Microvascular Information and Courses from MediaLab, Inc.

Currently, the most effective treatment for TTP is therapeutic plasma exchange (TPE). Fresh frozen plasma (FFP), preferably cryoprecipitate-poor plasma (that lacks von Willebrand factor), is used as the replacement fluid in the treatment. The exchange takes place over several days until the patient's platelet count stabilizes above 100 x 109/L.The logic of TPE is to rid the circulation of plasma containing ultra-large vonWillebrand factor (vWF) multimers. vWF is a large multimeric protein that is made by megakaryocytes and endothelial cells. It is is a key factor in platelet adhesion and also is responsible for carrying Factor VIII into the circulation. vWF binds glycoproteins Ib, IIb, and IIIa. The largest multimer is called ultra-large vWF and in normal plasma, it is cleaved into smaller fractions (necessary for balanced coagulation activity) by an enzyme processed by the gene, ADAMTS13. In patients with TTP, the enzyme activity is < 5% of normal and therefore, these ultra-large vWF molecules get into circulation, resulting in excessive platelet aggregation and microvascular thrombus formation.Therapeutic plasma exchange has decreased TTP mortality rate from 90% to 15% since the treatment first came into use as the standard primary treatment of TTP in the 1970's. TPE does not cure TTP, but it arrests the manifestations of the disease until spontaneous remission occurs.

Individuals with diabetes mellitus may excrete small amounts of albumin in the urine (microalbumin) which may signal the beginning of reduced glomerular filtration. Stabilizing the blood glucose level at this time may delay progression of diabetic nephropathy. Both type I and type II diabetes mellitus are leading causes of renal failure. Microvascular damage caused by excessive renal exposure to glucose can lead to diabetic nephropathy. By the time the urine protein level reaches the 30 mg/dL level that is necessary for detection by routine reagent strips, damage to the kidneys may have already occurred. Reagent strips are available that use a dye-binding technique rather than the traditional protein-error of indicators principle. These strips are more sensitive and specific for albumin, detecting levels as low as 8 mg/dL.Women in the last month of pregnancy may develop proteinuria as the first sign of impending eclampsia. Eclampsia is the gravest form of toxemia of pregnancy. The presence of protein in this situation must be evaluated by the physician in conjunction with other clinical symptoms.Benign transient proteinuria may be the result of: exposure to cold, strenuous exercise, dehydration, and/or high fever. Benign transient proteinuria may also occur during the acute phase of a severe illness. Patients over the age of 60 have a greater chance of having protein in their urine. Occult malignancies and glomerulonephritis, that occur more frequently in the elderly, may be signaled by the presence of proteinuria. Orthostatic proteinuria is a condition seen most often in young adults. The condition may be caused by pressure on the renal nerve. When this condition is suspected, two urine specimens are tested. One specimen is collected upon arising in the morning, and the second is collected several hours later. When this condition is present, the first morning specimen, after the patient has been in a supine position, will be negative for protein. The second specimen, taken after the patient has been upright for several hours, would be positive for protein.

The diabetic patient is at risk for many serious complications and often experiences a diminished quality of life. Angiopathy, damage to basement membranes of vessels, injures the linings of blood vessels and leads to microvascular and macrovascular damage.

Screening for early occurrence and low amounts of albumin in urine detects microvascular disease before impaired renal function and insufficiency occur. Regular screening of urinary albumin excretion (UAE) is recommended for individuals with both type 1 diabetes and type 2 diabetes as an early indicator of renal disease. It is recommended at the time of initial diagnosis and annually thereafter for patients with type 2 diabetes, and commencing annually 5 years after the initial diagnosis of type 1 diabetes. Control of blood pressure and blood glucose concentrations can slow the rate of renal function decline.