ABSTRACT
Congenital disorders of platelet function are a heterogeneous group of disorders that are often not detected until bleeding occurs. In clinical settings only a few methods have proven to be useful for identification and classification of inherited platelet disorders. For a rational diagnostic approach, a stepwise algorithm is recommended. Patient history and clinical investigation are mandatory. Von Willebrand disease and other coagulation disorders should always be ruled out prior to specific platelet testing. Platelet count, size, volume (MPV) and morphology may guide further investigations. The PFA-100® CT is suited for screening for severe platelet defects. Platelet aggregometry allows assessment of multiple aspects of platelet function. Flow cytometry enables diagnosis of thrombasthenia Glanzmann, Bernard-Soulier syndrome and storage pool defects. Molecular genetics may confirm a putative diagnosis or pave the way for identifying new defects. We present an unabridged version of the interdisciplinary guideline.
Subject(s)
Blood Platelet Disorders/diagnosis , Blood Platelet Disorders/genetics , Genetic Testing/standards , Hematology/standards , Molecular Diagnostic Techniques/standards , Platelet Function Tests/standards , Practice Guidelines as Topic , Blood Platelet Disorders/blood , Germany , Humans , Pediatrics/standardsABSTRACT
A top quality, effective treatment of haemophilia requires an integrated therapeutical concept and an excellent cooperation of an interdisciplinary team. Since years different models are discussed in Germany in order to enlarge the offers for a suitable care of patients with hard to treat diseases. The health-political targets are expressed in the changes of the Code of Social Law number V (SGB V) and in innovations in the statutory health insurance. This new legal basis provides opportunities to implement innovative treatment concepts outside university hospitals and paves the way for ambulant haemophilia centres to offer an integral care, all legally saved by a contract. The Coagulation Centre Rhine-Ruhr reveals as an example how haemophilia treatment in accordance with guidelines and with the latest results of international research can be realise in an ambulatory network.
Subject(s)
Ambulatory Care Facilities/organization & administration , Delivery of Health Care, Integrated/organization & administration , Delivery of Health Care/organization & administration , Hemophilia A/diagnosis , Hemophilia A/therapy , Models, Organizational , Outpatient Clinics, Hospital/organization & administration , GermanyABSTRACT
Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by quantitative and/or qualitative defects of the platelet glycoprotein (GP) IIb/IIIa complex. Physiologically, the integrin GPIIb/IIIa binds Von Willebrand factor and fibrinogen on activated platelets. GT is caused by genetic alterations in ITGA2B or ITGB3 (genes encoding GPIIb and GPIIIa).This study describes 2 siblings diagnosed with GT type I associated with homozygous point mutations in ITGA2B. All patients presented with typical bleeding disorder including moderate hematomas, petechiae, and mucocutaneous bleedings.Both siblings showed severely reduced platelet aggregation especially after stimulation with collagen and adenosine diphosphate. Absence of platelet GPIIb/GPIIIa complex was determined using flow cytometry. Molecular genetic analysis revealed 2 distinct homozygous point mutations in exon 18 of ITGA2B. Family 1 was identified with c.1878G>C and family 2 with c.1787T>C substitution. While the c.1787T>C mutation causes a single amino acid substitution p.I565T, the c.1878G>C mutation (p.Q595H) is predicted to induce a mRNA splicing anomaly.These mutations were identified as cause of GT type I in the described patients. Patients with GT should be documented in a prospective register to verify the correlation between the severity of bleeding symptoms and the pathogenic mutation. This can have effects on therapeutic decisions.
Subject(s)
Homozygote , Integrin alpha2/genetics , Mutation, Missense/genetics , Point Mutation/genetics , Thrombasthenia/genetics , Adolescent , Alleles , Amino Acid Substitution/genetics , Child , Child, Preschool , Chromosome Aberrations , Consanguinity , DNA Mutational Analysis , Exons/genetics , Female , Flow Cytometry , Genes, Recessive/genetics , Genetic Carrier Screening , Glutamine/genetics , Histidine/genetics , Humans , Male , Platelet Aggregation/genetics , RNA Splicing/genetics , RNA, Messenger/genetics , Thrombasthenia/diagnosisABSTRACT
UNLABELLED: The risk of thromboembolic events (TE) is increased by acquired or inherited thrombophilias (IT). We know that some hormonal contraceptives also increase the risk of thrombosis, thus, the use of such contraceptives are discussed as contraindications in women with IT. TEs are infrequent events in children and adolescents and in the majority of cases are associated with secondary complications from underlying chronic illness. Although adolescents are not typically considered to be at high-risk for TE, this cohort is frequently using hormonal contraception, leading to an increased risk in cases with unknown IT. The risk of TE with pregnancy alone is higher than associated with combined hormonal contraception. Progestin-only methods have not been found to increase the risk of TE with only moderate changes of coagulation proteins compared to normal reference values. CONCLUSION: Thrombophilic women are good candidates for progestin-only contraceptive methods.
Subject(s)
Contraceptive Agents, Female/adverse effects , Thromboembolism/chemically induced , Thrombophilia/chemically induced , Contraceptives, Oral, Synthetic/adverse effects , Contraindications , Female , Germany/epidemiology , Humans , Risk Factors , Thromboembolism/epidemiology , Thrombophilia/epidemiologyABSTRACT
BACKGROUND: HIV-associated lipodystrophy syndrome (LDS) as a long-term side effect of HAART is becoming increasingly important and negatively affects adherence to medication. Currently, an effective therapy is not available. There is some evidence that the drug class of thiazolidindiones might be effective in the treatment of LDS. PATIENTS AND METHODS: Prospective open-label study with 20 HIV-infected patients suffering from severe LDS. Patients received 4 mg rosiglitazone once daily for a 24-week study period. Efficacy was assessed by measurement of metabolic and anthropometric parameters, total body DXA scan, CT scan of the abdomen, photo documentation and self-assessment. RESULTS: Rosiglitazone treatment was well tolerated. DXA scans demonstrated a highly significant increase in adipose tissue of the limbs (2644 +/- 1334 g vs 3380 +/- 1614 g, p < or = 0.001) without any change in total fat mass. Abdominal CT-scans revealed a significant increase in subcutaneous adipose tissue (113.7 +/- 82.4 cm(2) vs 125.3 +/- 83.7 cm(2), p = 0.04). Abdominal circumference decreased significantly (94.7 +/- 8.7 cm vs 92.2 +/- 8.45 cm, p = 0.03) without any relevant change of body weight or BMI. We observed an increase in serum cholesterol (248 vs 281 mg/dl, p = 0.006) and serum triglycerides (301 vs 351 mg/dl, p = 0.1). Furthermore, no side effects of clinical relevance were observed. The insulin sensitivity index improved without reaching statistical significance. Thirteen patients (65%) reported general improvement of LDS symptoms. Evaluation of photo documentation by five HIV-experts revealed poor concordance and no relevant change of LDS. CONCLUSIONS: The results of this study suggest that rosiglitazone is safe in the treatment of HAART-associated lipodystrophy and has moderate clinical efficacy. We found a trend towards improved insulin sensitivity and as a possible limiting factor an unfavorable increase in serum cholesterol and triglycerides.
