scholarly journals Rituximab for Prevention of Recurrent Pregnancy Related Thrombotic Thrombocytopenic Purpura in High Risk Patients with Previous Episodes of Thrombotic Thrombocytopenic Purpura during Pregnancy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4940-4940 ◽  
Author(s):  
Anusiyanthan Isaac Mariampillai ◽  
Michael Garrison ◽  
Alice A. Zervoudakis
Keyword(s):  
High Risk ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Post Partum ◽  
Blood Chemistry ◽  
Peripheral Smear ◽  
Thrombocytopenic Purpura ◽  
History Of ◽  
Suspected Recurrence ◽  
Risk Of Relapse

Abstract Introduction We describe the use of rituximab for the successful prophylaxis and delivery of a multiparous female with a history of pregnancy related thrombotic thrombocytopenic purpura (TTP) now presenting with a high risk of relapse during subsequent pregnancy. Case Presentation A 33 year-old African American female with a history of post-partum TTP diagnosed two years prior was referred to the hematology clinic for suspected recurrence of her TTP at 22 weeks gestation. Two years ago the patient had presented with symptoms of severe headache and hypertension which began 1 week after the delivery of her 3rd child. She was referred to the emergency department where she was found to have microangiopathic hemolytic anemia with a hemoglobin of 7.6g/dL, platelets of 10k/uL and abundant schistocytes on peripheral smear. Her blood chemistry revealed renal failure with an elevated creatinine of 2.7mg/dL, LDH of 2001 IU/L. She was found to have a moderately low ADAMTS13 level of 16% (normal >66%) and an inhibitor was detected (1.0 BEU). Her ANA, HIV, hepatitis and lupus serologies were all negative. Her C3 level was 105 (normal 70-225mg/dL) and C4 was 20 mg/dL (normal 14-55 mg/dL). She was promptly initiated on plasma exchange in addition to magnesium supplementation and strict blood pressure control. She underwent 11 days of daily plasma exchange and steroids with improvement of her platelets and resolution of schistocytes on peripheral smear. Despite this, she again had rise in her parameters and rituximab was added to the regimen which she responded to with continued normalization of her hematologic parameters and clinical resolution of symptoms. Approximately 2 years later, the patient presented again at 22 weeks gestation of her fourth pregnancy for suspected recurrence of her TTP. Blood chemistry revealed a low ADAMTS13 (<3%), anemia (Hb 10.8g/dL) and moderate thrombocytopenia (platelets 156k/uL). Her liver and renal functions were unaffected and she had no evidence of bruising or bleeding on physical exam. Serial repeat testing showed persistently low ADAMTS13 level (<3%) and worsening thrombocytopenia (platelets decreased to 113k/uL) without development of other clinical manifestation of TTP. Prophylactic plasma exchange was offered to the patient however the patient declined due to its associated risks. She was initiated on weekly rituximab (375mg/m2) with decadron (6mg weekly) from 27th to 30th weeks of pregnancy. After 4 infusions, her platelets improved to 190k/uL along with an increase in ADAMTS13 level to 62%. A healthy male child weighing 3.2 kilograms was delivered by C-section at 36 weeks without complications. Post-partum, the patient's CBC remained stable with platelets above 100k/dL along with her LDH, haptoglobin and renal function and was subsequently discharged with no further documentation of relapse in her TTP. Discussion TTP is a severe, and often life threatening condition characterized clinically by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, neurologic changes and fever. Pregnancy is a known trigger for onset of TTP and has been well described in literature, usually presenting in the third trimester or post-partum period with a constellation of symptoms that may mimic other thrombotic microangiopathies (Martin JN Jr, et al. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol.2008; 199(2):98-104). Recurrent TTP complicating subsequent TTP is uncommon (George. JN, et al.Blood, 2014; 123 (11):1674-1680). Patients with a history of pregnancy related TTP continue to be at high risk of relapse with subsequent pregnancies and their management often presents as a challenge to both hematologist as well as obstetricians . While plasma exchange and immunosuppression is a cornerstone of successful treatment of confirmed pregnancy related TTP, literature regarding optimal prophylaxis to prevent the onset of subsequent TTP in women with a history of pregnancy related TTP is lacking. Rituximab for the prevention of TTP relapse during pregnancy may be a viable option. Disclosures No relevant conflicts of interest to declare.

Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura

Blood ◽  
2014 ◽  
Vol 124 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Miguel Hie ◽  
Julie Gay ◽  
Lionel Galicier ◽  
François Provôt ◽  
Claire Presne ◽  
...  
Keyword(s):  
High Risk ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Relapse Rate ◽  
Thrombocytopenic Purpura ◽  
Key Points ◽  
History Of ◽  
Adamts13 Deficiency ◽  
Risk Of Relapse

Key Points Patients with a history of acquired TTP and persistent severe ADAMTS13 deficiency during remission are at high risk of relapse and death. Preemptive infusions of rituximab in remission significantly decrease TTP relapse rate.

scholarly journals Validation of the Plasmic Score for Predicting ADAMTS13 Activity < 10% in Patients Admitted to Hospitals in Alberta with Suspected Thrombotic Thrombocytopenic Purpura

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2379-2379 ◽  
Author(s):  
Chris Wynick ◽  
Joanne Britto ◽  
Daniel Sawler ◽  
Arabesque Parker ◽  
Mohammad Karkhaneh ◽  
...  
Keyword(s):  
High Risk ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Risk Score ◽  
Predictive Value ◽  
Clinical Pathways ◽  
Low Risk ◽  
Intermediate Risk ◽  
Thrombocytopenic Purpura ◽  
Adamts13 Deficiency

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy (TMA), characterized by widespread intravascular thrombosis. Diagnosis of TTP is confirmed by a deficiency in ADAMTS13. However, given the urgency of prompt diagnosis and delayed turnaround time of ADAMTS13 assay in most labs, initial diagnosis is based on clinical acumen. Suspected TTP is empirically treated with plasma exchange (PLEX), which, while beneficial in TTP, may delay appropriate treatment for similar disorders. The PLASMIC score was developed by Bendapudi et al. (Lancet Hematology 2017) to utilize clinical signs and investigations to predict which patients had an ADAMTS13 score < 10%, and therefore TTP, who require PLEX. Validation studies have shown a very high sensitivity (90-98%) and high specificity (46-92%), although these studies included an enriched population with available ADAMTS13 assay results (Jajosky et al. Transfusion and Apheresis Science, 2017, Li et al. Journal of Thrombosis and Hemostasis 2018). The purpose of this study is to validate the PLASMIC score using a Canadian population of suspected TTP regardless if ADAMTS13 was ordered, and compare it to clinical gestalt. This is a retrospective cohort study of all adults aged 18 years or older who presented or were transferred to any of the two apheresis centres in Alberta, Canada with a suspected diagnosis of TTP from January 1, 2008 - December 31, 2018. A confirmed diagnosis of TTP was defined as an ADAMTS13 level prior to PLEX < 10%, or ADAMTS13 level between 10-20% if drawn after plasma infusion or PLEX. ADAMTS13 testing was done in accordance with the procedures at these institutions. The PLASMIC score was used to stratify patients into low (0-4), intermediate (5) and high (6-7) risk of TTP (Table 1). Descriptive analyses was performed to examine the proportion of patients with low-, intermediate-, and high-risk PLASMIC score who had ADAMTS13 testing done and who received PLEX. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PLASMIC score were calculated. Two PLASMIC score cutoffs were used for the analysis, 1) high risk vs low to intermediate risk, and 2) intermediate to high risk vs low risk. Receiver operator curve (ROC) analysis was used to test the association between severe ADAMTS13 deficiency and the PLASMIC score. PLASMIC scores were also compared to clinical gestalt, defined as initiation of PLEX within 48 hours of presentation. The C statistic was calculated from the area under the ROC and compared using the Z-test. As some patients who may have died from TTP did not have ADAMTS13 level sent, sensitivity analysis was performed to assess the ROC curve for the PLASMIC score in detecting both definite and probable TTP. A P-value of <0.05 was considered statistically significant. Of the 162 cases of suspected TTP, 61 (38%) had severe ADAMTS13 <10%. ADAMTS13 was sent prior to plasma exchange in 103 (64%) cases and shortly after PLEX initiation in 15 (9%). Using a high-risk PLASMIC score cut-off (6-7) vs low to intermediate-risk score (0-5), the sensitivity was 83.6%, specificity 67.3%, PPV 60.7% and NPV 87.2%. In contrast, using a cut-off of medium to high-risk PLASMIC score (5-7) vs low-risk score (0-4), the sensitivity improved to 96.7%, whereas the specificity was reduced to 30.7% (PPV 45.7% and NPV 93.9%). The C-statistics were 0.75 (95% CI 0.69-0.82) and 0.64 (95% CI 0.59-0.69) using the high PLASMIC score and medium-high PLASMIC score cut-offs, respectively (Figure 1). In contrast to PLASMIC score-based risk stratification, clinical gestalt has a comparable sensitivity of 83.6%, but a much lower specificity of 38.9%. There was very low correlation between PLASMIC score and clinical gestalt (kappa 0.0883 (95% CI -0.03-0.21). In our cohort, a high-risk PLASMIC score successfully predicted patients with severe ADAMTS13 deficiency in a Canadian TMA population, with similar sensitivity and improved specificity compared to clinical gestalt. Integration of this scoring system into institutional clinical pathways should be considered to supplement clinician judgment and reduce costs. Disclosures No relevant conflicts of interest to declare.

Successful Pregnancy Outcome in 5 Patients with Thrombotic Thrombocytopenic Purpura.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3016-3016
Author(s):  
Marie Scully ◽  
Richard Starke ◽  
Richard Lee ◽  
Ian Mackie ◽  
Samuel J. Machin ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Pregnancy Outcome ◽  
Post Partum ◽  
Blood Film ◽  
Activity Levels ◽  
Laboratory Monitoring ◽  
Igg Antibodies ◽  
Successful Pregnancy ◽  
Thrombocytopenic Purpura ◽  
History Of

Abstract Pregnancy is an initiating event for acute thrombotic thrombocytopenic purpura (TTP). Patients with a history of TTP have a high risk of relapse during pregnancy with associated maternal and fetal morbidity/mortality. We report 5 TTP patients who underwent serial clinical and laboratory monitoring (haemoglobin, platelets, blood film, reticulocytes, lactate dehydrogenase (LDH), ADAMTS-13 activity and IgG antibodies) and treatment within a specialist obstetric/haematology clinic, resulting in successful pregnancy outcomes. Patients: Cases 1 and 2 presented with TTP in their first pregnancy and had second trimester fetal losses. Case 3 had four TTP relapses and soon after achievement of clinical remission became pregnant. Case 4 had a single acute episode of TTP 6 years prior to pregnancy and normal ADAMTS 13 activity at the onset of pregnancy. Case 5 presented with acute TTP and a left sided stroke at 16 weeks gestation. ADAMTS-13 activity was <5% at onset of pregnancy in cases 1–3 and at presentation of TTP during pregnancy in case 5. Only case 3 had IgG antibodies to ADAMTS13. Cases 1–3 received regular plasma exchange (PEX) every 2 weeks initially, starting during the first trimester, with ADAMTS 13 activity levels maintained >15% during pregnancy (range 15–78%, normal range 66–126%) by collagen binding assay. Case 4 had normal laboratory parameters, including serial ADAMTS 13 activity levels, throughout pregnancy, requiring no specific therapy for TTP. Case 5 received intensive PEX (84 procedures) and pulsed methylprednisolone during pregnancy. Rituximab (375mg/m2, weekly for 4 weeks) was given at 28 weeks gestation with no observed toxicity except asymptomatic transient neonatal neutropenia. All 5 cases continued low dose aspirin (75 mg daily) throughout pregnancy. Case 1 and 2 received prophylactic low molecular weight heparin (LMWH) and cases 3 and 5 received treatment doses of LMWH for pulmunory emboli and TTP associated stroke at presentation. Live healthy infants were delivered in all 5 cases in the third trimester (31–41 weeks). These data suggest successful pregnancy outcome is achievable in patients with a history of TTP/acute TTP with therapy based on close clinical and laboratory monitoring. Regular PEX in patients with a history of TTP and severely reduced ADAMTS 13 activity/IgG antibodies to ADAMTS 13 at the onset of pregnancy was associated with successful pregnancy outcome. Serial ADAMTS 13 activity and antibody levels during pregnancy and post-partum provided a useful adjunct to decision making on intensity of treatment.

Pregnancy-associated Thrombotic Thrombocytopenic Purpura: A Single Institution's Experience

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4675-4675
Author(s):  
Jordana Boro ◽  
Katerina Pavenski ◽  
John J. Freedman ◽  
Marie B. Garvey ◽  
Lisa K Hicks
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Conflicts Of Interest ◽  
Post Partum ◽  
First Trimester ◽  
Fresh Frozen Plasma ◽  
Blood Film ◽  
Intrauterine Death ◽  
Thrombocytopenic Purpura ◽  
Fresh Frozen

Abstract Abstract 4675 Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening form of microangiopathic hemolysis that can be associated with pregnancy. Although the association between TTP and pregnancy is well recognized, the presentation, natural history, and ideal treatment of TTP in this population remain poorly understood. St. Michael's Hospital is a regional referral centre for TTP in Ontario, Canada. We conducted a retrospective review of all cases of TTP referred to our pheresis unit between July 1993 and May 2010. Ninety-four cases were identified, of these, ten patients were pregnant or up to one week post-partum at the time of TTP diagnosis. Median age at presentation was 34 (29-36). Only one patient had been previously diagnosed with TTP and then developed a TTP relapse while pregnant. At presentation, all patients had thrombocytopenia (platelets: < 3 to 124 × 106/ml), anemia (hemoglobin: 60 to 99 mg/L), elevated LDH (1.3 to 12.5 × ULN), and fragmentation on blood film. ADAMTS13 was assessed in six of ten patients. It was normal in four patients, and deficient in two patients. Seven patients had neurological symptoms at presentation, one of whom suffered permanent right sided paralysis. Six patients had depressed glomerular filtration ratio (GFR) at presentation, four of these six recovered normal GFR. Hypertension was present in only one patient, and no patients had abnormal coagulation parameters at presentation. ALT was normal in six patients, mildly elevated in two patients, and unavailable in two patients. There were no patient deaths in this series. Patients were treated with a median of 17 plasma exchanges (range: 9 to 55) using either fresh frozen plasma or cryosupernatant. Eight patients achieved complete remission with plasma exchange. Two patients had refractory disease which ultimately responded to splenectomy and rituximab respectively. There were two fetal deaths, one a first trimester miscarriage, and the second an intrauterine death in the second trimester. In conclusion, in our series of pregnancy associated-TTP, there were no maternal deaths and most women responded to a short course of plasma exchange. ADAMTS13 deficiency was uncommon in our series. Nonetheless, in our series, TTP was not difficult to distinguish from preeclampsia and/or disseminated intravascular coagulation using routine laboratory parameters. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Exudative Retinal Detachment Treatment in a Patient with Thrombotic Thrombocytopenic Purpura

2016 ◽  
Vol 7 (1) ◽  
pp. 90-95 ◽  
Author(s):  
Magali Sampo ◽  
Gaëlle Ho Wang Yin ◽  
Louis Hoffart ◽  
Danièle Denis ◽  
Vincent Soler ◽  
...  
Keyword(s):  
Retinal Detachment ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Rare Complication ◽  
Exudative Retinal Detachment ◽  
Radiological Assessment ◽  
Rapid Improvement ◽  
Thrombocytopenic Purpura ◽  
History Of ◽  
Total Disappearance

Purpose: We report a case of unilateral exudative retinal detachment in a patient with thrombotic thrombocytopenic purpura (TTP), without associated hypertension, successfully treated with plasmapheresis. Case Report: A 46-year-old woman with a medical history of TTP presented with unilateral exudative retinal detachment. Biological and radiological assessment eliminated other causes of exudative retinal detachment, including hypertension. Plasma exchange was performed, followed by a rapid improvement in visual acuity and total disappearance of serous detachment. Conclusion: Exudative unilateral retinal detachment is a rare complication of TTP and can be successfully treated by plasma exchange.

scholarly journals Relapse of Immune Thrombotic Thrombocytopenic Purpura Following Vaccination with COVID19 mRNA Vaccine

TH Open ◽  
2021 ◽  
Vol 05 (03) ◽  
pp. e335-e337
Author(s):  
Katerina Pavenski
Keyword(s):  
Case Report ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Previous History ◽  
Therapeutic Plasma Exchange ◽  
Patient Treatment ◽  
High Dose ◽  
Thrombocytopenic Purpura ◽  
History Of

AbstractAn 84 year old male with a previous history of immune thrombotic thrombocytopenic purpura (iTTP) received the first dose of COVID19 mRNA vaccine (Pfizer-Biontech). Seven days later he was diagnosed with iTTP relapse. He received in-patient treatment with therapeutic plasma exchange, high dose steroids and rituximab and subsequently recovered. This case report highlights the need to monitor patients with iTTP following vaccination.

Disseminated Malignancy Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Report of 10 Patients and a Systematic Review of Published Cases.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1062-1062
Author(s):  
Kristin K. Francis ◽  
Nalini Kalyanam ◽  
Deirdra R. Terrell ◽  
Sara K. Vesely ◽  
James N. George
Keyword(s):  
Systematic Review ◽  
Bone Marrow ◽  
Platelet Count ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Bone Marrow Biopsy ◽  
Thrombocytopenic Purpura ◽  
History Of ◽  
History Of Cancer ◽  
Systemic Malignancy

Abstract Patients with disseminated malignancy who present with microangiopathic hemolytic anemia and thrombocytopenia may be misdiagnosed as thrombotic thrombocytopenic purpura (TTP), resulting in inappropriate plasma exchange treatment, a procedure with major risk, and delay of appropriate chemotherapy. We report the 17 year experience of The Oklahoma TTP-HUS Registry, 1989–2005, and a systematic review of previously published case reports. Ten of 335 consecutive patients in the Oklahoma Registry who were initially diagnosed with their first episode TTP and treated with plasma exchange were subsequently discovered to have disseminated malignancy; only one had a history of cancer. These 10 patients were compared to the 133 concurrent patients with idiopathic TTP. Disseminated malignancy (n=10) Idiopathic TTP (n=133) P Data are median values. P-value for neurologic symptoms compares distribution of abnormalities. Number of patients who had ADAMTS13 measured is in parentheses. 8 idiopathic TTP patients never had plasma exchange (PE). Age (years) 56 47 0.106 Sex (% female) 30% 73% 0.008 Duration of sx (days) 21 8 0.005 Presenting sx Weakness 70% 53% 0.347 cough, dyspnea 70% 26% 0.007 Fever 50% 31% 0.292 abdominal pain 40% 35% 0.745 Nausea/vomiting 20% 53% 0.052 Neurologic abnormalities Severe 20% 47% 0.128 Minor 60% 29% None 20% 24% Laboratory data hematocrit (%) 21 22 0.868 platelet count (103/ml) 21,000 13,000 0.328 creatinine (mg/dL) 2.4 2.0 0.761 LDH (U/L) 2894 1260 0.045 ADAMTS13 Median activity (%) 50(8) 23 (81) 0.167 &lt;5% activity (% of pts) 0 30% 0.102 Response to PE 10% 82% (125) &lt;0.001 Death (within 30 days) 90% 20% &lt;0.001 Patients with disseminated malignancy had a longer duration of symptoms, were more often men, had more frequent presence of respiratory symptoms, higher LDH levels, more often failed to respond to plasma exchange treatment, and had a higher mortality. Neurologic abnormalities, hematocrit, platelet count, and serum creatinine were not different between the two groups. Diagnosis of malignancy was made by bone marrow biopsy in 6 patients but not until autopsy in 2 patients. A systematic review identified 19 additional patients, reported from 1965 to 2005, in whom TTP or HUS was initially suspected and systemic malignancy subsequently discovered. Only 5 patients had a history of cancer. Malignancy was not diagnosed until autopsy in 6 patients. Fourteen different malignant disorders were diagnosed in these 29 patients. CONCLUSIONS: Disseminated malignancy may be occult and may mimic TTP. A search for systemic malignancy, including a bone marrow biopsy, is appropriate when patients diagnosed with TTP have atypical clinical features or fail to respond to plasma exchange.

Thrombotic Thrombocytopenic Purpura At the Cleveland Clinic 2000–2012: Review of 100 Cases and Identification of Prognostic Factors

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3325-3325
Author(s):  
Shruti Chaturvedi ◽  
Desiree Carcioppolo ◽  
Li Zhang ◽  
Keith R. McCrae
Keyword(s):  
Rheumatoid Arthritis ◽  
High Risk ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Cleveland Clinic ◽  
Neurological Symptoms ◽  
First Episode ◽  
Refractory Disease ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura

Abstract Abstract 3325 BACKGROUND AND OBJECTIVE: The advent of plasma exchange has led to a dramatic improvement in the survival of patients with Thrombotic Thrombocytopenic Purpura (TTP). However 10–20% of patients do not respond to plasma exchange and up to a third suffer relapses. Recent studies suggest that Rituximab as an adjunct to plasma exchange and corticosteroids may be effective in refractory or relapsing disease, although clinical factors that identify patients at high risk for poor outcomes have not been clearly defined. This concern prompted a retrospective review of all patients with TTP treated at the Cleveland Clinic over the last 12 years in an attempt to identify factors associated with poor prognosis. Records from all patients were reviewed from the date of initial presentation until at least two years afterwards to determine the incidence of refractory disease and relapse. STUDY AND METHODS: A total of 284 patients who were diagnosed with a first episode of thrombotic microangiopathy at the Cleveland Clinic from January 2000 to March 2012 were identified. Records from these patients were reviewed and individuals with other explanations for thrombocytopenia and hemolytic anemia such as DIC, hypertensive crisis or HELLP were excluded. One hundred patients were included in the final analysis. Fischer exact test and t- test were used to compare variables. A p value of <0.05 was considered significant. RESULTS: Of the 100 patients with TTP, 73% were female, with an age range of 16 to 79 years (median 49 years). Fifty percent of patients were Caucasian, 45% African American and 2% Hispanic. Sixty seven percent of cases occurred without predisposing conditions while 12% were associated with autoimmune disease (6 with SLE, 2 with rheumatoid arthritis, one with SLE and rheumatoid arthritis, and one each with Sjogren's syndrome, dermatomyositis and mixed connective tissue disorder), 8% with pregnancy or the postpartum state, 6% each with cancer and solid organ transplantation and 2% each with bone marrow and stem cell transplant. ADAMTS13 activity was tested in 57% of cases of which 36 (63%) had <5% and 21 (37%) had 8% to 56% activity, respectively. All patients were treated with plasma exchange, and all but 17 received corticosteroids, while some received additional therapies including vincristine (10), rituximab (15) and splenectomy (7) for refractory disease. Mortality after a first episode of TTP was 8%, while 13% of patients had exacerbations (within 30 days) and 18% had relapses (11 patients had a single relapse, 6 patients had 2 relapses and 1 had three relapses). Non survivors were older (p=0.042) with this association particularly striking for patients greater than age 60 (OR 8.75, 95% CI 2.32–33.01, p=0.002). Non-survivors also presented more frequently with severe neurological symptoms including obtundation, focal deficits and seizures (p=0.001). A higher LDH level after 1 or 2 cycles of plasma exchange, i.e. LDH on day 3, 4 or 5 of admission was also strongly associated with mortality (p<0.01) as well as with prolonged duration of plasma exchange. ADAMTS13 activity and levels of inhibitory anti-ADAMTS13 antibodies were comparable between survivors and non-survivors. However, undetectable ADAMTS13 levels were associated with a lower incidence of adverse renal outcomes including need for dialysis during the acute episode (p=0.007) and the development of chronic kidney disease (p=0.033) and/or end stage renal disease at 2 years (p=0.015). CONCLUSION: The most significant independent variables predicting death in TTP were increasing age, especially age>60, severe neurological symptoms at presentation and a persistently high LDH level the second day after diagnosis and initiation of plasma exchange. These variables could be used to identify patients who would benefit from close monitoring and potentially from early institution of adjunctive therapy. Treatment of high risk patients in this manner could limit the duration of plasma exchange, improve outcomes, and decrease associated morbidity and costs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Heparin-Induced Thrombocytopenia Complicating Thrombotic Thrombocytopenic Purpura

2017 ◽  
Vol 24 (1) ◽  
pp. 43-48
Author(s):  
Galila F. Zaher ◽  
Maha A. Badawi
Keyword(s):  
Pulmonary Embolism ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Therapeutic Plasma Exchange ◽  
Low Molecular Weight ◽  
Early Interventions ◽  
Thromboembolism Prophylaxis ◽  
Thrombocytopenic Purpura ◽  
Heparin Induced Thrombocytopenia ◽  
History Of

Since the introduction of therapeutic plasma exchange for the management of thrombotic thrombocytopenic purpura, the prognosis of this disease improved signifi cantly. Some patients suffer from refractory disease and adjunctive therapy needs to be considered. In addition, alternative explanations for thrombocytopenia may bepresent. In this report we discuss a patient who presented with typical fi ndings of thrombotic thrombocytopenic purpura and responded initially to therapeutic plasma exchange and steroids. Shortlyafterwards, his platelet count deteriorated and he was found to have acute pulmonary embolism. Prior to the pulmonary embolism, the patient had received venous thromboembolism prophylaxis in the form of low molecular weight heparin and had a history of previous exposure to unfractionated heparin. Testing for heparin-induced thrombocytopenia antibodies was positive and the patient was started on an alternative anticoagulant. Despite these early interventions the patient did not survive. It is essential that physicians be aware of such possible associations to request appropriate investigations and start appropriate management, accordingly.

Monitoring of ADAMTS13 in Patients with Thrombotic Thrombocytopenic Purpura: Prediction of Response to Therapy, Risk of Relapse, and Long- Term Outcome.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2291-2291 ◽  
Author(s):  
Paul Knoebl ◽  
Silvia Koder ◽  
Peter Schellongowski ◽  
Peter Distelmaier ◽  
Peter Quehenberger ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Clinical Signs ◽  
Response To Therapy ◽  
First Episode ◽  
Adamts13 Activity ◽  
Term Outcome ◽  
Thrombocytopenic Purpura ◽  
Long Term Outcome ◽  
Risk Of Relapse

Abstract A severely reduced ADAMTS13 activity due to inhibitory autoantibodies is a key feature of acquired thrombotic thrombocytopenic purpura (TTP), leading to the persistence of ultralarge VWF multimers, platelet aggregation and disturbance of microcirculation. We followed 39 patients (8 male, 31 female, mean age 38 years) with clinical signs of TTP over a period between 5 days to 16 years and observed a total of 53 episodes of TTP. ADAMTS13 was measured with a collagen-binding assay and the FRETS-VWF73 based Technozym ADAMTS-13 assay (activity and antigen, respectively). ADAMTS13 inhibitor was measured with a modified Bethesda method with both the above mentioned assays, and with the Technozym ADAMTS-13 INH ELISA. Thirty-one patients had autoimmune TTP, and 47 episodes of TTP were analyzed in these patients. In all acute episodes, ADAMTS13 activity was below the detection limit (&lt;0.05 U/ml), but ADAMTS13:Ag levels were below 0.1 U/ml only in 55% of the episodes. Anti-ADAMTS13 antibodies were detected in all episodes. Treatment consisted of plasma exchange (89% of the episodes), immunoadsorption (6%), steroids (70%), rituximab (15%), splenectomy (11%), aspirin (74%). Median time to platelet count normalization was 20 days (range 4–91 days), not related to the ADAMTS13-inhibitor titer. Platelet counts, LDH levels, and reticulocyte counts were better predictors of treatment response. Plasma exchange did not directly influence ADAMTS13 levels or clear the inhibitors. Three patients died during the first episode (myocardial infarction), one in 2nd relapse. ADAMTS13 activity increased &gt;0.2 U/ml in 66% of the episodes (after median 160 days). In the remaining cases anti-ADAMTS13 antibodies persisted during remissions for up to 2 years. In 3 cases the antibody reoccurred after initial normalization of ADAMTS13 activity, and clinical relapses followed. In total, 21 relapses were observed after a median of 46 months (range 1– 87), all associated with low ADAMTS13 levels. Rituximab was given in 7 cases of relapsing TTP and resulted in complete, durable clearance of the antibodies in 100%. Determination of ADAMTS13-related parameters is useful to distinguish between autoimmune, hereditary, and secondary forms of TTP and to choose an appropriate therapy. It is also useful to predict the risk of relapse in patients with TTP in remission.

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