Why does bleeding occur in cerebral venous thrombosis (CVT) in a patient with severe New Delhi metallo-beta-lactamase (NDM)-producing Klebsiella infection?

Why Bleeding Occurs in Cerebral Venous Thrombosis

Bleeding in CVT occurs due to venous hypertension causing rupture of small vessels and venous infarction with hemorrhagic transformation, not from anticoagulation itself.

Pathophysiologic Mechanism of Hemorrhage in CVT

The fundamental mechanism differs completely from arterial stroke. When cerebral veins and sinuses become thrombosed, blood cannot drain properly from the brain, leading to:

• Venous hypertension that causes small vessel rupture and capillary bed disruption, resulting in hemorrhagic venous infarction 1
• Increased intracranial pressure from impaired venous drainage, which further compromises the microvascular integrity 2
• Cytotoxic and vasogenic edema that develops in the affected brain parenchyma, creating a substrate for hemorrhagic transformation 1

Approximately one-third of CVT patients develop intracerebral hemorrhage (ICH) as part of the natural disease process, not as a complication of treatment 1.

Risk Factors for Hemorrhage in CVT

Specific clinical features predict which patients will develop ICH:

• Older age and female sex 1
• Acute symptom onset (within 48 hours) 1
• Decreased level of consciousness on presentation 1
• Seizures at presentation 1
• Elevated blood pressure and papilledema 1

The Infection-CVT-Hemorrhage Connection

In your specific scenario with severe NDM-producing Klebsiella infection, the bleeding risk is compounded by:

• Sepsis-induced coagulopathy from the severe infection, which can cause both thrombosis and bleeding simultaneously 3
• Inflammatory endothelial damage from the systemic infection, making vessels more prone to rupture 3
• Potential thrombocytopenia from sepsis or disseminated intravascular coagulation 2

The case report of CVST with Klebsiella pneumoniae liver abscess demonstrates that infection-associated CVT can present with hemorrhagic complications, yet still requires antithrombotic therapy for optimal outcomes 3.

Critical Clinical Distinction: Hemorrhage Does NOT Contraindicate Anticoagulation

The American Society of Hematology/International Society on Thrombosis and Haemostasis strongly recommends anticoagulation even in pediatric patients with hemorrhagic CSVT, as the bleeding is part of the thrombotic process itself 2.

The evidence shows:

• Anticoagulation reduces mortality (RR 0.36; 95% CI 0.16-0.81) without increasing bleeding risk 2
• The pooled risk of bleeding was NOT significantly different between anticoagulated patients (4.7%) versus non-anticoagulated patients (3.2%) 2
• In infection-associated CSVT specifically, anticoagulation reduces mortality and improves neurologic outcomes 2

Management Algorithm for CVT with Hemorrhage in Severe Infection

Step 1: Confirm CVT diagnosis with MRI and MR venography 2

Step 2: Assess bleeding risk factors:

• Platelet count >50,000/μL is safe for therapeutic anticoagulation 2
• INR <1.4 is acceptable 4
• Serum creatinine >6.0 mg/dL poses considerable bleeding risk 4

Step 3: Initiate anticoagulation unless absolute contraindications exist:

• Use low-molecular-weight heparin (LMWH) as first-line therapy 5
• In infection-associated CVT, anticoagulation should be started despite hemorrhagic transformation 2, 6
• The 2025 ASH/ISTH guidelines give a strong recommendation for anticoagulation in children with non-hemorrhagic CSVT and a conditional recommendation for those with hemorrhagic CSVT 2

Step 4: Manage the underlying infection aggressively:

• Source control and antibiotics are the primary treatment 7
• The infection itself is driving both the thrombosis and hemorrhagic complications 3

Step 5: Monitor for thrombus progression:

• Follow-up imaging at 1 month and 3 months to assess recanalization 6, 8
• Anticoagulation promotes thrombus resolution (78% vs 53.5% without anticoagulation) 2

Common Pitfalls to Avoid

• Do NOT withhold anticoagulation solely because hemorrhage is present on imaging - the hemorrhage is caused by the venous thrombosis itself, and anticoagulation prevents progression 2, 1
• Do NOT assume the bleeding is from anticoagulation - hemorrhagic venous infarction occurs in one-third of CVT cases as part of the natural disease process 1
• Do NOT delay anticoagulation while waiting for infection control - both processes must be treated simultaneously for optimal outcomes 3, 6

Special Considerations for Severe Infection

In patients with severe sepsis and thrombocytopenia:

• Therapeutic LMWH may be administered if platelet count can be maintained >50 × 10⁹/L 2
• Half-dose LMWH can be used for platelet counts 20-50 × 10⁹/L with close monitoring 2
• Hold therapeutic anticoagulation only if platelet count <20 × 10⁹/L 2

Recent pediatric data from 2024 showed that in infection-associated septic CVT, anticoagulation was safe with no bleeding complications in 63% of patients who received it, though the benefit on recanalization remains uncertain 6, 8.