scholarly journals Refractory Thrombocytopenia in SLE with Evans Syndrome : A Case Report

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-13
Author(s):  
Ohoud F. Kashari ◽  
Noha Mohammad Alaqsam ◽  
Ebtisam Ahmad Mansour
Keyword(s):  
Platelet Count ◽  
Subdural Hematoma ◽  
Conflicts Of Interest ◽  
Unknown Etiology ◽  
High Dose ◽  
Normal Brain ◽  
Coombs Test ◽  
Evans Syndrome ◽  
Normal White Blood Cell ◽  
Positive Direct

Background: Evans syndrome (ES) is a rare autoimmune disorder of unknown etiology. It is characterized by the occurrence of two or more hematologic immune cytopenias, most often immune thrombocytopenia and autoimmune hemolytic anemia (AIHA). In this study we present a rare case of a 9-year-old girl, who was diagnosed with secondary ES associated with active systemic lupus erythematosus (SLE). Case presentation: On November 16th, 2018, a 9-year old girl, presented for the first time with recent onset of gum bleeding and decreased level of consciousness for two weeks. On examination, she was conscious but not oriented, unable to walk, showed scanty hair with oral and gum bleeding, and had multiple bruises and massive hepatosplenomegaly. No parental consanguinity, and no similar history in the family was noted. She had low platelet count (1×103 /μL), with high mean platelet volume (19 fl), anemia (HB 5.5 g/dL), with normal white blood cell count, positive direct Coombs test, and hemolysis with no malignant cells on a peripheral blood smear. Bone marrow evaluation showed hypercellularity, and increased number of megakaryocytes, with no other significant abnormalities. Her flowcytometry study was normal. Brain computed tomography (CT) revealed left subdural hematoma with elements of old brain atrophy (Photo 1), with significant dilatation of ventricular system. Chest X-ray showed mild right pleural effusion. Abdominal ultrasonography showed hepatosplenomegaly with no focal lesions, and mild-to-moderate ascites. Both antinuclear antibody and anti-phospholipid antibody tests showed positive results and C3 was low. Hepatitis and human immunodeficiency virus (HIV) serology were negative.Autoimmune lymphoproliferative syndrome gene sequence analysis was negative. The patient was diagnosed with SLE, after she fulfilled the American Rheumatology Association criteria, associated with Evans syndrome. Any planned surgery was postponed until thrombocytopenia correction, and their aim was to increase the platelet count to a level of above 100.The patient received packed red blood cells (RBCs) and platelets several times. To control her condition, several medications were tried. These medications included intravenous immunoglobulin (1 gm/kg) for two successive days, prednisolone (2 mg/kg/day); however, no improvement was observed after 10 days. Therefore, all of these medications were replaced with methylprednisolone pulse therapy (30 mg/kg for three days), with one dose of anti-D (75 mcg/kg IV). Our next choice was mycophenolate mofetil, which was stopped after finishing the course of five weeks, but the patient did not show any improvement. Moreover, platelets failed to respond to four doses of Rituximab (370 mg/m2/dose) for four weeks and to two cycles of high dose of dexamethasone 20mg/m2 for 4 days every 4 weeks. On 12/29/2018, chloroquine (4 mg/kg/day) was administered for two weeks in conjunction with cyclosporine (4 mg/kg/day). Splenectomy was an option but was not performed because her platelet levels never recovered. Her anemia started to improve on 1/9/2019 with combination of prednisolone and cyclosporine and Coombs test results were negative. On 1/23/2019, the patient was started on Eltrombopag, in a dose-escalated manner starting with 25 mg/kg/day up to 75 mg/kg/day in addition to corticosteroids. One week later, her platelet counts markedly improved (Photo 2). No major side effects were reported. On 2/12/2019, the patient underwent left side burr-hole evacuation of subdural hematoma, but her consciousness was never regained. She was maintained in intensive care unit and ventilated, but she developed multiple postoperative complication, including sepsis with high inflammatory markers and spiking fever. Her platelet count was continuously high, so the dose of Eltrombopag was decreased to 50 mg/kg/day to just keep the level between 50 and 100. Despite all of therapeutic interventions, she passed away one month later, on 3/13/2019, due to respiratory failure. Conclusion: The incidence of ES is quite rare, especially in children. Eltrombopag is a safe and effective drug for management of refractory thrombocytopenia in cases of ES associated with SLE. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals A full-term pregnant woman with secondary Evans syndrome caused by severe coronavirus disease 2019: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Damai Santosa ◽  
Muchlis A. U. Sofro ◽  
Farida ◽  
Nurvita Nindita ◽  
Eko A. Pangarsa ◽  
...  
Keyword(s):  
Platelet Count ◽  
Full Term ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Evans Syndrome ◽  
Dna Test ◽  
Indirect Bilirubin ◽  
Low Platelet Count ◽  
Laboratory Examinations ◽  
Positive Direct

Abstract Background In this report, we describe a very challenging case of a patient with secondary Evans syndrome caused by severe coronavirus disease 2019 infection in a pregnant full-term woman. Case presentation A 29-year-old full-term pregnant Indonesian woman presented with gross hematuria, dry cough, fever, dyspnea, nausea, anosmia, and fatigue 5 days after confirmation of coronavirus disease 2019 infection. Laboratory examinations showed very severe thrombocytopenia, increased indirect bilirubin, and a positive direct Coombs’ test. From peripheral blood, there was an increased number of spherocytes, which indicated an autoimmune hemolytic process. Antinuclear antibody and anti-double-stranded DNA test results were negative, and her virology serological markers are also negative for human immunodeficiency virus, cytomegalovirus, and hepatitis B and C. Despite aggressive treatment with platelet transfusion, high-dose steroid, and thrombopoietin receptor agonists, the platelet count did not recover, and a speculative cesarean delivery had to be done with a very low platelet count.

A Case Of Refractory Autoimmune Hemolytic Anemia In a Patient With Digeorge Syndrome Treated Successfully With Plasma Exchange

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4829-4829
Author(s):  
Moussab Damlaj ◽  
Chantal Séguin
Keyword(s):  
Plasma Exchange ◽  
Hemolytic Anemia ◽  
Digeorge Syndrome ◽  
Conflicts Of Interest ◽  
Fluid Replacement ◽  
Therapeutic Modality ◽  
High Dose ◽  
Erythroid Hyperplasia ◽  
Immune Hemolytic Anemia ◽  
Positive Direct

Background warm auto-immune hemolytic anemia (AIHA) results from targeted antibodies towards the RBCs and can be secondary to certain diseases (auto-immune disease or malignancy), drugs, infections or may be idiopathic in nature. Patients with DiGeorge syndrome are vulnerable to auto-immune conditions secondary to thymic hypoplasia with an estimated incidence in one series of 8.5% (Tison, Nicholas et al. 2011). First line therapy of AIHA consists of corticosteroids with an anticipated response rate of 80% (Lechner and Jager 2010). Relapses are not uncommon and are treated with splenectomy or rituximab. Case we describe an unusual case of an 18 year old female with DiGeorge syndrome who presented with AIHA refractory to usual modes of therapy. In this case, she was diagnosed with immune thrombocytopenia purpura (ITP) at age 13 with multiple relapses following successful standard therapy. Eventually, she was managed with monthly IVIG (intravenous immune globulin) infusions and thrombopoietin analogue romiplostim, maintaining her platelet count between 50 - 100 x 10 9/L. At 18 years of age she presented with severe anemia (Hb 55 g/L), positive hemolytic markers and a positive direct Coombs (3+ IgG and negative C3). A diagnosis of AIHA was established, and patient was started on prednisone (1-1.5 mg/kg) with transfusion support. Due to lack of response, high dose IVIG was administered followed by weekly rituximab 375 mg/m2. Due to hemodynamic instability, Rituximab was interrupted after the second dose. The finding of ineffective erythropoiesis evident by inappropriately low reticulocytosis prompted a bone marrow aspirate and biopsy. Aside from erythroid hyperplasia (M:E ratio of 1:4) with a left shift, no other anomaly was noted. PNH and G6PD screen was negative. The refractory nature of her AIHA required that the patient undergo a splenectomy. Hemolytic markers transiently improved however, within a few days, her hemolytic picture worsened and patient remained transfusion dependent. Given deterioration of her clinical status, decision was made to proceed with plasma exchange (PE) daily for 5 sessions with fresh frozen plasma fluid replacement. 24 hours following her first exchange session, there was a steady improvement of her hemolytic markers and patient became transfusion independent (Fig 1). Hb normalized eight days following the last exchange session. Additionally, platelets normalized following the splenectomy and she no longer required romiplostim. At her last follow up, 280 days following her last session of PE, Her Hb is within normal limits and hemolytic markers continue to be negative. During her admission, she required 42 bags of PRBCs (Fig 2). Conclusion This is the first reported case of a DiGeorge syndrome presenting with refractory AIHA successfully treated with PE. We conclude in this case that the combination of splenectomy followed by PE successfully controlled her hemolysis. Thus, we hope this report will give an additional insight on the use of PE as a therapeutic modality in refractory cases. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Autoimmune Cytopenias and Covid-19 Vaccination: Relapse and Suggested Treatment

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4141-4141
Author(s):  
Gregorio Campos-Cabrera ◽  
Francisco-Gerardo Torres-Salgado ◽  
Salvador Campos-Cabrera ◽  
Jose-Luis Campos-Villagomez ◽  
Virginia Campos-Cabrera
Keyword(s):  
Complete Remission ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
High Dose ◽  
Evans Syndrome ◽  
Autoimmune Thrombocytopenia ◽  
Platelet Counts ◽  
Autoimmune Cytopenias

Abstract Introduction: There are "de novo" and relapsed autoimmune diseases in patients with COVID-19 that includes autoimmune thrombocytopenia, Evans syndrome and autoimmune hemolytic anemia among others (Hematology 2021;26:225-239 and Curr Rheumatol Rev 2021;17:193-204). There is scanty material about relapse of autoimmune hematological diseases after vaccination for COVID-19 (Blood Adv 2021;13:2794-2798). Material and methods: Adult patients 18 years or older with autoimmune thrombocytopenia, Evans syndrome and autoimmune hemolytic anemia who completed SARS-Cov2 vaccination. Results: Between December 2020 and June 2021 there were identified 53 patients with autoimmune hematological disease that completed SARS-Cov2 vaccination. Thirty-six with autoimmune thrombocytopenia, all were preexisting. Twelve with autoimmune hemolytic anemia, 5 secondaries to previous COVID-19 and 7 preexisting. Five with Evans syndrome, all preexisting. Twenty-three patients with autoimmune thrombocytopenia did not develop any fall in the platelet count. Ten patients had a fall of 50 % from basal counts and recovered spontaneously. Three patients developed counts below 30,000 with purpuric symptoms and needed treatment that consisted in two courses of dexamethasone 40 mg daily for four days every three weeks; all patients reached complete remission without any further treatment. All patients with Evans syndrome developed hemolysis and low platelet counts. Two patients maintained Hb levels above 10 and platelet counts above 50,000; both patients had spontaneously recovery. Three patients developed Hb levels below 7 with anemic syndrome and platelets below 50,000 but without purpuric syndrome; they received the same treatment as patients with autoimmune thrombocytopenia and reached complete remission too. All five patients with autoimmune hemolytic anemia secondary to COVID-19 developed Hb levels below 7 with anemic symptoms and needed treatment as described. The remaining 7 patients with preexisting autoimmune anemia developed hemolysis; five with Hb levels above 7 and recovery without any treatment; two had Hb levels below 7 and received the same treatment with full recovery and complete remission. Conclusions: Autoimmune cytopenias can be trigger by vaccines and viral infections by involving molecular mimicry and circulating immune complexes, including SARS-Cov2. The viral protein spike from SARS-Cov2 has mimicry between the Ankyrin-1 in the erythrocyte surface, and has been linked as one of the pathogenesis pathways of autoimmune hemolytic anemia secondary to COVID-19 (Br J Haematol 2020;190:e92-e93 and Blood 2020;136:suppl8,138001). Relapse of autoimmune cytopenias after vaccination with SARS-Cov2 involves stimulation of autoantibodies production from preexisting B cells. Although relapses were observed in the three kinds of patients, all with hemolytic component developed a drop in the hemoglobin levels, most of them needed treatment. It is important to notice that patients with hemolytic autoimmune anemia secondary COVID-19 had severe relapse, event that support the mimicry mentioned lines above. It is important to follow up closely this kind of patients after SARS-CoV2 vaccination, we suggest weekly complete blood counts, and a short courses of high dose dexamethasone can induce curable responses if treatment is advised. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Case Report of Refractory Immune Thrombocytopenia (ITP) Following Reduced Intensity Conditioning (RIC) Hematopoietic Cell Transplantation (HCT) for Myelodysplastic Syndrome (MDS) Successfully Treated with Off-Label Use of Daratumumab

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4976-4976 ◽  
Author(s):  
Yazan Migdady ◽  
Ridhi Gupta ◽  
Asiri Ediriwickrema ◽  
Francisco Socola ◽  
Sally Arai ◽  
...  
Keyword(s):  
Platelet Count ◽  
Case Report ◽  
Peripheral Blood ◽  
Hematopoietic Cell Transplantation ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Antibody Testing ◽  
Bone Marrow Biopsies

Abstract Background: A source of treatment refractoriness in immune cytopenias appears to be residual CD138/38 positive lymphocyte populations (Audia S et al, Blood 118:4394-400,2011; Mahevas M et al, J Clin Invest 123:432-442, 2013). Persistence of recipient's plasma cells can lead to prolonged refractory thrombocytopenia following RIC-HCT. (Fasano RM et al, Br J Haematol 166(3):425-34, 2014). Daratumumab was effective in the treatment of a child with refractory autoimmune hemolytic anemia after HCT (Tolbert et al, Blood 128:4819, 2016). Case Report: The patient is a 60-year-old man with intermediate-high risk MDS who underwent RIC-HCT with total lymphoid irradiation and antithymocyte globulin with peripheral blood graft from a fully matched unrelated male donor. The patient had mild thrombocytopenia prior to HCT consistent with MDS and had not received platelet transfusions. He had not received any prior therapy for MDS. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. Cytomegalovirus (CMV) serologic testing for exposure was negative for the recipient and positive for the donor. Both the patient and the donor had evidence for prior exposure to Epstein-Barr virus (EBV). He achieved engraftment on day +12. His peripheral blood chimerism on day + 30 showed full donor origin (WB 98%,CD3 96%,CD15 95%, CD19 98%, CD56 95%) and has been maintained to date. Acute skin GVHD responded to corticosteroids. While on corticosteroid therapy, he developed an abrupt decline in platelet count from 156,000/mcl on day +152 to 9, 000/mcl on Day + 166 without evidence for recurrent or active GVHD. While this was initially attributed to simultaneous EBV and CMV reactivations, severe thrombocytopenia persisted after viral clearance. An extensive work up for other etiologies of thrombocytopenia was negative. Repeated bone marrow biopsies were normal, including adequate megakaryocytosis and no MDS recurrence. Platelet associated antibody testing and platelet antigen genotyping were not conclusive for autoimmune versus alloimmune etiology. Testing for platelet HLA antibodies showed calculated Panel Reactive Antibody of 31% and unsatisfactory corrected count increment after transfusion of HLA compatible platelets units. The patient experienced prolonged severe thrombocytopenia for over 26 weeks with platelet count less than 5000/mcl for 22 weeks and only above 10,000 /mcl on 6 occasions. Potentially responsible medications were discontinued serially, but testing for drug inducted ITP was not conducted. Therapy included high dose corticosteroids, high dose immune globulin, rituximab, plasma exchange, splenectomy, romiplostim 10 mcg/kg/week, eltrombopag 100 mg to 150 mg daily for over 24 weeks, and low dose danazol. Fostamatinib was not available. Prednisone dose was tapered over many weeks to 5 mg daily. The patient experienced recurrent life-threatening and vision-threatening bleeding. Cumulative transfusions following Day + 166 were 133 single donor platelet units and 42 red cell units. All products were from CMV negative donors. Eltrombopag and danazol were deemed ineffective and tapered to discontinuation. CD38 positive cells were present in spleen and marrow by immunohistochemistry. Daratumumab 1300 mg was infused weekly x 4. Four weeks after the last dose of daratumumab, his platelet count increased to 91,000/mcl. Platelet count normalized to 150,000/mcl in week 5 or HCT Day + 383. Hypogammaglobulinemia has been the only detectable toxicity. Testing to determine autoimmune versus alloimmune origin is ongoing. Conclusion: Clinical trials of daratumumab for the treatment of severe refractory ITP are indicated. Disclosures No relevant conflicts of interest to declare.

Cold Hemagglutinin Hemolysis and Hypercoagulable State Due to Mycoplasma Pneumoniae.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5094-5094
Author(s):  
Gaurav Gulati ◽  
Anthony A Donato ◽  
Shuchi Gulati ◽  
Daniel A Forman
Keyword(s):  
Platelet Count ◽  
Hemolytic Anemia ◽  
Mycoplasma Pneumoniae ◽  
Skin Necrosis ◽  
Conflicts Of Interest ◽  
Anticardiolipin Antibody ◽  
The United States ◽  
Cold Agglutinin ◽  
High Dose ◽  
Superficial Skin

Abstract Abstract 5094 Introduction Mycoplasma pneumoniae is responsible for 7 to 20% of community-acquired pneumonia in the United States. Up to 25% of patients develop extra-pulmonary complications. Hemolytic anemia associated with multiple vascular thromboses is a rare but severe complication of Mycoplasma pneumoniae. We present a case of cold agglutinin-associated hemolysis and skin necrosis. Case Presentation An 81 year-old male on Coumadin for atrial fibrillation who recently returned from a cruise, developed non productive cough without fever and dyspnea. He was treated with a course of azithromycin. One week later he developed bruising and skin de-pigmentation of the tips of the pinnae and tip of the nose. On presentation to the emergency department, his physical exam was unremarkable except for these finding and mild rhonchi over his right posterior chest. Laboratory workup revealed a Hemoglobin of 13.5 g/ dL, leukocytosis of 23,700 c/mm3 and platelet count of 57,000 c/mm3. Moderate renal insufficiency was also present with a creatinine of 2.02. Evaluation of peripheral smear revealed mild Schistiocytosis with anisopoikilocytosis. Within 1 week, hemoglobin dropped to 7.4, platelet count reached a nadir of 16,000. Hemolytic parameters included LDH of 647 IU/L with haptoglobin of 26 mg/dL, and reticulocyte count of 1.3%. Total complement levels were severely depressed at 4 U/ml (normal: 30 to 75 U/ml), while there was a slight decrease in C4 complement levels and the C3 levels were normal. Immunoglobulin levels were within limits and cryofibrogen was negative. ANA, anticardiolipin antibody, myeloperoxidase and p ANCA levels showed normal titers. A bone marrow biopsy showed hypercellular marrow with erythroid hyperplasia. Urine Strep. pneumoniae antigen was negative. Cold agglutinin titers were done, which were negative. Due to our strong suspicion for mycoplasma-related cold agglutinin hemolysis, we repeated cold agglutinin titers which turned positive very slowly on prolonged standing. The patient was treated with high dose prednisone and received multiple sessions of plasmapheresis which improved his condition and platelet counts returned to baseline with LDH and haptoglobin levels trending back to normal. Discussion Our patient had a wide differential ranging from Coumadin induced skin necrosis, auricular perichondritis, frost bite, local infections, TTP/ HUS syndrome, and Wegner's granulomatosis. But the clinical presentation of superficial skin necrosis of peripheral skin along with the presence of low complement, recent chest infection, hemolytic anemia and thrombocytopenia with acute renal failure all contributed to our final diagnosis confirmed by the presence of slow reactive Coomb's direct anticoagulation test and supported by improvement with plasmapheresis and steroid therapy. The astute clinician should always remember mycoplasma infection in setting of acute onset hemolytic anemia and suspect it in recently treated chest and sinus infections. Disclosures No relevant conflicts of interest to declare.

scholarly journals Refractory Thrombocytopenia Responds to Octreotide Treatment in a Case of Evans Syndrome with Gastric Neuroendocrine Tumor

2013 ◽  
Vol 2013 ◽  
pp. 1-5
Author(s):  
Kocfa Chung-Delgado ◽  
Alejandro Revilla-Montag ◽  
Sonia Guillén-Bravo ◽  
Hugo Ríos-Díaz ◽  
José C. Alva-Muñoz
Keyword(s):  
Platelet Count ◽  
Neuroendocrine Tumor ◽  
Hepatic Metastasis ◽  
Poor Response ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Evans Syndrome ◽  
Laboratory Findings ◽  
Regular Treatment ◽  
Octreotide Treatment

A 37-year-old woman with history of Evans Syndrome with poor response to high-dose corticoid treatment presented to the emergency department with gastrointestinal and vaginal bleeding. The patient was later diagnosed with severe thrombocytopenia and a stage G1, well-differentiated gastric neuroendocrine tumor, confirmed by a biopsy. A total gastrectomy was performed to eradicate the tumor. After being treated with a total splenectomy for her Evans Syndrome with no clinical or laboratory improvement, she began regular treatment with octreotide on the basis of a possible hepatic metastasis. Days after the initiation of the octreotide, an increase in the platelet count was evidenced by laboratory findings, from 2,000 platelets/mm3to 109,000 platelets/mm3. Weeks later, the hepatic metastasis is discarded by a negative octreotide-body scan, and the octreotide treatment was interrupted. Immediately after the drug interruption, a progressive and evident descent in the platelet count was evidenced (4000 platelets/mm3). The present case report highlights the possible association between octreotide treatment and a severe thrombocytopenia resistant to conventional treatment.

The North American Chronic Immune Thrombocytopenia Registry (NACIR): Demographics and Treatment Responses

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2509-2509
Author(s):  
Rachael F. Grace ◽  
Ellis J. Neufeld ◽  
A. Kim Ritchey ◽  
Manjusha Kumar ◽  
Michael R. Jeng ◽  
...  
Keyword(s):  
Platelet Count ◽  
North American ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Evans Syndrome ◽  
Chronic Itp ◽  
The North ◽  
Acute Itp ◽  
Positive Direct

Abstract Abstract 2509 Background: Chronic pediatric immune thrombocytopenia (ITP) has an incidence of 1–2/100,000. Due to its low incidence, large studies in pediatric chronic ITP are difficult. This registry includes patients from 16 sites in the US and Canada and represents one of the largest longitudinal datasets of children/adolescents with chronic ITP. Objective: To describe the North American Chronic ITP Registry (NACIR) study population and evaluate univariate predictors of platelet count response to therapies, including IVIG, anti-D globulin (anti-D), steroids (5–14 day course), and splenectomy. Registry methods and patient characteristics: After local IRB approval, 550 patients with chronic ITP enrolled in the NACIR between January 2004 and June 2010. Eligibility included: ages 6 months-18 years at ITP diagnosis, clinical diagnosis of ITP, and ITP duration >6 months. Primary ITP was defined as isolated thrombocytopenia without associated conditions. Secondary ITP included those patients with immune thrombocytopenia associated with other immune-mediated medical conditions, including Evans Syndrome. Treatment response was defined as a post-treatment platelet count ≥50,000/uL within 7 days of IVIG, 10 days of anti-D, 14 days of steroids, and 30 days of splenectomy. 365 subjects had at least one 6 month follow-up report after enrollment; median duration of follow-up was 2.1 yrs. Demographics of participants include: 46% male; 84% Caucasian, 7% Black, and 7% Asian; and 20% Hispanic. Mean age at diagnosis of acute ITP was 8.7 ± SD 5.2 years. At the time of enrollment in NACIR, subjects had received a median of 2 prior treatments (range 0–7). Results: The median platelet count at diagnosis of acute ITP was 11,000/uL (IQR 6,000–31,000/uL) and at chronic ITP was 35,000/uL (IQR 18,000–66,000/uL). 69 (12.5%) patients had secondary ITP or Evans syndrome. Of those tested, 25.6% (98/359) of patients had a positive ANA (titer > 1:40), and 75/337 (22.3%) had a positive direct anti-globulin test (DAT). 27.5% of patients had an antecedent viral illness. Of the 550 subjects, 2 (0.4%) experienced life-threatening bleeding. Patients were treated as follows: 259 (47.1%) with steroids, 253 (46%) with IVIG, 189 (34.4%) with anti-D, and 64 (11.6%) with splenectomy. Overall responses to therapy included: 69.1% response to steroids, 74.3% response to IVIG, 66.7% response to anti-D, and 85.9% response to splenectomy. Univariate predictors of response to treatments are shown in Table I. Higher platelet count at chronic ITP diagnosis and DAT positive predicted a platelet response to a short course of steroids in univariate analysis. This was confirmed in multivariable analysis of potential confounders, using logistic regression with a backwards elimination procedure. Response to one type of therapy was often strongly associated with a response to a second therapy. Gender, ethnicity, race, older age, and platelets ≥20,000/uL at acute ITP diagnosis were not associated with response to any single therapy. Conclusion: The demographics and laboratory findings of the large, well characterized NACIR population are consistent with other reports of young people with chronic ITP. The novel finding that DAT positivity predicts steroid response, even with multivariable adjustment for confounders, provides evidence that the NACIR is a robust and useful tool for trying to predict response to ITP treatment strategies. Disclosures: Klaassen: Novartis: Research Funding; Cangene: Research Funding. Lambert: Cangene: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Cytomegalovirus Induced Thrombocytopenia with No Platelets in an Immunocompetent Young Male

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4904-4904
Author(s):  
Sujatha Baddam ◽  
Jose Cavo ◽  
Jorge Diaz Castro
Keyword(s):  
Platelet Count ◽  
Viral Load ◽  
Immune Globulin ◽  
Influenza A ◽  
Conflicts Of Interest ◽  
Fatal Outcome ◽  
Laboratory Data ◽  
High Dose ◽  
Severe Epistaxis ◽  
Immunocompetent Adults

Introduction Immune thrombocytopenic purpura (ITP) is a common cause of acquired thrombocytopenia in an otherwise asymptomatic adult. It is generally believed to be caused by auto- antibodies against platelet antigens that destroy platelets peripherally and autoreactive cytotoxic T cells, as well as humoral and cellular autoimmunity directed at megakaryocytes, causing impaired platelet production. Cytomegalovirus (CMV) is a known cause of cause of morbidity and mortality in patients with immunosuppressed states, whereas in immunocompetent patients, it commonly manifest as asymptomatic or mononucleosis like syndrome. We are presenting a case of CMV induced thrombocytopenia with severe epistaxis and platelet count of 0 x10 9 in an otherwise healthy immunocompetent male who failed to improve after standard treatments with high dose steroids and intra venous immune globulin (IVIG). Case Description A 36-year-old Caucasian male without any past medical history presented to emergency room (ER) with flu like symptoms for five days associated with subjective fevers, anorexia, nausea, cough and weight loss of 15 lb. in two weeks. He also reported possible tick bite while working in the yard two days prior to admission. No dizziness, vomiting, diarrhea or any bleeding were reported. Denied any smoking, alcohol use or any illicit drug use. No significant family history was reported. On evaluation he was afebrile, normotensive with normal heart rate and respiratory rate. Physical examination was unremarkable. Initial laboratory data revealed hemoglobin of 11.2, platelet count 4 x109, white cell count of 13,100 with 4.5% atypical lymphocytes, aspartate aminotransferase of 41, alanine aminotransferase of 49, and creatinine of 1.4. He tested positive for Influenza A, CMV Immune globulin (Ig)M and IgG antibody. Serological tests for tick panel including anaplasma, babesia, Lyme disease and ehrlichia were negative. Epstein-Barr virus (EBV) antibody, parvo virus antibody, hepatitis screen, HIV screen, auto antibodies including anti-nuclear antibody and anti-double stranded DNA were negative. Coombs test was negative. Further work up includes ADAMTS13 activity was normal. No laboratory evidence of ADAMTS13 deficiency. After excluding all other causes, diagnosis of ITP was made. He was started on Tamiflu for Influenza A and high dose intra venous (IV) methyl prednisone for ITP. After platelet transfusion and two days of IV steroids platelet count improved 43 x 109 and he was discharged home with prolonged prednisone taper. Five days later, he presented to ER with severe epistaxis. Laboratory data revealed platelet count of 0 x109. Serum CMV-DNA was determined by PCR showed viral load of 8,790 copies/ml. Ultrasound abdomen showed mild splenomegaly. He received three doses of IVIG (1g/kg). Platelet count failed to improve after administration of IVIG. Bone marrow biopsy revealed hyper cellular marrow with trilineage hematopoiesis with no increase in CD 34 blasts. Per infectious disease and hematology recommendations, he was started on valganciclovir (900 mg PO BID). One month later, platelet count improved to 150 x 109 and CMV viral load dropped to 413 with subsequent resolution of patient's symptoms. Discussion Secondary ITP is an acquired thrombocytopenia caused by autoantibodies against platelets. Many patients with ITP are asymptomatic. For those who do have symptoms, initial presentations of ITP are petechiae, purpura and epistaxis, with a more severe progression to intracranial hemorrhage or gastrointestinal bleeding leading to a fatal outcome, if treatment is not started on a promptly manner. CMV induced thrombocytopenia in immunocompetent adults seems to be rare. we are presenting a case of CMV induced ITP which failed to improve after standard treatment with high dose steroids and IVIG but responded to anti-viral therapy with valganciclovir. In conclusion, it may be worthwhile to test for CMV infection in patients presenting with ITP. Further research is needed in order to establish treatment guidelines for CMV induced ITP in immunocompetent adults. Disclosures No relevant conflicts of interest to declare.

scholarly journals Indeterminate Serotonin Release Assays Are Associated with a High Mortality Rate

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-13
Author(s):  
Shawn Jindal ◽  
Christopher Leyton ◽  
Fred Cohen ◽  
Morayma Reyes Gil ◽  
Henny H. Billett
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Clinical Course ◽  
Conflicts Of Interest ◽  
Serotonin Release ◽  
Categorical Variables ◽  
High Dose ◽  
Heparin Binding ◽  
Antibody Testing ◽  
High Concentrations

INTRODUCTION: The serotonin release assay (SRA) is considered the gold standard for diagnosis of heparin-induced thrombocytopenia (HIT). While the SRA holds high sensitivity and specificity when results are definitive, up to 10% of samples from patients with suspected HIT yield "indeterminate" results. In classic HIT, the SRA typically reveals high levels of serotonin release when serum is mixed with low concentrations of heparin and low levels of serotonin release when serum is mixed with high concentrations of heparin. Results are considered "indeterminate" when high levels of serotonin release are seen at both low and high concentrations of heparin, indicating a failure of high-dose heparin to saturate the heparin binding sites of PF4 molecules and inhibit platelet activation. Explanations for indeterminate assays include the presence of heparin-binding proteins that interfere with the assay, high titers of HLA class I alloantibodies, or immune complexes. Since the diagnosis of HIT carries such significance and has so many ramifications, an indeterminate SRA may leave therapeutic indecision. The etiologies, platelet trends, clinical course and outcomes of patients that receive indeterminate SRA results are not well-understood. We conducted a retrospective review of 2,056 patients that underwent SRA testing as part of their evaluation for HIT. METHODS: Using the electronic medical record data extraction software Clinical Looking Glass, we identified patients that underwent SRA testing between 1/1/2014 and 12/31/2018. SRA results were considered "indeterminate" when serotonin release exceeded 19% at all heparin dilutions (0.1 U/mL, 0.5 U/mL and 10 U/mL). We conducted a retrospective chart review to study the clinical course among patients who had "indeterminate" SRA results, the trends in platelet count, the timing of platelet drops and the physician response to this result. Statistical analysis was performed using chi-square testing for categorical variables. RESULTS: We identified 2,056 patients that underwent SRA testing between 2014 and 2019. Of these, 90 patients (4.4%) had "positive" SRA results and 1,814 patients (88.2%) had "negative" SRA results. Among the 152 patients (7.4%) with "indeterminate" SRA results, the mean 4T score was just 2.9, corresponding to a HIT probability of <5%. One-hundred and twenty of these 152 patients (78.9%) had heparin-PF4 antibody testing with optical densities below 0.60 OD, while only 4 of 152 patients (2.6%) had optical densities above 2.00 OD. Seventy eight of 152 patients (51.3%) either continued or were re-exposed to heparin after the indeterminate SRA result, and in 71 of 78 cases (91.0%), the platelet count stabilized or improved despite heparin exposure. In the remaining 7 cases, no acute VTE were found and no diagnosis of HIT was made. Four of the 71 patients (5.6%) that continued or were re-exposed to heparin were noted to have an acute VTE. A significantly higher portion of patients with an indeterminate SRA died during admission compared to those with a positive or negative SRA (49.3% vs. 21.1% and 27.2%, p <2.4 x10-10). The prevalence of thrombocytopenia <50,000 was substantially higher in patients with an indeterminate or positive SRA, compared to those with a negative SRA (39.5% and 40.0% vs. 27.5%, p <4.0 x 10-4). Re-exposure or continuation of heparin did not affect mortality; patients that were given heparin after an indeterminate SRA had a 47.4% mortality, compared to 51.4% in those given no more heparin (p = 0.63). Table 1 summarizes these findings. CONCLUSIONS: This is the largest study to date looking at patients with indeterminate SRA testing results, in which platelets exhibit high levels of serotonin release at both low and high heparin concentrations. Our data suggest 1) the majority of patients with indeterminate SRAs likely did not have HIT, 2) as evidenced by the low 4T scores and heparin-PF4 antibody levels, an indeterminate SRA suggests thrombocytopenia related to in-vivo platelet activation, and 3) an indeterminate SRA is associated with increased mortality. SRA results warrant a case-by-case assessment of the clinical picture in order to avoid unnecessary cessation of heparin products. Further studies exploring the mechanism leading to high serotonin release at both low and high heparin concentrations, causing an "indeterminate" SRA result, are warranted. Disclosures No relevant conflicts of interest to declare.

scholarly journals Immune Hemolysis and Aseptic Meningitis after Intravenous Immunoglobulin

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4749-4749
Author(s):  
Arun Kumar Arumugam Raajasekar ◽  
Srikant Nannapaneni ◽  
William B. Solomon
Keyword(s):  
Adverse Effect ◽  
Intravenous Immunoglobulin ◽  
Aseptic Meningitis ◽  
Conflicts Of Interest ◽  
Blood Type ◽  
World Health ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
High Dose ◽  
Positive Direct ◽  
High Dose Ivig

Abstract INTRODUCTION Human intravenous immunoglobulin (IVIG) products are generally considered safe and are used for the treatment of a variety of autoimmune and pro-inflammatory states. However, controlled trials involving IVIG have been of small size with limited power and described only the most common adverse effects [1]. IVIG related hemolysis is a rare adverse effect and is usually self-limited, rarely requiring blood transfusions. A few case reports have also described aseptic meningitis after IVIG use. We describe a patient who developed severe hemolytic anemia and aseptic meningitis after IVIG use. CASE PRESENTATION A 54 year old woman was admitted with severe head ache, dark colored urine and shortness of breath twenty four hours after receiving IVIG. She was diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) a month ago and was started on IVIG. Physical exam was unremarkable. Laboratory tests showed severe anemia with a hemoglobin of 6.1 g/dl (baseline 13 g/dl), indirect hyper-bilirubinemia, low haptoglobin, elevated LDH and hemoglobinuria confirming hemolysis. Hematological testing revealed a positive direct antiglobulin test (DAT), DAT IgG, DAT CD3 and eluate testing were also positive. A lumbar puncture showed neutrophil pleocytosis but no bacteria. A diagnosis of IVIG induced hemolysis and aseptic meningitis was made. O negative packed red blood cells were transfused for severe symptomatic anemia and non-steroidal anti-inflammatory drugs were given for headache. Steroids were deferred since the source of antibodies causing hemolysis was extrinsic. She improved clinically and blood counts returned to baseline in three weeks. DISCUSSION Pooled IVIG is extracted from at least 1000 individuals and contains highly purified polyvalent IgG [2]. Hemolysis after IVIG is thought to be secondary to donor antibodies against host red blood cell antigens and resolves once IVIG is stopped. Risk factors for hemolysis include non-O blood types and the use of high dose IVIG. The patient described was of AB Rh positive blood type but did not receive high dose IVIG. Aseptic meningitis is another rare adverse effect that has been postulated to be related to antibodies in the IVIG that mimic antineutophil cytoplasmic antibodies (ANCA) which activate neutrophils causing neutrophilic pleocytosis [3]. One must be aware of these two rare complications of a commonly used drug. REFERENCES [1] Risks associated with the use of intravenous immunoglobulin. Pierce LR et al. Transfus Med Rev. 2003 Oct;17(4):241-51. [2] Appropriate uses of human immunoglobulin in clinical practice: memorandum from an IUIS/WHO meeting. Bull World Health Organ. 1982;60(1):43. [3] Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNF alpha-dependent and Fc-receptor-independent way. Jarius et al. Blood. 2007;109(10):4376. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document