Management of Extensive Proximal DVT (Iliofemoral + Long/Short Saphenous) in an 80-Year-Old with Hb 6 g/dL

Step 1 - Immediate Risk Assessment & Stabilisation

• Phlegmasia cerulea dolens - massive iliofemoral DVT can cause venous gangrene (blue, congested, painful leg). This is a limb-threatening emergency requiring urgent intervention.
• Pulmonary embolism - proximal DVT has high embolism risk; check for dyspnoea, tachycardia, hypoxia, right heart strain. Do CTPA or at minimum D-dimer + ECG + ABG if clinically suspected.
• Cause of Hb 6 - this is severe anaemia and must be investigated urgently. It directly affects anticoagulation decisions.

• CBC with peripheral smear, reticulocyte count
• Iron studies, B12/folate, renal function, LFTs
• PT/INR, aPTT (baseline before anticoagulation)
• Blood group and crossmatch (for transfusion)
• CTPA if PE suspected
• Serum creatinine/eGFR (critical for DOAC/LMWH dosing in elderly)
• Thrombophilia screen (Factor V Leiden, prothrombin mutation, antiphospholipid antibodies) - ideally before anticoagulation, though results won't change acute management
• Consider malignancy workup (CA-125, CT abdomen/pelvis) given age - DVT can be the presenting feature of occult cancer

Step 2 - Address Severe Anaemia (Hb 6 g/dL)

• Transfuse packed red cells to a target Hb of at least 8-9 g/dL before or concurrent with anticoagulation initiation. In an elderly patient with possible cardiovascular disease, transfuse slowly (1 unit at a time with furosemide cover if needed).
• Investigate the cause - iron deficiency anaemia (most common in elderly) vs. GI bleed (which would further elevate bleeding risk with anticoagulation) vs. chronic disease vs. haematological cause.
• If active GI bleeding is the cause of Hb 6, this substantially changes the anticoagulation risk-benefit calculus - seek GI input and consider IVC filter (see below).

Step 3 - Anticoagulation (Cornerstone of DVT Treatment)

Option A: LMWH (Preferred initial agent in most cases)

• Enoxaparin 1 mg/kg SC twice daily (or 1.5 mg/kg once daily)
• Key advantage: outpatient treatment possible, predictable pharmacokinetics, lower HIT risk vs. UFH
• Dose-adjust for renal impairment: CrCl 10-30 mL/min → reduce to 1 mg/kg once daily. Monitor anti-Xa levels in the elderly.
• "Numerous well-designed trials demonstrate a decrease in thrombotic complications, bleeding, and mortality with LMWHs" compared to UFH - Schwartz's Principles of Surgery 11th Edition

Option B: Unfractionated Heparin (UFH) - if renal failure or high bleeding risk where rapid reversal may be needed

• IV infusion, titrated to aPTT 60-100 seconds (1.5-2.5× control)
• Easily reversed with protamine sulfate - an important advantage in this elderly, anaemic patient
• Monitoring: aPTT every 6 hours initially

Option C: Direct Oral Anticoagulants (DOACs) - can be used as monotherapy

• Rivaroxaban: 15 mg twice daily with food for 21 days, then 20 mg once daily
• Apixaban: 10 mg twice daily for 7 days, then 5 mg twice daily
• These can be started directly without initial parenteral anticoagulation
• Caution in the elderly: renal clearance is significant - check eGFR before prescribing. Avoid rivaroxaban if CrCl <15 mL/min.
• No reliable reversal agent widely available for most (andexanet alfa reverses factor Xa inhibitors but is expensive and not universally available) - this matters given Hb 6.

1. Readily reversible (protamine for UFH/LMWH)
2. Easy dose adjustment with real-time monitoring
3. Safe bridge while anaemia is being investigated and treated

Step 4 - Duration of Anticoagulation

Step 5 - Consider Catheter-Directed Thrombolysis (CDT)

• Iliofemoral DVT - fits the profile
• Progressive limb-threatening swelling
• Young-onset or high functional need (less relevant at 80 years)

• Hb 6 = high bleeding risk - CDT significantly increases haemorrhagic complications (RR 1.73 in systemic thrombolysis trials)
• Age 80 - increased bleeding risk
• If cause of anaemia is GI or internal bleeding, CDT is absolutely contraindicated

Step 6 - IVC Filter

• Absolute contraindication to anticoagulation (e.g., active serious bleeding, intracranial haemorrhage)
• Recurrence of PE despite therapeutic anticoagulation
• Inability to achieve therapeutic anticoagulation

Step 7 - Supportive Measures

• Compression stockings (graduated elastic compression, 30-40 mmHg) once acute swelling allows - reduces post-thrombotic syndrome (PTS)
• Limb elevation - reduces oedema acutely
• Mobilisation - bed rest is not required; early ambulation is encouraged once anticoagulation is therapeutic
• Intermittent pneumatic compression devices for the contralateral leg during hospitalisation to prevent new DVT

Step 8 - Monitoring & Follow-Up

Summary Algorithm

Hb 6 + Extensive Proximal DVT (Iliofemoral)
          |
          ├── Investigate & transfuse (target Hb ≥8-9)
          |
          ├── Assess cause of anaemia (GI bleed? → IVC filter if anticoag contraindicated)
          |
          ├── Start anticoagulation:
          |    - UFH (IV) if severe renal failure or rapid reversal needed
          |    - LMWH (dose-adjusted for renal function) in most cases
          |    - DOAC (rivaroxaban/apixaban) once Hb stabilised and no active bleeding
          |
          ├── CDT: defer until Hb corrected; re-evaluate if phlegmasia develops
          |
          ├── IVC filter: only if true contraindication to anticoagulation
          |
          └── Compression stocking + elevation + early mobilisation
              Duration: min 3 months (extend if unprovoked/cancer)

• Phlegmasia cerulea dolens (blue, painful, pulseless leg) - emergency thrombectomy/CDT regardless of Hb
• Haemodynamic collapse - consider massive PE, urgent CTPA
• Progressive drop in Hb despite transfusion - find and control source before anticoagulation

Enoxaparin Duration and Switching to a DOAC

How Long to Continue Enoxaparin SC?

"When dabigatran or edoxaban are utilized, they must be preceded by upfront parenteral anticoagulation... based on how the clinical trials leading to drug approval were designed." - Fuster & Hurst's The Heart, 15th Edition

Practical Switching Protocol

If switching to Rivaroxaban (most commonly used)

• Standard minimum duration of enoxaparin before switching: 5 days (though rivaroxaban can technically be started from day 1 without any heparin lead-in)
• In your patient, since enoxaparin is already started and the anaemia is being corrected, a 5-day enoxaparin run is a safe and accepted approach
• Give first rivaroxaban dose at the time the next enoxaparin injection would have been due - do not overlap
• Dose: 15 mg twice daily with food for 21 days, then 20 mg once daily
• The 21-day loading phase essentially replaces what the parenteral phase was doing

If switching to Apixaban

• Same principle: enoxaparin for at least 5 days, then start apixaban when next enoxaparin dose is due
• Dose: 10 mg twice daily for 7 days, then 5 mg twice daily
• In your elderly patient, apixaban 5 mg twice daily (maintenance) has the most favourable bleeding profile among all DOACs in the elderly

If switching to Edoxaban

• Must complete at least 5-10 days of enoxaparin first - this is non-negotiable
• Dose: 60 mg once daily (reduce to 30 mg once daily if CrCl 15-50 mL/min, weight ≤60 kg, or concomitant P-gp inhibitor)

If switching to Dabigatran

• Must complete at least 5 days of parenteral anticoagulation
• Dose: 150 mg twice daily (reduce to 110 mg twice daily in elderly >80 years or high bleeding risk)
• Caution: dabigatran 110 mg twice daily is the approved dose in patients over 80 years in many guidelines - relevant here

Summary Timeline for Your Patient

Day 1-5:    Enoxaparin SC (dose-adjusted per renal function)
            Transfuse to target Hb ≥8-9 g/dL
            Investigate cause of anaemia
            Choose DOAC based on renal function + bleeding risk

Day 5:      At the time of the next scheduled enoxaparin dose:
            → STOP enoxaparin
            → START DOAC (first dose replaces that injection)

Day 5-26:   Rivaroxaban 15 mg BD with food (loading phase)
  OR        Apixaban 10 mg BD (days 5-11, i.e. 7 days of loading)

Long term:  Rivaroxaban 20 mg OD  OR  Apixaban 5 mg BD

Which DOAC to Prefer in This 80-Year-Old?

• Lowest bleeding rate among all DOACs in multiple trials
• Twice daily dosing helps with adherence monitoring
• Less renal-dependent than rivaroxaban (safer with age-related CrCl decline)
• No food requirement for absorption (rivaroxaban must be taken with food)

Key Points to Remember at Time of Switch

1. Do not overlap - stop enoxaparin when first DOAC dose is given
2. No INR monitoring needed with DOACs (unlike warfarin)
3. No routine anti-Xa monitoring needed for DOACs in normal use
4. Check renal function (eGFR) - dose-adjust as needed
5. Check for drug interactions (P-gp and CYP3A4 inhibitors/inducers)
6. Ensure Hb is stabilised before switching (bleeding risk assessment)
7. Continue for minimum 3-6 months total duration (enoxaparin days count toward this total)

If You Choose Warfarin Instead (Not Recommended Here)

• Overlap warfarin with enoxaparin for at least 5 days AND until INR is 2.0-3.0 on two consecutive readings
• Only stop enoxaparin once both conditions are met
• INR monitoring is inconvenient in the elderly and TTR (time in therapeutic range) is often poor - DOACs are strongly preferred for this patient

What Else to Evaluate - Full Workup Plan

1. Why did she get DVT? - Aetiological workup
2. Why is her Hb 6? - Anaemia workup

Track 1 - DVT Aetiology Workup

A. Malignancy Screen (Priority - USG abdomen was only a start)

The key point: USG abdomen has already been done and is normal. CT with contrast is a better tool for occult malignancy and should be the next imaging step if not already done.

B. Thrombophilia Testing

• Active thrombosis transiently depletes antithrombin, protein C, and protein S (false positive deficiency)
• Heparin reduces antithrombin levels
• Warfarin reduces protein C and S
• DOACs interfere with lupus anticoagulant assay

"Testing ideally should be performed in clinically stable patients after completion of oral anticoagulation at least 3 to 6 months after a thrombotic episode." - Goldman-Cecil Medicine

• Antithrombin III activity
• Protein C activity
• Protein S (free and total)
• Factor V Leiden
• Prothrombin 20210A
• Lupus anticoagulant
• Anticardiolipin antibodies (IgG and IgM)
• Anti-β2 glycoprotein I (IgG and IgM)
• Homocysteine level
• JAK2 V617F mutation

C. Haematological Causes of DVT

Track 2 - Anaemia Workup (Hb 6)

Step 1 - Classify the anaemia (do these NOW)

Step 2 - Based on MCV, pursue:

• Serum iron, TIBC, ferritin - iron deficiency anaemia
• If ferritin low → source of blood loss: upper and lower GI endoscopy (colonoscopy + OGD) - this is critical because GI bleed = contraindication to anticoagulation
• Haemoglobin electrophoresis - thalassaemia (less likely at 80 but possible in endemic areas)

• Renal function / eGFR - anaemia of chronic kidney disease
• Liver function tests
• TSH - hypothyroidism
• Bone marrow examination if peripheral smear shows abnormality

• Serum B12 level
• Serum folate (RBC folate more reliable)
• Reticulocyte count - if elevated, haemolysis
• Serum LDH and indirect bilirubin - haemolysis
• Direct Coombs test - autoimmune haemolytic anaemia

Step 3 - Bone marrow examination

• Peripheral smear shows blasts, leucoerythroblastic picture, or dimorphic red cells
• Pan-cytopaenia (not just isolated anaemia)
• Myeloma suspected (SPEP positive)
• Myelodysplastic syndrome (MDS) - very common cause of anaemia in elderly

Summary: Prioritised Investigation List

Do Urgently (before or concurrent with anticoagulation):

1. Peripheral blood smear + reticulocyte count
2. Iron studies (serum iron, ferritin, TIBC)
3. Serum B12 and folate
4. Renal function, LFTs, TFTs
5. SPEP (myeloma screen)
6. LDH, uric acid (lymphoma/haemolysis)
7. Antiphospholipid antibodies (anticardiolipin, anti-β2GPI) - before DOAC if possible
8. Factor V Leiden + Prothrombin G20210A (DNA-based, not affected by anticoagulation)
9. JAK2 V617F mutation
10. Homocysteine

Do Soon (within 1-2 weeks):

1. CT chest + CT abdomen/pelvis with contrast (better than USG for occult cancer)
2. Mammography
3. OGD + Colonoscopy (especially if iron deficiency - find the source)
4. Tumour markers as clinically guided (CA-125, CEA, CA 19-9)
5. PNH screen (flow cytometry) if unexplained haemolysis

Defer until 3-6 months off anticoagulation:

1. Antithrombin III, Protein C, Protein S (results unreliable on anticoagulation)
2. Lupus anticoagulant (if DOAC started, must be off for 48-72 hours before testing)

⚠️ DO NOT DISCHARGE - This is a Medical Emergency

Immediate Actions - Do Right Now

1. HOLD Apixaban Immediately

• Stop apixaban now - do not give next dose
• Apixaban half-life is ~12 hours in elderly patients (longer with renal impairment)
• The drug will clear over the next 24-48 hours naturally
• Also hold iron supplements - oral iron can darken stool and confuse the picture, but true melaena is tarry, offensive, and distinct

2. Resuscitate First

• Large bore IV access x2 (16G minimum)
• Urgent blood tests: CBC, PT/INR, aPTT, LFTs, RFTs, blood glucose, crossmatch 4 units PRBC, LDH, coagulation profile
• Repeat Hb - if she was already Hb 6 before this bleed, she may now be critically low
• Vital signs: BP, HR, RR, SpO2, urine output - assess haemodynamic stability
• IV fluids: Crystalloid resuscitation while awaiting blood
• Transfuse PRBC - in GI bleeding, target Hb ≥8 g/dL (restrictive transfusion strategy); transfuse 1 unit at a time with reassessment

3. Nasogastric Tube

• Insert NG tube and aspirate - bright red blood or coffee grounds confirms upper GI source
• Also helps clear blood before endoscopy

4. IV Proton Pump Inhibitor

• Pantoprazole 80 mg IV bolus, then 8 mg/hr infusion (or omeprazole equivalent)
• Start this immediately - it reduces rebleeding risk even before endoscopy confirms the source
• Reduces stigmata of recent haemorrhage at endoscopy

Reversal of Apixaban?

• FDA approved for life-threatening/uncontrolled bleeding from apixaban or rivaroxaban
• Low dose: 400 mg IV bolus at 30 mg/min, then 4 mg/min for up to 120 min
• High dose: 800 mg bolus at 30 mg/min, then 8 mg/min for up to 120 min (if last apixaban dose was >8h ago or unknown)

• 4-Factor Prothrombin Complex Concentrate (4F-PCC) - 25-50 units/kg IV - partially reverses anti-Xa activity, used as surrogate when andexanet not available
• This is a pragmatic choice in resource-limited settings

Urgent Endoscopy (OGD)

• Arrange emergency OGD within 24 hours (within 12 hours if haemodynamically unstable)
• Likely sources in this patient:
  • Peptic ulcer disease (gastric or duodenal) - most common
  • Erosive gastritis / NSAID/stress gastropathy
  • Oesophageal varices (less likely unless liver disease)
  • Mallory-Weiss tear
  • Angiodysplasia (common cause of occult GI bleed + anaemia in elderly - this may actually be the cause of her Hb 6 all along)
  • Gastric/oesophageal malignancy - important given age

"EGD should be performed when possible to diagnose the cause of bleeding... both interventional endoscopy and interventional angiography can be used therapeutically to find and stop bleeding." - Morgan & Mikhail's Clinical Anesthesiology

The Core Clinical Dilemma - Anticoagulation vs. Bleeding

Decision Framework:

• Hold apixaban completely
• Resuscitate + urgent OGD
• Achieve haemostasis endoscopically
• Insert retrievable IVC filter as bridge protection against PE while anticoagulation is interrupted

"The central indication for IVC filter placement is to prevent PE in patients with VTE who have a contraindication to anticoagulation." - Fishman's Pulmonary Diseases & Disorders

• Once bleeding is controlled and Hb is stable (usually 48-72 hours after endoscopic haemostasis), restart anticoagulation
• Restart at the lowest effective dose - apixaban 2.5 mg BD is the reduced dose option in elderly with bleeding risk, though 5 mg BD is the standard DVT treatment dose
• This restart decision should be multidisciplinary: gastroenterologist + haematologist/vascular medicine
• If the bleeding source has been treated endoscopically (e.g., ulcer band-ligated or clipped), resuming anticoagulation within 7-14 days is generally considered safe
• Cover with high-dose PPI (pantoprazole 40 mg BD orally) indefinitely while on anticoagulation

• Rule out H. pylori (rapid urease test at OGD) - treat if positive (eradication reduces rebleeding by >80%)
• Avoid NSAIDs, aspirin completely
• Continue PPI cover for duration of anticoagulation

IVC Filter - Practical Note

• Inserted percutaneously via femoral or jugular vein
• Protects against PE during the period anticoagulation is interrupted
• Must be retrieved within 3-6 months once anticoagulation is safely restarted
• Note: IVC filter does NOT treat the existing DVT - it only prevents embolisation. The DVT will need anticoagulation once bleeding is controlled.

Summary Action Plan

RIGHT NOW:
  1. Do not discharge
  2. Hold apixaban
  3. Large bore IV access x2 + bloods + crossmatch
  4. Resuscitate with IV fluids + PRBC transfusion
  5. IV pantoprazole 80 mg bolus → infusion
  6. Insert NG tube
  7. Urgent OGD within 12-24 hours
  8. Refer interventional radiology for retrievable IVC filter

WITHIN 24-48 HRS:
  9. H. pylori testing at OGD
 10. Endoscopic haemostasis of bleeding source

AFTER HAEMOSTASIS (48-72 hrs):
 11. Restart apixaban once bleeding controlled + Hb stable
 12. Add PPI cover long term
 13. Retrieve IVC filter once anticoagulation therapeutic for ≥3 months