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Haematological specialist consultation
Registration for the special consultation under Information for doctors
For patients with chronic forms of illness who come to us for the first time, it makes sense for us to receive the most important findings and reports in advance so that we can discuss the problem in the anaemia conference and plan internal functional examinations and consultation appointments. The same applies to patients whose place of residence is so far away that they have to be hospitalised or stay overnight in Ulm.
Clinical studies
Further information on the active studies can be found at:
Diagnostics and therapy in the Clinic for Internal Medicine III
Anaemia is one of the most common sequelae of numerous general diseases, especially infectious and non-infectious inflammations, deficiencies, kidney failure and neoplasia. In the majority of patients, diagnosis and cause-oriented treatment is carried out in general practice, by a registered internist or paediatrician. However, the involvement of a haematology specialist in the practice or clinic is necessary for some patients. This includes the diagnosis of patients with unexplained anaemia as well as the treatment and follow-up of rare forms such as autoimmune haemolytic anaemia and complex blood disorders (leukaemia, myelodysplastic syndrome, aplastic anaemia).
Patients with congenital anaemia, predominantly due to a wide range of genetic defects, present a particular problem. They are often diagnosed in childhood and are usually under paediatric care for years. Thanks to advances in treatment, the life expectancy of patients with congenital anaemia has improved considerably, meaning that an increasing number of secondary internal conditions and complications need to be managed. This requires comprehensive interdisciplinary care, even in adulthood. The incidence of patients with hereditary haemoglobinopathies such as thalassaemia or sickle cell disease is far higher than it used to be due to immigration from endemic regions. Only specialised care based on the findings from these countries allows professional intervention in crisis situations and an improvement in quality of life and normalisation of life expectancy. In contrast to the Mediterranean countries and the USA, Great Britain and France, which have been setting up special centres for the treatment of these patients for decades, there are as yet no structures in Germany to ensure the lifelong care of adult patients and advice for the doctors responsible at their place of residence.
In close cooperation with colleagues from the Department of Paediatrics and Adolescent Medicine and the Department of Transfusion Medicine, the diagnosis and treatment of rare acquired and congenital anaemia in adult patients is to be centralised and improved at the Department of Internal Medicine III. One example of this is the register for the documentation and counselling of patients with congenital dyserythropoietic anaemia (CDA), which has been in existence for over 20 years and is managed by Prof. Dr. med emerit. H. Heimpel (Clinic for Internal Medicine III) in collaboration with Prof. Dr med Kohne (Clinic for Paediatrics and Adolescent Medicine) and Prof. Dr med H. Schrezenmeier (Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, IKT). This is associated with continuous consultation and advice for medical colleagues from Germany and neighbouring European countries.
Laboratory diagnostics
Blood analysis: cell counting, erythrocyte indices, morphological blood count.
Bone marrow diagnostics: cytology, iron staining, flow cytometry, histology (Prof. Möller), cytogenetics, molecular diagnostics. Iron status, haptoglobin, other laboratory parameters in collaboration with the Institute of Clinical Chemistry.
Non-invasive measurement of iron content by MRI (Clinic for Diagnostic and Interventional Radiology).
Special haemolysis parameters, analysis of erythrocyte enzymes, eosin malein test (EMA test), biochemical and genetic haemoglobin analysis (Department of Paediatrics and Adolescent Medicine, Prof. Dr. med Kohne).
Flow cytometry for the detection of PNH, immunohaematology (IKT), genetic diagnostics for congenital dyserythropoietic anaemia and PNH: Institute for Clinical Transfusion Medicine and Immunogenetics (IKT) (Prof. Schrezenmeier, Dr. K. Schwarz).
Description of the clinical picture and basic information
Anaemia is when a reduction in haemoglobin levels (Hb) or haematocrit (Hk) below an age- and gender-specific reference value is detectable. Anaemia is one of the most common pathological changes worldwide and is usually the result of chronic inflammatory or neoplastic diseases. Anaemia occurs as a partial finding in many blood disorders. Anaemia is caused either by too rapid breakdown(haemolysis) - acquired through anti-erythrocytic autoantibodies or congenital through enzyme or membrane defects - reduced (e.g. aplastic anaemia) or ineffective (myelodysplastic syndrome, MDS) formation or a distribution disorder (pregnancy anaemia, hypersplenimus) of red blood cells. Reduced haemoglobin formation due to iron deficiency, vitamin deficiency or congenital anaemia can also lead to anaemia. Anaemia in chronic diseases - including tumour diseases - is usually caused by a combination of several factors.
Reference values:
14 - 70 years Men: Hb 13 - 17 g/dl; Hct 42 - 50 %; erythrocytes 4.3 - 5.6 T/l
14 - 60 years Women: Hb 12 - 16 g/dl; Hkt 38 - 44 %; erythrocytes 4.0 - 5.4 T/l
Definition of anaemia according to WHO:
Men Hb < 13 g/dl
Women Hb < 12 g/dl
Iron deficiency anaemia
One of the most common forms of anaemia is iron deficiency anaemia. The diagnosis is made on the basis of a characteristic constellation with evidence of hypochromic, microcytic anaemia with a reduction in the mean copuscular haemoglobin content (MCH) and/or the mean red cell volume (MCV). Iron deficiency anaemia is caused by a disturbed balance between iron loss and iron absorption. The most common cause is persistent blood loss, less frequently reduced iron absorption. It is not an independent disease, but a symptom of an underlying disorder. Finding the cause of the blood loss is the task of the doctor and should precede treatment with iron supplements. Common causes are blood loss via the intestines or the urinary tract and, in women, via menstruation. Iron deficiency can only be treated sustainably by eliminating the cause.
Anaemia in chronic illness
Anaemia of chronic disease (ACD) is also common. It occurs in the context of tumour diseases or chronic inflammatory processes (rheumatoid arthritis, lupus erythematosus, tuberculosis). ACD is usually normochromic-normocytic, in a third of cases hypochromic-microcytic and must then be differentiated from iron deficiency anaemia. The serum ferritin is usually elevated. Treatment is based on the underlying disease.
Anaemia due to vitamin B12 or folic acid deficiency
Megaloblastic anaemia develops as a result of a vitamin B12 or folic acid deficiency. It is characterised by hyperchromic (MCH > 34) and macrocytic anaemia (MCV > 100). It is characterised by low absolute reticulocyte counts and a frequently highly elevated lactate dehydrogenase (LDH). The diagnosis is usually made by the classic laboratory constellation in conjunction with a low vitamin level. Treatment consists of administering the missing vitamin.
Haemolytic anaemia
An excessively rapid breakdown of erythrocytes with the development of anaemia is called haemolytic anaemia. Acquired causes include autoimmune haemolysis with detection of antibodies that occupy and destroy the red blood cells as well as rare acquired membrane changes (paroxysmal nocturnal haemoglobinuria). Laboratory diagnostics include the classic haemolysis parameters (LDH, bilirubin, haptoglobin) as well as special diagnostics for the detection of autoantibodies (Coombs test) and membrane defects (FACS analysis).
Treatment varies and depends on the cause of the haemolysis. Autoimmune haemolysis is primarily treated with corticosteroids and/or immunosuppressants. PNH may require the use of the monoclonal antibody eculizumab. Patients with refractory haemoytic anaemia sometimes benefit from splenectomy.
Congenital anaemia
Thalassaemia
Thalassaemia is still rare in Germany, although its prevalence is increasing due to immigration from the Mediterranean, African and Asian regions. Thalassaemia is the most common form of congenital microcytic anaemia.
Causes
A genetic defect leads to a reduced production of haemoglobin chains. Depending on which of the chains is reduced, the disease is called alpha-thalassaemia (rare) or beta-thalassaemia (common). The survival time of the red blood cells is shortened, resulting in haemolysis.
Diagnosis
A suspected diagnosis can usually be made from the constellation of blood count parameters; it requires confirmation by haemoglobin analysis (beta-thalassaemia) or genetic testing.
Signs of the disease
The clinical picture depends on the genetic constellation:
Thalassaemia minor: Heterozygosity: only one allele (gene copy) is mutated, this is usually asymptomatic. The erythrocytes are small (MCV and MCH are reduced).
Thalassaemia intermedia: Usually compound heterozygosity: the two alleles are mutated at different sites, resulting in moderate anaemia with jaundice and splenomegaly. Depending on the severity, iron overload can develop.
Thalassaemia major: Usually homozygous: both alleles are mutated identically, resulting in severe anaemia occurring in childhood with increasing splenomegaly and growth retardation. In the past, the main cause of death was iron overload with organ damage.
Therapeutic options
All mild forms require no treatment. The moderate and severe forms require regular transfusions in childhood, resulting in iron overload (transfusion haemosiderosis). Control of this complication is therefore of crucial importance. The availability of chelating agents has significantly improved treatment, and in particular the use of modern drugs available as tablets has facilitated treatment. In the course of life, removal of the spleen may become necessary.
To date, the only potentially curative treatment is bone marrow or haematopoietic stem cell transplantation. Due to the associated risks, it is only used for severe forms.
Qualitative haemoglobin defects (haemoglobinopathies)
Qualitative haemoglobin defects (haemoglobinopathies)
Sickle cell disease
Sickle cell disease is the most common haemoglobinopathy worldwide. There are currently over 1000 patients living in Germany, exclusively migrants from Central and West Africa, the countries of the Eastern Mediterranean, the Middle East, India and Central Asia.
Causes
A point mutation at position 6 of the beta-haemoglobin chain (Glu-Val) alters the haemoglobin molecule (HbS) in such a way that in a low-oxygen state the haemoglobin changes from a soluble form to a polymer and gives the erythrocytes a sickle shape. Sickle cell carriers in which only one allele is affected are largely asymptomatic; in the case of homozygosity or in combination with thalassaemia, sickle cell disease develops.
Diagnostics
Blood smear with evidence of sickle cells (Figure 2: Blood smear of a patient with sickle cell anaemia). Haemoglobin analysis with detection of HbS and possibly other H. Molecular genetic analysis.
Signs of the disease
The deformation of the erythrocytes leads to a blockage of small and tiny blood vessels in internal organs (liver, spleen, bones, brain, retina, kidneys, lungs, etc.). Sickle cell disease leads to circulatory disorders and even infarcts. The following complications are common:
- Aplastic crisis with severe anaemia after viral infections (parvovirus B19)
- Infections with bacteria (pneumococci, salmonella)
- Acute chest syndrome: accumulation of blood in the vessels of the lungs with chest pain, shortness of breath, fever and oxygen deficiency
- Pain crises, especially in the back, arms, legs, chest and abdomen.
- Bone inflammation (osteomyelitis)
- Strokes, cerebral haemorrhages
Therapeutic options
Hydroxyurea reduces the number and intensity of pain crises in some patients and reduces mortality.
Transfusions should be given as sparingly as possible and only in sequestration crises and aplastic crises. In the event of severe complications with infarctions or organ failure, an exchange transfusion may be necessary.
Avoiding or minimising complications is crucial for the patient's prognosis. Timely antibiotic therapy for infections and prophylactic vaccinations are part of the treatment concept. The guidelines are regularly updated and can be viewed online at major centres in the USA and the UK (e.g. www. nhlbi.nih.gov/health/prof/blood/sickle/sc_mngt.pdf,http://www.sicklecelldisease.org )
The only potentially curative treatment to date is bone marrow or blood stem cell transplantation. Due to the risks involved, it is only used for severe forms.
Membrane defects
The most common defects in the erythrocyte membrane lead to spherocytic anaemia (hereditary spherocytosis). It is the most common congenital form of haemolytic anaemia in Central Europe. Diagnosis is sometimes only made in adulthood on the basis of the typical constellation with haemolysis (often compensated), splenomegaly and evidence of gallstones. The diagnosis is confirmed by detection of spherical cells in the blood smear, determination of osmotic resistance and a positive eosin-malein test (EMA test). Treatment Removal of the spleen (splenectomy) almost always normalises the blood count, but is only necessary in cases of severe haemolysis. There are also a number of other membrane disorders such as elliptocytosis and stomatocytosis, which can be diagnosed by detecting characteristic changes in the blood smear and/or by special tests.
Haemolytic anaemia due to enzyme defects
Congenital enzyme variants resulting in reduced enzyme activity lead to premature breakdown of the erythrocytes. Pyruvate kinase and glucose-6-phosphate dehydrogenase deficiencies are the most common. Defects in hexokinase, triosephosphate isomerase, diphosphoglycerate mutase and glutathione reductase are rarer.
Unstable haemoglobins
This term covers a group of diseases that are characterised by changes in the amino acid sequence of the haemoglobin molecule and lead to a significantly shortened survival time of the erythrocytes. The changes are named after the places where they were first described (e.g. Hb-Cologne). Diagnosis is based on haemoglobin analysis. What they all have in common is haemolysis with splenomegaly. Haemolysis is often triggered by medication. In severe haemolytic anaemia, it may be necessary to remove the spleen.
Sideroblastic (sideroachrestic) anaemia
Sideroblastic anaemias are a group of diseases characterised by a marked ineffectiveness of haemopoiesis. They are caused by both genetic factors (e.g. ALAS2 mutation in hereditary sideroblastic anaemia) and acquired factors (medication, lead poisoning).
Congenital dyserythropoietic anaemia
Very rare are the (congenital) congenital dyserythropoietic anaemias (CDA), which can be diagnosed on the basis of changes in the bone marrow and blood. Several diseases with varying degrees of severity are summarised under the term CDA. Less than 150 patients are currently known in German-speaking countries. The disease is characterised by ineffective haematopoiesis leading to anaemia. The majority of patients have a normal life expectancy, but are at risk of complications (gallstone formation, mononucleosis, aplastic crises) in the course of their lives.
Treatment of congenital anaemia
Treatment must be decided on an individual basis depending on the disease group and severity. This applies, among other things, to the indication for splenectomy, for which the advice of a specialist is required. In patients with iron overload, early initiation of iron deprivation treatment (iron chelation) is necessary.
Red Cell Centre Ulm
The Red Cell Center Ulm (RCCU) is an association of doctors in paediatrics and adolescent medicine, transfusion medicine and internal medicine/haematology. The aim is to provide integrative care for patients with congenital and acquired anaemia, in particular to ensure seamless care during the transition from paediatrics to internal medicine.