Circulating heparan sulfate proteoglycan anticoagulant from a patient with a plasma cell disorder.

A woman, aged 68, with multiple myeloma (immunoglobulin[Ig]A kappa type) developed an anticoagulant with properties suggestive of heparin. The anticoagulant prolonged the thrombin time but not the reptilase time and was resistant to boiling, proteolytic enzyme digestion, and trichloracetic acid precipitation. The thrombin time was corrected by the addition (in vitro) of protamine sulfate or the addition of purified platelet Factor 4 (PF4) to the plasma. The anticoagulant was isolated by PF4-Sepharose affinity chromatography and analyzed in terms of its molecular weight, uronic acid, and amino acid composition. The proteoglycan isolated had a mol wt of 116,000 and appears to consist of two 38,000 dalton polysaccharide units interconnected by peptide material totaling 39,000 daltons. Electrophoretic analysis of the pronase digested peptidoglycan using the lithium acetate-agarose technique suggested the material was of the heparan sulfate type. The peptidoglycan had about one-tenth the specific activity of commercially available heparin on a weight basis. The isolated proteoglycan was indistinguishable from commercial heparin when analyzed in terms of its ability to act as a cofactor in the antithrombin III inhibition of thrombin.

Myeloid, erythroid, and immune system defects in a family. A new stem-cell disorder?

Four of six siblings, offspring of Sicillian first cousins, developed a clinical disorder in early adulthood affecting the hematopoietic and immunoglobulin-producing systems. A female sibling died at age 21 with myeloid aplasia and agranulocytosis. A male sibling, at age 17, presented with erythroid and plasma cell aplasia with hypogammaglobulinemia. Two other female siblings, ages 21 and 35, had a lymphoproliferative disorder associated with hypogammaglobulinemia. In two of the affected subjects there was complete absence of the enzyme leukocyte alkaline phosphatase. Electron microscopic studies of the peripheral leukocytes from these two subjects and from one of the two asymptomatic siblings showed curious intranuclear and intracytoplasmic linear "crystalloid" structures in the mature neutrophils. It is postulated that the family contains a genetic defect, transmitted as an autosomal recessive by the heterozygous parents, that produces a stem-cell disorder manifested by myeloid, erythroid, and plasma cell aplasias, unique electron microscopic findings, and morphologic and functional abnormalities in later generations of cells.