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 greater than or equal to 6x 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 1.45x that for NZW (p = 0.001). Average WHHL mean platelet volume (MPV) was 0.94x 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 1.39x 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 micrograms/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.