Hemostatic Profile Research Articles

Haemostasis impairment in bitches with pyometra

It is well known that pyometra syndrome with endotoxemia and/or sepsis in bitches may impair different organ systems and functions including haemostasis, which may considerably influence the outcome if overlooked or underestimated. The present clinical study was carried out on thirty-seven clinical patients admitted to the Clinic for Small Animal Medicine and Surgery at the Veterinary Faculty in Ljubljana, Slovenia. Preoperative diagnosis was based on clinical signs, haematology results and ultrasonographic examination. Ovariohysterectomy was performed as final treatment. The study is aimed at the effects of pyometra syndrome on haemostatic functions as well as at the comparison between haemostatic functions and haematology and biochemistry results. Acute phase reaction with leucocytosis, neutrophilia, lymphopenia, hypoalbuminemia and hyperfibrinogenemia was identified preoperatively and up to 24 hours postoperatively. Changes in the haemostatic profile - prolonged activated partial thromboplastin time, shortened thrombin time, increased concentration of D-dimeres and thrombocytopenia - which were confirmed in the study, suggest the development of disseminated intravascular coagulation (DIC), most likely due to influence of E. coli endotoxin. The changes of haemostatic profile and concurrent acute phase reaction suggest the connection between inflammation and coagulopathy. Attention and early recognition of haemostatic function impairment should be addressed in pyometra syndrome patient in order to be able to timely substitute coagulation and anticoagulation factors with fresh blood, fresh or freshly frozen plasma or added heparin when appropriate.

Investigation of Tissue Factor and Other Hemostatic Profiles in Experimental Hypothyroidism

The influence of thyroid failure on hemostasis has been studied and is still not well understood. These patients have high risk for cardiovascular diseases because of the lipid metabolism and procoagulant agents. But the influence of thyroid failure on hemostasis is controversial. Tissue factor (TF) has an important role in the thromboembolic state. Recent experiments have demonstrated that TF-dependent activation of the coagulation cascade plays an important role in the pathophysiology of intravascular thrombus formation. The purpose of the present study was to investigate the contributions of TF, factor VII:C (FVII:C), factor XII:C (FXII:C), and fibrinogen in experimental hypothyroidism. TF was obtained from the thyroid gland and lung tissue of 10 rats following experimental hypothyroidism induced for 30 d and compared with similar tissue from 10 control rats. Significantly increased TF activities were found in hypothyroid rats. By contrast, FVII:C level was significantly decreased when compared with the control group. In this respect it is interesting to note that a hypercoagulable state due to increased thromboplastic activity may occur. Based on those results, elevated tissue factor activities (TFa) of the patients with low thyroid dysfunction may have another risk factor for cardiovascular diseases.

Distinct Hemostatic Profile of Leukocytes in Essential Thrombocythemia (ET) Carrying the JAK2 V617F Mutation.

The pathogenesis of the thrombotic diathesis of patients with ET is not completely clarified. Activation of polymorphonuclear leukocyte (PMN) occurs in these patients and is associated with a hypercoagulable state and increased number of circulating platelet/PMN aggregates. Further, increased procoagulant Tissue Factor (TF) expression in ET PMN is also reported. Recently, a gain-of-function JAK2 mutation (V617F) has been described in a high proportion of bcr/abl-negative myeloproliferative disorders. Specifically, in subjects with ET the mutation is present in about 50% of cases and retrospective data suggest an association with a higher rate of complications, including thrombosis. Aim of this study was to evaluate whether ET patients carrying the JAK2 mutation possess PMN with different hemostatic characteristics compared to ET subjects without JAK2 mutation and healthy controls. Twenty ET patients, 10 with and 10 without JAK2 mutation (median age: 50 years, range 32–61; platelet count: median 782 x 109/L, range 474–1,565 x 109/L), not receiving cytoreductive therapy (classified as low risk group), were included in the study; 16 age matched healthy subjects acted as controls. Expression of CD11b, TF and fibrinogen on PMN surface as well as PMN-platelet mixed aggregates (defined as the percentage of CD11b-positive PMN co-expressing a platelet-specific marker, i.e. CD42b or CD62P) were evaluated by whole blood flow-cytometry in both basal condition and after in vitro PMN stimulation by f-MLP. In washed isolated PMN samples the level of TF-mRNA was determined by RT-PCR. In basal conditions, significantly (p<0.01) increased levels of PMN/platelet aggregates (both CD42 and CD62P pos. PMN) compared to controls were found, independently from JAK2 mutation. Differently, PMN from JAK2 mutation carriers expressed significantly higher surface TF (18.2±9 %pos. cells) and fibrinogen (12.3±7 %pos. cells) antigens compared to non-carrier (TF: 11.6±5 %; fibrinogen: 7.2±2 %pos. cells) and control subjects (TF: 11.1±3 %; fibrinogen: 7.1±3 %pos. cells). In vitro stimulation with f-MLP increased the proportion of platelet/PMN aggregates (CD11b/CD42 and CD11b/CD62P) in all ET patients and controls. However, in JAK2 mutation carriers the levels of both CD62P and CD42b positive PMN were significantly greater than those of non-carrier ET patients and controls (p<0.05). Similarly, TF and fibrinogen levels on stimulated PMN surface were more elevated in the JAK2 mutation positive group compared to both the mutation negative and control groups. The analysis of PMN TF-mRNA showed a significantly higher expression in the whole ET patient group compared to controls, independently from the presence of JAK2 mutation. In conclusions, these data indicate that the expression of JAK2 mutation in ET patients may confer to PMN a different hemostatic phenotype in terms of increased interaction with platelets and increased expression of surface TF and fibrinogen, suggesting a new link of this mutation with a prothrombotic status.

Effects of meloxicam on the haemostatic profile of dogs undergoing orthopaedic surgery

The buccal mucosal bleeding time (BMBT), prothrombin time (PT), activated partial thromboplastin time (APTT) and intraoperative bleeding score (IBS) of 38 dogs that underwent orthopaedic surgical procedures and received meloxicam...

Hemostatic Factors and Estrogen during the Menopausal Transition

It has been speculated that gender differences in cardiovascular disease (CVD) mortality can be attributed to the effects of estrogens on inflammation and hemostatic marker profiles. Therefore, we evaluated endogenous hormone concentrations, menopause transition stages, and adoption of exogenous hormone use in relation to hemostatic and inflammation marker concentrations in women. Longitudinally, we studied 3302 participants from the Study of Women's Health Across the Nation, aged 42-52 yr at baseline and self-identified as African-American (28%), Caucasian (47%), Chinese (8%), Hispanic (8%), or Japanese (9%). Serum samples from baseline and years 2001, 2003, and 2005 were assayed for estradiol and FSH. Hormone concentrations were related to CVD markers, including fibrinogen, factor VII-c, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator, and human serum C-reactive protein (hsCRP). Lower estradiol levels were associated with higher levels of PAI-1 and tissue plasminogen activator, but there were no significant relationships with fibrinogen, factor VII-c, or hsCRP. Higher FSH concentrations were associated with higher PAI-1 and factor VII levels, but lower fibrinogen and hsCRP levels. Transitions from premenopause and early perimenopause to postmenopause were not associated with significant differences in levels of hemostatic factors. The hsCRP concentrations were approximately 25% higher, and the PAI-1 concentrations approximately 20% lower among women who initiated hormone therapy, compared with nonusers. Endogenous estrogens may reduce CVD risk via modulation of fibrinolytic factors, but not coagulation or inflammatory markers. Notably, conclusions derived from studies of exogenous hormones and CVD risk may not parallel or explain the effects of endogenous hormones or perimenopausal hormone changes on CVD risk.

Afibrinogenemia and a circulating antibody against fibrinogen in a Bichon Frise dog

A 1.5-year-old female Bichon Frise dog was evaluated for a life-threatening hemorrhagic condition that occurred after ovariohysterectomy, requiring 4 whole-blood transfusions. A hemostatic profile, including activated clotting time (ACT), one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), buccal mucosal bleeding time, and specific assays (heat-precipitation microhematocrit method and electroimmunoassay) for fibrinogen, were performed to investigate the coagulopathy. Clotting times for all tests having a fibrin clot endpoint (ACT, OSPT, APTT) and buccal mucosal bleeding time were prolonged. Plasma fibrinogen was not detected by heat-precipitation microhematocrit method or electroimmunoassay. Using the Ellis-Stransky method, a mixture of patient plasma and normal canine plasma with known fibrinogen content yielded substantially less than the calculated fibrinogen concentration, indicating the presence of an interfering substance. The interferent properties of the patient's plasma were retained following heat precipitation at 56 degrees C indicating the absence of a pyroglobulin or an abnormal fibrinogen molecule. Radial immunodiffusion assay using the patient's plasma and activated thrombin confirmed the existence of an inhibitor to the formation of fibrin. Western blot analysis using the patient's plasma identified an IgG antibody that reacted with the Beta- and gamma- but not the Alpha-subunits of canine fibrinogen. Antibody was detected in samples taken 8, 16, and 68 days after the surgery; peak titers were evident at day 16. These results supported a diagnosis of afibrinogenemia with a circulating antibody inhibitor to fibrin clot formation that developed secondary to blood transfusion.

Long-term prognostic value of protein C activity, erythrocyte aggregation and membrane fluidity in transmural myocardial infarction

The objective of this study was to evaluate the long-term predictive value of the haemostatic, inflammatory and haemorheologic disturbances in transmural myocardial infarction (MI). Sixty-four (59 male) consecutive survivors of a MI, with a mean age of 58.3 +/- 12.0 years, were followed over a period of 36 months. Eighteen patients had a cardiovascular event defined as the composite of death, non-fatal MI, unstable angina and stroke. The haemostatic (protein C activity-PtC, antithrombin III, plasminogen activator inhibitor-1), haemorheologic (blood fluidity and components, erythrocyte membrane fluidity) and inflammatory (polymorphonuclear elastase, leukocyte count) profiles were determined at hospital discharge, using standard methodology. Our results can be summarized as follow: (i) at hospital discharge, the subgroup of patients with events had higher leukoactivity, leukocyte count, membrane fluidity, prognosis cyte count (7833.0 +/- 1696.0 vs. 10294.0 +/- 3129.0; p = 0.011), lower PtC (100.65 +/- 19.08 vs.81.25 +/- 19.95; p = 0.002), and lower erythrocyte aggregation (14.26 +/- 5.94 vs. 11.47 +/- 3.45; p = 0.031) in relation to the ones without events; (ii) By Cox regression the protein C activity lower tertile (OR 0.169; 0.045-0.628; p = 0.008); erythrocyte membrane outer layer fluidity upper tertile (OR 0.067; 95% CI 0.011 - 0.393; p = 0.003); and erythrocyte aggregation lower tertile (OR 0.182; 0.038 - 0.876; p = 0.034) were independent predictors of the composite endpoint. We can conclude that some haemostatic, haemorheologic and inflammatory disturbances, at hospital discharge, are long-term independent predictors of recurrent cardiovascular events in transmural myocardial infarction survivors.

Relationship of physical fitness, hormone replacement therapy, and hemostatic risk factors in postmenopausal women

This cross-sectional study evaluated the relationship of physical fitness, hormone replacement therapy (HRT), and hemostatic profiles at rest and after an acute bout of maximal exercise in 48 healthy postmenopausal women. Subjects were categorized by fitness and HRT user status into four groups: unfit nonusers, fit nonusers, unfit users, and fit users. Fibrinolytic variables tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) activity, and antigen and prothrombin fragment 1 + 2, a molecular marker of in vivo thrombin generation, were measured before and after maximal exercise. Fibrinogen was also measured at rest. Higher tPA and lower PAI-1 activities (P <0.05) were seen in HRT users and fit groups. tPA and PAI-1 antigens were lower in HRT and fit groups (P <0.05) but not after correction for body mass index. Prothrombin fragment 1 + 2 was lower in the fit groups regardless of HRT status (P <0.05). Fibrinogen was similar in all groups. Favorable hemostatic profiles were observed in physically fit compared with unfit women, especially in HRT nonusers. Thus fitness is more strongly related to these hemostatic risk factors compared with HRT since HRT did not affect these hemostatic variables in fit postmenopausal women.

Hemostasis and thyroid diseases revisited

Several papers have reported various hemostatic abnormalities in patients with thyroid diseases. In this concise review, the traditional associations between hypercoagulable state and hyperthyroidism and between hypocoagulative state and hypothyroidism are critically revised on the basis of more recent literature data. In particular, we analyze the hemostatic balance (primary hemostasis, coagulation factors and fibrinolytic system) in different thyroid disorders. Although most of the studies published so far include limited numbers of patients and their results are sometimes contradictory, we can conclude that hyperthyroidism is generally accompanied by a hypercoagulable state, whereas the hemostatic profile in hypothyroidism and thyroid cancer depends on the severity of the disease.

Visceral Obesity and Hemostatic Profile in Patients with Type 2 Diabetes: the Effect of Gender and Metabolic Compensation

Type 2 diabetes (T2DM) patients are characterized by a very high risk of cardiovascular diseases. Among the factors that are responsible for this phenomenon are abdominal obesity and hemostatic abnormalities. To examine the association of the markers of coagulation and fibrinolysis with the parameters of abdominal obesity and metabolic compensation in T2DM patients. 46 T2DM patients participated in the study: 24 men (mean age 61.1 +/- 7.9 years) and 22 postmenopausal women (mean age 62.6 +/- 8.7 years). In each patient the content and distribution of fatty tissue was measured by a dual energy X-ray absorptiometry method (DEXA). The central abdominal fat/gynoid hip fat (CAF/GF) ratio was calculated. The following hemostatic parameters were measured: fibrinogen (Fb), factor VII (fVII), antithrombin III (ATIII), C protein (pC), tissue plasminogen activator inhibitor (PAI-1) and alpha 2 antiplasmin (alpha2 AP). In addition, the biochemical indices of metabolic compensation were measured: HbA1c, glucose levels and lipids. Patients of both genders were divided according to median CAF/GF ratio. The activity of PAI-1 was significantly higher in women with CAF/GF ratio >or= 0.88 as compared to those with CAF/GF < 0.88 (2.64 +/- 1.28 vs. 1.61 +/- 0.27 U/ml, p < 0.05). The activity of ATIII was significantly lower in men with CAF/GF ratio >or= 1.17, as compared to those with CAF/GF < 1.17 (105.10 +/- 10.02 vs. 113.42 +/- 10.72 %, p < 0.05). There was a significant correlation between the CAF/GF ratio and the activity of PAI-1 in women (r = 0.30, p < 0.05). In addition, in men the CAF/GF ratio was negatively correlated with ATIII activity (r = -0.44, p < 0.05). Multiple stepwise regression analysis demonstrated independent association between the CAF/ GF ratio and the activity of PAI-1 (p < 0.001), and between the CAF/GF ratio and the activity of alpha2 AP (p < 0.01). There was an independent association between the concentration of HbA1c and the concentration of Fb (p < 0.001) and between triglycerides and the activity of fVII (p < 0.01). The results of our study show that the patients with T2DM and with higher markers of abdominal obesity measured by DEXA show fibrinolysis impairment and thrombinogenesis elevation compared to those with lower abdominal obesity markers. Independent factors determining hypercoagulation also include metabolic control and lipids. Hemostatic disorders place subjects with diabetes and abdominal obesity at risk of developing vascular complications.

Haemostatic profile of small children during and following cardiopulmonary bypass.

We evaluated changes of the haemostatic system during pediatric cardiac surgery during and after cardiopulmonary bypass (CPB). Twenty-five children under 15 kg of body weight undergoing open-heart surgery were divided into three groups; 9 patients (Group A), no bank blood was used throughout the surgery; 8 patients (Group B), packed red cells were used in the priming of CPB circuit; 8 patients (Group C) in cyanotic condition, for whom surgery was performed without bank blood. CPB caused a significant decrease of platelet counts in all three groups, the levels of which remained similar next morning. Platelet counts decreased more significantly in Group C (59+/-27 k/mm3) than in Group A (119+/-42 k/mm3) and B (104+/-27 k/mm3). Platelet function-platelet activating factor test (HemoSTATUS) did not significantly decrease throughout the perioperative period in Group A. HemoSTATUS value decreased during CPB and recovered after CPB in Group B and C. Prothrombin time international ratio (PT-INR) and activated partial thromboplastin time were significantly prolonged just after CPB and recovered until next morning in all three groups. PT-INR was more prolonged in Group C (2.92+/-0.62) than in Group A (2.08+/-0.27) and B (2.42+/-0.42). There was no significant difference in postoperative bleeding for the first 12 hours among the three groups. Although extreme hemodilution during CPB significantly impairs the coagulation and platelet system, these changes are usually transient and tolerable with minimal postoperative hemorrhage. However, a prolonged CPB and preoperative cyanotic condition may induce a critical decrease of platelet counts and increase postoperative bleeding.

Effect of individual dietary fatty acids on postprandial activation of blood coagulation factor VII and fibrinolysis in healthy young men

Hypertriglyceridemia may represent a procoagulant state involving disturbances to the hemostatic system. Plasminogen activator inhibitor type 1 (PAI-1) is increased in the presence of hypertriglyceridemia. Free fatty acids (FFAs) in plasma may promote factor VII (FVII) activation. We tested the hypothesis that FVII activation would be less after consumption of saturated fatty acids than after other fatty acids. The effects of 6 matching dietary test fats, rich in stearic (S), palmitic (P), palmitic + myristic (M), oleic (O), trans 18:1 (T), and linoleic (L) acid, respectively, on the postprandial lipid and hemostatic profile (after 2, 4, 6, and 8 h) were investigated in 16 young men. High-fat meals (1 g fat/kg body wt; 43% from the test fatty acid) were served in the morning on 6 separate days. All fats increased FVII activation. The S fat resulted in a lower increase in activated FVII (FVIIa) than did the T fat and in a lower FVII coagulant activity (FVII:c) than did the O fat (P < 0.02, diet x time interaction). When the data were pooled, the saturated (S, P, and M) test fats resulted in a smaller postprandial increase in FVIIa (P = 0.036, diet effect), a smaller increase in FVII:c (P < 0.001, diet x time interaction), a greater rise in tissue plasminogen activator concentrations (P = 0.028, diet effect), and a tendency to a greater postprandial decline in PAI-1 (P = 0.06, diet effect) compared with the unsaturated test fats (O, T, and L). The increase in FVIIa was not significantly associated with the level of lipemia, plasma FFAs, or plasma lipoprotein lipase activity. Our results indicate a lesser increase in FVIIa after the consumption of saturated fats, especially the S fat, than after unsaturated test fats.

Hemostatic variables, carbohydrate metabolism and lipid profile in women with low body mass index

Hemostatic variables, carbohydrate metabolism and lipid profile in women with low body mass index

Evidence of prolonged disturbances in the haemostatic, hemorheologic and inflammatory profiles in transmural myocardial infarction survivors

SummaryHaemostatic, hemorheologic and inflammatory disturbances have been associated with acute coronary syndromes. Most knowledge is reported in cross sectional studies and are without time dependent evolution of these profiles.The aim of this study was to evaluate, during the first year, the evolution of the haemostatic, hemorheologic and inflammatory profiles determined at hospital discharge in survivors with transmural myocardial infarction (MI).Eighty eight (79 male; 9 female) mean age of 58 ± 11 years, survivors of a transmural MI were prospectively studied at discharge, 6 months and one year after the event. Haemostatic (protein C, antithrombin III and plasminogen activator inhibitor 1), hemorheologic (blood fluidity and components) and inflammatory profiles (polymorphonuclear elastase and leukocyte count) were determined using standard methodology.The results of the study can be summarized as follows: (1) Protein C decreased (p &lt; 0.05) over time while PAI-1 only varied significantly until 6th month. (2) Plasma viscosity and fibrinogen (p &lt; 0.001) decrease over time, while erythrocyte aggregation (p &lt; 0.001) and haematocrit increased. Whole blood viscosity did not vary. (3) Leukocyte decreased (p &lt; 0.001) and elastase did not (4). Those patients with cardiovascular events (n = 7) had higher PAI-1 concentration (p&lt;0.05) and leukocyte count (p &lt; 0.01), at discharge (5) Left ventricle ejection fraction correlated significantly with plasma viscosity (r = 0.35 p &lt; 0.05). The results of this longitudinal study show dynamic modifications of the haemostatic, hemorheologic and inflammatory profiles during the first year of a transmural myocardial infarction. In addition, there are interrelations between them and the clinical profile that could help to explain the clinical evolution of this group of patients.

Hemostatic variables ,carbohydrate metabolism and lipid profile in women with low body mass index

The aim of this study was to evaluate hemostatic variables in women according to different body mass index (BMI) values ,and then correlate them with some metabolic parameters - fasting insulin and glucose,total cholesterol ,high-density lipoprotein (HDL)-cholesterol ,low-density lipoprotein (LDL)-cholesterol and triglycerides. Eighty-four female patients aged 18-39 years were recruited ,and agreed to participatein the study. The study group was divided into three subgroups according to BMI: low BMI (BMI < 18.5 kg/m2; n = 43) ,normal-weight (control) (BMI 18.5-24.99 kg/m2; n = 21) and overweight/obese(BMI > 25 kg/m2; n = 20). BMI was calculated ,and the following measurements were taken: International Normalized Ratio ,antithrombin III ,tissue plasminogen activator (t-PA) activity ,t-PA-antigen,plasma fibrinogen level ,factor VII ,Plasminogen activator inhibitor (PAI)-1 activity and antigen and metabolic parameters: fasting insulin and glucose ,total cholesterol ,HDL-cholesterol ,LDL-cholesteroland triglycerides. The results were statistically analyzed. In the low BMI group ,a negative correlation between fasting insulin and PAI-1 activity ,and a positive correlation between fasting glucose andPAI-1 antigen were observed. Also ,a strong negative correlation between PAI-1 activity and insulin/glucose index was found. Plasma insulin levels were significantly lower in the low-BMI women than in theoverweight/obese group (p < 0.001) and with no difference compared to the control group. We did not find any difference in fasting glucose level between all groups. HDL-cholesterol showed the highestlevels in the normal BMI group and was significantly higher than in the low BMI and obese groups (p < 0.05 and p < 0.01 ,respectively). PAI-1 activity in the low BMI women revealed increased activityin comparison to control and overweight/obese women (p < 0.001 and p < 0.05 ,respectively). Lower antigen levels were also shown as compared to both these groups (p < 0.001 and p < 0.001 ,respectively).Similar results were obtained with t-PA antigen levels (p < 0.001 and p < 0.001 ,respectively). There were no differences in activity of t-PA in all groups. Obese women showed significantly higherfibrinogen levels than other BMI groups (p < 0.001 and p < 0.001 respectively). Analysis of hemostatic variables in women with a low BMI testify to the impaired fibrinolysis in this group ,also showinga strong correlation with carbohydrate metabolism.

Hyperhomocyst(e)inemia and Hemostatic Factors: The Atherosclerosis Risk in Communities Study

PURPOSE: To determine whether homocyst(e)ine (H(e)) is related to hemostatic factors in a population-based sample without evidence of cardiovascular disease. METHODS: A subsample of 660 participants—67 African-American women, 53 African-American men, 201 white women, and 339 white men—was selected from the Atherosclerosis Risk in Communities Study baseline cohort. This was based on carotid intimal-medial wall thickness above the 90th percentile or below the 75th percentile of the population distribution, assessed by B-mode ultrasonography. Unadjusted and multivariable-adjusted associations between fasting plasma H(e) and the hemostatic factors fibrinogen, factor VII:c, factor VIII:c, protein C antigen, hematocrit, platelet count, β-thromboglobulin (β-TG), tissue plasminogen activator (tPA), PAI-1, D-dimer, and lipoprotein[a] were examined. RESULTS: Mean age-adjusted H(e) was positively, albeit weakly, correlated with β-TG, tPA, hematocrit, D-dimer and PAI-1; inversely correlated with protein C; and was higher in smokers, men and African-Americans. In multivariable regression, β-TG, tPA, and factor VII:c were positively associated with H(e), as well as age, black race, male sex, and current cigarette smoking. CONCLUSIONS: These cross-sectional data for a biracial group of middle-aged individuals suggest that H(e) levels falling below values consistent with homocyst(e)inemia are associated with several prothrombotic factors after adjustment for sociodemographic factors. If H(e) change is antecedent to altered hemostasis, FDA-mandated fortification of grain products with folic acid for prevention of fetal neural tube defects may lead to both reduced plasma H(e) levels and improved hemostatic profiles.

Chemotherapy-Induced Activation of Hemostasis: Effect of a Low Molecular Weight Heparin (Dalteparin Sodium) on Plasma Markers of Hemostatic Activation

To evaluate the effect of standard chemotherapeutic regimens on the hemostatic profile of patients with breast and lung carcinoma; and to evaluate the effect of a single dose of a low molecular weight (LMW) heparin, dalteparin sodium, administered prior to the chemotherapy on markers of hemostatic activation. 11 patients with breast cancer and 10 patients with lung cancer receiving systemic chemotherapy were studied. 10 breast cancer patients and 9 lung cancer patients completed at least 1 cycle of treatment and had all hemostatic studies. Patients had a complete hemostatic and prothrombotic profile performed at study initiation. Markers of hemostatic activation consisting of immunoassays for thrombin-antithrombin (TAT) complex and D-dimer were measured in plasma samples obtained prior to chemotherapy and at 1, 24 and 48 h after treatment. A 2500 U dose of dalteparin was given prior to the 2nd cycle of chemotherapy; 5000 U of dalteparin was given prior to the 4th treatment cycle. Chemotherapy resulted in statistically significant increases in TAT and D-dimer for the 1, 24 and 48 h plasma samples in both the breast and lung cancer patients for all cycles of chemotherapy given without LMW heparin. There were statistically significant increases in basal thrombin generation over the 4 cycles of treatment which was unrelated to active cancer. Both pretreatment doses of dalteparin effectively prevented increases in the markers of hemostatic activation. However, in the lung cancer patients, who had significantly increased basal thrombin generation, the 5000 U dose dalteparin was more effective. Chemotherapy results in significant hemostatic activation in patients with breast and lung cancer. The effect of treatment appears to be cumulative. A single dose of LMW heparin administered prior to therapy can suppress hemostatic activation.

Activation of coagulation and fibrinolysis during coronary surgery: on-pump versus off-pump techniques.

The authors studied the changes in selected hemostatic variables in patients undergoing coronary surgery with on-pump coronary artery bypass grafting (CABG) or off-pump coronary artery bypass surgery (OPCAB) techniques. Platelet counts and plasma concentrations of antithrombin, fibrinogen, D dimer, alpha(2) antiplasmin, and plasminogen were measured preoperatively, 5 min after administration of heparin, 10 min after arrival in the intensive care unit, and 24 h after surgery in patients scheduled to undergo OPCAB (n = 15) or CABG (n = 15). To correct for dilution, hemostatic variables and platelet counts were adjusted for the changes in immunoglobulin G plasma concentrations and hematocrit, respectively. Adjusting for dilution, antithrombin and fibrinogen concentrations decreased to a similar extent in patients undergoing OPCAB or CABG (pooled means and 95% confidence limits of the mean: 95.5% of baseline, 93-98%, P = 0.002, and 91.7% of baseline, 88-95%, P = 0.0001), respectively, whereas alpha(2)-antiplasmin concentrations were unchanged. Only CABG was associated with a reduction in platelet counts (76% of baseline, 66-85%, P = 0.0001), plasminogen concentrations (96% of baseline, 91-99%, P = 0.011), and increased D-dimer formation (476%, 309-741%, P = 0.004). Twenty-four hours after surgery, platelet counts were still lower in patients undergoing CABG (P = 0.049), but all the investigated variables adjusted for dilution were similar in the two groups. Coronary surgery causes a net consumption of antithrombin and fibrinogen. A transient decrease in platelet counts, with plasminogen activation and increased D-dimer formation, however, is only observed with CABG. Twenty-four hours after surgery, the hemostatic profiles of patients in both groups are similar.

AIDS and thrombosis: retrospective study of 131 HIV-infected patients.

The recent literature contains reports of thrombotic episodes occurring in patients with human immunodeficiency virus (HIV) infection and various abnormalities predisposing to a hypercoagulable state have also been reported in such patients. To study the incidence of thrombosis in patients infected with HIV, and to assess the correlation of thrombosis with the degree of immunosuppression as well as the association with active illnesses and neoplasms, we reviewed the charts of 131 patients, which include all the patients with the diagnosis of HIV admitted or seen in the clinic between January 1, 1993, and January 1, 1998. The diagnosis of thrombosis was based on documented reports of venous plethysmography or venography for deep venous thrombosis and ventilation-perfusion scan or pulmonary angiography for pulmonary embolus. Risk factors for thrombotic disease were evaluated including general risk factors such as family history, ambulatory status, medications, and data were also collected regarding CD4 cell counts and the presence of concurrent or remote opportunistic infections, acquired immune deficiency syndrome (AIDS)-related malignancy or other AIDS-related diseases at the time of diagnosis of the thrombotic event. We also reviewed the medical literature via MEDLINE and found 45 cases of patients with HIV who developed thromboembolic complications. We found thrombotic complications in 9 of 37 patients with a CD4 count less than 200 cells/mm3 and in 1 of the remaining 94 patients with a CD4 count more than 200 cells/mm3. The difference was significant, with p = 0.00004, and the estimated odds of an event given CD4 cell counts less than 200/mm3 is 29.89 (95% confidence interval). Three patients had abnormalities of anticoagulation proteins. There was a history of opportunistic infections in 5 patients and malignancy in 3 patients. Two patients with autoimmune hemolytic anemia (AIHA) secondary to HIV-infection developed PE upon transfusion of packed red blood cells. The results of this study suggests that AIDS appears to predispose to thrombosis. It also revealed a significant correlation between thrombotic disease and CD4 counts (<200/mm3) as well as the presence of opportunistic infections, AIDS-related neoplasms, or autoimmune disorders associated with HIV such as AIHA. Therefore, clinicians caring for these patients should be aware of thromboembolic disease as a possible complication of AIDS. Further studies to elucidate the mechanisms underlying this abnormal hemostatic profile, the epidemiology, and to answer several questions such as should patients with risk factors for HIV infection who develop thromboembolic complications be further evaluated including tests for HIV are warranted.

Effects of short-term energy restriction and physical training on haemostatic risk factors for coronary heart disease in obese children and adolescents.

To study the changes of haemostatic risk factors for coronary heart disease during a weight reduction programme in obese children and adolescents. A short-term longitudinal study. Thirty-seven obese white girls (age, 12+/-1.8 y; body mass index (BMI), 26.9+/-5.25) and 19 obese white boys (age, 11.9+/-1.7 y; BMI, 26.2+/-5.2). Fibrinogen, factor VII coagulant activity, von Willebrand factor antigen, and soluble P-selectin were determined before and after a 3 week programme including energy restriction and physical activities. All determined haemostatic risk factors decreased significantly during the programme. Changes in risk factors were correlated to changes in body composition. Children and adolescents with the highest initial concentrations showed the greatest decreases. Energy restriction combined with physical activity improves the haemostatic risk profile in obese children and adolescents.