Management of pregnancy in women with antithrombin III congenital defect: report of four cases.

Four pregnant women with antithrombin III congenital deficiency underwent thrombosis prophylaxis including oral anticoagulants administered from the 16-18th week to the 36-37th week of pregnancy, subcutaneous heparin before the 16-18th week and after the 36-37th week, and a single infusion of AT III concentrate in the peripartum period in order to obtain a minimal level of 0.8 U/ml of AT III functional activity. The level of circulating AT III after the concentrate infusion needs to be evaluated by functional methods, because of a consistent amount in the concentrates of inactive AT III immunoreactive material. No thrombotic or haemorrhagic complication occurred after starting prophylaxis in any woman either in any newborn.

Further characterization of a pathological isoantithrombin with no affinity for heparin (antithrombin III Roma).

A molecular antithrombin III variant (Antithrombin III Roma) with an abnormal pattern of crossed immunoelectrofocusing was further investigated in order to identify the pathological isoforms. AT III crossed immunoelectrofocusing of the whole plasma from the affected patients showed a loop overlapping the peak normally present at pH 4.8-4.6. Affinity chromatography demonstrated the presence of an AT III fraction totally lacking in heparin affinity. Crossed immunoelectrophoresis on heparin-agarose (H-CIE) and crossed immunoelectrofocusing (CIEF) runs performed on the fractions obtained by heparin-agarose affinity chromatography confirmed that the functional defect was exclusively related to the pathological isoantithrombin (pH 4.8-4.6), which was also devoid of any progressive activity. The AT III fraction with normal affinity to heparin displayed H-CIE and CIEF patterns identical to the control AT III.

Antithrombin III Pescara: a defective AT III variant with no alterations of plasma crossed immunoelectrophoresis, but with an abnormal crossed immunoelectrofocusing pattern.

An abnormal AT III variant was found in five members from a family where a high incidence of thromboembolism occurred. In all the affected subjects AT III antigen concentration was normal, whereas antithrombin and antifactor Xa progressive activities as well as heparin cofactor activities were low. Crossed immunoelectrophoresis performed either in absence or in presence of heparin showed a normal plasma pattern. Further chromatographic investigations showed a normal affinity to heparin. An abnormal plasma pattern was evidentiated by crossed immunoelectrofocusing throughout all the AT III pH range. These data are consistent with the presence of an abnormal AT III variant with a defective binding to serine proteases and clearly identifiable only by crossed immunoelectrofocusing. This variant appeared different from the other qualitative AT III defects so far described and was named 'Antithrombin III Pescara'.

Effect of oral anticoagulant treatment on plasma and serum antithrombin III: a study on 172 patients at different levels of anticoagulation.

Antithrombin III (AT III) functional levels are much lower in serum than in plasma; during oral anticoagulation this difference is reduced. Plasma and serum of 172 patients taking vitamin K antagonists were tested for AT III antigen and both AT III heparin cofactor and anti-Xa heparin cofactor. Crossed immunoelectrophoresis of AT III on heparin-agarose was also carried out in plasma and serum. The patients were divided into four groups: (1) international normalized ratio (INR) 9.3-4.1, n = 25; (2) INR 4.0-2.5, n = 73; (3) INR 2.4-2.0, n = 40, and (4) INR 1.9-1.5, n = 34. 66 healthy subjects were used as controls. Plasma levels of AT III antigen, AT III heparin cofactor, and anti-Xa heparin cofactor were the same in all groups. In all groups all serum AT III parameters were higher than in controls; crossed immunoelectrophoresis of AT III on heparin-agarose indicated that this finding was due to a lower formation of complexed AT III in serum. AT III heparin cofactor serum values were the same whatever the INR over a large range (9.3-1.5); the highest anti-Xa heparin cofactor serum levels were noted in the groups treated more intensely (groups 1 and 2).

[Neurological complications of acute myeloid leukemia in adults]. / Le complicanze neurologiche in corso di leucemia mieloide acuta nell'adulto.

Neurological involvement in acute myeloid leukaemia has become more common in recent years. The increase seems to be related to the longer survival rates made possible by more intensive treatment protocols. The predictive elements appear to be the tumour mass, cytomorphological variety M5, splenomegaly and serum LDH. Prophylaxis with craniospinal radiotherapy or spinal chemotherapy does not modify the course of the leukaemia or diminish the frequency of neuromeningeal complications. Six cases of AML involving the central nervous system were examined, two at onset and 4 at first relapse. Neuromeningeal complications are to be feared since they are extremely difficult to eradicate completely and the prognosis is extremely unfavourable especially if a bone marrow relapse occurs simultaneously.