Martin Ellis

The postoperative blood-sparing efficacy of oral versus intravenous tranexamic acid after total knee replacement

To assess the blood-sparing efficacy of tranexamic acid (TA) administered orally or via a variable IV infusion, 80 healthy patients undergoing elective total knee replacement were studied according to a prospective, controlled, randomized, single-blinded study design. Patients were allocated to one of four treatment groups. In group TA-long, 30 min before deflation of the limb tourniquet, an IV bolus dose of TA 15 mg/kg was administered over 30 min. Thereafter, a constant IV infusion of 10 mg · kg−1 · h−1 was administered until 12 h after final deflation of the limb tourniquet. In group TA-short, a similar regimen was followed; however, the constant IV infusion was discontinued 2 h after final deflation of the limb tourniquet (time of discharge from the postanesthesia care unit). Thereafter, oral TA 1 g was administered after 6 and 12 h. In group TA-oral, 60 min before surgery an oral dose of TA 1 g was administered. After surgery, a similar dose of TA was administered every 6 h for the next 18 h. In the control group, TA was not administered. At patient discharge, postoperative allogeneic blood administration was significantly more in group Control when compared with each of the three TA treatment groups. Because oral drug administration is simple and does not require specific infusion equipment, the authors suggest that oral TA is a superior blood-sparing strategy compared with IV drug administration.

The effect of tourniquet application, tranexamic acid, and desmopressin on the procoagulant and fibrinolytic systems during total knee replacement

STUDY OBJECTIVE To assess the influence of tourniquet inflation-deflation as well as desmopressin and tranexamic acid (TA) administration on prothrombin fragment 1.2, fibrinogen, plasmin antiplasmin complex, and D-dimer concentrations during total knee replacement. DESIGN Randomized, placebo-controlled study. SETTING Large referral hospital. PATIENTS 30 ASA physical status I, II, and III patients undergoing total knee replacement. INTERVENTIONS Patients were randomized to one of three treatment groups. Patients received either tranexamic acid, desmopressin, or an equal volume of saline, intravenously. MEASUREMENTS AND MAIN RESULTS Cubital blood was drawn immediately before induction of anesthesia, 1 hour after tourniquet application, and 2 and 15 minutes after tourniquet deflation. Fibrinogen and D-dimer levels were measured using the Clauss Method and latex agglutination, respectively. Plasmin antiplasmin complex and prothrombin fragment 1.2 levels were measured by enzyme-linked immunosorbent assay (ELISA). All assays were performed in duplicate, and intra-assay variability was documented. No statistically significant difference in fibrinogen, D-dimer, plasmin antiplasmin complex, or prothrombin fragment 1.2 levels was demonstrated among the groups. Similarly, within each group there were no statistically significant differences in the variables studied. However, despite the lack of statistical significance, when compared with their levels during tourniquet application, an increase in D-dimer and plasmin antiplasmin complex levels was observed in all three groups at 2 and 15 minutes after tourniquet release. In contrast, no increase in prothrombin fragment 1.2 generation was noted. Significantly more allogeneic blood was transfused in the Control and Desmopressin Groups when compared with the tranexamic acid group (p< 0.02). CONCLUSIONS No evidence of tourniquet-induced fibrinolysis or thrombin generation was demonstrated in the systemic circulation. Desmopressin and tranexamic acid had no significant effect on the variables measured.

A comparative study of the postoperative allogeneic blood-sparing effect of tranexamic acid versus acute normovolemic hemodilution after total knee replacement

UNLABELLED Both acute normovolemic hemodilution (NVHD) and tranexamic acid (TA) are potentially useful allogeneic blood conservation strategies after total knee replacement. However, the relative efficacy of these blood-sparing techniques is unknown. Therefore, to compare the postoperative allogeneic blood sparing of NVHD and TA after total knee replacement, we investigated 40 patients in a prospective, single-blinded study protocol. In Group TA, 30 min before deflating the limb tourniquet, an IV infusion of TA, 15 mg/kg, was administered over a 30-min period. Thereafter, a constant IV infusion of 10 mg x kg(-1) x hr(-1) was administered until 12 h after deflation of the limb tourniquet. Before induction of anesthesia, NVHD patients were bled to a target hematocrit of approximately 28%. Intravascular blood volume was maintained with lactated Ringers solution. All autologous blood was transfused at the end of the surgery. Postoperatively, hematocrit was measured daily. In all cases, a hematocrit <27% was the postoperative transfusion trigger. Before discharge, deep vein thrombosis was excluded by Echo Doppler. Three months after surgery, the incidence of delayed thromboembolic events was assessed. The two groups were demographically comparable. In Group NVHD, 843 mL+/-289 of autologous blood was removed. Despite autologous blood transfusion, during the early postoperative period and until the third postoperative day, the NVHD group had significantly (P < 0.01) lower mean hematocrits when compared with the TA group. Thereafter, because of a significantly (P < 0.0008) greater allogeneic blood requirement in the NVHD group, no statistically significant difference in mean hematocrit recordings was noted among the groups. Blood accumulation in the surgical drain 12 h postoperatively, was significantly (P < 0.0008) higher in the NVHD group (259 mL+/-156) when compared with the TA group (110 mL+/-62). Significantly (P < 0.0008) more allogeneic blood was transfused in the NVHD group (19 U/13 patients) when compared with the TA group (2 U/2 patients). No abnormal Echo Doppler studies were reported. During the 3-mo follow-up period, a deep vein thrombosis and pulmonary embolus were documented in one patient in the NVHD group. We conclude that perioperative hemodynamic stability and allogeneic blood sparing is superior after tranexamic acid administration when compared with normovolemic hemodilution. IMPLICATIONS For total knee replacement, when compared with normovolemic hemodilution, tranexamic acid administration is associated with superior perioperative hemodynamic stability and allogeneic blood sparing.

The effect of storage on the expression of platelet membrane phosphatidylserine and the subsequent impacton the coagulant function of stored platelets

BACKGROUND: Platelet concentrates (PCs) derived from whole blood and stored under standard blood bank conditions undergo changes that are referred to as the platelet storage lesion. This study assesses the effect of PC preparation and storage on the distribution of phosphatidylserine (PS) in the platelet membrane and the effect that this distribution may have on the thrombogenic potential of stored PCs.

Internal jugular vein thrombosis in patients with ovarian hyperstimulation syndrome

OBJECTIVE To describe a case of bilateral internal jugular vein thrombosis complicating ovarian hyperstimulation syndrome (OHSS). DESIGN Case report. SETTING Internal medicine ward in a teaching hospital. PATIENT A 28-year-old nulliparous woman undergoing IVF. INTERVENTION(S) Ultrasonographic Doppler of the neck veins was performed because of pain and swelling in the neck, and bilateral jugular vein thromboses were detected. Laboratory evaluation revealed activated protein C resistance caused by factor V Leiden mutation. Low-molecular-weight heparin (enoxaparin) was administered for the remainder of the pregnancy and for 6 weeks after delivery. MAIN OUTCOME MEASURE Resolution of jugular venous thromboses documented by ultrasonographic Doppler and normal progression of pregnancy. RESULT(S) The patient delivered healthy twins at term. There were no complications arising from the jugular vein thromboses or the low-molecular-weight heparin treatment. CONCLUSION(S) Unusually located venous thrombosis should prompt an evaluation for a hypercoagulable state. The high prevalence (4%-7%) of factor V Leiden mutation in most Western populations and the mutations potential contribution to thrombotic complications in OHSS suggest that screening for this abnormality in women undergoing IVF may be indicated.

Autoimmune thyroid disease and antiphospholipid antibodies

Autoimmune thyroid disease (ATD) is associated with circulating autoantibodies reactive with epitopes on thyroid tissue and that are thought to be pathogenic in the development of these diseases. Antiphospholipid antibodies (APLA) are a family of immunoglobulins that recognize a variety of plasma proteins in association with anionic phospholipids. These antibodies may lead to a number of clinical syndromes including venous and arterial thromboses, thrombocytopaenia, and recurrent fetal loss. We have studied the prevalence of APLA in patients with ATD and have determined the prevalence of the APLA syndrome among APLA‐positive patients.

A comparative study of the postoperative allogeneicblood‐sparing effects of tranexamic acid and of desmopressin after total knee replacement

BACKGROUND: Tissue hypoxia and reperfusion induce abnormal hemostatic function. Therefore, bleeding after total knee replacement (TKR) may be a result of a tourniquet‐induced imbalance of the procoagulant and fibrinolytic systems. Because laboratory confirmation of tourniquet‐induced abnormal hemostasis is difficult to obtain, indirect evidence must be sought.

Thyroid Hormone Is a MAPK-Dependent Growth Factor for Human Myeloma Cells Acting via αvβ3 Integrin

Experimental and clinical observations suggest that thyroid hormone [l-thyroxine (T4) and 3,5,3′-triiodo-l-thyronine (T3)] can support cancer cell proliferation. T3 and T4 promote both tumor cell division and angiogenesis by activating mitogen-activated protein kinase (MAPK) via binding to a hormone receptor on the αvβ3 integrin, overexpressed on many cancer cells. We have studied the responsiveness of several MM cell lines to T3 and T4 and characterized hormonal effects on cell survival, proliferation, and MAPK activation. Overnight T3 (1–100 nmol/L) and T4 (100 nmol/L) incubation enhanced, up to 50% (P < 0.002), MM cell viability (WST-1 assay) and increased cell proliferation by 30% to 60% (P < 0.01). Short exposure (10 minutes) to T3 and T4 increased MAPK activity by 2.5- to 3.5-fold (P < 0.03). Pharmacologic MAPK inhibition blocked the proliferative action of T3 and T4. Antibodies to the integrin αvβ3 dimer and αv and β3 monomers (but not β1) inhibited MAPK activation and subsequent cell proliferation in response to thyroid hormone, indicating dependence upon this integrin. Moreover, tetraiodothyroacetic acid (tetrac), a non-agonist T4 analogue previously shown to selectively block T3/T4 binding to αvβ3 receptor site, blocked induction of MAPK by the hormones in a dose-dependent manner. This demonstration of the role of thyroid hormones as growth factors for MM cells may offer novel therapeutic approaches. Mol Cancer Res; 9(10); 1385–94. ©2011 AACR.

Severe juvenile vaginal bleeding due to Glanzmann's thrombasthenia : Case report and review of the literature

Glanzmanns thrombasthenia is a rare inherited hematological disorder defined by deficiency or abnormality of the glycoprotein (GP) IIb‐IIIa complex. Presenting symptoms are hemorrhagic events, mainly epistaxis, purpura, or menorrhagia. We describe the clinical course and management of a 14‐year‐old girl with Glanzmanns thrombasthenia and severe menorrhagia. Following treatment with 20 U of packed red blood cells, 37 U of platelets, 7 U of fresh frozen plasma, cryoprecipitate, intravenous estrogens, and methylergotrine maleate with no improvement, the uterine cavity was packed for 48 hr. This unusual procedure halted the bleeding and avoided the necessity for a hysterectomy. When treating acute menorrhagia in patients with Glanzmanns thrombasthenia, the physician should be familiar with the characteristics and all treatment modalities for this disorder. Am. J. Hematol. 57:225–227, 1998.

Hemorrhagic complications in patients treated with anticoagulant doses of a low molecular weight heparin (enoxaparin) in routine hospital practice

Low molecular weight heparins (LMWHs) are a rapidly growing class of anticoagulant drug. Their efficacy has been demonstrated in several clinical settings where they are rapidly becoming the anticoagulant of choice. Controlled clinical studies in patients with deep vein thrombosis, pulmonary embolism, and unstable angina have documented that the frequency of major hemorrhage is 0.5-4%. The purpose of the study was to determine the frequency of minor and major hemorrhage occurring in patients receiving anticoagulant doses of an LMWH (enoxaparin) during routine clinical practice. A prospective, observational study of consecutive patients receiving enoxaparin 1 mg/kg twice daily for at least 24 hours in five internal medicine wards of a university teaching hospital was performed. Five hundred forty-nine patients were studied. The mean age was 67.5±15.5 years and the mean duration of enoxaparin therapy was 3.8±1.5 days. Hemorrhage was documented in a total of 94 patients (17.3%). Major hemorrhage occurred in 14 patients (2.6%), injection-site hemorrhage occurred in 55 patients (10%), and minor hemorrhage (noninjection site) was documented in 25 patients (4.7%). There were two deaths attributed to hemorrhage. Patients with major hemorrhage were older than patients with minor or no hemorrhage (75.5±10.4 versus 66.8±15.2 years; p=0.03) and occurred in patients receiving enoxaparin for a longer period (5.14±3.8 days) than those with minor (4±2.5 days) or no hemorrhage (2.9±2.1 days). Major hemorrhage was significantly associated with impaired renal function, chronic liver disease, and concomitant treatment with warfarin or a proton pump inhibitor. Enoxaparin used in anticoagulant doses in unselected medical patients is not associated with more major hemorrhagic complications than observed in controlled clinical trials. Major hemorrhage may be more likely in older patients, in patients with chronic liver disease and impaired renal function, in patients receiving prolonged enoxaparin therapy, and in patients receiving warfarin or proton pump inhibitors.