Page 1255 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

862 PART 7: Hematologic and Oncologic Disorders

thrombi are present and largely confined to the kidney in cases of HUS.
67
These differences in organ involvement and thrombus composition sug-
gest a fundamental difference in pathogenesis of TTP and HUS. They
do not represent a spectrum of the same disease process, although a
recent study indicates that D+HUS, aHUS, and TTP are all diseases of
complement activation in the end. The hypothesis remains to be tested
15
in future research, and may have implications for therapy.
■ DIFFERENTIAL DIAGNOSIS

Differentiation of TTP from HUS: The most important differential diag-
nosis is between TTP and HUS (Table 91-1), particularly in pediatric
population, because the therapeutic strategy and potential outcome may
be quite different. Without treatment, TTP is universally fatal. However,
renal failure in HUS may recover or progress to ESRF. When a patient
comes to a clinic or hospital with low platelet count and MAHA or
jaundice, with or without renal failure or neurologic signs and symp-
toms, plasma ADAMTS13 activity and inhibitor assessment should
be performed and repeated if necessary. The normal range of plasma
ADAMTS13 usually ranges from 40% to 160%. 161,162 Severe deficiency of
FIGURE 91-4. Peripheral blood smear shows the fragmentation of red blood cells. Arrows
indicate the fragmentation of red blood cells or schistocytes obtained from a patient with HUS. plasma ADAMTS13 activity (<5% of normal) without inhibitors detected
suggests a potential diagnosis of hereditary TTP. Normal or moderately
reduced plasma ADAMTS13 activity favors the diagnosis of HUS,
159
D-dimer. Renal failure may be variably present in TTP, but invariably but does not exclude TTP of unknown etiology. 53,158 Mutation analysis
present in HUS. 50,159 Histologically, hyaline thrombi are detectable in on CFH, CFI, MCP, CFB, C3, and TM should be sought in patients
small arteries and capillaries in major organs, but the distribution of suspected to have aHUS. 63,64,163 In adults, the initial distinction between
microthrombi may be different in TTP from HUS. Platelet-rich thrombi TTP and HUS may be less important as plasma exchange is offered to all
are present in decreasing severity in the heart, pancreas, kidneys, patients with MAHA and thrombocytopenia without an apparent disease
adrenal glands, and brain in cases of TTP, but fibrin/red cell–rich or a condition that is known to cause these findings. 11,53,164,165

TABLE 91-1 Clinical Characteristics and Laboratory Findings in TTP, aHUS, and Other Conditions Causing TMA
Syndromes
Parameters TTP aHUS DIC SLE HELLP
Time of onset Any age Any age Any age Adults >34 weeks’ gestation
Nausea/vomiting ++ ++ ± ± ±
Abdominal pain ++ ++ ± ± ±
Fever ± ± ++ ± −
Proteinuria +/hematuria ++ ± ± ++
Hypertension ± ++ ± ± ++
Renal failure ± +++ ± ± +
RBC fragmentation +++ +++ +++ + +
Thrombocytopenia +++ ++ +++ ± ++
PT Normal Normal Prolonged Normal
PTT Normal Normal Prolonged Normal
Fibrinogen level Normal Normal Low Normal
Fibrin degradation products Low Low High Low
Elevated bilirubin +++ ± ± ± ±
Elevated transaminases + + + − +++
Complement levels Normal Abnormal Normal Low
Plasma ADAMTS13 activity <5% (most) Normal Normal or low Normal or low
Mutation of CFH, CFI, MCP, CFB, or C3 or TM None Positive None None
Autoantibody against ADAMTS13 Positive (acquired) Negative Negative Positive (some)
Autoantibody against CFH or CFI Negative Positive (acquired) Negative Negative
Histopathology Widespread VWF-rich Renal glomerular Hepatocyte necrosis fibrin in peripheral sinusoids
ADAMTS13, a disintegrin and metalloprotease with thrombospondin type 1 repeats; aHUS, atypical hemolytic uremic syndrome; C3, complement C3; CFB, factor B; CFH, factor H; CFI, factor I; DIC, disseminated intra-
vascular coagulation; HELLP, hemolysis, elevated liver enzyme, and low platelet count; MCP, membrane cofactor protein; PT, prothrombin time; PTT partial thromboplastin time; SLE, systemic lupus erythematosus;
TM, thrombomodulin; TTP, thrombotic thrombocytopenic purpura.
±, +, + +, and + + + + indicate various degrees of abnormalities from mild to severe.

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