Familial Thrombotic Thrombocytopenic Purpura in Three Siblings.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4042-4042
Author(s):  
Edyta Niewiadomska ◽  
Ulrich Budde ◽  
Klukowska Anna
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Clinical Symptoms ◽  
Fresh Frozen Plasma ◽  
Health Condition ◽  
Intestinal Bleeding ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Congenital Deficiency ◽  
Fresh Frozen

Abstract Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia, systemic platelet aggregation, organ ischemia, thrombocytopenia, and fragmentation of erythrocytes. The disease is caused either by congenital deficiency of von Willebrand factor-cleaving protease (ADAMTS 13) or due to acquired autoantibodies against ADAMTS 13. We have been treating three siblings with recurrent episodes of hemolytic anemia, thrombocytopenia, neurological and renal dysfunctions during last 10 years. The oldest brother presented with thromboangiopathic anemia, thrombocytopenia (platelets account below 30x103/μl), episode of unconsciousness, proteinuria and splenomegaly at the age of 15 years. Splenectomy was done with the improvement in thrombocytopenic purpura. But he has suffered from permanent microangiopathic hemolytic anemia, and developed renal insufficiency. He died due to intestinal bleeding last year. Two younger siblings, a 12 year old girl and an 11 year old boy also presented with recurrent symptoms of microangipathic hemolytic anemia and thrombopcytopenia with or without renal dysfunction since early childhood. The diagnosis of congenital TTP in this family was based on clinical symptoms and tests of ADAMTS 13 and its inhibitor. The activity of ADAMTS 13 in two younger siblings performed according to the method of Gerritsen et al. was unmeasurable (<3%, reference range 30 – 120%). The ADAMTS 13 inhibitor was undetectable. Both patients are treated with fresh frozen plasma (FFP) infusions every 4 weeks. Precise diagnosis is very important for proper treatment. Only regular FFP infusions as ADAMTS 13 supplementation can assure normal health condition of children with familial TTP.

scholarly journals Thrombotic Thrombocytopenic Purpura Associated with Mixed Connective Tissue Disease: A Case Report

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
João Tadeu Damian Souto Filho ◽  
Philipe Vianna de Barros ◽  
Aline Maria Yamaguti Rios Paes da Silva ◽  
Fernanda Alves Barbosa ◽  
Gustavo Fernandes Ribas
Keyword(s):  
Autoimmune Diseases ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Lupus Erythematosus ◽  
High Volume ◽  
Fresh Frozen Plasma ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Fresh Frozen ◽  
Frozen Plasma

Thrombotic thrombocytopenic purpura (TTP) is a multisystemic disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, which may be accompanied by fever, renal, or neurologic abnormalities. Cases are divided into acute idiopathic TTP and secondary TTP. Autoimmune diseases, especially systemic lupus erythematosus, in association with TTP have been described so far in many patients. In contrast, TTP occurring in a patient with mixed connected tissue disease (MCTD) is extremely rare and has only been described in nine patients. We describe the case of a 42-year-old female with MCTD who developed thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurological symptoms. The patient had a good clinical evolution with infusion of high volume of fresh frozen plasma, steroid therapy, and support in an intensive care unit. Although the occurrence of TTP is rare in MCTD patients, it is important to recognize TTP as a cause of thrombocytopenia and hemolytic anemia in any patient with autoimmune diseases. Prompt institution of treatment remains the cornerstone of treatment of TTP even if plasma exchange is not available like what frequently happens in developing countries.

scholarly journals Thrombotic Thrombocytopenic Purpura in Oman; Manifestations and Outcome. Retrospective Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5004-5004
Author(s):  
Khalid Nasser Al Hashmi ◽  
Samata Al Dowaiki
Keyword(s):  
Retrospective Study ◽  
Survival Rate ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Diagnostic Criteria ◽  
Hemolytic Anemia ◽  
Treatment Modalities ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Congenital Deficiency ◽  
Tertiary Center

Abstract Abstract: Background: Thrombotic Thrombocytopenic Purpura( TTP) is a rare life threatening disease. It is caused by congenital deficiency of metalloprotease ADAMTS -13 or acquired autoantibodies to this enzyme which normally cleaves vWF macromolecules. This results in Microangiopathic hemolytic anemia (haemolytic anemia, low platelets, and schiztocytes), systemic microvascular thrombi formation and subsequent end organ ischemia (renal and neurological manifestations). Nowadays the early recognition and treatment modalities resulted in survival rate reaching up to >=90%. So far, in Oman there have been no studies evaluating this rare disease. Aim: This is a retrospective study conducted in a tertiary center in Oman aims to describe the clinical and the demographic characteristics of Omani patients diagnosed of TTP, their remission rate, and survival. Methods:. We included all patients who were diagnosed between 2006 and 2018 who meet the diagnostic criteria of TTP and aged ≥ 12 years old. Data on patients' age, gender, region, ADAMTS-13 level, clinical presentation, lab results, treatment modalities and condition on discharge are described. Results: Total of 38 patients met diagnostic criteria of TTP during the study period. 25 Females (66%) and 13 Males (34%),with Female: Male ratio was 1.9:1. Age ranges between12-83 years (mean: 42 years). Mean age at onset: 36 years (range 1- 79 years). Majority of patients were from Governates Al-Batinah 39% and Muscat 21%. Clinical features in descending order of frequency: fever (63%), petechiae/ ecchymosis (31%), seizures (21%), high BP reading(21%), headache(15%) , confusion(15%), postpartum presentation(15%) and stroke (7.9%). The mean values at presentation are consistent with microangiopathic hemolytic anemia. Deranged RFT was found in 19 patients (50%), ADAMTS 13% was tested in 18 cases, congenital deficiency was found in 4 patients, deficiency due to autoantibodies was found in 7 patients. Treatment modality received were steroids and Plasma exchange (number of sessions ranges between 3-30 sessions, average 9 sessions). 19 cases required rituximab and 10 patients required cyclosporin. 5 patients (13%) had renal derangement requiring dialysis as inpatients, only 1 patient continued to dialyze after discharge. None of the 3 patients with documented stroke had neurological deficits on discharge. Patients who had seizures (3 patients) were free of seizures and on maintenance antiepileptic medications. Relapses after first presentation was noted in 7 patients (17%) with mean relapse ranges 1 to 7 years (mean of 3 years) after first presentation. There was 1 death with TTP in a relapsed Non- Hodgkin's lymphoma pateint. Overall survival rate was 97% at 10 years study period. Conclusion:This is the first study that demonstrates the demographic, clinical and survival rate of TTP patients in Oman, and provides a general picture of the TTP patients in our country Disclosures No relevant conflicts of interest to declare.

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 A Rare Case of Thrombotic Thrombocytopenic Purpura Caused by Acute Pancreatitis

2021 ◽  
Vol 51 (2) ◽  
Author(s):  
Emin Gemcioglu ◽  
Mehmet Kayaalp ◽  
Merve Caglayan ◽  
Ahmet Ceylan ◽  
Mehmet Sezgin Pepeler
Keyword(s):  
Renal Failure ◽  
Acute Pancreatitis ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Neurological Disorders ◽  
Rare Case ◽  
Rare Complication ◽  
Microangiopathic Hemolytic Anemia ◽  
Peripheral Smear ◽  
Thrombocytopenic Purpura

Thrombotic Thrombocytopenic Purpura is a syndrome of microangiopathic hemolytic anemia accompanied by thrombocytopenia, neurological disorders, renal failure and fever. Acute pancreatitis is a rare cause of Thrombotic Thrombocytopenic Purpura and this manifestation, at the same time, is a rare complication of acute pancreatitis. Thrombotic Thrombocytopenic Purpura is induced in acute pancreatitis by poorly understood mechanism, which involves multiple pathways apart from only ADAMTS-13 deficiency. Here, we analyze the case of a 47-year-old female who presented with an acute pancreatitis. She was diagnosed with Thrombotic Thrombocytopenic Purpura and an acute pancreatitis at the same time, with thrombocytopenia and peripheral smear findings at presentation. Therefore, Thrombotic Thrombocytopenic Purpura secondary to the pancreatitis was considered in this case. In this work, we have discussed details of our case and the different mechanisms involved in pathogenesis of Thrombotic Thrombocytopenic Purpura in acute pancreatitis and their outcome with prompt management.

scholarly journals Thrombotic Thrombocytopenia Purpura Case Series in Skmc 2016-2017

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4799-4799
Author(s):  
Mohamed Abu Haleeqa ◽  
Hanan Al Raeesi ◽  
Fatima Alkaabi
Keyword(s):  
Renal Failure ◽  
Mortality Rate ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Case Series ◽  
Therapeutic Plasma Exchange ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Patient Reported

Background and Purpose Thrombotic thrombocytopenic purpura (TTP) is a heterogeneous disease primarily characterized by thrombocytopenia and microangiopathic hemolytic anemia. Therapeutic plasma exchange has dramatically improved mortality, allowing for emergence of refractory, relapsing, and atypical presentations. in this case series we aim to present our institutional data for Apheresis in Sheikh khalifa medical City in AbuDhabi. We will also present patient demographic and clinical presentation and treatment protocol we use Methodology -Case series with Retrospective review. -Routine laboratory tests such as peripheral blood cell counts, reticulocyte count, coagulation profile, serum lactate dehydrogenase (LDH), bilirubin, serum creatinine, cardiac enzymes, and urinalysis, were performed. -ADAMTS13 levels and inhibitor titer were determined for all patient in outside lab -Baseline demographic characteristics were calculated in frequencies and percentages. (include age ,Gender , clinical manifestations and treatment strategy) Results and Discussions thrombotic thrombocytopenic purpura (TTP) pentad consisting of fever, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurological abnormalities, and renal failure. less than 5 % of patient reported in literature have all associated clinical features. -Total of 10 patients M:F 4:2 , Median Age 44yr 50% presented with Neurological manifestations and renal disease , 30% presented with Fever only 20% had cardiac manifestation on admission . None of the patient presented with all 5 pentad. -All patients received TPE , steroid . -90 % of the patients received Rituximab except for 1 because of Allergy. -All patients has low ADAMTS 13 , except one has normal ADAMTS13 but came with relapse and on first admission had low ADAMTS13 -All patient presented with MAHA and TCP except 2 patient whom had normal Hb but significant schistocytes on peripheral blood with TCP both patient where relapsed cases. -3 patient were relapsed 7 de novo , the 3 relapsed cases all did not receive Rituximab in first remission . One of them relapsed twice but did not received Rituximab due to allergy -Although some publication include large number of TTP patients, but only few case reports have evaluated the clinical feature, laboratory parameters and therapeutic outcome of TTP. Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange (TPE) mortality decreases to about 10%-20%. A disintegrin and metalloprotease with thrombospondin Type 1 motif, Member 13 (ADAMTS13) levels less than 5% are a hallmark of TTP. We do ADAMTS 13 Activity and inhibitor titre levels in outside facility TAWAM hospital with turn-around time of 7 days which is helpful in planning Rituximab treatment. with availability of Rituximab our relapse rates are low but not zero Conclusions -Thrombotic thrombocytopenic purpura (TTP) pentad consisting of fever, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurological abnormalities, and renal failure. -5 % of patient reported in literature have all associated clinical features. -We found that majority of patient presented with evidence of thrombocytopenia and MAHA only. -Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange (TPE) mortality decreases to about 10%-20%. -TPE ,steroid and rituximab was very effective in achieving sustain remission in 100% of ours patients with median follow up 8 month -More awareness is needed for early diagnosis and early referral to centers with appropriate tertiary care facilities. Figure Disclosures No relevant conflicts of interest to declare.

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