Anna Vantilborgh

Lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review of the literature

Lupus anticoagulant-hypoprothrombinemia syndrome (LA-HPS) is a rare acquired disorder caused by prothrombin antibodies. The disease is most common in the pediatric age group (<16 years), and more prevalent in women. There are well-established clinical diseases associated with LA-HPS, most notably systemic lupus erythematosus (SLE) and viral infections. The clinical manifestation of LA-HPS varies greatly in severity and it may cause severe life-threatening bleeding diathesis. LA-HPS is to be suspected when a patient presents with bleeding and a prolonged activated partial thromboplastin and prothrombin time, in combination with a lupus anticoagulant. The diagnosis is confirmed in the laboratory by identification of reduced prothrombin levels. There are no standardized recommendations for treatment of the hemorrhage associated with the syndrome; corticosteroids are used as first-line treatment. This review summarizes what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of LA-HPS, and presents two case reports.

Acquired hemophilia: a case report and review of the literature

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against clotting factor VIII (FVIII). FVIII autoantibody is characterized as polyclonal immunoglobulin G directed against the FVIII procoagulant activity. This disease occurs most commonly in the elderly population and with preponderance of men in nonpregnancy‐related AHA. There are well‐established clinical associations with AHA such as malignancy, other autoimmune diseases and pregnancy. However, up to 50% of reported cases remain idiopathic. The clinical manifestation of AHA includes mostly spontaneous hemorrhages into skin, muscles and soft tissues, or mucous membranes. AHA should be suspected when a patient with no previous history of bleeding presents with bleeding and an unexplained prolonged activated partial thromboplastin time. The diagnosis is confirmed in the laboratory by the subsequent identification of reduced FVIII levels and FVIII inhibitor titration. There is a high mortality, making prompt diagnosis and treatment vitally important. The principles of treatment consist in controlling the bleeding and eradicating the inhibitor. Because of the overall high relapse rate (15–33%), it is also recommended to follow up these patients. The review summarizes what is currently known about the epidemiology, pathogenesis, clinical features, diagnosis, treatment and prognosis of AHA and starts with a case report.

Doping control analysis of desmopressin in human urine by LC-ESI-MS/MS after urine delipidation.

The World Anti-Doping Agency (WADA) has recently added desmopressin, a synthetic analogue of the endogenous peptide hormone arginine vasopressin, to the Prohibited List, owing to the potential masking effects of this drug on hematic parameters useful to detect blood doping. A qualitative method for detection of desmopressin in human urine by high-performance liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated. Desmopressin purification from urine was achieved by means of delipidation with a 60:40 di-isopropyl ether/n-butanol and solid-phase extraction with WCX cartridges. The lower limit of detection was 25 pg/mL. Extraction recovery was determined as 59.3% (SD 29.4), and signal reduction owing to ion suppression was estimated to be 42.7% (SD 12.9). The applicability of the method was proven by the analysis of real urine samples obtained after intravenous, oral and intranasal administration of desmopressin, achieving unambiguous detection of the peptide in all the cases.

Agranulocytosis after cocaine use: a case of suspected levamisole contamination in Belgium.

Since 2005 cocaine use has significantly increased in Western urope, especially in recreational settings and among young peole (aged 15–34) [1]. With an average yearly prevalence of 1.3%, it s now the second most-used illicit drug after cannabis. Cocaine has een reported to cause a wide variety of psychiatric problems (e.g. uicidal ideation, addiction, depression, psychosis), cardiovascular e.g. arrhythmias, myocardial infarction, myocarditis) and cererovascular complications (e.g. cerebral infarction, subarachnoid aemorrhage) and rheumatologic syndromes (e.g. Raynaud’s pheomenon, vasculitis) [2]. Moreover, several unexplained cases of granulocytosis have emerged in cocaine abusers in New Mexico, anada and the United States [3,4]. Epidemiologic investigation ndicated that cocaine contaminated with levamisole was the likely ause of the agranulocytosis [5]. We report the first case of agranlocytosis in a patient after cocaine use in Belgium.

Myeloma of the central nervous system: report of a single center case series

Abstract Background: Neurologic manifestations often complicate the course of multiple myeloma, but direct involvement of the central nervous system (CNS) is rare. Objective: To describe the clinical course, neurological symptoms, laboratory findings and imaging of patients with CNS myeloma. This additional information may contribute to better recognition and more effective management of this complication in the future. Methods: We retrospectively identified 6 MM patients with CNS involvement diagnosed at our centre between April 2003 and April 2009. The clinical, biochemical and imaging data were collected and compared with previously reported cases. Results: At time of diagnosis of CNS myeloma, 3 patients had progressive disease and 3 were in good partial remission. The presenting symptoms included diplopia, vision loss, extremity weakness and paresis. All cases showed one or more features of aggressive disease at diagnosis, including high tumour burden, plasmablastic morphology and high-risk cytogenetic abnormalities. Prognosis was poor with a median survival of 4.8 months. Conclusion: CNS myeloma should be considered in patients with aggressive MM and unexplained neurological symptoms. The prognosis is poor despite intensive therapy.

Early recognition of malignant lactic acidosis in clinical practice: report on 6 patients with haematological malignancies

Abstract Background: Malignant lactic acidosis is a potentially overlooked but life-threatening complication in patients with haematological malignancies. The aim of this study is to describe the features of six patients with malignant lactic acidosis and to discuss how its initial presentation can be differentiated from that of severe sepsis. Methods: We prospectively collected data of all consecutive patients with haematological malignancies, admitted to the Ghent University Hospital Intensive Care Unit (ICU) between 2000 and 2007. Results: Of 372 patients with haematological malignancies admitted to the ICU for life- threatening complications, 58 presented with lactic acid levels ≥ 5 mmol/L. Six were diagnosed with malignant lactic acidosis. All patients with malignant lactic acidosis had high-grade lymphoblastic malignancies and were referred with a tentative diagnosis of severe sepsis or septic shock; lactic acid levels exceeded 9.45 mmol/L and lactate dehydrogenase (LDH) levels were at least 1785 U/L. Two patients had hypoglycaemia. All had a pronounced polypnea. In all patients hepatic malignant involvement was suspected. Two of the six patients survived their episode thanks to the early recognition of malignant lactic acidosis and the prompt administration of chemotherapy. One patient was still alive 6 months after initiating chemotherapy. Conclusion: Malignant lactic acidosis is a rare and often rapidly fatal metabolic complication if not promptly recognized and treated. An elevated lactic acid concentration, in disproportion with the level of tissue hypoxia, together with high serum LDH are cornerstones in the diagnosis. In contrast to septic shock patients, pronounced polypnea (Kussmaul’s breathing pattern) rather than the haemodynamic instability is prominent.

Screening for hereditary spherocytosis in routine practice: evaluation of a diagnostic algorithm with focus on non-splenectomised patients

Dear Editor, We have read with interest the recent paper of Mullier et al. [1] about the development of the hereditary spherocytosis (HS) diagnostic tool. The authors state that this diagnostic tool has a sensitivity of 100%, specificity of 99.3%, positive predictive value (PPV) of 75% and negative predictive value (NPV) of 100% and could be used routinely as an excellent screening method for the diagnosis of HS. As a university hospital, we have a large population of patients diagnosed with HS. Using our laboratory database, we evaluated retrospectively the value of the HS diagnostic tool. Complete data (reticulocytes and research parameters) were obtained from in total 2,593 individuals (including 25 patients with clinical diagnosis of HS) during the period July 2010 till December 2010. All measurements were performed on the XE-5000 (Sysmex, Kobe, Japan) as necessary for the tool. Using the diagnostic tool of Mullier et al. (Table 1), we obtained a sensitivity of 76% (95% CI=54.9–90.6%), specificity of 98% (97.4–98.5%), PPV of 26.8% (17.0– 38.6%) and NPVof 99.8% (99.5–99.9%). This performance is much lower than stated in the original paper. We missed 6/25 patients with known HS: 3 due to lower reticulocyte counts (range=50.6–69.2×10/L), possibly because they all were splenectomised, and 3 due to lower percentage of microcytic erythrocytes (MicroR, range=2.6–3.4%). The higher amount of false positives, and hence lower PPV, is probably due to more severe pathologies in our university hospital population including a lot of transplant patients (10/52 false positives with the criteria of Mullier et al.) and patients with hemoglobinopathy/thalassemia (7/52 false positives). Therefore, we propose to adapt the original diagnostic tool in order to improve the performance characteristics for our clinical setting (Table 2). By decreasing the percentage of MicroR in the severity rule from ≥3.5% to ≥2.6%, sensitivity is strongly improved without important loss of specificity and PPV. As our primary goal is to identify undiagnosed patients and as splenectomy evokes a decrease in reticulocyte count [2], we omitted the splenectomised patients (5/25). Consequently, the reticulocyte count precondition can be increased, as all non-splenectomised patients had reticulocyte counts of >140×10/L (range=142–1,010×10/L). Based on these observations, we adapted the HS diagnostic tool: reticulocytes ≥100×10/L instead of ≥80× 10/L and MicroR ≥2.6% instead of ≥3.5%. The new approach leads to a sensitivity of 100% (95% CI=83.0– 100%) for non-splenectomised HS patients and 84% (63.9– 95.4%) for all HS patients with respectively a PPV of 42.6% (28.3–57.8%) and 43.8% (29.5–58.8%). When the screening rule is positive, the presence of spherocytes is L. Persijn : C. Bonroy : J. Philippé :V. Stove (*) Laboratory of Clinical Biology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, De Pintelaan, 185 (2P8), 9000 Ghent, Belgium e-mail: veronique.stove@ugent.be

Dexamethasone-induced catatonia in a patient with multiple myeloma

Catatonia is a complex neuropsychiatric syndrome, caused by different underlying metabolic, neurologic, psychiatric and toxic conditions. Although catatonia is often associated with psychiatric disorders such as schizophrenia or depression, in about 20 to 39% of the patients a somatic illness is found. Unfortunately, this diagnosis is often missed although catatonia is characterized by a specific symptom complex. We report a case of acute catatonia with psychotic features in a patient with multiple myeloma (MM), caused by systemic use of dexamethasone. Physicians should be aware of possible psychiatric side effects when prescribing high doses of dexamethasone. Further, MM patients on corticosteroids should be closely monitored for mild psychological and/or psychiatric symptoms since they may be predictive for the onset of catatonia.

Influence of platelet clumps on platelet function analyser (PFA)‐200® testing

Sir, The platelet function analyser (PFA)-200 is widely used as a simple and rapid screening tool to measure global platelet haemostatic function to detect bleeding disorders as well as to monitor platelet inhibition by several antiplatelet drugs [1]. The PFA-200 simulates the process of platelet adhesion and aggregation triggered by either collagen/epinephrine (coll/EPI) or collagen/ADP (coll/ ADP) in vitro, reporting results as a ‘closure time’ (CT) [2]. The investigation of platelet function by PFA-200 is highly vulnerable to a broad series of pre-analytical variables. Sample collection and transportation may influence the results [3, 4]. Patient characteristics such as a platelet count <100 9 10/L and haematocrit <30% usually results in prolongation of the CT [5, 6], as well as the concentration of von Willebrand factor (vWF) in plasma [7]. The PFA-CT with coll/EPI test cartridge, but not the coll/ADP test cartridge, is usually prolonged by COX-1 inhibitors, such as aspirin [8]. According to manufacturer’s specification, the requirements for processing a specimen for PFA currently include the lack of microthrombi in the sample. Also haemolysed blood for PFA testing is not recommended [9]. Recently, we received a blood sample of a 56-year-old woman, to screen the platelet function before urgently needed neurosurgery; the aspirin (100 mg/day) therapy had been stopped since one day. PFA-200 was performed to evaluate the effect of antiplatelet therapy. The complete blood count revealed a platelet count of 500 9 10/L (normal range, 171–374 9 10/L) and haematocrit value of 32.8% (normal range, 35.8–43.7%). PFA-CT with coll/EPI and coll/ADP were both normal, respectively, 81 s (normal range, 82–150 s) with coll/EPI and 67 s (normal range, 62–100 s) with Coll/ADP in duplicate measurement. Because of the unexpected PFA result with normal CT, light transmission platelet aggregation (LTA) on platelet rich plasma with several agonists (epinephrine 10 lM, adenosine diphosphate (ADP) 2.5 lM and 5 lM, collagen 2.5 lg/mL and 5 lg/mL, ristocetin 0.5 mg/mL and 1.5 mg/mL, arachidonic acid, 0.25 mM and thromboxane A2 analogue U46619 10 lM) was performed on Chrono-log 700 (Chrono-Log, Havertown, PA, USA). The LTA showed normal aggregation with ADP, collagen, ristocetin and U46619. There was no aggregation with arachidonic acid, confirmed in repeated measurement. Although a normal coll/EPI CT the LTA with epinephrine was slightly reduced (an amplitude of 60%); this might be explained by the higher concentration of epinephrine used in the PFA cartridge. The LTA was compatible with the effect of aspirin (Figure 1). The complete blood count on citrated (0.109 mM or 3.2%) blood was performed on Sysmex KX-21N (Sysmex Corporation, Kobe, Japan) haematology analyser, and we noticed a flagging for platelet clumps. A microscopic review of the blood smear confirmed the presence of platelet clumps (Figure 2). This could explain the falsely shortened CT of the PFA with coll/EPI and the discrepancy with LTA. Other possible factors contributing to the short CT of the PFA could be the high platelet count (500 9 10/L) or an elevated vWF (not measured in this patient); however, we had little arguments to conclude to pronounced acute phase because the slightly elevated C-reactive protein (7.3 mg/L, normal range <5 mg/L). Platelet clumps are a frequent cause of flow obstructions and may cause cancellation of the test. We cannot exclude that the false short PFA-CT results in this patients may be due to platelet clumps not indicated as ‘flow obstruction’ by the instrument. In conclusion, we reported a discrepant result in a presurgery platelet function screening between PFA and LTA in a patient taking aspirin. Although variations in test results in regard to aspirin effect on PFA and LTA are described in the literature [10,11], we report another possible cause of false negative results with PFA. Considering the platelet count and haemotocrit is common practice in interpreting PFA-CT results. However, review for platelet clumps is not. Platelet clumps can falsely reduce the CT of the PFA and may lead to misdiagnosis of platelet function disorders, as well as inappropriate perceptions and clinical response related to antiplatelet therapy, as illustrated in this case.

IgM interference in the Abbott iVanco immunoassay: A case report

• We describe a case of falsely elevated vancomycin concentration due to IgM paraprotein interference