Day #134 - Thrombophilia

Fantastic case today. A young woman with recurrant thromboses including one on LMWH (in the context of thrombocytopenia) manifesting as a cardiac mass! I have previously blogged about DVT/PE here.

There are a good set of clinical guidelines for DVT/PE here.

The utility of the thrombophilia workup (or possible lack thereof) will be debated at next week's medical grand rounds. You should attend.

A couple of things I wanted to highlight:

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Thrombophilias:

• Factor V Leiden/Activated Protein C resistance
• Prothrombin mutation
• Protein C and S deficiencies
• Antithrombin III deficiency
• Elevated Factor VIII
• Antiphospholipid Antibody Syndrome
• Hyperhomocysteinemia
• Heparin Induced Thrombocytopenia

Our patient had none of these for her first ~5 embolic events -- but clearly she has some underlying thrombophilia which we probably have not discovered yet. A malignancy search has been negative.

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Use of D-Dimer in established thromboembolic disease

This can be used to assist in risk stratification. A positive D-dimer (1 month post stopping warfarin) predicts patients who have a high risk of recurrent thromboembolism (original NEJM article and meta-analysis)

A Canadian study sought to identify risk factors for recurrent DVT/PE in patients with one previous idiopathic DVT/PE and found that they could predict women at low risk who could safely stop anticoagulation. These women had 0 or 1 of the following:

• Post thrombotic signs (hyperpigmentation of limb, edema, redness)
• D-Dimer greater than 250
• BMI greater than 30
• Age greater than 65

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Heparin Induced Thrombocytopenia

This is a prothrombotic condition caused by anti-PF4 antibodies which bind to heparin-platelet complexes and activate platelets. This causes platelet consumption and activation with thrombosis (arterial or venous).

If you see a patient on heparin who develops thrombocytopenia and thrombosis you had better think about this diagnosis.
The diagnosis can be challenging; however, there is a clinical prediction rule, which in association with laboratory testing can be helpful in ruling out HIT. This is called the 4 T's.

1. Thrombocytopenia:
   • Greater than 50% drop in PLT and nadir greater than 20 = 2 points
   • 30-50% drop OR nadir 10-20 = 1 point
   • less than 30% drop OR nadir less than 10 = 0 points
2. Timing:
   
   • Drop @ 5-10 days (or less than 1 day with previous heparin within 30d) = 2 points
   • Drop after day 10, or unclear when drop, or less than 1 day with previous heparin greater than 30d ago = 1 point
   • Fall less than four days without previous exposure = 0 points
3. Thrombosis
   
   • New thrombosis = 2 points
   • Progressive or recurrant thrombosis or suspected (not proven) thrombosis = 1 point
   • None = 0 points
4. oTher cause of thrombocytopenia
   
   • None = 2 points
   • Possible = 1 point
   • Definite = 0 points

Total score:

• 0-3 low (0%)
  
• 4-5 intermediate (10%)
  
• 6-8 high (80%)

NB: our patient would score a minimum of 6 (if you assume there is a possible other cause of thrombocytopenia)

The authors suggest the following algorithm for diagnosis and management of HIT using the 4T's coupled with the widely available sensitive but non-specific anti-PF4 antibody assay to screen and the difficult to obtain serotonin release assay (SRA) to confirm.