Simultaneous occurrence of foetal and neonatal alloimmune thrombocytopenia and neonatal neutropenia due to maternal neutrophilic autoantibodies: a case study and review of the literature.

UNLABELLED: Foetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal neutropenia caused by maternal autoantibodies against neutrophils are rare disorders. We describe a newborn with severe thrombocytopenia and intracerebral bleeding caused by maternal anti-HPA-3a alloantibodies and mild neutropenia caused by maternal autoantibodies against HNA-1b. This appears to be the first case of simultaneous occurrence of these two conditions. CONCLUSION: This case report and review of the literature demonstrate that anti-HPA-3a antibodies can be overlooked by standard assays.

[Fetal and neonatal alloimmune thrombocytopenia]. / Føtal og neonatal alloimmun trombocytopeni er en mulig fatal tilstand.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may lead to intracranial haemorrhage (ICH) resulting in neurological damage or death. In FNAIT, transplacental maternal antibodies cause destruction of fetal platelets. Maternal immunisation occurs to fetal human platelet antigens (HPAs) inherited from the father. In the absence of screening the diagnosis often relies on a serious incident in a previous pregnancy or in a newborn sibling. Thus, a future reduction in the risk of ICH depends on prospective large trials to evaluate different diagnostic, treatment, and prevention strategies.

Maternal human platelet antigen-1a antibody level correlates with the platelet count in the newborns: a retrospective study.

BACKGROUND: Maternal plasma and/or serum levels of anti-HPA-1a at delivery were compared to neonatal platelet (PLT) counts. STUDY DESIGN AND METHODS: Samples from HPA-1bb women who gave birth to children with thrombocytopenia or had anamnestic information about a previous child with neonatal alloimmune thrombocytopenia (NAIT) were collected at delivery. A modified monoclonal antibody immobilization of PLT antigen method was used for quantification of anti-HPA-1a. RESULTS: The anti-HPA-1a level in women with severely thrombocytopenic children was higher than the corresponding level in mothers of children born with moderate thrombocytopenia or normal PLT counts. CONCLUSION: Our data show a significant correlation between maternal anti-HPA-1a level and the neonatal PLT count and indicate strongly that this may be a reliable predictive measure for NAIT. Suitable test systems for quantitative measurements of anti-HPA-1a must be developed and evaluated for this particular purpose.

Rituximab in chronic cold agglutinin disease: a prospective study of 20 patients.

Chronic cold agglutinin disease (CAD) is an acquired autoimmune hemolytic anemia. Previous therapeutic modalities, including alkylating cytostatics, interferon and prednisolone, have been disappointing. However, several case reports and small-scaled studies have demonstrated promising results after treatment with rituximab. We performed a phase II multicentre trial to investigate the effect of rituximab in CAD, including 20 patients studied from October 2002 until April 2003. Thirteen patients had idiopathic CAD and seven patients had CAD associated with a malignant B-cell lymphoproliferative disease. Rituximab was given in doses of 375 mg/m(2) at days 1, 8, 15 and 22. Sixteen patients were followed up for at least 48 weeks. Four patients were excluded after 8, 16, 23 and 28 weeks for reasons unrelated to CAD. Nine patients (45%) responded to the treatment, one with complete response (CR), and eight with partial response. Eight patients relapsed, one patient was still in remission at the end of follow-up. There were no serious rituximab-related side-effects. Our study confirms previous findings of a favourable effect of rituximab in patients with CAD. However, few patients will obtain CR and, in most patients, the effect will be transient.

Association of mannose-binding lectin polymorphisms with sepsis and fatal outcome, in patients with systemic inflammatory response syndrome.

Genetic factors may predispose critically ill patients to increased risk of developing sepsis. Mannose-binding lectin (MBL) is an important factor in innate immune defense. We investigated whether MBL gene polymorphisms causing low levels of MBL are associated with the development and progression of sepsis in adult patients in intensive care units. In 272 prospectively monitored patients with systemic inflammatory response syndrome, different MBL genotypes were compared, with respect to microbiology, sepsis development, and survival. The presence of MBL variant alleles was associated with the development of sepsis, severe sepsis, and septic shock. An increased risk of fatal outcome was observed in patients carrying variant alleles. These data show that MBL insufficiency plays an important role in the susceptibility of critically ill patients to the development and progression of sepsis and confers a substantial risk of fatal outcome.

Post-transfusion purpura (PTP) and disseminated intravascular coagulation (DIC).

A 47-yr-old female with acute pancreatitis received four units of fresh frozen plasma because of subtle signs of disseminated intravascular coagulation (DIC). Seven days later, she developed severe thrombocytopenia. Serological studies demonstrated antibodies against HPA-1a together with pan-reactive antibodies against platelet glycoproteins (GPIIb-IIIa, GPIb-IX and GPIa-IIa), which was consistent with the diagnosis of PTP. The patient was treated with platelet transfusions, corticosteroids and intravenous immunoglobulin (IVIG) without permanent beneficial effect. After treatment with plasma exchange the platelet count increased to normal values.

Parvovirus B19 and parvovirus V9 are not associated with Henoch-Schönlein purpura in children.

BACKGROUND: Based on single case reports, parvovirus B19 (B19) has repeatedly been proposed as an etiologic agent in patients with Henoch-Schönlein purpura (HSP), perhaps causing vasculitis by direct invasion of vascular endothelial cells because of the tissue distribution of the cellular B19 receptor. A cohort of children with HSP and other vasculitic diseases was investigated and compared with healthy control children to assess the role of B19 as well as parvovirus V9 (a putative emerging B19-like virus). PATIENTS AND METHODS: Serum samples from 36 children with HSP (n = 29) or other vasculitic diseases (n = 7) were examined, and 38 healthy bone marrow donors were used as controls. The presence of specific B19 and V9 IgM and IgG antibodies was determined with a recently developed enzyme-linked immunosorbent assay, and viral DNA was detected by a novel nested PCR. RESULTS: Specific IgM was not present in any of the patient or control serum samples. B19 DNA was detected in one patient, a previously healthy 8-year-old boy diagnosed with HSP, whereas none of the controls was B19-positive. V9 was not detected in any of the clinical or control samples. It seems likely that B19 infection might have triggered the development of HSP in the B19-positive patient, because B19 viremia is otherwise uncommon. CONCLUSIONS: Although causality is difficult to construe in single cases, the data indicate that B19 is not a common contributing factor in the pathogenesis of vasculitis and that this pathogen is only rarely associated temporally with HSP or vasculitic diseases in children.