Bleeding events and associated factors in a cohort of adult patients taking warfarin in Sarawak, Malaysia.

Evidence is emerging that rates of adverse events in patients taking warfarin may vary with ethnicity. This study investigated the rates of bleeds and thromboembolic events, the international normalised ratio (INR) status and the relationship between INR and bleeding events in Malaysia. Patients attending INR clinic at the Heart Centre, Sarawak General Hospital were enrolled on an ad hoc basis from May 2010 and followed up for 1 year. At each routine visit, INR was recorded and screening for bleeding or thromboembolism occurred. Variables relating to INR control were used as predictors of bleeds in logistic regression models. 125 patients contributed to 140 person-years of follow-up. The rates of major bleed, thromboembolic event and minor bleed per 100 person-years of follow-up were 1.4, 0.75 and 34.3. The median time at target range calculated using the Rosendaal method was 61.6% (IQR 44.6­74.1%). Of the out-of-range readings, 30.0% were below range and 15.4% were above. INR variability, (standard deviation of individuals' mean INR), was the best predictor of bleeding events, with an odds ratio of 3.21 (95% CI 1.10­9.38). Low rates of both major bleeds and thromboembolic events were recorded, in addition to a substantial number of INR readings under the recommended target range. This may suggest that the recommended INR ranges may not represent the optimal warfarin intensity for this population and that a lower intensity of therapy, as observed in this cohort, could be beneficial in preventing adverse events.

Serious complications of congenital antithrombin III (AT III) deficiency in a 7-year-old girl.

A 7-year-old gypsy girl developed venous and arterial thromboembolism. In this case AT III deficiency of hereditary nature was demonstrated as the cause of thromboembolism.

The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency.

Protein C is a vitamin K dependent protein involved in blood coagulation. A congenital deficiency in protein C antigen - which inherits as an autosomal dominant disorder - has been reported to be associated with a high risk for thrombo-embolic disease at relatively young age. In the present paper we report on the development of a functional assay for plasma protein C. In this assay protein C is adsorbed to Al(OH)3, eluted and activated by thrombin, after which the concentration of the activated protein C is measured with a peptide substrate (S2366). Normal values for protein C activity and protein C antigen were determined in healthy volunteers and patients on stable oral anticoagulant treatment. Protein C activity and antigen levels were compared in 28 patients from 9 different pedigrees with both congenital protein C deficiency and thrombotic disease. Two types of protein C deficiency could be recognized: in type I the deficiency is due to the absence or reduced presence of protein C molecules, while in type II the deficiency is caused by the presence of an abnormal protein C molecule with strongly reduced functional activity.

A new type of congenital dysfibrinogenaemia with defective fibrin lysis--Dusard syndrome: possible relation to thrombosis.

Congenital dysfibrinogenaemia is described in three members of a family presenting with recurrent thrombosis and in two other young members not yet affected. An abnormality in the polymerization of fibrin monomers was noted. In addition, the pathological fibrin clots were found to be less sensitive to degradation by a post venous occlusion euglobulin solution than normal fibrin. After fibrin clot incubation with lys-plasminogen at different concentrations, the biological activity of plasminogen in patient fibrin clot on S 2251 after SK-addition, was less than that observed with normal fibrin. It is speculated that defective in vivo thrombolysis might explain the recurrent thrombosis observed in this family. This finding represents a new concept in understanding thromboembolic diseases.