Thrombosis

Thrombophilia

• Present in about 5% of the population, but most never get VTE

HERITABLE thrombophilia screen:

• • Factor V Leiden
  • Prothrombin gene mutation
  • Protein S
  • Protein C
  • Anti-thrombin
  • (Protein S, C and anti-thrombin levels are impacted by acute thrombosis so might need to check it again later)

ACQUIRED thrombophilia

• • Anti-phospholipid antibodies (lupus anticoagulant, anti-cardiolipin antibody and anti-B2 glycoprotein I antibody)
    • Test if VTE is unprovoked or in an unusual site
    • Patient has a concomitant autoimmune disorder, previous arterial thromboses including CVA/MI, or a history of recurrent pregnancy failure or fetal death
    • Testing for lupus anticoagulant can be affected by DOAC (false positive)
  • Underlying myeloproliferative disease
    • Suspect with splanchnic vein thromboses or VTE in another unusual site
    • Can be present despite normal blood counts
    • Test is JAK2 kinase
    • Consider CALR mutation testing and a BM biopsy if JAK2 is negative in patients with a high index of suspicion
  • Consideration of malignancy
    • 10% of those with unprovoked VTE will be diagnosed with cancer in the first year
    • Medical history
    • Examination
    • FBE, calcium, LFts
    • CXR
    • Mammogram
    • Pap smear
    • PSA
    • NBCSP
    • Routine CT and tumour markers is not recommended, according to the Austin guidelines, but can be done depending on risk and clinical scenario
  • Hyperhomocysteinaemia - testing not recommended routinely

Anticoagulants in thrombosis

• DOAC - 3/12 is shortest acceptable treatment for provoked DVT
  • Apixaban 10mg BD for one week then 5mg BD
  • Rivaroxaban 15mg BD for 3 weeks then 20mg daily
• Warfarin preferred if: (starting dose 5mg daily in most patients)
  • Weight 120kg or BMI >40
  • Weight less than 40kg
  • APLS
  • Mechanical heart valve
  • Any contraindication to DOAC, including eGFR <30
• Warfarin starting dose 5mg daily in most patients. Need to bridge while loading for patients with VTE, until INR >2 for 2 consecutive days
• Enoxaparin - primarily for cancer-related thrombosis, pregnancy and superficial vein thrombosis. 1mg/kg BD or 1.5mg/kg daily.
  • Check enoxaparin anti-Xa levels in patients with renal failure, extremes of weight, suspected non-compliance or overdose. Therapeutic level (peak, 4 hours post dose) is 0.5-1.0 units/mL if on a twice daily regimen.
• Unfractionated heparin
  • Primarily used when rapid onset and offset is desired
  • Plasma heparin anti-Xa level can be used to guide dosing in some patients:
    • Failure to achieve an APTT result within the therapeutic range after 24 hours
    • Heparin resistance (i.e., requirement of >35,000 units of UFH per 24 hours to achieve an APTT result within therapeutic range)
    • Lupus anticoagulant (prolongs baseline APTT)
    • >100kg
    • Pregnant
    • Need to achieve therapeutic range rapidly
    • Markedly raised acute phase reactants

VTE Prophylaxis

The only surgical patients that don't get chemoprophylaxis (assuming no contraindication) are those with surgery <30 mins and NO risk factors

Risk factors

• Acquired
  • Previous VTE
  • Malignancy
  • Surgery
  • Trauma
  • Immobilisation
  • Age >65
  • Pregnancy
  • Chronic inflammatory bowel and liver disease
  • Cardiovascular disease
  • Drugs - hormonal, cancer therapy
  • Antiphospholipid antibodies
  • Kidney disease
  • Haematologic conditions
• Inherited
  • Thromobophilia
  • Anatomic
    • Varicose veins
    • Paget-Schroetter syndrome
    • May-Thurner syndrome
    • IVC abnormalities