Laboratory Medicine & Toxicology

Clinical chemistry and immunochemistry incl. Tumor markers and infectious serology screening (in collaboration with the Virology and Microbiology departments) / Endocrinology (in collaboration with the Endocrinology & Metabolism department)

The range of services offered by the diagnostic area of clinical chemistry and immunochemistry with around 200 analytes is aimed both at the broad basic care of the 11 clinic locations with very different medical backgrounds and at the special and intensive care wards with seriously ill patients.

Almost 90% of the analytes are determined on the most modern fully automatic devices of one type. From this point of view, parameters from other specialist areas (e.g. endocrinology, immunology, virology) can also be integrated here if fully automated sample processing of these parameters is possible.

Of particular interest are the new parameter developments (e.g. Copeptin, HE4), which represent the latest state of knowledge and promise a high diagnostic or therapeutic gain in action and can be included in the parameter spectrum at any time after extensive testing and in close coordination with the clinicians.

Emergency samples are analyzed around the clock at all locations within the specified processing times using the latest automatic analyzers of one type. The CVK and KNK central laboratories, where the vast majority of routine samples are also processed, have a very extensive range of emergency parameters available as a basis for this.

Samples are processed in the ten on-site laboratories according to a range of parameters that meets the requirements of emergency diagnostics and also takes into account the special medical features of a hospital site.

Emergency requests with a pharmaceutical or toxicological background that are not included in the specified processing spectrum are forwarded to the Toxicology & Pharmacology laboratory and processed there at any time of day.

As part of patient-oriented diagnostics (POCT), the blood gas, electrolyte and substrate analyses carried out in numerous clinics are monitored and controlled by the Clinical Chemistry department via a central quality control system.

The research activities of the department focus on the evaluation of laboratory parameters in the context of various clinical studies, but also on independent work, e.g. in the testing and application of cardiac markers or in the development and modification of methods.

The uniform and efficient structure and organization in all 11 laboratory locations is a good basis for the further implementation of comprehensive management in quality control as well as all measures in the training and further education of employees with the aim of continuing to meet high quality standards in the future.

Hematology

In the general haematology section of the Laboratory Medicine & Toxicology department, up to 5,000 blood counts are examined every day, including around 600 differential blood counts in routine and emergency diagnostics.

Basic haematological diagnostics are carried out in a highly automated process at all locations using state-of-the-art analysis systems. Using flow cytometric methods, they ensure high quality and standardization with a high sample throughput.

In addition, microscopy of blood smears continues to play an important role and is carried out by qualified medical-technical assistants and our doctors. As experts in cell morphology, they process samples that require manual microscopic assessment due to technical limitations or special issues.

Quantitative deviations such as anemia, thrombocytopenia and leukopenia and, in particular, qualitative deviations such as dysplastic and neoplastic changes are diagnosed in a qualified manner and time-critical values are communicated to the attending physicians by telephone. Unusual and difficult findings, as they frequently occur in our patient population, can be discussed with the experts from the special hemato-oncology department of Labor Berlin or from other institutions cooperating with us.

Our analysis spectrum includes:

• CBC with erythoblasts (NRBC)
• Large (differential) blood count (machine)
• Manual complete blood count (microscopic differentiation)
• Reticulocytes and reticulocyte haemoglobinization (automated)
• Hemoglobinopathy diagnostics (with differential diagnostics from chromatography to sequencing)
• Malaria diagnostics
• Fetal hemoglobin in the smear (Kleihauer-Betke test; Neukölln Clinic)
• Determination of HbA1c using HPLC

Urine diagnostics

Standardized urine analysis in the Department of Laboratory Medicine & Toxicology primarily involves the analysis of native urine. Adapted to the high requirements, the processing of urine samples is based on a fully automated modular solution concept. In the first step, the clinical-chemical standard test strip parameters are measured semi-quantitatively using reflectance photometry and the specific gravity is measured quantitatively using refractometry. Depending on the results of the clinical-chemical urine analysis, an internally defined set of rules is used to decide whether and which urine samples must be subjected to further urine particle analysis. The counting and classification of particles in urine is based on the new blue laser technology, which uses the combined principle of fluorescence flow cytometry and hydrodynamic focusing. Both the cell membranes and the intracellular components are stained specifically for each particle and analyzed using the aforementioned blue laser technology. The individual particle signals or “fingerprints” are translated into a 3D scattergram in which each point represents a specific particle. If pathological cylinders are present, for example, digital imaging of urine particles is performed in the third and therefore final analysis step. Abnormal results from previous chemical and sediment analyses are checked fully automatically using the latter digital imaging technology. The individual particles are identified according to their size and can be differentiated into eight different classes. The individual images provide a detailed view of the particles in the urine and are ultimately checked for plausibility by professionally trained medical-technical staff.

The fully automated urinalysis workflow described above has been established at the Campus Virchow Clinic for several years and enables rapid and comprehensive urinalysis without further sample preparation. All other laboratory locations of the Department of Laboratory Medicine & Toxicology, the so-called reference laboratories, are equipped with a semi-automated analysis system for clinical-chemical urinalysis. If necessary and via a regulated sample transport system, the conspicuous urine samples are promptly forwarded from the on-site laboratories to the central laboratory at the Campus Virchow Clinic for further urine particle analysis.

Diagnostics

The coagulation diagnostics department provides Labor Berlin’s consignors with the basic parameters of coagulation, thromboplastin time (Quick), aPTT, fibrinogen, antithrombin and D-dimers around the clock.

Special coagulation diagnostics are also offered. The focus here is on clarifying a bleeding tendency as well as a tendency to thrombosis or abortion.

A wide range of functional, immunological and chromogenic methods are used for this purpose; processing is usually automated.

The hemostaseological diagnosis of bleeding tendencies includes congenital disorders such as Von Willbrand syndrome, hemophilia A and B, rare factor deficiencies and platelet dysfunction, but also acquired disorders such as sepsis, liver and kidney diseases or drug-induced bleeding tendencies.

The diagnosis of thrombosis susceptibility includes the examination of APC resistance, protein C and S activity and lupus anticoagulant.

Another focus is the diagnosis of inhibitors in patients with congenital and acquired hemophilia.

There is a close link to molecular genetic diagnostics and autoimmune diagnostics.

Therapy monitoring

Specific monitoring of anticoagulation with unfractionated and low-molecular-weight heparin, fondaparinux, oral anti-Xa inhibitors, thrombin inhibitors and platelet function inhibitors is carried out as part of special coagulation diagnostics.

These tests are carried out in the central laboratory. Monitoring during substitution therapy for hemophilia patients is possible around the clock. Further details on the range of tests can be found in the Labor Berlin service catalog.

A central task is to be available as a competent contact for the questions of the submitting physicians regarding diagnostics, therapy and interpretation of results.

The Hemostaseology department is actively involved in clinical studies and research projects as well as in the evaluation of new devices and methods.

In collaboration with experts from other institutions, scientific training events are organized, such as the annual event “The haemostaseological laboratory – status and trends”.

Toxicology provides the following services:

Therapeutic drug monitoring (TDM)

Drug concentrations in human samples are determined as part of therapeutic drug monitoring. It is therefore used to test and monitor drug therapy. In this way, treatment with a drug can be optimized and drug safety increased.

In addition, the occurrence of adverse drug reactions, patient compliance (suspected non-adherence to the medication) or treatment failure may make personalized level monitoring necessary. The dosage can then be individually adjusted for the patient on the basis of various calculation models.

LC-MS devices are often used for the measurements. The purified sample is separated in a liquid chromatography process and the drug to be analyzed is then quantified using a mass spectrometer. The test methods used are sufficiently sensitive to determine even low concentrations. This means that only small sample quantities need to be used for the measurements. Chromatographic separation also makes it possible to reliably analyze the desired drug substance even in samples with complex compositions or to determine several drug substances side by side in one sample.

The following drug groups are routinely included in our scope of services:

• Psychotropic drugs
• Immunosuppressants
• Antiepileptic drugs
• Antifungals and antibiotics
• Cardiac

Serum or plasma samples must be sent in for the test. Immunosuppressants are quantified exclusively from whole blood.

• Toxicology routine request form

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For more details, please visit our service directory.

Drug tests for suspected abuse, to monitor abstinence or for substitution therapy

A qualified drug test as part of an abstinence check, substitution therapy or to detect substance abuse is very often requested.

In the first step, immunological test procedures are most frequently used for this purpose. These immunoassays can usually be carried out fully automatically, quickly and cost-effectively without major sample preparation and are used for qualitative detection. If a positive measurement result is obtained, this can then be verified in a mass spectrometric confirmation procedure. Drug confirmation analyses are much more time-consuming, especially in the preparation of the sample, and the sample processing up to the transmission of the analysis result takes longer than for an immunoassay. However, the individual substances of abuse can be specifically identified in this way. The results of these investigations are therefore conclusive.

The qualitative immunological detection and – at your request – the subsequent mass spectrometric confirmation for drugs and substances of abuse from urine can be requested here.

• Toxicology routine request form

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By testing several urine samples taken at suitable intervals in succession, it is possible to assess the course of the disease. Our toxicology team will be happy to advise you if you have any questions about when to take urine samples.

In addition to basic drug screening, the following analytes can also be requested from urine in extended drug screening:

• Ethyl glucuronide
• GHB
• Tilidine, nor-, bisnortilidine
• Tramadol, O-, N-desmethyltramadol
• Synthetic cannabinoids

If withdrawal symptoms are present in a newborn, detection of drugs in the meconium can be carried out. A positive result can serve as evidence of exposure during the last trimester of pregnancy. Immunoassays and LC-MS analyses are combined for the analysis.

• Toxicology routine request form

  pdf

Intoxication: carrying out toxicological search analyses in cases of suspected acute drug intoxication

Systematic toxicological screening (STA) is used to clarify acute poisoning with medicines or drugs. Various examination procedures have been established and are used for this purpose. It includes the identification and quantification of pharmaceuticals and drugs using immunoassay, HPLC-DAD, GC and LC-MS/MS.

The request for a toxicological search analysis is possible 24/7.

• Toxicology emergency request form

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EDTA blood, plasma, serum or urine can be submitted for the test. If drug intoxication is suspected, urine is the preferred test material.

Special screening programs are offered for the following selected substance groups:

• Glycols including methanol
• Oral antidiabetics including metformin
• Superwarfarins (rodenticides)
• Methotrexate, 7-OH-methotrexate after therapy with glucarpidase (Voraxaze(R))

Analyses as part of the determination of irreversible loss of brain function (IHA)

In preparation for the diagnosis of irreversible brain dysfunction (IHA), CNS-depressant drugs must be detected in the patient’s blood prior to explantation. These analyses are carried out in accordance with the guidelines of the Society for Toxicological and Forensic Chemistry (GTFCh).

• Toxicology emergency request form

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General information

• Specific details on preanalytics and detection methods as well as therapeutic reference ranges can be found in the list of services for the respective analysis parameters.
• Please use the request forms provided for each type of examination and complete them in full. In particular, information on the patient and sender must not be missing.
• Please observe the relevant legal regulations on packaging and shipping of human sample material.

For the range of substances currently available, please refer to the list of services or give us a call.

CSF analysis is a central component of neurological diagnostics. As part of the interdisciplinary cooperation with other departments of Labor Berlin – Charité Vivantes GmbH as well as the institutes and clinics of the Charité (Institute of Neuropathology, Department of Neurology), we offer a comprehensive examination program on issues of neurological and psychiatric diseases.

In particular, neuroinfectious, neuroimmunological, neurodegenerative and some neurooncological diseases can be diagnosed with the help of various examination methods in the cerebrospinal fluid. Depending on the problem and the requested test analytes, we use almost exclusively fully automated quantitative laboratory measurement technologies in CSF analysis in the Department of Laboratory Medicine & Toxicology.

Basic CSF diagnostics are offered around the clock, on weekends, weekends and public holidays, and include the fully automated determination of:

• Total cell count including mechanical predifferentiation of white cells into mononuclear and polymorphonuclear cells
• cells foreign to the liquor
• Erythrocytes
• Total protein
• Lactate
• Glucose

Further CSF diagnostics are carried out in the “protein diagnostics” section and include the detection of a disturbance in blood-brain barrier function and intrathecal antibody synthesis (“Reiber diagram”). If necessary, oligoclonal bands are also detected in CSF and serum pairs.

The cerebrospinal fluid cytologies are carried out professionally around the clock, the assessment is carried out both by employees of the department and by employees of the Institute of Neuropathology and Special Hematology/Oncology of the Charité.

The Department of Laboratory Medicine & Toxicology at Labor Berlin – Charité Vivantes GmbH, the Institute of Neuropathology and the Department of Neurology at Charité are ultimately involved in the preparation of the integrated CSF findings.

In the area of protein diagnostics and HPLC, blood, urine and cerebrospinal fluid diagnostics as well as the diagnostics of trace elements are supplemented with special protein-chemical methods, high-pressure liquid chromatography (HPLC) and atomic absorption photometry (AAS). For example, immunoglobulins are determined in the CSF, displayed in the Reiber diagram and evaluated with regard to a barrier disorder or intrathecal synthesis as part of the overall CSF assessment. This is supplemented by the detection or exclusion of oligoclonal bands using isoelectric focusing. The measurement of corresponding lead proteins in the urine enables the differentiation of prerenal, renal-glomerular, renal-tubular and postrenal forms of proteinuria. Capillary electrophoresis and immunofixation electrophoresis are used to detect monoclonal gammopathies or the excretion of monoclonal free light chains (“Bence-Jones proteins”). If required, the free light chains in the serum can also be determined quantitatively.

Catecholamines and their metabolites as well as the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIES) are measured using HPLC. The determination and differentiation of porphyrins in urine and the measurement of vitamins A, B1, B6 and E in serum or blood are also carried out using HPLC-based methods. AAS is used for the determination of trace elements such as copper, selenium and zinc.

When requesting tests from this area, the respective pre-analytical particularities, such as light protection (e.g. for vit. B1 and B6 or porphyrins), sample cooling (e.g. vit. B1), or the addition of stabilizers during sample collection (e.g. addition of hydrochloric acid for catecholamines and metabolites in urine) or the use of special blood collection tubes (e.g. for trace element determinations) must be observed. The relevant information can be found in the service specifications.

The genetic analysis offered in the laboratory area can be assigned to both predictive and diagnostic areas.

The Molecular Risk Diagnostics department deals with the detection of functionally relevant genetic polymorphisms that confirm or rule out a suspected diagnosis. The analysis is carried out with LightCycler® and is based on genomic DNA obtained from EDTA blood.

One focus is on thrombophilia diagnostics, which is intended in particular to contribute to a comprehensive assessment of the risk of recurrence and the correct treatment recommendation following thromboembolic events in the venous or arterial system.

In the field of pharmacogenetic diagnostics, high-frequency genotypes are examined that have a relevant influence on the metabolization of various drugs (e.g. platelet aggregation inhibitors, psychotropic drugs) and thus influence the probability of a good response to therapy or drug-related side effects.

Hemoglobinopathy diagnostics is a comprehensive area of growing importance. Labor Berlin has a comprehensive range of methods at its disposal: GAP-PCR, Triple-PCR, MLPA (Multiplex Ligation-dependent Probe Amplification), sequencing for all hemoglobin genes (HBA1, HBA2, HBB). These modern methods are used in stages according to indication and after a specialist analysis of the basic diagnostics (HPLC, blood count, iron status). This enables us to detect the wide variety of mutations due to ethnic heterogeneity, such as alpha and beta thalassemias, sickle cell disease, HbC, HbE, etc.

Consent in accordance with the Genetic Diagnostics Act must be obtained for all tests.
You can find more detailed information on our range of examinations in our list of services.

One of Labor Berlin’s main tasks is to provide immunohematological and transfusion medical care for Vivantes hospitals.

The analysis spectrum of immunohematology includes all tests that ensure the compatibility of a blood product for patients before a transfusion.

The spectrum includes the following analyses:

• Blood group determination (AB0 system, Rhesus factor / Rhesus formula, Kell, other characteristics if necessary)
• Antibody screening test
• Antibody differentiation
• Direct Coombs test
• Compatibility test (cross-match)

In all laboratories at the Vivantes sites, immunohematological diagnostics are carried out almost exclusively using state-of-the-art, fully automated analysis systems. For requirements that need to be processed very quickly and for special examinations, the medical-technical laboratory assistants are of course also proficient in manual methods.

24/7 staffing of the blood depots in the laboratories ensures that patients are supplied with blood reserves. Each on-site laboratory includes a blood depot for erythrocyte concentrates and frozen plasma (GFP). In the two largest clinics, in Neukölln and Friedrichshain, with a focus on accidents and maximum care, platelet concentrates are also stored in stock. This ensures a reliable supply of all necessary blood products to the locations.

The Department of Laboratory Medicine & Toxicology is also responsible for transfusion in accordance with the requirements of the Transfusion Act and the Haemotherapy Directive for Vivantes hospitals and provides round-the-clock advice to the clinics on immunohaematological and transfusion medicine issues.

The aim of urinary stone analysis is to identify all crystalline components of a urinary stone. The methods of urinary stone analysis that are most widely used and also provide the best results are:

1. Polarization microscopy on the grain preparation: The evaluation is based on the identification of crystal-optical characteristics such as colors, refraction, birefringence and interference colors
2. X-ray diffraction: As part of the measurement, the diffraction of X-rays on the crystal lattice is recorded
3. Infrared spectroscopy: Detection is based on absorption in the infrared spectral range

LaborBerlin is the only laboratory in Germany that can analyze the composition and structure of a urinary stone using these three methods. Based on the stone analysis, stone patients can be assigned to different groups, for which the targeted metaphylaxis recommendation is an important part of urinary stone therapy and thus helps to minimize the risk of recurrent stone formation as far as possible.

1. toxicological addiction analysis including emergency analysis and toxicological brain death diagnostics:

At least 5 mL blood in serum or plasma sample tube + 5 mL urine in urine tube

2. therapeutic drug monitoring (TDM):

At least 2 mL of blood in serum or plasma sample container
For the measurement of immunosuppressive substances: 2 mL whole blood (EDTA or heparin)
For the measurement of gentamycin in premature infants and newborns: 2 x 50 µl of blood in heparinized capillaries per sample

3. drug screening:

At least 5 mL spontaneous urine in urine sample container
For newborn screening: 1 gr. Meconium in microbiology sample container
The analysis of samples is only possible after consultation by telephone in individual cases.

General information:

• Specific details on preanalytics as well as detection methods, therapeutic reference ranges, etc. can be found in the list of services for the respective analysis parameters.
• Please use the request forms provided for each type of examination, which you should fill out as completely as possible.
• Please observe the relevant legal regulations on packaging and shipping of human sample material.

 

Downloads

 

• Requisition slip ABCB1 genotyping

  pdf

 

Downloads

 

• Requisition slip for cerebrospinal fluid diagnostics

  pdf