Volume 32, Issue 6

A myeloproliferative disorder is the main risk factor for portal venous thrombosis or Budd-Chiari syndrome. Other significant factors are hereditary or acquired prothrombotic states and different liver diseases. Approximately 25% of thromboses occur without an indication of possible etiology. However, some patients show signs of myeloproliferative disorders on bone marrow morphology. The identification of the Janus kinase V617F mutation, which was first described in 2005, allows new insights into both the pathobiochemistry and pathophysiology of this disease, and a substantial improvement of the diagnostics at least to some of the myeloproliferative disorders. A retrospective study of clinical trials of patients with Budd-Chiari syndrome or portal venous thrombosis showed that patients with thrombosis predefined as idiopathic carried the V617F mutation at a high percentage rate and, furthermore, that a part of this patient group developed a myeloproliferative disorder after the thrombotic event.

Abstract> A myeloproliferative disorder is the main risk factor for portal venous thrombosis or Budd-Chiari syndrome. Other significant factors are hereditary or acquired prothrombotic states and different liver diseases. Approximately 25% of thromboses occur without an indication of possible etiology. However, some patients show signs of myeloproliferative disorders on bone marrow morphology. The identification of the Janus kinase V617F mutation, which was first described in 2005, allows new insights into both the pathobiochemistry and pathophysiology of this disease, and a substantial improvement of the diagnostics at least to some of the myeloproliferative disorders. A retrospective study of clinical trials of patients with Budd-Chiari syndrome or portal venous thrombosis showed that patients with thrombosis predefined as idiopathic carried the V617F mutation at a high percentage rate and, furthermore, that a part of this patients group developed a myeloproliferative disorder after the thrombotic event.

Familial clustering of lupus anticoagulants and anticardiolipin antibodies has been reported in the past. Antiphospholipid autoantibodies within families were only occasionally associated with clinical events. Valid data on frequency and clinical relevance of this phenomenon are lacking. Indicating an immunogenetic predisposition, HLA DR4, DR7, DRw53 and DQw7 are associated with primary antiphospholipid syndrome, contrary to the HLA pattern of systemic lupus erythematosus. β2 glycoprotein I is important for binding of anticardiolipin antibodies. The Val247Leu polymorphism of the fifth domain of β2 glycoprotein I seems to affect antigenicity of β2 glycoprotein I.

Hereditary dysfibrinogenemia is a rare clotting disorder due to a structural defect in the fibrinogen molecule that results in a tendency for bleeding and thrombosis, as well as obstetric complications. We describe the laboratory results and clinical manifestations for 50 patients with a diagnosis of dysfibrinogenemia. Various different laboratory measurements of fibrinogen were performed on samples from these patients, including fibrinogen (Clauss), heat fibrinogen precipitation according to Schulz and immunological fibrinogen. Fifty patients were found with dysfibrinogenemia (52% female; median age 52, range 9–89 years). The fibrinogen level according to Clauss was low, with a median of 51 mg/dL (range 15–86 mg/dL; normal range 150–450 mg/dL). Determination of other fibrinogen levels revealed normal results: heat fibrinogen precipitation according to Schulz, 240 mg/dL; and immunological fibrinogen, 244 mg/dL. The median reptilase time was longer than normal, at 55 s (normal 20 s). Some 50% of the patients reported a distinct bleeding tendency, mostly a tendency for hematoma (60%) and secondary bleeding (44%). Thirteen patients had thrombotic events, of which 54% were located arterially. Some 12% of the patients reported a tendency for bleeding and for thrombosis, whereas 19% had miscarriages, sometimes recurrent. We found that functional fibrinogen levels (Clauss) were generally lower in patients with bleeding manifestations (43 vs. 57 mg/dL in other patients). Zusammenfassung Die angeborene Dysfibrinogenämie ist eine sehr seltene Gerinnungsstörung, basierend auf einem strukturellem Defekt im Fibrinogenmolekül, worunter eine Neigung zu Blutungen, Thrombosen und Aborten entstehen kann. Wir beschreiben die Ergebnisse der Labordiagnostik und die klinischen Manifestationen bei 50 Patienten mit Dysfibrinogenämie. Es wurden folgende Untersuchungen vorgenommen: Fibrinogen (Clauss), immunologisches Fibrinogen und Hitze-Fibrinogen nach Schulz. Unter den 50 Patienten mit Dysfibrinogenämie (52% weiblich; Altersmedian 52 Jahre, 9–89 Jahre) war die Fibrinogenkonzentration nach Clauss erniedrigt im Median mit 51 mg/dL (15–86 mg/dL; Norm 150–450 mg/dL). Die Bestimmungen der Fibrinogen-Antigen-Konzentrationen ergaben Normalbefunde: Hitze-Fibrinogen nach Schulz, 240 mg/dL; und immunologisches Fibrinogen, 244 mg/dL. Die Reptilasezeit war mit 55 s verlängert (Median; Norm <20 s). Fünfzig Prozent der Patienten hatten ein oder mehrere Blutungsereignisse, meistens eine deutliche Neigung zu Hämatomen (60%) oder Nachblutung (44%). Bei 13 Patienten ist ein thromboembolisches Ereignis aufgetreten. Bei 12% der Patienten war eine Neigung gleichzeitig zu Blutung und Thrombosen vorhanden. Bei 19% der weiblichen Patienten hatten einen oder mehrere Aborte. Bei Patienten mit stattgehabten Blutungssymptomen war die Konzentration von Fibrinogen nach Clauss mit 43 mg/dL im Median niedriger als bei Patienten ohne Blutungsproblemen (57 mg/dL).

Complete blood count including automated blood cell differential is one of the most frequent tests in the medical laboratory. How reliable is the method representing a diagnostic sieve in a stepwise diagnostic approach? Which pathologic conditions will be overlooked? Which body fluids can be investigated? What are the preanalytical requirements? When is a microscopic review required? Reimbursement has reached a level where a personal review of the diagram of cell clusters and of the blood film cannot be afforded. As the technology of blood cell analyzers has recently been described in this journal, this article focuses on the strengths and weaknesses of the automated blood cell differential. This allows judgment of the risks of a stepwise approach dependent on the medical discipline sending the sample.

Complete blood count including automated blood cell differential is one of the most frequent tests in the medical laboratory. How reliable is the method representing a diagnostic sieve in a stepwise diagnostic approach? Which pathologic conditions will be overlooked? Which body fluids can be investigated? What are the preanalytical requirements? When is a microscopic review required? Reimbursement has reached a level where a personal review of the diagram of cell clusters and of the blood film cannot be afforded. As the technology of blood cell analyzers has recently been described in this journal, this article focuses on the strengths and weaknesses of the automated blood cell differential. This allows judgment of the risks of a stepwise approach dependent on the medical discipline sending the sample.

Body cavity effusions are symptoms of different diseases. The microscopic examination of effusion fluid is a technically simple method, which in many cases may facilitate further diagnostic workup. In selected cases, a definitive diagnosis can be established. Zusammenfassung Körperhöhlenergüsse sind Symptome unterschiedlicher Grunderkrankungen. Die mikroskopische Untersuchung von Ergussflüssigkeit ist eine technisch wenig aufwendige, aber sehr aussagekräftige Methode, die in vielen Fällen eine diagnostische Weichenstellung und in Einzelfällen eine definitive Diagnose ermöglicht.

In contrast to calcitonin, which is primarily synthesized in the thyroid, procalcitonin is a prohormone which is synthesized in many different tissues of infected organs. To diagnose mild, localized, or early infections an assay needs to have a functional assay sensitivity of approximately 0.02 μg/L. We demonstrated that procalcitonin modifies the outcome of respiratory infections with regard to minimizing the use of antibiotics and duration of antibiotic treatment. High concentrations, especially over time, indicate high risk of a severe outcome. In this respect, procalcitonin is superior to other infection markers, such as C-reactive protein. High procalcitonin levels can also be found in non-bacterial diseases, such as malaria, severe trauma, burns, and medullar carcinoma of the thyroid. Procalcitonin, as a marker, has improved the diagnosis of bacterial infections. However, procalcitonin needs to be used in conjunction with other laboratory markers, clinical examination, and medical history.

In contrast to calcitonin which is primarily synthesized in the thyroid, procalcitonin is a prohormone which is synthesized in many different tissues of infected organs. To diagnose mild, localized, or early infections an assay needs to have a functional assay sensivity of approximately 0.02 μg/L. We demonstrated that procalcitonin modifies the outcome of respiratory infections with regard to minimizing the use of antibiotics and duration of antibiotic treatment. High concentrations, especially over time, indicate high risk of a severe outcome. In this respect, procalcitonin is superior to other infection markers, such as C-reactive protein. High procalcitonin levels can also be found in non-bacterial diseases, such as malaria, severe trauma, burns, and medullar carcinoma of the thyroid. Procalcitonin, as a marker, has improved the diagnosis of bacterial infections. However, procalcitonin needs to be used in conjunction with other laboratory markers, clinical examination, and medical history.

Serum levels of interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) were measured in 38 critically ill patients immediately after an increase in body temperature above 38.3°C. Ten healthy controls were also included for comparison. The onset of fever was accompanied by elevated circulating levels of all the 3 markers in comparison to healthy control subjects. However, only IL-6 levels were significantly higher (p<0.05) in nonsurvivors compared with survivors. Sensitivity, specificity, positive, and negative predictive values for survival were higher for IL-6 in comparison to levels of PCT and CRP. Areas under receiver characteristic operating curves revealed the highest area under the curve for IL-6 compared to PCT and CRP. These data suggest that IL-6 rather than PCT or CRP may be an early predictor of prognosis and mortality in patients with the onset of fever.

Serum levels of interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) were measured in 38 critically ill patients immediately after an increase in body temperature above 38.3°C. Ten healthy controls were also included for comparison. The onset of fever was accompanied by elevated circulating levels of all the 3 markers in comparison to healthy control subjects. However, only IL-6 levels were significantly higher (p<0.05) in nonsurvivors compared with survivors. Sensitivity, specificity, positive, and negative predictive values for survival were higher for IL-6 in comparison to levels of PCT and CRP. Areas under receiver characteristic operating curves revealed the highest area under the curve for IL-6 compared to PCT and CRP. These data suggest that IL-6 rather than PCT or CRP may be an early predictor of prognosis and mortality in patients with the onset of fever.

In adults, the majority of IgE-mediated food allergies is caused by cross-reacting allergen molecular structures that are present in inhalant as well as food allergens. On the one hand, synthesis of IgE stimulated by a cross-reactive allergen in pollen can result in a diverse pattern of sensitizations against various foods. On the other hand, even anaphylactic reactions may occur after first consumption of a food containing a cross-reactive allergen. In clinical practice, it is not sufficient to detect cross-reactivities by immunologic assays. Clinically relevant sensitizations have to be distinguished from clinically irrelevant IgE responses. Hence, in cases of unclear history oral challenge tests are necessary. A few open studies have demonstrated the therapeutic potential in pollen-related food allergy: in at least 50% of the cases, tree pollen immunotherapy led to an improvement of associated food allergies. However, these results have to be confirmed in placebo-controlled studies. As we are facing an increase of pollen allergies, a shift in sensitization patterns and changes in nutritional habits, the occurrence of new, so far unknown cross-reactions is expected.

Drug hypersensitivity reactions have to be tested to identify the culprit substance. The history includes the general information and specific data concerning used drugs, the classification and circumstances of the reaction. Skin tests are performed in all hypersensitivity reactions with allergic symptoms. Tests should be done between four weeks and six months after clearance of the symptoms by performing skin prick test, intradermal test, patch test or photopatch test. Validated tests for the detection of specific IgE antibodies in the serum are available for only few drugs, especially betalactam antibiotics. Other laboratory tests, e.g., the basophil activation test are done only in special cases. Provocation tests are indicated, if the culprit drug cannot be identified by the above mentioned tests. If possible, the evaluation of provocation tests should rely on objective parameters. The concluding assessment will be discussed with the patient and will be documented in an allergy pass.

Vitamin D has been attributed a role in the pathogenesis of various chronic diseases. Vitamin D status is best assessed by measuring serum 25-hydroxyvitamin [25(OH)D]. Serum 25(OH)D concentrations far above the deficiency threshold for skeletal health may be suboptimal with respect to long-term health consequences. No final consensus has so far been reached regarding an appropriate cutoff value. Diagnostic work-up in the clinical setting and the interpretation of scientific evidence are hampered by a lack of standardization in 25(OH)D assays. The present study compares quantification of serum 25(OH)D by means of three different assays: an in-house high-performance liquid chromatography method, and chemiluminescence immunoassays (CLI) from two different manufacturers (DiaSorin, Nichols). In addition, serum intact parathyroid hormone (iPTH) was measured using two different methods (CLI, DiaSorin; electrochemiluminescence immunoassay, Roche). Based on the inverse relationship between vitamin D and PTH in the regulation of serum calcium, receiver operating characteristic analyses were used to determine assay specific serum 25(OH)D cutoff values that best distinguished between normal and elevated serum iPTH as indicated by the manufacturer. The cutoff values identified varied from 22.9 μg/L for the HPLC method to 19.5 μg/L for the Nichols CLI and 14.4 μg/L for the DiaSorin CLI. Although these values need to be considered as warning thresholds, they fall within published reference limits for the 25(OH)D assays investigated. Serum iPTH-based cutoff values for serum 25(OH)D are not suitable as substitutes for assay-specific reference limits for various long-term adverse health outcomes that may be linked to vitamin D insufficiency.

Abstract> Vitamin D has been attributed a role in the pathogenesis of various chronic diseases. Vitamin D status is best assessed by measuring serum 25-hydroxyvitamin D(25[OH]D). Serum 25(OH)D concentrations far above the deficiency threshold for skeletal health may be suboptimal with respect to long-term health consequences. No final consensus has so far been reached regarding an appropriate cutoff value. Diagnostic work-up in the clinical setting as well as the interpretation of scientific evidence are hampered by a lack of standardization in 25(OH)D assays. The present study compares quantification of serum 25(OH)D by means of three different assays: an in-house high-performance liquid chromatograph (HPLC)-method, and two chemiluminescence immunoassays (CLI) from different manufacturers (DiaSorin, Nichols). In addition, serum intact parathyroid hormone (iPTH) was measured using two different methods (CLI, DiaSorin; electrochemiluminescence immunoassay [ECL], Roche). Based on the inverse relationship between vitamin D and PTH in the regulation of serum calcium, receiver operating characteristic (ROC) analyses were used to determine assay specific serum 25(OH)D cutoff values that distinguished at best between normal and elevated serum iPTH according to the manufacturers given reference ranges. Obtained cutoff values identified varied from 22.9 μg/L for the HPLC method to 19.5μg/L for the CLI (Nichols) and to 14.4 μg/L for the CLI (DiaSorin), respectively. While these values need to be considered as warning thresholds, they fall within published reference limits for the investigated 25(OH)D assays. Serum iPTH-based cutoff values for serum 25(OH)D are not apt to substitute for assay-specific reference limits for the various long-term adverse health outcomes that may be linked to vitamin D insufficiency.