Shaul Kochwa

The effect of salicylates on the hemostatic properties of platelets in man

Ingestion of 1.5 g of aspirin, but not of sodium salicylate, produced a significant prolongation of the bleeding time in six normal male subjects when compared with the effects of a placebo. Similar differences in the effect of the two drugs on platelets was also observed. Aspirin ingestion resulted in impaired platelet aggregation by connective tissue and was associated with a decreased release of platelet adenosine diphosphate (ADP); sodium salicylate had no effect on these values. In vitro, incubation of platelet-rich plasma with an optimum aspirin concentration of 0.50 mmole/liter (0.045 mg/ml) inhibited both the adhesion of platelets to connective tissue and the release of ADP as well as the secondary wave of platelet aggregation produced with ADP or epinephrine; sodium salicylate had no effect on these reactions, which were also normal in patients with von Willebrands disease. The inhibitory effect produced by ingesting a single 1.8 g dose of aspirin was detectable for 4-7 days at which time salicylate was no longer detectable in the blood, which suggested an irreversible effect on the platelet. Aspirin also inhibited the release of platelet adenosine triphosphate (ATP), but had no effect on the platelet surface charge, available platelet ATP or ADP, or the destruction of ADP by plasma ADPase. These studies lend further support to the hypothesis that ingestion of aspirin, in contrast to sodium salicylate, prolongs the bleeding time by inhibiting the release of platelet ADP, perhaps reflecting the findings in other cell systems which suggest that aspirin alters membrane permeability.

ISOAGGLUTININS ASSOCIATED WITH ABO ERYTHROBLASTOSIS

The occurrence and severity of erythroblastosis fetalis, due to maternal Rh isoimmunization, can be predicted through simple prenatal serological tests (1, 2). If Rh isoagglutinins are present in maternal serum, and if the incompatible Rh antigen is transmitted from the father, the newborn will have hemolytic disease, the severity of which is often proportional to the titer of the mothers serum Rh isoagglutinins (1, 2). In the event that the isoimmunized Rh negative mother delivers an Rh negative infant, the titer of Rh antibodies in the cord serum, except for saline agglutinins, is generally equal to the titer obtained in the maternal serum (3). For practical purposes, almost all maternal Rh isoagglutinins seem to cross the placental barrier freely, and their titration value affords guidance toward the effective management of hemolytic disease of the newborn. This has not been the case for erythroblastosis fetalis due to ABOincompatibility (1, 2). ABO erythroblastosis of sufficient severity to warrant exchange transfusion therapy for the control of hyperbilirubinemia, has a frequency equal to that of erythroblastosis due to Rh incompatibility (2, 4), and yet prenatal tests have been of little value thus far in identifying those mothers who may deliver affected infants (4). Since ABO erythroblastosis occurs often in the first incompatible pregnancy (5, 6), a reliable prenatal test would be of extreme importance in anticipating the occurrence of this disease for intelligent management. A varying proportion of maternal anti-A (a) and anti-B (,/) isoagglutinins can be demonstrated in the serum of the newborn (7, 8). Most ABO isoagglutinins cannot cross the placenta and therefore play no role in the pathogenesis of erythroblastosis. Fudenberg, Kunkel and Franklin (9)

Glycinuria, a hereditary disorder associated with nephrolithiasis

Abstract Excessive urinary glycine excretion was found in four members of a family and was associated in three members with nephrolithiasis. The glycinuria was due to a renal mechanism. Failure to reabsorb glycine was not associated with defective reabsorption of other amino acids or of phosphate or glucose. A kidney stone obtained from one of these patients was composed mainly of calcium oxalate and contained a small amount of glycine present in non-protein, non-peptide form.

A review of Rh serology and presentation of a new terminology.

The extensive accumulated literature pertaining to Rh blood group serology reveals a complexity that is to be expected in the absence of critical immunochemical data. Unfortunately the language that has been employed in scientific reports, as well as the choice of descriptive notations, has obstructed critical immunological interpretations and the opportunity to employ modern methods of dealing with large volumes of complex data. A new coding notation for Rh data has been devised to overcome these deficiencies.

Aggregation of IgG globulin in vivo: I. The hyperviscosity syndrome in multiple myeloma☆

Abstract Two patients with multiple myeloma had, at the onset of their disease, mucous membrane bleeding and retinal vascular disturbances which simulated Waldenstroms macroglobulinemia. This clinical state was related to serum hyperviscosity. Although both paraproteins were shown to be acid-dissociable IgG myeloma globulin aggregates of greater than 7S, they differed in their physicochemical properties and antigenic grouping. Serum viscosity was increased by the presence of these large molecules, not as a result of hypergammaglobulinemia per se . The combination of an expanded plasma volume, distention of vessels and interference with the formation of fibrin was probably responsible for bleeding. This type of myeloma can be distinguished from Waldenstroms macroglobulinemia by means of ultracentrifugation and immunoelectrophoretic analysis, although diagnosis may be difficult on clinical and morphological grounds. Plasmapheresis was an effective method of treatment.

Precipitating antifibrinogen antibody appearing after fibrinogen infusions in a patient with congenital afibrinogenemia

Abstract In a sixteen year old girl with congenital afibrinogenemia and rheumatic valvular heart disease an antifibrinogen antibody developed following repeated infusions of human plasma fraction I. The appearance of the antibody was associated with severe infusion reactions, an increase in plasma fibrinogen disappearance rate and skin hypersensitivity to fibrinogen. Postmortem examination revealed fibrinoid lesions of the cardiovascular system.

Afibrinogenemia in man following the bite of a rattlesnake (Crotalus adamanteus)

Abstract Described here is a fifty-one year old man in whom afibrinogenemia developed following the bite of an Eastern diamondback rattlesnake (Crotalus adamanteus). His platelet count remained within normal limits and there were only minimal decreases in other clotting factors. A single fibrinogen degradation product (FDP), detected by immunoelectrophoresis, was found in a plasma specimen obtained seven hours after the bite and identified as the slow moving fragment (D) obtained after digestion of fibrinogen by plasmin. Forty-four hours after being bitten the fibrinogen level returned spontaneously to normal and the FDP was no longer detectable. In vitro studies showed that the venom of C. adamanteus, like thrombin, converts fibrinogen to fibrin directly and has no activating effect on factors II, VII or X. Unlike thrombin, however, it does not cause platelet aggregation when added to citrated platelet-rich plasma. At high concentrations, the venom was also fibrinolytic. The combination of afibrinogenemia and a normal platelet count is in contrast to the usual findings in the defibrination syndrome. The in vitro studies suggest that the effect of the bite on the patients blood was the direct result of a venom which, like thrombin, clots fibrinogen, but does not significantly affect platelets or clotting factors.

Comparison of oral melphalan, CCNU, and BCNU with and without vincristine and prednisone in the treatment of multiple myeloma. Cancer and leukemia group B experience

A total of 361 evaluable patients with previously untreated multiple myeloma were randomized to receive oral melphalan (0.15 mg/kg/day for seven days, followed by 0.05 mg/kg/day after recovery from the nadir of the leukocytes), BCNU (150 mg/m2 intravenously every six weeks) or CCNU (100 mg/m2 orally every six weeks). All patients received a tapering six‐week course of prednisone starting at 0.8 mg/kg for the first two weeks. At week 22, one‐half of the patients were randomized to receive vincristine (1 mg/m2) and prednisone (0.6 mg/kg for seven days) every two months in addition to previous therapy. The melphalan treated patients showed a significantly higher overall objective response frequency (59%), according to Myeloma Task Force criteria, when compared to those treated with BCNU (40%) or CCNU (42%). The survivals for all patients were not statistically different for the three treatment programs. However, the good‐risk patients treated with melphalan had significantly longer survival (P = 0.02) than the equivalent patients who received BCNU or CCNU. The addition of vincristine and prednisone at week 22 did not significantly increase the percentage of subsequent objective responses or prolong the subsequent survival of any treatment group. It is concluded that oral melphalan is superior to BCNU and CCNU in producing objective responses and in prolonging survival in good risk patients. Cancer 50:1669‐1675, 1982.

Improved isolation of purified siderophilin from individual sera.

Summary A method for isolation of over 95% of siderophilin from individual serum samples was described. The final product is contaminated with only small quantities of γ globulin of β mobility.

Antihaemophilic Globulin (AHG) in Multiple Myeloma and Macroglobulinaemia

Summary Anti‐haemophilic globulin (AHG) was markedly increased in eight out of 11 untreated patients with γG myeloma, two out of eight patients with γA myeloma and two out of six patients with macroglobulinaemia.