Page 1256 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 91: TTP, HUS, and Other Thrombotic Microangiopathies 863

Differentiation of TTP from Disseminated Intravascular Coagulation: TTP be made, therapy should be directed at that disorder, rather than at the
should then be distinguished from disseminated intravascular coagu- associated hematologic problems.
lation (DIC) syndrome (Table 91-1). In the case of acute DIC, an
underlying clinical abnormality is usually apparent, including obstetric
complications such as amniotic fluid embolus, retained products of con- TREATMENT
unexplained bleeding during or after a surgical procedure may be the ■ INITIAL ICU MANAGEMENT
ception, and abruptio placentae, sepsis, and trauma. In trauma patients,
first manifestation of DIC. In the setting of head injury, as many as 70% The clinical manifestations of TTP or HUS are varied as to the extent of
166
of patients have clinical evidence of DIC. In a more chronic form of thrombotic lesions. Neurologic manifestations in cases of TTP can range
DIC, clotting factor synthesis and marrow cell production compensate from mild (altered mental status) to severe (focal neurologic abnor-
for consumption, and patients can present with thrombosis rather than malities, seizures, and coma). 53,62,181,182 Similarly, the spectrum of renal
hemorrhage. Thrombotic problems include deep vein or superficial dysfunction in TTP and HUS varies as patients can present with no
thrombophlebitis, pulmonary embolus, and cerebrovascular accidents, renal dysfunction or acute renal failure. Patients with severe neurologic
or nonbacterial endocarditis. Laboratory findings may help distinguish abnormalities, shock, acidosis, renal failure, or respiratory failure will
TTP from DIC. 167,168 Low serum fibrinogen levels, prolongation of the require ICU admission. As patients with TTP or HUS can deteriorate
prothrombin time (PT), and partial thromboplastin time (PTT) are rapidly, timely diagnosis and initiation of plasma exchange therapy is of
often seen in patients with DIC. Systemic intravascular coagulation critical importance. Treatment should be considered in all patients pre-
activation and thrombosis can lead to the activation of the fibrino- senting with thrombocytopenia and MAHA without another etiology.
In critically ill patients, plasma exchange has ■
lytic system, resulting in the increase of fibrin degradation products
(FDPs) in the serum. 167-169 TREATMENT OF TTP
been shown to reduce the renal failure and mortality rate regardless of As TTP is a hematologic emergency, all patients with MAHA and
diagnosis. 170-172 Therefore, when the differential diagnosis is unsettled, a thrombocytopenia without an obvious etiology should be admitted
trial of plasma exchange should be considered. and receive emergency treatment. Plasma exchange is the current
standard of care. However, infusion of FFP should be given when a
Differentiation of TTP from Pregnancy-Associated Complications: A sub- plasma exchange facility is not available. 11,50,52 In a study comparing plasma
set of patients with preeclampsia or eclampsia may have two cardinal exchange therapy with plasma infusion, plasma exchange is clearly
hematological abnormalities (thrombocytopenia and MAHA) of TTP superior to plasma infusion, particularly for patients with acquired TTP,
or HUS. Evidence of MAHA was reported in 2% to 15% of women with a survival rate of 78% versus 51%. Patients should receive plasma
52
with preeclampsia/eclampsia, and thrombocytopenia was reported in as exchange of 1.5 × patient plasma volume. The replacement fluid is FFP.
many as 18% of patients. Plasma ADAMTS13 activity may decrease as Cryoprecipitate-poor plasma (CPP), solvent/detergent FFP, and 24-hour
173
pregnancy progresses. However, low plasma ADAMTS13 activity in plasma appear to have equal efficacy to FFP. 183-187 Plasma exchange should
161
conjunction with high plasma VWF antigen has been shown to be a risk be offered daily until platelet counts have normalized (>150 × 10 /L)
9
factor for the development of preeclampsia or eclampsia. A subset of for at least 3 days. Plasma exchange is terminated or tapered at the clini-
99
patients may have MAHA and thrombocytopenia with marked elevation cian’s discretion. If available, plasma ADAMTS13 activity and inhibitors
of serum liver enzymes (ie, HELLP syndrome that mimics the presen- should be periodically monitored, which may be helpful in guiding
tation of TTP) (Table 91-1). 174,175 Right upper quadrant pain is often whether adjunctive therapies such as rituximab are needed. If plasma
present and may mimic cholecystitis or peritonitis. Plasma exchange is ADAMTS13 activity remains low (<10%) or inhibitors are detect-
shown to be effective in a subset of patients, particularly in those who able after extensive plasma exchange therapy, rituximab (anti-CD20
have hereditary or acquired severe deficiency of plasma ADAMTS13 monoclonal antibody) 188-192 or cyclosporine/cyclophosphamide 182,193,194
activity, to reduce the maternal mortality and morbidity, as well as fetal should be considered. In some cases, immunosuppressive therapies
demise. 21,99 However, prompt delivery remains the treatment of choice. such as rituximab or cyclosporine 193,195,196 should be given earlier dur-
192
Postpartum TTP or HUS is characterized by predominant renal ing the course of plasma exchange therapy. All patients should receive
involvement; neurologic signs and fever are usually absent. It has been corticosteroids 11,50,53,182 to suppress the production of inflammatory
suggested that this syndrome is a clinical counterpart of the general- cytokines that may be the triggering factors for acute episodes of TTP.
ized Schwarzman reaction in which bacterial endotoxins or vasoactive Neurological signs and symptoms resolve quickly, followed by the nor-
amines are discharged into the maternal circulation and either stimulate malization of platelet counts, MAHA, renal function, and peripheral
the coagulation cascade or initiate thrombosis by damage to the vascular blood smears. The clinical response generally precedes the pathologic
endothelium. In rare cases, postpartum HUS is caused by mutations in response. To date, the mortality rate for idiopathic TTP patients
the CFH gene. 176,177
approaches 10%. The most significant independent variables that deter-
Differentiation of TTP from Systemic Lupus Erythematosus with Vasculitis: It mine death in idiopathic TTP are age, severe cerebral involvement, and
197
is important to differentiate TTP from lupus-associated vasculitis serum LDH levels 10 × normal or over. However, the mortality rate
(Table 91-1). In one review, evidence of lupus was found in 7 of 64 cases for nonidiopathic TTP, which is associated with other diseases or condi-
(11%) that were initially diagnosed as having TTP or HUS. The mor- tions including hematopoietic progenitor cell transplantation and dis-
2
tality rate of TTP or HUS during lupus is from 34% to 62.5%. Plasma seminated malignancy, remains quite high (∼54%-90%), 53,198 although
ADAMTS13 activity may be extremely low (<5%-10% activity), 21,178,179 it is difficult to know whether these patients died of underlying diseases
consistent with acquired TTP on top of lupus, or normal to moderately or TTP. 53
been reported that TTP or HUS may rarely be association with other ■ TREATMENT OF HUS
suggestive of a lupus flare. It has also
reduced plasma ADAMTS13,
21,180
connective vascular diseases (CVDs) such as rheumatoid arthritis, D+HUS: The outcome and prognosis of the D+HUS associated
systemic sclerosis, rheumatoid arthritis, vasculitis, and mixed con- with E coli O157 : H7 are usually excellent after supportive care.
nective diseases. 21,180 On the other hand, vasculitis in association with Approximately 4% of patients die and 25% of patients develop chronic
lupus or another CVD may mimic TTP or HUS with findings of renal renal insufficiency. 56,156 Dialysis may be necessary in approximately
failure, fever, neurologic disturbance, thrombocytopenia, and MAHA. 50% of cases; red cell transfusion has been given to 75% of patients.
199
Antinuclear antibodies are positive in the great majority of patients with Plasma exchange and use of antibiotics were found to be ineffective
lupus. These CVD screening tests are indicated in all patients with a in the past. The use of antibiotics was regarded to be harmful as a
tentative diagnosis of TTP or HUS. If a diagnosis of a specific CVD can result of increased release of Shiga toxin in the gut. However, a recent

section07.indd 863 1/21/2015 7:42:53 AM