Joel L. Moake

Telangiectasia and von Willebrand's Disease in Two Families

Two families are described with members who have both von Willebrands disease and telangiectasias. Family A has four members in three consecutive generations that have both von Willebrands disease and telangiectasias. von Willebrands disease in this family is characterized by decreased ristocetin cofactor (FVIII-vWF), variably depressed factor VIII coagulant (FVIII-AHG), and factor VIII-related antigen (FVIII-AGN) levels. FVIII-AGN mobility on two-dimensional crossed immunoelectrophoresis was found to be normal. Four generations in Family B have von Willebrands disease characterized by decreased FVIIII-AHG, FVIII-vWF, FVIII-AGN, and prolonged template bleeding times. Two members of this family also have telangiectasias and recurrent gastrointestinal bleeding. Results in these two families suggest an association between von Willebrands disease and telangiectasia--perhaps a defect in vascular endothelial cell function.

Intravascular Hemolysis, Thrombocytopenia, Leukopenia, and Circulating Immune Complexes after Jejunal-Ileal Bypass Surgery

Two years after jejunal-ileal bypass surgery for obesity, a 25-year-old man developed intravascular hemolysis, thrombocytopenia, and neutropenia. The patients erythrocytes were coated with complement components (C4/C3) and his serum induced complement-dependent immune lysis of chromium-51-labeled platelets. Serum [125I]-C1q binding activity (a measure of the presence of immune complexes) was increased, and serum C4 and C3 hemolytic titers were depressed. Immune complex-mediated complement activation apparently accounted for the blood cell destruction in this patient.

Dynamic Rheological Studies of Coagulation and Fibrinolysis

A Weissenberg rheogoniometer in the oscillatory mode was employed to determine the effect of fibrinolysis and fibrinogen degradation products (FDP) on the development of the dynamic shear moduli in coagulating platelet‐free plasma (PFP) and platelet‐rich plasma (PRP). While the FDP produced by incubation of PFP for 3 min with streptokinase (SK) increased the maximum  shear storage modulus (Gmax′) of PFP, these early FDP decreased the Gmax′ of PRP clots significantly. The FDP produced at longer incubation periods reduced the Gmax′ of PRP clots also. The decreased Gmax′ in PRP containing FDP appears due to FDP inhibiting the binding of polymerizing fibrin to the platelet membrane. While 10 μ/ml of SK did not produce FDP or induce significant fibrinolysis, clot lysis was complete and rapid in the presence of 20 μ/ml SK. Experiments with crosslinking inhibitors indicate that poorly crosslinked clots are more susceptible to fibrinolysis. In addition, a model for coagulation is presented which accurately fits t...

Effects of colchicine and vinblastine on platelet contractility and release

Pre-incubation of normal platelet-rich plasma for 30 minutes at 37 degrees C with concentrations of colchicine (2.5 x 10(-4)M) or vinblastine (1.1 x 10(-4)M) which disrupt platelet microtubles did not inhibit aggregation induced by ADP or collagen. Even following pre-incubation of platelets with a 10-fold higher concentration of colchicine (2.5 x 10(-3)M), platelets released 14C-serotonin and aggregated in response to collagen. In the presence of a 10-fold higher vinblastine concentration (1.1 x 10(-3)M), platelets lysed and released 51Cr. Dynamic viscoelastic measurements on recalcified platelet-rich plasma in a Weissenberg rheogoniometer demonstrated that neither colchicine (2.5 x 10(-4)M to 5 x 10(-3)M) nor vinblastine (1.1 x 10(-4)M) interferes with the initiation, rate of generation, or extent of contractile force produced in platelet-fibrin clots. These results indicate that polymerized tubulin is not essential for collagen-induced release of platelet dense granule contents. In addition, intact tubulin polymers are not required to support the platelet surface configuration necessary for platelet-fibrin adherence and the platelet contractile events which result in platelet-fibrin clot retraction.