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.

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.

Retrospective Observational Study on Multiple Myeloma Cases Admitted to Kfsh – Dammam Between 1st of June 2006 till the End of December 2013

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5995-5995
Author(s):  
Omar Zeid Abduljalil ◽  
Abid Mohiuddin ◽  
Hani Hassan Al Hashmi
Keyword(s):  
Multiple Myeloma ◽  
Observational Study ◽  
Patient Population ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
The United States ◽  
Response To Therapy ◽  
Poor Performance Status ◽  
High Dose ◽  
Primary Therapy

Abstract Introduction: Multiple myeloma (MM) is characterized by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. It accounts for approximately 1 percent of all cancers and slightly more than 10 percent of hematologic malignancies in the United States. There is a scarcity on the information of myeloma in the kingdom of Saudi Arabia.Hence was this observational study from a single center in Dammam, Saudi Arabia. . Method: Retrospective chart review of consecutive patients Diagnosed with Multiple myeloma in the period between 1st of May 2006 until end of December 2013 at King Fahd Specialist Hospital in Dammam (KFSHD). Purpose: to describe the presenting characteristics of MM patients in our region, treatment patterns prescribed with the outcome of therapy that include progression free survival and overall survival. Result: 63 patients with multiple myeloma were diagnosed and treated during this period. The percentage of patients with ECOG (≥2) is 52.3 % . 60 % of the patients had stage III international staging system (ISS). Only 17.4% received Triple agents as primary therapy as most of our patients received duplet therapy. 46% received High Dose therapy and Autologous stem cell transplantation. the PFS was 41.1 % and the OS of 69.1% at 95 months. Conclusion: Our results showed that we had rather younger patient population with a median age of 60 compared to the average western myeloma patient population. Despite the relatively young age those patients unfortunately had relatively poor performance status and high ISS stage which correlate with worse clinical outcome. However, the response to therapy and the outcome of our patients were superior to the outcome of any cohort of patients with similar disease characteristic. This observation worth further studying which could be due to an unknown disease or treatment related factors that might affect positively the patient’s outcome. Disclosures No relevant conflicts of interest to declare.

scholarly journals Thrombocytopenia and Microangiopathic Hemolytic Anemia Precipitated By Acute Pancreatitis: A Single Center Experience of Five Cases

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1377-1377 ◽  
Author(s):  
Mary Salib ◽  
Anne-Sophie Lemay ◽  
Megan Buchholz ◽  
Katerina Pavenski
Keyword(s):  
Acute Pancreatitis ◽  
Platelet Count ◽  
Hemolytic Anemia ◽  
High Dose ◽  
Significant Heterogeneity ◽  
Adamts13 Activity ◽  
Microangiopathic Hemolytic Anemia ◽  
Complement Protein ◽  
Advisory Boards ◽  
Adamts13 Deficiency

Abstract Introduction Thrombotic thrombocytopenic purpura (TTP) is a prothrombotic disorder characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. It has been associated with a deficiency or dysfunction of ADAMTS13, an enzyme responsible for cleaving ultra-large von Willebrand factor multimers, thus preventing spontaneous platelet adhesion and aggregation. In its absence, platelet aggregates accumulate in the microvasculature causing neurological symptoms, cardiac ischemia and renal dysfunction. Most cases in adults are idiopathic, and associated with severe ADAMTS13 deficiency (<10%) and anti-ADAMTS13 antibodies. Acquired TTP due to various conditions, such as HIV, drugs, malignancy, collagen disease, bone marrow transplant and acute pancreatitis (AP), have also been described. Some cases of these secondary TTP may be associated with no to moderate ADAMTS13 deficiency and are referred to as thrombotic microangiopathies (TMAs). If plasma exchange (PLEX) has been the treatment of choice for acquired TTP, it has not been shown to be very effective for TMAs. AP-associated MAHA and thrombocytopenia (MAHA-T) might be one exception. Methods To better understand the relationship between AP and MAHA-T and to evaluate its response to PLEX, we retrospectively reviewed all cases of suspected TTP/ MAHA-T treated by PLEX in the context of AP in our institution from 2005 to 2015. For the purpose of this report, we preferred to use the term MAHA-T to describe this phenomenon since TMA usually refers to a pathologic diagnosis. Finally, a literature review of published cases was also performed. Results Five patients were treated with PLEX for suspicion of TTP in the context of AP between January 1st, 2005 and December 31st, 2015 at our centre. Median age was 36 (31-60). Etiologies for pancreatitis were alcohol (3/5) or idiopathic (2/5). Peak lipase level ranged between 426 and 5853 U/L. One patient had 3 episodes of MAHA-T following AP, always in the context of alcohol abuse. Two patients had evidence of MAHA-T on admission, while the remaining 3 patients had an unremarkable CBC at presentation followed by an abrupt drop in platelet count (nadir, 9-23 x 109/L). All patients showed simultaneously signs of MAHA (Hb nadir between 47 and 93 g/L) with fragmentation on the blood smear and abnormal hemolytic parameters: LD level 1104-8097 U/L, bilirubin 36-176 umol/L, reticulocyte count 130-541 x109/L and undetectable haptoglobin. The median time from AP presentation to the development of laboratory or clinical features of MAHA-T in these cases was 2 days (1-3). Acute kidney injury was present in all cases with creatinine levels ranging between 118-906 umol/L. One patient required hemodialysis. Other observed end organ damage included neurologic symptoms (3/5 patients), elevated troponin (5/5 patients) and transaminitis (4/5). One patient experienced a cardiac arrest. All patients had ADAMTS13 activity measured. One patient had severe deficiency on two separate episodes (ADAMTS13 was <1% and 6% respectively). Three other patients had normal ADAMTS13 activity (average 69%) and one had a moderate deficiency by a qualitative assay. In 4 patients, where tests were performed, there was significant heterogeneity in complement protein and function studies between patients ranging from normal to depressed C3 and C4 and normal to elevated CH50. Complement genetics screen was performed in 3 cases and was normal in all 3 cases. PLEX was initiated in all patients and remission (platelet count over 150 x 109/L) was seen for all after a median of 10 daily treatments (2-12). High dose steroids were used in 4 patients. All patients survived to discharge and completely recovered their kidney function. Conclusion TTP/MAHA-T precipitated by AP is increasingly recognized and more than 40 cases have been described in the literature. Similar to our findings, time to MAHA-T occurrence is generally reported within the first 4 days after admission for AP, often when markers for pancreatitis are improving, and most patients do not have severe ADAMTS13 deficiency. While many have looked at ADAMTS13 level, to our knowledge, none have yet reported thorough complement studies and genetics. The 3 cases described herein are then the first cases suggesting this is not a complement mediated disorder. Finally, our review and cases confirm that PLEX is effective and prognosis is good in almost all cases. Disclosures Pavenski: Alexion Pharmaceuticals Inc.: Honoraria, Other: attended an entity's advisory boards.

scholarly journals Cell Derived Microparticles (MP) in Different Phases of Thrombotic Thrombocytopenic Purpura (TTP) and Effect of Exchange Plasmapheresis (EPP) on Their Profiles

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3736-3736
Author(s):  
Robert A Ali ◽  
Yonette Paul ◽  
Robert Forestal McCauley ◽  
Miriam Yaniz ◽  
Martha Q. Gonzalez ◽  
...  
Keyword(s):  
Platelet Count ◽  
Hemolytic Anemia ◽  
Acute Phase ◽  
Clinical Course ◽  
Conflicts Of Interest ◽  
Response To Therapy ◽  
Red Cell ◽  
Adamts13 Activity ◽  
Clotting Factors ◽  
Remission Phase

Abstract BACKGROUND: Cell derived MPs are small membrane vesicles released during cell activation or apoptosis. They express an inside-out membrane, which exposes the negatively charged phospholipid layer outside, allowing clotting factors to be anchored and generate thrombin. Among various species of MPs, RMP (red cell MPs), PMP (platelet MPs), LMP (leukocytes), EMP (endothelial cells) are of special interest. They play an important role in hemostasis, thromboses, and inflammation. MPs mirror early injury of parent cells and are sensitive early biomarkers of underlying disorders. TTP is a microangiopathy mediated by antibody-induced depletion of ADAMTS13, a von Willebrand factor-cleaving protease. Endothelial injury promotes platelet clumping and formation of platelet rich microthrombi in the microcirculation. Subsequent platelet sequestration leads to impaired microcirculation, thrombocytopenia and red cell fragmentation with a microangiopathic hemolytic anemia. Exchange plasmapheresis (EPP) is the standard therapy. It removes antibodies to ADAMTS13, replacing it with ADAMTS13 rich plasma. It is possible that EPP removes thrombogenic MPs to improve the clinical course of TTP. In this study, we investigated MP profiles in active and remission phase of TTP and the effect of EPP on MP profiles. We also aimed to determine if MP profiles may be a useful measure for monitoring clinical course and tracking progress of therapy. METHODS: A retrospective study was conducted evaluating MP assays in patients with TTP. MP profiles were reviewed in acute and remission phases of TTP. Acute phase was defined as thrombocytopenia, clinical evidence of microangiopathy and hemolytic anemia and low ADAMTS13 activity. Remission was defined as sustained normalization of laboratory parameters and no further microangiopathy for at least one month. Patients were studied longitudinally, with MP assays before and after EPP. EMP were measured by CD31+/CD42b− (EMP31), CD62E+ (EMP62); PMP by CD31+/CD42b+ (PMP42) and CD41+ (PMP41). All were measured in platelet-poor plasma by flow cytometry. All MP data are presented in units of x105/µL. The differences in MP patterns among TTP patients in active and remission phases of disease, as well as the effect of EPP on MP profiles were assessed. RESULTS: Among 20 patients with TTP, 8 (40%) were in acute phase and 12 (60%) in remission. An average of 10.7 EPP were performed. The average platelet count prior to EPP was 50.6x103/µL, which increased to 248 x103/µL following the last EPP. ADAMTS13 activity was generally <10% at the onset. For patients in the acute phase, PMPs were low: PMP41 0.32 (±0.11), PMP42 3.11 (±2.56), but consistently increased following EPP to the point of statistical significance at the last treatment: PMP41 1.26 (±0.71), p=0.005 and PMP42 7.65 (±5.03), p=0.039. Moreover, levels were higher in the remission phase for both PMPs, but only statistically significant for PMP41: 1.39, p=0.034. Conversely, EMP62E was initially elevated on presentation, but declined with successive EPP: 6.07 (±3.02) prior to initiation of EPP to 4.5 (±3.1) upon the last day of EPP. Furthermore, this pattern continued into remission, with EMP62E of 2.72 (±2.11), p=0.009. Similar to the trend in EMP62E, RMP was elevated in the acute phase (25.1 [±18.5]) before steadily declining with EPP (19.65 [±12.53]). This progressive drop in RMP persisted for those in remission phase of TTP 10 (±5.42), p=0.015. DISCUSSION/CONCLUSION: Taken collectively, cell derived MP's were found to reflect disease activity and response to therapy. There was a linear correlation between PMP levels and platelet count. Low PMPs in the acute phase reflects the initial thrombocytopenia characteristic of TTP. When EPP was initiated, the disease improved and there was a rise in PMP which mirrored the rise in platelets. This rise was sustained in the remission phase. Conversely, EMP62E and RMP are increased in acute phase TTP due to endothelial activation, microthrombi deposition and red cell fragmentation. After EPP the disease is quiescent, hence the progressive decline of EMP62E and RMP. These results show promising utility of cell derived MP profiles as a clinical tool to surveil chronic TTP patients and to predict disease relapse at an early stage. After EPP is initiated, change in MP Profiles may be used to monitor response to therapy and determine the appropriate time to wean EPP. Disclosures No relevant conflicts of interest to declare.

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 &lt;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 &lt;2.4 x10-10). The prevalence of thrombocytopenia &lt;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 &lt;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.

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