Download
1 / 69
690 likes | 873 Views
Laboratoriumhematologie in de pediatrie. Jan Philippé UZ Gent - UGent. Referentiewaarden. Referentiewaarden Hgb. Referentiewaarden. Referentiewaarden aantal immature RBC op de eerste geboortedag na verschillende zwangerschapsperioden. Referentiewaarden. Referentiewaarden.
E N D
Laboratoriumhematologie in de pediatrie Jan Philippé UZ Gent - UGent
Referentiewaardenaantal immature RBC op de eerste geboortedag na verschillende zwangerschapsperioden
Congenital sideroblastic anaemia is a rare inherited abnormality in haem synthesis that is characterized by the presence of ring sideroblasts in the bone marrow. The blood film is characteristically dimorphic with a mixture of hypochromic microcytes and normocytic, normochromic cells. As in this case, there may also be poikilocytosis.
Most types of congenital sideroblastic anaemia are caused by a defect in haem synthesis, specifically a mutation in the ala synthase gene. Iron is taken up into the developing red cell but because of the lack of haem cannot be incorporated into haemoglobin. Iron is deposited in the mitochondria as haemosiderin and is apparent as a ring of iron-containing granules around the nucleus. Over 10% of NRBC are sideroblasts. DD with plumbism (acquired).
α thalassaemia trait means that there is loss of one or two of the normal complement of four α genes. This film, from an individual with α thalassaemia trait attributable to loss of two α genes, shows hypochromia and microcytosis. The diagnosis of α thalassaemia trait is difficult since it requires DNA analysis. Usually it is a presumptive diagnosis only, when no other explanation can be found for microcytic red cells.
Haemoglobin H disease is a thalassaemic disorder with a marked reduction in a chain synthesis, usually caused by deletion of three of the four α genes. The blood film in haemoglobin H disease shows marked anisocytosis, poikilocytosis and hypochromia. The reticulocyte count is increased. The diagnosis of haemoglobin H disease is confirmed by demonstration of haemoglobin H on haemoglobin electrophoresis and on a haemoglobin H preparation.
Haemoglobin electrophoresis in a patient with haemoglobin H disease (samples b and c) showing a minor fast band which is haemoglobin H. In haemoglobin H disease the percentage of the abnormal haemoglobin varies from 2 to 40%.
A haemoglobin H preparation shows that patients with haemoglobin H disease have a significant proportion of cells containing haemoglobin H inclusions [blue arrow]. These are small pale blue inclusions distributed evenly through a red cell, giving an appearance which has been compared to a golf ball. Increased numbers of reticulocytes [red arrows] are also apparent.
Β thalassaemia trait or β thalassaemia heterozygosity means that an individual has inherited a β thalassaemia gene from one parent and a normal β gene from the other parent. This film from a healthy person with β thalassaemia trait shows minimal morphological abnormality. There is microcytosis, slight hypochromia and slight poikilocytosis. Such cases are more readily suspected from the characteristic red cell indices than from the subtle abnormalities on the blood film.
Although the diagnosis of β thalassaemia trait can be suspected from the blood film, red cell indices and ethnic origin, definitive diagnosis requires measurement of the haemoglobin A2 percentage. This is elevated in β thalassaemia trait, as shown by this densitometric trace of an electrophoretic strip, whereas it is normal or reduced in α thalassaemia trait and iron deficiency anaemia. HbA2 > 3.5% in heterozygous β thalassaemia
β thalassaemia major is the name given to β thalassaemia of sufficient severity to require blood transfusion to maintain life. Anaemia becomes apparent at 3-6 months. This blood film is from a patient already receiving blood transfusions. It is therefore dimorphic with a mixture of the patient's thalassaemic red cells and normal donor cells. The patient's own red cells show hypochromia, target cell formation and Pappenheimer bodies [red arrow]. One red cell contains an inclusion that represents an α chain inclusion [blue arrow]. There are three NRBC. In β thalassaemia major Hb F > 80%
a siderotic granule (the equivalent of a Pappenheimer body) demonstrated with an iron stain
DD aangeboren hemolytische anemie • SCA/hemoglobine C • Hemoglobine C • Hemoglobine E hemoglobinopathieën • Sikkelcelanemie • Erfelijke sferocytose • Erfelijke elliptocytose • Erfelijke stomatocytose • Pyruvaat kinase deficiëntie • G-6-PDH deficiëntie (meest frequente oorzaak)
Haemoglobin electrophoresis on cellulose acetate at alkaline pH in haemoglobin C trait (strip d and e). At alkaline pH the findings in haemoglobin C trait and haemoglobin E trait are similar. If haemoglobin electrophoresis is also performed on agarose at acid pH the distinction is easy since haemoglobin E then has the same mobility as haemoglobin A whereas haemoglobin C does not.
Blood film in haemoglobin C disease showing target cells and irregularly contracted cells. These two features are typical of haemoglobin C homozygosity. There may also be microcytosis. Rare haemoglobin C crystals may be seen.
The first haemoglobinopathy recognized was sickle cell anaemia, resulting from homozygosity for the HbS gene. -sickle cell (red arrow), -several boat-shaped cells (blue arrows) -and a Howell-Jolly body. -Hgb is decreased (7-10 g/dL) -RBC and Hct are similarly reduced -MCV and MCH are reduced in some patients. -RDW and reticulocyte count are increased. As hyposplenism develops there is a tendency for the neutrophil, lymphocyte and platelet counts to rise. The WBC and neutrophil count may rise further during sickle cell crisis.
Blood film in sickle cell trait showing target cells and mild microcytosis. It should be noted that the blood film is often normal in sickle cell trait.
Hereditary elliptocytosis is a heterogeneous group of congenital haemolytic anaemias consequent on an inherited abnormality of the red cell membrane. Most cases are caused by a mutation in either the a or the b spectrin gene. Inheritance is usually autosomal dominant. Most patients have compensated haemolysis. Some have a mild, moderate or severe haemolytic anaemia.
Blood film in hereditary stomatocytosis showing basophilic stippling and numerous stomatocytes. Hereditary stomatocytosis is a heterogeneous group of disorders resulting from an inherited abnormality of the red cell membrane. Inheritance is usually autosomal dominant. There may be compensated haemolysis or mild, moderate or severe haemolytic anaemia. Cation flux across the membrane may be abnormal. The film sometimes shows target cells, in addition to stomatocytes. Another inherited cause of stomatocytosis is Rh null disease so that Rhesus typing is indicated in congenital haemolytic anaemia associated with stomatocytosis.
The commonest cause of congenital haemolytic anaemia is glucose-6-phosphate dehydrogenase (G6PD) deficiency which affects millions of people world-wide. Most individuals with G6PD deficiency suffer only intermittent haemolysis. The blood film then shows irregularly contracted cells [deep red arrows] and sometimes hemighosts [deep blue arrow] in which all the haemoglobin appears to have retracted to one side of the erythrocyte. It has an X-linked recessive inheritance so occurs mainly in males. In high incidence areas female homozygotes occur and have the same features as male hemizygotes. Haemolysis is precipitated by infection and exposure to exogenous oxidants such as broad beans, naphthalene and certain drugs. Between acute haemolytic episodes the blood film is normal.
Blood film in glucose-6-phosphate dehydrogenase (G6PD) deficiency showing a hemighost [red arrow] and a keratocyte [blue arrow]. Keratocytes are formed when a Heinz body is removed from an erythrocyte by the spleen. During acute haemolysis a Heinz body preparation is positive.
Macrocytaire anemie “Fout” macrocytair - koude agglutininen - diabetes mellitus “Echt” macrocytair - reticulocytosis - verstoorde DNA- synthese - leverlijden - medicatie - CDA type I en III
Screening bij vermoeden van een abnormale bloeding • PBO en uitstrijkje • PT • APTT • Fibrinogeen • Trombinetijd (reptilasetijd) • Bloedingstijd
Wat vind je niet met deze screening? • Trombocytopatieën zonder morfologische afwijkingen • Matige deficiënties van stollingsfactoren (tot ± 50%) (normaal ook geen klinische problemen) • Een aantal vormen van vWD • Een minderheid van patiënten met lupus anticoagulans • FXIII deficiëntie • (Verhoogde tromboseneiging)
Bijzonderheden in de pediatrische stollingsanalysen • Zie de referentiewaarden • Stollingscomponenten gaan niet door de placentabarrière, daarom kunnen een aantal deficiënties bij het jonge kind niet betrouwbaar opgespoord worden: • Matige deficiëntie van F IX (= normaal laag) • De meeste gevallen van vWD (vWF normaal hoog) • Heterozygote deficiënties van de inhibitoren (C, S, AT; normaal laag) • Bij het (algemeen) zieke kind kunnen sommige waarden lager zijn dan verwacht • Bloedplaatjestelling is niet erg verschillend, maar bij aggregatietesten zijn normaal verstoord voor ADP, adrenaline en collageen
Referentiewaarden: stollingsinhibitoren * Vrij PS is relatief meer aanwezig omwille van lage C4 BP spiegels
Bijzonderheden in de pediatrische stollingsanalysen • Zie de referentiewaarden • Stollingscomponenten gaan niet door de placentabarrière, daarom kunnen een aantal deficiënties bij het jonge kind niet betrouwbaar opgespoord worden: • Matige deficiëntie van F IX (= normaal laag) • De meeste gevallen van vWD (vWF normaal hoog) • Heterozygote deficiënties van de inhibitoren (C, S, AT; normaal laag) • Bij het (algemeen) zieke kind kunnen sommige waarden lager zijn dan verwacht • Bloedplaatjestelling is niet erg verschillend, maar aggregatietesten zijn normaal verstoord bij neonati voor ADP, adrenaline en collageen
Small bruises and bilateral haemorrhage into the knee joints (haemarthroses) in haemophilia A.
The descendants of Queen Victoria, showing the inheritance of haemophilia A. Because inheritance is sex-linked recessive the great majority of sufferers are male whereas asymptomatic carriers are female.
