Thrombotic Throbocytopenic Purpura
last authored: April 2012, David LaPierre
last reviewed:
Introduction
Thrombotic Throbocytopenic Purpura (TTP) is a life-threatening syndrome characterized by thrombocytopenia (low platelets) and microangiopathic hemolytic anemia (MAHA). These abnormalities, which are believed to be related to abnormal enzyme function, can lead to thrombus (clot) formation in arterioles and organ damage.
The five classic symptoms of TTP are as follows:
- Decreased platelets
- hemolysis
- CNS manifestations (due to neurological damage)
- fever
- renal failure (due to kidney damage
TTP shares many similarities with hemolytic-uremic syndrome (HUS) in regards to clinical manifestations and pathophysiology, though they are believed to be different disease entities.
The Case of...
a simple case introducing clincial presentation and calling for a differential diagnosis to get students thinking.
Causes and Risk Factors
As described under 'Pathophysiology', TTP is believed to be due to deficiency of metalloproteinase enzyme. This can be due to the following conditions:
- congenital (ADAMTS-13)
- pregnancy
- oral contraceptives
- AIDS
- autoimmune disease: APLA, SLE, scleroderma
- cancer
- medications: chemotherapy
- clopidogrel
Pathophysiology
von Willebrand factor (vWF) is secreted by endothelial cells in a large polymer. It is normally rapidly cleaved by ADAMTS-13, a metalloproteinase enzyme. However, in situations where ADAMTS-13 is defective or absent, vWF multimers lead to platelet aggregation. Endothelial damage can follow thrombus formation, which has the most significant effect on arterioles in the kidney, brain, pancrease, adrenals, and heart.
Congenital absence of ADAMTS-13 can lead to vWF aggregation. Other mechanisms of setting off this reaction include:
- autoantibody formation against ADAMTS-13, platelets, or endothelial cells
- direct endothelial injury
Signs and Symptoms
- history
- physical exam
History
Symptoms begin acutely and are typically non-specific, including:
- nausea and vomiting, abdominal pain
- fatigue and weakness
- fever
Neurological symptoms are present in up to 90% of cases, and can include:
- headache
- confusion, altered mental status
- focal deficits
- seizures
- stroke
Renal symptoms can include:
- hematuria
- oliguria
- anuria
Thrombocytopenia and hemolysis can lead to:
- bruising, purpura, or petichiae
- epistaxis, gingival bleeding
- menorrhagia
- GI bleeding
- visual abnormalities due to hemorrhage
Physical Exam
Physical exam may reveal:
- fever
- shock if hemorrhage has been extensive
- skin: jaundice, bruising, petichiae, purpura
- abdomen: tenderness (nonspecific), melena or bright red bleeding per rectum
- head and neck: icterus, retinal hemorrhage, epistaxis
- neurological: confusion, focal neurological deficit
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
Renal failure: abnormal urinalyis, oliguria, ARF
CBC and
- PT and PTT normal
- hemolysis: inc uncong bili, LDH, dec haptoglobin
- negative Coombs' test
- BUN, creatinine
peripheral smear
- schistocytes and dec platelets
Diagnostic Imaging
Differential Diagnosis
Treatments
Plasmapheresis and steroids are the treatments of choice. Plasma infusion should be given if plasmapheresis is not immediately available.
Do NOT give platelets, as this can increase rates of intravascular thrombosis.
Consequences and Course
TTP rates of mortality are 90% if untreated.
Resources and References
Topic Development
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