Management of alloimmune thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets

Neonatal alloimmune thrombocytopenia (NAIT) can cause severe bleeding in the central nervous system (CNS) and death or severe neurologic sequelae. The expression of the PLA1 antigen is detectable as early as 19 weeks of gestation. Alloimmunization can therefore lead to fetal thrombocytopenia very early in pregnancy. Until recently, we have had no means of detecting and assessing the severity of fetal thrombocytopenia during pregnancy. The level of the maternal antibody is not of a predictable value since 20% of the mothers had no circulating antibodies in our series. An alternative approach is to carry out investigations on fetal blood samplings. This management leads to an exact knowledge of the fetal status and antenatal diagnosis is feasible as early as the 21st week of gestation. Early diagnosis facilitates appropriate management and makes possible such therapeutic options as in utero maternal platelet transfusions. We report our experience in the antenatal diagnosis and management of nine cases with in utero transfusion in the six cases with severe thrombocytopenia. All neonates did well, with no signs of bleeding at birth. No side effects of therapy were noted after a period ranging from 6 months to 3 years.     

Stromal cells from human long-term marrow cultures are mesenchymal cells that differentiate following a vascular smooth muscle differentiation pathway

In human long-term marrow cultures connective tissue-forming stromal cells are an essential cellular component of the adherent layer where granulomonocytic progenitors are generated from week 2 onward. We have previously found that most stromal cells in confluent cultures were stained by monoclonal antibodies directed against smooth muscle- specific actin isoforms. The present study was carried out to evaluate the time course of alpha-SM-positive stromal cells and to search for other cytoskeletal proteins specific for smooth muscle cells. It was found that the expression of alpha-SM in stromal cells was time dependent. Most of the adherent spindle-shaped, vimentin-positive stromal cells observed during the first 2 weeks of culture were alpha- SM negative. On the contrary, from week 3 to week 7, most interdigitated stromal cells contained stress fibers whose backbone was made of alpha-SM-positive microfilaments. In addition, in confluent cultures, other proteins specific for smooth muscle were detected: metavinculin, h-caldesmon, smooth muscle myosin heavy chains, and calponin. This study confirms the similarity between stromal cells and smooth muscle cells. Moreover, our results reveal that cells in vivo with the phenotype closest to that of stromal cells are immature fetal smooth muscle cells and subendothelial intimal smooth muscle cells; a cell subset with limited development following birth but extensively recruited in atherosclerotic lesions. Stromal cells very probably derive from mesenchymal cells that differentiate along this distinctive vascular smooth muscle cell pathway. In humans, this differentiation seems crucial for the maintenance of granulomonopoiesis. These in vitro studies were completed by examination of trephine bone marrow biopsies from adults without hematologic abnormalities. These studies revealed the presence of alpha-SM-positive cells at diverse locations: vascular smooth muscle cells in the media of arteries and arterioles, pericytes lining capillaries, myoid cells lining sinuses at the abluminal side of endothelial cells or found within the hematopoietic logettes, and endosteal cells lining bone trabeculae. More or less mature cells of the granulocytic series were in intimate contact with the thin cytoplasmic extensions of myoid cells. Myoid cells may be the in vivo counterpart of stromal cells with the above-described vascular smooth muscle phenotype.     

Effect of HLA Bw4/Bw6 compatibility on platelet transfusion responses of refractory thrombocytopenic patients

Platelet transfusions from donors matched for cross-reactive antigens have been shown to be effective in providing hemostasis in alloimmunized thrombocytopenic patients. A significant number of these transfusions, however, fail to provide posttransfusion platelet recoveries. We investigated incompatibility in the Bw4/bw6 system as a possible explanation for these failures. The Bw4/Bw6 system is a biallelic antigen system closely associated with HLA-B. HLA-B locus antigens that are cross-reactive frequently differ in their Bw4/Bw6 specificity. Posttransfusion platelet recoveries from 21 alloimmunized thrombocytopenic patients homozygous for Bw4 or Bw6 and transfused with both Bw4/Bw6 compatible and incompatible platelets were analyzed. The mean 1-hr posttransfusion recovery was 84% following Bw4/Bw6-compatible platelets versus 52% with Bw4/Bw6-incompatible platelets (p less than 0.02). Twenty-four hours following transfusion, mean recoveries were 44% and 24%, respectively, (p less than 0.01). A subgroup of 8 patients (38%) was identified who had markedly lower responses following Bw4/Bw6- incompatible transfusions as compared to Bw4/Bw6-compatible transfusions (mean recoveries: 1 hr--compatible 100%, incompatible 27%, p less than 0.001; 24 hr--compatible 45%, incompatible 7%, p less than 0.01). These data suggest that the Bw4/Bw6 antigen system has clinical significance for some patients requiring platelet transfusion therapy and, when appropriate, should be considered in the selection of donors.     

Neutrophil adhesiveness during prostacyclin and heparin hemodialysis

We evaluated neutrophil adhesive function in patients undergoing chronic hemodialysis using either prostacyclin or heparin as antithrombotic agents. Patients underwent successive hemodialyses with prostacyclin (4 ng/kg/min) and heparin. There were no significant differences noted in neutrophil adhesive function during either dialysis: transient neutropenia developed in each case; impaired neutrophil adhesiveness to plastic developed during both dialyses; neutrophil aggregation was diminished when compared to predialysis responses during both dialyses. Furthermore, the number of circulating Fc-receptor-bearing neutrophils fell significantly during both prostacyclin and heparin hemodialysis. Our study demonstrates that substitution of prostacyclin for heparin in doses that do not cause hypotension, does not prevent neutropenia or alter the diminished neutrophil adhesiveness that occurs during heparin hemodialysis.     

Neurologic complications after allogeneic marrow transplantation for sickle cell anemia [see comments]

Seven of 21 patients with sickle cell anemia developed neurologic complications 5 to 243 days (median, 33 days) after allogeneic marrow transplantation. Among these 7 patients, indications for transplantation included either a past history of stroke (4 patients) or recurrent severe vaso-occlusive events (3 patients). All received marrow from an HLA-identical sibling after preparation with busulfan and cyclophosphamide, and in 4 patients with antithymocyte globulin. Five of 6 patients developing seizures received anticonvulsant and supportive treatment with resolution of neurologic abnormalities. Three patients experienced intracranial bleeding, which was fatal in two. Of the 14 patients free of neurologic complications, 4 patients had experienced stroke before transplantation. However, among all patients with prior stroke, the incidence of intracranial hemorrhage was 38% (3/8), whereas none of the 13 patients without prior stroke developed posttransplant intracranial bleeding (P = .026). We conclude that patients with sickle cell anemia are at increased risk for neurologic complications after marrow ablative therapy and that patients with prior stroke are at increased risk for intracranial hemorrhage. Transplantation of patients before the onset of overt stroke may reduce this risk.     

Crohn's disease with spontaneous ileoumbilical and ileovesical fistulae

Summary A 17-year-old male with Crohn's disease involving the terminal ileum and cecum developed an umbilical fistula in the absence of previous surgery. While on intravenous hyperalimentation he developed an enterovesical fistula and was successfully treated by surgical resection. This combination of an enterovesical and umbilical fistula has not been previously reported. An aggressive approach to treatment is suggested.     

Acute pseudo-obstruction of the colon in thermally injured patients

Summary and Conclusions Five (1 per cent) of 529 thermally injured patients experienced pseudo-obstruction of the colon over a two-year period. All patients had classic non-painful abdominal distention. Infection was the most common associated problem and possible triggering mechanism in these patients. After confirmation of the colonic dilation on a plain abdominal roentgenogram, distal obstruction was ruled out by contrast enema. Occasionally, Gastrografin enema seemed to ameliorate the distention. Conservative medical management should be attempted initially. Colonoscopy should be employed at the earliest possible time. Exploratory laparotomy and tube cecostomy are usually adequate when surgical decompression is necessary. Patients who have accompanying small-intestinal distention seemed to tolerate this condition better, possibly due to a decompressing effect of an incompetent ileocecal valve. “Hinge-type” kinks, which occur in time at both hepatic and splenic flexures, become obstructing in themselves, and can be a barrier to conservative treatment. Read at the meeting of the American Society of Colon and Rectal Surgeons, San Diego, California, June 11 to 15, 1978. The opinions or assertions contained herein are the private view of the authors and are not to be construed as official or as reflecting the view of the Department of the Army or the Department of Defense.     

Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization

In situ hybridization was used to localize the cells that produce erythropoietin (EP) in anemic murine kidneys. Kidneys from anemic and nonanemic mice were fixed and processed for paraffin embedding. Sections were hybridized with a 35S-labeled RNA probe complementary to mRNA coding for EP. An uncommon, but specific type of cell was intensely labeled in the cortices of anemic kidneys. The labeled cells were clearly nonglomerular and nontubular. Their location outside of the tubular basement membrane was consistent with that of a subset of interstitial cells or capillary endothelial cells.