THROMBOCYTOPENIA

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THROMBOCYTOPENIA

• Hrach Ike Kasaryan

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Introduction

• Definition-
• Platelet count less than 150000 cells/microliter
• It is a common problem that one encounters in the
  in patient setting
• So it is important to have a good understanding
  of how to approach thrombocytopenia

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The life of a platelet

• Platelets arise from MEGAKARYOCYTES which are
  located with in the bone marrow
• They are formed by pinched of pieces of cell
  membrane from the megakaryocyte

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The life of a platelet

• After leaving the marrow about 1/3 of platelets
  get sequestered with in the spleen
• The remaining 2/3 circulate for about 7-10 days
• During hemostasis only a small fraction of the
  platelets get used up
• So the usually way a platelets life ends is by
  becoming senescent and being lunch for the bodys
  phagocytes
• The normal count is 150000 to 450000
  cells/microliter

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The life of a platelet

• A decrease in the platelet stimulates the release
  of Thrombopoetin (TPO)
• There is a receptor for this molecule on the
  Megakaryocyte
• This triggers an increase in size and number of
  Megakaryocytes which beging churn out more
  platelets to make up for the deficit
• Just as younger neutrophils are released during
  infection younger platelets are released when
  trying to make up for the deficit
• This can easily be detected on the peripheral
  smear which can be seen as Larger than normal
  platelets

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Thrombocytopenia Sx

• The Sx depend on the degree
• At counts 50000 to 90000 there are usually NO
  Symptoms
• At counts of 20000 to 50000 the patient may
  report EASY BRUISABILITY but no spontaneous
  bleeding is seen
• At counts lt20000 patients are AT HIGH RISK FOR
  SPONTANEOS BLEEDING (GI bleeds Mucous Membranes
  Petechiae)

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Thrombocytopenia CAUSE

• There are Four Mechanisms that may lead to a
  patient having a decreased platelet count
• Decreased Bone Marrow Production
• Increased Splenic Sequestration
• Accelerated Destruction in the periphery
• Pseudo-Thrombocytopenia!!

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PSUEDO-Thrombocytopenia

• It is important when ever a low platelet count is
  found to rule this out
• It is due to the specimen being collected using
  EDTA as the anticoagulant leading to clumping of
  platelets together leading to false low readings
• Looking at the Blood smear is a quick way to see
  if it is true or not
• Also if the collection is using EDTA you can
  request of the nurse (Do so at your own caution)
  to use heparin as the anticoagulant when sending
  the sample
• If with the heparin anticoagulated sample the
  count is still low than you have a true
  thrombocytopenia

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Impaired Platelet Production

• Disorders that damage stem cells or prevent their
  proliferation usually cause thrombocytopenia
• Typically in this case other cell lines would be
  affected as well so you wouldnt just have an
  isolated thrombocytopenia
• So in this case you would expect a pancytopenia
• Bone marrow biopsy in these patients would show a
  decrease cellular bone marrow with decreased
  megakaryocytes
• The mneumonic to remember the causes of decreased
  production is PANCYTO (which is also helpful
  because it reminds us that we see a pancytopenia
  along with it)

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Impaired Platelet Production

• P Paroxysmal Nocturnal Hgb-uria (this is also a
  cause of increased destruction)
• A Aplasias Aplastic Anemias
• N Neoplasms and Near Neoplasms
  (myelodysplasias leukemias metastic
  malignancies)
• C no c
• Y V looks like Y so Vitamin Deficiencies (B12
  and Folate deficiencies are a rare cause of it)
• T Toxins Drugs Radiation (Ethanol Thiazides
  Estrogens Chemo can all inhibit production)
• O Over whelming infections (sepsis TB Fungi
  HIV)

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Increased Destruction

• This mechanism can further be broken down into
  Immunologic vs non-Immunologic
• NON-IMMUNOLOGIC destruction
• Abnormal vessels Micro Angiopathic Hemolytic
  Anemia Intravascular Prosthetics (valves) and
  fibrin thrombi can all cause increased
  destruction of platelets
• IMMUNOLOGIC destruction
• Drugs (HEPARIN) Viral or Bacterial Infections
  chronic Idiopathic Thrombocytopenic Purpura are
  all causes of immune destruction
• Drugs such as heparin or ITP are caused by ABs
  directed against platelets where as in other
  cases the platelet is the innocent bystander
  caused to lyse by complement activation

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SO HOW ARE YOU GOING TO WORK IT UP
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THE WORK UP!

• THE ABSOLUTE FIRST THING IS TO RULE OUT
  PSUEDO-THROMBOCYTOPENIA
• HISTORY-
• Try to find risk factors for any of the three
  mechanisms (ETOH New Drug Use HIV risk Occult
  Malignancy) Medication List is of extreme
  importance
• PHYSICAL EXAM
• Searching for splenic enlargement is key

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THE WORK UP!

• LABS
• Peripheral Blood smear this can be a tremendous
  help.
• Seeing large platelets implies the bone marrow is
  churning out immature platelets suggesting the
  problem is elsewhere
• Schistocytes (fragmented RBCs) implies
  microangiopathic hemolytic anemia and the
  platelets are being destroyed by getting rammed
  into and through clots
• Serologies
• In the patient with the right history and risk
  factors HIV SLE Toxo ANA EBV CMV or other
  serologies can help confirm there presence
• Anti-Platelet ABs are rarely ordered

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THE WORK UP!

• BONE MARROW BIOPSY all other possibilities
  such as drugs should be exhausted before going to
  this step do the invasiveness of this test
• If decreased Megokaryocytes are found this can
  lead to a direct diagnosis of either
  infiltration fibrosis etc and the cause in
  decreased production
• If increased Megakaryocytes are found than the
  bone marrow is trying to make up for peripheral
  losses and the problem is elsewhere
• Myelodysplasio may also be found on the biopsy

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Treatments

• The First Best step is checking the meds and with
  drawing the offending agent to see if the
  platelets correct
• The platelet count should return to normal in
  7-10 days
• Heparin Induced thrombocytopenia should be
  suspected on any patient with recent starting of
  heparing and low platelet counts.
• Unfortunately the antibodies formed in HIT
  80-90 cross react with LMWH
• Thiazides are also one of the most common drugs
• Some other common offenders are
  Chemotheraputics Sulfonamides PCN Cephs and
  very rarely ACEs can do it to!

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Treatments

• Platelet Transfusions
• Generally you want to avoid this as much as
  possible because they actually may make the
  patient worst!!
• This is due to an immune resistance!
• Platelet transfusion are usually not indicated
  for patients with Platelet counts greater than
  20000 and with no evidence of bleeding
• SO when to transfuse platelets
• In patients with sever bleeding the platelets
  should be maintained at 50000
• IN mild bleeding they should be maintained above
  20000
• To prevent spontaneous bleeding keep above
  10-20000
• Prior to Surgery as well keep above 5000