Piperacillin and vancomycin induced severe thrombocytopenia in a hospitalized patient

In hospitalized patients with complex medical problems on numerous drugs, thrombocytopenia may have a multiple confounding etiology. Keeping this in mind, it is of utmost importance to monitor the platelet count regularly during hospitalization and on subsequent follow-up visits, even after the most probable etiology has been identified/most likely causative drug has been withdrawn. Isolated thrombocytopenia with no evidence of microangiopathic hemolysis on the peripheral blood smear in an acutely ill hospitalized patient implicated sepsis, disseminated intravascular coagulation and drugs as the most probable causes. Our patient represents an uncommon case of antibiotic-induced severe immune thrombocytopenia, as he developed both vancomycin-dependent and piperacillin-dependent antibodies, while being treated for cellulitis (vancomycin-specific antibodies of the IgG isotype, and both IgG and IgM antibodies specific for piperacillin were identified in laboratory testing). Vancomycin was stopped before the reports were available. Following this, the patient's platelet count showed a transient upward trend, but then the thrombocytopenia worsened drastically reaching a nadir of 10,000/μL. The platelet count returned to normal only after piperacillin/tazobactam was stopped after a week, thus establishing it as the cause of the more severe thrombocytopenia, which occurred later on; this was subsequently confirmed by the laboratory results. Vancomycin is an established cause of drug-induced immune thrombocytopenias, especially in acutely ill, hospitalized or elderly patients, whereas incidents of piperacillin/tazobactam-induced immune thrombocytopenia are uncommon. In case clinical suspicion is high, workup should include immunoprecipitation and flow cytometry studies to confirm antiplatelet antibodies.     

万古霉素致失代偿期肝硬化患者重度血小板减少1例

万古霉素是一种糖肽类抗生素,临床主要用于治疗包括耐甲氧西林金黄色葡萄球菌在内的侵袭性革兰阳性菌感染。该药常见不良反应为皮疹、肾毒性及耳毒性,较少引起血小板减少。本文报道1例由万古霉素导致重度血小板减少的失代偿期肝硬化患者,为此类不良反应的临床监测及治疗提供参考。     

肝素诱导性血小板减少症亚心诊疗要点

肝素诱导性血小板减少症是由IgG抗体介导的促血栓形成性免疫性疾病。临床表现为肝素治疗后数天至数月发生血小板减少计数（与肝素治疗前相比）减低与伴或不伴新发血栓,呈现高凝与血栓矛盾状态。发病隐蔽,死亡率高。这为临床诊疗带来极大挑战。本文根据武汉亚洲心脏病医院185例疑似HIT患者的诊疗数据结合最新欧美HIT管理指南汇集成以下疑似HIT诊疗思路,降低HIT患者不良事件发生率。     

Catastrophic thromboses and severe thrombocytopenia during heparin therapy in a patient with anti-phospholipid syndrome

Catastrophic anti-phospholipid syndrome (CAPS) is a medical emergency characterized by thromboses of multiple small vessels of internal organs and the brain. Herein we present a patient with primary anti-phospholipid syndrome who developed CAPS manifested by hepatic, renal and splenic artery thromboses, as well as cerebral venous thrombosis. The course was further complicated by severe thrombocytopenia and haemolytic anemia. Two episodes of catastrophic thrombosis developed within 24–36 h after the initiation of heparin therapy, suggesting a role of heparin in triggering thromboses. The patient had no anti-platelet-factor-4 antibodies in repeated measurements, making clinical diagnosis of heparin-induced thrombocytopenia unlikely. The possible role of heparin in induction of thromboses and its therapeutic implication are detailed.     

Use of systemic bivalirudin with catheter‐directed thrombolysis in a patient with heparin‐induced thrombocytopenia: A case report

In patients with submassive pulmonary embolism, the use of catheter‐directed thrombolysis (CDT), using low‐dose alteplase is associated with improvement in overall hemodynamics. The data for use of CDT in patients with heparin‐induced thrombocytopenia are limited. We report a case of CDT in a patient with HIT using bivalirudin anticoagulation. Data of the use of bivalirudin and argatroban for systemic anticoagulation with CDT are limited.     

Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia

In pregnant women with antecedents of autoimmune thrombocytopenia (AITP), no predictive factor for severe fetal thrombocytopenia has been identified. We evaluated the relationships between the course of the maternal disease before and during pregnancy and the risk of severe fetal thrombocytopenia, in 64 pregnant women with known chronic AITP antecedents, over a 12-year period. 28 pregnant women had undergone splenectomy before pregnancy and 17 experienced severe thrombocytopenia (< 50 × 10⁹/l) during pregnancy (monthly determination). Eight infants presented with severe thrombocytopenia at birth (12.5%), and four in the following days (6.25%). No severe haemorrhage was observed. Severe thrombocytopenia at birth was present in 57% (CI 95% 18–90%) of the infants born to mothers with severe pregnancy-associated thrombocytopenia and splenectomy antecedents, and in 0% (CI 95% 0–15%) of the infants born to mothers who presented none of these antecedents ( P  = 0.001). In thrombocytopenic mothers the infant platelet counts at birth were positively correlated to the nadir maternal platelet count during the index pregnancy ( r  = 0.42, P  = 0.0075).
These results suggest that severe autoimmune disease is a risk factor for severe fetal thrombocytopenia, and that pregnant women with no antecedent of splenectomy nor severe thrombocytopenia during pregnancy have a very low risk of severe fetal thrombocytopenia.     

Acute thrombocytopenia in patients treated with amiodarone is caused by antibodies specific for platelet membrane glycoproteins

Amiodarone has been implicated as a cause of thrombocytopenia but the responsible mechanism is unknown. We performed studies in three patients to characterize the pathogenesis of this complication. No amiodarone‐dependent, platelet‐reactive antibodies were identified using conventional serological techniques. However, water‐insoluble amiodarone solubilized in methanol and diluted to 1·0 mg/ml in aqueous buffer reproducibly promoted binding of IgG antibodies in patient serum to platelets. Solid phase assays identified drug‐dependent antibodies specific for platelet glycoproteins (GP)Ia/IIa (integrin α₂β₁) in each patient and a second antibody specific for GPIIb/IIIa (α_IIbβ₃ integrin) in one patient. When studied by ion mobility analysis and transmission electron microscopy, the serologically active amiodarone preparation, a milky suspension, was found to consist of particles 2–30 nm in diameter, typical of a coacervate, a state characteristic of amiodarone in aqueous medium. The findings provide evidence that thrombocytopenia in the three patients studied was caused by drug‐dependent antibodies specific for platelet glycoproteins GPIa/IIa and/or GPIIb/IIIa. We postulate that, in vivo, amiodarone may become incorporated into occult lipophilic domains in platelet glycoproteins, producing structural modifications that are immunogenic in some individuals, and that the resulting antibodies can cause platelet destruction in a person taking this drug.     

Catheter-directed thrombolysis of acute lower extremity arterial thrombosis in a patient with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an underdiagnosed problem, and the optimal treatment of arterial thrombosis in patients with HIT remains controversial. There are many angiographic procedures which require heparin as an adjunctive agent; however, some of the heparin-related complications and their management remains unclear. We are presenting a 77-year-old male patient with HIT, who developed acute lower extremity limb threatening ischemia due to arterial thrombosis. In our case, the patient has been successfully treated with percutaneous catheter-directed thrombolysis with tissue plasminogen activator and a direct thrombin inhibitor argatroban.     

Chryseobacterium indologenes subcutaneous port‐related bacteremia in a liver transplant patient

Chryseobacterium indologenes is a rare cause of infection in select immunosuppressed hosts. Most prior reports are from Taiwan, in patients with diabetes mellitus or malignancies. Infections caused by C. indologenes are generally associated with indwelling devices, and the organism may be resistant to many commonly utilized broad‐spectrum antibiotics. We report the first case, to our knowledge, of C. indologenes subcutaneous port‐related bacteremia in a liver transplant recipient. The isolates were resistant to antibiotics previously reported as active, and device removal was required for treatment success.     

Thromboembolism after cardiac surgery in a patient with cancer-related thrombosis and severe thrombocytopenia: A case report

Rationale:Patients with cancer have elevated risk of both venous thromboembolism and bleeding compared with patients without cancer due to cancer- and patient-specific factors. Balancing the increased and competing risks of clotting and bleeding in these patients can be difficult because management of cancer-associated thrombosis requires anticoagulation despite its known increased risks for bleeding. The adjustment of blood transfusion or cessation of anticoagulants can be a challenge in surgical diagnosis or treatment of cancer patients with such an imbalanced coagulate status.Patient concerns:A 45-year-old woman with no underlying disease was suspected of ovarian cancer and was awaiting diagnostic laparoscopic exploration surgery.Diagnoses:While waiting for the surgery, the patient developed chest pain and underwent stent insertion under diagnosis of myocardial infarction. Two weeks later, endocarditis developed, and replacement of the aortic valve and mitral valve was planned. In addition, the patient developed multiple thromboembolisms and was administered anticoagulants to eliminate vegetation of valves and multiple thromboses. Her blood test showed anemia (7.4 g/dL) and severe thrombocytopenia (24 × 10⁹/L).Interventions:The patient underwent double valve replacement.Outcomes:A color change of the left lower extremity was noted 5 hours after double valve replacement, and angiography was performed. Thrombectomy was performed under diagnosis of thrombosis in the left iliac artery. One month later, the patient underwent laparoscopic exploration surgery as scheduled.Lessons:This case will help establish the criteria of blood coagulation for surgical treatment of cancer patients with imbalanced clotting and bleeding.     

Interferon-α induced severe thrombocytopenia:A case report and review of the literature

We report a case of severe thrombocytopenia following pegylated interferon-α 2a(Peg-IFN-α 2a)treatment of hepatitis C virus infection and summarize the clinical characteristics of 16 cases of IFN-α induced severe thrombocytopenia and its immune-mediated mechanism.Discontinuation of IFN-α and early administration of immunosuppressants are the effective therapy for IFN-αinduced severe thrombocytopenia.     

Co-existence of heparin-induced thrombocytopenia and thrombotic thrombocytopenic purpura in a postoperative cardiac surgery patient

Up to 50% of patients undergoing coronary artery bypass surgery will develop antibodies against the heparin-platelet factor 4 complex, and a small percentage of those will go on to develop heparin-induced thrombocytopenia. Thrombotic thrombocytopenic purpura has also been reported post-coronary artery bypass surgery. In this case report, we describe a patient who developed both heparin-induced thrombocytopenia and thrombotic thrombocytopenic purpura post-coronary artery bypass surgery. This patient had clinical features consistent with both entities, and the clinical picture could not be explained by either heparin-induced thrombocytopenia or thrombotic thrombocytopenic purpura alone. It is hypothesized that these two entities may be related in this patient population, and this case report emphasizes the challenges in the diagnosis of thrombocytopenia in this patient population.     

Effectiveness of a clinical decision support system to identify heparin induced thrombocytopenia

Background Subtle decreases in platelet count may impede timely recognition of heparin-induced thrombocytopenia (HIT), placing the patient at increased risk of thrombotic events. Objective A clinical decision support system (CDSS) was developed to alert physicians using computerized provider order entry when a patient with an active order for heparin experienced platelet count decreases consistent with HIT. Methods Comparisons for timeliness of HIT identification and treatment were evaluated for the year preceding and year following implementation of the CDSS in patients with laboratory confirmation of HIT. Results During the intervention time period, the CDSS alert occurred 41,922 times identifying 2,036 patients who had 2,338 inpatient admissions. The CDSS had no significant impact on time from fall in platelet count to HIT laboratory testing (control 2.3 days vs intervention 3.0 days P = 0.30) and therapy (control 19.3 days vs intervention 15.0 days P = 0.45), and appeared to delay discontinuation of heparin products (control 1.3 days vs. intervention 2.9 days P = 0.04). However, discontinuation of heparin following shorter exposure duration and after smaller decrease in platelet count occurred during the intervention period. The HIT CDSS sensitivity and specificity were each 87% with a negative predictive value of 99.9% and positive predictive value of 2.3%. Conclusions Implementation of a CDSS did not appear to improve the ability to detect and respond to potential HIT, but resulted in increased laboratory testing and changes in clinician reactions to decreasing platelet counts that deserve further study.     

Molecular Adsorbent Recirculating System (MARS®) removal of piperacillin/tazobactam in a patient with acetaminophen‐induced acute liver failure

The objective of this study was to illustrate the pharmacokinetic removal of piperacillin/tazobactam in an anuric patient on Molecular Adsorbent Recirculating System (MARS^®). The patient was a 32‐year‐old woman who presented to a medical intensive care unit with acute liver failure secondary to an acetaminophen overdose. While awaiting transplant, she was started on MARS therapy as a bridge to liver transplant and empirically started on piperacillin/tazobactam therapy. MARS is an extracorporeal hemofiltration device, which incorporates a continuous venovenous hemofiltration (CVVHD) machine linked to an albumin‐enriched dialysate filter to normalize excess electrolytes, metabolic waste, and protein‐bound toxins. In addition to protein‐bound waste, MARS removes water‐soluble, low molecular‐weight molecules. The patient received piperacillin/tazobactam 4.5 g infused intravenously over 3 h. A steep decline in serum levels occurred between hours 4 and 6 while MARS continued and no antibiotic was infused. The elimination rate constant (k_e) for the removal of piperacillin in this patent was 0.453 h^?1 and the half‐life (λ) was 1.53 h. The k_e was 2.9‐fold higher than with CVVHD alone and the λ was 3.7‐fold shorter. Low levels of piperacillin are achieved during MARS therapy, but in the treatment of more resistant organisms, such as Pseudomonas aeruginosa, these low levels may not be adequate to achieve bactericidal activity. Drug levels following a standard infusion of 30 min would likely be even lower. Formalized pharmacokinetic studies of piperacillin/tazobactam removal in patients on MARS therapy are necessary to make clear dosing recommendations.