Increase in platelet count is not affected by the platelet yield of single donor pheresed platelets

OBJECTIVES: To determine if the rise in platelet count after transfusion in neonates is associated with platelet yield of the pheresed platelet unit. STUDY DESIGN: Cohort study of infants in a level 3 Neonatal Intensive Care Unit that received single donor platelets (SDP). Platelet rise in infants were compared between 3 groups: underproduction, destruction, and idiopathic. The main outcome variable studied was the rise in platelet count posttransfusion. Statistical analysis included analysis of variance, Pearson correlation, and multivariate linear regression. RESULTS: The gestational age was 28+/-4.5 weeks. The platelet yield was 4.2+/-0.7 (x10(11)) and resultant platelet rise was 71+/-58.6x1000/mm3. Infants with platelet underproduction (n=30) had a greater rise compared with infants with platelet destruction (n=51) after transfusion (95.3+/-58 vs. 59.6+/-57.5x1000/mm3, P=0.01). After controlling for confounding variables, there was no correlation between the platelet yield and platelet rise, but the etiology of the thrombocytopenia remained associated with increased platelet rise. CONCLUSIONS: There was no association between platelet yield of SDP and platelet rise. Infants with thrombocytopenia related to platelet underproduction had a greater rise in platelets after transfusion compared with those with platelet destruction, independent of yield or volume of the SDP transfusion.     

Alpha-interferon therapy induces improvement of platelet counts in children with chronic idiopathic thrombocytopenic purpura

PURPOSE: To investigate alpha-interferon (IFN) therapy for children with chronic idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: Patients with refractory ITP lasting more than 12 months from diagnosis were included if they had platelet counts <50 x 10(9)/L and had received no treatment during the past month. Patients received IFN (3 x 10(6) U/m2 per dose), three times per week for 4 weeks; if partial (<150 x 10(9)/L) or no response was obtained, the same dose was continued for another 8 weeks. In patients with favorable response and subsequent decrease to pre-treatment values, an additional 4 weeks of treatment could be administered. RESULTS: Fourteen patients (ages 4-20 y) receiving 17 IFN courses were included. Mean initial platelet count was 29 +/- 15 x 10(9)/L. A significant increase was achieved during 14 of 17 courses (82.4%). All but two responses were transitory, and platelets returned to initial values after IFN discontinuation (mean 44 +/- 26 days). Considering the best response achieved by each patient, we observed: 1) 10 patients who achieved a sustained improvement of platelet count throughout the treatment period, decreasing to initial values after therapy was stopped; 2) one patient who achieved platelet count >150 x 10(9)/L, remaining with normal platelets at 18 months; 3) one patient who achieved platelet count >150 x 10(9)/L, remaining with platelets between 100 and 140 x 10(9)/L at 48 months; 4) one patient who had no response; and 5) one patient in whom therapy worsened the thrombocytopenia. A mild to moderate flu-like syndrome and a moderate decrease of the absolute neutrophil count were the only side effects observed. CONCLUSION: Interferon therapy induces a significant increase of platelet count and seems to be a valid alternative therapy to attempt the achievement of prolonged remission in refractory ITP, to defer splenectomy in younger children, or to improve platelet count before planned splenectomy.     

Sustained engraftment post bone marrow transplant despite anti-platelet antibodies in Glanzmann thrombasthenia

BACKGROUND: Patients with Glanzmann thrombasthenia (GT) have normal platelet counts but abnormal platelet aggregation and carry the risk of life-threatening bleeding. We report three patients who received bone marrow transplantation (BMT) for type I GT and discuss the risk and management of anti-platelet antibodies. PATIENTS AND RESULTS: Diagnosis of GT was made through abnormal platelet aggregation studies or the absence of GPIIb/IIIa by flow cytometry. All patients had severe bleeding requiring multiple red blood cell transfusions. One patient received an unrelated donor transplant and two received matched sibling donor transplants following conditioning therapy with busulfan, cyclophosphamide, and fludarabine. Two patients developed an anti-platelet antibody, treated in one with intravenous immune globulin (IVIG). Engraftment of white blood cells and platelets was achieved on day +13 to +14 and +17 to +25, respectively. Complete donor chimerism and GPIIb/IIIa+ platelets are sustained at +22 to +30 months post transplant. CONCLUSIONS: In summary, patients with GT and history of severe hemorrhage can be cured with BMT, but the presence of anti-platelet antibodies should be sought and platelet transfusions minimized prior to transplant. IVIG may be helpful in cases of refractory immune thrombocytopenia related to anti-platelet antibodies. Improvement in transplant-related complications with current transplant regimens allows consideration of BMT for life-threatening non-malignant disorders such as GT.     

Effects of oxygen-induced lung damage on megakaryocytopoiesis and platelet homeostasis in a rat model

The association between lung injury and thrombocytopenia was investigated by comparing the megakaryocyte and platelet counts, and platelet activation using P-selectin as a marker, between the prepulmonary (right atrial) and postpulmonary (left atrial) blood in adult and neonatal (preterm and term) rats with and without hyperoxic lung injury. In the healthy controls, the postpulmonary blood had lower megakaryocyte count (prepulmonary versus postpulmonary: Preterm: 8.7[0.6] versus 3.9[0.3] per ml, p < 0.001; Term: 8.7[1.1] versus 2.6[0.4] per ml, p < 0.001; Adult: median [interquartile ranges]: 2.5[1.0, 5.0] versus 1.0[0, 3.0] per ml, p < 0.001), higher platelet count (prepulmonary versus postpulmonary: Preterm: 491.2[11.1] x 10(9)/L versus 595.1[10.2] x 10(9)/L, p < 0.001; Term: 472.5[19.9] x 10(9)/L versus 579.3[26.2] x 10(9)/L, p < 0.001; Adult: 513.9[31.5] x 10(9)/L versus 664.7[28.8] x 10(9)/L, p < 0.001), but similar P-selectin expression. In contrast, the lung-damaged animals did not show any such differences in either megakaryocyte or platelet count, but P-selectin expression was greater in the postpulmonary blood (prepulmonary versus postpulmonary: Preterm: 38.7[3.9] versus 56.4[4.9]% platelets, p = 0.02; Term: 40.9[2.0] versus 54.0[4.2]% platelets, p = 0.002; Adults: 30.0[3.6] versus 49.1[4.7]% platelets, p = 0.003). Peripheral platelet and intra-pulmonary megakaryocyte counts in the lung-damaged rats were significantly lower than those in their respective controls. Intra-pulmonary thrombi or platelet aggregation were detected in the lung-damaged rats but not in the controls. These findings showed that hyperoxic lung damage reduced circulating platelets through (1) failure of the lungs to retain and fragment megakaryocytes to release platelets, and (2) platelet activation leading to platelet aggregation, thrombi formation and platelet consumption. The magnitude of platelet reduction was physiologically significant, as demonstrated by higher counts of megakaryocyte colony forming units in the bone marrow culture of the animals in the hyperoxia group when compared with the controls.     

Autoimmune thrombocytopenic purpura: maternal and fetal disease.

We have followed up 63 pregnancies in women with autoimmune thrombocytopenic purpura (ATP). Of these, 15 were previously splenectomized. The characteristics of the sample can be summed up as follows: average age 27 years (17-41); platelets at the beginning of pregnancy, mean 129.5 x 10(9)/l (range 16-488); platelets at delivery, mean 133 x 10(9)/l (range 8-477); PA-IgG at delivery, mean 320 ng IgG/10(7) platelets (range 10-1000); SPB-IgG at delivery, mean 262 ng IgG/10(7) platelets (range 10-1000). There were 30 spontaneous deliveries and 33 cesarean sections. Forty-two newborns had a platelet count within the normal range while nine had a platelet count less than or equal to 150 x 10(9)/l, while six had less than or equal to 100 x 10(9)/l and a further six less than or equal to 50 x 10(9)/l. The aim of this study is the evaluation of maternal risk and of possible feto-neonatal thrombocytopenia at birth. In this regard, the following parameters were considered: previous maternal splenectomy; the platelet count at the beginning of pregnancy; the platelet count and the titres of PA-IgG and SPB-IgG at delivery. Preliminary statistical evaluation of these parameters enabled us to identify a risk score. From this it was possible to obtain an optimum management of the final stage of pregnancy regarding the therapeutic approach and the timing of delivery.     

Juvenile cyclic amegakaryocytic thrombocytopenia: a novel entity

Cyclic thrombocytopenia is a rare disorder described in adults, characterized by periodic platelet count fluctuations of unknown etiology. The authors describe a boy with cyclic changes in platelet counts ranging from 2 x 10(9)/L to 224 x 10(9)/L with a periodicity of 25 days. Since birth, the patient had periods of bruising. Platelet counts were periodically low during these periods. Thrombopoietin plasma levels oscillated inversely with the platelet count, whereas glycocalicin levels oscillated in phase with the platelets. No oscillation was seen in neutrophil and reticulocyte numbers. The bone marrow showed periodic reduction in megakaryocyte counts. In an in vitro megakaryocytopoiesis assay, the patient's CD34+ cells showed megakaryocyte formation, although to a lower level than controls. Addition of patient plasma, collected during the rise in platelet numbers, to cultures with normal bone marrow-derived CD34+ cells caused an increase in the development of CD41+ megakaryoblasts. Because the periods with bruising had existed since birth, apparently this is a form of congenital cyclic thrombocytopenia. The underlying mechanism of the cyclic thrombocytopenia in this patient is not yet clear, and until now, no therapy has been found for this patient. However, platelet transfusions have resulted in cessation of bleeding during thrombocytopenic periods.     

Allogeneic stem cell transplantation for Glanzmann thrombasthenia

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by normal platelet count, but lack of platelet aggregation. The molecular basis is linked to quantitative and/or qualitative abnormalities of the membrane glycoprotein IIb/IIIa complexes. Usually it is associated with mild bleeding but may lead to severe and potentially fatal hemorrhages. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. However, because of the risks associated with HSCT, it is generally not recommended unless there are life threatening hemorrhages, or the patient has developed refractoriness to platelet transfusion due to antibody formation. Herein, we report an 11‐year‐old female from United Arab Emirates (UAE) with severe GT and anti platelet alloimmunization successfully treated with HSCT from her HLA‐identical sibling. Pediatr Blood Cancer 2009;52:682–683. © 2008 Wiley‐Liss, Inc.     

High-dose steroids in childhood acute idiopathic thrombocytopenia purpura

Nine newly diagnosed, previously untreated children (mean age: 4.2 years, range: 1-9 years) with severe acute idiopathic thrombocytopenia purpura (mean platelet count: 5.8 X 10(9)/L, range: 1-12 X 10(9)/L) were treated with high-dose steroids (prednisone 4-8 mg/kg/day). Steroid dose was based on platelet count at presentation: Group I (platelets less than 5 X 10(9)/L) was started on 8 mg/kg/day; Group II (platelets 5-15 X 10(9)/L) received 6 mg/kg/day. All patients had serologic and histologic evidence of acute idiopathic thrombocytopenia purpura. On this protocol, it took a mean number of 1.9 days (1-3 days) to reach a platelet count of at least 20 X 10(9)/L and 9.2 days (3-26 days) to reach a normal platelet count. No significant toxicity was observed except for weight gain ranging from 3-10% and mild behavioral problems. Both groups were on high-dose steroids (4-8 mg/kg/day) for 7.3 +/- 2.1 days. Only one patient had a brief relapse to a platelet count of 18 X 10(9)/L while on therapy (day 14), but responded promptly to an increase in prednisone dose. Presently, all nine patients are in remission and have not required maintenance medication.     

Neonatal thrombocytopenia: what we do and don't know

The evaluation and management of thrombocytopenia is a frequent challenge for neonatologists, as it affects 22-35% of infants admitted to the neonatal intensive care unit. Multiple disease processes can cause neonatal thrombocytopenia, and these can be classified as those inducing early thrombocytopenia (72 h). Most cases of neonatal thrombocytopenia are mild to moderate, and do not warrant intervention. In approximately 25% of affected neonates, however, the platelets count is <50x10(9)/L, and therapy with platelet transfusions is considered to decrease the risk of hemorrhage. The existing evidence to establish platelet transfusion triggers in neonates is very limited, but it suggests that transfusing platelets to non-bleeding neonates with platelet counts >50x10(9)/L does not decrease the risk of intraventricular hemorrhage (IVH), and that 30x10(9)/L might be an adequate threshold for stable non-bleeding neonates. However, adequately powered multi-center studies are needed to conclusively establish the safety of any given set of neonatal transfusion guidelines.     

Glanzmann’s Thrombasthenia

Glanzmann’s thrombasthenia (GT) is an uncommon cause of bleeding in children. We diagnosed two siblings as having GT on the basis of flow cytometric studies. Both had cutaneous bleedings and epistaxis since early childhood. Hematological investigations revealed prolonged bleeding time and a normal platelet count. Both the patients had absence of aggregation of platelets with the agonist adenosine diphosphate. Absence of the GPIIb/ IIIa receptor was confirmed by flow cytometry. A short review of the disorder is presented.     

异基因造血干细胞移植治疗IV期儿童神经母细胞瘤

目的：儿童IV期神经母细胞瘤生存期短,且目前尚无有效治疗措施。 该文通过异基因造血干细胞移植治疗IV期儿童神经母细胞瘤来评价其安全性及疗效。方法：对1例7岁IV期神经母细胞瘤患儿进行异基因造血干细胞移植治疗,供者为患儿母亲,HLA配型半相合,采用氟达拉滨,马法兰为预处理方案,G-CSF动员的外周血和骨髓联合移植。结果植入成功,移植后＋10 d中性粒细胞>0.5×109/L,＋11 d血小板>20×109/L。移植后+8 d出现II度肠道急性移植物抗宿主反应,治疗后缓解。随访210 d健康生存。结论： 对IV期儿童神经母细胞瘤患者,以父母为供体的半相合移植是一种可选择的、安全的、有效的挽救性治疗措施之一。     

The effect of dexamethasone upon platelets and neutrophils of preterm infants with chronic lung disease

The effect of a 21-day (reducing dose) course of dexamethasone upon platelet numbers, neutrophil numbers and neutrophil morphology in ventilator-dependent preterm infants with chronic lung disease is reported. Forty-one infants, who were sepsis-free throughout the treatment period, received 46 courses of dexamethasone. In these infants the circulating platelet count increased significantly from 235 +/- 157 to 476 +/- 208 X 10(9)/L. Both total neutrophil numbers (7.94 +/- 7.16 to 19.56 +/- 12.40 X 10(9)/L) and immature neutrophil numbers (1.19 +/- 1.22 to 2.68 +/- 2.58 X 10(9)/L) also showed a significant increase reaching a peak on day 7 of treatment and decreasing thereafter. The immature:total (I:T) neutrophil ratio remained essentially unchanged. Eight other infants who developed serious sepsis during the treatment period showed a fall in both platelets (293 +/- 236 to 140 +/- 170 X 10(9)/L) and total neutrophil numbers (18.61 +/- 10.83 to 15.76 +/- 10.53 X 10(9)/L), together with an increase in immature neutrophils (2.30 +/- 2.80 to 8.22 +/- 13.91 X 10(9)/L) and consequent increase in I:T ratio.     

Aggressive combination therapy in the successful management of life-threatening intracranial hemorrhage in a patient with idiopathic thrombocytopenic purpura

We describe acute therapy for a 13-year-old female from Panama with chronic idiopathic thrombocytopenia purpura (ITP) refractory to steroids, splenectomy, vinca alkaloids, and azathioprine. She presented with neurologic deterioration from a posterior fossa intracranial hemorrhage (ICH). This followed a 3-month history of severe dysfunctional uterine bleeding, progressive from menarche, which had required multiple red cell transfusions. Steroid and vinblastine therapy and transfusion of 40 U of platelets failed to increase the platelet count above 10,000/microliter. Development of a second larger ICH (frontal) produced morbid increase in intracranial pressure that necessitated neurosurgical decompression. Plasma exchange and colloid repletion with intravenous gamma globulin (1 g/kg) and an infusion of 20 U of platelets resulted in a transient rise in platelet count to 160,000/microliter, permitting surgery without bleeding. Danazol (800 mg/day) and conjugated estrogen (Premarin 25 mg/day) were begun to control the uterine bleeding. Intensive plasma exchange and i.v. IgG infusions were continued daily for 24 days, then twice weekly for several weeks. Platelet-bound IgG decreased almost 500% over the first 10 days of therapy, and platelets increased dramatically to 600,000/microliter after 3 weeks of therapy. The patient has remained amenorrheic with a normal platelet count for more than 24 months on daily danazol therapy and monthly infusions of i.v. IgG (0.4 g/kg/dose).     

Platelet dysfunction in homozygous beta-thalassemia

This report details the results of studies performed in nine patients with homozygous beta-thalassemia evaluating platelet function and prostaglandin formation. Platelet malonyldialdehyde (MDA) formation in the presence of N-ethyl maleimide (NEM 1 mM) or thrombin (0.5 u/ml) was used as an indicator of platelet prostaglandin synthesis. The data on the nine patients revealed two distinct subgroups of patients. Six of nine thalassemics, demonstrated platelet abnormalities. Their mean bleeding time was 7.5 +/- 2.5 min (1 SD), significantly prolonged (P less than 0.005) when compared to a value of 3.5 +/- 1.0 min in normal controls. MDA formation in the presence of NEM was significantly decreased (P less than 0.005) to 2.41 +/- 0.49 (1 SD) when compared to a control value of 3.24 +/- 0.33 nmoles MDA/10(9) platelets. Similarly, the mean value for thrombin induced MDA was 0.98 +/- 0.18 nmoles which was decreased (P less than 0.02) when compared to a value of 1.26 +/- 0.2 in the controls. Platelet aggregations with adenosine diphosphate (ADP), epinephrine, and collagen were abnormal in all six patients. However, when platelets from these patients were mixed with platelets from donors who had ingested aspirin 2-8 hr before donation mutual correction and secondary irreversible aggregation of the mixture resulted. No mutual correction was observed when the thalassemic platelets were preincubated with aspirin in vitro before mixing with platelets from donors who had recently ingested aspirin. Although the total amount of platelet malonyldialdehyde formed by the thalassemic platelets in response to NEM and thrombin was decreased when compared to normal controls, this reduction was not the cause of the platelet aggregation abnormalities. This appears to be so because the amount of MDA, and, thus, prostaglandin endoperoxides synthesized by these platelets in response to external stimuli was sufficient to cause irreversible aggregation of platelets from donors who had recently ingested aspirin, and were, therefore, unable to synthesize their own endogenous platelet endoperoxides. In the remaining three patients, bleeding times, platelet aggregation, and MDA formation was normal. No correlation was observed between the platelet abnormalities noted and the magnitude of iron overload, presence of fibrin degradation products, liver function abnormalities, or the use of iron chelators in the individual patient. Family studies were normal. Although the platelet dysfunction does not appear to be of major significance in the usual patient with thalassemia major under normal circumstances, antiplatelet aggregating agents should be used with caution. Aspirin inhibits platelet endoperoxide and prostaglandin formation and this effect may potentiate the platelet dysfunction present in some patients with thalassemia major.     

Transfusion-associated fall in platelet count in very low birthweight infants

Thirty-three infants with a birthweight of less than 1500 g were investigated retrospectively for the incidence and aetiology of thrombocytopenia occurring during the first week of life. The platelet count fell below 100 x 10(9)/l in 16 infants (48%). There was a moderately strong inverse correlation between the platelet count at its nadir during the first week or the first value below 100 x 10(9)/l and the percentage of blood volume transfused prior to this (r = -0.61; P less than 0.0001). When the platelet count was expressed as a percentage of the initial count the correlation was -0.74 (P less than 0.0001). The results were not affected by the elimination of the 10 infants with clinical conditions regarded as a probable cause of thrombocytopenia. The fitted least-squares regression line suggests that a transfusion equal to 10% of the blood volume on average reduced the platelet count by 19 x 10(9)/l or by 7% in these very low birthweight infants during the first week of life.     

Neonatal thrombocytopenia: new insights into pathogenesis and implications for clinical management

The healthy fetus has a platelet count of greater than 150 x 10(9)/L by the second trimester of pregnancy and only 2% of term infants are thrombocytopenic at birth. Severe thrombocytopenia (platelets < 50 x 10(9)/L) occurs in fewer than three per 1000 term infants, the most important cause being alloimmune thrombocytopenia. In contrast, in infants admitted to neonatal intensive care units, thrombocytopenia develops in 25% and in up to half of sick preterm infants. Recent evidence shows that these infants mostly have evidence of underlying impaired fetal megakaryocytopoiesis and platelet production following pregnancy complications characterized by placental insufficiency or fetal hypoxia. The mechanism of this is unknown. However, many neonatal complications exacerbate this thrombocytopenic potential and 20% of thrombocytopenias in neonatal intensive care unit patients are severe. Evidence-based guidelines for platelet transfusion therapy in these patients are yet to be defined, but as platelet underproduction underlies most neonatal thrombocytopenias, recombinant hemopoietic growth factors, including thrombopoietin and interkeukin-11, may be useful future therapies.     

Neonatal thrombocytopenia

Thrombocytopenia (platelets <150 x 10(9)/L) is one of the most common haematological problems in neonates, particularly those who are preterm and sick. In those preterm neonates with early thrombocytopenia who present within 72 h of birth, the most common cause is reduced platelet production secondary to intrauterine growth restriction and/or maternal hypertension. By contrast, the most common causes of thrombocytopenia arising after the first 72 h of life, both in preterm and term infants, are sepsis and necrotizing enterocolitis. The most important cause of severe thrombocytopenia (platelets <50 x 10(9)/L) is neonatal alloimmune thrombocytopenia (NAIT), as diagnosis can be delayed and death or long-term disability due to intracranial haemorrhage may occur. Platelet transfusion is the mainstay of treatment for severe thrombocytopenia. However, the correlation between thrombocytopenia and bleeding is unclear and no studies have yet shown clinical benefit for platelet transfusion in neonates. Studies to identify optimal platelet transfusion practice for neonatal thrombocytopenia are urgently required.     

Intratumoral consumption of indium-111-labeled platelets in a child with splenic hemangioma and thrombocytopenia

The authors report Kasabach-Merritt syndrome (KMS) in a patient with thrombocytopenia and splenic hemangioma. A 13-month-old boy with a history of anemia, thrombocytopenia, and abdominal mass was admitted to the hospital. The scintigraphic studies showed that a large mass contiguous to the spleen was responsible for the platelet uptake. After partial splenectomy, the platelet count returned to normal. This report of KMS in a child with splenic hemangioma suggests that the scintigraphic studies are mandatory to confirm diagnosis. Indium-111-labeled platelets are useful in identifying hemangiomatous sequestration of platelets in patients with thrombocytopenia.     

Thrombopoietin has a primary role in the regulation of platelet production in preterm babies.

Thrombocytopenia in the first days of life, in association with evidence of reduced megakaryocytopoiesis and platelet production at birth, is common in sick preterm babies. Thrombopoietin (Tpo) is the major regulator of platelet production in adults. However, these babies have low Tpo levels at birth, suggesting that the Tpo response to thrombocytopenia may be impaired. To test this hypothesis we 1) measured Tpo levels, 2) measured circulating megakaryocyte progenitors serially over the first 12 d of life in 13 preterm babies with early onset thrombocytopenia and in 14 control babies with evidence of normal megakaryocytopoiesis, and 3) measured Tpo levels in thrombocytopenic children (n = 13). In control babies, platelet counts and progenitor numbers remained normal and Tpo levels were consistently low-d 1:160+/-23 pg/mL (mean+/-SEM), d 4/5: 154+/-18 pg/mL and d 12: 150+/-58 pg/mL. In thrombocytopenic babies, platelet counts and megakaryocyte progenitor numbers were significantly lower than controls at d 1: platelets 130+/-14 x 10(9)/L versus 255+/-20 x 10(9)/L (p < 0.001) and megakaryocyte progenitors 552 versus 3907 colonies/mL (mean, p < 0.001), and fell further to nadir on d 4/5: platelets 76+/-6 X 10(9)/L versus 259+/-21 x 10(9)/L (p < 0.001) and MK progenitors 479 versus 2742 colonies/mL (p < 0.05). Tpo levels were only slightly raised on d 1:247+/-52 pg/mL (p = 0.24), but then rose sharply by d 4/5: 425+/-75 pg/mL (p < 0.001). By d 12, platelet count, megakaryocyte progenitors and Tpo level (145+/-29 pg/mL) had returned to control levels. Tpo levels at platelet nadir in thrombocytopenic babies were significantly lower than in thrombocytopenic children: mean 425 versus 1383 pg/mL (p < 0.001). These data show that Tpo is important in platelet homeostasis in preterm babies, with a close reciprocal relationship with platelet count and progenitor numbers during thrombocytopenia. However, the increase in Tpo levels seen in these babies was modest, despite significantly impaired megakaryocytopoiesis, and when compared with that seen in children with thrombocytopenia. This offers further evidence that preterm babies have an impaired Tpo response to thrombocytopenia and suggests that recombinant human Tpo may have a role in the prevention/treatment of preterm thrombocytopenia.     

Retrospective analysis of the clinical course of 12 children given the diagnosis essential thrombocythemia

BACKGROUND: Essential Thrombocythemia (ET) is an acquired myeloproliferative disorder (MPD) characterized by excessive production of platelets. The disorder is usually affecting adults and is rarely diagnosed in children. PATIENTS UND METHODS: In this retrospective study we describe 12 children aged 5-16 years in whom ET was presumed. RESULTS: Median follow-up was 59 months (range 10-72). At diagnosis 7 patients had clinical symptoms (syncope, poor concentration, fatigue, abdominal pain and mild bleeding), 5 patients were diagnosed accidentally (operation, allergy, enuresis, pneumonia, routine examination). Median platelet count at diagnosis was 1 325 x 10 (9)/L (range 600-3 050). In 11 cases bone marrow morphology was consistent with ET, one patient had chronic idiopathic myelofibrosis. Cytogenetics were normal in all studied cases. Within 6 months after the initial presentation one patient who was diagnosed accidentally developed thrombosis, another patient had mild bleeding. 8 patients were treated with acetylsalicylic acid (in addition, 1 patient received hydroxyurea, 2 patients received anagrelide). On last follow-up all patients were alive, none had developed leukemia. 5 patients experienced hematological remission. 2 of these children had not received any therapy. CONCLUSIONS: Many patients had symptoms attributable to ET. The clinical course is heterogeneous with complete normalization of platelets in the absence of cytoreductive therapy in some children. Due to the low incidence of ET in children indications for therapy are unclear and can only be deduced from findings obtained from studies in adults.