treat TTP with plasmaphresis and steroid

It is rare for a patient with TTP to have the full classic pentad (fever, MAHA, thrombocytopenia, renal failure, and neurologic symptoms).  The presence of MAHA and thrombocytopenia (not due to other causes) is enough to diagnose suspected TTP and initiate treatment with plasma exchange (even without fever, as in this patient).  Measurement of ADAMTS13 activity is not required to make the diagnosis.  Replacement of ADAMTS13 via plasma exchange stabilizes and improves most cases of idiopathic TTP.  Failure to institute timely therapy can lead to devastating end-organ consequences.  Initiating plasma exchange therapy while waiting for additional test results is the most appropriate next step in management.  Patients refractory to plasma exchange therapy may respond to rituximab or cyclosporine. Contrast this with ITP (ITP immune thrombocytopenia)

Corticosteroids and other immunosuppressive drugs may reduce antibody formation in idiopathic TTP or prevent bleeding when the platelet count is very low.  These are usually given as an adjunct to plasma exchange or later in the course of the disease pending initial response to plasma exchange.

In the past, therapeutic plasma exchange (not plasma infusion) was considered the gold standard treatment for TTP, but more recent evidence and new guidelines recommend a combination approach with up-front corticosteroids added to therapeutic plasma exchange when a diagnosis of TTP is first suspected, while awaiting confirmatory ADAMTS13 testing results (choice C is incorrect). Corticosteroids help by decreasing production of antibodies against ADAMTS13. The guidelines also recommend early consideration of caplacizumab and rituximab, when low ADAMTS13 is confirmed, or if the patient is critically ill with severe neurologic or cardiac findings and other forms of critical illness.

This patient would be in an intermediate to high-risk category. In recent studies, caplacizumab resulted in faster normalization of the platelet count; a lower incidence of a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the treatment period; and a lower rate of recurrence of TTP during the trial than placebo. Caplacizumab is an anti-VW factor immunoglobulin that inhibits interactions between VW multimers and platelets. Where this drug will fit in TTP treatment is not yet clearly delineated but should be considered after low ADAMTS13 levels are identified and earlier with a presumptive diagnosis in the critically ill. Rituximab helps to prevent relapse by inhibiting B-cell production of antibodies against ADAMTS13. Treatment for TTP continues until the thrombocytopenia has resolved to the range of ≥150 × 103/µL (150 × 109/L).

Corticosteroids alone would not be appropriate in TTP, although they could be of benefit in ITP, which is not present here. Patients with ITP present with petechiae and bleeding and usually do not have schistocytes on peripheral blood smear (choice B is incorrect). Platelet transfusion in TTP may be associated with adverse events. Platelet transfusions would not be indicated unless platelet counts are below 10 × 103/µL (10 × 109/L), below 20 × 103/µL (20 × 109/L) if the patient is febrile or has sepsis, below 50 × 103/µL (50 × 109/L) if the patient is bleeding or for lower risk procedures, or below 100 × 103/µL (100 × 109/L) for major procedures (choice A is incorrect).11234

  • plasmapheresis:
    • centrifuge
    • removes plasma with immunoglobulins
    • not good at removing IgG
    • add donor plasma
  • pulse dexamethasone: decrease antibody
  • rituximab
  • aspirin
  • caplacizumab

Footnotes

  1. Scully M, Cataland SR, Peyvandi F, et al; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335-346. PubMed ↩ ↩2

  2. Zheng XL, Vesely SK, Cataland SR, et al. Good practice statements (GPS) for the clinical care of patients with thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2503-2512. PubMed ↩

  3. Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2486-2495. PubMed ↩

  4. Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2496-2502. PubMed ↩