Hematology - Platelet Disorders

Bleeding Signs

• Petechiae: Small, pinpoint round spots on the skin due to bleeding under the surface. Size: <2mm.

• Purpura: Larger areas of bleeding under the skin. Size: >3mm to 1cm.

• Ecchymosis: Larger area of bleeding leading to a bruise-like appearance. Size: >1cm.

Quantitative Platelet Disorders

• Thrombocytopenia: Platelet count < $150 \times 10^9/L$

  • Decreased Production of Platelets

    • Aplastic Anemia

    • Chlorothiazide Suppression

    • Thrombocytopenia with Absent Radius (TAR)

    • Myelodysplastic Syndrome

  • Aplastic Anemia

    • Generalized bone marrow suppression leads to a decrease in all cell types (pancytopenia).

    • May be acquired through radiation or chloramphenicol therapy.

  • Chlorothiazide Suppression

    • Selective suppression of megakaryocytes by chlorothiazide (a diuretic).

  • Thrombocytopenia with Absent Radius (TAR)

    • Absent or decreased, and abnormal bone marrow megakaryocytes with deformities of the arm.

  • Myelodysplastic Syndrome

    • A group of acquired clonal hematologic disorders affecting the hematopoietic stem cell, leading to pancytopenia.

    • Also known as preleukemia.

  • Dilutional Loss

    • Extensive blood transfusion is often accompanied by thrombocytopenia, the degree of which is directly proportional to the number of units transfused.

  • Immune Platelet Destruction

    • Immune Thrombocytopenic Purpura (ITP)

      • Platelet destruction by immune mechanisms, associated with increased levels of IgG or complement on the platelet surfaces.

  • Non – Immune Platelet destruction

    • Artificial Surfaces

      • Induce platelet adherence as well as the formation of platelet microaggregates.

      • Examples: Cardiovascular prosthetic devices, vascular grafts, dialysis membranes.

  • Microangiopathic Hemolytic Anemia (MAHA) with Thrombocytopenia

    • Fibrin is deposited in small vessels, causing RBCs to fragment.

      • Disseminated Intravascular Coagulation

      • Hemolytic Uremic Syndrome (HUS)

      • Thrombotic Thrombocytopenic Purpura (TTP)

      • Disseminated Intravascular Coagulation

        • Systemic clotting (activation of the coagulation cascade) due to toxins or conditions that trigger the release of procoagulants. Multiple organ failures due to clotting.

      • Hemolytic Uremic Syndrome (HUS)

        • A type of MAHA most commonly associated with E.coli 0157:H7 infection (enterohemorrhagic E.coli) / Shiga toxin.

        • The toxin causes extensive vessel damage and clot formation systematically, but is typically seen in kidney vessels, causing renal damage.

      • Thrombotic Thrombocytopenic Purpura (TTP)

        • Due to ADAMTS 13 deficiency that is responsible for the breakdown of large VWF multimers. When multimers are not broken down, clots form, causing MAHA.

  • Increased Platelet Sequestration by Spleen

    • Splenomegaly

      • More than 1/3 of platelets are sequestered, causing pseudothrombocytopenia.

Thrombocytosis

• Thrombocytosis: Platelet count > $400 \times 10^9/L$

  • Primary Thrombocytosis

    • Uncontrolled proliferation of platelets (megakaryocytes), a characteristic of myeloproliferative disorders (CML, PCV, ET).

  • Secondary Thrombocytosis (reactive)

    • A broad spectrum of acute and chronic illnesses elicit an increase in platelet production.

Qualitative Platelet Disorders

1. Adhesion Defects

   • Bernard – Soulier Syndrome

   • Von Willebrand disease

2. Aggregation Defects

   • Glanzmann Thrombasthenia

   • Afibrogenemia

3. Storage Pool Defects

   • Alpha Granule Deficiency

     • Gray Platelet Syndrome

   • Dense Granule Deficiency

     • Wiskott – Aldrich Syndrome

     • Hermansky – Pudlak Syndrome

     • Chediak – Higashi Syndrome

Adhesion Defects

• Bernard – Soulier Syndrome

  • Autosomal recessive disorder characterized by severe thrombocytopenia.

  • Deficiency of or dysfunctional GPIb/IX/V receptor.

  • Prolonged bleeding time.

  • Normal aggregation in response to all aggregators except ristocetin.

  • Presence of giant platelets.

• Von Willebrand Disease

  • A bleeding disorder characterized by deficiency or dysfunction of von Willebrand Factor (VWF).

  • Normal platelet count.

  • Prolonged bleeding time and APTT.

  • VWF

    • Synthesized in the endothelium and megakaryocytes.

    • Carrier of Factor VIII (8).

    • Anchors platelets to the subendothelium.

Aggregation Defects

• Glanzmann Thrombasthenia

  • Disorder of platelet aggregation affecting GP IIb/IIIa function, the most abundant platelet surface receptor.

  • Prolonged bleeding time and normal platelet count.

  • Normal platelet aggregation using Ristocetin.

• Afibrinogenemia

  • Lack of fibrinogen in the plasma.

  • Prolonged bleeding time, PT, aPTT, and thrombin time.

Storage Pool Defects

• Alpha Granule Deficiency

  • Gray Platelet Syndrome

    • Platelets lack alpha granules and are characterized by large platelets that appear gray or blue-gray in Wright stain.

• Dense Granule Deficiency

  • Wiskott – Aldrich Syndrome

    • Triad: recurrent infection, thrombocytopenia, and eczema.

  • Hermansky – Pudlak Syndrome

    • Patients exhibit oculocutaneous albinism and are prone to hemorrhage.

  • Chediak – Higashi Syndrome

    • Defective WBC lysosomal function. Large lysosomes in all types of WBC.

    • Patients also may exhibit bleeding, albinism, recurrent infections, and neurologic issues.