Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, a condition in which microthrombi, consisting primarily of platelets, form and occlude the microvasculature (i.e., the arterioles and capillaries). TTP occurs primarily in adults and is typically due to acquired autoantibodies against a proteolytic enzyme (ADAMTS13) that cleaves von Willebrand factor (vWF). The classic pentad of findings (fever, neurological abnormalities, thrombocytopenia, microangiopathic hemolytic anemia, and impaired renal function) is seen in a minority of patients. TTP is a hematologic emergency. If TTP is strongly suspected and initial laboratory tests support the diagnosis, treatment with plasma exchange should begin immediately, as the condition may be fatal if left untreated.
- Primarily adult individuals (median age at diagnosis: ∼ 40 years)
- More common in women and in Black populations
Epidemiological data refers to the US, unless otherwise specified.
TTP is a thrombotic microangiopathy, a condition in which microthrombi form and occlude the microvasculature. The other main thrombotic microangiopathy is (HUS). Although TTP and HUS share similarities in both pathophysiological findings and clinical features, these conditions differ in etiology; TTP, unlike HUS, is caused by a deficiency of ADAMTS13.
- Autoantibodies or gene mutations → deficiency of ADAMTS13; (a metalloprotease that cleaves von Willebrand factor)
- ↓ Breakdown of vWF multimers → vWF multimers accumulate on endothelial cell surfaces
- Platelet adhesion and microthrombosis
- Microthrombi → fragmentation of RBCs with schistocyte formation → hemolytic anemia
- Arteriolar and capillary microthrombosis → end-organ ischemia and damage, especially in the brain and kidneys (potentially resulting in acute kidney injury or stroke)
TTP patients are typically previously healthy adults. Microangiopathic hemolytic anemia and thrombocytopenia may be the only presenting signs. However, the classic pentad of clinical findings consists of: 
- Neurological signs and symptoms
- Low platelet count (i.e. thrombocytopenia)
- Microangiopathic hemolytic anemia
- Impaired renal function
The typical patient is a previously healthy adult presenting with mental status changes, fever, petechiae, fatigue, and pallor. Laboratory tests will then indicate hemolytic anemia and possibly acute kidney injury (AKI). Impaired kidney function may not be present, and only a minority of patients will present with all five clinical findings.
- Suspect TTP in patients with microangiopathic hemolytic anemia and thrombocytopenia.
- Obtain laboratory studies and targeted clinical history to:
- Obtain further diagnostic studies as indicated to identify a secondary cause and rule out thrombotic complications.
Laboratory studies 
Initial tests 
- Peripheral blood smear
- Hemolysis studies
- Coagulation studies
- Liver chemistries: ↑ indirect bilirubin
- BMP: ↑ BUN and ↑ creatinine may be seen.
- Troponin: to rule out cardiac ischemia 
- Urinalysis: hematuria, proteinuria
While PT and aPTT are normal or only mildly elevated in TTP and HUS (no consumption coagulopathy), they are markedly elevated in disseminated intravascular coagulation (consumption of platelets and all coagulation factors).
Confirmatory tests 
Obtain ADAMTS13 activity and inhibitor testing in all patients.
- < 10%: positive (severe deficiency)
- 10–20%: borderline
- > 20%: negative
- ADAMTS13 inhibitor or anti-ADAMTS13 IgG
The PLASMIC score is a clinical risk assessment tool, based on easily attainable clinical information, that is used to predict the likelihood of severe ADAMTS13 deficiency in patients with suspected TTP. The total score helps direct further management.
|PLASMIC score |
|Platelet count < 30,000/mm3||1|
|No active malignancy in the past year||1|
|No history of stem cell or solid organ transplant||1|
|MCV < 90 μm3||1|
|INR < 1.5||1|
|Serum creatinine < 2.0 mg/dL||1|
Likelihood of severe ADAMTS13 activity deficiency (activity level < 10%) 
Additional testing 
Consider the following studies as indicated to identify serious complications and secondary causes of TTP.
- Admit all patients with suspected or confirmed TTP to an ICU.
- Obtain prompt central venous access.
- Provide supportive care for all patients.
- Consult hematology for guidance.
- Initiate empiric treatment with:
- Plasma exchange therapy
- Provide targeted treatment if ADAMTS13 activity levels are available.
Supportive care 
- Continuous and
- Serial s
Fluids and electrolytes
- Correct electrolyte disturbances.
- Provide as indicated.
- Identify and correct .
Empiric therapy 
- Initiate treatment in consultation with hematology.
- Prompt initiation of plasma exchange therapy (PEX)
- High-dose glucocorticoids (off label)
- Patients with a high pretest probability of TTP (based on clinical judgment or PLASMIC score ≥ 6)
- Consider early caplacizumab if ADAMTS13 activity testing is available. 
- Consider rituximab if ADAMTS13 activity testing is not available.
Response to treatment 
Clinical signs of response include : 
TTP can result in microthrombus formation and complications in many organs of the body. 
- CNS: seizures, coma, stroke, paresis
- GI tract: hemorrhagic colitis; bowel necrosis, perforation, stricture; peritonitis; intussusception
- Heart: ischemia and fluid overload
- Pancreas: transient or permanent diabetes mellitus
- Liver: hepatomegaly, transaminase elevations
- Kidney: hypertension, chronic kidney disease (CKD), end-stage renal disease (ESRD)
We list the most important complications. The selection is not exhaustive.