Thrombotic Thrombocytopenic Purpura
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Contents |
Introduction
- Acute disorder of increased platelet consumption. TTP is a medical emergency.
Etiology
- non familial form of TTP is due to an inhibitor of vWF-cleaving protease
- familial form of TTP is due to deficiency of vWF-cleaving protease ( ADAMTS13)
- secondary causes:
- mitomycin C
- bleomycin
- cyclosporin A
- quinine
- E. coli 0157
- radiation
- association with pregnancy & use of oral contraceptives
- immune-mediated drug hypersensitivity
Epidemiology
- generally affects younger adults
- peak incidence in 3rd decade of life
- 70% of patients are female
Pathology
- ultra-large von-Willebrand's proteins may be observed
- endothelial cell injury
- subendothelial cell deposits
- glomerular lesion also seen with:
- malignant hypertension
- scleroderma
- post-partum renal failure
Genetics
- (familial form)
- autosomal recessive
- defects in ADAMTS13 are associated with congenital thrombotic thrombocytopenic purpura ( TTP)
Clinical-manifestations
- severe thrombocytopenia
- microangiopathic hemolytic anemia
- fluctuating neurologic signs
- progressive renal failure is uncommon
- fever (variable)
- severe hypertension
- purpura
- familial form:
Laboratory
-
- erythrocyte fragments
- diminished platelets
- increased reticulocyte count
- serum chemistries
- serum lactate dehydrogenase ( LDH) increased
- serum urea nitrogen increased
- serum creatinine increased
- serum bilirubin: increased unconjugated (indirect) bilirubin
- WBC ( pyuria)
- RBC
- hemoglobin ( hematuria)
- large amounts of albumin ( albuminuria)
- prothrombin time (PT) is generally normal
- activated partial thromboplastin time ( aPTT) is generally normal
- direct antiglobulin test ( Coomb's test) is negative
- plasma fibrinogen is normal
- antinuclear antibody (rule out lupus erythematosus)
Differential-diagnosis
-
- normal LDH
- no erythrocyte fragments on peripheral smear
Management
- plasmapheresis - continue until patient improves or expires
- other treatments if plasmapheresis not available
- high-dose gamma globulin
- plasma exchange with fresh frozen plasma ( FFP)
- 30 mL/kg in the 1st 24 hours
- then 15 mL/kg/day, until apheresis can be performed
- fluid overload is common
- begin diuretic therapy simultaneously
- whole blood exchange transfusion
- anti-platelet drugs (if FFP is ineffective)
- vincristine
- steroids may be useful because of difficulty distinguishing TTP from vasculitis
- discontinue offending medications
- splenectomy
- mortality rate is 25%
- best prognostic indicators
- platelet count return to normal
- decreasing LDH
- resolution of neurologic symptoms
- relapse months to years later in 20-30%
- prior to plasma exchange, patients either died (75%) or recovered without relapse (25%)
More General Terms
Additional Terms
- A disintegrin & metalloproteinase with thrombospondin type 1 motif 13; ADAMTS-13; ADAM-TS 13; ADAM-TS13; von Willebrand factor-cleaving protease; vWF-cleaving protease; vWF-CP (ADAMTS13, C9orf8, UNQ6102/PRO20085)
- HELLP syndrome
- hemolytic uremic syndrome (HUS)
Internet Database
OMIM: 274150
References
- Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 590
- Furlan M et al von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. NEJM 339:1578-84, 1998 PMID: [1]
- Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 418, 611
- Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15 American College of Physicians, Philadelphia 1998, 2006, 2009
