Thrombotic Challenges at High Altitude: A Case Report of Cerebral, Pulmonary, and Ventricular Thrombosis in a 21-Year-Old

Introduction

Venous thrombosis, which mainly includes deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE), is among the 5 most common vascular diseases in most countries. The lifetime risk of venous thrombosis is estimated to be 8% overall among US adults [1,2], but multi-system thrombosis induced by high-altitude exposure has not been previously reported. Approximately 30% of right-heart thrombi progress to massive pulmonary embolism, with a mortality rate of about 45% [3,4]. CVST accounts for 3% of all cases of stroke. Patients with CVST have a favorable prognosis, but chronic symptoms are not uncommon, which can reduce the quality of life [5,6].

The formation of thrombosis is affected by factors such as genetics, infections, malignancies, and pregnancy [7]. In high-altitude regions, the incidence of thrombotic events has been increasingly recognized, particularly as healthcare conditions improve. The unique environmental factors at high altitudes, including low atmospheric pressure, hypoxia, and cold temperatures, can lead to vasoconstriction and endothelial injury, thereby altering coagulation function. These changes can result in increased red blood cell counts and blood viscosity, which, when combined with factors such as reduced blood volume, decreased physical activity, infections, and dehydration, can accelerate thrombus formation [8]. Importantly, patients with thrombosis always exhibit nonspecific and insidious clinical symptoms, which can increase mortality at high altitude [9].

This report describes the case of a 21-year-old man working at high altitude for 3 days who developed cerebral venous sinus thrombosis, pulmonary thromboembolism, and right ventricular thrombosis.

Case Report

A 21-year-old man urgently commenced work in a high-altitude area (5100 m) without prophylactic measures for altitude sickness. Comprehensive examinations, including electrocardiogram (ECG), echocardiography, chest X-ray, limb ultrasound, cranial CT scan, and complete blood tests yielded results within normal limits. On day 3, he developed sore throat, cough, vomiting, and diarrhea (5–6 times per day). He was treated with oral cefixime (0.1 mg, twice daily) for 3 days, but with minimal effect. On day 7, he experienced headache, seizures, dizziness, and blurred vision, and was transferred to our medical institution (at an altitude of 800 m) for treatment.

On admission, the patient had a temperature of 37.8°C, respiratory rate of 20 breaths/min, heart rate of 98 beats/min, blood pressure of 120/85 mmHg, and a BMI of 23.7 kg/m2. He was alert but exhibited right hemiplegia, with a National Institutes of Health Stroke Scale score of 3. Funduscopic exam revealed papilledema. Magnetic resonance (MR) venography revealed intracerebral hemorrhage in the left frontal lobe, and left transverse venous sinus thrombosis extending into the jugular vein (Figure 1A, 1B). Ultrasound revealed thrombosis in the right ventricle (Figure 1C), pulmonary hypertension, right ventricular dilation, D-shaped left ventricle, and normal ejection fraction, with no thrombi detected in the deep veins of the limbs. CT pulmonary angiography suggested mural thrombi in the lower lobes of both lungs and pleural effusion (Figure 1D). Admission laboratory test results were significant for elevated D-dimer levels (2.13 mg/L) and K/α angle (K, 1.02 min; α, 75°). The results of a thorough hypercoagulability workup, including homocysteine, anticardiolipin antibodies, antithrombin III, protein C, protein S, prothrombin gene mutation, Factor V Leiden genetic mutation, and beta-2-glycoprotein, were unremarkable. Electrocardiography showed sinus rhythm with a normal electrocardiogram, with a cardiothoracic ratio of 0.55 on chest radiography. There was no family history of thrombotic disease and the patient did not take any pro-thrombotic medications. Physical examination before arriving at a high altitude revealed no history of thrombosis. Finally, the diagnosis of cerebral venous sinus thrombosis (CVST) complicated by pulmonary thromboembolism (PTE) and right ventricular thrombosis was confirmed.

The patient was not indicated for surgery, and was administered LMWH at a dose of 1 mg/kg subcutaneously twice daily. Due to limited medical resources at high altitudes, the absence of new oral anticoagulants necessitated the use of warfarin (3 mg/d for 3 months, INR 2–3) for anticoagulation. During the 6-month follow-up, the pulmonary hypertension gradually improved, with no recurrence of cerebral infarction. MRI revealed hemosiderosis in the left frontal lobe, ultrasound showed no thrombosis in the right ventricle, and a CT pulmonary angiogram showed mural thrombi in the pulmonary arteries.

Discussion

This case report provides an example of multi-system thrombotic disease in a young patient under extreme high-altitude conditions. From this report, we can learn that in the early stages of entering high-altitude areas, symptoms such as headache and chest pain should not only be considered as high-altitude diseases but also differentiated from thrombotic diseases, as the treatment approaches for the 2 are different. Extensive dehydration therapy can exacerbate the thrombotic process.

Multiple-system thrombosis is a rare condition that should arouse the attention of medical staff, especially in high-altitude areas where medical resources are limited. Previous studies have shown that compared with low-altitude areas, the incidence of cerebral venous sinus thrombosis in high-altitude areas is higher. However, they only reported intracranial thrombosis and did not report cerebral venous sinus thrombosis complicated with pulmonary embolism and right ventricular thrombosis [10]. Our patient was a young man who rapidly progressed to cerebral venous sinus thrombosis (CVST), pulmonary thromboembolism (PTE), and right ventricular thrombosis within 1 week of working at high altitude. Generally, the formation of a thrombus requires a certain amount of time, but our patient experienced accelerated disease progression. We also reviewed the literature and found that some patients developed thrombosis, including not only venous but also arterial thrombosis, within 1 week of trekking at high altitude [11–16]. This may be attributed to the unique high-altitude environment, characterized by low atmospheric pressure, cold temperatures, and hypoxia, which can lead to vasoconstriction, endothelial injury, and changes in coagulation function. Additionally, increased red blood cell count and blood viscosity can further facilitate thrombus formation. In this case, the patient’s concurrent infection and dehydration likely exacerbated the progression of thrombosis. Our patient experienced headache and dizziness in the early stage of entering the high-altitude area. We did not quickly diagnose and treat it as acute mountain sickness. Instead, after completing the relevant examinations, we confirmed the diagnosis of multi-system thrombosis. In the absence of new oral anticoagulant drugs, we chose low-molecular-weight heparin and warfarin for conservative treatment. The patient had a good prognosis after follow-up. Compared with previously reported thrombotic diseases in high-altitude areas, our patient was younger, had a more rapid disease progression, and had a better long-term prognosis.

To expedite work at high altitude for financial gain, our patient did not undertake preventive measures or pharmacological interventions for altitude sickness, traveling from an altitude of 1300 meters to 5100 meters within a single day. The lack of these precautionary measures contributed significantly to the patient’s disease onset and progression [17–19]. Ultrasonography consistently failed to detect venous thrombosis in the limbs, possibly due to thrombosis having already migrated to the cerebral, pulmonary, or cardiac chambers. On day 7, clinical deterioration was noted, with physical examination revealing papilledema, likely due to high-altitude cerebral edema, as cranial CT scans did not exhibit edema signs in the early stages of the disease [20]. Acute cerebral edema can precipitate cerebral venous thrombosis formation, and dehydration can accelerate thrombus development. Although dehydration treatment was not administered, the patient’s condition progressed rapidly due to severe diarrhea and vomiting, which promoted the dehydration process [21]. Cerebral venous thrombosis is rare [22,23], but the overall mortality rate of cerebral venous thrombosis combined with PTE was reported to be 95.6% [24]. To facilitate an intuitive understanding of cerebral venous thrombosis, we created a schematic diagram (Figure 2) of the pathogenesis of cerebral venous thrombosis, using available software (https://app.biorender.com) [25]. Based on previous guidelines, we used LMWH and oral anticoagulants for treatment [26,27], and the patient had a good outcome after 6 months of follow-up.

The rapid disease progression and severe hypoxia observed in our patient were notable. By the 7th day, when the relevant examinations were completed, he had already developed severe pulmonary hypertension, right ventricular enlargement, and a D-shaped left ventricle. The relevant literature indicates that the pathophysiological process of pulmonary hypertension in high-altitude areas includes early hypoxic pulmonary vasoconstriction (HPV) and subsequent hypoxic pulmonary artery remodeling (HPAR). HPV is a functional change, while HPAR is an organic lesion that is challenging to reverse in the later stages [28]. The severe pulmonary hypertension that developed within 1 week in our patient may be attributed to the early hypoxic pulmonary vasoconstriction phase. The underlying mechanisms involve hypoxic pulmonary vasoconstriction, excessive activation of the sympathetic nervous system, endothelial dysfunction, inadequate ventilatory response to hypoxia, and abnormal function of autocrine and paracrine vasoactive substances in the pulmonary vasculature and lung tissue. The elevated pulmonary arterial pressure led to changes in the pressure of the right heart system. Right ventricular hypertension can compress the left ventricle, causing it to become flatter and take on a D shape. This morphological change is an indirect effect of elevated right ventricular pressure on the left ventricle and often improves after the patient leaves the high-altitude environment or receives appropriate treatment [29–32]. Follow-up of our patient also indicated that the cardiac chambers returned to their normal shape after treatment.

This case demonstrates that the combination of low atmospheric pressure, hypoxia, and cold temperatures at high altitude can precipitate acute thrombotic events. This case also highlights the necessity for clinicians to consider the diagnosis of thrombosis when presented with patients exhibiting sudden headache, chest pain, or dyspnea in high-altitude settings [33,34]. The clinical presentation can mimic conditions such as high-altitude pulmonary edema or cerebral edema, yet the treatment approaches differ significantly, necessitating an accurate diagnosis for effective management.

In summary, this case demonstrates that thrombotic diseases in high-altitude areas can be insidious and life-threatening, with potentially faster progression, and should attract the attention of clinical workers.

Conclusions

This report shows the presentation of multiple thrombotic events developing at high altitude, and the approach to diagnosis and management.