Anemia-induced increase in the bleeding time: implications for treatment of nonsurgical blood loss.

BACKGROUND: Preoperative bleeding time (BT) does not correlate with postoperative bleeding in patients subjected to surgical procedures. A significant positive correlation has been reported between the BT 2 hours after cardiopulmonary bypass surgery and the nonsurgical blood loss during the first 4 hours after bypass surgery. This study was done to investigate the effect of Hct and platelet count on the BT measurement in normal, healthy men and women. STUDY DESIGN AND METHODS: To assess the relative effect of RBCs and platelets on the BT, 22 healthy male and 7 healthy female volunteers were subjected to the removal of 2 units of RBCs (360 mL), followed by the return of the platelet-rich plasma (PRP) from both units and the infusion of 1000 mL of 0.9-percent NaCl. Four of the men and all seven women received their RBCs 1 hour after their removal. Shed blood levels of thromboxane B(2) (TXB(2)), 6-keto prostaglandin F(1 alpha), and peripheral venous Hct were measured. BTs were measured in 15 men and 13 women before and after a plateletpheresis procedure to collect 3.6 x 10(11) platelets per unit. RESULTS: The 2-unit RBC apheresis procedure produced a 60-percent increase in the BT associated with a 15-percent reduction in the peripheral venous Hct and a 9-percent reduction in the platelet count. The plateletpheresis procedure produced a 32-percent decrease in the platelet count, no change in peripheral venous Hct, and no change in the BT. After the removal of 2 units of RBCs, the shed blood TXB(2) level decreased significantly. Reinfusion of 2 units of RBCs restored the BT and restored the TXB(2) level to the baseline levels. CONCLUSION: The acute reduction in Hct produced a reversible platelet dysfunction manifested by an increase in BT and a decrease in the shed blood TXB(2) level at the template BT site. Return of the RBCs restored both the BT and the shed blood TXB(2) level to normal. The platelet dysfunction observed with the reduction in Hct was due in part to a reduction in shed blood TXB(2) and other, unknown mechanisms.

The red cell transfusion trigger: has a sin of commission now become a sin of omission?

The benefits of a Hct range of 30 to 35 percent include improved oxygen delivery and enhanced hemostasis, which help minimize complications in patients at high risk for ischemia and perioperative nonsurgical bleeding. In these settings, the conservative transfusion practice of using a lower Hct range should be replaced with a more aggressive approach. The known risks of blood transfusion would appear to be sufficiently low and the benefits sufficiently high to justify maintaining a Hct of at least 30 percent. An even higher Hct, of 35 percent, may be desirable in patients who have overt cardiopulmonary disease or who are at high risk for myocardial ischemia. Many retrospective studies have been conducted to persuade us that a conservative transfusion trigger is a safe and prudent practice, but retrospective studies are not what we need. What we need is a series of well-designed, prospective, randomized trials to evaluate the impact of a more aggressive transfusion policy on perioperative mortality, morbidity, and nonsurgical bleeding in patients with known cardiopulmonary disease or who are at high risk for myocardial and cerebrovascular ischemia.

The volume of blood shed during the bleeding time correlates with the peripheral venous hematocrit.

The relation among the bleeding time, the peripheral venous hematocrit, and the amount of blood shed at the template bleeding time site has not been previously defined. We studied this relation in 227 persons: 26 were patients with idiopathic thrombocytopenic purpura (ITP), 137 were patients with a variety of other bleeding disorders, and 64 were healthy subjects. The bleeding time (mean +/- SD) for the healthy group was 7.1 +/- 1.2 minutes, and the amount of shed blood was 136.4 +/- 47.2 microL; in patients with ITP the bleeding time was 14.0 +/- 4.1 minutes and the shed blood was 508.1 +/- 387 microL; and in the group with other bleeding disorders, the mean bleeding time was 9.0 +/- 3.5 minutes, and the amount of shed blood was 224.7 +/- 184 microL. Bleeding times for all persons studied showed a significant correlation of 0.75 for the amount of shed blood on the filter paper and a significant correlation of 0.28 for the peripheral venous hematocrit. There was also a significant correlation between the bleeding time and the platelet count in patients with ITP. This study demonstrates that the volume of blood shed at the bleeding time site correlates with the peripheral venous hematocrit and emphasizes the contribution of the hematocrit to primary hemostasis in healthy subjects and patients with bleeding disorders.

Laparoscopic accessory splenectomy for recurrent idiopathic thrombocytopenic purpura.

This report describes the use of laparoscopic accessory splenectomy in treating recurrent idiopathic thrombocytopenic purpura (ITP). The patient presented 36 months after initial splenectomy with a platelet count of 16,000 cells/microl and nontolerance of medical therapy. A technetium-99 labeled, heat-damaged red blood cell scan revealed two small foci in the upper left quadrant. This finding was confirmed by an abdominal computed tomography scan. After laparoscopic accessory splenectomy, the patient was discharged (23 h after surgery) and at 9 months showed a platelet count of 234,000 cells/microl with no medical therapy. A minimally invasive approach to accessory spleen removal can be beneficial to patients with recurrent ITP and documented accessory splenic tissue.

Late recurrence of Hodgkin's disease after partial splenectomy.

The use of laparotomy and splenectomy for staging purposes in patients with Hodgkin's disease (HD) gained popularity in the early 1970s. Accurate staging and more effective treatment regimens, including combined chemotherapy and irradiation, have resulted in improved patient survival rates. Similarly, an increased number of late complications have been reported, including the development of thyroid disease, second malignancies, and septic complications related to splenectomy. Partial splenectomy has been proposed as one method of preventing overwhelming postsplenectomy sepsis. The authors present a case of recurrence of HD, which occurred in the splenic remnant 13 years after the initial treatment. This case demonstrates that the spleen is a potential for recurrent intraabdominal Hodgkin's disease after partial splenectomy; thus, the use of partial splenectomy for HD should be discouraged.

Immune responses to major histocompatibility complex homozygous lymphoid cells in murine F1 hybrid recipients: implications for transfusion-associated graft-versus-host disease.

Graft-versus-host disease (GVHD) is currently encountered after bone marrow transplantation and transfusion. GVHD associated with transfusion (TA-GVHD) in apparently immunocompetent recipients has been recently reported with increasing frequency. A consistent finding in many of these cases is that the recipient received blood from a donor homozygous for one of the recipient's HLA haplotypes. However, the observed frequency of TA-GVHD is much lower than the estimated probability of this donor/recipient combination. The potential role of recipient immune responses in controlling TA-GVHD was investigated using an analogous murine model in which GVHD is induced by the injection of parental lymphoid cells into unirradiated F1 hybrid recipients. The effect of various immune manipulations of the recipient of GVHD induction was assessed by determining the number of donor lymphoid cells required to induce GVHD responses. Whereas depletion of recipient CD4+ cells increased the number of donor cells needed to induce GVHD, depletion of recipient CD8+ and natural killer cells resulted in fewer donor cells being needed to induce a GVHD response. These studies suggest a central role for functioning recipient CD8 and natural killer cells in the down-regulation of TA-GVHD development in recipients.

Thrombotic thrombocytopenic purpura and HIV infection.

We report on a man who was HIV-seropositive and who was initially admitted following multiple episodes of syncope. He gradually developed fulminant thrombotic thrombocytopenic purpura (TTP). Twenty-one patients with TTP who were HIV-positive have been reported previously. Of these 22 patients, all treated with plasmapheresis, 7 died from TTP and 3 suffered relapse but eventually recovered. Delay in initiating plasmapheresis may be fatal. We have correlated the laboratory data of these patients at time of admission with subsequent clinical outcome; only the platelet count correlated with outcome. Patients with lower platelet counts were less likely to relapse or die with therapy. Physicians caring for patients infected with HIV should always consider the possibility of TTP in those patients with thrombocytopenia of unknown etiology. Review of the peripheral blood smear, allowing the detection of microangiopathic hemolytic anemia, is an important clue, enabling one to consider the correct diagnosis.

Therapeutic support of the patient with thrombocytopenia.

This article provides an update on the methods of collection, preservation, storage, and administration of platelet concentrates. The current indications for platelet transfusions are reviewed, and current knowledge concerning alloimmunization and its prevention is summarized. In addition, the ongoing controversies related to prophylactic administration of platelets versus therapeutic administration are reviewed.

Low density lipoprotein cholesterol and whole blood viscosity.

Whole blood viscosity (WBV) was measured in a normal population and was analyzed in relation to packed cell volume, (hematocrit, PCV), fibrinogen, white blood cell count (WBC), platelet count, and plasma lipids, including total cholesterol, triglycerides, high density lipoprotein cholesterol (HDLc) and low density lipoprotein cholesterol (LDLc). Conventional assays were used for all blood and lipid measurements. Whole blood viscosity was measured under disaggregating conditions with a disposable, porous bed viscometer. As expected, the strongest correlation was seen between WBV and PCV (r = 0.78, p < 0.001). Significant positive correlations also were demonstrated between WBV and cholesterol (r = 0.22, p < 0.001), triglycerides (r = 0.14, p < 0.001) and LDLc (r = 0.21, p < 0.001). A significant negative correlation was found between HDLc and WBV (r = -0.20, p < 0.001). Correlation analysis by sex showed only the correlation of LDLc was significant for both men and women. A stepwise multiple regression analysis of WBV indicated that LDLc, fibrinogen (Fbg) and platelet (Plt) counts correlated independently of PCV to WBV. The equation derived from multiple regression and partial correlation analysis was: WBV (mPa.sec) = -9.317 + 0.0047 (LDLc) + 0.381 (PCV) + 0.00152 (Plt) + 0.0021 (Fbg). The calculated mean specific contribution of PCV was 90.8 percent, LDLc 3.5 percent, and fibrinogen 3.3 percent to observed mean WBV. This study shows that LDLc is the principal lipoprotein independently influencing whole blood viscosity and its effect is similar in magnitude to fibrinogen. Further studies to elucidate the mechanism and clinical significance of the effects of LDLc on WBV are indicated.

Infusion of stroma-free cross-linked hemoglobin during acute gram-negative bacteremia.

Twelve dogs were divided into two groups of six each, and were infused with bis-3,5-dibromosalicyl fumarate stroma-free hemoglobin (DBBF-Hb) or albumin. Their responses to an intravenous bolus of Escherichia coli were followed for 4 hr. Bacterial clearance from the blood stream was studied using standard colony counting methodology as well as blood counts, blood chemistries, and clotting factor analysis. There was a significant difference in mean arterial pressure (MAP) over time between DBBF-Hb-treated dogs and those treated with albumin (P < 0.02). While the DBBF-treated dogs had a higher MAP during the 10 min of bacteremia, after 1 hr, there were no longer any appreciable differences between septic dogs treated with DBBF-Hb vs. albumin. Consumption of clotting and natural anticoagulant factors was observed to be similar in both groups, as were endotoxin levels. Blood urea nitrogen (BUN) increased slightly in both groups, while white blood cell counts and clotting factor levels fell in both groups in a similar fashion. There was a more pronounced fall (P < 0.04) in platelet counts in the animals treated with DBBF-Hb. In the dogs treated with DBBF-Hb, there was also a late rise in pCO2 (P < 0.01), a more pronounced fall in pO2, and greater acidosis, which suggested that ventilation perfusion abnormalities may have been exacerbated by DBBF-Hb treatment. Since the exacerbation of respiratory abnormalities was not related to diminished bacterial or endotoxin clearance, the possibility is raised that DBBF-Hb interferes with compensatory respiratory changes during sepsis.

Perioperative paraplegia and multiorgan failure from heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia and thrombosis syndrome is a rare but devastating complication. We report a patient with heparin-induced thrombocytopenia in whom heparin-induced thrombocytopenia and thrombosis syndrome developed after a cardiac operation, complicated by acute thrombosis of the aorta followed by renal failure, paralysis, and ischemic necrosis of the lower extremities. The literature suggests aspirin, dipyridamole, and iloprost as effective prophylactic agents for perioperative heparin-induced thrombocytopenia and thrombosis syndrome. This unfortunate complication underscores the importance of close platelet count monitoring in all preoperative patients undergoing prolonged heparin therapy.

Easy bruisability, aspirin intolerance, and response to DDAVP.

Easy bruisability raises the issue of bleeding during otolaryngological surgery. Ten female patients with easy bruisability were evaluated by aspirin challenge; clinical history and screening coagulation studies in these patients had revealed no evidence of a bleeding disorder. The baseline Ivy bleeding time (BT) test (4.5 to 9.5 minutes) was found to be normal in 6 patients and prolonged in 4 patients. Following treatment with aspirin, the bleeding time prolonged significantly in the three groups evaluated: normal controls (6.0 +/- 1.5 minutes vs. 8.4 +/- 2.0 minutes), patients with easy bruisability and a normal baseline (7.8 +/- 1.3 minutes vs. 12.0 +/- 1.6 minutes), and patients with easy bruisability and an abnormal baseline (11.0 +/- 0.7 minutes vs. 14.5 +/- 0.9 minutes). Administration of DDAVP (desmopressin acetate) 0.3 microgram/kg normalized the prolonged bleeding times in all groups after 7 days of daily aspirin therapy. Performing bleeding times before aspirin challenge, after aspirin challenge, and after DDAVP therapy following aspirin challenge is both a useful way of confirming aspirin sensitivity in patients with easy bruisability as well as a useful way of documenting improved hemostasis after DDAVP administration.

Blood rheology and 2,3-diphosphoglycerate levels after erythropoietin treatment.

Twenty-seven transfusion dependent patients with end-stage renal disease on long-term dialysis had blood cell counts, serum chemistries, blood pressure, and whole blood viscosity measured, as well as having transfusion requirements assessed. Three months after the institution of recombinant human erythropoietin (rHU-EPO) (75 u per kg per wk), there was an 88 percent fall in transfusion requirement. After four months, the hematocrit increased from 24 +/- 3.8 to 25.6 +/- 4.2 percent, mean corpuscular volume from 93 +/- 4.9 to 97 +/- 6.6 fl, 2-3-diphosphoglycerate (2,3-DPG) from 13.2 +/- 3.2 to 15.6 +/- 4.3 microM per g of Hb. Whole blood viscosity fell from 14.1 +/- 2.1 to 12.7 +/- 2.3 seconds, and ferritin levels fell from 3282 +/- 3889 to 2131 +/- 2441 ng per ml. In eight patients in whom the dose of rHU-EPO was further increased by up to 50 units per kg three times weekly for three months, the hematocrit rose further to 29.3 +/- 3.0 percent and the rise in hematocrit was accompanied by a further increase in 2,3-DPG to 17.9 +/- 2.8 microM per g of Hb (p < 0.03). There were no major side effects or vascular complications.

Comparing the transfusion medicine content of the NBME's examinations in 1984-1985 and 1989-1990.

Recognition of the seriousness of transfusion-transmitted diseases has been demonstrated by U.S. medical schools through the integration of transfusion medicine (TM) content into their curricula. To evaluate the degree to which these changes in curricula have been reflected in the National Board of Medical Examiners' (NBME) examinations, a study conducted in 1991 evaluated the proportions of TM-related items on Parts I and II of the NBME examinations for 1984-1985 versus 1989-1990. Both Part I (basic sciences) and Part II (clinical sciences) demonstrated significant gains in TM items between the comparison periods (p less than .001), with Part II having the higher gain. An analysis of students' knowledge revealed that students in 1989-1990 tended to perform better on TM items than on examination items generally. The increases in TM content and student performance on TM items on the 1989-1990 examinations suggest that the national effort to expand and improve teaching of TM in U.S. medical schools has been effective.

Whole blood viscosity in beta thalassemia minor.

Patients with heterozygous beta-thalassemia minor have a decreased hematocrit (HCT). Since the HCT is a primary determinant of whole blood viscosity, the known reduction in HCT in beta-thalassemia minor should lead to a measurable reduction of whole blood viscosity. The influence of the relatively lower mean corpuscular volume and consequent higher red blood cell count and beta-thalassemia minor on whole blood viscosity using a microporous viscometer has not previously been the subject of investigation. Accordingly, the blood of a group of normal and beta-thalassemia minor subjects was examined with a microporous viscometer to elucidate further the relations between whole blood viscosity, HCT, and red blood cell count. The data show that for normal and beta-thalassemia minor subjects a significant positive correlation (r = 0.65, p less than 0.01) exists between HCT and whole blood viscosity. However, the slope of the regression of whole blood viscosity and HCT of beta-thalassemia minor subjects was significantly higher z = 3.14, p less than 0.001) than that of normals. Thus, for any given HCT their whole blood viscosity was higher than that of normals. Studies of the relation of red blood cell counts to whole blood viscosity indicate the higher whole blood viscosity at a given HCT was related to the increased red blood cell counts in beta-thalassemia minor subjects. Because of the opposing interactions of HCT and red blood cell counts, the mean whole blood viscosity of the group of beta-thalassemia minor subjects examined was not significantly lower than the normal whole blood viscosity.(ABSTRACT TRUNCATED AT 250 WORDS)