography (CT) scan of the right knee joint revealed a proximal tibial fracture, partially intra-articular, classified as AO/OTA type B, indicating a complete, closed fracture pattern (Figure 1A, 1B). The complete clinical course, including the temporal relationship between the ischemic stroke, traumatic injury, and rapid thrombus development, is summarized in Figure 4.

Comprehensive serological testing, including screening for syphilis (TPPA/RPR), HIV (ELISA/WB), stool routine analysis, thyroid function (TSH, FT4), tumor markers (CEA, CA19-9, PSA), prostate-specific antigen (PSA), thrombophilia panel (protein C/S activity, antithrombin III levels, factor V Leiden mutation), and autoimmune hypercoagulability studies (lupus anticoagulant, anticardiolipin antibodies IgG/IgM, homocysteine levels), revealed no significant abnormalities. Notably, metabolic testing demonstrated marked hyperglycemia, with a fasting plasma glucose level of 14 mmol/L (reference range: 3.9–5.6 mmol/L) and elevated glycated hemoglobin (HbA1c) of 11.9%, indicating poor long-term glycemic control. These findings are diagnostic of uncontrolled diabetes mellitus, warranting prompt endocrinologic evaluation and therapeutic intervention.

The patient presented with a triad of: (1) Acute ischemic stroke; (2) Type 2 diabetes mellitus (poorly controlled, as evidenced by HbA1c of 11.9%); (3) Femoral condylar fracture (right knee, AO/OTA type B, classified). Contrast-enhanced echocardiography (bubble study) demonstrated no evidence of right-to-left shunt, effectively excluding patent foramen ovale (PFO)-mediated paradoxical embolism as a stroke mechanism (Figure 5). The 24-hour ambulatory Holter monitoring revealed no atrial arrhythmias, with particular attention to the absence of atrial fibrillation or flutter, thereby reducing the likelihood of a cardioembolic stroke origin.

The patient presented with an acute ischemic stroke prior to the traumatic event, manifesting solely as neurological deficits, including dizziness, mild cognitive slowing, and right homonymous hemianopsia, with preserved motor function in all extremities. Initial venous duplex ultrasonography performed during ED evaluation demonstrated no evidence of deep venous thrombosis in the lower extremities. Notably, subsequent imaging revealed thrombus formation in the lower extremity venous system at precisely 7.5 hours after trauma. The literature consistently demonstrates that the peak incidence of deep venous thrombosis (DVT) following traumatic injury typically occurs within a 24- to 72-hour window after injury, with most cases developing after the first 24 hours. Our case challenges this conventional timeline by demonstrating radiologically-confirmed DVT formation within 7.5 hours after trauma. An emergency CTT pulmonary angiography (CTPA) was performed to evaluate for potential pulmonary embolism, revealing no radiologic evidence of acute or chronic pulmonary embolism. Following admission, he underwent definitive orthopedic surgical intervention for proximal tibia fracture. In accordance with current VTE prophylaxis guidelines for high-risk postoperative patients, therapeutic anticoagulation was initiated with subcutaneous enoxaparin (4000 anti-Xa IU q12h). Serial laboratory monitoring demonstrated a favorable response to anticoagulation, with D-dimer levels declining to 1.14 mg/L FEU (reference range <0.5 mg/L FEU) by May 28, 2024. A comprehensive lower-extremity venous duplex ultrasound was performed 2 weeks after admission (Figure 3C). The thrombus had no interval increase in size (maximal diameter remaining stable at ≤5 mm), a quantitative volume reduction of approximately 30% in thrombotic burden as measured by volumetric assessment, and the development of partial recanalization channels as evidenced by color flow Doppler demonstrating >50% restored luminal patency, indicating that the thrombus had decreased in size.

Discussion

The knee joint is the largest and most anatomically sophisticated articulation in human anatomy, and is formed by 3 principal osseous components: the distal articular surfaces of the femoral condyles, the proximal tibial plateau with its medial and lateral facets, and the patella (kneecap) anteriorly. The popliteal vein is one of the deep veins in the lower limbs, originating from the popliteal fossa behind the knee joint and accompanying the popliteal artery. The wall of the popliteal vein is thin and the lumen is small, making it susceptible to trauma and compression. The popliteal artery is the deepest, and the popliteal vein is located between the nerve and the artery [3]. Our patient had a proximal tibia fracture, accompanied by knee joint hemorrhage, significant swelling of the soft tissue around the knee joint, and increased pressure in the popliteal fossa. Initially, compression of the popliteal vein occurred, leading to obstruction of venous blood flow distal to the popliteal vein. This condition can readily predispose to the formation of deep-vein thrombosis in the lower limb [4].

A retrospective study has revealed that among trauma patients, the positivity rate for deep vein thrombosis (DVT) screening within 48 hours of admission is approximately 8%. The positivity rate for late-onset DVT, which occurs after 48 hours, is approximately 23% [5]. Lower-limb venous thrombosis is a common and severe peripheral vascular disorder, associated with a variety of risk factors that can be categorized into genetic and acquired factors. Genetic predispositions, often due to specific genetic mutations, can lead to recurrent episodes of arterial and venous thrombosis in affected individuals [6]. This factor is typically challenging to modify, but obtaining a clear family history can aid in assessing the risk of venous thrombosis. Acquired factors are mostly temporary or reversible and mainly include the following aspects [7]: Blood hypercoagulability encompasses conditions such as malignant tumors, use of oral contraceptives, obesity, pregnancy or the postpartum period, polycythemia, macroglobulinemia, myelodysplastic syndrome and other hematologic disorders, and medical procedures like the use of artificial blood vessels, which can all lead to a hypercoagulable state. With the increase of age, the incidence rate of lower-limb venous thrombosis gradually increases. Due to the gradual decline in physical function and exercise volume, elderly people are more likely to develop venous thrombosis as their blood vessel elasticity weakens [8]. Smoking can damage the endothelium of blood vessels, making it easier for blood to clot. Smoking is also a risk factor for a variety of chronic diseases, such as heart disease and diabetes. These diseases can also increase the risk of thrombosis [9]. Excessive alcohol consumption can impair the blood coagulation mechanism and thereby increase the risk of thrombosis. Insufficient hydration can lead to increased blood viscosity, which in turn heightens the risk of thrombus formation [10]. Our patient had no history of thrombosis or positive family history, and no signs of swelling or pain in the lower limbs were present prior to the trauma. An ultrasound examination conducted in the ED revealed no evidence of thrombus formation. However, after the proximal tibia fracture, swelling developed in the right lower limb, which we considered to be a secondary thrombosis resulting from the trauma.

The time interval from the initiation of coagulation to thrombus formation involves a complex and variable process, and it is challenging to specify an exact time frame [11]. When the endothelium of blood vessels is compromised, the underlying tissue is exposed, thereby triggering a coagulation cascade. When blood flow is sluggish or stagnant, such as during long-term bed rest or prolonged sitting, platelets and coagulation factors in the blood are more likely to come into contact with the vessel wall, thereby increasing the risk of thrombosis. Stasis of blood and a hypercoagulable state are crucial factors in the formation of venous thrombosis [12]. Venous thrombosis can develop gradually over several days or even a week. Certain physiological or pathological conditions can induce a hypercoagulable state in the blood, such as pregnancy, the postpartum period, the use of oral contraceptives, and malignant tumors. Genetic hypercoagulable disorders, such as antithrombin deficiency, protein C deficiency, or protein S deficiency, can also significantly shorten the time required for thrombus formation [13]. In patients with comorbidities such as hypertension, diabetes, and hyperlipidemia, the vascular endothelium is more prone to injury, blood viscosity is increased, the risk of thrombosis is elevated, and the time frame for thrombus formation may be relatively brief. The coagulation system varies among individuals, and the rate of thrombus formation as well as the activity of coagulation factors will also differ [14]. Therefore, in clinical practice, the time of thrombus formation can vary significantly. While conventional clinical paradigms maintain that thrombogenesis typically occurs 48–72 hours after injury [2], our patient had a mere 7.5 hours from the occurrence of trauma to the detection of lower-limb venous thrombosis, which is currently the earliest reported instance of thrombosis and may be associated with diabetes and significant swelling of the knee joint affecting lower-limb venous return.

The time required for the formation of lower-limb venous thrombosis following a fracture varies depending on individual differences, fracture site, fracture severity, treatment methods, and postoperative care [15]. Multiple fractures can lead to systemic inflammatory response syndrome (SIRS), which activates the coagulation system and increases the risk of deep vein thrombosis (DVT). The incidence of DVT in patients with multiple fractures (involving 3 or more sites) is significantly higher than that in patients with single fractures, and it can reach up to 50% [1]. The anatomical site most susceptible to venous thrombosis following a limb fracture is typically closely associated with the type and location of the fracture [16].

In long-term prevention, to reduce the risk of thrombosis, fracture patients should undergo anticoagulant therapy under the guidance of a physician and engage in appropriate movement of various body parts to avoid prolonged maintenance of the same posture. Anticoagulants such as low-molecular-weight heparin sodium injection and warfarin sodium tablets can be administered according to medical advice to prevent thrombosis [17]. Mechanical prophylaxis, such as graduated compression stockings, can also be used. By applying compression to the legs, these stockings reduce venous stasis, increase blood flow velocity, and thereby lower the risk of venous thromboembolism (VTE) [18].

Conclusions

This study establishes a new record for the shortest documented time to deep vein thrombosis (DVT) formation after trauma, at ≤7.5 hours. Notably, AO/OTA type B fractures exhibit a high propensity for fresh thrombus development. These findings underscore critical clinical implications: (1) Multidisciplinary team coordination must be emphasized, particularly in early-phase management; (2) Orthopedic protocols should prioritize DVT screening within 12 hours for high-risk fracture subtypes; (3) The conventional anticoagulation window requires advancement to mitigate thrombotic risks. It is reasonable to prevent lower-limb venous thrombosis within a few hours after onset of acute ischemic strokes and acute fracture.