Clinical Background
Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are thrombotic microangiopathies associated with hemolysis and renal and neurologic dysfunction in adults and children.
Epidemiology
- Incidence - 4-10/1,000,000
- Age
- TTP - almost exclusively in adults except for inherited forms
- HUS - bimodal distribution in children and older adults
- Gender - equal distribution
Risk Factors
- TTP
- Autoimmune disorders
- Black race
- Certain drugs (e.g., quinine)
- Malignancy (e.g., lymphoma)
- Obesity
- Pregnancy
- HUS
- Gastroenteritis - specifically highest risk with E. coli 0157:H7, although S. dysenteriae and other toxin-producing species are also a risk factor
- Use of antimotility drugs or antibiotics during the course of above diarrheas
Pathophysiology
- Characterized by systemic or intrarenal aggregation of platelets leading to the hallmark thrombocytopenia
- Microvascular aggregation leads to organ ischemia
- TTP associated with severe deficiency of ADAMTS13 (von Willebrand factor cleaving protease)
Clinical Presentation
- TTP
- Nonspecific symptoms - nausea, vomiting, diarrhea, abdominal pain, weakness, fever
- Hallmark of the presentation is hemolytic anemia and thrombocytopenia
- Neurologic - confusion, fluctuating neurologic deficits, seizures, coma
- Renal - renal insufficiency, hematuria
- HUS
- Oliguria
- Thrombocytopenia
- Microangiopathic hemolysis
- Acute renal failure
Treatment
- TTP
- Mainstay is plasma exchange, begun early in the disease course
- Mortality approaches 90% in untreated patients
- HUS
See Also
Diagnosis
Diagnosis
- Laboratory testing
- Complete blood count demonstrating thrombocytopenia and anemia
- Peripheral smear - evidence of hemolysis, including schistocytes, helmet cells and reticulocytes
- BUN/creatinine - elevated
- Indirect evidence - elevated indirect bilirubin, negative Coombs testing, elevated lactate dehydrogenase (LDH)
Differential Diagnosis
- Acute renal failure
- Adverse drug reaction
- Disseminated malignancy
- Disseminated intervascular coagulation (DIC)
- Heparin-associated antibody syndrome
- Malignant hypertension
- Pregnancy-related TMA
- Sepsis
- Stroke
Tests generally appear in the order most useful for common clinical situations
| Test name: CBC with Platelet Count & Automated Differential
|
| ARUP #: 0040003 |
| Methodology: Automated Cell Count with Flow Cell Differential
|
| Use: Confirm anemia and thrombocytopenia |
| Test name: CBC with Platelet Count
|
| ARUP #: 0040002 |
| Methodology: Automated Cell Count
|
| Use: Confirm anemia and thrombocytopenia |
| Test name: Lactate Dehydrogenase, Serum or Plasma
|
| ARUP #: 0020006 |
| Methodology: Enzymatic
|
| Use: Confirm hemolysis |
| Test name: Antibody Detection, RBC
|
| ARUP #: 0010004 |
| Methodology: Hemagglutination
|
| Use: Exclude immune hemolytic anemia |
| Test name: Direct Coombs (Anti-Human Globulin)
|
| ARUP #: 0013008 |
| Methodology: Hemagglutination
|
| Use: Exclude immune hemolytic anemia |
| Test name: Bilirubin, Direct & Total, Serum or Plasma
|
| ARUP #: 0020426 |
| Methodology: Spectrophotometry
|
| Use: Confirm hemolysis |
| Test name: Bilirubin, Total (Neonatal), Plasma or Serum
|
| ARUP #: 0020114 |
| Methodology: Spectrophotometry
|
| Use: Confirm hemolysis |
| Test name: Bilirubin, Total, Body Fluid
|
| ARUP #: 0020510 |
| Methodology: Spectrophotometry
|
| Use: Confirm hemolysis |
| Test name: Bilirubin, Total, Serum or Plasma
|
| ARUP #: 0020032 |
| Methodology: Spectrophotometry
|
| Use: Confirm hemolysis |
| Test name: ADAMTS13 Activity
|
| ARUP #: 0030056 |
| Methodology: Fluorescence Resonance Energy Transfer
|
| Use: Confirm the diagnosis of TTP |
References
General References
Besbas N, Karpman D, Landau D, Loirat C, Proesmans W, Remuzzi G, Rizzoni G, Taylor CM, Van de Kar N, Zimmerhackl LB. A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Kidney Int.
2006;
70(
3):
423-431.
Brecher ME. How I approach a thrombotic thrombocytopenia purpura patient. Transfusion.
2006;
46(
5):
687-689.
Franchini M. Thrombotic microangiopathies: an update. Hematology.
2006;
11(
3):
139-146.
George JN. Evaluation and management of patients with thrombotic thrombocytopenic purpura. J Intensive Care Med.
2007;
22(
2):
82-91.
Knobl P. Unraveling the immunologic response in thrombotic thrombocytopenic purpura. J Thromb Haemost.
2006;
4(
11):
2352-2354.
Mannucci PM. Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome: much progress and many remaining issues. Haematologica.
2007;
92(
7):
878-880.
Mannucci PM. Thrombotic thromboytopenic purpura: another example of immunomediated thrombosis. Pathophysiol Haemost Thromb.
2006;
35(
1-2):
89-97.
Matzdorff AC. Thrombotic thrombocytopenic purpura. N Engl J Med.
2006;
355(
6):
630-.
Moake JL. Thrombotic thrombocytopenic purpura: survival by "giving a dam". Trans Am Clin Climatol Assoc.
2004;
115:
201-219.
Nguyen QV, Descombes E. Etiology-based classification of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. What about hemolytic uremic syndrome associated with urinary tract infections?. Kidney Int.
2007;
71(
5):
466-.
Rehberg JF, Briery CM, Hudson WT, Bofill JA, Martin JN Jr. Thrombotic thrombocytopenic purpura masquerading as hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome in late pregnancy. Obstet Gynecol.
2006;
108(
3 Pt 2):
817-820.
Sadler JE. Thrombotic thrombocytopenic purpura: a moving target. Hematology Am Soc Hematol Educ Program.
2006;
:
415-420.
Schech SD, Brinker A, Shatin D, Burgess M. New-onset and idiopathic thrombotic thrombocytopenic purpura: incidence, diagnostic validity, and potential risk factors. Am J Hematol.
2006;
81(
9):
657-663.
Thachil J. Thrombotic thrombocytopenic purpura: is there more than ADAMTS-13?. J Thromb Haemost.
2007;
5(
3):
634-635.
Zimrin AB, Hess JR. Thrombotic thrombocytopenic purpura: Going with the evidence. Crit Care Med.
2006;
34(
8):
2247-2248.
References from the ARUP Institute for Clinical and Experimental Pathology Research®
Werner TL, Agarwal N, Carney HM, Rodgers GM. Management of cancer-associated thrombotic microangiopathy: what is the right approach?. Am J Hematol.
2007;
82(
4):
295-298.
Medical Reviewers
Lehman, Christopher M., M.D. Co-Medical Director, University Hospital Clinical Laboratory; Associate Professor, Clinical Pathology, University of Utah
Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah
Rodgers, George M. III, M.D., Ph.D. Medical Director, Hemostasis/Thrombosis at ARUP Laboratories; Professor, Medicine, Adjunct Professor, Pathology, University of Utah
Comprehensive Review: November 2007
Last Update: January 2008
