AD 6/02

Thrombotic Thrombocytopenic Purpura

TTP Key Take-Home Points
1. High clinical suspicion of TTP if patient presents with microangiopathic hemolytic anemia (MAHA) and
thrombocytopenia without coagulopathy
2. Serum LDH is greatly elevated in these patients and should increase the degree of suspicion for TTP/HUS
3. The pentad is present in 1/3 of the cases, triad in 3/4. LDH is elevated in 98%.
4. Plasma exchange has a cure rate of 78%
History: 1) First described in 1924 by Moschcowitz. 16yo girl who presented with petechiae, anemia hematuria,
fever and upper extremity weakness. The girl died 13 days later. Until the 1960s, fewer than 5% of adult patients
with TTP-HUS survived. Rubenstein reported in 1959 and unusual remission in a patient with TTP after whole
blood exchange. In 1998 discovery of a von Willebrand factor cleaving protease that is TTP is either deficient or has
an antibody directed against it.
Pathophysiology: Formation of platelet microthrombi, leading to vascular occlusion and tissue hypoxia affecting the
microvasculature in all organs (most notably the brain, kidneys, heart, lungs and spleen). The MAHA is due to the
stress on the RBCs as they transverse the microvasculature blocked by microthrombi. The thrombi are rich in
platelets and vWF (not fibrinogen and fibrin like DIC). Plasma exchange removes multimers and autoantibodies
against protease, and plasma infusion supplies missing enzyme.
Clinical:
Classic Triad: anemia, thrombocytopenia, and neurologic dysfunction
Classic Pentad : anemia, thrombocytopenia, neurologic dysfunction, fever and renal dysfunction
Breakdown of symptoms/signs from UCSF experience in 50 consecutive episodes of TTP/HUS in 44 pts from 19801991: fever 61%, neuro sx 78%, renal disease 44%, triad 78%, pentad 30%
Epidemiology from UCSF in 44 pts
Female predominance (70%)
Median age 43 years
98% had a markedly elevated LDH
Essentially normal coagulation parameters (PT/PTT, D-Dimers, fibrinogen)
PBS: Schistocytes, spherocytes
Treatment:
Superiority of plasma-exchange over plasma infusion as initial therapy for TTP (remission 78% vs 31%)

Plasmapheresis should utilize FFP or cryosupernatant (depleted of vWF, fibrinogen, factor XIII)
If a delay in institution of plasma exchange is unavoidable for technical reasons, appropriate to initiate therapy
with plasma infusion
Plasmapheresis should continue for a few days after the platelet count, serum LDH , blood smear, and
neurologic status have normalized. Plasma exchange should then be tapered over a period of 1 to 2 weeks. 1/3
of patients will have exacerbation of disease.
Plasmapheresis most common complication bacteremia, catheter problems, allergic response, hypotension,
citrate toxicity (paresthesias, tetany)
Contraindication of platelet transfusions: 55pts with TTP, 13/25 (52%) died in those who received platelets vs.
2/30 (7%) dying in those who did not receive platelets.
Glucocorticoids: before era of plasma exchange, 10% response rate. Appropriate in initial management
Adjunctive therapy with possible but unproven benefit (steroids, dipyridamole, ASA, azathioprine, vincristine)
Salvage splenectomy of unclear benefit but may be most helpful in preventing relapses
If poor response to daily plasma exchanges, increase number of exchanges, add prednisone, try infusion of
cryosupernatant of plasma, consider splenectomy
(UCSF experience: Daily plasma exchanges (60-80 ml/kg/d), replaced with FFP. Median # of exchanges for
TTP was 9)

Outcomes: order of recovery: neuro sx -> LDH -> platelet ct -> renal function
* 78% overall survival (no difference in HIV patients) with plasma exchange but only 50% with plasma infusion
* Those with previous splenectomy had 100% response rate
* Relapse most common within first 60 days after tx
* In a series of 319 pts, 64% experienced a relapse, most of whom (84%) had a single relapse. No predictors of
patients likely to relapse.
* Pts who have had TTP should have indefinite regular monitoring of blood parameters.
* Relapse did not confer a state of resistence as the number of plasmapheresis txs required did not differ from the
number needed for the first remission.
Sources: 1) Bill Plauth. Cover Sheet: Thrombotic Thrombocytopenic Purpura 2) Thompson, CE. Thrombotic Microangiopathies in the 1980s:
Clinical Features, Response to Treatment, and the Impact of the Human Immunodeficiency Virus Epidemic. Blood. October 1992; 80 (8): 18901895. 3) Kwaan, HC. Management of Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome. Seminars in Hematology. April
1997; 34(2): 159-166. 4) Bell, WR. Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome Relapse: Frequency, Pathogenesis, and
Meaning. Seminars in Hematology. April 1997; 34 (2). 5) UpToDate 2002 on TTP 6) Ferrara, et al. Vincristine in the treatment of TTP. Annals
of hem. Jan 2002.