Vincristine sulfate for the treatment of thrombotic thrombocytopenic purpura refractory to plasma‐exchange

Bobbio-Pallavicini, E; Porta, Camillo; Centurioni, Riccardo; Gugliotta, Luigi; Vianelli, Nicola; Tacconi, F; Billio, Atto; Ascari, E

doi:10.1111/j.1600-0609.1994.tb00649.x

Cited by 59 publications

(22 citation statements)

References 21 publications

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“…The platelet count began to increase reaching 65,000 /mm³ after 3 days of starting VCR and 175,000 /mm³ after 8 days. The total dose of VCR given to the patient was 4 mg without apparent side effects and this agrees with some studies using doses ranging from 2 mg up to 14 mg (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Ziman et al, reported 100 percent survival in their retrospective data of 12 TTP patients (PLT counts ranging 4,000/mm³ to 36,000/mm³) treated with standardized protocol of PE and VCR without side effects.…”

Section: Discussionsupporting

confidence: 69%

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Thrombotic Thrombocytopenic Purpura Refractory to Plasmapheresis Treated Successfully with Vincristine: A Case Report

Elrewihby¹,

Zaghloul²,

Saber³

et al. 2017

J Blood Disord Transfus

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Section: Discussionsupporting

confidence: 69%

“…Successful vincristine use has been described in various small studies and case reports, usually as a rescue therapy in refractory TTP [17,[24][25][26][27][28][29][30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Thrombotic Thrombocytopenic Purpura Refractory to Plasmapheresis Treated Successfully with Vincristine: A Case Report

Elrewihby¹,

Zaghloul²,

Saber³

et al. 2017

J Blood Disord Transfus

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“…For example, in the 1980s, 3 patients with chronic TTP were described as having very low levels of a serum prostacyclin-binding activity, 33 which was later identified as ApoA-I. 34 Although treatment of plasmapheresis-resistant TTP patients with prostacyclin homologs was unsuccessful, 35 the association of low ApoA-I levels with TTP has not been explained; our results suggest that the reduced ApoA-I levels in patients with TTP and sepsis may worsen these disorders. Replenishment of HDL may contribute to the effectiveness of plasmapheresis in the treatment of TTP in addition to providing ADAMTS13 and For personal use only.…”

Section: Discussionmentioning

confidence: 83%

High-density lipoprotein modulates thrombosis by preventing von Willebrand factor self-association and subsequent platelet adhesion

Chung

Chen

Ling

et al. 2016

Blood

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• High-density lipoprotein and its major apolipoprotein ApoA-I prevent von Willebrand factor self-association. • Targeting von Willebrand factor self-association could be a new approach to treating thrombotic disorders.The ability of von Willebrand factor (VWF) to initiate platelet adhesion depends on the number of monomers in individual VWF multimers and on the self-association of individual VWF multimers into larger structures. VWF self-association is accelerated by shear stress. We observed that VWF self-association occurs during adsorption of VWF onto surfaces, assembly of secreted VWF into hyperadhesive VWF strings on the endothelial surface, and incorporation of fluid-phase VWF into VWF fibers. VWF adsorption under static conditions increased with increased VWF purity and was prevented by a component of plasma. We identified that component as high-density lipoprotein (HDL) and its major apolipoprotein ApoA-I. HDL and ApoA-I also prevented VWF on the endothelium from self-associating into longer strands and inhibited the attachment of fluid-phase VWF onto vessel wall strands. Platelet adhesion to VWF fibers was reduced in proportion to the reduction in selfassociated VWF. In a mouse model of thrombotic microangiopathy, HDL also largely prevented the thrombocytopenia induced by injection of high doses of human VWF. Finally, a potential role for ApoA-I in microvascular occlusion associated with thrombotic thrombocytopenic purpura and sepsis was revealed by the inverse relationship between the concentration of ApoA-I and that of hyperadhesive VWF. These results suggest that interference with VWF self-association would be a new approach to treating thrombotic disorders. are characterized by systemic endothelial activation and microvascular occlusion. In recent studies, von Willebrand factor (VWF) secreted from the endothelium as a result of systemic endothelial activation has been shown to contribute to microvascular dysfunction and occlusion. A portion of the newly secreted VWF remains attached to the endothelial surface, from which it is normally removed through cleavage by the plasma metalloprotease ADAMTS13. 6 However, when ADAMTS13 is inhibited, as during episodes of TTP, or when VWF removal is delayed, as in conditions of intense inflammation such as sepsis and malaria, 7 the secreted VWF self-associates into long, thick strands that bind platelets to form occlusive thrombi in the small blood vessels. 6 VWF synthesis is a complex process. VWF homodimers first form in the endoplasmic reticulum through disulfide bonds involving cysteine residues near the VWF carboxyl terminus. In the Golgi apparatus, these dimers are linked together into chains through disulfide bonds at the amino termini, producing a ladder of multimeric molecules, each differing from the next largest by the molecular mass of a VWF dimer. The largest multimers found in blood can be enormous, reaching a molecular mass of more than 20 million Da. These gargantuan molecules can form even larger structures by associating with other VWF multime...

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“…[59][60][61] The side-effect profile includes mild peripheral paresthesias, muscle weakness, paralytic ileus, leukopenia, and transient alopecia. 62 Vincristine may work better when used in the initial treatment of patients with TTP, rather than for treating refractory patients.…”

Section: Cyclophosphamide and Vincristinementioning

confidence: 99%

How I treat refractory thrombotic thrombocytopenic purpura

Sayani¹,

Abrams

2015

Blood

145

143

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Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA) without an obvious cause, and may include fever, mild renal failure, and neurologic deficits. It is characterized by a deficiency of the von Willebrand factor (VWF) cleaving enzyme, ADAMTS13 (a disintegrin and metalloproteinase, with a thrombospondin type 1 motif, member 13), resulting in formation of microthrombi in the high sheer environment of the microvasculature. This causes microvascular occlusion, MAHA, and organ ischemia. Diagnosis is based on the presence of clinical symptoms, laboratory aberrations consistent with MAHA, decreased ADAMTS13 activity, and possibly presence of anti-ADAMTS13 autoantibodies. Upfront treatment of acute TTP includes plasma exchange and corticosteroids. A significant number of patients are refractory to this treatment and will require further interventions. There are limited data and consensus on the management of the refractory TTP patient. Management involves simultaneously ruling out other causes of thrombocytopenia and MAHA, while also considering other treatments. In this article, we describe our management of the patient with refractory TTP, and discuss use of rituximab, increased plasma exchange, splenectomy, and immunosuppressive options, including cyclophosphamide, vincristine, and cyclosporine. We also review recent evidence for the potential roles of bortezomib and N-acetylcysteine, and explore new therapeutic approaches, including recombinant ADAMTS13 and anti-VWF therapy. (Blood. 2015;125(25):3860-3867) Case A 25-year-old previously healthy woman presented with a 3-day history of fatigue, nausea, abdominal pain, and easy bruising. She was alert, oriented, afebrile, had mild abdominal tenderness, and purpura on her extremities. Her hemoglobin was 8.4 g/dL; platelets, 15 3 10 9 /L; creatinine, 1.1 mg/dL; and her lactate dehydrogenase and reticulocytes were increased. Schistocytes and nucleated red blood cells were easily seen on her peripheral blood smear. In the absence of other obvious precipitators of thrombocytopenia and microangiopathic hemolytic anemia (MAHA), she was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP). Blood samples were sent for ADAMTS13 (a disintegrin and metalloproteinase, with a thrombospondin type 1 motif, member 13) activity and inhibitor levels, and the patient was immediately started on plasma exchange (PEX) and prednisone 1 mg/kg per day. She responded well initially, and her platelets rose to 105 000/mL on day 4. However, on day 5, she was febrile and her platelets dropped to 40 000/mL. BackgroundAcquired TTP was initially characterized by thrombocytopenia, MAHA, renal failure, neurologic deficits, and fever. However, it is now well accepted that neither renal failure nor high fevers are key diagnostic features. Thrombocytopenia and MAHA are required for diagnosis when TTP is suspected. TTP is a hematologic emergency, with a mortality of 90% if untreated. Treatment with PEX and cortico...

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Vincristine sulfate for the treatment of thrombotic thrombocytopenic purpura refractory to plasma‐exchange

Cited by 59 publications

References 21 publications

Thrombotic Thrombocytopenic Purpura Refractory to Plasmapheresis Treated Successfully with Vincristine: A Case Report

Thrombotic Thrombocytopenic Purpura Refractory to Plasmapheresis Treated Successfully with Vincristine: A Case Report

High-density lipoprotein modulates thrombosis by preventing von Willebrand factor self-association and subsequent platelet adhesion

How I treat refractory thrombotic thrombocytopenic purpura

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