Phenytoin-Induced Severe Thrombocytopenia: A Case Report.

Phenytoin is a commonly prescribed antiepileptic medication for the prevention and treatment of tonic-clonic or partial seizures. Thrombocytopenia is a rare and serious adverse effect of phenytoin. This case report presents the case of a patient with severe thrombocytopenia induced by phenytoin for the treatment of tonic-clonic seizures. A 63-year-old male received 300 mg/day of phenytoin for the treatment of tonic-clonic seizures. Seven days after receiving the first dose of phenytoin, he was diagnosed with severe thrombocytopenia (platelet count 44 x 109/L) without hemorrhage. Phenytoin was discontinued, and seizures were controlled with levetiracetam. Seven days after stopping phenytoin, his daily platelet count improved from 44 to 177 x 109/L. The Naranjo algorithm score of 7 was at a probable level for phenytoin-induced thrombocytopenia. Thrombocytopenia is a serious adverse drug reaction that can result in life-threatening bleeding. Phenytoin-induced thrombocytopenia commonly begins 1-90 days after administration, and the recovery time is 3-21 days. The potential mechanism of phenytoin-induced thrombocytopenia is drug-induced immune thrombocytopenia. Drugs that enhance the concentration of phenytoin epoxide may be a contributing factor in phenytoin-induced thrombocytopenia. Phenytoin-induced thrombocytopenia is a rare but serious hematological complication. It should be recognized early, particularly in patients with a high risk of hemorrhage or concurrently with medications that increase phenytoin epoxide. Regularly consecutive complete blood count tests may be essential in order to detect an early decrease in platelet count in these patients.

Valproic Acid-Induced Thrombocytopenia in Treatment-Resistant GABRB3 Genetic Epilepsy: A Case Report.

Valproic acid (VPA) is utilized in the management of a variety of seizure and mood disorders. A rare side effect of this medication is dose-dependent thrombocytopenia. In this case, we report a patient with a treatment-resistant epilepsy GABRB3 genetic variant phenotype who was admitted for sepsis and found to have significant thrombocytopenia with clinical manifestations of epistaxis and easy bruising, which was found to be due to VPA use rather than secondary to other clinical pathologies. The patient's clinical condition improved with supportive treatment including fluid rehydration. Platelet counts normalized after a transfusion and holding of her valproate. She experienced breakthrough seizures despite the initiation of diazepam. The decision was made to restart VPA per Neurology consult recommendations for better seizure control. She had no breakthrough seizures reported after restarting VPA in the hospital. This case highlights the importance of monitoring antiseizure medication side effects, especially in populations at higher risk due to treatment resistance.

Anti-Tubercular-Therapy-Induced Severe Thrombocytopenia Presenting as a Vocal Cord Bleed With Massive Hemoptysis Causing Mortality: A Catastrophic Combination.

Severe thrombocytopenia induced by anti-tubercular therapy (ATT) is a rare but potentially life-threatening complication. Severe thrombocytopenia is a known adverse effect of ATT, but its association with fatal hemoptysis is rare. Hematemesis and hemoptysis are two serious symptoms that indicate bleeding from the upper gastrointestinal and the lower respiratory tract, respectively. We report a rare case of a 65-year-old man, a diagnosed case of tuberculosis on ATT, who presented with massive hemoptysis. On navigating the bleed, the source was found to be a vocal cord bleed, which further led to massive clot formation in the left bronchus, leading to the collapse of the subsequent lung, leading to mortality. This case emphasizes the importance of recognizing ATT as a potential cause of bleeding and considering causes of massive hematemesis that are not gastrointestinal. It also highlights the need for a thorough evaluation of the airway in such patients.

Discontinuation of Levetiracetam and Valproic Acid Due to Adverse Effects in Early Post-traumatic Seizure Prophylaxis.

INTRODUCTION: Levetiracetam (LEV) and valproic acid (VPA) are two anti-epileptic drugs (AEDs) routinely used for post-traumatic seizure (PTS) prophylaxis at our institution. In our practice, VPA is used for its beneficial effects on behavioral agitation and headaches, but it is also associated with abnormal liver function tests (LFTs). Both medications may be associated with thrombocytopenia. There is less literature comparing the adverse effect profiles and discontinuation rates of LEV and VPA in the context of PTS prophylaxis. We conducted a quality improvement (QI) analysis to determine the safety of LEV and VPA for traumatic brain injury (TBI) patients at our institution. In particular, our QI analysis involved calculating the rates of discontinuation or change of drug regimen due to the adverse effects. METHODS: Our QI analysis focused on patients treated for TBI at our institution during a six-year period. We recorded the AED used and if the AED was discontinued or switched due to thrombocytopenia, behavioral agitation, headaches, or elevated LFTs (including elevated aspartate aminotransferase or alanine aminotransferase values). We also recorded the incidence of early PTS, defined as seizures within seven days of the TBI. RESULTS: Our QI analysis included patients with a mean age of approximately 49 years with nearly 75% males. The mean Glasgow Coma Scale (GCS) score was 12.88, with 73.11% of patients having a mild GCS. The three leading injury mechanisms were fall, assault, and motor vehicle collision. The three leading types of TBI were traumatic subarachnoid hemorrhage, subdural hematoma, and cerebral contusion. Among patients with no prior history of seizures, we found an early PTS incidence of 7.28%. For patients administered LEV and VPA, 0.11% (1/898) and 3.85% (4/104) had the medication discontinued or changed because of thrombocytopenia (p < 0.001), respectively. For patients on LEV, 4.01% (36/898) and 1.78% (16/898) had the medication discontinued or changed because of behavioral agitation and headaches, respectively. For patients on VPA, 2.88% (3/104) had the medication discontinued or changed because of hepatotoxicity. In total, 5.90% versus 6.73% (p > 0.5) of patients on LEV and VPA, respectively, had their medication regimens changed due to the adverse effects. CONCLUSIONS: The incidence of early PTS in our patients is within the range of what has been reported in the literature. The rate of discontinuation of LEV and VPA on account of adverse events is low in the context of PTS prophylaxis. Both medications had similar overall rates of discontinuation. VPA was discontinued more frequently than LEV due to thrombocytopenia, but discontinuation was not common in either case. LEV is associated with behavioral agitation and headaches, which makes VPA a desirable alternative for patients suffering from these symptoms.

Ceftriaxone-Induced Thrombotic Thrombocytopenic Purpura Treated Successfully With Plasmapheresis and Eculizumab: A Rare Case Report.

Thrombotic Thrombocytopenic Purpura (TTP) is a subtype of thrombotic microangiopathy (TMA) resulting in thrombocytopenia, anemia, fever, renal and neurological deficits. Although many drugs have been associated with drug-induced TTP, ceftriaxone has never been reported. Our case reports a patient who was started on ceftriaxone and developed TTP. Peripheral smear showed schistocytes and thrombocytopenia. Surprisingly, antibody formation against the metalloproteinase (ADAMTS13) levels were low-normal. The patient was treated with plasmapheresis and eczulimab, leading to platelet recovery and symptom resolution. TTP is a rare disorder and can be acquired or idiopathic. TTP can be diagnosed with normal ADAMTS13 as well. Further research is required to assess the mechanism by which ceftriaxone causes TTP. Physicians should consider the possibility of TTP in patients with similar presentations following ceftriaxone therapy and use it for timely diagnosis and treatment. Early diagnosis and treatment of ceftriaxone-induced TTP can prevent devastating consequences.

Autoimmune Heparin-Induced Thrombocytopenia: A Diagnostic and Management Challenge After Transcatheter Aortic Valve Replacement.

Heparin-induced thrombocytopenia (HIT) is a commonly encountered condition, especially in inpatient settings, and is often attributed to high mortality and prolonged hospital stays. A rare entity, autoimmune heparin-induced thrombocytopenia (aHIT) refers to a condition in which antiplatelet factor-4 (PF4) antibodies activate platelets even in the absence of heparin. Our patient presented 12 days after transcatheter aortic valve replacement (TAVR) with altered mental status and severe thrombocytopenia. Further work-up revealed acute thromboembolic cerebrovascular accident (CVA), and the HIT antibody was positive. He was started on intravenous argatroban infusion with poor response. Platelet factor-4 antibodies were positive as well, and he was started on intravenous immunoglobulins (IVIG) therapy resulting in platelet recovery. This case is a reminder to consider autoimmune HIT, especially when platelet count fails to improve with conventional therapy.

Drug-Induced Thrombocytopenia: A Case Involving Vancomycin.

Drug-induced thrombocytopenia (DIT) is a rare adverse effect that occurs when administering various medications. The medications associated with this possible adverse effect include heparin, penicillin, furosemide, vancomycin, non-steroidal anti-inflammatory drugs, ranitidine, and many others. DIT causes a rapid decrease in platelet counts after drug administration and typically resolves once the offending agent has been discontinued. The induced thrombocytopenia increases the bleeding risk and possibility of adverse effects throughout a hospital course. In this case report, we look at the presenting symptoms and treatment course of an interesting case of DIT that occurred following the administration of vancomycin.

Drug-Induced Thrombocytopenia Due to Nintedanib during Treatment of Idiopathic Pulmonary Fibrosis.

Nintedanib is a tyrosine kinase inhibitor that was approved for the treatment of patients with idiopathic pulmonary fibrosis in 2014. The most common side effect of Nintedanib is diarrhea, and thrombocytopenia is a rare side effect of Nintedanib. The exact mechanism is unknown, and the literature lacks case reports of this phenomenon. Here, we report the case of a patient who developed thrombocytopenia 12 weeks after starting treatment with Nintedanib. The patient underwent an extensive work up for infectious, hematological, autoimmune, and neoplastic diseases. The patient's thrombocytopenia resolved following cessation of Nintedanib. This case is significant as it reports a rare side effect that might have detrimental consequences if not recognized and treated timely. Additionally, the onset of thrombocytopenia was delayed, 3 months after the initiation of Nintedanib. We also highlight the various literature regarding drug-induced thrombocytopenia and explore the necessary work-up needed to exclude other potential diagnoses. We hope to advocate for multidisciplinary teams to be aware of patients with pulmonary fibrosis on Nintedanib so that this adverse effect can be recognized promptly.

Contezolid, a novel oxazolidinone antibiotic, may improve drug-related thrombocytopenia in clinical antibacterial treatment.

One of the major limitations in the clinical use of existing oxazolidinone antibiotics is their characteristic adverse reactions, in particular thrombocytopenia. In anti-infective treatment, if patients are suspected of having drug-induced thrombocytopenia, the first step is to immediately discontinue the offending drug. Even in patients with severe infections, the antibacterial drug may need to be changed or the antibacterial treatment may need to be discontinued because thrombocytopenia may have a more serious clinical prognosis. In addition, if the patient needs to continue antibacterial treatment after discharge, the lack of conditions for monitoring platelet levels may also pose hidden dangers to the patient. Contezolid is an orally administered oxazolidinone antibacterial agent approved by the National Medical Products Administration of China in 2021. We found that contezolid may have an improved safety profile with a significantly reduced potential for myelosuppression based on the results of our observational clinical study. In this article, we review the advantages of contezolid as a new oxazolidinone antibiotic and describe three typical clinical cases of patients who experienced drug-induced thrombocytopenia after using linezolid. The platelet levels of these different patients were all significantly improved to varying degrees after initiation of contezolid treatment.

A Case of Vancomycin-Induced Severe Immune Thrombocytopenia.

A male in his 60s presented with left lower extremity fractures following a vehicle accident. Hemoglobin, initially, was 12.4 mmol/L, and platelet count was 235 k/mcl. On day 11 of admission, his platelet count initially dropped to 99 k/mcl, and after recovery it rapidly decreased to 11 k/mcl on day 16 when the INR was 1.3 and aPTT was 32 s, and he continued to have a stable anemia throughout admission. There was no response in platelet count post-transfusion of four units of platelets. Hematology initially evaluated the patient for disseminated intravascular coagulation, heparin-induced thrombocytopenia (anti-PF4 antibody was 0.19), and thrombotic thrombocytopenic purpura (PLASMIC score of 4). Vancomycin was administered on days 1-7 for broad spectrum antimicrobial coverage and day 10, again, for concerns of sepsis. Given the temporal association of thrombocytopenia and vancomycin administration, a diagnosis of vancomycin-induced immune thrombocytopenia was established. Vancomycin was discontinued, and 2 doses of 1000 mg/kg of intravenous immunoglobulin 24 h apart were administered with the subsequent resolution of thrombocytopenia.

A Possible Case of Nitrofurantoin-Associated Immune Thrombocytopenia in a Healthy 45-Year-Old Caucasian Female.

Patients presenting with immune thrombocytopenia (ITP) may have an associated underlying medical condition or medication exposure serving as the cause of their disease, but oftentimes, ITP is due to an idiopathic, autoimmune cause. While molecular mimicry is recognized as the pathogenesis behind infectious-related causes of ITP, drug-induced ITP is likely due to hapten formation, leading to an inappropriate immune-mediated response. Several drugs are associated with the development of ITP. Nitrofurantoin, a commonly prescribed antibiotic for the treatment of uncomplicated urinary tract infections (UTIs), is a medication not previously associated with the development of ITP, with only one case reporting the development of thrombotic thrombocytopenic purpura (TTP) after nitrofurantoin use. Herein, we report a case of a middle-aged Caucasian female with a history of anxiety and hypothyroidism who developed ITP following exposure to nitrofurantoin three weeks prior to presentation. The patient presented with signs and symptoms consistent with ITP: an isolated low platelet count of 1 x 109/L, petechia, fatigue, normal coagulation parameters, recurrent epistaxis, and melena. Subsequently, she was hospitalized for five days, receiving a total of four units of platelets during her stay. She was started on daily high-dose intravenous corticosteroids and received a one-time dose of intravenous immunoglobulin (IVIG). After achieving a platelet count greater than 30 x 109/L, she was discharged from inpatient care, having responded well to corticosteroid treatment. Upon follow-up with outpatient hematology, her platelet levels were maintained above 150 x 109/L, with full resolution of her acute illness. An autoimmune laboratory workup was negative except for an isolated, newly positive antinuclear antibody IgG with an elevated titer of 1:640, leading to the conclusion that an immunological response to nitrofurantoin had occurred. To our knowledge, this is the first report that describes an association between nitrofurantoin use and ITP. We hope this report aids clinicians in recognizing the various immune-mediated adverse reactions associated with nitrofurantoin.

Pantoprazole-induced Thrombocytopenia: Unresponsive to Corticosteroid and Thrombocyte Concentrate Transfusion.

Introduction: Pantoprazole is a proton pump inhibitor (PPI) class drug that is widely used in the treatment of SRMD (stress-related mucosal disease in critical ill patients. PPI are one class of drugs used commonly both for treatment and prophylactic therapy for stress ulcers in intensive care unit (ICU). Case: We report a case of a 51-year old male who was referred to PKU Hospital. He was admitted to ICU with diagnosis of Hyperosmolar Hyperglymic State and bronchopneumonia. Thrombocytopenia was noted in admission. There was more than 70% decrease in platelet count after initiation of pantoprazole. Patient received Thrombocyte Concentrate (TC) transfusion and corticosteroid iv for several days, but only had minor increase in platelet count. The platelets recovered after stopping pantoprazole. Discussion: In the present case report, another exposures to parenteral pantoprazole in a dose of 40 mg once daily reproduced the same adverse drug reaction. In comparison to lansoprazole, thrombocytopenia from pantoprazole is more severe that necessitate TC transfusion and corticosteroid trial. However, in the present case, TC transfusion and corticosteroid fail to escalate platelet count. This finding suggests probability of non-immune mechanism of pantoprazole-induced thrombocytopenia. Conclusion: Pantoprazole may induce thrombocytopenia with new features that were immediately developed, resulting a decrease in platelet count >70%. The mechanism found in this case may be non-immune. Drug-induced thrombocytopenia is one of the rare complications that has to be kept in mind with the use of pantoprazole.

Piperacillin-Tazobactam-Induced Immune Thrombocytopenia: A Case Report.

Drug-induced immune thrombocytopenia is an isolated thrombocytopenia caused by accelerated platelet destruction from drug-dependent, platelet-reactive antibodies. Heparin-induced thrombocytopenia is the most common drug-induced immune thrombocytopenia. Common implicated antibiotics for drug-induced immune thrombocytopenia include ceftriaxone, trimethoprim-sulfamethoxazole, vancomycin, and penicillin. The platelet nadir can be less than 20 × 10 (9)/L and typically occurs within 1 to 2 weeks of exposure to the inciting drug. Although rare, drug-induced immune thrombocytopenia can be fatal. Diagnosis is made by excluding other causes of thrombocytopenia. Laboratory testing for drug-dependent antiplatelet antibodies is often helpful but not required. Thrombocytopenia typically improves within 1 to 2 days of drug discontinuation and platelet count returns to normal within a week. Identifying and discontinuing the implicated medication is key to prevention of serious complications. A patient case of drug-induced immune thrombocytopenia is described after initiation of empiric piperacillin-tazobactam for refractory right foot cellulitis in the setting of right fourth toe diabetic ulcer.

Eptifibatide-Induced Severe Thrombocytopenia After ST-Elevation Myocardial Infarction (STEMI): A Case Report.

Eptifibatide is a platelet glycoprotein (GP) IIb/IIIa inhibitor that is used in certain cases of acute coronary syndrome, including those with high thrombus burden or with no-reflow. It can rarely be associated with severe thrombocytopenia, which brings up a dilemma in managing those patients who require antiplatelet therapy. We discuss a patient who had ST-elevation myocardial infarction (STEMI) and developed severe thrombocytopenia after eptifibatide infusion. He was managed with platelet transfusion, stopping eptifibatide, and interrupting dual antiplatelet therapy (DAPT).

Piperacillin-Tazobactam Induced Rapid Severe Thrombocytopenia Without Known Exposure.

Thrombocytopenia is one of the commonly encountered laboratory abnormalities in the inpatient setting. The process of excluding life-threatening causes can be daunting and may result in overlooking iatrogenic sources such as medications. Antibiotics are known culprits; however, there are limited reports of rapid and severe onset thrombocytopenia following piperacillin-tazobactam (TZP) that were frequently observed in critically ill or immunocompromised patients with previous exposure to the antibiotic. This case describes a patient being treated for a soft tissue infection with vancomycin and TZP. Initiation of antimicrobial therapy resulted in severe thrombocytopenia and a platelet nadir of approximately 4,000 within 24 hours of the first doses. Thrombocytopenia resolved within three days of TZP withdrawal. To the best of our knowledge, there have not been any cases described of rapid drug-induced thrombocytopenia without previous exposure to the medication. Medications should always be reviewed when evaluating a patient with rapid and severe thrombocytopenia, which can obviate the need for unnecessary invasive or non-invasive treatments.

A Comprehensive Review of Thrombocytopenia With a Spotlight on Intensive Care Patients.

Thrombocytopenia is a common entity seen in ICU patients and is associated with increased morbidity such as bleeding and transfusions, and mortality in ICU patients. Various mechanisms such as decreased platelet production, sequestration, destruction, consumption, and sometimes a combination of these factors contribute to thrombocytopenia. An understanding of the mechanism is essential to diagnose the cause of thrombocytopenia and to help provide appropriate management. The management strategies are aimed at treating the underlying disorder, such as platelet transfusion to treat complications like bleeding. Several studies have aimed to provide the threshold for platelet transfusions in various clinical settings and recommend a conservative approach in the appropriate scenario. In this review, we discuss various pathophysiological mechanisms of thrombocytopenia and the diverse scenarios of thrombocytopenia encountered in the ICU setting to shed light on the varied thresholds for platelet transfusion, alternative agents to platelet transfusion, and future directions for the implementation of thromboelastography (TEG) in multiple clinical scenarios to assist in the administration of appropriate blood products to correct coagulopathy.

Furosemide-Induced Thrombotic Thrombocytopenic Purpura: A Report of a Rare Case.

Drug-induced immune thrombocytopenia (DITP) refers to drug-dependent, antibody-mediated platelet destruction. Although several drugs have been implicated as the cause of DITP, the most commonly encountered are heparin, sulfonamides, quinine, vancomycin, and beta-lactam antibiotics. However, furosemide has been rarely reported as the cause of thrombocytopenia. We present a unique case of furosemide-induced thrombotic thrombocytopenia in a 64-year-old female referred by her primary care provider for low platelets, rash, and bleeding. She was recently started on oral furosemide for diastolic heart failure two weeks before this presentation. She was admitted to the intensive care unit and was worked up for new-onset thrombocytopenia. Labs revealed anemia, thrombocytopenia, elevated lactate dehydrogenase, and low haptoglobin with normal serum creatinine. Peripheral smear showed schistocytes, low platelets, and ADAMTS13 level was 0.03. The patient was diagnosed with thrombotic thrombocytopenic purpura and treated with steroids, rituximab, and plasmapheresis, which led to rapid recovery of the platelet count to normal. Based on this case report, clinicians should consider furosemide as one of the drugs potentially causing thrombotic thrombocytopenia. Early detection and prompt management can be lifesaving.

Impact of Venlafaxine on Platelet Count and Activity-Case Report and Narrative Review.

Venlafaxine (VEN) is considered to be one of the most effective antidepressants. It belongs to the group of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs). NA and 5-HT have receptors on the surface of platelets and are involved in platelet aggregation. In this case study, we present the case of a patient treated for one of the types of myeloproliferative neoplasm (MPN), essential thrombocythemia (ET), in whom VEN was added to pharmacotherapy during the treatment of a severe episode of depression with psychotic symptoms. We observed a gradual reduction in platelet count when increasing the dose of VEN. We also present a narrative review of literature about the effect of VEN on platelet counts and activity. We conclude that, in the group of patients taking VEN, attention should be paid to the rare adverse effect of a decrease in the number of platelets.

A Rare Case of Vancomycin-Induced Immune Thrombocytopenia.

Vancomycin-induced immune thrombocytopenia (ITP) is a rare type of drug-induced immune thrombocytopenia (DITP) that can lead to life-threatening consequences as a result of its use. We herein report a case of a 74-year-old male with a history of diabetes mellitus type II, Alzheimer's disease, and stroke who presented to the ICU with sepsis. The patient was on heparin for 20 days prior to presentation, with platelet levels at the time within normal limits as per his baseline. Following the introduction of vancomycin to his clinical regimen in the treatment of sepsis, the patient developed a significant drop in platelet count from 400 x10³/mm³ to 70 x10³/mm³. Discontinuation of the drug leads to improvement of the platelet counts confirming the diagnosis of vancomycin-induced ITP.

Pantoprazole-Associated Thrombocytopenia: A Literature Review and Case Report.

Proton-pump inhibitors (PPIs) are commonly utilized in the treatment of upper gastrointestinal bleeds (UGIBs) due to their ability to stabilize blood clot formation. PPIs have been shown to reduce rebleeding after endoscopic hemostasis and reduce signs of bleeding at index endoscopy. While PPIs are well-tolerated and commonly administered to patients suffering from acute UGIBs, significant adverse effects may occur. Patients have reported various mild systemic symptoms during short-term PPI use, including headache, rash, dizziness, nausea, abdominal pain, flatulence, constipation, and diarrhea. In general, serious side effects of PPIs tend to be mild during treatment periods under two weeks; however, as the treatment duration increases, side effects have been observed to increase in frequency and severity. PPI-induced thrombocytopenia is an exceedingly rarely reported adverse reaction that remains largely unstudied due to the dearth of patient cases. This adverse effect continues to be a diagnosis of exclusion, and there are no current evidence-based recommendations to approach this complication. Thrombocytopenia increases the risk of rebleeding and hemodynamic instability, which may be devastating to patients suffering from UGIBs. Here, we present a case of thrombocytopenia that began after the introduction of pantoprazole in the setting of a UGIB. The thrombocytopenia resolved promptly after cessation of the medication. We highlight this case to increase awareness of this rare finding given the lack of recommendations for short-term PPI-induced thrombocytopenia.