Myelodysplastic Syndromes

Thrombotic thrombocytopenic purpura (TTP) is a devastating hematologic disorder clinically characterized by the diagnostic pentad of: 1) severe microangiopathic hemolytic anemia associated with a very high serum lactic dehydrogenase (LDH) and a blood smear that typically shows schistocytes and helmet cells;
2) thrombocytopenia which is moderate to severe and in which megakaryocytes are increased in the bone marrow and peripheral platelet survival is shortened; 3) fever, which is occasionally quite high; 4) central nervous system dysfunction that may begin with transient and intermitten signs and symptoms which include agitation, headche, and disorientation, and which may progress rapidly to hemiparesis, seizures, coma, and death; 5) renal disease which is usually mild, producing only moderate elevations of the serum creatinine and urine protein.

TTP tends occur between the ages of 10 and 40 years and is slightly more frequent in women. The exact pathogenic mechanisms that are responsible for TTP are still uncertain. One hypothesis is that the primary mechanism is the release of a factor that aggregates platelets or stimulates them to aggregate and adhere to arterioles causing microvascular obstruction and damage to passing red cells. Ultimately, this produces distal ischemic effects. Another hypothesis suggests that the defect is extensive arteriolar endothelial damage which leads to subsequent platelet activation, adherence, occlusion, and fibrin strand formation ultimately producing thrombocytopenia and microangiopathic hemolysis. A third and related hypothesis is that in the chronic relapsing form of TTP, the factor VIII-von Willebrand factor (vWF) complex is in the form of unusually large multimers which may aggregate and lead to adherence and damage to the vascular endothelium. Current evidence suggests that platelet and endothelial cell derived unusually large von Willebrand factor multimers as well as the largest vWF multimers in plasma,form thrombi which are deposited in and obstruct the microvascular circulation. This would explain and support why the platelet transfusion should be avoided.

Therapeutic plasma exchange is thought to effectively remove these large multimers whereas the infusion of normal plasma may contain proteolytic enzymes that degrade large multimers to a normal size.

(From Greco F et Al., "Apheresis" ,S.Chiara Hospital - Pisa)

But plasma eschange is rejected from Jehovah's Witnesses. A possible solution is exchange with albumin + crystalloid solutions