What is the best course of treatment for a 60-year-old female patient with metastatic gastric adenocarcinoma, bilateral lower extremity DVT, and suspected HAI, who is currently experiencing increasing heart rate and decreasing oxygen saturation while on UFH and antibiotics, including Vancomycin and Cefepime?

Optimal Management of Cancer-Associated DVT with Clinical Deterioration

This patient requires immediate transition from subcutaneous UFH to therapeutic-dose LMWH (dalteparin 200 units/kg daily or enoxaparin 1 mg/kg twice daily) for long-term management, urgent evaluation for pulmonary embolism given worsening vital signs, and continuation of broad-spectrum antibiotics with close monitoring for both bleeding and thrombotic complications. 1

Immediate Priorities: Address Clinical Deterioration

Evaluate for Pulmonary Embolism

• The increasing heart rate (89→106 bpm) and declining oxygen saturation (95%→92%) strongly suggest possible PE progression from bilateral proximal DVT 1
• Obtain urgent CT pulmonary angiography or ventilation-perfusion scan to rule out PE 1
• If massive PE with hemodynamic compromise develops, thrombolytic therapy (urokinase, streptokinase, or tissue-type plasminogen activator) should be considered despite cancer and infection 1

Assess Bleeding Risk

• The current platelet count of 320 × 10⁹/L is adequate for full anticoagulation (threshold <50 × 10⁹/L would require modification) 2
• Monitor hemoglobin/hematocrit every 2-3 days for the first 14 days, then every 2 weeks, given the patient's baseline anemia (Hgb 10.2) and gastric cancer with potential GI bleeding risk 1
• The elevated ALP (154) and liver metastases increase bleeding risk but do not contraindicate anticoagulation 1

Anticoagulation Strategy: Transition to LMWH

Why Change from Current UFH Regimen

• The current subcutaneous UFH dosing (12,500 units twice daily) is suboptimal for cancer-associated VTE 1
• LMWH is superior to both UFH and warfarin for cancer-associated VTE, with lower recurrence rates without increased bleeding 1
• Cancer patients have 3-fold higher VTE recurrence and 3-6 fold higher bleeding risk on warfarin compared to LMWH 1

Recommended LMWH Regimen

• Dalteparin 200 units/kg subcutaneously once daily for 30 days, then 150 units/kg daily for months 2-6 (Category 1 recommendation) 1
• Alternative: Enoxaparin 1 mg/kg subcutaneously every 12 hours 1, 3
• Dalteparin is the only LMWH with FDA approval for cancer-associated VTE and has the strongest evidence base 1

Duration of Anticoagulation

• Continue anticoagulation indefinitely as long as active metastatic disease is present 1
• Reassess periodically for bleeding risk and disease progression 1
• Do not plan a scheduled stop date for anticoagulation in this patient with metastatic gastric cancer 1

Management of Suspected Healthcare-Associated Infection

Continue Current Antibiotic Coverage

• The combination of vancomycin 1 gm IV twice daily plus cefepime 1 gm IV three times daily provides appropriate broad-spectrum coverage for healthcare-associated infection 4
• Cefepime has demonstrated efficacy in febrile neutropenic cancer patients with comparable outcomes to imipenem 4
• Monitor for clinical response: resolution of fever, declining leukocytosis (current WBC 14.38), and improvement in respiratory symptoms 4

Antibiotic-Anticoagulation Interactions

• No significant drug interactions exist between UFH/LMWH and vancomycin/cefepime 1
• Continue antibiotics until infection source is controlled and clinical improvement documented 4

Monitoring Requirements

Anticoagulation Monitoring

• LMWH does not require routine aPTT or anti-Xa monitoring in patients with normal renal function (current Cr 0.61 is normal) 1, 3
• Monitor CBC with platelets every 2-3 days for first 14 days, then every 2 weeks 1
• Assess for clinical signs of bleeding daily: unusual bruising, hematuria, melena, hematemesis 5

Vital Signs Monitoring

• Continuous pulse oximetry and frequent vital signs given current deterioration 2
• Escalate care immediately if SpO2 continues to decline or hemodynamic instability develops 1

Critical Pitfalls to Avoid

Do Not Use Warfarin in This Patient

• Warfarin is inferior to LMWH in cancer patients due to drug interactions with chemotherapy, malnutrition effects, and liver dysfunction causing INR fluctuations 1
• The patient's liver metastases make warfarin particularly problematic 1

Do Not Use DOACs as First-Line

• While rivaroxaban and apixaban are acceptable alternatives, LMWH remains preferred for cancer-associated VTE 1
• The patient's gastric cancer creates high risk for GI bleeding, making DOACs less favorable 1
• Edoxaban showed increased major bleeding (6.9% vs 4.0%, HR 1.77) in the Hokusai VTE-Cancer trial 1

Do Not Delay PE Evaluation

• The worsening respiratory status demands immediate imaging to exclude PE progression 1
• Bilateral proximal DVT (involving CFV, SFV, and PV bilaterally) carries extremely high PE risk 1

Do Not Underdose Anticoagulation

• Full therapeutic dosing is required despite infection and cancer 1
• Prophylactic doses are inadequate for established DVT 1

Special Considerations for This Patient

IVC Filter Consideration

• IVC filter should only be considered if PE recurs despite adequate anticoagulation or if absolute contraindication to anticoagulation develops (active uncontrollable bleeding, platelet count <50,000) 1
• Current clinical status does not warrant IVC filter placement 1

Oncology Coordination

• Coordinate anticoagulation management with oncology team regarding chemotherapy plans 1
• LMWH can be continued throughout chemotherapy cycles 1
• Reassess bleeding risk before invasive procedures 1