TOC | HEME
TTP (Thrombotic thrombocytopenic purpura) REF: TTP 2008.pdf
The thrombotic microangiopathies are
microvascular occlusive disorders characterized by systemic or intrarenal
aggregation of platelets, thrombocytopenia, and mechanical injury to
In thrombotic thrombocytopenic purpura (TTP), systemic microvascular aggregation of platelets causes ischemia in the brain and other organs.
In the hemolyticuremic syndrome, plateletfibrin thrombi occlude predominantly the renal circulation.
Thrombotic microangiopathies are characterized by
TTP is characterized by:
Diagnosis is suggested by:
Therapy (as suggested by Dr. Stanley Schrier of Stanford:)
Therapy for Thrombotic Thrombocytopenic Purpura NEJM August 22, 2002 - Joel L. Moake
Infants or young children with familial thrombotic thrombocytopenic purpura
produce a functionally defective ADAMTS. Their episodes of thrombotic thrombocytopenic purpura are reversed or prevented by the infusion of platelet-poor fresh-frozen plasma, cryoprecipitate-poor plasma (cryosupernatant), or plasma that has been treated with a mixture of an organic solvent and detergent (all contain the active metalloprotease) about every 3 weeks. Plasmapheresis is not required. Since a plasma level of only about 5 percent is sufficient to prevent or shorten episodes of thrombotic thrombocytopenic purpura, gene therapy may induce lasting remissions in children with the chronic relapsing form of the disease.
Adults and older children with acquired acute idiopathic thrombotic
require daily plasma exchange - the combination of
Plasma exchange allows about 90 percent of these patients to survive an episode of thrombotic thrombocytopenic purpura, usually without permanent organ damage.
Some patients with acquired acute idiopathic thrombotic thrombocytopenic
purpura and high titers of antibodies against ADAMTS 1397 do not respond
to plasma exchange alone. It may be possible to interfere with autoantibody
production through treatment with
splenectomy or to depolymerize platelet
microtubules and alter exposure of surface receptors by
Rituximab, the monoclonal antibody
against CD20 on B-lymphocytes, is under investigation. In the absence of
life-threatening hemorrhage or intracranial bleeding, it is prudent to avoid
platelet transfusions, which can exacerbate microvascular thrombosis.
* Aspirin may provoke hemorrhagic complications in patients with severe thrombocytopenia.
Improved survival with plasma exchange in patients with TTP-hemolytic
AJ Med, Dec. 1999;107:6:573-579 - Primo N. Lara, etc.
PURPOSE: Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are uncommon disorders that are generally fatal if left untreated. Plasma exchange therapy is associated with high response rates and improved short-term survival, but most previous studies have been limited by small numbers of patients or short duration of follow-up.
RESULTS: The overall 30-day mortality was 10% of the 122 patients who received plasma exchange as their principal treatment (a median of 9 exchanges and a mean cumulative infused volume of 43 ± 77 L fresh frozen plasma); 56% were complete responders and 21% were partial responders. The relapse rate was 13%. The estimated 2-year survival was about 60%; among patients without serious underlying comorbid conditions, the estimated 2-year survival was about 80%. Each unit increase in clinical severity score (on a 0 to 8 scale) was associated with a 2.2-fold (95% confidence interval [CI]: 1.3 to 3.9) increase in the odds of 30-day mortality. Patients who were febrile at presentation were substantially less likely to suffer a relapse (odds ratio = 0.2; 95% CI: 0.03 to 0.9).
CONCLUSION: Plasma exchange therapy produced high response and survival rates in this large cohort of patients with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. The Clinical Severity Score may be useful in predicting 30-day mortality, whereas fever at onset was associated with a lesser risk of relapse. Prospective studies should stratify patients according to these prognostic factors.
TTP-hemolytic uremic syndrome: Dx & Rx - Cleveland Clinic J Med Oct. 2001
Quinine is a common cause of drug-associated TTPHUS and can cause death and chronic renal failure. When the disorder is described as TTPHUS rather than only as HUS, the severity of neurologic abnormalities and the occasional absence of renal failure are emphasized. If recurrent disease is to be prevented, clinicians must recognize quinine as a possible cause. Ann Intern Med. Dec. 18, 2001;135:1047-1051. (Full text)
REVIEW: Thrombotic Microangiopathies (TTP & Hemolytic-Uremic Synd.)
NEJM August 22, 2002 - Joel L. Moake