Caplacizumab Therapy without Plasma Exchange for Acquired Thrombotic Thrombocytopenic Purpura

Design

Case report

Case presentation

A 63-year-old female with no known medical problems presented to the emergency department with spontaneous purpura (with no other symptoms). Her hemoglobin (Hb) was 11.6 g/dL, and her platelet count was 14,000/µL. The initial diagnosis was primary immune thrombocytopenia, and she was started on dexamethasone.

On day 2, her labs suggested thrombotic thrombocytopenic purpura (TTP) with a haptoglobin level< 30 mg/dL, negative results on a direct antiglobulin test, a creatinine level of 0.8 mg/dL, and a lactate dehydrogenase level of 605 U/L. On day 4, her TTP diagnosis was confirmed with a low (< 5%) level of ADAMTS13.

Since the patient was a Jehovah’s Witness, she declined plasma exchange. Instead, she was treated with glucocorticoids, rituximab, and antihemophilic factor VIII (Koate-DVI). The patient had multiple episodes of transient right facial droop and aphasia and became progressively more confused up to day 10 of hospitalization.

On day 7, she was started on treatment with caplacizumab (only available for compassionate use), but the FDA approved it on day 11. Caplacizumab was started at 10 mg/day with a first intravenous dose and subsequent subcutaneous doses.

On day 12, her platelet count had increased from 23,000/µL to 83,000/µL; after the third daily treatment, the platelet count had increased to 200,000/µL. After the first dose of caplacizumab, the patient had no new purpuric lesions or neurologic symptoms (previous issues resolved); however, she did have a minor epistaxis episode after the first dose. The patient was discharged from the hospital on day 20, and glucocorticoids were discontinued; she continued to receive caplacizumab until day 40 (30 days total) and rituximab. Follow-up 31 days after caplacizumab discontinuation found normal ADAMTS13 activity and no new problems.

Study Author Conclusions

Caplacizumab acts immediately to prevent platelet adhesion to von Willebrand factor multimers and thereby helps to prevent microvascular thrombosis. However, caplacizumab is not a sufficient treatment for acquired TTP; remission requires immunosuppression to block the production of autoantibodies against ADAMTS13.

This case report suggests that caplacizumab, together with glucocorticoids and rituximab, may be an effective treatment for patients with TTP who are unable or unwilling to undergo plasma exchange because of religious prohibitions, lack of availability, inaccessible venous access, or a history of severe immune reaction to plasma. However, a clinical trial to evaluate the regimen of caplacizumab plus glucocorticoids and rituximab without plasma exchange in selected patients with mild TTP is needed to confirm the safety and effectiveness of this treatment regimen.

Early Response to Caplacizumab and Rituximab After Anaphylaxis to Octaplas Plasma in a Patient with Thrombotic Thrombocytopenic Purpura

Design

Case presentation

A 39-year-old female was admitted to the emergency department (ED) for bruises at the upper and lower limbs in association with mild anemia (Hb 10.5 g/dL) and severe thrombocytopenia (PLT 30,000/mm³), in the absence of neurological, cardiac, or abdominal symptoms. Testings indicated a high risk of thrombotic microangiopathy due to severe ADAMTS-13 deficiency. The patient was soon initiated on steroids (methylprednisolone 40 mg for 24 hr, followed by prednisone 1 mg/kg/day for 1 month) with folic acid and daily plasma exchange (PEX) using Octaplas as the replacement product (1 to 1.5 plasma volumes exchange, 40 to 60 mL/kg). The patient's ADAMTS13 activity (FRET methodology) showed 1.4%, confirming a diagnosis of thrombotic thrombocytopenic purpura (TTP). 

During the third and fourth PEX, the patient suddenly and dramatically presented with anaphylaxis accompanied by respiratory distress, severe hypotension, tachycardia, progressive urticaria, psychomotor agitation, a feeling of impending doom, diffuse pain, mild nausea, and fever. Plasma exchange was immediately stopped, and the resuscitation protocol was repeated. The severe clinical presentations resolved after 120 to 150 minutes, but residual effects (transient mild headache, lower limb paraesthesia, moderate increase in platelets counts, persistent transfusion-dependent anemia) persist the next day. 

Considering symptoms occurrence and intolerance to plasma, the patient was started on weekly rituximab at a dose of 375 mg/m² for 4 weeks and daily caplacizumab 10 mg subcutaneously (first dose intravenous). This approach was well tolerated, without any drug-related adverse events or bleeding. Caplacizumab was interrupted (after 16 doses) when ADAMTS13 activity was at 20.6% (Day 19). After discharge, steroids were tapered, and ADAMTS13 was restored to 64.5% two months later.

Study Author Conclusions

This appears to be the first experience of early discontinuation of caplacizumab achieved through ADAMTS-13 activity monitoring in a patient untreatable with plasma exchange. This strategy may allow optimization of healthcare resources.  

This case also suggests that plasma exchange could be safely avoided in the treatment strategy of autoimmune TTP and possibly replaced by caplacizumab; this is at least feasible when plasma exchange cannot be carried out. This PEX-free approach might reduce the intrinsic infectious and anaphylactic risks of human plasma and could also be cost-effective, reducing not only the period of hospital stay but also the median number of plasma exchanges if an earlier response could be obtained.