Platelet
Thrombotic Thrombocytopenic Purpura
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Thrombotic Thrombocytopenic Purpura
, TTP
See Also
Thrombocytopenia
Hemolytic Uremic Syndrome
Microangiopathic Anemia
Plasmic Score
(
ADAMTS13 Enzyme Activity Prediction Tool
)
Epidemiology
Peak age 30 to 40 years old
Slightly more common in women
Rare: 4 to 11 cases per year per 1 million people per year in the United States
Pathophysiology
ADAMTS13 Protease dysfunction
Von Willebrand Factor
(vWF) is exposed when intravascular injury occurs
vWF is analogous to a net that traps platelets, forming a transient plug
The plug is typically limited and stops bleeding without thrombosing the vessel
ADAMTS13 normally cleaves the long chain
Von Willebrand Factor
(vWF), thus limiting the plug
When ADAMTS13 is defective or absent, vWF forms traps large complexes of platelets
Vessel blocks with these large complexes of vWF and platelets resulting in thrombosis
ADAMTS13 deficiency predisposes to TTP
ADAMTS13 deficiency may be acquired or via genetic mutation (Upshaw-Schulman Syndrome)
Those with ADAMTS13 deficiency may develop TTP in response to stress or infection
Overlap with several
Gastroenteritis
related conditions
Shiga-toxin Enterocolitis
Hemolytic Uremic Syndrome
(
E. coli 0157
:H7 esp. in children)
Risk Factors
Obesity
African American
Female gender
HIV Infection
Rheumatologic Disease
Clopidogrel
(
Plavix
)
Symptoms
Headache
s
Paresthesia
s
Signs
Classic Presentation
Triad: Most common presentation (75% of cases)
Thrombocytopenic
Purpura
Microangiopathic Hemolytic Anemia
Neurologic changes (
Seizure
s,
Transient Ischemic Attack
) at presentation or prior and resolved
Additional features as part of full classic presentation (5 features present in less than a third of patients)
Fever
Acute Renal Failure
Signs
Fever
(90% of cases)
Skin
Petechiae
or
Purpura
Bleeding sites
Jaundice
Neurologic changes (often transient effects due to unstable platelet clots)
Altered Level of Consciousness
Transient Ischemic Attack
Abdominal exam
Splenomegaly
(most patients with TTP)
Differential Diagnosis
See
Thrombocytopenia
See
Hemolytic Anemia
Hemolytic Uremic Syndrome
Most common in children (esp. 6 months to 4 years old)
Children rarely have TTP without HUS, but adults can uncommonly present with HUS during outbreaks
Presents as TTP and
Acute Renal Failure
, bloody
Diarrhea
and
Abdominal Pain
Associated with Shiga toxin-producing
Escherichia coli
infection (E Coli 0157)
Evans Syndrome
Thromboyctopenia with
Microangiopathic Hemolytic Anemia
(
MAHA
)
However ADAMTS levels are normal
Treated with
Corticosteroid
s
Better prognosis than standard Thrombotic Thrombocytopenic Purpura
Labs
Initial
Complete Blood Count
Platelet Count
<50,000
Hemoglobin
<10 g/dl
Acute Kidney Injury
Serum Creatinine
increased (severe cases)
Hemolysis
Unconjugated Bilirubin
increased
Urinalysis
Hematuria
Proteinuria
Peripheral Smear
with
Hemolysis
signs (obtain on all patients suspected for TTP)
Schistocyte
s (RBC fragments) suggests
Microangiopathic Hemolytic Anemia
(
MAHA
)
MAHA
is also seen in
Hemolytic Uremic Syndrome
Labs
Specific
ADAMTS13 Levels (including activity and inhibitors) decreased
Von Willebrand Factor
gel electrophoresis
Diagnosis
See
Plasmic Score
(
ADAMTS13 Enzyme Activity Prediction Tool
)
Thrombocytopenia
and
Microangiopathic Hemolytic Anemia
(
MAHA
)
Without obvious alternative diagnosis, manage
Thrombocytopenia
and
MAHA
as TTP
Also seen in
Hemolytic Uremic Syndrome
(see differential diagnosis above)
Management
Treat as a hematologic emergency
Early Hematology
Consultation
Admit all patients
Immediate management
High dose
Corticosteroid
s (
Methylprednisolone
)
Plasmapheresis
Withdrawal via 17 gauge intravenous catheter
Return via 18 gauge intravenous catheter
Plasma exchange with Cryosupernate or FFP
Cryosupernate (preferred) or
Fresh Frozen Plasma
replace withdrawn fluid
Cryosupernate and FFP contain functional ADAMTS13
Adjunctive measures
Aspirin
or
Dipyridamole
(consider as
Platelet Count
s are improving >50k and no signs of bleeding)
Avoid
Platelet Transfusion
unless catastrophic bleeding (e.g.
Intracranial Hemorrhage
)
Obtain central venous access
Refractory case management
Rituximab
Indicated for frequent relapses or failure to respond to plasma exchange
Splenectomy
Gammaglobulin
Vincristine
Prognosis
Untreated: 80% mortality within 3 months
Treatment with plasmapheresis: 17% mortality
References
Arora and Herbert in Majoewsky (2013) EM:Rap 13(3):1
Marx (2002) Rosen's Emergency Med, p. 1693
Merrill and Gillen (2016) Crit Dec Emerg Med 30(3): 3-8
Kessler (2012) J Emerg Med 43(3): 538-44 [PubMed]
Nabhan (2003) Hematol Oncol Clin North Am 17:177-99 [PubMed]
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