Potentially life-threatening emergency
Thrombotic thrombocytopenic purpura
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Synopsis
TTP is a subtype of the thrombotic microangiopathy (TMA) syndromes. Other subtypes of TMA include Shiga toxin-mediated TMA (Shiga toxin hemolytic-uremic syndrome), drug-mediated TMA, and complement-mediated TMA, among others. Accurate diagnosis of TTP and prompt initiation of treatment are essential to prevent morbidity and mortality.
The cause may be acquired or, in rare cases, hereditary (Upshaw-Schulman syndrome). In acquired TTP, also known as immune-mediated TTP (iTTP), autoantibodies form against the plasma metalloprotease ADAMTS13, which normally cleaves von Willebrand factor (vWF). As a result, vWF multimers accumulate, causing platelet aggregation and microvascular occlusion. Hereditary TTP results from genetic mutations in the ADAMTS13 gene, resulting in the absence or severe deficiency of ADAMTS13.
Classically, TTP was thought to be associated with a "pentad" of clinical and laboratory findings including microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, fever, and renal dysfunction. However, the latter 3 findings are not reliably present in TTP, and consequently the presence of microangiopathic hemolytic anemia and thrombocytopenia are sufficient for a diagnosis of TTP.
Clinical features of TTP are varied and may include gastrointestinal symptoms (abdominal pain, nausea, vomiting), fatigue, malaise, neurologic abnormalities (altered mental status, confusion, headache), and purpuric rash.
Due to its rarity and variety of ADAMTS13 mutations, there is still much to learn about hereditary TTP. Patients with hereditary TTP can present at birth or remain asymptomatic into adulthood. Specific signs and symptoms may be related to the severity of ADAMTS13 mutations, with more severe cases related to lower ADAMTS13 activity. When symptoms first manifest, presentation can be quite variable and may be similar to an acquired TTP episode.
Although patients with hereditary TTP may remain asymptomatic for many years, their increased risk of critical thrombosis is always present. Overt thrombotic episodes in patients with hereditary TTP are associated with states of increased vWF concentrations, such as during pregnancy or the neonatal period or due to trauma, excessive alcohol intake, infection, or inflammation. However, clinically silent infarcts may occur outside of such states.
TTP is more common in women and in Americans of African descent. Hereditary TTP is usually initially recognized before age 10 or during a woman's first pregnancy. Acquired TTP typically presents between the ages of 30 and 50. For acquired TTP, overall survival rates with therapy are above 80%, although relapse occurs in up to 40% of cases.
Codes
ICD10CM:M31.19 – Other thrombotic microangiopathy
SNOMEDCT:
78129009 – Thrombotic thrombocytopenic purpura
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Diagnostic Pearls
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Differential Diagnosis & Pitfalls
Acquired TTP is much more common in adults than children. In contrast, hereditary TTP is more commonly diagnosed in children.Thrombotic microangiopathy syndromes (microangiopathic hemolytic anemia, thrombocytopenia):
- Shiga toxin-mediated TMA (hemolytic-uremic syndrome) – diarrheal illness as prodrome; severe renal dysfunction (particularly important to rule out in pediatric patients)
- Drug-mediated TMA (quinine, quetiapine, gemcitabine, and calcineurin inhibitors, among others)
- Complement-mediated TMA
- Disseminated intravascular coagulation (DIC)
- Systemic lupus erythematosus
- Systemic sclerosis
- Antiphospholipid antibody syndrome
- Systemic infection (eg, cytomegalovirus, herpes simplex virus, meningococcus)
- Idiopathic thrombocytopenic purpura (ITP)
- Evans syndrome
- HELLP syndrome – hemolysis, elevated liver function tests, and low platelets
- Preeclampsia
- Eclampsia
- Rh incompatibility
- ABO incompatibility
- G6PD deficiency
- Pyruvate kinase deficiency
- Hereditary spherocytosis / elliptocytosis
- Alpha thalassemia / beta thalassemia
- Sickle cell disease
- Sepsis
- Necrotizing enterocolitis
- Chronic fetal hypoxia due to gestational hypertension / gestational diabetes / intrauterine growth restriction (IUGR)
- Congenital viral infections
- Perinatal bacterial infections
- Perinatal asphyxia
- Chromosomal aneuploidy
- Inherited platelet disorders
- Metabolic diseases
- Congenital leukemia
- Autoimmune disease
- Kasabach-Merritt syndrome
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Therapy
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Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.Subscription Required
References
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Last Reviewed:04/29/2020
Last Updated:11/30/2022
Last Updated:11/30/2022
Potentially life-threatening emergency
Thrombotic thrombocytopenic purpura