ABSTRACT
Combined severe deficiencies of blood clotting factors IX and X were observed in 2 patients who suffered from systemic amyloidosis. This unique deficiency state was marked by refractoriness to Vitamin K as well as to transfusion therapy. Increased antithrombin activity was present in both individuals and corresponded in time to the emergence of a monoclonal IgG kappa light chain paraprotein in 1. Both patients demonstrated profound bleeding disorders. It is hypothesized that the Vitamin K dependent factors have special affinity for amyloid deposits due to an unusual amino acid (gamma-carboxyglutamic acid) present in these factors.
Subject(s)
Amyloidosis/complications , Blood Coagulation Disorders/complications , Factor X Deficiency/complications , Hemophilia B/complications , Hypoprothrombinemias/complications , Adult , Amyloidosis/pathology , Blood Coagulation Tests , Factor X Deficiency/pathology , Female , Hemophilia B/pathology , Humans , Middle AgedSubject(s)
Disseminated Intravascular Coagulation/etiology , Trypanosomiasis, African/complications , Adult , Anemia, Hemolytic/etiology , Botswana , California , Complement System Proteins/analysis , Coombs Test , Environmental Exposure , Hematocrit , Humans , Immunoglobulins/analysis , Male , Suramin/therapeutic use , Trypanosomiasis, African/blood , Trypanosomiasis, African/drug therapyABSTRACT
Hemoglobin C is less soluble than hemoglobin A in red cells, in hemolysates, and in dilute phosphate buffer. Its relative insolubility may be explained by electrostatic interactions between positively charged beta6-lysyl groups and negatively charged groups on adjacent molecules. Red cells from patients with homozygous hemoglobin C (CC) disease exhibit aberrant physical properties which suggest that the cells are more rigid than normal erythrocytes. They pass through membrane filters less readily than normal red cells do, and their viscosity is higher than that of normal cells. Differences from normal cells are exaggerated if mean corpuscular hemoglobin concentration (MCHC) is increased, by suspension in hypertonic salt solution. Increased rigidity of CC cells, by accelerating their fragmentation, may be responsible for formation of microspherocytes. These small dense cells are exceptionally rigid, and probably are even more susceptible to fragmentation and sequestration. Rigidity of CC cells can be attributed to a "precrystalline" state of intracellular hemoglobin, in which crystallization does not occur, although the MCHC exceeds the solubility of hemoglobin in hemolysates.
