TTP-like syndrome associated with hemoglobin SC disease treated successfully with plasma and red cell exchange

Abstract

Background Sickle cell hemoglobinopathies are associated with end organ damage but very rarely present with a clinical and laboratory picture of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, characteristic of thrombotic microangiopathy (TMA). Case presentation We present a patient with HbSC disease who developed thrombotic microangiopathy, needing both RBC exchange transfusion and therapeutic plasma exchange (TPE) for complete clinical recovery. Conclusion Although literature showed therapeutic plasma exchange alone can abrogate a similar clinical scenario, we did an in-depth review which concluded that in most of the TMA cases secondary to sickle cell disease, treatment with both with plasma exchange and red cell exchange transfusion are necessary.

Thrombotic microangiopathy in patients with sickle cell disease

“…Plasmapheresis resulted in a significant improvement in survival from 10 to 78% in patients with TMA due to TTP, being crucial for a favorable outcome in these conditions. 12 Regarding TMA associated with SCD, several authors have shown a good response with plasma exchange therapy, [8][9][10][11] as well as our patients. The first of them only received plasma replacement and the second had plasma exchange, both with progressive clinical and laboratory improvement.…”

“…8 Both patients had neurological symptoms with lowered level of consciousness, a symptom also frequently reported by other authors. [8][9][10][11] Regarding the pathophysiology of TMA secondary to SCD, Shome et al hypothesized that the endothelial activation that occurs during a vaso-occlusive crisis may lead to greater release of multimers of von Willebrand factor, and inhibition or reduction of the activity of ADAMTS-13 by hyperhemolysis, proteolysis and/or reduction of its synthesis, thus decreasing the cleavage of von Willebrand multimers, which leads to microangiopathic thrombosis. 8 This hypothesis can be supported by the fact that these patients respond well to plasma therapy.…”

ADAMTS13 and von Willebrand factor assessment in steady state and acute vaso‐occlusive crisis of sickle cell disease

“…The unexpected presence of nonrelevant ADAMTS13 IgGs in half of our patients further supports the nonspecific immune activation/dysfunction targeting the vascular endothelium in SCD possibly induced by a partial loss of the phagocytic function of the spleen. However, these results should not keep physicians from investigating ADAMTS13 in case of TMA suspicion in patients with SCD because TTP‐like syndrome and TTP remain tricky differential diagnoses of SCD vaso‐occlusive and thrombotic complications 9‐15 . In addition, because VWF is likely not only a biomarker of SCD‐associated endothelial inflammatory activation but also a pivotal actor of the microvascular thrombotic complications of SCD, anti‐VWF nanobodies may be a new therapeutic perspective in the most severe grades of this hemoglobinopathy.…”

“…28 However, these results should not keep physicians from investigating ADAMTS13 in case of TMA suspicion in patients with SCD because TTP-like syndrome and TTP remain tricky differential diagnoses of SCD vaso-occlusive and thrombotic complications. [9][10][11][12][13][14][15] In addition, because VWF is likely not only a biomarker of SCDassociated endothelial inflammatory activation but also a pivotal actor of the microvascular thrombotic complications of SCD, anti-VWF nanobodies may be a new therapeutic perspective in the most severe grades of this hemoglobinopathy.…”

“…1 The complex pathophysiology of SCD is multifactorial, including inflammatory vasculopathy resulting in a state of coagulation hyperactivation [5][6][7] and complement activation. [2][3][4] VOC/ACS/MOF may be worsened by thrombotic complications including venous thromboembolism and strokes 1,2,[5][6][7] and, more rarely, thrombotic microangiopathies (TMAs) like thrombotic thrombocytopenic purpura (TTP)-like syndrome 8,9 or even TTP, [10][11][12][13][14][15] a disease caused by the blood accumulation of the platelet-adhesive protein von Willebrand factor (VWF) secondary to a severe deficiency of its specific cleaving protease ADAMTS13. Among primary hemostasis actors, VWF was first established as a strong marker of SCD-related endothelial injury.…”