Approach to Thrombocytopenia

  1. What are the three levels of severity of thrombocytopenia?
    • Mild: no problem expected with or without trauma or surgery
    • Moderate: may bruise with mild trauma but usually not spontaneously; excessive bleeding is likely to occur at surgery 
    • Severe: risk of spontaneous bruising and bleeding, which may be life threatening (e.g. intracranial hemorrhage)
  2. What are the three possible causes/classifications of thrombocytopenia?
    Decreased production of platelets, increased destruction, or sequestration
  3. What are possible causes of decreased production of platelets?
    • Bone marrow suppression or aplasia due to drugs/toxins, viruses, or ideopathic such as aplastic anemia
    • Marrow infiltration such as in leukemia and secondary tumours or myelofibrosis
    • Ineffective production due to vitamin B12/folate deficiency or myelodysplasia
    • Hereditary
  4. What cells to platelets come from?
  5. What are causes of increased sequestration of platelets?
    • Hypersplenism
    • Cardiopulmonary bypass
    • Post liver transplantation
  6. What are possible causes of increased destruction of platelets?
    • Immune: idiopathic, secondary (SLE, CLL, lymphoma)
    • Non-immune: TTP/HUS, DIC, sepsis
  7. What are the principles of managing thrombocytopenia?
    • Avoidance of aggravating factors such as meds that would affect platelet function and intramuscular injections
    • Investigate and treat underlying cause
  8. Why should you be weary of a low platelet count found using a CBC?
    The platelets may be clumping together, giving a falsely low score. Look on a film to confirm.
  9. What are petechiae? What are purpura?
    • Petechiae: pinhead size, non-palpable red marks on skin. Non-blanching and caused by RBC extravasation from capillaries. 
    • Purpura: confluent petechiae that are purplish
  10. What causes immune thrombocytopenic purpura and how do you diagnose it?
    • It is caused by autoreactive antibodies binding to platelets and shortening their lifespan, due to clearance by the reticularendothelial system. 
    • It is a diagnosis of exclusion (try to think of everything else that could be the cause first)
  11. What can immune thrombocytopenic purpura (ITP) occur in association with?
    Viral/bacterial infections, autoimmune disease, drugs, lymphoproliferative disorders, post transfusion, idiopathic
  12. What are clinical manifestations of immune thrombocytopenic purpura?
    Asymptomatic, excessive bleeding or bruising, no splenomegaly
  13. Is acute immune thrombocytopenic purpura more common in adults or children? Males or females?
    More common in children (80%). Equally as common in males and females.
  14. How long does acute immune thrombocytopenic purpura usually last? What normally causes it and how does it resolve?
    Usually lasts less than 6 months. It usually precedes a viral infection by 2-21 days. Acute ITP usually has spontaneous remission in 1-2 months.
  15. How do you treat acute immune thrombocytopenic purpura?
    Treat only if symptomatic. In children you may give IVIG to avoid effects of steroids. In adults, you may prescribe prednisone.
  16. Is chronic immune thrombocytopenic purpura more common in adults or children? Males or females?
    More common in adults (80%), also 3x more common in females.
  17. Does chronic immune thrombocytopenic purpura usually resolve spontaneously? What other disorders is it associated with?
    No, rarely resolves spontaneously. It usually has insidious onset and is associated with SLE and lymphoproliferative disorders.
  18. How do you treat chronic immune thrombocytopenic purpura?
    Prednisone, splenectomy is prednisone failure/intolerant, IVIG in patients who don't respond to steroids or if patient is bleeding, Rh immune globulin, platelet transfusion only in extreme cases because of very short life span of transfused platelets
  19. How long after a patient starts heparin may they develop heparin induced thrombocytopenia? Is it dose dependent?
    • 5-14 days
    • yes
  20. What is the pathologic mechanism of heparin induced thrombocytopenia?
    Antibody to heparin which has an affinity for Fc receptors (PF4) on platelets binds, resulting in platelet activation and consumption. This is associated with arterial or venous thrombi.
  21. What are some of the symptoms of Thrombotic Thrombocytopenia purpura (TTP)/HUS? What is a possible cause? What factor is missing in this case?
    • Fever, hemolysis, thrombocytopenia, renal insufficiency, and neurological symptoms
    • Causes: E. coli, HIV, medications
    • Absence/deficiency of von Willebrand cleaving protease
  22. What are some clinical abnormalities you would expect someone with TTP/HUS?
    • CBC: anemia, thrombocytopenia
    • Blood smear: RBC fragments, thrombocytopenia
    • Urea/creatinine increased due to renal failure
  23. How do you treat TTP/HUS?
    Plasmapheresis/plasma infusion
  24. True or false: in HUS you expect to see hemolysis, thrombocytopenia and renal failure.
  25. True or false: HUS is more common in adults
    False: it is more common in children
  26. True or false: HUS may follow diarrheal illness
  27. What is disseminated intravascular coagulopathy (DIC)?
    widespread intravascular deposition of fibrin with consumption of coagulation factors and platelets with accelerated fibrinolysis
  28. What are possibly underlying causes of DIC?
    • Malignancy: mucin secreting adenocarcinoma, leukemia (esp. M3)
    • Sepsis
    • Obstetrical accidents
    • Trauma, widespread tissue injury
  29. What are some expected clinical findings in DIC?
    • CBC: anemia, thrombocytopenia
    • Blood film: RBC fragments, thrombocytopenia
    • INR/PTT: prolonged due to consumptive coagulopathy 
    • Fibrinogen: decreased
    • increased presence of D-dimer due to accelerated fibrinolysis
  30. How do you treat DIC?
    • supportive care with blood products
    • identify and treat underlying cause
  31. What are the 6 steps in the approach to thrombocytopenia?
    • 1. Rule out pseudothrombocytopenia (ie. due to EDTA, examine peripheral smear, repeat platelet count using citrate as anticoagulant)
    • 2. Screen for medications and alcohol use
    • 3. Exclude liver disease and hypersplenism through abdominal ultrasound and liver function tests
    • 4. Exclude bone marrow disease
    • 5. Exclude possibility of TTP/HUS and DIC
    • 6. Look for secondary causes of immune thrombocytopenic purpura: autoimmune diseases, lymphoproliferative diseases, viral, medications
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Approach to Thrombocytopenia