American Journal of Hematology

doi: 10.1002/ajh.2830080301pmid: N/A

Corrigan, James J.; Earnest, David L.

doi: 10.1002/ajh.2830080302pmid: 6774611

Four coagulation factors (II, VII, IX, X) are synthesized in the liver as precursor forms. Vitamin K is necessary for their conversion to functional factors. Factor II precursor is antigenically similar to factor II and can be activated to form thrombin by Echis carinatus venom. Forty‐one patients with liver disease and 30 patients with vitamin K deficiency (Warfarin treated), were compared with 51 normal patients. Rats with CCl4‐induced hepatic necrosis and animals given Warfarin were also studied. The following measurements were made: standard prothrombin time; Echis clotting time; factor II coagulant assay with thromboplastin; factor II assay with Echis venom; and factor II antigen (human) by electroimmunoassay. In animals and humans with liver disease, factor II was reduced, as measured by all techniques. With vitamin K deficiency functional factor II was reduced, but factor II antigen and Echis factor II activity were normal. The data suggest that the prothrombin time and Echis coagulation methods can be used to differentiate whether the coagulopathy in liver disease is due to reduced precursor levels of factor II, vitamin K deficiency (ie, impaired formation of functional from precursor factor II), or both.

Mazza, Joseph J.; Gatlin, Patience F.; Marx, James J.

doi: 10.1002/ajh.2830080303pmid: 6251719

A sensitive in vitro technique was used to demonstrate the inhibitory effects of histamine on human blood platelets. Platelet aggregation by epinephrine was completely inhibited at 10−3 M concentrations of histamine. Persistent elevations of cyclic AMP levels were shown to occur in the platelets when histamine was added and corresponded to the inhibitory effects on platelet aggregation. In contradistinction to the analogous inhibitory effects by histamine on other cellular elements of the hematopoietic system, this inhibitory effect on platelets could not be blocked by equimolar concentrations of either of the classes of histamine antagonists presently available. It is suggested that there may be other additional histamine receptors on the surface of membranes of platelets or that histamine mediated its inhibitory effect on platelets through a mechanism other than surface receptors.

Ruíz‐Argüelles, G. J.; Sánchez‐Medal, L.; Loría, A.; Piedras, J.; Córdova, M. S.

doi: 10.1002/ajh.2830080304pmid: 7416157

Hemoglobin (Hb), packed cell volume (PCV), red blood cells (RBCs), mean cell volume (MCV), and mean cell hemoglobin concentration (MCHC) were measured by a single operator in a single laboratory by means of an electronic particle counter in 942 healthy adults (491 females and 451 males) residing at five altitudes: 0, 1000, 1860, 2220, and 2670 meters above sea level. The subjects were carefully screened clinically, and subjects with low transferrin saturation ( < 15%) were excluded. In both sexes there was a differential behavior as a function of altitude, of Hb and PCV on the one hand, and number of RBCs on the other. The findings suggest the presence of two sequential mechanisms of adaptation to progressively lower atmosphere oxygen pressure: One operating from sea level to 1860 meters, which leads to a progressively increasing number of relatively microcytic RBC; and a second one – from 1860 to 2670 meters – in which there is an increased but constant number of progressively more normocytic RBC, so that a simplistic model of equal magnitude increases in the three parameters and is seen at 2670 meters, but not at the intermediate altitudes. The middle group's comparativity, essential to these interpretations, apparently was achieved with regard to time elapsed between sampling and testing and with regard to the people integrating the groups.

Morse, Bernard S.; Conlan, Maureen; Giuliani, Dennis G.; Nussbaum, Murray

doi: 10.1002/ajh.2830080305pmid: 7416158

Anemia accompanies arsenic intoxication in man. The present studies were undertaken to clarify further the effects of arsenic on erythropoiesis. A dose‐related inhibition of red cell 59Fe incorporation and reticulocyte response was observed in normal mice treated with a single injection of arsenic. Arsenite was approximately two times as inhibitory as arsenate. The effects of arsenic on erythropoietin‐induced erythroid differentiation revealed a significant inhibitory effect on young, proliferating marrow nucleated erythroid precursor cells. More mature, nonproliferating nucleated erythroid cells were resistant to the toxic action of arsenic. A dose‐related inhibitory effect of arsenic on DNA synthesis was observed in fetal liver nucleated erythroid cells incubated with 3H thymidine. Ineffective erythropoiesis as well as the megaloblastic morphology accompanying aberrant DNA synthesis – manifestations of arsenic toxicity in man – were not evident in the present studies.

Tsukada, Toshiyasu; Tango, Toshiro

doi: 10.1002/ajh.2830080306pmid: 7416159

The International Committee for Standardization in Hematology recommended three methods for calculating objectively the mean platelet survival time, ie, weighted mean of linear estimate and logarithmic estimate, truncated exponential model, and gamma model. For determining which method is better, data of the survival study were fitted to each of three methods, as well as the Paulus polynomial and exponential polynomial models, and the mean survival time and the mean square error were compared. Mean survival obtained by each method was always longest in healthy controls and shortest in ITP. In 3rd degree of polynomial estimate and 2nd and 3rd degrees of logarithmic estimate, several cases showed practically outlying mean survival time of more than 12 days. In healthy controls, highest mean square error was observed in 1st degree logarithmic estimate, and in cases with short mean survival time the highest one was obtained in 1st degree polynomial estimate. Mean square error in ITP pre‐ and postsplenectomy and in aplastic anemia was smallest in the gamma model. Among nine methods recommended by the International Committee for Standardization in Hematology and by Dr. Paulus, the gamma model so far provides the best method for calculating the mean survival time of 51Cr‐platelets.

Vettore, Luciano; De Matteis, Maria Concetta; Zampini, Patrizia

doi: 10.1002/ajh.2830080307pmid: 7416160

A new density system for the separation of human red blood cells by density‐gradient centrifugation is described. The gradient medium is made with colloidal silica particles coated with polyvinylpyrrolidone suspended in aqueous solution of meglamine diatrizoate. By this method, more than 10 red‐cell fractions can be separated. These show different ages (by creatine content and 59Fe in vivo labelling) and different characteristics (ie, potassium content). A 40‐fold enrichment in reticulocytes can be obtained in the top layers, with a great improvement of specific activity in labelling procedures of newly synthesized globin chains. The method is simple, rapid, inexpensive, reliable, nontoxic for erythrocytes, and is suitable for globin synthesis and other studies of erythrocyte metabolism.

Takahashi, Hoyu; Sakuragawa, Nobuo; Shibata, Akira

doi: 10.1002/ajh.2830080308pmid: 6774612

Two cases of von Willebrand disease (VWD) that revealed an increased ristocetin‐induced platelet aggregation (RIPA) and a qualitative abnormality of the factor VIII protein are reported. The threshold concentration of ristocetin giving a 30% increase in light transmission was 0.5 mg/ml in the proband and 0.4 mg/ml in her father (normal: 1.16 ± SD 0.18 mg/ml) although both patients showed reduced plasma von Willebrand factor activity (VIIIR:WF). In both patients, the amount of factor VIII related antigen (VIIIR:AG) in their platelets were normal, but an increased binding affinity of platelets to plasma factor VIII was demonstrated. The qualitative abnormality of the factor VIII protein was characterized by an increased anodal migration of VIIIR:AG in crossed immunoelectrophoresis (CIE), a delayed elution pattern as demonstrated by gel filtration on Sepharose 2B, and a decreased precipitation with concanavalin A (Con A). The response to DDAVP was also investigated.

Seeler, Ruth Andrea; Jacobs, Norman M.

doi: 10.1002/ajh.2830080309pmid: 7416161

Diarrhea with fever was a significant complaint in 26 of 280 (9.3%) of non‐SS children with S. pneumoniae bacteremia and four of 30 (13%) children with sickle syndromes and S. pneumoniae bacteremia. Two additional children with sickle‐cell disease and S. pneumoniae bacteremia developed diarrhea within hours of hospital admission; four of the six died. The mortality rate among 24 additional SS patients with S. pneumoniae bacteremia without diarrhea was 12.5% (3/24). Only one of 26 non‐SS patients with diarrhea and S. penumoniae bacteremia died; she was surgically asplenic and had fulminant 9‐hour course. The seasonality of the diarrhea cases was similar to our overall experience, and the serotypes associated with the diarrhea cases were also representative of our overall experience. Although predominantly seen in infants, the oldest non‐SS patient was 12 years, and the oldest SS patient was nine years.

Chusid, Michael J.; Pisciotta, Anthony V.; Duquesnoy, Rene J.; Camitta, Bruce M.; Tomasulo, Peter A.

doi: 10.1002/ajh.2830080310pmid: 7416162

Congenital neutropenia (CN) was diagnosed in a five‐month‐old boy. A variety of studies was performed to define the pathogenesis of his disease. Opsonic antineutrophil antibodies were present in his serum. Transfused normal granulocytes circulated poorly. Incubation of the patient's serum with normal granulocytes failed to alter their metabolic or functional activity. The patient's marrow demonstrated increased numbers of colony‐forming units (CFUs) in vitro compared with control marrow. The patient's parents had low marrow CFU activity. The patient's serum and peripheral lymphocytes failed to inhibit normal marrow CFU activity. The patient's marrow did inhibit CFU growth of an HLA‐identical‐sibling's marrow in coculture. Histocompatibility studies demonstrated the HLA‐B12 antigen in this patient, a histocompatibility marker previously associated with CN. These studies suggest some cases of CN are associated with a genetically transmitted marrow factor capable of suppressing myelopoiesis in normal marrow.