The standard of care for immune thrombotic thrombocytopenic purpura today

Abstract

Immune thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal blood disorder, primarily caused by acquired deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin-1 Domain, member 13), 1,2 a plasma metalloprotease that cleaves von Willebrand factor (VWF). 3,4 VWF is a multimeric adhesive glycoprotein that is synthesized and released from endothelial cells and megakaryocytes/platelets. 5,6 The proteolytic cleavage of endothelial ultra-large VWF (ULVWF) by plasma ADAMTS-13 is essential for normal hemostasis. An inability to cleave the ULVWF anchored on endothelial surface, in circulating blood, and at the sites of vascular injury leads to exaggerated platelet adhesion, agglutination, and formation of occlusive thrombi in small arterioles and capillaries, 7-9 a characteristic feature of iTTP pathology. 10 Without early recognition and prompt management, iTTP is universally fatal. Therapeutic plasma exchange (TPE) has been the standard of care for nearly three decades; it reduces mortality rate to less than 10% to 20%. [11][12][13] Remarkable progresses have been made in recent years in rapid diagnosis and prompt management of acute iTTP, leading to further reduction of the mortality rate.

Immune-Mediated Thrombotic Thrombocytopenic Purpura Following mRNA-Based COVID-19 Vaccine BNT162b2: Case Report and Mini-Review of the Literature

“…Patients with VITT present typically with moderate-to-severe thrombocytopenia and arterial or venous thrombosis, often at unusual sites such as cerebral sinus veins, splanchnic, and portal veins, but deep venous thrombosis and pulmonary embolism may be present as well ( 35 – 37 ). Patients with acute iTTP episodes usually present with severe thrombocytopenia (<30 G/L), marked hemolysis and diffuse microvascular thrombosis, and although macrovascular thrombosis is possible, it is rare at presentation ( 1 – 3 ). iTTP is characterized by the formation of auto-antibodies against ADAMTS13, which induce a severe ADAMTS13 deficiency through increased clearance of ADAMTS13 or by inhibiting ADAMTS13 function.…”

“…An increasing number of case reports have associated vaccinations against coronavirus disease 2019 (COVID-19) with immune-mediated thrombotic thrombocytopenic purpura (iTTP), a very rare and potentially life-threatening form of thrombotic microangiopathy ( 1 – 3 ). In iTTP, autoantibodies to ADAMTS13 lead to a severe deficiency of ADAMTS13 activity (<10% of that in normal plasma) ( 1 – 3 ). Under physiological conditions, ADAMTS13 cleaves the ultra-large von Willebrand factor (vWF) multimers secreted by endothelial cells into smaller, less sticky vWF units.…”

“…Under physiological conditions, ADAMTS13 cleaves the ultra-large von Willebrand factor (vWF) multimers secreted by endothelial cells into smaller, less sticky vWF units. In the absence of ADAMTS13, ultra-large vWF multimers persist and bind platelets spontaneously, leading to microvascular thrombosis with variable degrees of ischemic organ damage, consumptive thrombocytopenia, and microangiopathic hemolytic anemia due to fragmentation of red blood cells as evidenced by schistocytes on the peripheral blood smear ( 1 – 3 ). Therapeutic plasma exchange (TPE) with replacement of plasma ( 4 ), together with immunosuppressants (corticosteroids, and often rituximab), have reduced mortality from >90% to <5% in centers experienced in the care of iTTP patients.…”

“…With the addition of the anti-vWF A1 domain nanobody caplacizumab, recently available in many countries, mortality rates seem to decline further. Relapses, however, remain an issue and occur in at least 40–50% of survivors of an initial iTTP episode ( 1 – 3 ). With regular ADAMTS13 activity measurements at hand, survivors are nowadays followed up and may benefit from preemptive immunosuppressive therapy upon the reappearance of anti-ADAMTS13 antibodies and ADAMTS13 deficiency ( 5 ).…”

Acquired Thrombotic Thrombocytopenic Purpura After BNT162b2 COVID-19 Vaccine: Case Report and Literature Review

“…Although the treatment of choice for TTP is plasma exchange (PE), immunosuppressive therapy has significantly improved outcomes with a reduced length of hospitalization. 2 …”