Summary: The role of natural anticoagulants, fibrinolytic cascade factors and common prothrombotic gene polymorphisms in modulating disease severity were studied in 35 ‘clinically mild’ and 37 ‘clinically severe’ haemophilia patients with severe factor VIII or IX deficiency (<0·01 IU/ml). Strong association of deficiencies of proteins C and S, antithrombin III, tissue factor pathway inhibitor and tissue plasminogen activator, together with factor V Leiden and endothelial protein C receptor 23 bp insertion polymorphisms were observed in the ‘clinically milder’ group as compared with the ‘clinically severe’ group. These results indicate a synergistic modulation of bleeding tendency in haemophilia patients by factors in the anticoagulant and fibrinolytic systems.

Glanzmann's thrombasthenia is an autosomal recessive disorder, rare in a global context, but a relatively more common platelet function defect in communities where consanguineous marriages are more frequent. On clinical grounds alone, it cannot be distinguished from other congenital platelet function defects. Epistaxis, gum bleeding, menorrhagia are the common clinical manifestations, whereas large muscle hematoma or hemarthrosis seldom occur in these patients. Essential diagnostic features are a normal platelet count and morphology, a greatly prolonged bleeding time, absence of platelet aggregation in response to ADP, collagen, epinephrine, thrombin and to all aggregating agents which ultimately depend on fibrinogen binding to platelets for this effect, flow cytometry, studies of GPIIb-IIIa receptors on the platelet membrane surface using monoclonal antibodies. The present review describes some of the uncommon features of the disorders and the currently available options which the treating physicians should be aware of during the management of these patients. Although by definition all patients with Glanzmann's thrombasthenia have a virtually complete failure of platelet aggregation, a number of variant forms of GT have been described in which the glycoproteins are present in normal or near normal amounts but are functionally defective. Understanding the pathophysiology of the disorder by the treating physicians is of utmost importance. Presence of high affinity platelet receptors resulting in thrombasthennia-like phenotype may require an antagonistic treatment atypical of classical GT management. It has now been established that different genetic mutations of either GPIIb or IIIa genes results in such a heterogeneity of thrombasthenia phenotype. Glanzmann's thrombasthenia is a paradigm for treating coronary artery disease patients with GPIIb-IIIa antibody and inhibitors. By using these medicines we create a temporary GT-like situation. Hence, understanding this disease is of utmost importance to the practicing cardiologist. As mutations for different variant forms of GT become known, our understanding of how GPIIb-IIIa molecules can be activated to act as a receptor for fibrinogen molecules will be increased. Such understanding undoubtedly will help us to devise better drugs with GPIIb-IIIa inhibitors. Molecular biology techniques have enabled us to equivocally detect heterozygote carriers who are clinically asymptomatic. However, there may be several laboratories in the developing world, which have no access to molecular biology techniques. Development of more robust techniques of quantitation of platelet receptors has enabled an accurate diagnosis of heterozygote carriers or an unborn fetus in the second trimester. The importance of the GPIIb-IIIa polymorphisms in carrier and prenatal diagnosis has not been properly studied. Nowadays the less direct method of PLA1 typing (determination of the levels of platelet antigen) of the foetal platelets as early as 16 weeks of intrauterine life can be used for prenatal diagnosis of GT.

Arthropathies and joint deformities in patients with severe hemophilia result in prolonged immobilization, reduced physical activity, and predispose them for osteoporosis. This can lead to an increasing tendency of bone fragility and fractures in patients after trivial trauma. The aim of this study was to find out (i) the prevalence of osteoporosis in hemophilia patients and (ii) the association of osteoporosis with hemophilic arthropathy and related restricted physical activity. In this case–control study, 50 consecutive severe hemophilia patients aged between 20 and 50 years were evaluated for osteoporosis with measurement of bone mass density (BMD) by a DEXA scan and values were compared with that of 50 sex matched normal healthy controls. Major joints of the limbs were evaluated to determine the extent of joint damage and related disability. Forty‐two patients had severe hemophilia A and 8 patients severe hemophilia B (efficient factor activity < 0.01 U/ml). BMD values (gms/cm²) of lumbar spine and left hip of the patients were significantly lower than that of controls (0.825 vs. 0.939; P < 0.0001 and 0.725 vs. 0.938; P < 0.0001, respectively). The incidence of osteoporosis (T score: −2.5 or more) was significantly higher in hemophiliacs. Incidence of fractures in adult life was also significantly higher in hemophiliacs compared to controls (12% vs. 0%). There was statistically significant correlation between joint evaluation scores and BMD of hip, but not with that of the lumbar spine. There was no correlation between Hepatitis‐C virus status and BMD of any site. This shows that development of osteoporosis is a significant problem in patients with severe hemophilia in this country. Hence appropriate preventive measures such as early treatment and adequate mobilization, exercises, encouragement to participate in sporting activities, early assessment of bone density, and administration of anti‐osteoporotic therapy is recommended. Am. J. Hematol., 2007.

Indian J Med Res, Official publication of Indian Council of Medical Research,India

The β-thalassemias and sickle cell disorders are a major health burden in India. Diagnosis and management of these disorders both in adults and in newborns using appropriate approaches and uniform technology are important in different regions of a vast and diverse country as India. In view of a National Thalassemia Control Program to be launched soon, a need was felt for guidelines on whom to screen, cost-effective technologies that are to be used as well as for establishing prenatal diagnosis programs in regional centers. Newborn screening for sickle cell disorders is in its infancy in India and uniform approaches need to be followed. Also, included are guidelines for monitoring and managing patients who are now growing older and need comprehensive care as well as management of complications of the disease.