scholarly journals Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management

2021 ◽  
Vol 10 (3) ◽  
pp. 536
Author(s):  
Senthil Sukumar ◽  
Bernhard Lämmle ◽  
Spero R. Cataland
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Initial Therapy ◽  
Fresh Frozen Plasma ◽  
Organ Injury ◽  
Severe Thrombocytopenia ◽  
Front Line ◽  
Thrombocytopenic Purpura ◽  
Fresh Frozen ◽  
Biallelic Mutations ◽  
Line Setting

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemic end organ injury due to microvascular platelet-rich thrombi. TTP results from a severe deficiency of the specific von Willebrand factor (VWF)-cleaving protease, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13). ADAMTS13 deficiency is most commonly acquired due to anti-ADAMTS13 autoantibodies. It can also be inherited in the congenital form as a result of biallelic mutations in the ADAMTS13 gene. In adults, the condition is most often immune-mediated (iTTP) whereas congenital TTP (cTTP) is often detected in childhood or during pregnancy. iTTP occurs more often in women and is potentially lethal without prompt recognition and treatment. Front-line therapy includes daily plasma exchange with fresh frozen plasma replacement and immunosuppression with corticosteroids. Immunosuppression targeting ADAMTS13 autoantibodies with the humanized anti-CD20 monoclonal antibody rituximab is frequently added to the initial therapy. If available, anti-VWF therapy with caplacizumab is also added to the front-line setting. While it is hypothesized that refractory TTP will be less common in the era of caplacizumab, in relapsed or refractory cases cyclosporine A, N-acetylcysteine, bortezomib, cyclophosphamide, vincristine, or splenectomy can be considered. Novel agents, such as recombinant ADAMTS13, are also currently under investigation and show promise for the treatment of TTP. Long-term follow-up after the acute episode is critical to monitor for relapse and to diagnose and manage chronic sequelae of this disease.

Rituximab in Chronic Relapsing Acquired Thrombotic Thrombocytopenic Purpura.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3997-3997
Author(s):  
Gaetano Giuffrida ◽  
Amalia Figuera ◽  
Rocca Cingari ◽  
Santo Maccarone ◽  
Ernesto Di Francesco ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Intravenous Immunoglobulins ◽  
Fresh Frozen Plasma ◽  
Additional Treatment ◽  
Treatment Modalities ◽  
First Episode ◽  
Thrombocytopenic Purpura ◽  
Fresh Frozen ◽  
Platelet Aggregates ◽  
Von Willebrand

Abstract Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, renal failure and neurological manifestation. It is caused by a severe decreased of Von Willebrand factor cleaving protease activity (ADAMTS-13), leading to persistence of unusually ultra-large Von Willebrand multimers (ULVWF) in the circulation that bind to platelets, causing platelet aggregates, microangiopathic hemolysis and thrombocytopenia. A lack of ADAMTS-13 activity can be caused by autoimmune inhibitors or may be due to a constitutional deficiency of this protein. Recently, the ADAMTS-13 gene that encodes for the ADAMTS-13 protein was found. It was mapped to chromosome 9q34 and consists of 29 exons. Several mutations has been identified in the ADAMTS gene in patient with the congenital form of TTP. Although TTP usually occurs as an acquired form due to autoantibodies against ADAMTS-13. The determination of the activity of ADAMTS-13 and of antibodies against ADAMTS-13 are important part in the workup of patients with TTP. Plasma exchange (PE) with fresh frozen plasma replacement is the standard treatment in the acquired TTP. The efficacy of PE is likely due to the removal of both antibodies and ULVWF and the infution of ADAMTS-13. Additional treatment modalities include glucocorticoids, splenectomy, vincristine, cyclophosphamide, azathioprine, cyclosporin A, combination chemotherapy, intravenous immunoglobulins and, recently, rituximab, a monoclonal antibody against CD20 present on B-limphoid cells. We report a case of chronic relapsing acquired idiopathic TTP successfully treated with rituximab. The patient, an 50-year old woman, developed her first episode of TTP in May 2001. Remission was achieved after 12 sessions of PE, four dose of vincristine at dose of 0,02 mg/kg/die, corticosteroids at dose of 1 mg/kg/die and increased dose of prociclide from 10 to 60 mg /kg/die. From 2001 to 2004, she had six relapses responding to treatment with PE, vincristine, and corticosteroids. The relapse in 2004 was followed by a protracted course despite the addition of cyclosporine A and she become dependent on PE. On May 2004 she was treated with splenectomy. The postoperative course was uneventful. The inhibitors against ADAMTS-13 disappared, but after 8 months the patient relapsed and received six PE and corticosteroids, and then rituximab therapy (four doses of 375 mg/mq weekly). ADAMTS-13 activity and inhibitor levels were monitored. ADAMTS-13 activity was initially, pre-rituximab,<6% (n.v. 46–160%) and inhibitor’s titre against ADAMTS-13 was 12 U/ml (n.v. <1 U/ml). After rituximab, the inhibitor against ADAMTS-13 disappeared rapidly after one month, while ADAMTS-13 activity has remained very low (<6%). After six months from rituximab therapy, there wasn’t full recovery of ADAMTS-13 activity. Follow up is now 6 months, responses are manteined, ADAMTS-13 activity has remained <6% and inhibitors have not reappeared. Our experience suggests that rituximab, by eliminating an important source of B-lymphocytes producing inhibitory ADAMTS-13 autoantibodies, may be a useful immunomodulating adjunct in the treatment of refractory chronic relapsing acquired TTP, before than others immunosoppressors and/or splenectomy.

scholarly journals Congenital thrombotic thrombocytopenic purpura presenting in adulthood with recurrent cerebrovascular events

2019 ◽  
Vol 12 (10) ◽  
pp. e229481
Author(s):  
Emma Tenison ◽  
Ashar Asif ◽  
Mathew Sheridan
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Fresh Frozen Plasma ◽  
Vessel Occlusion ◽  
Thrombocytopenic Purpura ◽  
Antibody Titres ◽  
Fresh Frozen ◽  
Life Threatening ◽  
History Of ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
A Disintegrin And Metalloproteinase

Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, life-threatening disease, characterised by episodes of microangiopathic haemolytic anaemia (MAHA), thrombocytopenia and small vessel thrombosis. We describe a case of cTTP first diagnosed at age 70 years in a female presenting with an acute ischaemic stroke and thrombocytopenia, in whom A Disintegrin And Metalloproteinase with a Thrombospondin type 1 Motif, member 13 (ADAMTS13) levels were <10%, suggestive of thrombotic thrombocytopaenic purpura (TTP). The patient underwent plasma exchange and started rituximab for presumed immune TTP; however, anti-ADAMTS13 antibody titres were negative on two occasions. This, together with a history of pregnancies complicated by presumed disseminated intravascular coagulation, and two previous episodes of sepsis with MAHA, prompted investigation for cTTP, which was confirmed by genetic testing. Despite treatment with infusions of solvent/detergent-treated, virus-inactivated fresh frozen plasma, she has re-presented with further neurological deficit, associated with new infarcts on imaging. cTTP has a varied phenotype which, as demonstrated in this case, can include large vessel occlusion.

Cryosupernatant and Solvent Detergent Fresh Frozen Plasma (Octaplas, Octapharma) Usage in Acute Thrombotic Thrombocytopenic Purpura-Review of 50 Episodes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4139-4139
Author(s):  
Marie Scully ◽  
Michael Flynn ◽  
Jenny Berryman ◽  
Samuel J. Machin
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Fresh Frozen Plasma ◽  
Severe Allergic Reaction ◽  
Central Vein ◽  
Allergic Reactions ◽  
Refractory Disease ◽  
Thrombocytopenic Purpura ◽  
Significant Difference ◽  
Fresh Frozen ◽  
Frozen Plasma

Abstract Thrombotic thrombocytopenic purpura (TTP) is an acute, life threatening disorder. The mainstay of treatment is plasma exchange (PEX) as a source of ADAMTS 13. In the UK, 20–25% of all plasma consumed is in patients with TTP. In our protocol (up until 31st December 2005) apheresis was initially with cryosupernatant (National Blood Service, UK) unless patients had a previous severe allergic reaction or refractory disease. Apheresis therefore continued with Solvent-Detergent Fresh Frozen Plasma (S/D FFP) Octaplas, (Octapharma, Vienna Austria) virally inactivated plasma, available throughout Europe. We reviewed 50 acute TTP episodes involving 32 patients. Thirteen episodes used cryosupernatant only and in 15 episodes, treatment started with cryosupernatant and changed to Octaplas. The reasons for changing were refractory disease in 2 episodes and major or recurrent allergic reactions to cryosupernatant in 13 cases. Once Octaplas had been used, it was continued on further admissions. In 22 episodes, Octaplas was used exclusively; in 4 cases as physicians choice and in the remaining due to previous reactions to cryosupernatant. The total volume of cryosupernatant used was 508250mls, 27.6% of all plasma; total volume of Octaplas was 1327600mls, 72.4% of all plasma. Citrate mediated reactions associated with symptomatic hypocalcaemia during apheresis were present in 11% of Octaplas and 20% of cryosupernatant. Acute or delayed urticarial or allergic reactions were noted in 5% of Octaplas and 10% cryosupernatant procedures. A particular complication of apheresis is central line infection. There were 21 line infections and in 43% of cases the infection was associated with a reduction in platelet count < 150 × 109/L. In all 50 episodes, the only documented thrombosis was a superficial non central vein in a patient who had received Octaplas. Prevention of venous thrombosis is by use of thromboembolic stockings, low dose aspirin and low molecular weight heparin in patients when platelet counts >50 × 109/L. In episodes receiving only cryosupernatant or Octaplas, there was no significant difference in the median number of PEX to remission, 7(3–14) and 8.5 (5–30) respectively. Baseline viral screen in all episodes was negative after discharge following an acute TTP episode. In conclusion: cryosupernatant and S/D FFP (Octaplas) appear equally efficacious. However, the risk of allergic/urticarial reactions was twice as common with cryosupernatant, as were citrate reactions. Milder allergic reactions to cryosupernatant are possibly higher, but may have been treated with antihistamines and data not recorded. There was no documented viral transmission with either product.

scholarly journals Combination of Fresh Frozen Plasma and Cryosupernatant Plasma for Therapeutic Plasma Exchange in Thrombotic Thrombocytopenic Purpura: A Single Institution Experience

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Qiuyan Lin ◽  
Liping Fan ◽  
Haobo Huang ◽  
Feng Zeng ◽  
Danhui Fu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Fresh Frozen Plasma ◽  
Therapeutic Plasma Exchange ◽  
Dominant Group ◽  
Thrombocytopenic Purpura ◽  
Replacement Fluid ◽  
Fresh Frozen ◽  
Frozen Plasma

Purpose. To evaluate the impact of a combination of fresh frozen plasma (FFP) and cryosupernatant plasma (CP) as a replacement fluid in therapeutic plasma exchange (TPE) on early therapeutic response and long-term survival of patients with thrombotic thrombocytopenic purpura (TTP). Materials and Methods. A total of 44 patients with suspected TTP were screened by Bentley and PLASMIC scores. Twenty-seven patients treated with TPE using the FFP and CP combination as the replacement fluid were enrolled and divided into two groups: 11 patients who received TPE with CP-dominant replacement fluid (FFP/CP<1) and 16 patients who received TPE with FFP-dominant replacement fluid (FFP/CP>1). Results. There were no significant differences in the demographic and clinicopathological characteristics between the two groups except for the international normalized ratio (INR). The number of TPE procedures was lower, and time to achieve complete response was shorter in the CP-dominant group than in the FFP-dominant group. There were no significant differences in overall survival between the two groups. Conclusion. The CP-dominant replacement fluid was superior to the FFP-dominant replacement fluid in early response to TPE in patients with TTP, but did not impact the patients’ overall survival.

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