From EM Quick Hits 63: “Thrombotic Thrombocytopenic Purpura”

Today, I review, and excerpt from EM Quick Hits 63’s Thrombotic Thrombocytopenic Purpura.*

*Helman, A. Freedman, S. Morgenstern, J. McArther, M. Petrosoniak, A. Long, B. Gotlieb, M. EM Quick Hits 63 – S-TEC and HUS, IM Epinephrine in OHCA, Dengue, Geriatric Trauma Imaging, TTP. Emergency Medicine Cases. March, 2025. https://emergencymedicinecases.com/em-quick-hits-march-2025/. Accessed May 4, 2025.

All that follows is from the above resource.

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TTP recognition and management

Thrombotic thrombocytopenic purpura (TTP) is a rare but important disorder as it is associated with a mortality rate of 4-30%, even with early recognition and treatment.

In TTP, enzyme ADAMTS13 (responsible for cleaving large von Willebrand factor (vWF) becomes dysfunctional, resulting in large vWF multimers which accumulates in platelets, form clots, and destroys RBCs, leading to thrombocytopenia and hemolysis.

The classic pentad is seen in less than 7% of patients with TTP, and many of these findings can be transient:

• Thrombocytopenia (petechiae, purpura in ~50%)
• Microangiopathic hemolytic anemia
• Fever (seen in ~10% of cases)
• Neurologic symptoms
  • 40% of patients may have confusion, seizures, stroke
  • ~25% of patient swill have minor symptoms including headache or transient confusion
  • Up to 1/3 of patients have no neurologic symptoms
• Acute renal injury

Lab work for TTP

• End organ dysfunction: renal and liver dysfunction
• Hemolytic anemia: Hgb <10 g/dL, platelet <150 x10^9/L., ADAMTS13 activity level <10%, schistocyte on blood smear, increased indirect bilirubin, increased LDH, decreased haptoglobin, reticulocytosis
• Others: HIV, coagulation panel with normal INR, D-dimer, normal fibrinogen, troponin, urinalysis

A PLASMIC Score ≥5 has a 99% sensitivity and 57% specificity for TTP (incorporates elements including platelet count, hemolysis, active cancer, solid organ or stem cell transplant, low MCV, INR <1.5, Cr <2mg/dL).

Management of TTP:

1. Address the underlying etiology and end organ dysfunction
2. Consultation with hematology
3. Focused treatment of TTP: FFP (limited success), plasma exchange therapy, and methylprednisolone 1mg/kg/d. Rituximab (limited evidence from RCTs)
   1. Active bleeding is rare and transfusions are generally not necessary
   2. Platelet transfusions can be given if patients have major bleeding or are severely thrombocytopenic (current evidence suggests no significant impact on mortality)
   3. Low-molecular weight heparin + ASA for patients with platelet >50 as thromboembolic prophylaxis

Bottom line: Patients with TTP may not present with all elements of the classic pentad. Early identification and therapy can significantly improve mortality. The PLASMIC score can be used to assist in identifying patients with TTP.

1. EMDocs article on TTP: http://www.emdocs.net/thrombotic-thrombocytopenic-purpura-pearls-and-pitfalls/
2. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017 May 25;129(21):2836-2846. doi: 10.1182/blood-2016-10-709857. Epub 2017 Apr 17. PMID: 28416507.
3. Chiasakul T, Cuker A. Clinical and laboratory diagnosis of TTP: an integrated approach. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):530-538. doi: 10.1182/asheducation-2018.1.530. PMID: 30504354; PMCID: PMC6246034.
4. Griffin D, Al-Nouri ZL, Muthurajah D, Ross JR, Ballard RB, Terrell DR, Vesely SK, George JN, Marques MB. First symptoms in patients with thrombotic thrombocytopenic purpura: what are they and when do they occur? Transfusion. 2013 Jan;53(1):235-7. doi: 10.1111/j.1537-2995.2012.03934.x. PMID: 23294213; PMCID: PMC3541531.
5. Bendapudi PK, Li A, Hamdan A, Uhl L, Kaufman R, Stowell C, Dzik W, Makar RS. Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative. Br J Haematol. 2015 Dec;171(5):836-44. doi: 10.1111/bjh.13658. Epub 2015 Aug 28. PMID: 26314936.
6. Blombery P, Kivivali L, Pepperell D, McQuilten Z, Engelbrecht S, Polizzotto MN, Phillips LE, Wood E, Cohney S; TTP registry steering committee. Diagnosis and management of thrombotic thrombocytopenic purpura (TTP) in Australia: findings from the first 5 years of the Australian TTP/thrombotic microangiopathy registry. Intern Med J. 2016 Jan;46(1):71-9. doi: 10.1111/imj.12935. PMID: 26477687.
7. George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood. 2010 Nov 18;116(20):4060-9. doi: 10.1182/blood-2010-07-271445. Epub 2010 Aug 4. Erratum in: Blood. 2011 May 19;117(20):5551. PMID: 20686117.
8. George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med. 2006 May 4;354(18):1927-35. doi: 10.1056/NEJMcp053024. PMID: 16672704.
9. Sayani FA, Abrams CS. How I treat refractory thrombotic thrombocytopenic purpura. Blood. 2015;125(25):3860-3867. Blood. 2017 Oct 5;130(14):1684. doi: 10.1182/blood-2017-08-803171. Erratum for: Blood. 2015 Jun 18;125(25):3860-7. doi: 10.1182/blood-2014-11-551580. PMID: 28983021; PMCID: PMC5630016.
10. Blombery P, Scully M. Management of thrombotic thrombocytopenic purpura: current perspectives. J Blood Med. 2014 Feb 5;5:15-23. doi: 10.2147/JBM.S46458. PMID: 24523598; PMCID: PMC3921093.
11. Sarode R, Bandarenko N, Brecher ME, Kiss JE, Marques MB, Szczepiorkowski ZM, Winters JL. Thrombotic thrombocytopenic purpura: 2012 American Society for Apheresis (ASFA) consensus conference on classification, diagnosis, management, and future research. J Clin Apher. 2014 Jun;29(3):148-67. doi: 10.1002/jca.21302. Epub 2013 Oct 17. PMID: 24136342.