Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acquired (idiopathic) TTP: acute episode

1st line – plasma exchange

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ACUTE
|
acquired (idiopathic) TTP: acute episode
1st line – 

plasma exchange

Plasma exchange should be started within 24 hours of presentation, because delay decreases the chance of response.[53] Single volume plasma exchange daily has been reported; however the British Committee for Standards in Haematology recommends urgent initiation of 1.5 plasma volume exchanges to reduce mortality.[4][54][55][56]

Plasma exchange is ineffective in children with suspected hemolytic uremic syndrome (which must be excluded) and is less likely to be effective in bone marrow transplant-associated TTP; it should not be given in these situations.

Plasma exchange should be titrated as needed based on clinical status, platelet count, and LDH. Withdrawal should commence once the patient's platelet count and LDH are improved and stable; waiting for 3 days before initiating the slow taper is optimal.

Patients are tapered to a plasma infusion gradually and are then tapered off plasma altogether. Approximately 90% of patients will respond to plasma exchange within 3 weeks (with most responding within 10 days).

If plasma exchange is not available, patients should be transferred to a location where plasma exchange can be performed. If the initiation of plasma exchange is delayed, plasma infusion can be used (30 mL/kg/day).

Early testing for pregnancy, HIV, and hepatitis B and C has been suggested before plasma exchange (if possible), as pregnancy and HIV are considered risk factors for TTP, and hepatitis B and C infection have been associated with TTP.[4]

Plus – corticosteroids

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ACUTE
|
acquired (idiopathic) TTP: acute episode
Plus – 

corticosteroids

Treatment recommended for ALL patients in selected patient group

Patients receiving plasma exchange should also be given corticosteroids.

This combination is standard of care, despite the fact that there has been no study specifically comparing plasma exchange alone versus plasma exchange with corticosteroids.[59] There is no agreement about type of corticosteroid that should be given.

Primary options

prednisone: 1 mg/kg/day orally

OR

methylprednisolone: 1 g/day intravenously for 3 days

Consider – caplacizumab

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ACUTE
|
acquired (idiopathic) TTP: acute episode
Consider – 

caplacizumab

Treatment recommended for SOME patients in selected patient group

Caplacizumab may be prescribed as an adjunctive therapy in adults.

Caplacizumab is the first therapeutic agent approved for acquired TTP. It is a humanized, bivalent variable-domain-only immunoglobulin fragment that blocks the interaction between von Willebrand factor and platelets. In a phase III trial of adults with acquired TTP, caplacizumab (in combination with plasma exchange and corticosteroids) reduced TTP-related death, recurrence, or major thromboembolic event (a composite outcome) compared with placebo (12% vs. 49%, P <0.001).[60] Caplacizumab also resulted in significantly shorter time to normalization of platelet count.

Primary options

caplacizumab: first day of treatment: 11 mg intravenously as a single bolus dose at least 15 minutes prior to plasma exchange, followed by 11 mg subcutaneously after completion of plasma exchange on day 1; subsequent doses: 11 mg subcutaneously once daily following each daily plasma exchange, and continuing for 30 days following the last daily plasma exchange

Consider – aspirin

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ACUTE
|
acquired (idiopathic) TTP: acute episode
Consider – 

aspirin

Treatment recommended for SOME patients in selected patient group

Aspirin may be combined with plasma exchange and corticosteroids, but this remains controversial. TTP pathophysiology involves platelet aggregation leading to microthrombi; therefore use of aspirin makes theoretical sense.

Once the acute episode resolves, patients may be kept on aspirin long term to decrease platelet aggregation.

In patients with severe thrombocytopenia (i.e., platelet count <10 x 10³/microliter), some practitioners would advocate avoiding antiplatelet agents because of concerns regarding bleeding complications.

Primary options

aspirin: 81-325 mg orally once daily

Consider – folic acid and/or transfusions

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ACUTE
|
acquired (idiopathic) TTP: acute episode
Consider – 

folic acid and/or transfusions

Treatment recommended for SOME patients in selected patient group

Patients can be given folate supplementation for a presumed relative folate deficiency from hemolysis and high demand for folate. However, high doses of folic acid might obscure a vitamin B12 deficiency, and supplementation can also result in nausea, loss of appetite, irritability, and loss of sleep.

Patients can receive red-cell transfusions according to clinical need as there is no single reliable cut-off.

Platelet transfusion should be considered for a bleeding patient or when invasive procedures and central lines are required for plasmapheresis. Although this was previously thought to trigger worsening of disease, a retrospective review does not support this.[62]

The risk of a transfusion-transmitted infectious disease from a standard unit of fresh frozen plasma is the same as for a unit of red cells: HIV risk is 1:2,100,000; human T-lymphotropic virus (HTLV) risk is 1:2,000,000; hepatitis C risk is 1:1,900,000; and hepatitis B risk is 1:58,000 to 1:269,000.

Primary options

folic acid (vitamin B9): 3-5 mg orally once daily

2nd line – immunosuppression

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ACUTE
|
acquired (idiopathic) TTP: acute episode
2nd line – 

immunosuppression

Rituximab is a monoclonal antibody specific for the CD20 B-cell marker. It is used frequently for the treatment of B-cell non-Hodgkin lymphoma. Studies have evaluated its use in autoimmune processes, including acquired (idiopathic) TTP, because it is a relatively safe and easy method for targeting antibody production.[63] Rituximab is becoming more commonly used than the other immunosuppressive agents in the US. In the past it has been used in the salvage setting with suboptimal response, whereas now it is being used in the frontline setting, resulting in a reduced risk of relapse.[64] One meta-analysis suggests treating with rituximab in the acute phase may also reduce mortality.[65]

There are case reports and small retrospective studies to suggest that vincristine may be temporally associated with platelet recovery in refractory TTP.[66][67][68]

Support for the use of cyclophosphamide in the treatment of refractory TTP comes from small case reports and the theoretical benefit of immunosuppression.[69][70][71]

Cyclosporine is associated with an increased risk of post-bone marrow transplantation microangiopathy but has also shown some activity in the treatment of refractory, severe intermittent, and postautologous bone marrow transplantation TTP.[72][73] The optimal duration of treatment is unclear, and there appear to be relapses after stopping therapy.

Primary options

vincristine: see local specialist protocol for dosing guidelines

OR

rituximab: consult specialist for guidance on dose

Secondary options

cyclophosphamide: consult specialist for guidance on dose

OR

cyclosporine modified: consult specialist for guidance on dose

3rd line – splenectomy

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ACUTE
|
acquired (idiopathic) TTP: acute episode
3rd line – 

splenectomy

In the preplasma exchange era, splenectomy had been tried in combination with corticosteroids for the treatment of acquired (idiopathic) TTP, with some long-term responses. With the advent of plasma exchange, its benefit has been questioned. A review looked at the 20-year experience with TTP at a single center and found that 9 out of the 10 patients who underwent splenectomy for refractory TTP developed a complete response.[74]

After splenectomy, patients are at higher risk of fatal bacterial infections, at approximately 1 per 1500 patient-years, and should be instructed to seek emergent medical treatment in the case of febrile illness.

At least 2 weeks before splenectomy, patients should receive polyvalent pneumococcal vaccine, Haemophilus influenzae b vaccine, and quadrivalent meningococcal polysaccharide vaccine.

ONGOING

acquired (idiopathic) TTP: following resolution of acute episode

1st line – long-term aspirin

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ONGOING
|
acquired (idiopathic) TTP: following resolution of acute episode
1st line – 

long-term aspirin

Patients are kept on aspirin long term to decrease platelet aggregation.

Primary options

aspirin: 81-325 mg orally once daily

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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