[Sickle cell disease]. / Sichelzellkrankheit.

The term "sickle cell disease" covers a group of genetic blood disorders caused by sickle hemoglobin (HbS) alone or in combination with other variants of the ß­globin locus. Sickle cell disease occurs frequently in sub-Saharan Africa, but is also common in Turkey, Greece, Sicily, the Middle East, India, and the Americas. Polymerization of deoxygenated sickle hemoglobin leads to decreased deformability of red blood cells. These altered erythrocytes can obstruct small blood vessels and cause acute episodes of pain, hemolytic anemia, and organ damage. Complications can vary between the different genotypes and it is important to be aware of the special features of the disease. Hydroxycarbamide has been shown to reduce the morbidity and mortality of patients with sickle cell disease. New drugs and novel treatment approaches such as gene therapy are currently being tested.

[Hemoglobin disorders]. / Hämoglobinkrankheiten.

Hemoglobin disorders such as the thalassemias and sickle cell disease have been present in Germany since the arrival of immigrants from the eastern Mediterranean region, Africa, and Asia in the 1950s. These hereditary diseases not only require very complex treatment, but also render screening for asymptomatic carriers necessary, in order to prevent the birth of an affected child in the next generation. Pediatricians, internists, general practitioners, and gynecologists have to rise to this challenge.

Newly diagnosed immune thrombozytopenia--German guideline concerning initial diagnosis and therapy.

Newly diagnosed immune thrombocytopenia occurs in 3-5/100 000 children < 14 y per year. Bleeding symptoms do not correlate with platelet count. Diagnostic approach includes history, clinical examination and analysis of blood count with blood smear by experienced hematologist. Additional investigations are only necessary in atypical cases and cases with additional symptoms or inadequate response to therapy. The decision to treat ITP should be made cautiously and not entirely be based on the platelet count. Decisions based on clinical symptoms and progress of the illness are more reasonable. There is no evidence, that therapy at the time of diagnosis influences the further course and can avoid intracerebral hemorrhage.

Osteosarcoma after allogeneic bone marrow transplantation. A report of four cases from the Cooperative Osteosarcoma Study Group (COSS).

Osteosarcoma, one of the most frequent secondary malignancies after the treatment of young patients with cancer, has only very rarely been observed in association with hematopoietic stem cell transplantation (HSCT). We report four patients who were identified by searching the database of the Cooperative Osteosarcoma Study Group (COSS) for patients whose osteosarcoma arose following HSCT. Transplant indications had been acute lymphoblastic leukemia (3). and sickle cell disease (1). and the stem cell source was bone marrow in all cases (three allogeneic, one syngeneic). All four had received chemotherapy with alkylators as part of their conditioning regimen and/or first line therapy. The conditioning regimen included total body irradiation in three patients. The osteosarcomas arose at the age (adolescence) and sites (around the knee) typical for the disease. All four patients received chemotherapy as part of multimodal osteosarcoma treatment, and all four are currently alive, three in continuous remission at 5 7/12, 2 11/12, and 0 6/12 years and one with relapsed osteosarcoma at 4 1/12 years. One of the osteosarcoma-free survivors suffered a third malignancy, myelodysplastic syndrome. Osteosarcoma should be included among the secondary malignancies that can arise following HSCT. Multi-modal therapy according to guidelines for de novo osteosarcoma can lead to long-term survival in selected patients.

[Anemia and hemoglobin diseases in patients with migration background]. / Anämien und Hämoglobinkrankheiten bei Patienten mit Migrationshintergrund.

Among the German population with migration background there are probably 150 000-200 000 carriers of thalassemia (α und ß) and sickle cell disease, respectively, who have no or little symptoms. Compared to neighboring countries the number of sickle cell (1000-1500) and thalassemia patients (500-600) in Germany is rather low. This may explain the fact that hemoglobin diseases are not yet considered a public health problem in Germany. With optimal care 85-90 % of children with sickle cell disease and 100 % of children with thalassemia reach adulthood. In order to increase awareness for patients with hemoglobin diseases we discuss the most pertinent disease manifestations of adult patients and point out possibilities to obtain information. Specialists in regional centers should be addressed for acute management problems. Up to now it is difficult for many adult sickle cell and thalassemia patients to find a physician well enough informed and experienced to take over the care of their complex disease. Many adult patients are still taken care of by pediatricians. Urgently needed are reference centers with experience in management of hemoglobin diseases who are qualified for training hematologists and who can assure the transition of these patients from pediatrics to adult medical care.

Haemoglobinopathies and newborn haemoglobinopathy screening in Germany.

Germany has been an immigration country since the early 1950s. In December 2007, 6.7 million non-German citizens lived in the country. However, the total number of citizens with a migration background is 15-20 million, about 9 million of whom come from countries where sickle cell disease and thalassaemias are frequent. In a country with 82 million inhabitants health authorities are not worried by the presence of probably 1000-1500 sickle cell and 450 transfusion-dependent thalassaemia patients, and therefore no screening or preventive measures have been taken so far on a national scale. There are plans for a pilot project (1 year) to screen all newborns for sickle cell disease in obstetric hospitals in 4-5 cities with more than 20% migrants. Funding and lack of an infrastructure to provide counselling are major problems.

Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia.

Although haematopoietic cell transplantation (HCT) is curative for sickle cell anaemia (SCA), concerns about its short- and long-term toxicities limit its application. A potential toxicity is an adverse effect on growth. To identify an HCT growth effect, serial height and weight measurements from 53 children and adolescents with SCA after receiving a transplant were compared to historical controls. Hierarchical Linear Models for longitudinal data were used for analysis. In general growth was not impaired by HCT for SCA in young children; however, diminished growth may occur if HCT is carried out near or during the adolescent growth spurt.

[Sickle cell disease in Germany -- disease manifestations, therapeutic options and possibilities for improvement of care]. / Sichelzellkrankheit in Deutschland -- Krankheitsmanifestationen, Therapieoptionen und Möglichkeiten der Optimierung der Betreuung.

The number of sickle cell patients in Europe is steadily increasing due to continuing immigration and increase of average life expectancy. In 2005 probably up to 1,000 sickle cell patients were living in Germany, most of them in former West-Germany. Precise figures are not available as registration of sickle cell patients into a German surveillance study register that was initiated 1987 is on a voluntary basis. In December 2005 the register included a total of 514 patients, with 273 patients (208 children, 65 adults) still actively participating in the study. They were followed at 92 different institutions all over the country. We report on data regarding the origin of these patients, their genotypes, disease manifestations, social integration, therapy and causes of death. We discuss difficulties in the delivery of care and make suggestions for improvement.

Acute aphasia and loss of vision with desferrioxamine overdose.

Reversible aphasia, loss of vision, bradycardia, and mild hypotension occurred in a 6-year-old girl with aplastic anemia and transfusion-related iron overload after inadvertent increase of her intravenous desferrioxamine drip. Signs and symptoms were reversed promptly by intravenous fluids, suggesting that desferrioxamine, when given as a sudden intravenous bolus, may upset vasoregulation. Three possible mechanisms are discussed that could explain this phenomenon. High-dose intravenous desferrioxamine ought to be given by pump infusion only, in order to avoid accidental overdose.

[Sickle cell disease and pregnancy]. / Sichelzellerkrankungen und Schwangerschaft.

Three million out of 4.5 million foreigners in Germany are from countries, where sickle cell anaemia is found. Today, this disease occurs in Germany with sufficient frequency and this makes it imperative for every physician to be familiar with it. Most of the sickle cell patients today attain the reproductive age. During pregnancy, sickle cell patients need very thorough medical care, because of the high foetal and maternal morbidity in this patient group. The main features of sickle cell disease are discussed and a survey of complications in pregnant sickle cell patients is presented. Suggestions are made regarding contraception and prenatal care.

[Immune thrombocytopenia in childhood--how much diagnosis and therapy is reasonable?]. / Die ITP (Immunthrombozytopenie) im Kindesalter--Wieviel Diagnostik und Therapie ist sinnvoll?

Acute and chronic ITP in childhood are both relatively mild diseases that only rarely result in live threatening complications. In most cases diagnostic measures can be limited to a detailed history, thorough physical examination, a complete blood count and evaluation of platelet size on smear. A bone marrow aspirate is only necessary if the diagnosis of ITP is not straightforward. Because of large platelet size and vascular stability bleeding tendency in childhood ITP is mild even with very low platelet counts. 90% of children with acute IPT recover spontaneously within 12 months. Therefore therapy can safely be limited to a few situations: necessary surgical intervention during thrombocytopenia, live threatening bleeding, major trauma. In most instances optimal management of ITP consists in a "wait and see" approach in addition to giving detailed and thorough information to patients or parents about the benign nature of the disease, the likelihood of spontaneous recovery and the importance of avoiding aspirin and contact sports. Controversies in regards to diagnosis and therapy of ITP in childhood are discussed and the various therapeutic possibilities are presented.

[Splenic sequestration in patients with sickle cell disease. ]. / Milzsequestrationen bei Patienten mit Sichelzellerkrankungen - Eigene Erfahrungen, Epidemiologie, Klinik, Prävention und Therapie.

Splenic sequestration is a potentially life threatening event that is characteristic for sickle cell disease. For reasons unknown a fraction of or even the entire blood volume is trapped in the splenic sinuses within a few hours and thus is no longer available for circulation. The result is splenomegaly, hypovolemia, anemia and extreme reticulocytosis. If the sequestered blood volume is very large the patient goes into fatal hypovolemic shock unless transfused instantly. If the sequestered volume is small there is a chance of spontaneous resolution. The etiology of splenic sequestration is not known. Children with homozygous sickle cell disease (HbSS) are at risk until age 6 years while individuals with compound heterozygous disease (HbSbetaThal, HbSC, HbSD) may develop splenic sequestration even in adulthood. Parents of infants and toddlers with sickle cell disease need to learn how to palpate the spleen in order to detect splenomegaly as early as possible and take the child to the hospital. Splenic sequestration with a drop in hemoglobin of more than 3 g/dl below the patient's usual hemoglobin level is a clear indication for splenectomy regardless of the patient's age as splenic sequestration tends to recur.

[Indications for bone marrow transplantation in sickle cell anemia]. / Indikation zur Knochenmarktransplantation bei Sichelzellanämie.

Sickle cell disease is a hemoglobin disorder which is characterized by live-threatening organ damage, both acute and chronic. It can be cured by bone marrow transplantation (BMT), mortality and severe morbidity being 10-15%. Severity of clinical manifestations in sickle cell disease varies considerably from patient to patient. As there are as yet no reliable criteria to predict a patient's individual course there is a dilemma when it comes to selecting patients for BMT. The presently existing protocols for BMT in sickle cell patients, Belgian, American and a British, are selecting patients who already had severe clinical problems without, however, showing signs of irreversible organ damage. As the number of sickle cell patients in Germany is very small (ca. 250) we plan to join one of the existing BMT studies.

[Visceral leishmaniasis. Personal observation and review of epidemiology, clinical aspects and therapy]. / Die viszerale Leishmaniose. Eigene Beobachtung und Ubersicht über Epidemiologie, Klinik und Therapie.

A 5 year old German girl contracted visceral leishmaniasis during a vacation in Spain, either 32 or 20 month prior to the manifestation of disease. She presented with fever, hepatosplenomegaly and pancytopenia. A bone marrow aspirate proved the diagnosis. Therapy with a pentavalent antimony drug brought about immediate improvement. Visceral leishmaniasis has to be suspected in individuals with fever, hepatosplenomegaly and pancytopenia who have resided in endemic areas (Mediterranean countries, India, East Africa, South America) during the previous years. If untreated, visceral leishmaniasis runs a fatal course. Therefore, early diagnosis by morphological and serological means and specific therapy with pentavalent antimony drugs are mandatory.

[Manifestations of sickle cell disease in adolescents and young adults. Clinical aspects and therapy references]. / Manifestationen der Sichelzellerkrankung bei Adoleszenten und jungen Erwachsenen. Klinik und Therapiehinweise.

In Germany about 300 sickle cell patients are being seen at more than 100 different hospitals. One third of these patients are adolescents and young adults. Since this is a congenital chronic disease, the majority of these teenagers and young adults are being cared for by pediatricians. Sickle cell disease in patients older than 15 years is characterized by the development of chronic organ damage, in addition to the occurrence of acute manifestations of disease such as pain crises, splenic sequestration, aplastic crises and Acute Chest Syndrome. Pediatricians who care for older sickle cell patients have to handle not only internal medicine problems but also to answer questions concerning pregnancy and contraception. In this paper the specific problems of adolescents and young adults with sickle cell disease are presented and suggestions are offered for the care of this group of patients.

[Disorders of consciousness as an initial symptom of intestinal invagination]. / Bewusstseinsstörungen als Erstsymptom einer Invagination.

Two infants with intussusception were presented with lethargy and vomiting. Initially, the classical abdominal manifestations of the disease were missing. In order to avoid a delay of the correct treatment, intussusception should be considered in infants with altered consciousness and ultrasonography of the abdomen should be included in the diagnostic work up.

[Therapeutic experiences with high-dose ARA-C and L-ASP]. / Therapieerfahrungen mit hochdosiertem ARA-C und L-ASP.

Five patients, 4 with ALL, 1 with AML received 8 cycles of HD-ARA-C (Capizzi protocol). One complete remission was achieved, 2 patients died shortly after cycle 1 and could not be evaluated. Two patients responded partially. Toxicity was considerable.

The clinical course of immune thrombocytopenic purpura in children who did not receive intravenous immunoglobulins or sustained prednisone treatment.

OBJECTIVE: To demonstrate the result of watchful waiting without specific therapy in unselected children with acute immune thrombocytopenic purpura (ITP). STUDY DESIGN: Between May 1992 and October 1999, 55 consecutive children (aged 2 months to 16 years; 28 boys and 27 girls) with acute ITP did not receive intravenously administered immune globulin G (IVIG) or sustained prednisone treatment. Patients with extensive mucosal bleeding were given prednisone, 2 mg/kg/d, for 3 days. RESULTS: In 37 of 55 patients the initial platelet count was <10,000/microL. Ten of these patients had active mucosal bleeding. Five additional patients with bleeding had platelet counts between 10,000 and 20,000/microL. Four patients were given a 3-day course of prednisone. Chronic ITP occurred in 7 (13%) of the patients; 29 patients achieved remission within 6 weeks, and 19 patients, between 6 weeks and 6 months. No life-threatening bleeding occurred, and no patient died. CONCLUSION: Most children with severe thrombocytopenia do not have active mucosal bleeding. This management approach, which did not administer specific therapy, avoided side effects, reduced cost, and was effective.

[Pain crises in patients with sickle cell diseases. Pathogenesis, clinical aspects, therapy]. / Schmerzkrisen bei Patienten mit Sichelzellerkrankungen. Pathogenese, Klinik, Therapie.

About 70% of all patients with sickle cell disease suffer from pain crises. Pain crises are recurrent episodes of pain that range in severity from mild to severe, usually occur very abruptly and are often localized around joints. Pain crises are caused by vaso-occlusions in the vascular bed of the bone marrow, leading to necrosis, edema and increased pressure. For effective analgesia morphine or morphine analogues are often required. When treating a pain crisis the patient's complaints need to be taken seriously and analgesic therapy should be started promptly with analgesics in proportion to the severity of the patient's pain. With mild pain oral non-opioid analgesics are sufficient, in moderate pain they are given in combination with oral codeine. Severe pain requires IV morphine, also combined with a non-opioid analgesic. Intravenous morphine makes a thorough monitoring of ventilation and level of consciousness mandatory. Sickle cell patients do not become drug dependent if given morphine for adequate analgesia. While bone marrow transplantation has become an accepted treatment modality for sickle cell patients with severe pain crises, treatment with hydroxyurea to increase HbF levels and reduce incidence and severity of pain crises, however, is still experimental.

Enumeration of platelets by multiparameter flow cytometry using platelet-specific antibodies and fluorescent reference particles.

The correct enumeration of platelets is still an elusive matter. This is mainly due to the fact that commercial instruments which are used for platelet counting cannot discriminate platelets from other cellular particles and precipitates that cause similar signals. Visual (chamber counting) methods are still frequently used in routine laboratories to verify low automated platelet counts (< 50 x 10/l) despite obvious technical and statistical drawbacks. The following report shows how platelet counts can be measured by multiparameter flow cytometry with the help of reference particles (fluorescent latex beads) and platelet-specific antibodies i.e. anti-GPIIb/IIIa(CD41a), anti-GP Ib-alpha (CD42b) and anti-GP IIIa (CD61). The linearity of this method was highly satisfactory and the observed imprecision was within acceptable limits. At a platelet concentration of 10 x 10(9)/l the coefficient of variation (CV, n = 10) ranged from 5.3% (PCV = 0.456) to 5.6% (PCV = 0.148). Accuracy was evaluated by comparing results to the ICSH-selected method for platelet counting. The correlation of both methods was significant (P < 0.005) and Passing-Bablok's linear regression analysis showed no systematic differences between the two methods. Comparisons of this new platelet counting technique were also performed with routine visual methods, automated blood analysers (Technicon H-1, Sysmex E-5000) and a different flow cytometric method using only forward and side light scatter properties of platelets for their discrimination. The linear correlation of all methods was significant (P < 0.01) at platelet concentrations above 50 x 10(9)/l. At lower platelet concentrations, our new platelet counting technique correlated significantly only with the visual and the forward/side scatter methods.(ABSTRACT TRUNCATED AT 250 WORDS)