Karl landsteiner and his major contributions to haematology

Karl Landsteiner was born in Vienna in 1868. He graduated from the Vienna Medical School in 1891, which dominated one of his most productive and formative periods in the following years. Although he devoted himself to research in bacteriology, haematology and immunology, he tried to maintain a close relationship with clinical medicine. Landsteiner’s intellectual curiosity was centred on fundamental questions about the specificity of antisera directed against various antigens. His research with chemically modified proteins also led to the concept of the specificity of serological reactions, defined in his classical book on this subject. The attachment of small organic molecules to proteins, which in 1921 he called ‘haptens’, was the foundation for future immunological research into the nature of antibody-combining sites, antigenic determinants and antibody–antigen binding forces. In 1930, Landsteiner was awarded the Nobel Prize for his description of the human ABO blood group system, which he himself considered an accidental discovery. Karl Landsteiner discovered human blood groups in 1900 and laid the foundation for the modern medical practice of blood transfusion. The ABO blood groups have a role in physiology beyond their importance for blood transfusion. In the past few years, red cell antigens (A and B carbohydrate structures) have been found on a variety of cells, tissues and proteins, indicating that these antigens might be involved in different physiological processes. The blood group O has an edge in Darwin’s concept of the survival of the fittest because it confers protection from vascular diseases. Many studies have established a relationship between the ABO blood groups and the risk of coronary heart disease, atherosclerosis and venous thrombosis (Souto et al, 2000). Hypercoagulation is a risk factor for vascular diseases. It can be caused by excessive concentrations of proteins whose function is to maintain haemostasis. Such proteins include factor VIII (FVIII) and von Willebrand factor (VWF). Lower concentrations of VWF and FVIII are found in the circulation of people who have blood group O than in those with blood group A, B or AB (Souto et al, 2000). The mean VWF antigen concentration is 25% lower in blood group O than in other blood groups (Moeller et al, 2001; O’Donell & Laffan, 2001). This often leads to diagnostic difficulties in distinguishing mild forms of the inherited bleeding disorder, type I von Willebrand’s Disease (VWD), from a healthy blood group O (Nitu-Whalley et al, 2000). Plasma phenotypes differ between OO and non-OO genotypes. Recently a link was found between the ABO gene locus and the VWF antigen concentration, and one was suggested between the ABO gene locus and FVIII coagulation activity (Souto et al, 2000). Blood groups influence the VWF antigen level not only in normal subjects but also in heterozygous VWF-deficient subjects who have a null allele with certain missense mutations in the VWF gene. The heterogeneity of plasma phenotypes in heterozygous carriers for type 3 VWD might be due to blood groups (Castaman & Elkenboom, 2002). Von Willebrand factor is a large multimeric glycoprotein that is synthesized in endothelial cells and megakaryocytes. It has a dual role in haemostasis. In primary haemostasis, VWF is essential for the adhesion of platelets to sites of vascular injury. In its second role, VWF is crucial to intrinsic coagulation because it binds to the amino-terminal part of FVIII and preserves it in the circulation (Schwarz et al, 2002). Mature VWF is heavily glycosylated, containing 12 ASN-linked 10 Ser ⁄Thr-linked oligosaccharide chains. The N-linked oligosaccharide chains contain the ABO blood group antigens (Matsui et al, 1993; Sarode et al, 2000). Studies on ABO-mismatched bone marrow transplantations indicate that platelet-derived VWF synthesized in megakaryocytes does not contain these blood group antigens in contrast to the endothelial-cell-synthesized VWF found in plasma (Matsui et al, 1999). The only other known plasma proteins that contain ASN-linked ABO blood group antigens are alpha 2 macroglobulin and FVIII (Matsui et al, 1993). The biological function of blood group antigens on VWF and FVIII is still not clear but blood group sugar chains might influence the functional properties of VWF such as ristocetin-induced platelet agglutination or the metabolic clearance of VWF and its susceptibility to proteolysis (Sarode et al, 2000). The first description of the congenital dysfunctional state of VWF in causing bleeding was published by Erik von Willebrand (von Willebrand, 1931), 1 year after Karl Landsteiner was awarded the Nobel Prize in Physiology or Medicine for the discovery of human blood groups.