Lecture 9 & 10 - trombositopenia PSPDG

Thrombocytopenia Overview

  • Defined as a low platelet count in the blood.

  • Can result in increased bleeding and various clinical manifestations.

Platelet Biochemistry

A. Platelet Production and Structure

  • Production: Platelets originate from megakaryocytes in bone marrow through pseudopod formation and septation.

  • Life Span: 5-7 days in circulation.

  • Size: 2-3 microns in diameter.

  • Structure: Lack a nucleus, but contain mitochondria and messenger RNA.

  • Granules: Two types visible under electron microscope; functionally three types:

    • Dense granules

    • Alpha granules

    • Lysosomal granules

Clinical Features of Platelet Disorders

  • Hemorrhage Risk: Increases when platelet count falls below 50,000.

  • Sites of Bleeding:

    • Cutaneous (petechiae, purpura, ecchymosis, venipuncture sites)

    • Mucosal (epistaxis, menometrorrhagia, hemorrhagic bullae, gastrointestinal bleeding)

    • Central nervous system (CNS)

Clinical Manifestations Associated with Falling Platelet Counts

Platelet Count per Microliter

Clinical Manifestations

50,000-20,000

Increased bleeding during surgery and trauma

<20,000

Increased risk of spontaneous hemorrhage

<10,000

Increased risk of spontaneous intracerebral hemorrhage

Quantitative Platelet Disorders

  • Thrombocytopenia: Defined as decreased platelet count caused by various factors.

Causes of Thrombocytopenia by Decreased Platelet Production

  1. Primary Bone Marrow Disorders:

    • Aplastic anemia, Fanconi anemia, Leukemia, Myelodysplasia

  2. Bone Marrow Invasion:

    • Metastatic cancer, Myelofibrosis, infections (e.g. tuberculosis)

  3. Bone Marrow Injury:

    • Chemicals (e.g. benzene), drugs (e.g. chemotherapy agents), radiation, infection

  4. Nutritional Disorders:

    • Vitamin B12, Folate, Copper deficiencies

  5. Hereditary Syndromes:

    • Hypomegakaryocytic thrombocytopenia, ineffective platelet production syndromes (e.g., May-Hegglin anomaly)

Increased Destruction of Platelets Causes

  • Immune-Mediated Thrombocytopenia:

    • Autoimmune conditions (e.g., ITP), Alloimmune thrombocytopenia, Drug-induced immune thrombocytopenia (e.g. Heparin-induced thrombocytopenia)

Non-Immune-Mediated Thrombocytopenia

  • Conditions:

    • Disseminated Intravascular Coagulation (DIC)

    • Thrombotic Thrombocytopenic Purpura (TTP)

    • Hemolytic Uremic Syndrome (HUS)

Differential Diagnosis of Acquired Destructive Thrombocytopenias

Condition

PT

aPTT

Platelet Count

Schistocytes

DIC

Increase

Increased

Decreased

Sometimes present

ITP

Normal

Normal

Decreased

None

TTP

Normal

Normal

Decreased

Present

HUS

Normal

Normal

Decreased

Present

Clinical Thresholds for Surgery

  • Neurosurgery or ocular surgery: Platelet count should be >100,000/microL

  • Major surgeries: Platelet count should be >50,000/microL

  • Endoscopic procedures: 50,000/microL for therapeutic; 20,000/microL for low-risk diagnostic

  • Central line placements: <20,000/microL

  • Dental Alerts:

    • Routine treatment contraindicated if platelet count <50,000/mm3

    • Platelet count must be >75,000/mm3 for outpatient surgery, ideally >100,000/mm3 for major surgical procedures in OR.