Platelet-specific antibodies in HLA-immunized patients receiving chronic platelet support.

BACKGROUND: In HLA-alloimmunized patients, the unexpected failure of HLA-matched platelet transfusions usually raises the suspicion about concomitant platelet-specific antibodies. As the reported frequency of platelet-specific antibodies in multitransfused patients varies widely, the aim of this study was to determine the prevalence of such antibodies in a population of chronic thrombocytopenic patients with HLA antibodies. STUDY DESIGN AND METHODS: From 1985 to 1997, 11,777 determinations of HLA antibodies were performed in 1330 hematologic patients receiving chronic platelet support. Fifty-two patients with HLA alloimmunization that lasted more than 1 month were selected. The search for platelet-specific antibodies was performed by using a monoclonal antibody immobilization of platelet antigens assay, thus allowing the identification of platelet-specific antibodies directed against the platelet glycoproteins (GP) Ib/IX, GPIIb/IIIa, and GPIa/IIa. Specificity of the platelet-specific antibodies was further investigated by using a solid-phase assay with chloroquine-treated platelets. RESULTS: Only 2 (3.8%) of the 52 patients had platelet-specific antibodies. One antibody reacted with an epitope of the GPIIb/IIIa that was present in all the panel platelets, and that probably was an autoantibody. The other was an anti-HPA-5b. CONCLUSIONS: The prevalence of platelet-specific antibodies in patients with HLA alloimmunization is very small. The search for concomitant platelet-specific antibodies would be indicated only when other causes of refractoriness to HLA-matched platelets are ruled out.

[Neurological form of onset in haemophagocytic lymphohistiocytosis]. / Forma de debut neurológico de la linfohistiocitosis hemofagocítica.

INTRODUCTION: Haemophagocyte lymphohistiocytosis (HLH) is a hematological disorder, autosomal recessive and in which there is benign proliferation of histiocytes with intense phagocytic activity of hematopoietic cells. The clinical features include fever, pancytopenia, coagulation disorders, liver dysfunction, the presence of histiocytes and haemophagocytes in the bone marrow, lymph nodes, spleen and liver. The nervous system is always involved and sooner or later patients develop a nervous system disorder with variable symptoms which may include irritability, disorders of consciousness, convulsions, ataxia, nystagmus or signs of intracranial hypertension. CLINICAL CASE: Onset of the disease showing purely neurological features is rare. We therefore describe the case of an 8 month old baby with HLH with a purely neurological condition involving irritability, horizontal rapid eye movements and vertical saccadic movements of both eyes and focal convulsive seizures. Initial complementary examinations were normal, except for study of the CSF with a lowered protein level and cells (monocytes). Finding hepatosplenomegaly and pallor, together with the laboratory investigations, made it advisable to do a bone marrow punch biopsy to detect haemophagocytes which would be diagnostic of HLH. In spite of chemotherapy there was rapid neurological deterioration, with alterations of the white matter and hydrocephaly which required insertion of a ventriculo-peritoneal shunt. The patient died when he was 10 months old. CONCLUSIONS: The cases of HLH in which cerebromeningeal disorders alone precede systemic symptoms are extremely rare. Hence the interest in reporting this case, so that it may be borne in mind in other cases of acute neurological onset. In this case initially there was encephalitis alone, but this was rapidly followed by systemic complications.

[Microangiopathic hemolytic anemia and thrombocytopenia. Thrombotic thrombocytopenic purpura]. / Anemia hemolítica microangiopática ytrombocitopenia. ¿Púrpuratrombótica trombocitopénica?

OBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) or Moschovitz' syndrome is rare and is even rarer in childhood. Clinically, it is characterized by microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, fever and renal dysfunction. The etiology is still unknown, although different factors such as large von Willebrand factor multimers and prostacyclin have been implicated. The acute form is more frequent, and in most cases the course is fulminant if treatment is not initiated. Laboratory data typically reveal hemolytic anemia, with schistocytes on the peripheral smear, diminished serum haptoglobin, and thrombocytopenia. MATERIAL AND METHODS: We present the clinical cases of two children, aged 4 and 7 respectively, with TTP, but with different evolution and treatment. Evolution was favorable in both patients. The first child recovered spontaneously. In the second plasmapheresis was required and produced remission of all the symptomatology. Normality has been maintained for 36 and 24 months respectively, and the children have presented no clinico-biological alterations.

Anemia hemolítica microangiopática y trombocitopenia. ¿Púrpuratrombótica trombocitopénica? / Microangiopathic hemolytic anemia and thrombocytopenia. ¿thrombotic thrombocytopenic purpura?

La púrpura trombótica trombocitopénica (PTT) o síndrome de Moschcovitz es un síndrome clínico poco frecuente, menos incluso en la edad pediátrica que en la adulta. Clínicamente se caracteriza por la presencia de anemia hemolítica microangiopática, trombocitopenia, sintomatología neurológica, fiebre y afectación renal. Su etiología es aún desconocida, aunque se han relacionado diferentes factores como los multímeros de factor Von Willebrand y la prostaciclina (PGI2). Es más frecuente la forma aguda de la enfermedad, y en la mayoría de los casos el curso es rápido y fulminante si no se inicia tratamiento. Los datos de laboratorio muestran típicamente una anemia de características hemolíticas, con abundantes hematíes fragmentados o esquistocitos, disminución de la haptoglobina y plaquetopenia. Se presentan los casos clínicos de 2 niños, de 4 y 7años respectivamente, con cuadro clínico compatible con PTT, pero con evolución y necesidades terapéuticas diferentes. La evolución de los pacientes fue buena. En el primer caso el cuadro remitió de forma espontánea y en el segundo caso precisó de plasmaféresis, con lo que desaparecieron los síntomas. La normalidad se ha mantenido durante 36 y 24 meses, respectivamente, y no han vuelto a presentar ninguna alteración clinicobiológica (AU)

Forma de debut neurológico de la linfohistiocitosis hemofagocítica / Neurological form of onset in haemophagocytic lymphohistiocytosis

Introducción. La linfohistiocitosis hemofagocítica (LHH) es una enfermedad hematológica, autosómica recesiva, en la que se produce una proliferación benigna de histiocitos con intensa actividad fagocítica de células hematopoyéticas. Cursa con fiebre, pancitopenia, trastornos de la coagulación, disfunción hepática, presencia de histiocitos y hemofagocitos en médula ósea, nódulos linfáticos, bazo e hígado. El compromiso del sistema nervioso es constante y todos los pacientes desarrollan más tarde o más temprano un cuadro neurológico que puede manifestarse con síntomas variables como irritabilidad, trastornos de conciencia, convulsiones, ataxia, nistagmo o signos de hipertensión intracraneal. Caso clínico. El debut de la enfermedad con un cuadro exclusivamente neurológico es poco común y por ello presentamos la observación de un lactante de 8 meses con LHH que presenta un cuadro exclusivamente neurológico, en forma de irritabilidad y movimientos oculares rápidos horizontales y sacádicos verticales de ambos ojos y crisis convulsivas focales. Los exámenes complementarios iniciales fueron normales, excepto el estudio del LCR que reveló hiperproteinorraquia y celularidad (monocitos). La evidencia de sustancia blanca con áreas de edema, necrosis y atrofia cortical [1,3,5]. una hepatoesplenomegalia y palidez, junto a la analítica, aconsejó practicar una punción biopsia de médula ósea que detectó hemofagocitos, diagnóstico de LHH. A pesar del tratamiento quimioterápico se produjo un rápido deterioro neurológico, con alteraciones en la sustancia blanca y acompañado de hidrocefalia que requirió derivación ventriculoperitoneal. El paciente falleció a los 10 meses. Conclusión. Los casos de LHH en los que el compromiso cerebromeníngeo exclusivo precede a los síntomas sistémicos es extremadamente raro, de aquí el interés en comunicarlo y tenerlo en cuenta frente a un paciente con una clínica neurológica aguda, en este caso exclusivamente de encefalitis pero que se complicó rápidamente con manifestaciones sistémicas (AU)

Clinical and laboratory factors associated with platelet transfusion refractoriness: a case-control study.

In recent years clinical factors have largely surpassed alloimmunization as the predominant cause of platelet refractoriness. This makes it necessary to properly identify and weigh the non-immune factors that have a major impact of refractoriness. A case-control study is suitable for such an analysis, and to our knowledge has not previously been performed to assess this issue. Fifty-two refractory patients were compared with 52 control patients who were transfused at the same time. Only one transfusion event was analysed per patient. Clinical and laboratory data were recorded at the time of selected transfusion, and their association with refractoriness was investigated by the contingency table method and the Cox stepwise logistic regression. There were 16 (31%) patients with HLA antibodies in the index group and only one in the control group. The corrected count increment in the group of patients refractory due to HLA antibodies was significantly lower than that in non-alloimmunized refractory patients [median (range): 48.5 (-3560, 4614) and 4058 (-4417, 6886), respectively; U = 493, P < 0.0001]. In the multivariate analysis, factors associated with refractoriness were the presence of HLA antibodies (odds ratio (OR) 50.7; 95% CI 5.5-463); fever (odds ratio 7.2; 95% CI 2.5-21) and BMT because of chronic myeloid leukaemia (odds ratio 7.3; 95% CI 1.8-30). The latter two were the only factors that remained independently associated with refractoriness after excluding alloimmunized patients and their controls. We conclude that HLA antibodies are strongly associated with platelet transfusion refractoriness, but account for less than a third of these patients. Fever and BMT because of chronic myeloid leukaemia were the only non-immune factors independently associated with refractoriness.

[Identification of a variant D(IVa) with anti-D in serum]. / Identificación de una variante D(IVa) con anti-D en suero.

The first D(IVa) variant described so far in Spain is presented. This variant was identified, by means of a commercial monoclonal antibodies panel, in a RhD positive patient with anti-D in her serum. Differential diagnosis is discussed and the clinical relevance of identifying these variants is commented.

Influence of the red blood cell preparation method on the efficacy of a leukocyte reduction filter.

The performance of a leukocyte reduction bedside filter with different types of RBC concentrates was analyzed. Three types of RBCs were prepared: buffycoat-depleted RBCs suspended in saline-adenine-glucose-mannitol (SAGM)-additive solution (BC-RBCs; n = 20), RBCs suspended in SAGM-additive solution without buffy coat removal (SAGM-RBCs; n = 20), and RBCs drawn in CPDA-I conservative solution and processed for component preparation by the platelet-rich plasma method (CPDA-RBCs; n = 20). The units were filtered within 8 h of collection. One filter was used for every 2 units. High numbers of residual WBCs were found even in the units filtered first. Filtration of CPDA-RBCs resulted in a higher residual WBC content than SAGM-RBCs or BC-RBCs (p = 0.0032 and p = 0.0002, respectively). The filter performance strikingly decreased when the WBC load per filter exceeded 4 x 10(9) or the platelet load was less than 100 x 10(9). We conclude that filter performance varies with the WBC and platelet content of the RBC concentrates. Under the experimental conditions assayed in this study CPDA-RBCs are the least appropriate ones to be used for bedside leukocyte reduction.

[Alpha interferon treatment of idiopathic myelofibrosis]. / Tratamiento con interferón alfa de la mielofibrosis idiopática.

Idiopathic myelofibrosis is a chronic myeloproliferative syndrome for which there is no effective treatment. The good results obtained with interferon in other chronic myeloproliferative syndromes have led their being tested in idiopathic myelofibrosis, but to date the experience is scarce. Four patients out of a total of 12 diagnosed with idiopathic myelofibrosis over a period of 3 years were selected for interferon treatment. Patients with low leukocyte or platelet counts or with contraindication for administration of the drug were excluded. Alpha-2b interferon was administered at an initial dose of 3 MU/day which was increased at 4-6 weeks to 5 MU/day in cases of insufficient response and if tolerance so permitted. In patients in whom favorable response was observed a maintenance schedule was initiated with low doses of interferon. Treatment was discontinued in two patients due to bad tolerance at 6 and 8 weeks of initiation of treatment with no response having been observed until that time. In the other patients favorable response was reported to interferon after 5 months of treatment with disappearance of the symptomatology, normalization of the hemo-peripheral values and a marked reduction of splenomegaly. This responses was accompanied by a decrease in bone marrow fibrosis in one case and total disappearance of the same in the other patient. Alpha-2b interferon constitutes an effective therapy for a selected number of patients with idiopathic myelofibrosis. Greater experience would allow the identification of the subgroup of patients who may benefit from this type of treatment.

[Transient appearance of anti-erythrocyte autoantibodies during Rh alloimmunization]. / Aparición transitoria de autoanticuerpos antieritrocitarios durante la aloinmunización Rh.

Transient appearance of anti-erythrocyte autoantibodies was demonstrated in two women in the first stages of Rh alloimmunization. Any mimicking antibodies, or concurrent autoimmune haemolytic anaemia could be reasonably discarded in both patients. These facts are discussed on the basis of polyclonal activation followed by clonal selection driven by the antigen, as a mechanism of the humoral immune response. Investigation of such cases seems of great interest in subjects with recent alloimmunization in order to assess the incidence of this phenomenon and the antigen systems involved.

Anti-Sa cold agglutinin of IgA class requiring plasma-exchange therapy as early manifestation of multiple myeloma.

The case of a patient (Col) with multiple myeloma presenting as chronic cold agglutinin (CA) syndrome is reported. The CA (Col) was a monoclonal IgA/k paraprotein which recognizes an antigen fully expressed in adult and newborn erythrocytes, sialidase sensitive and partially resistant to proteases. Hemagglutination-inhibition studies showed that immunodominant N-acetylneuraminic acid bound alpha 2-->3 to O-glycans of glycophorins represents the CA(Col) epitope. These serological and biochemical findings fit with the anti-Sa specificity, of which only two previous examples are known. The clinical manifestations of CA (Col) were characterized by marked acrocyanosis, generalized livedo reticularis, and incapacitating dyspnea, but only mild hemolysis. Plasma-exchange therapy was effective in quickly removing the CA and relieving the associated clinical manifestations, but such benefit was only temporary. This is the first reported example of anti-Sa CA of IgA isotype and the first case of IgA CA syndrome treated by plasma exchange.

Penicillamine-induced rapidly progressive glomerulonephritis in a patient with rheumatoid arthritis.

A 67-year-old woman with rheumatoid arthritis presented rapidly progressive glomerulonephritis (RPGN) after 5 months of D-penicillamine (250 mg/day) treatment. Light microscopy study showed severe glomerulonephritis with crescent formation in 60% of the glomeruli and infiltration of inflammatory cells in the wall of an arteriole. Immunofluorescence revealed scanty granular IgG, IgA and C3 deposits along the capillary walls and mesangium. The patient was treated with steroid pulse, plasmapheresis, cyclophosphamide and antiplatelet agents. A complete recovery of renal function was achieved in a few weeks. This new case of RPGN in the course of D-penicillamine treatment emphasizes the need for frequent monitoring of renal function and evaluation of urinary sediment and proteinuria in these patients. The prompt discontinuation of D-penicillamine and vigorous treatment measures could allow for a good prognosis as in this case.

[Chronic myeloid leukemia beginning as thrombocythemia. Analysis of 5 cases]. / Leucemia mieloide crónica de inicio trombocitémico. Análisis de cinco casos.

The clinico-haematological and evolutive features of five patients with Ph'-positive chronic myelogenous leukaemia (CML) whose initial profile suggested the diagnosis of essential thrombocythaemia (ET) were analysed. The patients were women with severe thrombocytosis (greater than or equal to 1000 x 10(9)/L) and moderate leucocytosis (less than 25 x 10(9)/L), and only two of them had splenomegaly. Increased basophil count in peripheral blood was present in all cases, and peripheral myelocytosis was seen in three. The molecular analysis showed rearrangement of the BCR gene in the three patients on which it was performed. Increasing leucocyte count was seen in the three patients with extended follow-up, this reaching values in accordance with CML. Finally, the three patients who died suffered a blastic crisis. The analysis of this series, along with others reported in the literature, suggests that such cases correspond to atypical forms of CML rather than actual TE patients.