Hematology: Thrombocytopenia

Thrombocytopenia

Definition

  • Platelet Count < 150,000

Common Causes

Complications

  • Bleeding
  • Easy Bruising

General Transfusion Threshold

  • For Surgery:
    • 100,000: Neurosurgery or Ocular Surgery
    • 50,000: Major Surgery or Therapeutic Endoscopy
    • 20,000: CVC, LP or Diagnostic Endoscopy
  • 10,000: Transfuse All Patients to Reduce Risk for Spontaneous Bleeding

Idiopathic Thrombocytopenic Purpura (ITP)

Definitions

  • Definition: Autoimmune Destruction of Platelets
  • Type:
    • Primary ITP: Triggered by an Underlying Condition
    • Secondary ITP: Not Triggered by an Underlying Condition
  • Secondary Causes:
    • Infection (HIV, CMV, COVID)
    • Leukemia
    • Systemic Lupus Erythematosus (SLE)
    • Antiphospholipid Syndrome
  • Phases:
    • Newly Diagnosed: < 3 Months
    • Persistent: 3-12 Months
    • Chronic: > 12 Months
  • About 20% of Children that Develop ITP Develop Chronic ITP (> 12 Months)

Pathogenesis

  • Antibodies Produced by Helper T Cells
  • Primary Antigen Presenting Cells: Splenic Macrophages
  • Primary Site of Platelet Clearance: Spleen
    • Some Clearance Can Also Occur in Liver, Bone Marrow & Lymph Nodes

Presentation

  • Often Asymptomatic
  • Bleeding
    • Ecchymosis
    • Petechiae
    • Purpura
    • Gingival Bleeding
    • Epistaxis
  • Thrombocytopenia (< 100,000/microL)
  • Thrombosis

Diagnosis

  • Primarily a Diagnosis of Exclusion with Thrombocytopenia (< 100,000/microL)
  • Antiplatelet Antibody Testing Has Very Low Sensitivity & Generally is Not Used
  • Generally Negative Findings:
    • No Neutropenia or Leukocytosis
    • No Anemia
    • No Splenomegaly
    • No Lymph Node Enlargement

Indications for Treatment

  • Plt < 20,000-30,000/microL
  • Critical or Severe Bleeding

Treatment

  • Acute Bleeding:
    • Life-Threatening Bleeding: Platelet Transfusion, IVIG & Steroids
      • IVIG: 1 g/kg/Day x 1-3 Days
      • Steroids: Methylprednisolone, Dexamethasone or Prednisone
    • Severe Bleeding: IVIG & Steroids
    • Moderate-High Bleeding Risk: IVIG or Steroids
      • Similar Efficacy
      • IVIG Faster
      • Steroids Easier & Less Expensive
  • Chronic Disease:
    • First-Line: Steroids or IVIG
    • Second-Line if Others Fail: Splenectomy, Rituximab or TPO-RA
      • TPO-RA: Thrombopoietin Receptor Agonist (Eltrombopag, Romiplostim)

Splenectomy for ITP

  • Avoid in Young Children (< 5 Years Old)
  • Should Wait Until at Least 12 Months from Initial Diagnosis – May Have Spontaneous Remission
  • If Giving Platelets – Give After Splenic Artery Ligation (Avoid Sequestration)
  • Abdominal US Preoperatively to Rule Out Accessory Spleen

Thrombotic Thrombocytopenic Purpura (TTP)

Definition

  • Thrombotic Microangiopathy from Loss of Platelet Inhibition
    • Due to ADAMTS13 Defect – Cleaves Von Willebrand Factor
  • Results in Small-Vessel Thrombi & Infarction
  • High Mortality – Medical Emergency
    • 90% Mortality if Untreated
    • 10-15% Mortality After Treatment

Types/Causes

  • Immune TTP: Autoantibodies Against ADAMTS13
    • Antiplatelet Drugs
    • Immunosuppression
    • Hormonal Birth-Control
    • Pregnancy
    • Drug Reaction
    • Infections (HIV)
  • Hereditary TTP: Inherited Mutation in ADAMTS13

Presentation

  • Classic Pentad: Mn
    • Fever
    • Hemolytic Anemia
    • Thrombocytopenia
    • Renal Dysfunction
    • Neurologic Dysfunction/Altered Mental Status
  • Most Common Affected End-Organ: Brain (#1) & Kidney (#2)
  • Most Common Cause of Death: Intracerebral Hemorrhage

Diagnosis

  • Presumptive Diagnosis Based on History & Initial Labs
    • Includes CBC (Anemia & Thrombocytopenia) & Direct Coombs Test (Negative)
    • Can Use PLASMIC Score
  • Definitive Diagnosis: ADAMTS13 Assays
    • Results are Often Delayed

PLASMIC Score

  • Used to Help Determine a Presumptive Diagnosis of TTP
  • Factors:
    • Platelet Count < 30,000/micoL
    • Hemolysis (Reticulocyte Count > 2.5%, Undetectable Haptoglobin or Indirect Bilirubin > 2.0)
    • Active Cancer Treated within the Past Year
    • Solid-Organ or Stem-Cell Transplant History
    • MCV < 90 fL
    • INR < 1.5
    • Cr < 2.0
  • Results:
    • Score 0-4: Low Risk
    • Score 5: Intermediate Risk
    • Score 6-7: High Risk

Treatment

  • Primary Treatment: Urgent Plasma Exchange (Plasmapheresis) & Steroids
  • Should Initiate Treatment Based on Presumptive Diagnosis & Not Delay for Definitive ADAMTS13 Testing
  • May Also Consider Rituximab – Monoclonal Antibody Against CD20 (Protein on Mature B Cells)

Mnemonics

Classic Presentation of TTP

  • “FAT-RN”
    • Fever
    • Anemia
    • Thrombocytopenia
    • Renal Dysfunction
    • Neurologic Dysfunction