Guidelines Summary
British Committee for Standards in Haematology
Guidelines on the diagnosis and treatment of thrombotic thrombocytopenic purpura (TTP) were published by the British Society for Haematology in 2012. [23] Recommendations regarding diagnosis include the following:
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The diagnosis of TTP should be treated as a medical emergency.
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The initial diagnosis of TTP should be made on the basis of the patient's clinical history, examination, and routine laboratory parameters, including blood film review.
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Because of the high risk of preventable early deaths in TTP, treatment with plasma exchange should be initiated as soon as possible, preferably within 4–8 h, if a patient presents with a microangiopathic hemolytic anemia (MAHA) and thrombocytopenia in the absence of any other identifiable clinical cause.
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Pre-treatment samples should be obtained to measure ADAMTS13 activity levels and to detect anti-ADAMTS13 antibodies. Measurement of ADAMTS13 antigen levels is also useful in congenital TTP cases.
Additional recommended laboratory tests for patients with a suspected diagnosis of TTP, with samples taken before the first plasma exchange, and expected results, include the following:
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Complete blood cell count and peripheral smear - Anemia, thrombocytopenia, fragments on smear
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Reticulocyte count - Raised
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Haptoglobin - Reduced
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Coagulation screen, including fibrinogen - Normal
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Liver function tests - Usually normal
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Lactate dehydrogenase - Raised due to hemolysis
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Direct antiglobullin test - Negative
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Hepatitis A, B, and C and HIV serology
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Blood type and crossmatch - To permit transfusions
Assessment of organ involvement may involve the following:
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Heart - Troponin T and I, electrocardiogram
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Kidneys - Blood urea nitrogen and electrolytes, urinalysis
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Brain - CT/MRI
Tests to consider for a possible underlying cause include the following:
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Thyroid function tests - To exclude Graves disease
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Autoantibody screen (antinuclear antibody, rheumatoid factor, lupus antibody, anticardiolipin antibodies) - To exclude associated automimmune disease
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Stool culture - For pathogenic Escherichia coli, in patients with diarrhea
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CT of chest/abdomen/pelvis (if indicated, with or without tumor markers - To exclude underlying malignancy
Congenital TTP:
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Consider congenital TTP in neonates presenting with severe jaundice, but be aware that patients may not present until later in childhood or adulthood.
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Consider the diagnosis of congenital TTP in children and adults with unexplained thrombocytopenia.
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The diagnosis of congenital TTP is confirmed by ADAMTS13 activity < 5%, absence of antibody, and confirmation of homozygous or compound heterozygous defects of the ADAMTS13 gene.
Treatment:
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Start plasma exchange with 1.5 plasma volume (PV) exchanges, using solvent/detergent-treated fresh frozen plasma in all age groups and reassessed daily.
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The volume of exchange can be reduced to 1.0 PV when the patient's clinical condition and laboratory test results are stabilizing.
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Intensification in frequency and or volume of plasma exchange procedures should be considered in life-threatening cases.
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Daily plasma exchanges should continue for a minimum of 2 d after platelet count has been > 150 × 10 9/L and should then be stopped.
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Intravenous daily methylprednisolone (eg, 1 g/d for three consecutive days – adult dose) or high-dose oral prednisolone (eg, 1 mg/kg/d) should be considered in addition to plasma exchanges.
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In patients with acute idiopathic TTP who have neurological/cardiac pathology, treatment with rituximab should be considered on admission, in conjunction with plasma exchange and steroids. Rituximab should also be offered to patients with refractory or relapsing immune-mediated TTP.
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Cyclosporine may be considered for second-line therapy in patients with acute or chronic relapsing acquired TTP.
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Splenectomy may rarely be considered in the non-acute period of immune-mediated TTP but has limited proven benefit.
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Low-dose aspirin (75 mg OD) may be given during platelet recovery (platelet count > 50 × 10 9/L).
Supportive therapy recommendations include the following:
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Red cell transfusions should be administered according to clinical need, especially in patients with cardiac involvement.
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Folate supplementation is required during active hemolysis.
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Platelet transfusions are contraindicated in TTP unless the patient has life-threatening hemorrhage.
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Thromboprophylaxis with low molecular weight heparin is recommended once the platelet count has reached > 50 × 10 9 /L).
For treatment of congenital TTP, the guidelines recommend infusion of solvent/detergent-treated plasma or intermediate-purity plasma-derived factor VIII (FVIII) concentrates, although there is no guaranteed constant quantity of ADAMTS13 in such concentrates. Treatment regimens for congenital TTP should be individualized according to the patient's phenotype, with some patients requiring regular infusions and others with a mild phenotype needing only occasional treatment. Pregnant women with congenital TTP should attend a specialist center and receive ADAMTS13 supplementation regularly throughout pregnancy and the post-partum period.
International Society on Thrombosis and Haemostasis
The International Society on Thrombosis and Haemostasis (ISTH) issued guidelines on the treatment of TTP in 2020. [11] Recommendations for treatment of acute events in patients with immune-related TTP ( iTTP) are as follows:
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For treatment of a first acute event, the ISTH panel recommends therapeutic plasma exchange (TPE) plus corticosteroids over TPE alone.
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For treatment of a first acute event, the panel suggests the addition of rituximab to corticosteroids and TPE.
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For treatment of relapse, the panel recommends TPE plus corticosteroids over TPE alone.
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For treatment of relapse, the panel suggests the addition of rituximab to corticosteroids and TPE.
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For treatment of a first acute event or a relapse, the panel suggests using caplacizumab.
ISTH recommendations for management of patients with TTP who are in remission are as follows:
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For patients with iTTP who are in remission, but still have low plasma ADAMTS13 activity with no clinical signs/symptoms, the panel suggests the use of rituximab for prophylaxis.
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For patients with hereditary or congenital TTP (cTTP) who are in remission, the panel suggests either plasma infusion or a watch and wait strategy.
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For patients with cTTP who are in remission, the panel suggests against the use of FVIII concentrate.
ISTH recommendations for management of TTP in pregnant patients are as follows:
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For patients with iTTP who are pregnant and have decreased plasma ADAMTS13 activity but no clinical signs/symptoms, and for those with cTTP, the panel recommends prophylactic treatment. For prophylaxis in pregnant patients with cTTP, the panel suggests plasma infusion rather than FVIII products.
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Differential diagnosis of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP), and disseminated intravascular coagulation (DIC).
