scholarly journals Acute Immune-Mediated Thrombocytopenia due to Oxaliplatin and Irinotecan Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Eric L. Tam ◽  
Padma L. Draksharam ◽  
Jennifer A. Park ◽  
Gurinder S. Sidhu
Keyword(s):  
Colon Cancer ◽  
Flow Cytometry ◽  
Severe Thrombocytopenia ◽  
Flow Cytometry Assay ◽  
Drug Induced ◽  
Advanced Colon Cancer ◽  
Platelet Antibodies ◽  
Immune Mediated ◽  
Drug Dependent ◽  
Underlying Mechanisms

We describe a case of a 63-year-old woman with advanced colon cancer and liver metastases who was treated with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and cetuximab chemotherapy. She tolerated 13 cycles of chemotherapy without any significant hematological side effects, but after the 14th cycle, she developed melena and was admitted for severe thrombocytopenia. After supportive care, the platelet counts rapidly improved to 76,000/μL. Upon initiation of FOLFIRI and cetuximab chemotherapy, she again developed rectal bleeding and severe thrombocytopenia with a platelet count of 6000/μL. Lab testing was positive for oxaliplatin and irinotecan drug-dependent platelet antibodies on flow cytometry assay. Drug-induced thrombocytopenia (DITP) is associated with several classes of drugs with several proposed underlying mechanisms. Prospective studies are needed to further address different mechanisms of drug-induced thrombocytopenia.

scholarly journals Drug-induced thrombocytopenia: pathogenesis, evaluation, and management

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 153-158 ◽  
Author(s):  
James N. George ◽  
Richard H. Aster
Keyword(s):  
Single Dose ◽  
Causal Relation ◽  
Severe Thrombocytopenia ◽  
Antithrombotic Agents ◽  
Drug Induced ◽  
Level Of Evidence ◽  
Common Cause ◽  
Fibrinogen Binding ◽  
Immune Mediated ◽  
Drug Dependent

AbstractAlthough drugs are a common cause of acute immune-mediated thrombocytopenia in adults, the drug etiology is often initially unrecognized. Most cases of drug-induced thrombocytopenia (DITP) are caused by drug-dependent antibodies that are specific for the drug structure and bind tightly to platelets by their Fab regions but only in the presence of the drug. A comprehensive database of 1301 published reports describing 317 drugs, available at www.ouhsc.edu/platelets, provides information on the level of evidence for a causal relation to thrombocytopenia. Typically, DITP occurs 1 to 2 weeks after beginning a new drug or suddenly after a single dose when a drug has previously been taken intermittently. However, severe thrombocytopenia can occur immediately after the first administration of antithrombotic agents that block fibrinogen binding to platelet GP IIb-IIIa, such as abciximab, tirofiban, and eptifibatide. Recovery from DITP usually begins within 1 to 2 days of stopping the drug and is typically complete within a week. Drug-dependent antibodies can persist for many years; therefore, it is important that the drug etiology be confirmed and the drug be avoided thereafter.

Tamoxifen-Induced Immune-Mediated Platelet Destruction. A Case Report

1993 ◽  
Vol 79 (3) ◽  
pp. 231-234 ◽  
Author(s):  
Alfonso Candido ◽  
Stefano Bussa ◽  
Raffaele Tartaglione ◽  
Rosalba Mancini ◽  
Carlo Rumi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Severe Thrombocytopenia ◽  
Platelet Destruction ◽  
Drug Induced ◽  
New Era ◽  
Elderly Female ◽  
Immune Mediated ◽  
Drug Dependent ◽  
Reliable Methods

Drug-induced immunologic thrombocytopenia, a fairly common disorder, is characterized by drug-dependent antiplatelet antibodies that destroy circulating platelets in the presence of the provoking drug or its metabolites. The development of reliable methods for the detection of platelet-bound immunoglobulins causing in vivo platelet destruction, such as the use of monoclonal antibodies tagged with fluorescein and flow cytofluorimetric analysis, has ushered in a new era to differentiate between immune and non-immune thrombocytopenias. A severe thrombocytopenia developed in an elderly female patient treated with tamoxifen, a non-steroidal antiestrogen drug, after surgery for breast cancer. A tamoxifen-dependent platelet antibody was detected in the patient's serum and linked on the platelet membranes. This antibody reacted only in the presence of the offending drug and showed platelet specificity. Withdrawal of drug restored platelet count to normal levels.

Drug-Induced Thrombocytopenia

2009 ◽  
Vol 133 (2) ◽  
pp. 309-314
Author(s):  
Barton Kenney ◽  
Gary Stack
Keyword(s):  
At Risk ◽  
19Th Century ◽  
Clinical Management ◽  
Drug Induced ◽  
Medication Withdrawal ◽  
Platelet Antibodies ◽  
Patients At Risk ◽  
Drug Dependent ◽  
The 19Th Century ◽  
Prompt Diagnosis

Abstract Drug-induced thrombocytopenia was first described in the 19th century, yet our understanding of its pathogenesis continues to evolve. The list of drugs implicated in drug-induced thrombocytopenia is extensive and growing. Many, if not most, of these medications induce thrombocytopenia by immune mechanisms. Because the degree of thrombocytopenia can put patients at risk for serious bleeding, a prompt diagnosis is key to clinical management. The laboratory approach to diagnosing drug-induced thrombocytopenia is 2-pronged. First, nondrug causes of thrombocytopenia must be ruled out. Second, testing for drug-dependent platelet antibodies, available at specialized reference laboratories, often can identify the offending medication, although usually not in time for initial clinical management. Once a medication is suspected of causing thrombocytopenia, it must be discontinued promptly, and the patient should be monitored closely. Thrombocytopenia generally resolves quickly after offending medication withdrawal, and the prognosis of drug-induced thrombocytopenia is then excellent.

Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Thomas L. Ortel
Keyword(s):  
Platelet Count ◽  
Heparin Therapy ◽  
Severe Thrombocytopenia ◽  
Drug Induced ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Increased Risk ◽  
Antibody Levels

Abstract Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.

scholarly journals An Antibody From a Patient With Ranitidine-Induced Thrombocytopenia Recognizes a Site on Glycoprotein IX That Is a Favored Target for Drug-Induced Antibodies

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2359-2365 ◽  
Author(s):  
G. Gentilini ◽  
B.R. Curtis ◽  
R.H. Aster
Keyword(s):  
Tight Binding ◽  
Chinese Hamster ◽  
Severe Thrombocytopenia ◽  
H2 Receptor Antagonist ◽  
Drug Induced ◽  
Histamine H2 Receptor ◽  
H2 Receptor ◽  
Drug Dependent ◽  
A Site ◽  
Common Target

Although thrombocytopenia associated with the use of histamine H2 receptor (H2R) antagonists has been described, a drug-dependent, platelet-reactive antibody has not previously been identified in such cases. We studied serum from a patient who developed acute, severe thrombocytopenia after exposure to the H2 receptor antagonist, ranitidine, and identified an antibody that reacted with normal platelets in the presence of this drug at pharmacologic concentrations. In flow cytometric and immunoprecipitation studies, the antibody was shown to be specific for the glycoprotein Ib/IX complex (GPIb/IX). From the pattern of monoclonal antibody (MoAb) inhibition and the reactions of antibody with Chinese hamster ovary (CHO) cells transfected with GPIX and GPIbβ, we found that the patient's antibody is specific for an epitope on GPIX close to, or identical with a site recognized by the MoAb SZ1 that is a common target for antibodies induced by quinine and quinidine, drugs structurally unrelated to ranitidine. These findings provide evidence that immune thrombocytopenia can be caused by sensitivity to an H2 R antagonist and suggest that the SZ1 binding site on GPIX may be a common target for drug-induced antibodies. Further studies of the epitope for which SZ1 is specific may provide clues to the mechanism(s) by which drugs promote tight binding of antibody to a membrane glycoprotein and cause platelet destruction in patients with drug sensitivity.

scholarly journals Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Blood ◽  
1994 ◽  
Vol 84 (11) ◽  
pp. 3691-3699 ◽  
Author(s):  
TE Warkentin ◽  
CP Hayward ◽  
LK Boshkov ◽  
AV Santos ◽  
JA Sheppard ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Procoagulant Activity ◽  
Severe Thrombocytopenia ◽  
Drug Reactions ◽  
Heparin Induced Thrombocytopenia ◽  
Circulating Microparticles ◽  
Thrombotic Complications ◽  
Drug Dependent

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.

scholarly journals An Antibody From a Patient With Ranitidine-Induced Thrombocytopenia Recognizes a Site on Glycoprotein IX That Is a Favored Target for Drug-Induced Antibodies

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2359-2365 ◽  
Author(s):  
G. Gentilini ◽  
B.R. Curtis ◽  
R.H. Aster
Keyword(s):  
Tight Binding ◽  
Chinese Hamster ◽  
Severe Thrombocytopenia ◽  
H2 Receptor Antagonist ◽  
Drug Induced ◽  
Histamine H2 Receptor ◽  
H2 Receptor ◽  
Drug Dependent ◽  
A Site ◽  
Common Target

Abstract Although thrombocytopenia associated with the use of histamine H2 receptor (H2R) antagonists has been described, a drug-dependent, platelet-reactive antibody has not previously been identified in such cases. We studied serum from a patient who developed acute, severe thrombocytopenia after exposure to the H2 receptor antagonist, ranitidine, and identified an antibody that reacted with normal platelets in the presence of this drug at pharmacologic concentrations. In flow cytometric and immunoprecipitation studies, the antibody was shown to be specific for the glycoprotein Ib/IX complex (GPIb/IX). From the pattern of monoclonal antibody (MoAb) inhibition and the reactions of antibody with Chinese hamster ovary (CHO) cells transfected with GPIX and GPIbβ, we found that the patient's antibody is specific for an epitope on GPIX close to, or identical with a site recognized by the MoAb SZ1 that is a common target for antibodies induced by quinine and quinidine, drugs structurally unrelated to ranitidine. These findings provide evidence that immune thrombocytopenia can be caused by sensitivity to an H2 R antagonist and suggest that the SZ1 binding site on GPIX may be a common target for drug-induced antibodies. Further studies of the epitope for which SZ1 is specific may provide clues to the mechanism(s) by which drugs promote tight binding of antibody to a membrane glycoprotein and cause platelet destruction in patients with drug sensitivity.

A Comparison of Two Assays for Platelet Antibodies

1979 ◽  
Author(s):  
J.G. Kelton ◽  
A. Giles ◽  
P.B. Neame ◽  
M. Blajchman ◽  
J. Hirah
Keyword(s):  
Multiple Myeloma ◽  
Immune Thrombocytopenia ◽  
Test System ◽  
Healthy Controls ◽  
Fluorescent Assay ◽  
Drug Induced ◽  
Optimal Method ◽  
Platelet Antibodies ◽  
Immune Mediated ◽  
Fluorescence Test

The optimal method for assaying platelet bound antibody is uncertain. We have compared a fluorescent assay (FA) with a (quantitative) antiglobulin consumption assay for platelet associated IgG (PAIgG) in normals and thrombocytopenics with ITP, SLE, non-immune and drug-induced thrombocytopenia. Forty-eight of 49 hospitalized and healthy controls had normal PAIgG levels by the antiglobulin consumption assay (2.6 ± 0.2 fg IgG/platetet, ± SE, normal 0-5 fg) and the FA was negative in 41. The PAIgG level was elevated (20.0 ± 1.9 fq IgG/platdet) in 42 of 45 determinations on ITP patients. The FA was positive in 21. Positivity in the FA test did not relate closely to PAIgG level. The PAlqG was elevated (29.0 - 7.3) in 14 of 15 assays in thrombocytopenic SLE patients. The FA was positive in 3. The PAIgG level was elevated in all 9 patients with drug-induced thrombocytopenia (42.4 ± 23.2) without addition of the drug to the test system. The FA was positive in 5. In 2 of 12 patients with non-immune thrombocytopenia the PAIgG level was slightly elevated (both patients had multiple myeloma) and the FA was positive in 5. The results suggest that the quantitative antiglobulin consumption assay is more sensitive than the fluorescent assay in the diagnosis of immune mediated throinbocytopenia. The significance of the lack of correlation between positivity in the fluorescence test and the PAIgG levels found in patients with ITP is uncertain.

scholarly journals Patients with quinine-induced immune thrombocytopenia have both “drug-dependent” and “drug-specific” antibodies

Blood ◽  
2006 ◽  
Vol 108 (3) ◽  
pp. 922-927 ◽  
Author(s):  
Daniel W. Bougie ◽  
Peter R. Wilker ◽  
Richard H. Aster
Keyword(s):  
Immune Thrombocytopenia ◽  
Drug Sensitivity ◽  
Soluble Form ◽  
Severe Thrombocytopenia ◽  
Membrane Glycoproteins ◽  
Drug Induced ◽  
Specific Antibodies ◽  
Cellular Targets ◽  
Surrogate Measure ◽  
Drug Dependent

AbstractImmune thrombocytopenia induced by quinine and many other drugs is caused by antibodies that bind to platelet membrane glycoproteins (GPs) only when the sensitizing drug is present in soluble form. In this disorder, drug promotes antibody binding to its target without linking covalently to either of the reacting macro-molecules by a mechanism that has not yet been defined. How drug provides the stimulus for production of such antibodies is also unknown. We studied 7 patients who experienced severe thrombocytopenia after ingestion of quinine. As expected, drug-dependent, platelet-reactive antibodies specific for GPIIb/IIIa or GPIb/IX were identified in each case. Unexpectedly, each of 6 patients with GPIIb/IIIa-specific antibodies was found to have a second antibody specific for drug alone that was not platelet reactive. Despite recognizing different targets, the 2 types of antibody were identical in requiring quinine or desmethoxy-quinine (cinchonidine) for reactivity and in failing to react with other structural analogues of quinine. On the basis of these findings and previous observations, a model is proposed to explain drug-dependent binding of antibodies to cellular targets. In addition to having implications for pathogenesis, drug-specific antibodies may provide a surrogate measure of drug sensitivity in patients with drug-induced immune cytopenia.

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.

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