Differentials
Hemolytic uremic syndrome (HUS)
SIGNS / SYMPTOMS
More commonly seen in children.
Patients demonstrate more renal failure and fewer neurologic symptoms.
Some experts believe that it is impossible to distinguish between TTP and HUS and that they are a continuum of a pathology, whereas others believe that they are distinct entities.
Caution should be used in making this diagnosis because it would be harmful to withhold potentially life-saving plasma-exchange treatment if the true diagnosis is TTP.
INVESTIGATIONS
Associated with Escherichia coli O157:H7 infection, which is detected in the stool.
Atypical hemolytic uremic syndrome (aHUS)
SIGNS / SYMPTOMS
Clinical symptoms may be analogous to TTP/HUS in the acute setting.
Recurrent nature of symptoms, or if patient is refractory to conventional plasmapheresis, should raise the suspicion for this diagnosis.
INVESTIGATIONS
Diagnosed by excluding TTP and HUS (i.e., normal ADAMTS-13 level; negative stool culture for Escherichia coli O157:H7) in the correct clinical setting.
Levels or genetic tests for complement regulators associated with aHUS, if present, are useful; however, in 30% to 50% of patients these assays could be negative due to novel or unknown mutations.[47][48]
Hypertension, malignant
SIGNS / SYMPTOMS
Patients can present with microangiopathy, anemia, thrombocytopenia, renal impairment, and neurologic dysfunction. However, it is extremely unlikely that a patient with TTP will present with severe hypertension. Microangiopathic hemolysis in patients with malignant hypertension clears and thrombocytopenia resolves with blood pressure (BP) management.
Patient will have severe hypertension: for example, systolic BP >200 mmHg, diastolic BP >130 mmHg.
INVESTIGATIONS
Clinical diagnosis.
Disseminated intravascular coagulation (DIC)
SIGNS / SYMPTOMS
DIC patients typically appear more acutely ill than patients with TTP. They can also have delayed bleeding after trauma, such as needle sticks.
Sometimes DIC associated with occult or frank malignancies can be hard to distinguish from TTP. A search for systemic malignancy, including a bone marrow biopsy, is appropriate when patients with TTP have atypical clinical features or do not respond to plasma exchange.[49]
INVESTIGATIONS
Prolonged prothrombin time and activated partial thromboplastin time with elevated D dimer suggests DIC.
Sepsis
SIGNS / SYMPTOMS
Signs and symptoms of sepsis include shivering, dizziness, nausea and vomiting, muscle pain, feeling confused or disoriented, tachycardia, tachypnea, hypotension, fever (>100.4°F) or hypothermia (<96.8°F), prolonged capillary refill, mottled or ashen skin, cyanosis, low oxygen saturation, newly altered mental state, reduced urine output. Treatment of the underlying infection should correct the thrombocytopenia.
INVESTIGATIONS
Patients often have more pronounced fever and elevated white count with left shift. Peripheral smear might show vacuoles in the cytoplasm of neutrophils, which is highly specific for bacteremia. Blood cultures might be positive and should be taken immediately, and preferably before antibiotics are started, provided their sampling will not delay the administration of antibiotics. Other cultures (e.g., sputum, stool, and urine) should be taken as clinically indicated. Continuing evaluation to document a systemic infection (e.g., with serum lactate, C-reactive protein, CBC, serum urea, creatinine and electrolytes, liver function tests) is recommended to determine the appropriateness of continued plasma exchange.[50]
Immune thrombocytopenic purpura
SIGNS / SYMPTOMS
These patients do not have renal insufficiency, neurologic symptoms, microangiopathy, or fever, which are seen in patients with TTP.
INVESTIGATIONS
Peripheral smear is bland, other than the presence of thrombocytopenia. They should not have schistocytes.
Preeclampsia
SIGNS / SYMPTOMS
New BP elevation and proteinuria after 20 weeks of gestation in a pregnant woman.
Although pregnancy is a risk factor for TTP and proteinuria can be present, patients with TTP do not generally have elevated BP.
INVESTIGATIONS
Clinical diagnosis
Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome
SIGNS / SYMPTOMS
It can be difficult to distinguish between TTP and HELLP syndrome in some pregnant women. HELLP is suggested by preceding proteinuria and hypertension followed by preeclampsia. HELLP develops in the third trimester, whereas TTP can occur at any point during pregnancy.
INVESTIGATIONS
Blood work shows hemolysis with a microangiopathic blood smear, elevated liver enzymes, and a low platelet count. Might have evidence of DIC on coagulation studies.
Connective tissue disorder-associated vasculitis
SIGNS / SYMPTOMS
Clinical features of connective tissue disease such as systemic lupus erythematosus (SLE) or antiphospholipid syndrome.[51]
INVESTIGATIONS
Positive ANA in SLE.
Positive anticardiolipin and anti-beta-2-glycoprotein I antibodies in antiphospholipid syndrome.
Hemorrhagic fevers
SIGNS / SYMPTOMS
History of travel to an endemic area.
Lead to hemorrhagic manifestations including petechiae, ecchymoses, or overt bleeding from gums, nose, mucosae, or phlebotomy sites. May mimic TTP.
INVESTIGATIONS
Peripheral blood smear usually negative but may reveal schistocytes.
Serologic testing confirms diagnosis.
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