Day #28 - Thrombocytopenia

Today we talked about a case of an elderly man who presented with isolated acute, relatively asymptomatic, severe thrombocytopenia.

We discussed an approach to the differential diagnosis of thrombocytopenia:

• Decreased production: i.e. myelodysplasia, leukemia/lymphoma, other infiltrative malignancy (i.e. breast cancer), substrate deficiency (B12/folate), toxins (ETOH, methotrexate, chemo), infections (measles, mumps, rubella, EBV),
  
• Sequestration in the spleen
  
• Increased destruction:
  
  • Immune mediated: collagen vascular disease including SLE and APLA, viral - HIV/HBV/HCV/EBV/CMV, Idiopathic Thrombocytopenia Purpura, drug related - i.e. vancomycin/septra/quinine, heparin induced thrombocytopenia (HIT), post-transfusion purpura
    
  • Non-immune mediated: DIC, TTP/HUS, HELLP syndrome, sepsis
    
• Congenital/Gestational

We used this differential to focus our history and physical exam, then used that information recursively to make come up with an investigation plan.

After reviewing the lab tests including bone marrow biopsy we decided that the most likely diagnosis in today's case was ITP and then touched upon treatment. There are guidelines on treatment published but these date back to 1997.

NB: Patients should be immunized against pneumococcus, haemophilus, and neiserria species on diagnosis in case splenectomy is required.

Treatment for ITP

1. When: Risk of bleeding complications is greater than the risk of treatment
   
   • Is there severe or life threatening bleeding ==> TREAT
   • Is the risk of bleeding high because PLT <10> TREAT
   • Is the PLT count <30-50?
     
     • Bleeding? ==> TREAT
     • Asymptomatic but risk of bleeding due to lifestyle or other conditions ==> consider TREATING, discuss with patient
       
   • Is the PLT count >30-50 ==> Observe
2. How:
   
   • Steroids:
     
     • Prednisone 1mg/kg PO OD -- should work within 1-2 weeks. If not consider other method. Taper over 4-6 weeks after PLT count normalized
     • Dexamethasone 40mg PO OD x 4 days -- repeat in 14-28d as needed to complete 4-8 "cycles". Head to head trial with prednisone is underway
     • Pulse solumedrol -- small studies suggest benefit, large studies pending
       
   • IVIG -- 1g/kg/day x 1-2 days. Response in a few days, duration several weeks
   • Second line therapy:|
     
     • Splenectomy -- 4-6 weeks of treatment should happen first to allow for spontaneous remission. Will induce remission in ~ 65%. Risk of overwhelming post splenectomy infection (OPSI) of ~ 1/1000 per year.
     • Rituximab -- insufficient evidence to recommend. Use limited to patients with an unacceptably high risk from splenectomy
   • Refractory ITP (Plt <50,> 3 months, failed splenectomy)
     
     • Specialty consultation required. Consider observation, chronic steroids, rituximab, cyclophosphamide, other immunosuppressives/modulatories