Academic literature on the topic 'Thrombophilia. eng'

Patients with glomerular diseases develop a wide variety of biochemical disturbances and pathophysiologic alterations leading to overt clinical manifestations. Collectively, these abnormalities give rise to the classical syndromes of glomerular disease. The clinical abnormalities resulting from these disturbances in renal pathophysiology require management in order to minimize or avoid disabling symptoms, often referred to as symptomatic therapy. This chapter provides an introduction to and overview of these abnormalities. It then covers therapies for a variety of manifestations of primary glomerular diseases, including haematuria, oedema, hypertension, hyperlipidaemia (e.g. hypercholesterolaemia), the ‘hypercoagulable’ or ‘thrombophilic’ state, non-disease-specific strategies designed to retard the progression of renal disease (loss of glomerular filtration rate, GFR), and more.

Patients with glomerular diseases develop a wide variety of biochemical disturbances and pathophysiologic alterations leading to overt clinical manifestations (Remuzzi, 1993; Glassock et al., 1995, Remuzzi and Bertani, 1998; Schrier and Fassett, 1998; Vaziri, 2003; Floege and Feehally, 2007; Kim et al., 2007; Haraldsson et al., 2008). These occur as a direct result of injury to the capillary wall and disturbances in normal glomerular function, including loss of filtration capacity and excessive transfer of erythrocytes and/or plasma proteins from blood to tubular lumina eventuating in hematuria and/or proteinuria. Proteinuria—which is believed to be the consequence of disturbed glomerular capillary wall permselectivity (Haraldsson et al., 2008) —when substantial, can lead to hypoproteinemia and thereby to a reduction in plasma oncotic pressure. Changes in the synthesis, turnover, and plasma concentration of various proteins and lipids develop and can lead to an imbalance of pro-thrombotic and anti-thrombotic factors promoting a ‘thrombophilic’ state (Vaziri, 2003; Crew et al., 2004; Glassock, 2007) Disturbances in the renal handling of sodium chloride (NaCl) and water are often associated with edema formation and/or hypertension (Perico and Remuzzi, 1993; Schrier and Fassett, 1998). Finally, the rapid or slow loss of the glomerular filtration capacity (glomerular filtration rate, GFR) due to damage of single nephrons (perhaps mediated by filtered proteins and their reabsorption) as well as by the ‘drop out’ of functioning nephrons from the overall population of nephrons in the two kidneys is responsible for ultimate progression to end-stage renal disease (ESRD) in many, but not all, of the primary glomerular disorders (Drummond et al., 1994; Remuzzi and Bertani, 1998; Squarer, et al., 1998; Floege and Feehally, 2007). Collectively these abnormalities give rise to ‘syndromes’ of glomerular disease. These ‘syndromes’ can be arbitrarily, but usefully, grouped into five categories which may overlap to some degree; namely, the acute nephritic syndrome, rapidly progressive glomerulonephritis, the nephrotic syndrome, ‘symptomless’, haematuria and/or proteinuria, and slowly progressive ‘chronic’ nephritis (Glassock et al., 1995). The cardinal features of these syndromes and the diseases to which they are most closely associated are discussed in this monograph. This monograph will deal largely with those glomerular diseases which primarily affect the kidneys and in which the extra-renal manifestations are the consequence of the impairment or disturbance of kidney function itself (the so-called primary glomerular diseases).

Effective thrombolysis in human patients and experimental animals by tissue-type plasminogen activator (t-PA) usually requires t-PA plasma levels in the microgram range. Compared to that physiological plasma levels of t-PA are about 100 - 1000 times lower. To investigate the effects of t-PA at physiological blood levels rat studies were performed in vitro and in vivo employing highly purified recombinant single-chain t-PA (sct-PA: 500,000 IU/mg).t-PA activity in rat whole blood as assessed by dilute blood clot-lysis time (DBC-LT) was increased by addition of sct-PA as low as 3 ng/ml (20 % decr