Carfilzomib-induced thrombotic microangiopathy. A case report

2021 ◽  
pp. 107815522110674
Author(s):  
Valentina Scheggi ◽  
Irene Merilli ◽  
Edoardo Cesaroni ◽  
Bruno Alterini
Keyword(s):  
Multiple Myeloma ◽  
Case Report ◽  
Thrombotic Microangiopathy ◽  
Proteasome Inhibitors ◽  
Causal Association ◽  
Drug Induced ◽  
General Outcome ◽  
Life Threatening ◽  
Drug Dependent ◽  
New Onset

Introduction Drug-induced thrombotic microangiopathy (DITMA) is an acquired condition resulting from exposure to a drug that induces the formation of platelet-rich thrombi in small arterioles or capillaries secondary to drug-dependent antibodies or direct tissue toxicity. Carfilzomib is a selective proteasome inhibitor approved to treat selected patients with Multiple Myeloma (MM). It is one of the drugs with the strongest evidence for a causal association with non-antibody-mediated DITMA. Case Report A 75-year-old man presented to the emergency department for the outbreak of vomit, asthenia, oliguria and dark stool emission. He was recently diagnosed with multiple myeloma, treated with lenalidomide, dexamethasone and carfilzomib. Laboratory exams were significant for microangiopathic haemolytic anaemia, thrombocytopenia and new-onset renal failure. ADAMTS-13 levels were in range, and no infectious signs were found both in blood nor in stool test. Management & Outcome A carfilzomib induced thrombotic microangiopathy was soon suspected. Thus, since daily haemodialysis and supportive care did not seem to get a fast enough recovery, the patient was treated with eculizumab with a good general outcome. Discussion Drug-induced thrombotic microangiopathy is a rare and often life-threatening acquired condition whose diagnosis can be challenging and whose therapy is not always limited to supportive treatment and drug avoidance. Carfilzomib, along with other proteasome inhibitors, is one of the described potential drugs which can trigger such a manifestation.

scholarly journals Drug-induced Thrombotic Microangiopathy During Maintenance Treatment in a Patient With Multiple Myeloma

HemaSphere ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. e192 ◽  
Author(s):  
Víctor Higuero Saavedra ◽  
Verónica González-Calle ◽  
Eduardo Sobejano ◽  
Josefa Sebastiá ◽  
Mónica Cabrero ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Thrombotic Microangiopathy ◽  
Maintenance Treatment ◽  
Drug Induced

scholarly journals Thrombocytopenia in Young Patient due to Anti Tuberculosis Drugs : A Case Report

2020 ◽  
Vol 6 (1) ◽  
pp. 5
Author(s):  
Aryani Prawita Sari ◽  
Winariani Koesoemaprodjo
Keyword(s):  
Complete Blood Count ◽  
Clinical Problem ◽  
Drug Induced ◽  
Platelet Antibodies ◽  
Laboratory Confirmation ◽  
Chief Complaints ◽  
Life Threatening ◽  
Rapid Destruction ◽  
Underlying Causes ◽  
Drug Dependent

Background: Most anti-tuberculosis (ATD) drugs are relatively safe, but unusual serious reactions can occur. Thrombocytopenia is an uncommon but potentially life-threatening complication of certain ATDs and is characterized by rapid destruction of platelets whenever an offending drug is taken by a susceptible person. Rifampicin is the most common cause of thrombocytopenia.Case: A 25 years old woman came with chief complaints, shortness of breath since 1 week before admission and cough with phlegm since 2 months before admission. The patient received antibiotic and ATD. In the course of improving on sepsis and pneumonia, the patient had thrombocytopenia accompanied by melena on day 4 of treatment.Discussion: Thrombocytopenia is defined as a disorder, which showed an abnormality on the low amount of thrombocyte. Thrombocytopenia was commonly cofounded when Complete blood count (CBC) was performed. The majority of the mechanism associated with thrombocytopenia is the immune. Drug-induced Thrombocytopenia (DITP) is an exclusion diagnosis, which is obtained by ruling out other underlying causes that resulted in thrombocytopenia.Conclusion: This case illustrates that the discovery of isolated thrombocytopenia in a patient taking several medications presents a challenging clinical problem. Laboratory confirmation of drug-induced thrombocytopenia at the time of initial presentation is not possible because tests for drug-dependent anti-platelet antibodies are not available in most clinical laboratories. The diagnosis of drug-induced thrombocytopenia can be supported only by resolution of thrombocytopenia after discontinuation of therapy with the suspected drug.

scholarly journals Plasma exchange for thrombotic microangiopathy secondary to dermatomyositis associated with acute kidney injury and complement activation: a case report with literature review

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Norifumi Hayashi ◽  
Keiichirou Okada ◽  
Yuko Tsuruyama ◽  
Yu Kagaya ◽  
Sho Kumano ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Intensive Care ◽  
Case Report ◽  
Plasma Exchange ◽  
Complement Activation ◽  
Thrombotic Microangiopathy ◽  
Kidney Injury ◽  
Ivig Therapy ◽  
Case Presentation ◽  
Life Threatening

Abstract Background Thrombotic microangiopathy (TMA) in patients with connective tissue disease is rare but life-threatening. In particular, the survival rate of patients with dermatomyositis (DM) that develop TMA is low. The effectiveness of plasma exchange (PEX) therapy is unclear for the treatment of TMA secondary to DM. Case presentation We describe a case of a 28-year-old woman who developed severe DM complicated by aspiration pneumonia from dysphagia and acute kidney injury. The patient was unresponsive to corticosteroids and intravenous immunoglobulin (IVIG) therapy and developed TMA. In this case, immunofluorescence of skin biopsy revealed that complement activation was involved in the pathogenesis of DM. After 6 PEX therapies, thrombocytopenia improved. She was successfully treated by intensive care and PEX therapy. Conclusions PEX therapy was effective to treat TMA secondary to DM associated with complement activation.

scholarly journals Long-Term Disease Control by Pomalidomide-/Dexamethasone-Based Therapy in a Patient with Advanced Multiple Myeloma: A Case Report and Review of the Literature

2015 ◽  
Vol 8 (1) ◽  
pp. 189-195 ◽  
Author(s):  
Sophia Danhof ◽  
Martin Schreder ◽  
Susanne Strifler ◽  
Hermann Einsele ◽  
Stefan Knop
Keyword(s):  
Multiple Myeloma ◽  
Case Report ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Infectious Complications ◽  
Term Treatment ◽  
Novel Agents ◽  
Virus Reactivation ◽  
Long Term Treatment

Background: Therapy for multiple myeloma (MM) has substantially improved in the era of immunomodulatory drugs and bortezomib. However, the prognosis of patients with progressive disease despite treatment with these ‘novel agents' remains poor. Recently, pomalidomide was approved in this setting, but a median progression-free survival of <4 months still leaves room for improvement. Pomalidomide-based combination therapies are currently under investigation, but data on long-term treatment are lacking. Case Report: We present the case of a 68-year-old woman with refractory MM who received pomalidomide in combination with various drugs including anthracyclines, alkylators and proteasome inhibitors. Initially, major hematological toxicities and infectious complications including a hepatitis B virus reactivation were encountered. With careful dose adjustments and selection of combination partners, pomalidomide treatment was maintained for over 4 years and led to a sustained partial remission. In particular, the well-tolerated regimen of bortezomib, cyclophosphamide and dexamethasone together with pomalidomide was administered for >30 cycles. Conclusion: This case illustrates the value of an individualized approach to myeloma care given an increasing availability of ‘novel agents'. Tailored treatment using these drugs as a backbone is essential to achieve long-lasting responses and minimize side effects.

scholarly journals Vitamin B12 deficiency masquerading Addison’s disease: a case report of an adolescent male

2020 ◽  
Vol 8 (5) ◽  
pp. 1932
Author(s):  
Sudhaa Mani M. ◽  
Yasmeen Ahamed S. ◽  
Nanitha Lakshmi Kavitha Giri ◽  
Jesudasan A.
Keyword(s):  
Case Report ◽  
Clinical Manifestations ◽  
Vitamin B12 Deficiency ◽  
Ultra Violet ◽  
Adolescent Male ◽  
Drug Induced ◽  
Ultra Violet Radiation ◽  
Life Threatening ◽  
B12 Deficiency ◽  
Violet Radiation

Intraoral pigmentations range from innocuous physiologic pigments to life-threatening malignant conditions. It is at the discretion of the observing clinician to identify the abnormal clinical manifestations and provide necessary intervention. There are controversies about delineating the definite etiology of the pigmentation such as race, exposure to ultra-violet radiation, drug-induced pigmentation post-inflammatory pigments of the oral cavity.

Thrombotic thrombocytopenic purpura with typical pentalogy in a child: a case report and literature review

2021 ◽  
Author(s):  
Qian Wan ◽  
Yao Ye ◽  
Xiaohong Zhong ◽  
Zhongjin Xu ◽  
Jian Li
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Renal Insufficiency ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Thrombotic Microangiopathy ◽  
Typical Case ◽  
Microangiopathic Hemolytic Anemia ◽  
Thrombocytopenic Purpura ◽  
Life Threatening

Abstract Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy with clinical quintuple symptoms, including fever, thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, and renal insufficiency. TTP onset in children is rare, and the percentage of acute TTP with these five symptoms at the same time is <10%. In this study, we reported a typical case of TTP onset in a child with clinical quintuple symptoms.

Drug-Dependent Murine Monoclonal Antibodies (mAbs) Mimic Antibodies Found in Patients with Drug-Induced Immune Thrombocytopenia (TP).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 731-731
Author(s):  
Daniel W. Bougie ◽  
Jessica Birenbaum ◽  
Scott Ahl ◽  
Richard H. Aster
Keyword(s):  
Molecular Basis ◽  
Immune Thrombocytopenia ◽  
Tight Binding ◽  
Human Platelets ◽  
Soluble Form ◽  
Membrane Glycoproteins ◽  
Drug Induced ◽  
Life Threatening ◽  
Drug Dependent ◽  
Covalently Linked

Abstract Drug-induced immune thrombocytopenia (DITP) is a serious and sometimes life-threatening complication of treatment with many drugs. In most instances (excluding heparin-induced TP), platelet (plt) destruction is caused by antibodies (abs) that recognize distinct epitopes on platelet membrane glycoproteins (GP) only when the sensitizing drug is present in soluble form. How drug at pharmacological levels promotes tight binding of antibody to a specific target is unknown, in part because only polyclonal human abs have been available for study. We sought to produce monoclonal abs (mAbs) that mimic the behavior of human drug-dependent abs to create tools that can be used to study the molecular basis for this interaction. Mice were immunized with GPIIb/IIIa isolated from human platelets together with soluble quinine (Qn), tirofiban (Tf), or eptifibatide (Ef), three drugs that commonly cause DITP. Hybridomas were prepared from splenic B cells using a standard protocol and approximately 550 supernatants from each cultured hybrid line were screened for DDAbs by flow cytometry using normal platelets as targets. To date, 11 Abs that react with GPIIb/IIIa only in the presence of the immunizing drug (2 Qn-, 3 Tf- and 6 Ef-specific) have been identified. Preliminary studies show that the Qn-specific abs bind reversibly to GPIIb/IIIa at 50 nM Qn, a concentration much lower than is achieved pharmacologically, and are not inhibited by Qn at 5 mM, the limit of solubility. Quinidine (Qd) the diastereoisomer of Qn, supports only weak ab binding at a concentration of 50 uM. The tirofiban and eptifibatide-dependent abs recognize GPIIb/IIIa occupied by these RGD ligand-mimetic GPIIb/IIIa inhibitors. In each of these respects, reaction patterns of the three groups of mAbs closely resemble those of abs from patients experiencing TP after treatment with one of these drugs. These findings show that mAbs mimicking the behavior of human drug-dependent abs can be produced by immunizing mice with GP and soluble drug to produce probes suitable for characterizing the molecular basis of ab-drug-target interactions leading to platelet destruction in DITP. It is noteworthy that these mAbs were induced using soluble drug and protein for immunization because this suggests that the immune response leading to DITP does not require the sensitizing drug to be covalently linked to a protein, i.e, does not require the drug to act as a classical hapten.

Thrombotic Microangiopathy in Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5317-5317 ◽  
Author(s):  
Jennifer Yui ◽  
Jan Van Keer ◽  
Ravi Vij ◽  
Kenar Jhaveri ◽  
Efstathios Kastritis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Hemolytic Anemia ◽  
Thrombotic Microangiopathy ◽  
Research Funding ◽  
Proteasome Inhibitors ◽  
Temporal Correlation ◽  
Organ Damage ◽  
Initial Presentation ◽  
Hematopoietic Stem ◽  
Cell Transplants

Abstract Background: Thrombotic microangiopathy (TMA) is a hematologic syndrome associated with endothelial injury, microvascular thrombosis, and hemolytic anemia resulting in end organ damage. TMA is rarely associated with multiple myeloma (MM) and is usually reported in the setting of allogeneic hematopoietic stem cell transplants (AHSCT), with associated graft versus host disease and calcineurin inhibitor use. We present 11 cases of TMA in MM patients not associated with AHSCT. Methods: Cases were collected from multiple centers in patients with confirmed diagnosis of MM. TMA was diagnosed by the presence of thrombocytopenia and evidence of microangiopathic hemolytic anemia. Results: Eleven patients with MM were identified to have developed TMA during the course of their disease. Two patients presented with TMA at the time of MM diagnosis. A third had been off treatment for over a year prior to presenting with a TMA which correlated with a significant increase in her free light chains. The other cases occurred during active treatment. All remaining patients received proteasome inhibitors, with three patients on bortezomib-based regimens and five patients on carfilzomib. One patient on a bortezomib-based regimen had been stable prior to developing a TMA in the setting of sepsis. In the remaining patients, the TMA developed rapidly after initiating the proteasome inhibitor. In all cases, the TMA improved after drug withdrawal. One patient was later rechallenged with bortezomib and again developed TMA. Discussion: A review of the literature reveals only nine cases of TMA with MM. Of these, 4 patients had TMA as the initial presentation of MM, and 5 patients were on treatment, most often bortezomib-based regimens. Our series patients match those in the literature closely and demonstrate that TMAs can occur in MM outside of the context of AHSCT. In roughly one third of patients, TMAs were the initial presentation of MM and improved with treatment of the MM. In others, the use of proteasome inhibitors appears to be associated with development of TMA. In these cases, the temporal correlation, resolution of TMA after medication withdrawal, and the instance of recurrence of TMA with rechallenge of bortezomib, support a causal relationship between the medication and the TMA. Thus, a high clinical suspicion for TMA must exist for patients on proteasome inhibitors who develop worsening anemia and thrombocytopenia. Medication should be withdrawn if TMA is diagnosed. Disclosures Vij: Onyx: Consultancy, Honoraria, Research Funding, Speakers Bureau; Millennium: Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy; Takeda: Consultancy, Research Funding; Novartis: Consultancy; Sanofi: Consultancy; Janssen: Consultancy; Merck: Consultancy.

Quinine-induced thrombocytopenia: drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro

Blood ◽  
2011 ◽  
Vol 117 (22) ◽  
pp. 5975-5986 ◽  
Author(s):  
José Perdomo ◽  
Feng Yan ◽  
Zohra Ahmadi ◽  
Xing-Mai Jiang ◽  
Roland Stocker ◽  
...  
Keyword(s):  
Cell Size ◽  
Production Capacity ◽  
Drug Induced ◽  
Average Cell Size ◽  
Average Cell ◽  
Human Cd34 ◽  
Cd34 Cells ◽  
Life Threatening ◽  
Drug Dependent

Abstract The development of immune cytopenias is a well-recognized side effect of many drugs. Quinine- and quinidine-dependent antibodies are classic examples of drug-induced effects that cause severe, life-threatening thrombocytopenia. Whereas the effects of drug-dependent antibodies on platelets have been well documented, their effects on megakaryocyte (Mk) biology are still unclear. We analyzed sera from several quinine-induced thrombocytopenia (QITP) patients on highly pure Mks (98% glycoprotein IIb-positive [GPIIb+]; 92% GPIX+) derived from human CD34+ cells cultured with human thrombopoietin. We demonstrate by flow cytometry and confocal microscopy that QITP IgGs bind Mks efficiently in the presence of quinine. Incubation of day-4 Mks with QITP sera or purified IgG resulted in induction of apoptosis, a significant decrease in cell viability, and an increase in cell death. Furthermore, QITP sera preferentially reduced the number of late GPIX+/GPIbα+ Mks and the number of receptors per cell in the surviving population. Ploidy distribution, lobularity, and average cell size of Mks remained unchanged after treatment. In addition, treated Mks showed a marked decrease in their proplatelet production capacity, suggesting that drug-dependent antibodies hinder platelet production. Therefore, QITP antibodies considerably reduce the proplatelet production capabilities of Mks despite undetectable effects on DNA content, morphology, and cell size.

Carfilzomib-induced tumor lysis syndrome in relapsed multiple myeloma: a report of two cases

2018 ◽  
Vol 105 (6) ◽  
pp. NP24-NP27
Author(s):  
Esra Terzi Demirsoy ◽  
Elif Birtas Atesoglu ◽  
Necmi Eren ◽  
Ayfer Gedük ◽  
Ozgur Mehtap ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Case Report ◽  
Proteasome Inhibitor ◽  
Tumor Lysis Syndrome ◽  
Proteasome Inhibitors ◽  
Hematologic Malignancies ◽  
Metabolic Abnormalities ◽  
Fatal Complication ◽  
Tumor Lysis ◽  
Proven Efficacy

Background: Tumor lysis syndrome (TLS) is a potentially fatal complication of cancer therapy characterized by severe electrolyte and metabolic abnormalities such as hyperphosphatemia, hyperkalemia, and hypocalcaemia. TLS usually occurs in aggressive hematologic malignancies such as Burkitt lymphoma and acute leukemia. TLS has rarely been observed in multiple myeloma (MM). Case report: We present 2 patients with relapsed MM who developed TLS after the first cycle of carfilzomib treatment. Conclusion: Carfilzomib is a next-generation proteasome inhibitor with proven efficacy in relapsed/refractory MM. Recently, increasing frequency of TLS has been reported in MM, especially after treatment with proteasome inhibitors. The potential complications of TLS should be considered especially during the first cycle of carfilzomib treatment.

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