Platelet dysfunction in myeloproliferative syndromes

Abstract

The most common abnormality of the platelets in 43 patients with a variety of myeloproliferative syndromes was impaired or absent aggregation when stimulated with collagen and adrenaline. Eight unselected cases studied in more detail showed a normal prostaglandin synthesis pathway as evidenced by normal aggregation with arachidonic acid and the production of normal amounts of malonyldialdehyde. Mixing experiments with aspirin-tested platelets showed correction of the abnormal adrenaline and collagen responses and confirmed that the nature of the defect was different from that induced by aspirin. Stimulation of "myeloproliferative" platelets with thrombin after blocking the prostaglandin pathway with aspirin resulted in reduced aggregation, indicating either a deficiency of the storage pool of adenine nucleotides in the platelets or an abnormality of a membrane receptor for thrombin.

An abnormal pattern of multiple platelet function abnormalities and increased thromboxane generation in patients with primary thrombocytosis and thrombotic complications

“…Moreover, we have observed a similar pattern (reduced extent of PA and increased serum TXB, synthesis) in patients with unstable angina (30) where enhanced thrombin generation, assessed by elevated plasma fibrinopeptide A (a marker of thrombin generation (36)) levels was reported (37). A reduced extent of PA, particularly to epinephrine, and elevated plasma PTG levels were reported in CMPD patients (10,14,16,18,39). However, the greatly increased shape change, the enhanced serum TXB, generation and the normal one in PRP in spite of a reduced extent of PA, have not been reported as yet.…”

“…In CMPD patients, bleeding and arterial (mostly microvascular) or venous thrombosis are common complications (1)(2)(3)(4)(5)(6)(7)(8) where mechanisms are still unclear. Qualitative functional platelet abnormalities frequently observed in CMPD patients (1,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) have been correlated with these complications (8,13,19). Such abnormalities encompass decreased platelet aggregation (PA) to adenosine diphosphate (ADP), collagen and particularly epinephrine (14,15,18) and acquired storage pool disease (16) as well as platelet hyperfunction indicated by enhanced PA (4,13), increased levels of plasma P-throm-boglobulin (PTG) (15,17) and shortened platelet survival time (1 5).…”

“…Qualitative functional platelet abnormalities frequently observed in CMPD patients (1,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) have been correlated with these complications (8,13,19). Such abnormalities encompass decreased platelet aggregation (PA) to adenosine diphosphate (ADP), collagen and particularly epinephrine (14,15,18) and acquired storage pool disease (16) as well as platelet hyperfunction indicated by enhanced PA (4,13), increased levels of plasma P-throm-boglobulin (PTG) (15,17) and shortened platelet survival time (1 5). In addition, molecular and morphological abnormalities including a decrease in a adrenergic and PGD, receptor sites (21,22), number of a granules and dense bodies or in the concentration of glycoprotein I (1) were reported.…”

Differential regulation of metalloprotease steady‐state mRNA levels by IL‐1 and FGF in rabbit articular chondrocytes

“…These growth factors, when added alone, did not induce any enzyme synthesis [12][13][14][15]. The rnetalloproteases are synthesized as precursor proteins and require activation [1][2][3][4], but very little is known about the early postreceptor events that lead to the induction of the enzymes. We were particularly interested in understanding the similarities and differences between the induction of metalloproteases by IL-I, either alone or in combina-ties with fibroblast growth factor (FGF).…”

Platelet function in myeloproliferative disorders: Characterization and sequential studies show multiple platelet abnormalities, and change with time

“…Bleeding and thrombosis are common complications in patients with myeloproliferative disorders (MPD), sometimes occurring sequentially in the same patient during the course of the disease. Qualitative platelet abnormalities are frequently found in these patients and range from platelet hypofunction as demonstrated by defective in vitro platelet aggregation (1)(2)(3), acquired storage pool disease (4, 5 ) and/or platelet membrane defects (6,7), to abnormalities suggesting increased platelet reactivity by exhibiting enhanced platelet aggregation (8-lo), increased plasma B thromboglobulin levels (2,7,11) or shortened platelet survival (2).…”