THROMBOCYTOPENIA

1
THROMBOCYTOPENIA

• Hrach Ike Kasaryan

2
Introduction

• Definition-
• Platelet count less than 150,000 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

3
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

4
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 150,000 to 450,000
  cells/microliter

5
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

6
Thrombocytopenia Sx?

• The Sx depend on the degree
• At counts 50,000 to 90,000 there are usually NO
  Symptoms
• At counts of 20,000 to 50,000 the patient may
  report EASY BRUISABILITY but no spontaneous
  bleeding is seen
• At counts lt20,000 patients are AT HIGH RISK FOR
  SPONTANEOS BLEEDING (GI bleeds, Mucous Membranes,
  Petechiae)

7
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!!

8
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

9
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)

10
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)

11
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

12
(No Transcript)
13
SO HOW ARE YOU GOING TO WORK IT UP?
14
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

15
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

16
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

17
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!

18
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
  20,000 and with no evidence of bleeding
• SO when to transfuse platelets?
• In patients with sever bleeding , the platelets
  should be maintained at 50,000
• IN mild bleeding, they should be maintained above
  20,000
• To prevent spontaneous bleeding, keep above
  10-20,000
• Prior to Surgery as well, keep above 50,00