What is the best course of action for a 36-year-old female with left leg pain, numbness, and tingling, and a history of adenomyosis, heavy menstrual bleeding, and elevated Total Iron Binding Capacity (TIBC), to address potential Deep Vein Thrombosis (DVT) and iron deficiency anemia?

Immediate DVT Evaluation and Management

This patient requires urgent proximal compression ultrasound (CUS) of the left leg today, and if negative, either a highly sensitive D-dimer test or serial ultrasound in one week to definitively rule out DVT, given her acute worsening of symptoms with shortness of breath, leg redness, and severe pain. 1, 2

Clinical Probability Assessment

• This patient has high pretest probability for DVT based on: unilateral leg pain and swelling, acute worsening 5 days ago with 10/10 pain, leg redness and tenderness, shortness of breath (concerning for possible pulmonary embolism), and prolonged symptoms of leg pressure/numbness for 3 years 1, 3

• The Wells score would likely categorize her as moderate-to-high probability given active symptoms, localized tenderness, and entire leg swelling 3

Immediate Diagnostic Workup

Primary Imaging

• Perform proximal CUS immediately (femoral and popliteal veins) as the first-line test for high pretest probability DVT 1

• If proximal CUS is positive, treat immediately for DVT without confirmatory venography 1

• If proximal CUS is negative but clinical suspicion remains high, proceed with either: (1) whole-leg ultrasound to evaluate calf veins, OR (2) highly sensitive D-dimer testing, OR (3) repeat proximal CUS in 1 week 1

Special Imaging Considerations

• Given the extensive leg symptoms (mid-thigh to calf) with 3-year history of leg pressure, if proximal CUS is negative, consider iliac vein imaging (CT venography or MR venography) to exclude isolated iliac DVT, which can be missed on standard ultrasound 1, 2

• Whole-leg ultrasound may be preferred over serial testing given her severe symptoms and the 3-year history of numbness/tingling, as isolated calf DVT could be present 1

Pulmonary Embolism Evaluation

The acute onset of shortness of breath during showering 5 days ago is a red flag for possible PE and requires immediate assessment 2

• Perform CT pulmonary angiography (CTPA) if she has ongoing dyspnea, chest pain, or hemodynamic instability 2

• Even with negative lower extremity ultrasound, PE can still be present, as syncope and dyspnea can be presentations of PE despite negative DVT imaging 2

• If CTPA is not immediately indicated, maintain high clinical suspicion and perform if symptoms worsen or DVT is confirmed 2

Pre-Treatment Laboratory Testing

Before initiating anticoagulation (if DVT is confirmed), obtain: 4

• Complete blood count with platelet count - establishes baseline and identifies contraindications to anticoagulation (note: her labs already show anemia with low MCH and MCHC) 4

• Coagulation profile (PT/INR, aPTT) - guides initial anticoagulant therapy 4

• Comprehensive metabolic panel - assesses kidney and liver function to influence anticoagulant selection and dosing 4

• D-dimer is NOT needed if DVT is already established by imaging, as it has no role in monitoring treatment 4

Iron Deficiency Anemia Considerations

Thrombotic Risk from Anemia

• Elevated TIBC (451) with low MCH (26.4) and low MCHC (30.8) confirms iron deficiency anemia, likely from chronic heavy menstrual bleeding (4-6 extra-large pads daily with clots) 5, 6

• Iron deficiency is an under-recognized but important risk factor for venous thromboembolism through induction of reactive thrombocytosis, creating a hypercoagulable state 5, 7

• Iron deficiency can cause both arterial and venous thrombosis, and is particularly relevant in this patient with adenomyosis causing chronic blood loss 6, 7

Anemia Management

• Check complete blood count including platelet count - iron deficiency commonly causes reactive thrombocytosis (elevated platelets), which increases thrombotic risk 5, 6, 7

• Initiate iron replacement therapy once DVT workup is complete, as this is both therapeutic for anemia and potentially preventive for future thrombotic events 7

• The combination of severe iron deficiency and possible thrombocytosis makes her thrombotic risk higher than typical DVT patients 6, 7

Anticoagulation Decisions

If DVT is Confirmed

• Initiate anticoagulation immediately with either low molecular weight heparin, unfractionated heparin, fondaparinux, or a direct oral anticoagulant 1

• Check baseline platelet count before starting heparin and monitor closely, as heparin-induced thrombocytopenia (HIT) can occur 8

• Contraindications to anticoagulation include: severe thrombocytopenia, uncontrollable active bleeding, and inability to monitor coagulation parameters 8

If Isolated Calf DVT is Found

• Two management options exist: (1) anticoagulation, OR (2) serial ultrasound surveillance (at 1 and 2 weeks) to detect proximal extension 1

• Favor anticoagulation over surveillance in this patient because she has multiple risk factors for thrombus extension: 1

  • Severe symptoms (10/10 pain, redness, swelling)
  • Extensive thrombosis (mid-thigh to calf involvement)
  • Active risk factor (iron deficiency with likely thrombocytosis)
  • History of chronic symptoms suggesting possible chronic venous issues
  • Shortness of breath suggesting possible PE

• If surveillance is chosen, approximately 15% of untreated isolated distal DVTs extend into proximal veins within 2 weeks 1

Treatment Duration (If DVT Confirmed)

• If DVT is provoked by iron deficiency/heavy menses: treat with anticoagulation for 3 months minimum 1

• If DVT is unprovoked (no clear reversible risk factor): treat for at least 3 months, then evaluate for extended therapy based on bleeding risk 1

• Given her iron deficiency is a potentially reversible risk factor (treatable with iron supplementation and adenomyosis management), this would likely be considered a provoked DVT 1

Adenomyosis and Bleeding Management

• Address the underlying cause of iron deficiency - her adenomyosis with heavy menstrual bleeding (menorrhagia) requiring 4-6 extra-large pads daily 9

• Consider gynecology referral for adenomyosis management options (hormonal therapy, uterine artery embolization, or definitive surgical management) to prevent recurrent severe anemia 9

• Note contraindication: if DVT is confirmed, estrogen-containing contraceptives are contraindicated due to increased thrombotic risk; progestin-only options may be considered 1

Critical Pitfalls to Avoid

• Do not dismiss the shortness of breath - this requires PE evaluation even if lower extremity ultrasound is negative, as PE can occur without detectable leg DVT 2

• Do not delay imaging - the acute worsening 5 days ago with 10/10 pain, redness, and dyspnea represents a medical urgency requiring same-day evaluation 1, 2

• Do not overlook iliac vein thrombosis - her 3-year history of leg pressure during menses with extensive current symptoms warrants iliac vein imaging if proximal CUS is negative 1, 2

• Do not ignore the iron deficiency as a thrombotic risk factor - this is an underestimated but important contributor to her thrombotic risk that requires treatment 5, 7

• Do not start anticoagulation without baseline labs - failure to check CBC, platelets, and coagulation studies can lead to complications in patients with undiagnosed bleeding disorders 4

• Do not use D-dimer as a standalone test in this high pretest probability patient - proceed directly to imaging 1