Heterogeneity of the "Classical" Antithrombin III Deficiency

Abstract

SummaryWe investigated two thrombophilia families with the "classical" type of antithrombin III deficiency, i.e., with a low antithrombin III level measured both by immunochemical and functional methods.We obtained different antithrombin III patterns in the plasma of the affected members of the two families with the modified two dimensional immunoelectrophoresis method (heparin in agarose). In one family, the electrophoretic mobility of the antithrombin III is identical with that of normal antithrombin III. In the other, the antithrombin III displayed a decreased electrophoretic mobility in the heparinized agarose gel. The relatively low affinity of this antithrombin III to heparin could be directly proved by the heparin-agarose affinity chromatography, too. These two different antithrombin III patterns were observed by other investigators at different families as well.On the basis of our simultaneous observations of these two families we propose a classification of the inherited congenital antithrombin III deficiencies.

Antithrombin Budapest 3 An antithrombin variant with reduced heparin affinity resulting from the substitution L99F

“…This would be consistent with previous laboratory evidence that both parents were heterozygous for this AT variant and would suggest consanguinity within the family. The absence of clinical thrombotic disease in the parents and other family members who appear to be heterozygous on laboratory testing [3] is consistent with the previous demonstration that thrombosis in individuab hetero~gous for heparinbinding variants is very uncommon [13].…”

Dysfunctional Antithrombin III in Sick Premature Infants

“…For some cases (8,23,25,32) a qualitative AT-111 deficiency was proposed based on the lack of correlation between AT-I11 antigen levels and AT-111 activity, similar to our observation. Others have noted an abnormal afinity for heparin and two-dimensional immunoelectrophoresis in the presence of heparin has revealed two peaks of AT-I11 (28,30,33,36). The dysfunctional AT-111 in this study appears to be an acquired, not an inherited, phenomena.…”

Phenotypic variation of human antithrombin III in normal plasma: Detection by isoelectric focusing

“…Several abnormalities of AT-III molecule were reported and their functional activities were significantly depressed (Sas et al, 1974(Sas et al, , 1975(Sas et al, , 1980Brozovib et al, 1978;Wolf et al, 1979;Williams and Murano, 1981). However, in the present…”

“…Recently, Borsodi and Narasimhan (1978) and Kera and Yamasawa (1982) have demonstrated the microheterogeneities of the purified or plasma AT-III by preparative or analytical isoelectric focusing. Several abnormalities of AT-III molecule have been reported in the cases of AT-III deficiencies (Sas et aL, 1974(Sas et aL, , 1975(Sas et aL, , 1980Brozovi6 et aL, 1978;Wolf et aL, 1979;Matsuo et al, 1979;Williams and Murano, 1981). However, up to the present day, no variation of AT-III molecule in the normal plasma has been observed.…”