Thrombotic Thrombocytopenic Purpura In Pregnancy Research Articles

Thrombotic Thrombocytopenic Purpura in Pregnancy Presented with Stroke at 29 Weeks: A Case Report

Thrombotic Thrombocytopenic Purpura in Pregnancy Presented with Stroke at 29 Weeks: A Case Report

Acute vision loss as an initial manifestation of thrombotic thrombocytopenic purpura in pregnancy: a case report

Acute vision loss as an initial manifestation of thrombotic thrombocytopenic purpura in pregnancy: a case report

A safe and effective use of caplacizumab in pregnancy-related acquired thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is not uncommonly seen in pregnancy, either with the first episode or with the exacerbation of known disease. The management of TTP in pregnancy can be challenging if there is refractoriness to the use of therapeutic plasma exchange (TPE) and high-dose corticosteroids. Caplacizumab, a vWF-directed humanized antibody fragment, is approved for the treatment of acquired TTP but there is sparse data on its use in pregnant patients. Antenatal and peripartum haemorrhage is a theoretical concern with the use of the medication in the obstetric population. However, as options for treatment of TTP in the patients who have refractory disease are significantly limited, off-label use of caplacizumab to achieve disease control and prevent maternofetal morbidity and mortality is a reasonable consideration. This article described the successful use of caplacizumab in a pregnant patient with acquired TTP and the associated favourable outcome. The patient suffered an exacerbation following initial TPE and became refractory to both plasma exchange and high-dose corticosteroids. Off-label use of caplacizumab resulted in hematologic recovery and successful delivery of a healthy neonate. This case represents a contribution to the sparse literature on the use of this effective medication in an often-challenging clinical situation.

Thrombotic thrombocytopenic purpura in pregnancy. Giving birth or not giving birth, that is the question

Introduction. Pregnancy is one of the most frequent triggers of congenital and acquired forms of thrombotic thrombocytopenic purpura (TTP).Aim — to develop tactics for the treatment of pregnant women with TTP.Results. TTP was associated with pregnancy in 55.5 % of all cases of TTP in women. In 5 pregnancies in which the diagnosis of TTP was known before pregnancy, or established in the early stages, TTP was treated throughout the pregnancy. In the congenital form, plasma transfusions were performed once every two weeks until the 20th week of pregnancy, or weekly, if thrombocytopenia < 150 × 109 /L persisted. Plasma transfusions were performed weekly after the 20th week with the goal of achieving clinical remission. With acquired TTP, glucocorticosteroids and plasma exchanges were used as treatment, in 1 case — rituximab, with the aim of achieving a clinical remission and an ADAMTS13 activity > 20 %. In this group of pregnant women, 1 caesarean section was performed and there were 4 cases of vaginal deliveries, with a total of 5 children being born with an average Apgar score of 7.5. In 7 pregnancies in which TTP fi rst manifested late, leading to a delayed diagnosis, preventive and curative measures were not carried out before delivery. In this group there were 2 abortions of pregnancy, 5 surgical deliveries, 3 cases of preeclampsia, 3 acute cerebral circulatory disorders, 1 intraabdominal bleeding, 1 case of acute renal failure, with two women undergoing mechanical ventilation. There was 1 case of antenatal fetal death, with a total of 4 children being born, who were assessed on the Apgar scale with an average of 5 points.Conclusion. Timely diagnosis as well as ongoing therapeutic and preventive measures help to avoid complications during childbirth in pregnant women with TTP.

Rituximab related non-infectious lung injury complicating treatment of severe TTP in pregnancy – literature review and case-report

Background: Thrombotic thrombocytopenic purpura (TTP) in pregnancy is a rare but potentially life-threatening condition. Management of severe, refractory TTP during pregnancy is challenging and includes multidisciplinary approach. The prognosis of cases with a variety of hematological and autoimmune diseases, including TTP has changed profoundly after the rituximab therapy was introduced into clinical practice. However, adverse pregnancy outcomes associated with biological agents should be kept in mind and the decision to treat should be weighed by measurement of potential risks vs benefits. Case report: We reported the first documented case of noninfectious lung toxicity in pregnancy related to rituximab use for TTP treatment. 26 y/o patient at 23 weeks gestation initially presented to ED secondary to numbness, headache, and slurred speech with negative brain imaging. Her laboratory findings revealed severe deficiency of platelets, hemoglobin and ADAMT13 activity. She underwent multiple therapeutic interventions including plasmapheresis, intravenous immunoglobulins (IVIG), prednisone, and eventually required more often hospitalizations. Ultimately, the decision was made to proceed with rituximab therapy. After the third infusion of rituximab, she developed non-infectious lung injury without evidence of SARS-CoV-2 or other infections, pulmonary edema, or pulmonary embolism. The maternal condition worsened acutely resulting in significant desaturation that required intubation and eventual emergent premature delivery at 31-weeks’ gestation via C-section. Conclusion: Rituximab therapy for TTP management in pregnancy may be associated with significant adverse maternal-fetal outcomes. Risks and benefits of treatment should be discussed with each patient and during multidisciplinary communications. Physicians should maintain high index of suspicion for non-infectious lung injury associated with rituximab treatment in order to be able to diagnose this complication early and start treatment to avoid severe mortality and morbidity.

Unfolding the pathophysiology of congenital thrombotic thrombocytopenic purpura in pregnancy: lessons from a cluster of familial cases

Thrombotic thrombocytopenic purpura (TTP), a rare, potentially life-threatening thrombotic microangiopathy, manifests either as congenital TTP or acquired forms. It is caused by the absence or severe depletion of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) protease, leading to the accumulation of ultra large von Willebrand factor multimers as well as extensive platelet adhesion and clumping, which can ultimately cause severe secondary end-organ damage. Pregnancy can provoke or exacerbate TTP, leading to maternal and fetal complications. In this report, we focused on pregnancy outcomes in a recently recognized cohort of congenital TTP patients of Bedouin Arab descent in southern Israel who were all homozygous for a novel c.3772delA variant of the ADAMTS13 gene, leading to the clinical manifestations of TTP largely during pregnancy. All patients presented in this study belong to 2 closely related families of Arab Bedouin descent and were found to be homozygous for a novel ADAMTS13-c.3772delA variant. The cohort consisted of 19 females; 16 of them had congenital TTP and had been pregnant and were thus included. Patient data were collected from electronic medical records. Of note, 13 women from our cohort, who delivered 14 fetuses (owing to 1 twin pregnancy), were diagnosed with congenital TTP following complicated pregnancies, which included recurrent pregnancy loss, stillbirth, early onset preeclampsia (both mild and severe), hemolysis, elevated liver enzymes and low platelet count syndrome, intrauterine growth restriction with abnormal Doppler flow, preterm premature rupture of membranes, and a total perinatal mortality rate of 30.7% (4/13). An additional 3 women, who were diagnosed owing to complications outside of pregnancy and at older ages, experienced TTP during their pregnancies, which occurred before diagnosis. Subsequent pregnancies were treated with fresh frozen plasma leading to a 100% fetal survival rate in the pregnancies that reached fetal viability. All placentas had lesions consistent with maternal vascular underperfusion. However, the severity and frequency of these lesions were lower in the 8 placentas from pregnancies treated with fresh frozen plasma. This case series details a distinctive cohort of congenital TTP patients, all homozygous for the same, novel ADAMTS13 variant, who presented with clinical complications during pregnancy and maternal vascular lesions of underperfusion in the placenta. Our findings imply that the variant identified in the ADAMTS13 gene in our cohort may have a specific functional impact on the placenta, and that treatment with fresh frozen plasma during pregnancy ameliorates the course of the disease, leading to a milder phenotype or a normal pregnancy in the majority of cases.

Severely Deficient ADAMTS13 Activity Predicts Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Pregnancy

Background: It is commonly accepted that severely deficient ADAMTS13 activity in remission increases the risk for relapse, but relapse in severely deficient ADAMTS13 activity in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) is not uniform. Mouse models and published studies have suggested that a "second hit" is required in addition to severely deficient ADAMTS13 activity to lead to clinical relapse. Our initial published experience led us to preliminarily conclude that pregnancy could serve as the second hit in addition to severely deficient ADAMTS13 activity and lead to relapse. The aim of this study was to evaluate the risk of relapse and outcomes of pregnant patients with a diagnosis of iTTP. Methods: Since the initiation of the Ohio State University TTP Research Program in 2003, patients were consented at enrollment and followed longitudinally in our IRB approved iTTP registry, usually every three to six months. During pregnancy, patients were seen and CBC, LDH and ADAMTS13 activity were obtained monthly. Due to prior reports of iTTP relapses during pregnancy, it is our practice to offer prophylaxis with cyclosporine to pregnant patients with a diagnosis of iTTP and severely deficient ADAMTS13 activity. The clinical diagnosis of iTTP (defined as thrombocytopenia, microangiopathic hemolytic anemia, without an alternative explanation was confirmed by severely deficient ADAMTS13 activity (<10%) in all cases. ADAMTS13 activity was determined using a SELDI-TOF mass-spectrometer-based method. Results: During the study time, we have followed 11 pregnancies from eight patients with iTTP. Two pregnancies occurred at the time of their initial diagnosis, and nine pregnancies occurred during follow up. Two patients were black, nine were white. Median age was 26 ( range 20-36). Of the nine pregnancies in patients with a previous diagnosis of iTTP, three resulted in relapses, two in the same patient; one at 23 weeks that resulted in fetal demise, and the next one occurred one week after delivery at 36 weeks. The other patient relapsed at 35 weeks and the baby was delivered early at 36 weeks. All relapses were preceded by a documented ADAMTS13 <10%, with a normal platelet count, LDH and no associated symptoms, while none of the other pregnancies had a documented ADAMTS13 <10% (Figure 1). Interestingly, one of the relapses occurred while the patient was taking cyclosporine during pregnancy as preemptive therapy to prevent relapses. She initially responded to therapy with an increase in her ADAMTS13 activity but subsequently lost the response which preceded her relapse post-partum. Conclusions: Pregnancy in patients with a diagnosis of iTTP is a risk factor for iTTP relapse. To our knowledge, this is the first report of the relationship between ADAMTS13 and the risk of relapse during pregnancy. Our results demonstrate that severely deficient ADATMS13 activity uniformly leads to relapse in pregnancy. It also highlights the clinical relevance of monitoring ADAMTS13 activity closely in patients with a history of iTTP that become pregnant. Figure 1 Disclosures Masias: Rigel Pharmaceuticals: Consultancy. Cataland:Alexion: Consultancy, Research Funding; Ablynx/Sanofi: Consultancy, Research Funding. OffLabel Disclosure: the use of cyclosporine for prevention of TTP relapses

Thrombotic thrombocytopenic purpura in pregnancy: A case report

Thrombotic thrombocytopenic purpura in pregnancy: A case report

Validation of the PLASMIC score, a clinical prediction tool for thrombotic thrombocytopenic purpura diagnosis, in Chinese patients

BackgroundThe recently published PLASMIC score was shown to be an excellent diagnostic model to identify patients with severe ADAMTS-13 deficiency. However, it is unclear if this score is suitable for Chinese patients with suspected thrombotic thrombocytopenic purpura (TTP). MethodsWe retrospectively studied a Chinese cohort of 134 consecutively hospitalized patients with thrombotic microangiopathy, ADAMTS-13 test results, and clinical information between January 2015 and June 2018, the PLASMIC score's distinguishing ability in this cohort was evaluated. We also combined the lactate dehydrogenase (LDH)-to-aspartate aminotransferase (AST) ratio with the PLASMIC score to determine its predictive value for TTP in pregnancy. ResultsIn this Chinese cohort, 39 patients were diagnosed with TTP using ADAMTS13 testing. When stratified at high (score, 6–7) vs. low–intermediate (score, 0–5) risk, the PLASMIC test predicted TTP with a positive predictive value of 51%, negative predictive value of 92%, sensitivity of 85%, and specificity of 58%. In pregnant patients, a combination of the PLASMIC score of 6–7 and LDH-to-AST ratio of ≥5.5 showed a higher positive predictive value for TTP compared with the PLASMIC score alone (71% vs. 35%, P < 0.001). Removing the component MCV < 90 fL from the PLASMIC score did not reduce its distinguishing power, as measured using the C statistic (0.837, 95%CI 0.767–0.907 vs. 0.797, 95%CI 0.718–0.877; P = 0.771). ConclusionsCombination with a higher LDH-to-AST ratio improves the positive predictive value of the PLASMIC score in pregnant patients. A simpler score without MCV < 90 fL can be used to identify TTP in Chinese patients.

Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes

AbstractPregnancy can precipitate thrombotic thrombocytopenic purpura (TTP). We present a prospective study of TTP cases from the United Kingdom Thrombotic Thrombocytopenic Purpura (UK TTP) Registry with clinical and laboratory data from the largest cohort of pregnancy-associated TTP and describe management through pregnancy, averting fetal loss and maternal complications. Thirty-five women presented with a first TTP episode during pregnancy: 23/47 with their first congenital TTP (cTTP) episode and 12/47 with acute acquired TTP in pregnancy. TTP presented primarily in the third trimester/postpartum, but fetal loss was highest in the second trimester. Fetal loss occurred in 16/38 pregnancies before cTTP was diagnosed, but in none of the 15 subsequent managed pregnancies. Seventeen of 23 congenital cases had a missense mutation, C3178T, within exon 24 (R1060W). There were 8 novel mutations. In acquired TTP presentations, fetal loss occurred in 5/18 pregnancies and 2 terminations because of disease. We also present data on 12 women with a history of nonpregnancy-associated TTP: 18 subsequent pregnancies have been successfully managed, guided by ADAMTS13 levels. cTTP presents more frequently than acquired TTP during pregnancy and must be differentiated by ADAMTS13 analysis. Careful diagnosis, monitoring, and treatment in congenital and acquired TTP have assisted in excellent pregnancy outcomes.

Preventing maternal deaths due to acquired thrombotic thrombocytopenic purpura

In order to identify the cause of maternal deaths due to thrombotic thrombocytopenic purpura (TTP) and identify future preventative measures we retrospectively reviewed all maternal deaths due to TTP in London from 2003 to 2008 that were confirmed on post-mortem examination. There were three maternal deaths due to sudden cardiac arrest within 1, 5 and 2 days of presentation, respectively. Post-mortem findings revealed they all died with intramyocardial microvascular thrombosis, the thrombi being characteristically platelet rich (CD61+, fibrin-). Platelet thrombi in the coronary microvasculature are the cause of early sudden death in TTP in pregnancy. If TTP cannot be excluded in the differential diagnosis of thrombotic microangiopathies of pregnancy, then plasmapheresis should be instituted as a medical emergency. ADAMTS-13 levels are helpful in making the diagnosis, but results should not be awaited before instituting plasmapheresis.

A case of severe ADAMTS 13 deficiency presenting as thrombotic thrombocytopenic purpura in pregnancy

Thrombotic thrombocytopenic purpura is a rare life-threatening disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia. It is caused by the absent or severe deficiency of the von Willebrand Factor-cleaving protease named ADAMTS13. Pregnancy is a well recognized factor precipitating the appearance of the disease both in women that had reduced levels of ADAMTS13 activity prior to gestation and in those with other inherited or acquired thrombophilic syndromes. We report a 25-year old woman with severe ADAMTS13 deficiency presented early in her 1st pregnancy and relapsed in two subsequent gestations. This presentation is uncommon for thrombotic thrombocytopenic purpura is associated with pregnancy (ADAMTS13 deficiency < 5%, without an inhibitor). In the first pregnancy she started with daily plasma exchange 1.5 x volume, corticosteroids and IV immunoglobulin and finally entered remission after 23 sessions and termination of pregnancy. In the second pregnancy she did not receive prophylactic treatment and relapsed in the 3rd trimester. Prophylactic treatment during the third pregnancy with plasma infusions proved also ineffective to prevent relapse. Many issues regarding treatment and prevention of thrombotic thrombocytopenic purpura relapses in subsequent pregnancies are unclear. Proposed guidelines recommend that the same treatment should be performed on pregnant and non pregnant patients without modification of plasma replacement dose according to ADAMTS13 levels. In addition, many authors suggest that pregnant patients with history of thrombotic thrombocytopenic purpura and severe deficiency of ADAMTS13 levels should received prophylactic treatment for prevention of relapses in the subsequent pregnancies. Severe ADAMTS 13 deficiency may present as thrombotic thrombocytopenic purpura of pregnancy. Pregnant women with thrombotic thrombocytopenic purpura and especially with severe deficiency of ADAMTS13 levels require specific consideration regarding treatment and prophylaxis in subsequent pregnancies.

Pregnancy-associated thrombotic thrombocytopenic purpura

Thrombocytopenia during pregnancy is a common diagnostic and management problem. Several differential diagnosis must be considered including manifestations of thrombotic thrombocytopenic purpura (TTP). We report here on a case of a 21-year-old pregnant woman who presented initially severe thrombocytopenia (8 Gpt/l) in the 20(th)+1 week of gestation. The patient had an antibody against ADAMTS13, and enzyme activity was <5%. Immediate plasmapheresis treatment was initiated, followed by plasma infusions, and again plasmapheresis. A male neonate was delivered by caesarean section in the 32(nd )week of gestation. The child had an uncomplicated postnatal development. After delivery, the mother's platelet count and ADAMTS13 activity increased to normal values. This case shows interesting aspects of TTP in pregnancy and a close cooperation between obstetricians, nephrologists and pediatricians is necessary for a successful outcome of the pregnancy.

Limitations of ADAMTS-13 Activity Level in Diagnosing Thrombotic Thrombocytopenic Purpura in Pregnancy

In pregnancy, it may be difficult to differentiate the syndrome of hemolysis, elevated liver enzymes, and low platelets from thrombotic thrombocytopenia purpura. Severely depressed (<5%) or absence of a disintegrin and metalloproteinase with thrombospondin motifs-13 activity levels are associated with thrombotic thrombocytopenia purpura and mildly decreased levels are associated with other disease processes, including pre-eclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. We present a case of a patient that presented at 20 weeks gestation with elevated liver enzymes and thrombocytopenia. The diagnosis was unclear at the time of presentation. She underwent induction of labor, and during the postpartum course, she was eventually diagnosed with thrombotic thrombocytopenia purpura; however, her activity level of a disintegrin and metalloproteinase with thrombospondin motifs-13 was only moderately depressed at 15% (normal pregnancy value 41%-105%).

315: Thrombotic thrombocytopenic purpura in pregnancy: A multi-center case series

315: Thrombotic thrombocytopenic purpura in pregnancy: A multi-center case series

Pathology of Thrombotic Thrombocytopenic Purpura in the Placenta, with Emphasis on the “Snowman Sign”

Thrombotic thrombocytopenic purpura (TTP) commonly affects women of childbearing age. Although cases of TTP in pregnancy have been reported, the pathology of TTP in the placenta has not been described. In other organs, TTP has a distinctive pathology of arteriolar aneurysms with segmental intramural hyaline deposits. Published many decades ago, these classic papers antedate modern computerized literature searches, so this information has not been included in many modern reviews on TTP. We report 2 cases of TTP in pregnancy, both leading to fetal loss in the 2nd trimester. We noticed a distinctive pathology of TTP in the spiral arteries on the maternal surface of the placenta, particularly the "snowman sign," which differs somewhat from TTP in other organs due to the fact that TTP is superimposed on trophoblast-induced changes in these spiral arteries. In one of our cases, where the clinical diagnosis of TTP was difficult, the distinctive placental findings helped reinforce the clinical decision to perform potentially life-saving plasmapheresis.

Surge of Anti–SS-A Antibody Associated With Fulminant Thrombotic Thrombocytopenic Purpura in Pregnancy

Thrombotic thrombocytopenic purpura (TTP) is an uncommon clinical syndrome and is rarely associated with systemic lupus erythematosus (SLE). Diagnosis of TTP in patients with SLE, especially those who are pregnant, is challenging. We report the case of a pregnant woman with a high level of anti-SS-A antibody (162,143 U/mL) and fulminant TTP. The patient responded to plasma exchange treatment. Recent studies indicate that patients with SLE and another serologic abnormality, such as the presence of antiphospholipid antibody, may be at high risk for TTP. We explore the possible pathogenesis of acute TTP in patients with SLE and summarize the risk factors for acute TTP in patients with SLE and the current treatments for SLE-associated TTP.

Surge of Anti-SS-A Antibody Associated With Fulminant Thrombotic Thrombocytopenic Purpura in Pregnancy

Thrombotic thrombocytopenic purpura (TTP) is an uncommon clinical syndrome and is rarely associated with systemic lupus erythematosus (SLE). Diagnosis of TTP in patients with SLE, especially those who are pregnant, is challenging. We report the case of a pregnant woman with a high level of anti-SS-A antibody (162,143 U/mL) and fulminant TTP. The patient responded to plasma exchange treatment. Recent studies indicate that patients with SLE and another serologic abnormality, such as the presence of antiphospholipid antibody, may be at high risk for TTP. We explore the possible pathogenesis of acute TTP in patients with SLE and summarize the risk factors for acute TTP in patients with SLE and the current treatments for SLE-associated TTP.

Thrombotic thrombocytopenic purpura in pregnancy

Thrombotic thrombocytopenic purpura in pregnancy

Chronic relapsing thrombotic thrombocytopenic purpura in pregnancy: A case report

Thrombotic thrombocytopenic purpura (TTP) is a disorder of unknown etiology affecting the microcirculation of multiple organ systems. Plasma therapy has significantly reduced the mortality rate; thus, an increased incidence of recurrence has been noted. Since corticosteroids, antiplatelet agents, and splenectomy do not prevent recurrences, monthly plasma infusions have been instituted to decrease the risk of recurrence. However, in pregnancy, increase in frequency of plasma infusions to weekly or biweekly intervals has been associated with avoidance of placental infarcts. This is the first report of a successful pregnancy in which bimonthly prophylactic single plasma-exchange plasmapheresis was the treatment regimen with no obvious maternal-fetal morbidity. © 1996 Wiley-Liss, Inc.