Thrombotic thrombocytopenic purpura differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2] Anum Ijaz M.B.B.S., M.D.[3]

Overview

The main differential diagnosis of TTP is hemolytic-uremic syndrome. TTP should be diffrential from the other disaeses such as TMA syndromes, disseminated intravascular coagulation ,hypertension, immune thrombocytopenic purpura (ITP)

• Malignant hypertension
• Hematological abnormalities
• Ischemic manifestations linked to autoimmune diseases

Differential Diagnosis

The main differential diagnosis of TTP is hemolytic-uremic syndrome (HUS, which has neurosymptoms, renal failure, hypertension and fever). Note that ADAMTS13 activity is normal in HUS.

The table below helps differentiate TTP from other thrombotic microangiopathies.

Diagnosisa	Hemolysisb	Platelet count, ×10^9/Lc	Creatinine level, mg/dLc	Key Featuresd	Therapies
Thrombotic thrombocytopenic purpura	Yes	<30	<2	ADAMTS13 deficiency (<10%-20%)	Immune: therapeutic plasma exchange, immune suppression, caplacizumab; Congenital: donor plasma or recombinant ADAMTS13
Complement-mediated thrombotic microangiopathy	Yes	>30 <100	>2	Complement dysregulation	Complement inhibitors
Infection
Shiga toxin producing Escherichia coli (O157:H7)	Yes	Variable	Variable	Variable	Supportive care; Disease-specific antivirals/antimicrobials
Advanced HIV infection
Sepsis
Autoimmune
Systemic lupus erythematosus	Yes	Variable	Variable	Variable	Corticosteroid with-without other immunosuppressant. Anticoagulation with/without therapeutic plasma exchange.
Catastrophic antiphospholipid syndrome
Pregnancy
Preeclampsia	Yes	Variable	Variable	Variable	Delivery of fetus
HELLP syndrome (hemolysis, elevated liver enzyme levels, low platelet count)
Cardiac
Malignant hypertension	Yes	Variable	Variable	Variable	Treatment of hypertension or valvular disease
Malfunctioning mechanical valve
Cancer
Disseminated cancer	Yes	Variable	Variable	Variable	Treatment of cancer
Transplant
Hematopoietic cell	Yes	Variable	Variable	Variable	Treatment of rejection or graft-vs-host disease, supportive care, stop offending drugs
Solid organ
Drugs
Quinine	Yes	Variable	Variable	Variable	Stop offending drug
Ticlopidine
Tacrolimus
Gemcitabine
Mitomycin

Abbreviation: ADAMTS13, a disintegrin and metallopeptidase with thrombospondin type 1 motif 13.

a Common etiologies are listed, although the list is not meant to be exhaustive.

b Hemolysis: low hemoglobin level, high reticulocyte count/serum lactate dehydrogenase level/indirect bilirubin, low haptoglobin levels.

c Common laboratory values at presentation, although patients may differ.

d All thrombotic microangiopathies can have neurologic, cardiac, and abdominal features due to involvement of microvasculature.

SI conversion factor: To convert creatinine values to μmol/L, multiply by 88.4.