Empirical treatment of febrile, neutropenic patients with tobramycin and latamoxef

One hundred and two febrile episodes in neutropenic patients were treated with intravenous tobramycin and latamoxef. After 48 h latamoxef at 6 g day-1, patients were randomized to continue this regimen or latamoxef at 3 g day-1. Infections responded to these regimens in 67% and 71% of patients, respectively. Two-thirds of the infections which failed to respond were due to coagulase-negative staphylococci in Hickman catheters, a trend which may necessitate the inclusion of additional antibiotics in future empirical regimens. Prolonged prothrombin times due to antibiotic therapy were seen in nine patients but there was only one episode of bleeding and this responded quickly to treatment with vitamin K and fresh frozen plasma. In 35 patients, coagulopathy was present before antibiotics were started, and these cases also responded to vitamin K. The study shows that the response to tobramycin and latamoxef is comparable to other broad-spectrum antibiotic regimens and that a reduction in the dose of latamoxef after 48 h treatment may safely permit cost savings.     

A high incidence of bleeding is observed in a trial to determine whether addition of metronidazole is needed with latamoxef for prophylaxis in colorectal surgery

A prospective randomized trial has compared the use of latamoxef sodium (two doses) with latamoxef and metronidazole for elective colorectal surgery. The incidence of wound infection in patients receiving latamoxef alone was 34 per cent compared with 32 per cent in patients receiving latamoxef and metronidazole. Only eight of the 36 wound infections in this study could be classified as major. Only two patients developed an intra-abdominal abscess postoperatively and there was only one episode of septicaemia. Postoperative haemorrhage was recorded in 17 patients (15 per cent). Twelve episodes of bleeding occurred in the first 97 patients who entered the trial and prolongation of the prothrombin time was recorded in eight of 16 patients. In view of these findings 10 mg vitamin K was given with each dose of latamoxef to the last group of patients. However, bleeding occurred in five of 13 patients receiving vitamin K and entry to the study was therefore discontinued.     

The effects of cefotetan disodium on haemostasis

A 7-day course of intravenous cefotetan disodium was given to nine patients. No significant changes were observed in haematological or biochemical parameters and serum vitamin K1 levels, prothrombin times, factor VII levels, thrombin times and activated partial thromboplastin times remained within the normal ranges throughout the treatment period in all patients. There was no evidence of clinical bleeding in any patient although in two the bleeding time was prolonged up to 13.0 min after 7 days' therapy. Notably, adenosine-5-diphosphate (ADP)-induced platelet aggregation responses were significantly increased (P less than 0.05) at the end of the treatment period. These data indicate that cefotetan disodium at a dose of up to 4 g daily can be used without risk of a bleeding diathesis. In situations associated with vitamin K1 deficiency, potential prolongation of the prothrombin time should be avoided by prophylactic vitamin K1 administration.     

Single-dose antibiotic prophylaxis of abdominal surgical wound infection: a trial of preoperative latamoxef against peroperative tetracycline lavage.

A randomized controlled clinical trial was undertaken in 542 consecutive emergency and elective abdominal operations, with one group of patients receiving tetracycline peritoneal and wound lavage and the other a single intravenous injection of 1 g latamoxef at induction of anaesthesia. Seventy-five patients were withdrawn because no potentially contaminated hollow viscus was opened, and a further 36 because they could not be assessed for wound infection. Of the remaining 431 patients, 212 received latamoxef resulting in 5 major and 8 minor wound infections in hospital; another 4 minor infections occurred at home (total incidence 8.0%). In the tetracycline group (n = 219) there were 7 major and 19 minor wound infections in hospital and 10 minor infections later (total incidence 16.4%). This is significantly higher than the rate with latamoxef (P = 0.012). Monitoring of operative and postoperative bleeding revealed no evidence (except in one doubtful case) of excessive bleeding associated with the use of a single dose of latamoxef. It is concluded that single-dose preoperative latamoxef is more effective than peroperative tetracycline lavage for the prevention of wound infections after potentially contaminated abdominal operations.     

Comparison of the absorption and effect on platelet function of a single dose of n-3 fatty acids given as fish or fish oil

To compare their relative absorption and effect on platelet function, concentrated fish oil and tuna were given to 10 subjects in a randomized crossover study. Although plasma enrichment of eicosapentaenoic acid (EPA) from either preparation was similar, relative absorption of EPA from tuna was significantly greater than that from fish oil (46.6 +/- 3.0 mg.L-1.g EPA-1 from tuna compared with 16 +/- 1.0 mg.L-1.g EPA-1 from fish oil, P less than 0.001). Relative absorption of docosahexaenoic acid (DHA) was equivalent (54.0 +/- 9.0 mg.L-1.g DHA-1 from tuna, 56 +/- 9.0 mg.L-1.g DHA-1 from fish oil, NS). Platelet aggregation in response to the endoperoxide analog U46619 was significantly diminished after either preparation but aggregation in response to other agonists, bleeding time, and membrane n-3 (omega-3) fatty acid content were not changed. Thus, n-3 fatty acids are well absorbed after one dose of either tuna or fish oil but EPA absorption appears to be more efficient from tuna. Additionally, a single dose of n-3 fatty acids decreases platelet aggregation by a mechanism not requiring incorporation into platelet membranes.     

Chronic consumption of raw but not boiled Welsh onion juice inhibits rat platelet function

Welsh onion has been consumed for prevention of cardiovascular disorders. To study if it has antithrombotic effects, 9-wk-old male Sprague-Dawley rats were studied. Some rats were fed raw or boiled Welsh onion juice (2 g. kg(-1). d(-1)) for 4 wk, and the remaining acted as the control. Before and after feeding, their systolic blood pressure was measured by a tail-cuff method. Two days after the treatment period, tail bleeding time, platelet function (including platelet aggregation and adhesion), plasma levels of prostaglandins, and platelet cyclic nucleotide levels were determined. In comparison to the control, raw Welsh onion juice consumption significantly (1) lowered resting systolic blood pressure; (2) prolonged the bleeding time; (3) diminished platelet adhesion on a fibrinogen-coated surface, ADP-evoked platelet aggregation and ADP-stimulated thromboxane release; (4) elevated the concentration of cyclic AMP, but not cyclic GMP, in platelets; (5) increased the plasma level of 6-keto-prostaglandin F(1alpha), the stable prostacyclin metabolite, but not the plasma nitrite level. On the contrary, boiled Welsh onion juice consumption was totally ineffective. In conclusion, consuming raw Welsh onion juice, but not boiled juice, has blood pressure lowering and antithrombotic effects in rats. These effects may be mediated by PGI(2)-cAMP pathway.     

Effect of D-003 on intravascular platelet aggregation induced with collagen in rats

D-003 is a mixture of higher aliphatic primary acids purified from sugar-cane (Saccharum officinarum L.) wax that inhibits platelet aggregation induced ex vivo by addition of agonists to platelet-rich plasma (PRP) of rats, guinea pigs, and healthy human volunteers. Because the ex vivo platelet aggregation model does not mimic properly platelet aggregation occurring inside the arteries, since all blood factors regulating the formation of a platelet aggregate or thrombus are not present in PRP, this work was undertaken in order to investigate the effects of different oral doses of D-003 on platelet aggregation induced by collagen in vivo in rats. Effects of single (5, 25, 100, and 200 mg/kg) or repeated doses (1, 5, 25, 100, and 200 mg/kg during 10 days) of D-003 on in vivo platelet aggregation in rats were studied. D-003 (5-200 mg/kg) orally administered as single or repeated doses inhibited significantly and dose-dependently collagen-induced platelet aggregation in rats. The minimal dose investigated effective in both single and repeated administration schemes was 5 mg/kg. The highest dose assessed in both cases was 200 mg/kg, causing inhibitions of 61.5% (single doses) and 74.4% (repeated doses). Thus, the effects of repeated doses were more pronounced than those obtained with single administration. The mean 50% effective dose of D-003 in both schemes was 2.3 mg/kg, which indicates a promising anti-thrombotic potential of D-003.     

Ovulation inhibition with nafarelin acetate nasal administration for six months

A group of 24 women with normal menstrual cycles were treated with nafarelin acetate administered in doses of either 125 ug or 250 ug daily intranasally for 6 months. Each subject was studied for one ovulatory control cycle, six treatment cycles, and post-treatment until the return of ovulation was documented. Once a week progesterone, estradiol, follicle stimulating hormone, and luteinizing hormone were measured in the serum. Acute hormone responses to nafarelin acetate were determined on-day 1, day 98 and day 186 of treatment.

Two subjects failed to complete the treatment phase. One subject using the 250 ug daily dose of nafarelin acetate discontinued treatment on the sixth day because of heavy uterine bleeding. One subject using the 125 ug daily dose of the study drug terminated treatment on day 126 because of a 21-pound weight gain.

There were significantly less presumed ovulatory cycles at the higher dose (2 out of 60 cycles) than at the lower dose (10 out of 54 cycles) (p<0.01). On the average menstrual cycles were reestablished 28.5 ± 8.3 (S.D.) days after discontinuing the 125 ug daily dose and 33.7 ± 17.9 (S.D.) days after terminating the 250 ug daily dose. With the higher dose of nafarelin acetate there were significantly fewer bleeding episodes, less number of days of bleeding, and longer cycles. During the treatment phase the area under the LH curve was significantly less and the acute response of LH in the last week of treatment was significantly less with the higher dose of drug. With both doses of nafarelin acotate the acute responses of LH, FSH and estradiol were significantly greater on day 1 than on either day 98 or day 186. Side effects observed during this study included galactorrhea (2 subjects) and vasomotor symptoms (7 subjects).     

In vitro effects of trace elements on blood clotting and platelet function. B--Zinc and magnesium.

The in vitro effects of zinc and magnesium salts on blood coagulation mechanism and platelet aggregation were studied on rat plasma. Addition of zinc sulphate to pooled rat plasma in a range of concentrations (0.3-1 mg/ml) caused a dose dependent significant prolongation of recalcification, prothrombin and partial thromboplastin times. These effects reached a peak after 30 minutes while the thrombin clotting time was not significantly altered and was even shortened in the presence of highest concentration of zinc tested (1 mg/ml). Incubation of thrombin with zinc sulphate (150 micrograms/ml) for up to 30 minutes did not affect significantly the action of thrombin. Incubation of the same concentrations of zinc sulphate with fibrinogen produced non clotting of fibrinogen after 0-minutes. Addition of rising concentrations of zinc sulphate to rat PRP produced inhibition of ADP-induced platelet aggregation. On the other hand, collagen-induced aggregation was insignificantly inhibited in the presence of zinc. In contrast, in vitro additions of rising concentrations of magnesium sulphate (2-5 mg/ml) to pooled rat plasma exerted no effect on recalcification time immediately after addition (0-minutes), but after 5 minutes following incubation it produced significant shortening of recalcification time in all the doses tested. The prothrombin time showed a general trend of shortening, maximal after 5-minutes incubation. The results of partial thromboplastin times revealed clotting before addition of calcium chloride. The thromboplastin time also showed progressive shortening with rising concentrations of magnesium sulphate. When thrombin solution was exposed to magnesium sulphate (2.5 mg/ml) no effect on the activity of thrombin was seen for up to 30 minutes. Fibrinogen solution similarly exposed to the same concentration of magnesium sulphate did not show any significant effect on its clottability with thrombin for up to 30 minutes. Magnesium sulphate in the range of doses tested significantly enhanced platelet aggregation of PRP in response to both ADP and collagen, and the responses observed were not dose dependent. The mechanisms underlying the effects of these two metals on blood clotting and platelet aggregation are discussed.     

High-dose immunoglobulin therapy in four patients with onyalai

Onyalai, a form of immune thrombocytopenia in Africa, has a recorded death rate of 9.8% in the acute phase due to haemorrhagic shock or central nervous system bleeding. Four patients with active bleeding and a mean platelet count of 6 x 10(9)/litre were each treated with 0.67 g/kg intravenous globulin (Sandoglobulin) daily on 3 successive days. Clinical bleeding ceased within 3 d and all patients responded with a rise in the platelet count, which peaked at 19-21 d. No side effect was recorded. Intravenous globulin therapy may reduce the morbidity of the acute phase of onyalai.     

不同负荷剂量氯吡格雷治疗急性冠脉综合征的临床应用研究

目的比较不同负荷剂量氯吡格雷在经皮冠脉介入治疗(PCI)术前应用对治疗急性冠脉综合征(ACS)的有效性和安全性,对更高负荷剂量的氯吡格雷安全性进行评估。方法120例诊断为ACS的患者随机分为A、B、C三组(na=nb=nc=40),三组患者临床基本资料差异无统计学意义(p>0.05)。A、B、C三组分别于术前6h给予600mg、450mg和300mg负荷剂量氯吡格雷,观察服药前?服药后2h、4h、6h血小板聚集率,30天主要终点事件(住院期间休克、死亡、靶血管重建、再发心梗、心绞痛、脑卒中)及术后30天出血事件和不良反应发生情况。结果与标准的300mg方案相比,氯吡格雷600mg比氯吡格雷450mg前6h内对血小板激活的抑制程度更大。氯吡格雷负荷剂量的增加可减少30天主要心血管事件的发生率。三组30天出血事件和不良事件发生情况差异无统计学意义(p>0.05)。结论与300mg氯吡格雷负荷剂量相比,较高的氯吡格雷负荷剂量能够产生更快、更强的血小板抑制,且安全性相似。     

多壁纳米碳圈对血小板聚集与止血功能的影响

目的 观察多壁纳米碳圈(MWCNOs)对大鼠血小板聚集和止血功能的影响.方法 采用Born比浊法通过体内和体外试验测定MWCNOs对大鼠血小板聚集的影响.(1)体外试验:测定溶剂和不同剂量MWCNOs(0.2、2.0、20.0 μg/ml)对大鼠血小板聚集的影响.(2)体内试验:将20只成年健康雄性SD大鼠随机分为溶剂组和MWCNOs组(2、4和8 mg/kg),观察尾静脉注射染毒12 h后MWCNOs对血小板数量、出血时间和凝血指标的影响.同时观察尾静脉注射4 mg/kg MWCNOs和等体积溶剂作用不同时间(0.5、6和12 h)后对血小板数量和血小板聚集的影响.结果 MWCNOs对由二磷酸腺苷引起的血小板聚集有明显的抑制作用,并且随着剂量的增加,抑制作用增强.最高剂量组(20.0 μg/ml)血小板聚集率(50.0%±6.9%)明显低于溶剂组(73.2%±4.3%),差异有统计学意义(P<0.01).体内试验结果同样观察到MWCNOs存在抑制血小板聚集的作用,2、4、8 mg/kg MWCNOs组的血小板聚集率(分别为51.2%±4.5%、54.3%±7.8%、56.8%±3.0%)均低于溶剂组(64.3%±3.4%),但差异无统计学意义(P>0.05).未发现MWCNOs对大鼠血小板数量、出血时间和凝血指标有明显影响.结论 在该研究条件下,MWCNOs对血小板聚集可能存在抑制作用,但并不影响机体的止血功能.

Abstract：

Objective To observe the effects of multiwall carbon nano-onions (MWCNOs) on platelet aggregation and hemostatic function. Methods The platelet aggregation was determined with Born' s method at different concentration of MWCNOs (0, 0.2, 2.0, 20.0 μg/ml) in vitro. Twenty male SD rats were randomly divided into 4 groups which were exposed to 0, 2, 4 and 8 mg/kg MWCNOs, respectively. Then platelet count, platelet aggregation, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), bleeding time (BT) and platelet count (PC) were measured at 12 h after receiving tail intravenous injection of MWCNOs. The effects of MWCNOs (4 mg/kg) on platelet aggregation and platelet count at different time points were observed. Results In vitro, MWCNOs exhibited the potent inhibitory effects on rat platelet aggregation caused by ADP in a concentration-dependent manner. The platelet aggregation in the highest dosage of 20.0 μg/ml group was 50.0%±6.9% which was significantly lower than that ( 73.2% ±4.3% ) in control group (P<0.01). In vivo, the highest inhibitory was up to 20.4% , but there was no significant difference, as compared with control group. MWCNOs did not affect the APTT, PT, TT, BT and PC. Conclusion Under this experimental condition, MWCNOs might inhibit platelet aggregation but not affect hemostatic function.     

Contraceptive and hormonal properties of a new 1,4-dihydro-2-oxoquinoline derivative (compound 84-182) in rodents and rhesus monkeys

Compound 84-182 prevented pregnancy when administered subcutaneously at 10 mg/kg dose on days 3-8 post-coitum in hamsters and on days 6-10 post-coitum in guinea pigs. At lower doses, while in hamsters there was a marked reduction in implantation number, majority of implantations in guinea pigs showed signs of resorption. The compound was ineffective when administered at 10 mg/kg dose on days 1-3 or 6-7 post-coitum in hamsters and on days 1-5 or 4-8 post-coitum in rats. In rhesus monkeys, treatment with the compound at 5 and 10 mg/kg doses on days 16-21 of the menstrual cycle induced frank vaginal bleeding between days 21 and 24. Treatment on days 21-30 or after confirmation of pregnancy on days 32-36 was ineffective. In conventional bioassays, the compound was devoid of any estrogenic, antiestrogenic, progestational, antiprogestational, androgenic or antiandrogenic properties at the contraceptive dose. In competitive protein binding assay, the compound showed relative binding affinity (RBA) of less than 0.1% and 0.28% of progesterone, respectively, for rabbit and hamster uterine cytosol progesterone receptors. Its RBA for rat uterine cytosol estrogen receptors was less than 0.1% of estradiol-17 beta.     

Clinical use of recombinant human activated factor VII (rFVIIa) in the prevention and treatment of bleeding episodes in patients with Glanzmann's thrombasthenia

Glanzmann's thrombasthenia (GT) is a congenital qualitative platelet disorders due to the deficiency or defect of platelet membrane GPIIb/IIIa (integrin alpha(IIb)beta3). The standard treatment for bleeding is platelet transfusion but repeated transfusion may result in the development of anti-platelet antibodies (to HLA and/or GPlIbIIIa) rendering future platelet transfusion ineffective. Alternative effective agent(s) are needed. There are increasing reports documenting efficacy of high dose rFVIIa in GT patients with adverse events uncommon. The efficacy is supported by evidence that high concentration FVIIa binds to activated platelet surface and improves thrombin generation to enhance deposition (adhesion) and aggregation of platelets lacking GPIIb/IIIa. While there are increasing clinical experiences, evidence-based clinical data are not available. There is a need for more clinical studies, particularly clinical trials, to further assess the efficacy, safety (particularly thrombotic events) and optimal regimen ofrFVIIa in GT patients, either singly or in combination with other hemostatic agents such as platelet transfusion. In the absence of this data, for treatment of severe bleeding in GT patients with platelet antibodies and platelet refractoriness, rFVIIa at dose 90 microg/kg every 2 h for 3 or more doses could be considered. This more "optimal regimen" derived from a recent International Survey needs confirmation with larger studies. What the optimal regimen for surgical coverage is remains unresolved.     

In vitro effects of trace elements on blood clotting and platelet function. A--Iron, copper, and gold.

The present in vitro study of the effects of iron on the blood coagulation mechanism in rats showed that addition of ferrous sulphate to pooled rat plasma resulted in inhibition of blood coagulation, as shown by prolongation of the clotting parameters tested, an effect which was dose-dependent. In vitro addition of ferrous sulphate to rat PRP in doses of 2-5 mg/ml significantly decreased platelet aggregation in response to ADP, while collagen-induced aggregation was significantly diminished in presence of the higher doses of ferrous sulphate (4-5 mg/ml). Also, preincubation of ferrous sulphate with thrombin or with pure fibrinogen indicated that iron could produce decrease of thrombin activity as well as impairment of fibrinogen clottability. In vitro addition of copper sulphate (300-1000 micrograms/ml) elicited an anticoagulant effect, though thrombin time was markedly shortened with all tested concentrations of copper sulphate. Addition of copper sulphate to PRP produced inhibition of platelet aggregation in response to PRP produced inhibition of platelet aggregation in response to ADP and to collagen. Preincubation of copper sulphate with thrombin resulted in slight enhancement of thrombin activity followed by inhibition, while preincubation of copper sulphate with pure fibrinogen caused only minimal impairment of fibrinogen clottability. Also, addition of gold chloride in doses of 50-500 micrograms/ml to plasma in vitro produced a dose-dependent progressive prolongation of all clotting parameters tested, the effects reaching a maximum after 30 min. incubation. Further the in vitro addition of gold chloride to rat PRP resulted in marked inhibition of platelet aggregation in response to both ADP and collagen. In addition, preincubation of gold chloride with thrombin or with pure fibrinogen showed that gold exerted an antithrombin action and prolonged the fibrinogen clotting time indicating impaired fibrinogen clottability.     

Endometrial morphology and peripheral steroid levels in women with and without intermenstrual bleeding during contraception with the 300 μg norethisterone (NET) minipill

The peripheral levels of estradiol and progesterone were analyzed in blood samples withdrawn three times a week (Mondays, Wednesdays and Fridays) from 24 normally menstruating volunteers during a pretreatment (control) cycle and then every day during the second month of administration of daily oral doses of 300 μg norethisterone (NET). An endometrial biopsy was also taken on days 23–25 of the control cycle for morphometric, microfluorometric and ultramicroscopic quantitation.Intermenstrual bleeding occurred in 12 subjects during the second month of NET administration; the number of days with bleeding and spotting (13.4 ± 5.1 days) in this group significantly exceeded that found in their control cycle (6.3 ± 1.2), or in the group of “non-bleeders” (6.0 ± 1.2) taking the same dose of NET.Within 6 hours after the onset of intermenstrual bleeding, another endometrial biopsy was taken, after which the subjects were allocated at random to two types of treatment:6 subjects were given daily oral doses of 50 μg of ethinylestradiol for 7 days and 6 subjects received placebo for the same period of time. Daily blood samples were withdrawn during this period.Daily blood samples were also withdrawn from “non-bleeders” during the second month of NET administration and an endometrial biopsy was taken between days 23 and 25 of this month.     

Epistaxis caused by an acquired thrombocytopathy

Epistaxis may be the sole manifestation of a platelet aggregation dysfunction. Bleeding time according to Ivy within normal ranges does not exclude a severe disturbance of primary haemostasis. In two women (aged 53 and 76 yr, respectively) persistent epistaxis could not be stopped by local therapy. The bleeding time according to Ivy was within normal ranges in both cases. In one patient a bleeding disorder was not recognized as laboratory screening tests were normal and her situation became life-threatening. Anamnesis, clinical history and platelet aggregation tests led to the correct diagnosis; in one patient the relation with acetylsalicylic acid treatment was clear. After administration of platelet concentrate the bleeding stopped within a few hours in both cases and did not recur.     

Ornithine alpha-ketoglutarate and glutamine supplementation during refeeding of food-deprived rats.

The aim of this study was to compare the efficiency of ornithine alpha-ketoglutarate (OKG) and glutamine supplementation in an experimental model of denutrition that provides well-characterized disturbances of amino acid patterns. Male Wistar rats (187 +/- 11 g; five in each group) were starved for 3 days and then refed for 7 days with an oral diet (192 kcal kg-1.day-1 and 2.25 g of nitrogen kg-1.day-1), supplemented with 0.19 g of nitrogen kg-1.day-1 in the form of OKG, glutamine, or casein (control group). Food deprivation induced a fall in most tissue amino acids, with the notable exception of muscle leucine and liver glutamate, which increased by 43% (p < .01), and 11% (p < .05), respectively. The main effect of OKG was seen in the viscera, with a normalization of most amino acid pools (including proline and branched-chain amino acids) in the small bowel and liver. The main effect of glutamine was observed in the muscle, with a normalization of the glutamine and leucine pools. We conclude that, in this model and with the doses used, OKG and glutamine act in different target tissues, ie, splanchnic areas and muscle, respectively.     

Does non-acetylated salicylate inhibit thromboxane biosynthesis in human platelets?

Ingestion of aspirin (acetyl salicylic acid: ASA) may promote bleeding complications due to inhibition of thromboxane biosynthesis, which results in the prolongation of bleeding time. The effect is believed to be achieved by the irreversible acetylation of the enzyme cyclooxygenase by aspirin. This alteration in platelet function by aspirin prohibits its use in patients with bleeding disorders such as haemophiliacs. Choline magnesium trisalicylate (CMT; Napp Laboratories Ltd) is a non-acetylated salicylate with analgesic and anti-inflammatory effects similar to that of aspirin. However, despite a comparable salicylate absorption from the two drugs, CMT is found to have no inhibitory action in platelet aggregation and to cause less gastric mucosal damage and gastrointestinal blood loss than aspirin. To investigate the role of the acetyl moiety in the inhibition of platelet thromboxane biosynthesis, we studied the effect of CMT and ASA on bleeding time, serum thromboxane B2 (TxB2) and thromboxane (Tx) generation in healthy volunteers.     

Impaired hemostasis and platelet function in rats fed low zinc diets based on egg white protein

Zinc-deficient rats exhibit impaired hemostasis, a pathological sign related to defective platelet function. The original observation was made in rats fed a low zinc diet based on soy protein. The present study was designed to test the effect of feeding a low zinc, egg white-based diet on bleeding time and platelet aggregation. The reversibility of the defect and the response of washed platelets from rats fed low zinc (less than 1 mg/kg) and control (100 mg/kg) diets were also assessed. Immature male rats were fed the respective diets for 11 d, the controls being both ad libitum- and pair-fed. To test reversibility, rats depleted for 11 d were then fed the control diet for an additional 7 d. Saline bleeding time was increased, and aggregation of platelet-rich plasma (PRP) from rats of low zinc status was impaired. The rate of the secondary phase of aggregation was significantly less than that of controls, but it was not different from that of controls after 7 d of zinc repletion. Aggregation of washed platelets was also impaired by low zinc status, showing that the defect is associated with the platelet, not the plasma. Egg white as a source of protein in the low zinc diet resulted in abnormal hemostasis and platelet aggregation, including a defective response of washed platelets.