Fulminant bilateral upper limb thrombophlebitis following traumatic brain injury in a patient with chronic substance use: A fatal case of trauma-associated immunothrombosis

Abstract

Background

Bilateral upper limb superficial thrombophlebitis is rare in trauma patients and typically indicates systemic thromboinflammatory activation rather than localized vascular injury. Trauma-associated immunothrombosis is increasingly recognized as distinct from classical disseminated intravascular coagulation (DIC).

Case presentation

A 35-year-old male presented with severe traumatic brain injury (TBI) following an unwitnessed fall. On hospital day six, he developed progressive discoloration of the left hand, rapidly involving the right upper limb. Doppler ultrasonography confirmed bilateral cephalic and basilic vein thrombosis without deep venous involvement. Platelet count declined from 40,000/μL on day seven to 10,000/μL on day eight, while prothrombin time and INR remained normal and fibrinogen levels were elevated. Admission chest radiograph was normal; however, repeat imaging on day eight demonstrated diffuse bilateral alveolar opacities. HRCT revealed extensive multilobar consolidation with surrounding ground-glass opacities, radiologically suggestive of severe diffuse alveolar injury with features compatible with alveolar hemorrhage. CTPA showed no large central pulmonary embolism. Repeat CT brain demonstrated stable extradural hematoma with resolution of subarachnoid hemorrhage and partial resolution of subdural hematoma. Anticoagulation was withheld due to intracranial hemorrhage and profound thrombocytopenia. The patient developed refractory hypoxemic respiratory failure and died on hospital day eight.

Conclusion

This case highlights a rare and catastrophic systemic thromboinflammatory complication following TBI. Early recognition and multidisciplinary management are essential in similar rapidly progressive cases.

Background

Superficial thrombophlebitis in trauma patients is typically unilateral and related to intravenous cannulation [1]. Bilateral upper limb involvement is uncommon and should raise suspicion for systemic thromboinflammatory activation [2].

TBI is associated with endothelial disruption, tissue factor release, platelet activation, and inflammatory cytokine surge, creating a transient hypercoagulable state [3], [4]. Acute traumatic coagulopathy may initially manifest as hypercoagulability before progressing to consumptive patterns [5], [6].

Immunothrombosis represents the interface between innate immune activation and coagulation pathways, mediated by neutrophil extracellular traps (NETs), monocyte-derived tissue factor, and platelet–leukocyte aggregates [7], [8], [9]. Unlike classical DIC, global coagulation factors may remain preserved.

Chronic alcohol and cannabis use may exacerbate endothelial dysfunction and platelet activation, potentially amplifying trauma-induced thromboinflammatory responses [10], [11], [12], [13].

Case presentation

A 35-year-old male was brought unconscious after being found near a railway track. On arrival, his Glasgow Coma Scale score was 6/15 (E1V2M3). A 4 × 1 × 0.5 cm laceration was noted over the left parietal region.

Initial non-contrast CT brain demonstrated:

• •Left parietal extradural hematoma (EDH) with swirl sign
• •Falx and tentorial subdural hematoma (SDH)
• •Subarachnoid hemorrhage (SAH)
• •Minimally displaced temporal squamous fracture

He was managed conservatively with neurocritical monitoring.

A repeat CT brain performed on hospital day eight to exclude ongoing bleeding demonstrated stable EDH size, resolution of SAH, and partial resolution of SDH, without evidence of active hemorrhage.

The patient had a 10-year history of daily alcohol consumption and chronic cannabis use.

On hospital day six, bluish discoloration and edema of the left hand were observed. By day seven, contralateral involvement occurred. On day eight:

• •The left hand exhibited complete violaceous discoloration with marked edema.
• •The right hand showed mild bluish discoloration. Fig. 1

Fig. 1.

Bilateral upper limbs on hospital day 8. (A) Left hand showing complete violaceous discoloration and edema. (B) Right hand showing mild bluish discoloration.

Doppler ultrasonography confirmed thrombosis of the bilateral cephalic and basilic veins without deep venous involvement.

Laboratory evaluation demonstrated:

• •Platelet count decline from 40,000/μL (day 7) to 10,000/μL (day 8)
• •Normal prothrombin time and INR
• •Elevated fibrinogen
• •Markedly raised D-dimer

The laboratory profile did not fulfill ISTH criteria for overt DIC.

Therapeutic anticoagulation was considered; however, it was withheld due to:

• •Presence of intracranial hemorrhage
• •Severe thrombocytopenia (10,000/μL)
• •High risk of catastrophic intracranial bleeding

Admission chest radiograph (day 0) was normal. On hospital day eight, repeat radiograph demonstrated diffuse bilateral alveolar opacities. Fig. 2

Fig. 2.

Serial chest radiographs. (A) Admission radiograph (day 0) demonstrating normal lung fields. (B) Radiograph on day 8 showing diffuse bilateral alveolar opacities.

HRCT chest revealed:

• •Extensive consolidation with surrounding ground-glass opacities involving the entire right lower lobe, superior and inferior lingular segments of the left upper lobe, and entire left lower lobe.
• •Multifocal patchy ground-glass opacities in the anterior and apicoposterior segments of the left upper lobe, apical and anterior segments of the right upper lobe, and medial and lateral segments of the right middle lobe.

The radiologic pattern was suggestive of severe diffuse alveolar injury with features compatible with alveolar hemorrhage in the context of systemic thromboinflammatory activation.

CT pulmonary angiography did not demonstrate large central pulmonary embolism.

The patient developed progressive hypoxemia culminating in refractory hypoxemic respiratory failure and death on hospital day eight.

Clinical timeline

Day	Clinical course
0	Admission; EDH, SDH, SAH; normal chest X-ray
6	Left hand discoloration
7	Bilateral involvement; platelet 40,000/μL
8	Left hand complete discoloration; right mild involvement; platelet 10,000/μL; HRCT extensive multilobar consolidation; refractory hypoxemia; death

Discussion

Bilateral superficial thrombophlebitis following isolated TBI is rare and suggests systemic thromboinflammatory activation rather than localized vascular injury [2].

The stable intracranial hematoma on repeat CT excluded active bleeding and argues against consumptive coagulopathy. Severe thrombocytopenia with preserved PT/INR and elevated fibrinogen supports trauma-associated immunothrombosis rather than classical DIC.

HRCT demonstrated multilobar consolidation with surrounding ground-glass opacities. In the absence of large central pulmonary embolism on CTPA, these findings likely reflect microvascular thrombosis and diffuse alveolar injury secondary to systemic endothelial activation [14], [15].

Although a postmortem examination was performed, the report could not be accessed because of legal and administrative restrictions; therefore, diffuse alveolar hemorrhage could not be histopathologically confirmed in our review. The pulmonary findings should therefore be interpreted as radiologically suggestive rather than definitive, although the combination of bilateral diffuse ground-glass opacities, multilobar consolidation, refractory hypoxemia, and absence of large central pulmonary embolism strongly supported severe diffuse alveolar injury with possible alveolar hemorrhage.

Anticoagulation decisions in severe TBI remain individualized because evidence-based guidelines are limited. In many neurocritical care settings, repeat CT brain imaging within 24–48 h is performed to assess hematoma stability. Stable or improving intracranial hemorrhage on repeat imaging may support consideration of pharmacologic thromboprophylaxis in selected patients, although profound thrombocytopenia and ongoing bleeding risk may still preclude therapeutic anticoagulation. In the present case, despite stable repeat neuroimaging, the platelet count of 10,000/μL represented a major contraindication to anticoagulation.

Retrospective review suggested that earlier serial monitoring of platelet count, D-dimer, fibrinogen, and inflammatory markers may have identified progressive thromboinflammatory activation before overt limb discoloration became evident. Earlier multidisciplinary involvement, including neurocritical care, hematology, vascular surgery, and pulmonology teams, may have improved assessment of evolving thrombotic risk and the feasibility of preventive interventions.

To our knowledge, bilateral upper limb superficial venous thrombosis following isolated TBI with concurrent diffuse thromboinflammatory lung involvement has not been previously described.

Learning points

• •Bilateral superficial thrombophlebitis after TBI should prompt suspicion for systemic immunothrombosis.
• •Severe thrombocytopenia with preserved PT/INR may indicate thromboinflammatory activation rather than DIC.
• •Intracranial hemorrhage significantly complicates anticoagulation decisions.
• •Diffuse alveolar injury may represent pulmonary manifestation of systemic immunothrombosis.

Limitations

This report has several limitations. Although a postmortem examination was performed, the report could not be accessed because of legal restrictions, and histopathologic confirmation of alveolar hemorrhage was therefore unavailable to the treating team. In addition, serial inflammatory biomarkers and coagulation assays such as thromboelastography were not available, limiting further characterization of the thromboinflammatory process.

Conclusion

This case illustrates a rare and fatal systemic thromboinflammatory complication following traumatic brain injury. In patients with severe TBI, serial monitoring of platelet count, D-dimer, fibrinogen, PT/INR, and inflammatory markers during the first week after injury may help identify evolving thromboinflammatory complications. New limb discoloration, unexplained thrombocytopenia, or worsening hypoxemia should prompt urgent vascular imaging and repeat chest imaging. Early multidisciplinary discussion involving neurocritical care, hematology, vascular surgery, pulmonology, and radiology teams may assist in balancing thrombotic risk against hemorrhagic risk and guide decisions regarding anticoagulation and further imaging.

CRediT authorship contribution statement

Naman Jain: Writing – original draft, Data curation, Conceptualization. Minakshi Gadhire: Validation, Supervision, Formal analysis. Ashish Kumar Lallan Prasad Yadav: Writing – review & editing. Kalyani Dnyaneshwar Aher: Writing – review & editing, Supervision.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary data

Supplementary Video 1

Non-contrast CT brain demonstrating left parietal extradural hematoma with swirl sign and associated intracranial hemorrhages at presentation.