Platelet

Thrombotic Thrombocytopenic Purpura

search

Thrombotic Thrombocytopenic Purpura, TTP

  • Epidemiology
  1. Peak age 30 to 40 years old
  2. Slightly more common in women
  3. Rare: 4 to 11 cases per year per 1 million people per year in the United States
  • Pathophysiology
  1. ADAMTS13 Protease dysfunction
    1. Von Willebrand Factor (vWF) is exposed when intravascular injury occurs
      1. vWF is analogous to a net that traps platelets, forming a transient plug
      2. The plug is typically limited and stops bleeding without thrombosing the vessel
    2. ADAMTS13 normally cleaves the long chain Von Willebrand Factor (vWF), thus limiting the plug
      1. When ADAMTS13 is defective or absent, vWF forms traps large complexes of platelets
      2. Vessel blocks with these large complexes of vWF and platelets resulting in thrombosis
    3. ADAMTS13 deficiency predisposes to TTP
      1. ADAMTS13 deficiency may be acquired or via genetic mutation (Upshaw-Schulman Syndrome)
      2. Those with ADAMTS13 deficiency may develop TTP in response to stress or infection
  2. Overlap with several Gastroenteritis related conditions
    1. Shiga-toxin Enterocolitis
    2. Hemolytic Uremic Syndrome (E. coli 0157:H7 esp. in children)
  • Risk Factors
  1. Obesity
  2. African American
  3. Female gender
  4. HIV Infection
  5. Rheumatologic Disease
  6. Clopidogrel (Plavix)
  • Symptoms
  • Signs
  • Classic Presentation
  1. Triad: Most common presentation (75% of cases)
    1. Thrombocytopenic Purpura
    2. Microangiopathic Hemolytic Anemia
    3. Neurologic changes (Seizures, Transient Ischemic Attack) at presentation or prior and resolved
  2. Additional features as part of full classic presentation (5 features present in less than a third of patients)
    1. Fever
    2. Acute Renal Failure
  • Signs
  1. Fever (90% of cases)
  2. Skin
    1. Petechiae or Purpura
    2. Bleeding sites
    3. Jaundice
  3. Neurologic changes (often transient effects due to unstable platelet clots)
    1. Altered Level of Consciousness
    2. Transient Ischemic Attack
  4. Abdominal exam
    1. Splenomegaly (most patients with TTP)
  • Differential Diagnosis
  1. See Thrombocytopenia
  2. See Hemolytic Anemia
  3. Hemolytic Uremic Syndrome
    1. Most common in children (esp. 6 months to 4 years old)
      1. Children rarely have TTP without HUS, but adults can uncommonly present with HUS during outbreaks
    2. Presents as TTP and Acute Renal Failure, bloody Diarrhea and Abdominal Pain
    3. Associated with Shiga toxin-producing Escherichia coli infection (E Coli 0157)
  4. Evans Syndrome
    1. Thromboyctopenia with Microangiopathic Hemolytic Anemia (MAHA)
    2. However ADAMTS levels are normal
    3. Treated with Corticosteroids
    4. Better prognosis than standard Thrombotic Thrombocytopenic Purpura
  • Labs
  • Initial
  1. Complete Blood Count
    1. Platelet Count <50,000
    2. Hemoglobin <10 g/dl
  2. Acute Kidney Injury
    1. Serum Creatinine increased (severe cases)
  3. Hemolysis
    1. Unconjugated Bilirubin increased
  4. Urinalysis
    1. Hematuria
    2. Proteinuria
  5. Peripheral Smear with Hemolysis signs (obtain on all patients suspected for TTP)
    1. Schistocytes (RBC fragments) suggests Microangiopathic Hemolytic Anemia (MAHA)
    2. MAHA is also seen in Hemolytic Uremic Syndrome
  • Labs
  • Specific
  1. ADAMTS13 Levels (including activity and inhibitors) decreased
  2. Von Willebrand Factor gel electrophoresis
  • Diagnosis
  1. See Plasmic Score (ADAMTS13 Enzyme Activity Prediction Tool)
  2. Thrombocytopenia and Microangiopathic Hemolytic Anemia (MAHA)
    1. Without obvious alternative diagnosis, manage Thrombocytopenia and MAHA as TTP
    2. Also seen in Hemolytic Uremic Syndrome (see differential diagnosis above)
  • Management
  1. Treat as a hematologic emergency
    1. Early Hematology Consultation
    2. Admit all patients
  2. Immediate management
    1. High dose Corticosteroids (Methylprednisolone)
    2. Plasmapheresis
      1. Withdrawal via 17 gauge intravenous catheter
      2. Return via 18 gauge intravenous catheter
      3. Plasma exchange with Cryosupernate or FFP
        1. Cryosupernate (preferred) or Fresh Frozen Plasma replace withdrawn fluid
        2. Cryosupernate and FFP contain functional ADAMTS13
  3. Adjunctive measures
    1. Aspirin or Dipyridamole (consider as Platelet Counts are improving >50k and no signs of bleeding)
    2. Avoid Platelet Transfusion unless catastrophic bleeding (e.g. Intracranial Hemorrhage)
    3. Obtain central venous access
  4. Refractory case management
    1. Rituximab
      1. Indicated for frequent relapses or failure to respond to plasma exchange
    2. Splenectomy
    3. Gammaglobulin
    4. Vincristine
  • Prognosis
  1. Untreated: 80% mortality within 3 months
  2. Treatment with plasmapheresis: 17% mortality
  • References
  1. Arora and Herbert in Majoewsky (2013) EM:Rap 13(3):1
  2. Marx (2002) Rosen's Emergency Med, p. 1693
  3. Merrill and Gillen (2016) Crit Dec Emerg Med 30(3): 3-8
  4. Kessler (2012) J Emerg Med 43(3): 538-44 [PubMed]
  5. Nabhan (2003) Hematol Oncol Clin North Am 17:177-99 [PubMed]