eMedicine Specialties > Neurology > Pediatric Neurology

Thrombotic Thrombocytopenic Purpura: Follow-up

Author: Robert Stanley Rust Jr, MD, MA, Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia; Chair-Elect, Child Neurology Section, American Academy of Neurology
Contributor Information and Disclosures

Updated: Jan 27, 2010

Follow-up

Further Inpatient Care

  • In some instances, admission for rehabilitation may be necessary after the acute phase of illness is managed.

Further Outpatient Care

  • In some instances, outpatient rehabilitation is indicated.
  • Patients with persistent renal failure may need outpatient renal dialysis.
  • Other patients require follow-up for neurologic or cardiologic disease
  • The importance of following and attempting to lower elevated anti – ADAMTS-13 autoantibody titers has been stressed. This preemptive approach may lower the risk of relapses and of morbidity and mortality.63

Deterrence/Prevention

  • Preventing the first episode of TTP is difficult because the heritable predilection due to ADAMTS-13 deficiency is usually not recognized before the first event.
  • After this predilection is recognized, avoidance of provocative circumstances could be contemplated, though this, too, may prove difficult.
  • Ensuring that meat is well cooked may prevent the rare occurrence of TTP in adults due to the acquisition of enterohemorrhagic E coli infection.

Complications

  • Aside from untoward events due to TTP itself (eg, stroke, cardiac conduction abnormality), additional complications are the result of therapies, particularly plasma exchange and plasmapheresis.

Prognosis

  • The old observation that recurrence cannot be predicted on a clinical or laboratory basis66 remains true except that recurrence tends to occur in patients who have TTP due to heritable ADAMTS-13 deficiency.
    • Severe ADAMTS deficiency manifesting in infancy (Schulman-Upshaw syndrome) is especially prone to recurrence. Individuals with this presentation tend to have particularly poor outcome because the first presentation is often severe, and correct diagnosis and specific therapeutic intervention is often delayed.
    • With repeated episodes, individuals with Schulman-Upshaw syndrome are likely to develop brain lesions due to severe ischemia.
  • Two large studies of more than 130 episodes of TTP in adults receiving plasma exchange showed a 8-25% mortality rate during the acute phase of disease management. The risk of relapse was as high as 21%, and the risk of end-stage renal failure requiring dialysis was 16%.67,55 Relapses portend elevated risks for high morbidity and mortality.63
    • The risk for unfavorable outcomes or death may not be predictable on the basis of clinical or laboratory variables at initial presentation.
    • Persistently high titers of anti-ADAMTS antibodies predispose individuals for TTP recurrence. Following the autoantibody titer closely and treating to lower persistently elevated autoantibody titers may be an effective preemptive strategy to avoid TTP relapses.63
    • As many as 58% of survivors continued to have health problems.
  • Studies of 169 adults treated with plasmapheresis for TTP showed a 7-9.6% mortality rate. The rate of unresponsiveness to therapy was 6.7%, and the risk for end-stage renal disease requiring dialysis was as high as 36%.68,69
    • The estimated risk for end-stage renal disease was as high as 82% in the patients compared with similar populations of TTP not treated with plasmapheresis.
    • Lara et al found that 6.7% of their patients did not respond to plasmapheresis, and though follow-up was incomplete, at least 13% of patients had relapses at 3 weeks to 152 months after plasmapheresis.69
    • Deaths during the acute phase of illness may result from cerebral hemorrhage, septic shock, or other complications of illness and treatment.
    • As with plasma exchange, clinical and laboratory features of illness were not predictive of poor outcome in the study by Hollenbeck et al.68
    • Lara et al found that the absence of fever during the acute initial episode of TTP was a risk factor for recurrence.69
  • Devenoulas et al found that advanced age at the first episode of TTP indicated an increased risk for a poor outcome, as did severe renal impairment (defined as serum creatinine level >2 mg%).
  • In some instances, dialysis is discontinued after intervals as long as 6 years in acute TTP.
  • Most available outcome data are based on studies of heterogeneous populations of adults treated for TTP.
  • Epidemic occurrences of TTP may pose a high risk for poor outcome, as was seen in the 1996 outbreak of TTP after infection with enterohemorrhagic E coli O157:H7. Among 22 individuals who developed TTP, 16 were treated with plasma exchange. Five (31%) died, and 4 (24%) of the survivors required dialysis.
  • Available relapse data almost certainly underestimate the lifetime risk for relapse, abnormal renal function, and hypertension.
  • Some have suggested that, with proper support, the neurologic outcome of TTP among adults who survive the initial episode is reasonably good. However, newer data have confounded older data by suggesting that less than one half of all patients with neurologic manifestations of TTP have a substantial improvement in neurologic function after adequate treatment.8
  • Among the difficulties most often reported are chronic fatigue and difficulties with memory and concentration. A recent study by Lewis et al of 118 individuals who had recovered from TTP without overt disability found that the first year after recovery showed modest but significant lowering of 10 standardized measurements of quality of life (HRQoL self-reporting scales), as compared to control values within the first 2 years after recovery from the acute phase of illness.70 Function improved thereafter for all self-reported indicators except for bodily pain.
  • ADAMTS-13 deficiency–related TTP with onset at the 20th week of pregnancy that is thereafter carefully and effectively managed until the delivery of a healthy baby at 32 weeks' gestational age has been described with excellent outcome and postpartum resolution of TTP.60
  • The myocardial outlook is guarded in patients who have clinical or ECG changes consistent with clinically significant myocardial disease.

Patient Education

  • Ensure that meat is well cooked.

Miscellaneous

Medicolegal Pitfalls

  • Medicolegal pitfalls are not unlike those encountered in any other area of medicine. The pitfalls chiefly consist of the failure to recognize and appropriately manage TTP.
  • The involvement of individuals skilled in the use of plasmapheresis and plasma infusion is important in the management of these disorders.
  • If immunosuppressive drugs are to be used in patients with relapse, the weight of evidence and the potential risks of such therapy should carefully be reviewed with the patient and his or her family.
  • Platelet transfusion poses a substantial risk and should be avoided in TTP, according to some authorities.
  • Antiplatelet agents should be used with caution, as noted in Medical Care.
  • Authorities have considered anticoagulation to be contraindicated in HUS.
 


More on Thrombotic Thrombocytopenic Purpura

Overview: Thrombotic Thrombocytopenic Purpura
Differential Diagnoses & Workup: Thrombotic Thrombocytopenic Purpura
Treatment & Medication: Thrombotic Thrombocytopenic Purpura
Follow-up: Thrombotic Thrombocytopenic Purpura
References
[ CLOSE WINDOW ]

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Further Reading

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Keywords

TTP, thrombocytic acroangiothrombosis, Schulman-Upshaw syndrome, Upshaw-Schulman syndrome, constitutional TTP, severe ADAMTS13 deficiency, thrombotic microangiopathy, TMA, hemolytic uremic syndrome, HUS, TTP-HUS, TTP/HUS, ADAMTS13, ADAMTS-13, Shiga toxin, Stx

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Contributor Information and Disclosures

Author

Robert Stanley Rust Jr, MD, MA, Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia; Chair-Elect, Child Neurology Section, American Academy of Neurology
Robert Stanley Rust Jr, MD, MA is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Headache Society, American Neurological Association, Child Neurology Society, International Child Neurology Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

David A Griesemer, MD, Professor, Departments of Neuroscience and Pediatrics, Medical University of South Carolina
David A Griesemer, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Epilepsy Society, Child Neurology Society, and Society for Neuroscience
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
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