Low Protein Z levels in patients with plasma cell neoplasms are inversely correlated with IL-6 levels.

Patients with multiple myeloma (MM) have an increased thrombotic risk, but pathogenesis remains uncertain. Low levels of Protein Z (PZ), a vitamin K-dependent plasma protein, are associated with venous as well as arterial thrombosis. The purpose of this study was to analyze PZ levels in patients with plasma cell neoplasms. PATIENTS AND METHODS: The study consisted of 64 plasma cells neoplasm patients and 42 healthy individuals. Clinical investigations included measurement of plasma PZ and IL-6 levels. RESULTS: PZ levels in patients with plasma cell neoplasms were significantly lower compared to healthy controls in the entire cohort (1392±659 vs.2010±603ng/mL, P<0.01), as well as in specific disease subgroups; symptomatic MM (1428±652ng/mL, p<0.01), smoldering MM (1437±883ng/mL, p=0.045) and monoclonal gammopathy of undetermined significance (MGUS) (1247±593ng/mL, p=0.01). PZ was negatively correlated with IL-6 levels in MM patients (r=-0.7, P<0.01). There was no significant difference in PZ levels between patients with or without thrombotic event. CONCLUSION: Plasma cell neoplasm patients have low levels of PZ. This is presumably related to the increased IL-6 production by the bone marrow microenvironment, and could have a potential role in the increased thrombotic tendency in those patients.

Blood bank protocols for large-scale civilian casualty events: experience from terrorist bombing in Israel.

Terrorist attacks in crowded places cause multiple casualties that are evacuated by quick succession to nearby hospitals. The study goals were to analyse the issues of patient misidentification and excessive blood request and to develop recommendations for the management of such episodes. A retrospective analysis of nine explosion attacks was performed. In nine consecutive events, 450 casualties were reported by the National Ambulance Service, 82 of whom (18%) died on the explosion site and 368 were admitted to nearby trauma centres. Red blood cell units were typed and cross-matched for 70 patients. Seventy-three per cent of the blood supplied over the first 24 h was administered during the first 2 h. The cross-matched/transfused ratio was 2.52 +/- 1.42, reflecting the overestimation of blood requirement in mass casualty episodes. In the mass casualty setup, blood bank personnel should be alert to a potential mistransfusion or a blood collection error. Unidentified patients are subjected to errors due to only one-digit difference in their temporary identification number. Application of the system using an additional sequential four-digit number printed in bold and large size font for patients at admission reduced the possibility of misidentification. Modern technologies, including error-reduction design wristbands, barcode-based system or radiofrequency identification tags may also increase reliability of patient identification in the mass casualty setup.

Rebound thymic enlargement on CT in adults.

The objective of this study is to report the development of thymic enlargement in adults, mainly associated with chemotherapy for malignancy. The typical CT features of this phenomenon are described. The clinical data and CT studies of 13 adult patients with newly appearing thymic enlargement on CT were reviewed. These patients were followed-up mainly for malignancy. Further follow-up CTs were studied when available. Medical records were reviewed as to the primary disease, its medical treatment and the time of initial appearance of the enlarged thymus in relation to treatment. The study group included 13 adult patients, 12 with malignant disease and one with a slowly resolving pneumonia. The enlarged thymus appeared as a triangular, arrowhead-shaped structure, with a bilobed configuration and convex borders. Density measurements were consistent with homogeneous soft tissue. Location was in the anterior mediastinum, in the normal site of the thymus. In nine patients, follow-up studies were available. The observation period ranged from 5 months to 8 years from the initial appearance of the enlarged thymus. In five of the nine patients, the thymic enlargement resolved after 1-4.5 years. In four of the nine patients, the thymus remained enlarged during a follow-up ranging from 5 months to 2.5 years. Thymic enlargement, while a rare phenomenon in adults, may occur, mainly after chemotherapy. This phenomenon should be included in the differential diagnosis of a soft tissue mass appearing in the anterior mediastinum on follow-up CT in adult patients particularly following treatment for malignancy.

H-deficient Bombay and para-Bombay red blood cells are most strongly agglutinated by the galactophilic lectins of Aplysia and Pseudomonas aeruginosa that detect I and P1 antigens.

The galactophilic lectins Aplysia gonad lectin (AGL) and Pseudomonas aeruginosa lectin (PA-IL), which detect human I and P1 RBC antigens, were examined for hemagglutination of H+ (group O and B) and H-deficient (Bombay and para-Bombay phenotype) RBCs. The results were compared with those obtained using two other galactophilic lectins, Maclura pomifera lectin (MPL) and Arachis hypogaea (peanut) agglutinin (PNA), which share T-antigen affinity, and two fucose-binding H-specific lectins, Ulex europaeus (UEA-I) and Pseudomonas aeruginosa lectin (PA-IIL), as well as with those achieved with anti-I serum. The results revealed that, in contrast to UEA-I and PA-IIL, which preferentially agglutinated H+ RBCs, and to MPL and PNA, which similarly agglutinated all examined RBCs, AGL, PA-IL, and the anti-I serum agglutinated the H-deficient RBCs more strongly than did the H+ RBCs. These findings could be attributed to increased levels of I and P1 antigens on those RBCs resulting from the use of the free common H-type 2 precursor for their synthesis. Since both PA-IL and PA-IIL are regarded as potential pathogen adhesins, it would be interesting to statistically compare the sensitivities of individuals of H+ and H-deficient RBC populations to P. aeruginosa infections.

Persistent anti-Dra in two pregnancies.

The Drori (Dr(a)) antigen is one of the ten high-prevalence antigens of the Cromer blood system, which are carried on decayaccelerating factor (DAF, CD55). The Dr(a-) phenotype was first described in a 48-year-old Jewish woman from Bukhara. Her serum contained an antibody to a high-prevalence antigen named anti-Dra. Most known individuals with the Dr(a-) phenotype are Jews from the geographic area of Bukhara, but individuals from Japan have also been described. Antibodies in the Cromer blood group system, including anti-Dra,have never been reported to cause HDN. In most of the cases with anti-Dra examined in Israel, the antibodies have been subtyped as IgG2 and IgG4. This report is of a woman with Dr(a-) phenotype and an anti-Dr(a) titer of 256 to 512 in her serum, observed during two successive pregnancies. At birth, the RBCs of the first- and second-born child were negative and positive in the DAT, respectively, and neither manifested clinical signs of HDN. The disappearance of Cromer system antibodies, including anti-Dra in midpregnancy, has been described in a previous study. In that study, it was theorized that the antibodies in the serum of the women were adsorbed onto placental DAF. The finding of a high anti-Dra titer in two successive pregnancies in this patient, with a positive DAT for the RBCs of one of the two babies at term, differs from published reports, suggesting that a different mechanism might be involved.

Factor VII deficiency in a patient with retinal arteriolar tortuosity syndrome.

PURPOSE: To report a pedigree with hereditary retinal arteriolar tortuosity with macular haemorrhage and abnormality of the coagulation system. METHODS: Case report and literature review. RESULTS: A 49-year-old woman was referred due to macular haemorrhage in both eyes. Her 16-year-old son had recurrent retinal haemorrhages which presented at age 16 years and had mild retinal arteriolar tortuosity. Coagulation studies in the son revealed normal activated partial thromboplastin time (APTT), prolonged prothrombin time (PT) and 30% activity of factor VII. CONCLUSIONS: Factor VII deficiency may aggravate the haemorrhages in retinal arteriolar tortuosity syndrome. We therefore suggest conducting routine coagulation studies (PT, APTT) in all patients with retinal arteriolar tortuosity syndrome. Determination of factor VII activity is warranted only in patients with normal APTT and prolonged PT.

Enhanced generation of monocyte tissue factor and increased plasma prothrombin fragment1+2 levels in patients with polycythemia vera: mechanism of activation of blood coagulation.

Polycythemia vera (PV) is associated with a high incidence of thrombosis. The association of apparent and secondary polycythemia with thrombosis is not clear. It was suggested that activation of the coagulation system contributes to thrombus formation in PV. However, the mechanism of activation is unknown. Monocytes generate a potent tissue factor (TF) upon stimulation with various substances, which is involved in thrombus formation in various disorders. Therefore, we studied the possibility that the factor is involved in the activation of coagulation and thrombus formation also in PV. Unstimulated peripheral blood mononuclear cells (PBMC) from each of the different types of polycythemia expressed weak TF activity (2 U) and antigen (41.4 to 52.9 pg/ml), which were similar to normal controls. Following stimulation with endotoxin, PBMC from normal controls and from apparent and secondary polycythemia showed a 3.9- to 4.5-fold increase in TF, while cells from PV showed a 21-fold increase (P<0.001). Similar levels were generated by PBMC after treatment of PV and at the spent phase. TF was generated by monocytes but not by lymphocytes. Plasma prothrombin fragment1+2 (F1+2) levels, assayed at the same time, were significantly higher in PV (2.46 nm) compared to normals and apparent and secondary polycythemia (0.22 to 0.32 nm), and were in a significant correlation with monocyte TF activity and antigen levels (r = 0.77, 0.87). The high levels of F1+2 confirm that the coagulation system is activated in PV. The increased capacity of monocytes to generate TF may be responsible for the activation of the coagulation system and thrombus formation. The hypercoagulability state that is induced by this mechanism suggests that long-life oral anticoagulation should be considered once thrombosis has been developed in PV.

Benign familial microcytic thrombocytosis with autosomal dominant transmission.

Familial thrombocytosis is an extremely rare disorder, so far reported in only a handful of families. In the majority of cases the characteristics were of essential thrombocythemia. Most patients presented with a platelet count above 800,000/mm3, were diagnosed as having a myeloproliferative disease, and some required chemotherapy. We describe a benign form of familial thrombocytosis with autosomal dominant inheritance in five healthy members of three generations of a family, all of whom had moderate thrombocytosis within the range 422,000-662,000/mm3, characterized by low mean platelet volume. A careful medical history and a 5-year follow up of the subjects did not reveal any untoward clinical development. This variant of familial thrombocytosis is therefore of a benign nature. Possible mechanisms linking thrombocytosis with platelet microcytosis in this family are discussed.