Microcytic thrombocytosis, small megakaryocytes, platelet lipids and hyperreactivity to collagen, lymphocytopenia, eosinophilia, and low blood volume in genetically hyperlipidemic rabbits

Three- to 15-month-old rabbits with Watanabe heritable hyperlipidemia (WHHL) were tested to determine if hematological abnormalities would accompany the known hyperlipidemia and deficiency of receptors for low-density lipoprotein; the findings were compared to those of New Zealand white (NZW) rabbits of the same ages. WHHL plasma cholesterol and triglyceride levels were always ≥6 x those of NZW, and both were lower in older than in younger WHHL rabbits. From age 7 to 18 months, WHHL platelet counts were higher than those of age-matched NZW; the average for all WHHL was 1.45 x that for NZW (p = 0.001). Average WHHL mean platelet volume (MPV) was 0.94 x that for NZW (p = 0.025), with a tendency for greater microcytosis to occur at more advanced ages; electron microscopy supported the small size of WHHL platelets. WHHL platelet mass per microliter of blood (platelet count x MPV) was 1.39 x that of NZW (p = 0.001), with differences occurring after the age of 6 months. The average WHHL blood volume was 18.3% less than in NZW (33.5 vs 41.0 ml/kg body weight) (p = 0.00005), so platelet count and mass per kilogram of body weight were similar in the two strains. The predominant ploidy of mature megakaryocytes from each strain was 32N; megakaryocytes were smaller in WHHL than NZW due to a smaller size of 32N cells (p = 0.002). Total leukocyte counts were the same in WHHL and NZW rabbits, but eosinophils were 32% higher (p = 0.037) and lymphocytes 34% lower (p = 0.008) in WHHL. Hematocrits and reticulocytes did not differ. Platelet-free cholesterol was 1.2x, esterified cholesterol 11.3x, phospholipids 0.9x, triglyceride 2.4x, and free cholesterol/phospholipid molar ratio 1.29x corresponding values in NZW platelets. WHHL platelets released more serotonin in response to a small dose (5 μg/ml) of collagen than did NZW platelets. These findings suggest that: 1) megakaryocytopoiesis and leukopoiesis are affected by lipid metabolism and/or LDL receptors, and 2) platelet production may be regulated more by the total mass of platelets than by their concentration in the blood.