1/9. Sustained response to combination therapy in a patient with chronic hepatitis c and thrombocytopenia secondary to alpha-interferon.Recent data suggest that hepatitis c viral (HCV) infection may induce a significant autoimmune reaction to platelets, but the mechanism is unknown. Many patients with chronic hepatitis c, in fact, have high levels of platelet-associated immunoglobulin g (PAIgG) and HCV-rna is present in the platelets of 100% of those patients with thrombocytopenia and high PAIgG levels. hepatitis c virus infection has been associated with the development of thrombocytopenic purpura, sometimes triggered during interferon (IFN) therapy. In such cases, the treatment of the underlying disease is a difficult problem to solve. We report the case of a patient with chronic hepatitis c, who developed life-threatening thrombocytopenic purpura after a prolonged course of IFN-alpha2b over a 4-year period. Treatment with anti-immunoglobulin gammaglobulin (Polyglobin; Quimica Farmaceutica Bayer, Barcelona, spain) had a transient effect on the platelet count, but prolonged therapy with prednisone was necessary for definitive relief of the haematological complication. Two years later, the patient was treated with combined therapy, including ribavirin (1200 mg/day) and IFN-alpha2b (5 mU, t.i.w.) for 12 months. This therapy induced a sustained response, both biochemical and virological, without haematological complications. This observation suggests that ribavirin may be of benefit in the treatment of immune-mediated thrombocytopenia in patients with chronic hepatitis c, preventing the harmful effect of IFN-alpha but also allowing both drugs to be combined so as to increase the probability of sustained remission of the liver disease.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
2/9. Prolonged thrombocytopenia associated with isotretinoin.OBJECTIVE: To report a case of severe prolonged thrombocytopenia possibly associated with isotretinoin. CASE SUMMARY: A 27-year-old white woman developed severe thrombocytopenia and elevated transaminases after 3(1/2) months of treatment with isotretinoin. Prior to the onset of thrombocytopenia, the patient had also received a 10-day course of cephalexin. Rectal bleeding was reported by the patient, who was otherwise asymptomatic. liver enzyme values returned to normal approximately 1 week after discontinuation of isotretinoin; however, platelet counts required approximately 2 months to normalize. Based on the Naranjo probability scale, possible causality exists between isotretinoin and thrombocytopenia. DISCUSSION: The exact mechanism by which isotretinoin caused thrombocytopenia in this patient is not clearly understood. To our knowledge, only 3 previous cases of isotretinoin-associated thrombocytopenia have been reported. The long recovery process that occurred in our patient is possibly a direct result of the long elimination half-life of both the parent compound and active metabolites of isotretinoin. CONCLUSIONS: Clinicians prescribing isotretinoin should be aware of the potential life-threatening consequence of thrombocytopenia, and a complete blood cell count with platelets should be part of the routine monthly monitoring in all patients receiving isotretinoin therapy.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
3/9. Lepirudin in heparin-induced thrombocytopenia and extracorporeal membranous oxygenation.OBJECTIVE: To report a case of intermediate-probability suspected heparin-induced thrombocytopenia (HIT) treated with lepirudin in a patient requiring continuous extracorporeal membranous oxygenation (ECMO). CASE SUMMARY: A 17-year-old girl was admitted with multiple traumatic injuries including severe bilateral pulmonary contusions. Within 48 hours, she developed progressive pulmonary failure despite mechanical ventilation, and was placed on ECMO. Anticoagulation of the ECMO circuit was facilitated by unfractionated heparin (UFH). The platelet count of 116 x 10(3)/mm(3) after initiation of ECMO gradually decreased over 5 days to 44 x 10(3)/mm(3). On ECMO day 5, a highly positive enzyme-linked immunosorbent assay for HIT antibodies was reported, and the UFH infusion was discontinued. Lepirudin was immediately started with a bolus of 0.1 mg/kg, followed by an infusion of 0.12 mg/kg/h, with a target activated partial thromboplastin time (aPTT) ratio approximately 2 times control. The ECMO circuit was maintained without any unexpected bleeding complications or thrombosis for 6 additional days until the patient died secondary to pulmonary failure after ECMO was removed. DISCUSSION: Use of ECMO typically requires continuous infusion of UFH to keep the circuit from clotting. In patients with HIT, alternative anticoagulation using a direct thrombin inhibitor may be warranted. Lepirudin was effectively used to maintain the circuit despite continued presence of heparin molecules impregnated into the ECMO circuit tubing. The aPTT was successfully used to monitor and adjust the lepirudin infusion. CONCLUSIONS: In patients requiring ECMO in the presence of HIT, anticoagulation of the ECMO circuit may be accomplished using a continuous infusion of a direct thrombin inhibitor such as lepirudin.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
4/9. Interleukin 11 May improve thrombocytopenia associated with imatinib mesylate therapy in chronic Myelogenous leukemia.During therapy with imatinib (Gleevec), 20-30% of patients with CML in chronic phase develop grade > or =3 thrombocytopenia. This leads to treatment interruptions and dose reductions that result in a decreased probability of achieving a cytogenetic response. interleukin-11 (oprelvekin) is a megakaryopoietic cytokine that reduces the incidence and severity of thrombocytopenia associated with chemotherapy. We report on the use of interleukin-11 in three CML patients with grade > or =3, imatinib-induced thrombocytopenia. In all three patients, interleukin-11 led to improved platelets, uninterrupted administration of imatinib and improved cytogenetic response. This observation suggests that interleukin-11 may be beneficial for patients with imatinib-induced thrombocytoepnia.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
5/9. valproic acid-induced hyperammonemia and thrombocytopenia in an elderly woman.OBJECTIVE: To describe a case of oral valproic acid-induced hyperammonemia and thrombocytopenia in an elderly patient. CASE SUMMARY: A 76-year-old white woman presented to the emergency department with generalized weakness, confusion, nausea, and vomiting. She was taking sodium divalproex 750 mg 3 times daily, with valproic acid concentration 144 mg/L. She was admitted to the medical ward. The dose of sodium divalproex was decreased and discontinued. During her hospital stay, the woman's ammonia level rose to 211 microg/dL despite a normal valproic acid concentration. She was confused, somnolent, and had decreased mobility. Her platelet count decreased from 133 to 86 x 10(3)/mm(3). Gabapentin was prescribed for seizure control. The patient's mental status, ammonia level, and platelet count returned to baseline following discontinuation of valproic acid. DISCUSSION: It has been reported that valproic acid can interfere with the enzyme carbamoylphosphate synthetase, which is responsible for incorporating ammonia into the urea cycle. It has also been reported that valproic acid can increase the transport of glutamine across the mitochondrial membrane in the kidney, thereby increasing the production of ammonia. The etiology of valproic acid-induced thrombocytopenia has not been elucidated. Using the Naranjo probability scale, a probable relationship between hyperammonemia and valproic acid and a possible relationship between thrombocytopenia and valproic acid were determined. CONCLUSIONS: valproic acid can be associated with hyperammonemia and thrombocytopenia. Clinicians should be aware of changes in patients' cognitive and functional capacity, especially elderly patients on sodium divalproex.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
6/9. Suspected beta-antagonist-induced thrombocytopenia.OBJECTIVE: To report a case of possible beta-antagonist-induced thrombocytopenia. CASE SUMMARY: A 44-year-old African American woman with systemic lupus erythematosus developed thrombocytopenia. Splenic sequestration was suspected, but the rise in platelets after splenectomy was temporary. Bacterial and viral etiologies were ruled out, since thrombocytopenia continued 6 months after splenectomy. Her medications acetaminophen, amitriptyline, amlodipine, beta-antagonists, and diphenhydramine were suspected. nadolol and labetalol were started immediately prior to splenectomy. Six months after splenectomy, the woman was hospitalized for pneumonia; the platelet count was 50 x 10(3)/mm(3). nadolol was discontinued on day 2. Within 24 hours, the platelet count rose to 128 x 10(3)/mm(3) and exceeded 200 x 10(3)/mm(3) by day 7. labetalol was discontinued on day 8, but no additional significant rise occurred. The patient developed thrombocytopenia one year later when placed on nadolol and famotidine during admission for a gastrointestinal bleed. The platelet count decreased during the admission. Both drugs were discontinued after the last platelet count (100 x 10(3)/mm(3)). The platelet count had normalized by the follow-up visit 16 days later and remained normal until the patient's death almost a year later. DISCUSSION: thrombocytopenia is not a common adverse effect of beta-antagonist therapy. As of February 1, 2005, only 4 case reports of suspected beta-antagonist-associated thrombocytopenia have been published in English, and the medications cited are unavailable within the US. After splenectomy, the thrombocytopenia might have resolved if the beta-antagonists had not been present. Since thrombocytopenia resolved within 24 hours of discontinuation of nadolol, it is likely that the continued thrombocytopenia was beta-antagonist induced. The likelihood that the beta-antagonist caused the adverse event is possible according to the Naranjo probability scale. CONCLUSIONS: The temporal association between the discontinuation of nadolol and the rise in platelets suggests that the thrombocytopenia resulted from nadolol.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
7/9. thalidomide-associated thrombocytopenia.OBJECTIVE: To report thrombocytopenia in a patient prescribed thalidomide for multiple myeloma (MM). CASE SUMMARY: A 70-year-old woman was diagnosed in 2003 with MM. At diagnosis, melphalan 0.25 mg/kg/day and prednisolone 2 mg/kg/day were started; however, the patient became refractory to therapy. melphalan and prednisolone were discontinued, and monotherapy with dexamethasone 40 mg for 12 days per month was started. The patient's hematologic condition deteriorated again after about one year; dexamethasone was discontinued, and treatment with oral thalidomide 200 mg/day was initiated. About 2 weeks after thalidomide administration, the woman developed disabling adverse effects (flu-like symptoms, swollen fingers, rash and hematoma on her legs, shortness of breath, dry mouth, multiple petechiae). Laboratory testing showed neutropenia (neutrophils 0.4 x 10(9)/L) and thrombocytopenia (platelets 58 x 10(9)/L). thalidomide was promptly discontinued; within 3 weeks, the laboratory values returned to pretreatment levels (1.3 x 10(9)/L and 267 x 10(9)/L, respectively) and her symptoms disappeared. DISCUSSION: thrombocytopenia is a rarely reported hematologic adverse consequence of thalidomide therapy. A recent report identified 5 patients who developed thrombocytopenia while undergoing monotherapy with thalidomide for MM. According to the Naranjo probability scale, thalidomide was classified as the probable cause of thrombocytopenia in our patient. CONCLUSIONS: Unlike other antineoplastic drugs, thalidomide is rarely reported to cause severe hematologic toxicity. We present this case to increase clinicians' awareness for the potential of thalidomide to adversely affect platelet counts, particularly because its effectiveness in MM will likely result in expansion of its clinical use.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
8/9. Pantoprazole-induced thrombocytopenia.OBJECTIVE: To report 2 cases of thrombocytopenia associated with pantoprazole treatment and discuss existing reports on this drug-induced adverse event. CASE SUMMARIES: This paper describes the course of thrombocytopenia associated with pantoprazole 40 mg in 2 hospitalized patients. In both cases, thrombocytopenia appeared after the initiation of pantoprazole and rapidly improved after discontinuation of pantoprazole, although complete resolution of thrombocytopenia occurred in only one patient prior to discharge from the hospital. DISCUSSION: The mechanism of drug-induced thrombocytopenia is often poorly understood, and proton-pump inhibitors are generally not strongly suspected as a cause of thrombocytopenia. However, an objective causality assessment using the Naranjo probability scale revealed a probable relationship between thrombocytopenia and pantoprazole in both of the cases. It is unknown whether this is a class effect. CONCLUSIONS: Although drug-induced thrombocytopenia with pantoprazole appears to be rare, it represents a potentially severe adverse effect. This supports the judicious prescribing of pantoprazole and possibly other proton-pump inhibitors.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
9/9. Pseudo-pulmonary embolism as a sign of acute heparin-induced thrombocytopenia in hemodialysis patients: safety of resuming heparin after disappearance of HIT antibodies.heparin-induced thrombocytopenia (HIT) is a syndrome caused by platelet-activating antibodies that recognize complexes of platelet factor 4 (PF4) and heparin. thrombocytopenia is the most common clinical feature of HIT. HIT can be considered as a hypercoagulable state, with a high risk of thrombosis. Another feature of HIT is an acute systemic reaction that characteristically begins 5-30 min after receiving an intravenous bolus of unfractionated heparin, such as is commonly given for hemodialysis (HD). Here we present 4 patients who developed acute HIT at or near the start of their chronic HD. All patients were anticoagulated with the low-molecular-weight heparin, nadroparin, for HD. Three of our patients underwent surgery approximately 1-2 weeks before developing HIT. All patients presented with an acute systemic reaction during HD. All patients were treated and further dialyzed with lepirudin. Under this treatment we observed a quick recovery of the platelet count, and patients remained symptom-free. antibodies against the PF4-heparin complex were detected with a combination of a 'quick test' and an enzyme-linked immunosorbent assay test. The likelihood of having HIT previous to the detection of antibodies was estimated with the pre-test probability score criteria. The tests for PF4-heparin antibodies remained positive for an average of 165 days. Three patients underwent a rechallenge with nadroparin after disappearance of the HIT antibodies in their serum. All 3 remained symptomless when they were further hemodialyzed on nadroparin. Our observations indicate that nadroparin can be successfully reintroduced for HD anticoagulation once the patient's HIT antibodies have disappeared.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |