Thrombocytopenia

    • Normal platelet count range: 150 – 400 x 109/Lthrombocytopenia
    • Thrombocytopenia at < 100 x 109/L; bleeding occurs at <20 x 109/L
    • Thrombocytopenia results from:
    1. decreased bone marrow production (which usually affect RBC and WBC production)
    2. sequestration, usually in an enlarged spleen
    3. increased platelet destruction or consumption
    • Isolated thrombocytopenia indicates consumption or destruction of platelets or a hereditary disorder.
    • Thrombocytopenia associated with anemia and leukopenia indicates hemodilution, hypersplenism, or bone marrow malfunction.

    Approach

    • First step is to review the peripheral blood smear to rule out pseudothrombocytopenia (in vitro artifact caused by platelet agglutination via antibodies when Ca decreased by EDTA in purple top tubes…it’s a testing error that causes clumping)
    • Bone marrow should be examined in patients > 60 exhibiting isolated thrombocytopenia b/c myelodysplasia could be present

    Hemodilution

    • Decrease of 20 – 70% occurs in patients following major surgery à decrease peaks at an average of 2 days, then levels increase to 2 -3 times the norm after about 14 days.
    • Massive blood or plasma transfusion may cause dilutional thrombocytopenia b/c blood stored for more than 24 hours and RBCs reconstituted for transfusion have no platelets.

     

    Hypersplenism

    • 30-40% of circulating platelets are normally sequestered in the spleen. Splenomegaly leads to greater sequestering, as much as up to 90% of platelets à
    • Use radiology to determine splenomegaly and assess if the thrombocytopenia is caused by hypersplenism.

    Decreased Platelet Production

    • Caused by congenital or acquired bone marrow disease, and usually manifests as pancytopenia.
      • Rarely, isolated thrombocytopenia is seen in MYH9-associated thrombocytopenias
      • You need to look at the peripheral blood smears to determine diagnosis of primary bone marrow disorder.
        • The presence of very large platelets along with neutrophil inclusions suggests MYH9-associated thrombocytopenia, which is a hereditary disorder. Large platelets are caused by a defect in the nonmuscle myosin heavy chain.
      • Trends suggest marrow disorders like myelodysplasia and chronic lymphoid leukemia.
      • Can also be caused by HIV, which suppresses production of megakaryocytes.
      • Drug-Inducted Thrombocytopenia: Predictable in chemotherapies due to bone marrow suppression.

    Platelet Consumption

    • Disseminated intravascular coagulation (DIC) or consumptive coagulopathy via pathological activation is usually accompanied by thrombocytopenia. (note: coagulation assays may not be markedly elevated.)
    • Thrombotic thrombocytopenic purpura (TTP) causes excessive consumption leading to deficiency. TTP is characterized by widespread platelet thrombi in arterioles and capillaries of the heart, brain and kidneys; thrombocytopenia; and fragmentation of erythrocytes as they circulate through these occluded vessels causing hemolytic anemia and jaundice. Exact pathogenesis is unclear, but it appears to involve the introduction of one or more platelet-aggregating substance into circulation.
    • Bacteremia and fungemia are common causes of consumptive thrombocytopenia.
      • Pathogenesis multifactorial: thrombin-mediated, increased macrophage clearance of platelets, decreased marrow platelet production, and effects of microbial toxins.

    Platelet Destruction

    • Pathological factors destroy platelets directly or indirectly as a result of antibody production. (antibody-mediated thrombocytopenic disorders). The antibodies target the platelet membrane glycoproteins. Non-immune destruction of platelets can result due to mechanical injury.
    • Chronic autoimmune thrombocytopenia: Immune thrombocytopenic purpura (ITP) is an acquired, antibody-mediated disease characterized by persistent decrease in platelet count. (autoantibodies attack platelets leading to their destruction).
      • IgG antibody commonly bind to 2 membrane glycoproteins. The platelets are thus more susceptible to phagocytosis and are destroyed in the spleen and liver.
      • Splenomegaly accompanies.
    • Drug-Induced Thrombocytopenia:
      • Drug-dependent antibodies are antibodies that react with specific platelet surface antigens, resulting in thrombocytopenia only when the drug is present. Many drugs are capable of inducing these antibodies, but it is more commonly seen with quinine and sulfonamides. These drugs act as haptens and induce antigen-antibody responses and formation of immune complexes that cause platelet destruction by complete-mediated lysis.
        • Patients exhibit a rapid fall in platelet count within 2-3 days of resuming a drug or 7 or more days after starting a drug for the first time. Platelet count rises quickly after discontinuation of the drug
      • Heparin-Induced Thrombocytopenia: HIT results from heparin-dependent antiplatelet antibodies that cause aggregation of platelets and their removal form circulation. The antibodies often bind to vessel walls, causing thrombosis and complications such as stroke and MI. Complications start typically 5 days after the start of therapy.