When blood is thinner than water.

Antagonists of vitamin K dependant clotting factors are commonly used as treatment/prophylaxis for anticoagulation. Due to their narrow therapeutic window, a wide range of complications including death may occur. International normalized ratio (INR) is monitored to measure adequacy/excess of anticoagulation. There is a plethora of risk factors that may contribute to the uncontrollably high INR values. We describe our experience of a case of deep venous thrombosis wherein the patient had an overshoot of INR during anticoagulation therapy. We review the literature and discuss management in such scenarios.

Treatment of acute infectious purpura fulminans with activated protein C.

Infectious purpura fulminans is associated with high mortality and morbidity despite standard antimicrobial therapy. We report satisfactory clinical outcome in two children with sepsis associated purpura fulminans who were treated with activated protein C (APC). There is need for proper evaluation of the efficacy of this extremely expensive therapeutic modality by randomized controlled trials before it is made standard of care in childhood infectious purpura fulminans.

Comparing the effect of two different hormonal therapy regimens on the activity coagulation factors VII, VIII, IX and serum lipids in menopausal women

During extrinsic coagulation pathway, a complex is developed between factor VII, calcium and tissue factor [a cell membrane lipoprotein that is exposed after cell injury]. Factor VII needs calcium and vitamin K for its biologic activation. Coronary artery disease [CAD] can be induced by increased level and activity of the coagulation factors VII, VIII and IX. In postmenopausal women, estrogen decreases blood lipids and thereby decreases risk of CAD. However, the exact effects of the estrogen on the other predisposing factors of CAD are unknown. This study was conducted to evaluate the effects of oral hormone therapy regimen on fibrinogen and other coagulation factors. Sixty menopausal women with history of hysterectomy were randomly allocated in 2 groups. One group was treated with conjugated estrogen 0.625 mg/day and the other group was treated with conjugated estrogen 0.625 mg/day and medroxyprogesterone 2.5 mg/day. Serum fibrinogen level and activity of coagulation factors VII, VIII and IX and blood lipids level were checked before and 3 months after treatment. In the group treated with estrogen alone, mean factor VII activity showed significant increase 3 months after treatment as compared to before hormone therapy [P<0.05]. There were no significant changes in mean activities of coagulation factors VIII, IX and serum fibrinogen level in patients treated with estrogen or estrogen/medroxyprogesterone after treatment [P>0.05]. In both groups, hormone therapy significantly decreased serum cholesterol level and LDL-C and increased HDL-C [P>0.00], but serum triglyceride level increased in the group only treated with estrogen. Significant increase of coagulation factor VII and serum triglyceride in estrogen-treated patients is logical. This study confirms that hormone therapy with this protocol does not change mean serum fibrinogen levels and activity of coagulation factor VIII and IX. This may be a genuine finding or may be due to inadequacy of samples, given the wide normal range of coagulation factors and serum fibrinogen. Studies with more prolonged follow-up or more samples are warranted

Effect of oral contraceptives [LD and cilest] on clotting factors Vlll ix

Based on epidemiologic data, women who take oral contraceptives seem to have an increased risk of developing thromboembollic disease. The thrombotic effects of oral contraceptive [OC] are probably mediated, at least partly through their effects on the coagulation system. Plasma levels of several clotting factors have been shown to be elevated in OC users, and this increase is graduated according to the dose of estrogen. In this study, fifty healthy and non smoking women, aged 18-35 years, were randomly assigned to treatment with 2 different OCs: a monophasic pill containing 30 pg of ethinyl estradiol plus 150micro g levonorgestrel [LD] and a monophasic pill containing 35micro g ethinylestradiol plus 250pg norgestimate [Cilest]. Factor VIII plasma values were significantly decreased [P<0.05] only in women treated with the preparation LD, but the levels of factor VIII were not significantly different in the group treated with Cilest. Factor IX plasma values were significantly increased [P<0.05] only in women treated with the preparation Cilest, but the levels of factor Ix were not significantly different in the group treated with LD. In LD and cilest users factors VIII and IX were not significantly changed [P<0.05] in overweight and obese subjects in comparison to normal weight

Variantes moleculares de los factores de la coagulación dependientes de la vitamina K / Molecular variantts of vitamin K-dependient coagulation factors

Se presenta una revisión de algunas características bioquímicas y funcionales de los factores de la coagulación que dependen de la vitamina K para su síntesis, así como de las variantes moleculares descritas para cada factor, las que se caracterizan por tener una actividad funcional disminuída o ausente, con una actividad antigénica generalmente normal. El estudio de algunas de estas variantes ha permitido conocer con exactitud el defecto estructural que ellas presentan y también conocer mejor la estructura de estas proteínas, sus interacciones y la función que realizan en el mecanismo hemostático