Prevention Of Postoperative Venous Thrombosis Research Articles

Utilization of the Caprini Score for Risk Stratification of the Arthroplasty Patient in the Prevention of Postoperative Venous Thrombosis.

Venous thromboembolism (VTE) is a serious and predictable complication following arthroplasty. It has been recognized that a strategy utilizing individualized anticoagulation choices based on patient risk stratification results in improved patient outcomes. A 2013 version of the Caprini Risk Score has previously been validated for use in total joint arthroplasty. A Caprini score of 10 or greater assesses the patient as "high risk" while 9 or less is considered "low risk." Patients scored as "low risk" for postoperative VTE receive enteric coated aspirin 81 mg twice a day for 6 weeks. Patients scored as "high risk" for VTE are prescribed apixaban. This retrospective cohort study was conducted to assess the safety and efficacy of the thromboprophylaxis treatment prescribed based on a standardized risk assessment protocol for the calendar year 2020. Patients having total hip arthroplasty, total knee arthroplasty, revision total hip arthroplasty, revision total knee arthroplasty, or bilateral arthroplasties by 13 surgeons (N = 873) were reviewed. Patients were risk assessed using the Caprini Risk Score and thromboprophylaxis was prescribed based on the score obtained. The annual rate of VTE was 0.2%. The Caprini Risk Score is an effective approach to individualize thromboprophylaxis choices after total joint arthroplasty.

Highlights of the American Society of Hematology Meeting 2014: Hemostaseology

In patients suffering from venous thromboembolism, the subsequent anticoagulation treatment significantly reduces the risk of recurrence of further thromboembolic events. However, all available treatment options put the patients at risk of potential life-threatening bleeding complications. Consequently, during the 56th Annual Meeting 2014 of the American Society of Hematology in San Francisco researchers focused on optimizing the use of the current available anticoagulants. Therefore, in the Choosing Wisely® campaign the expert committee recommended to treat patients suffering from their first venous thromboembolism in the setting of major transient risk factors for (not longer than) 3 months. In addition, a French national multicenter trial showed that—if indefinite anticoagulation is not indicated—extended treatment after spontaneous thromboembolism does not reduce the risk of recurrence after stopping the anticoagulation therapy. In patients with cancer-associated thromboembolism, a multicenter study demonstrated the superiority of low molecular heparins over vitamin K antagonist. Finally, a novel, promising target for dissecting hemostasis and antithrombotic effects might be the plasma contact system. Downregulation of factor XI levels in patients undergoing elective knee arthroplasty was an effective method for prevention of postoperative venous thrombosis without increasing the risk of bleeding.

Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis

BackgroundExperimental data indicate that reducing factor XI levels attenuates thrombosis without causing bleeding, but the role of factor XI in the prevention of postoperative venous thrombosis in humans is unknown. FXI-ASO (ISIS 416858) is a second-generation antisense oligonucleotide that specifically reduces factor XI levels. We compared the efficacy and safety of FXI-ASO with those of enoxaparin in patients undergoing total knee arthroplasty.MethodsIn this open-label, parallel-group study, we randomly assigned 300 patients who were undergoing elective primary unilateral total knee arthroplasty to receive one of two doses of FXI-ASO (200 mg or 300 mg) or 40 mg of enoxaparin once daily. The primary efficacy outcome was the incidence of venous thromboembolism (assessed by mandatory bilateral venography or report of symptomatic events). The principal safety outcome was major or clinically relevant nonmajor bleeding.ResultsAround the time of surgery, the mean (±SE) factor XI levels were 0.38±0.01 units per milliliter in the 200-mg FXI-ASO group, 0.20±0.01 units per milliliter in the 300-mg FXI-ASO group, and 0.93±0.02 units per milliliter in the enoxaparin group. The primary efficacy outcome occurred in 36 of 134 patients (27%) who received the 200-mg dose of FXI-ASO and in 3 of 71 patients (4%) who received the 300-mg dose of FXI-ASO, as compared with 21 of 69 patients (30%) who received enoxaparin. The 200-mg regimen was noninferior, and the 300-mg regimen was superior, to enoxaparin (P<0.001). Bleeding occurred in 3%, 3%, and 8% of the patients in the three study groups, respectively.ConclusionsThis study showed that factor XI contributes to postoperative venous thromboembolism; reducing factor XI levels in patients undergoing elective primary unilateral total knee arthroplasty was an effective method for its prevention and appeared to be safe with respect to the risk of bleeding. (Funded by Isis Pharmaceuticals; FXI-ASO TKA ClinicalTrials.gov number, NCT01713361.)

The Future Landscape of Anticoagulation Management

Back then we had warfarin and unfractionated heparin, and we thought that we knew all we needed to know in order to manage those anticoagulants optimally. We were wrong then, and we are probably more subtly wrong now. But I have been asked to comment on what I anticipate the future holds for anticoagulation management and the role of pharmacy in it. Because of the nature of progress, I realize that the more detailed my vision of the future, the greater is the certainty that that vision will be wrong. First, I will focus on what I believe is needed in the near term and then address how I imagine patient selfmonitoring, novel oral anticoagulants, and pharmacogenomics—three topics discussed in this special issue of Pharmacotherapy that reflect areas of change—will affect the future of anticoagulation management.

Heparins and Venous Thromboembolism: Current Practice and Future Directions

Unfractionated heparin (UFH) in adjusted doses and low-molecular-weight heparins (LMWH) in fixed doses are the chosen therapy for the initial treatment of venous thromboembolism. The use of UFH protocols ensures that virtually all patients will promptly achieve the therapeutic range for the activated partial thromboplastin time. However, proper use of UFH requires considerable expertise, can cause inconvenience and has limitations. Unmonitored therapy with subcutaneous LMWH is at least as effective and safe as adjusted-dose UFH, is associated with a considerable reduction of mortality in cancer patients, and permits the treatment of suitable patients in an outpatient setting. LMWH in high prophylactic doses is more effective than UFH and oral anticoagulants for prevention of postoperative venous thrombosis in major orthopedic surgery. Whether thromboprophylaxis should be continued for a few additional weeks after hospital discharge is controversial. LMWH and UFH are equally effective for prevention of postoperative deep-vein thrombosis in cancer patients. In a recent controlled randomized trial, enoxaparin in high prophylactic doses was an effective and safe measure of thromboprophylaxis in ordinary bedridden patients. The efficacy and safety of pentasaccharide (the smallest antithrombin binding sequence of heparin) in the treatment and prevention of venous thromboembolic disorders is currently under investigation.

The effect of the position of the limb on venous impulse foot pumps.

Compression foot pumps are widely used for the prevention of postoperative venous thrombosis. We tested the efficiency of the pump in ten healthy subjects; the velocity of venous blood flow in the common femoral vein was measured in the horizontal, Trendelenberg (foot-up) and reverse-Trendelenberg (foot-down) positions. Application of the foot pump produced an increase in the venous velocity in all subjects. The mean increase in the horizontal position was 27.2% and in the Trendelenberg position 15.4%. In the reverse-Trendelenberg position, the foot pump produced a mean increase of 102.8%. The efficiency of the compression foot pump in increasing venous return is improved by adopting the reverse-Trendelenberg position. This may increase its thromboprophylactic effect.

The effect of the position of the limb on venous impulse foot pumps

Compression foot pumps are widely used for the prevention of postoperative venous thrombosis. We tested the efficiency of the pump in ten healthy subjects; the velocity of venous blood flow in the common femoral vein was measured in the horizontal, Trendelenberg (foot-up) and reverse-Trendelenberg (foot-down) positions. Application of the foot pump produced an increase in the venous velocity in all subjects. The mean increase in the horizontal position was 27.2% and in the Trendelenberg position 15.4%. In the reverse-Trendelenberg position, the foot pump produced a mean increase of 102.8%. The efficiency of the compression foot pump in increasing venous return is improved by adopting the reverse-Trendelenberg position. This may increase its thromboprophylactic effect.

Low molecular weight heparin(oid)s. Clinical investigations and practical recommendations.

Unfractionated heparin (UFH) is traditionally used for prevention and treatment of thrombosis. However, its use is associated with a clinically relevant bleeding risk. Low molecular weight heparin(oid) [LMWH] preparations have been designed to improve upon the efficacy and safety ratio of UFH. They have been investigated in clinical studies following the favourable outcome of extensive animal experimentation to determine their efficacy in the prevention and treatment of venous thromboembolism and in arterial thrombotic conditions such as ischaemic stroke, percutaneous transluminal coronary angioplasty (PTCA) and unstable angina. Indeed, an improved efficacy/safety ratio of LMWHs in the prevention of postoperative venous thrombosis in high risk orthopaedic surgery patients has been observed as compared to UFH prophylaxis. No significant differences with respect to antithrombotic efficacy and bleeding complications were observed in patients with relatively lower risk such as in those undergoing general surgery. Subsequently, these agents have been investigated for the treatment of venous thromboembolism. The results of a series of clinical trials reveal that LMWHs are at least as safe and effective as UFH for initial treatment, with the additional advantage of the possibility of home treatment without the requirement of laboratory control and with a reduced risk of heparin-induced thrombocytopenia. Preliminary data suggest that LMHWs may be suitable for thromboprophylaxis in neurosurgery and stroke patients; in addition, they may have a place in the treatment of patients with acute stroke, unstable angina and individuals in the post-myocardial infarction stage. However, additional confirmatory data for these potential indications are required before definite recommendations can be given. LMWH compounds have at least a similar efficacy and safety as UFH in haemodialysis. In addition, they simplify the anticoagulant regimen because of the efficacy of a single predialysis bolus injection.

A randomized trial of low-dose heparin and intermittent pneumatic calf compression for the prevention of deep venous thrombosis after gynecologic oncology surgery

Our aim was to determine the relative efficacy and complications of low-dose heparin and intermittent pneumatic calf compression for the prevention of postoperative venous thrombosis in patients undergoing surgery for gynecologic malignancy. Randomized trial comparing 107 patients treated with low-dose heparin to 101 patients treated with intermittent pneumatic calf compression was performed. All patients were evaluated with iodine-125 fibrinogen scanning of the legs. Clinical and laboratory variables associated with bleeding complications were recorded prospectively. Venous thrombosis was diagnosed in seven patients receiving low-dose heparin and in four receiving intermittent pneumatic calf compression (p = 0.54). Low-dose heparin patients received more blood transfusions postoperatively (p = 0.02), had increased volume of retroperitoneal drainage (p = 0.02), and the activated partial thromboplastin time was more frequently prolonged (p = 0.001). Low-dose heparin and intermittent pneumatic calf compression provide similar reduction in reducing the incidence of postoperative venous thrombosis. However, low-dose heparin is more frequently associated with postoperative bleeding complications.

Rationale for development of low-molecular-weight heparins and their clinical potential in the prevention of postoperative venous thrombosis

Interest in low-molecular-weight heparins (LMWHs) as potential antithrombotic agents was stimulated by two observations in the mid-1970s and early 1980s. The first was the finding that LMWH fractions prepared from unfractionated heparin (UFH) progressively lost their ability to prolong the activated partial thromboplastin time (APTT) while retaining their ability to inhibit Factor Xa. The second was the observation that LMWHs prepared by chemical depolarization of UFH are antithrombotic in experimental animal models but produce less microvascular bleeding in experimental models for an equivalent antithrombotic effect than the UFH from which they are derived. Subsequently, it was shown that LMWHs inhibit platelet function and impair vascular permeability less than standard heparin and that LMWHs have a longer biological half-life than standard heparin. A number of LMWHs have been evaluated in clinical trials in general and orthopedic surgery and in the treatment of venous thrombosis. LMWHs are highly effective in orthopedic surgery, where they appear to be more effective than standard heparin. LMWHs have also been shown to be either as effective or more effective than UFH in preventing postoperative thrombosis following general surgery. In preliminary studies, LMWHs appear to be as effective as standard heparin in the treatment of venous thrombosis, but larger studies are required using clinically relevant outcome measures.

Pharmacotherapeutic Aspects of Unfractionated and Low Molecular Weight Heparins

Standard unfractionated heparin is a mixture of mucopolysaccharide chains of various length that may vary from 5000 to 30,000 daltons. Heparin is only effective as an anticoagulant in the presence of a plasma protein termed antithrombin III, with which it forms a complex. High- and low-affinity heparin are 2 types that readily bind or do not bind, respectively, to antithrombin III. The pharmacokinetics of unfractionated heparin are compatible with a model based on the combination of a saturable and a linear mechanism. The primary indication for intravenous infusion of conventional heparin is to prevent extension of an established arterial, venous or intracardiac thrombus. The average requirement is 400 U/kg/24h. Subcutaneous administration of 5000U of concentrated unfractionated heparin, administered every 8 or 12 hours, is effective and safe in the prevention of postoperative venous thrombosis and pulmonary embolism in patients at medium thrombotic risk. Adequate prophylaxis is also obtained in patients at high thrombotic risk if 5000U of heparin combined with 0.5mg dihydroergotamine is given subcutaneously 3 times daily, or by monitoring the 3 subcutaneous doses of heparin in order to maintain an adjusted activated partial thromboplastin time (APTT) of around 50 to 70 seconds. Low molecular weight heparins have been produced by a variety of techniques and their molecular weights range from 3000 to 9000 daltons. These preparations have a ratio of anti-factor Xa activity to anti-factor IIa activity of about 4, while the ratio for unfractionated heparin is 1. After intravenous administration of low molecular weight heparin, the half-life of the anti-factor Xa activity is considerably longer than for unfractionated heparin, while the anti-factor IIa half-lives are similar. In contrast to unfractionated heparin, low molecular weight heparin is completely absorbed after subcutaneous administration and its biological half-life is almost twice as long. In spite of certain differences with regard to the ratio between factor Xa and IIa inhibition, the various low molecular weight preparations show a rather similar absorption pattern. The bioavailability of all low molecular weight heparin fractions is substantially higher than that of unfractionated heparin, which renders their use more simple. Low molecular weight heparins less readily enhance platelet aggregation although there is no evidence that low molecular weight heparins are less antigenic or that they do not interact with platelet IgGFc receptor. A lower bleeding incidence for equivalent antithrombotic efficacy of fractionated heparins when compared to unfractionated heparins has yet to be established in humans.(ABSTRACT TRUNCATED AT 400 WORDS)

Antithrombin III prophylaxis of venous thromboembolic disease after total hip or total knee replacement

The use of antithrombin III (ATIII) replacement in combination with low-dose heparin therapy in prevention of postoperative venous thrombosis in patients following total hip replacement or total knee replacement was evaluated. A randomized prospective venographically controlled trial in hip replacement compared treatment with dextran 40 with a regimen of ATIII (1,500 units preoperatively and 1,000 units daily for five days) and low-dose heparin. Patients receiving ATIII/heparin had significantly higher postoperative ATIII concentrations than dextran-treated patients and also had a low incidence of venous thromboembolic disease (7 percent). The ATIII/heparin regimen was well tolerated with no increase in bleeding or significant prolongation of the activated partial thromboplastin time. Two cohorts of patients undergoing total knee replacement were studied using different doses of ATIII in combination with heparin. An initial 10 patients were treated with the same ATIII dose used for patients undergoing total hip replacement, with a 50 percent incidence of venous thrombosis. A second group of 11 patients was treated with twice the dose of ATIII, and an incidence of venous thrombosis of 27 percent was found. The higher ATIII dose resulted in significantly higher ATIII concentrations and maintained the postoperative ATIII concentration above normal. Among patients receiving prophylaxis with either warfarin. dextran, or ATIII/heparin, no clear association was found between reduced ATIII concentrations and occurrence of venous thrombosis. It is concluded that ATIII replacement following total hip or knee replacement corrects the postoperative ATIII deficiency and that the combination of ATIII and low-dose heparin is an effective prophylactic regimen following total hip replacement.

Prevention of Postoperative Venous Thrombosis: A Randomized Trial Comparing Unfractionated Heparin with Low Molecular Weight Heparin in Patients Undergoing Total Hip Replacement

A double blind randomized trial comparing subcutaneous enoxaparin (40 mg once daily) with standard unfractionated calcium heparin administered at a dose of 5,000 units every 8 hours in patients undergoing elective hip replacement has been performed. Treatment regimens began 12 hours preoperatively with enoxaparin, 2 hours preoperatively with standard unfractionated calcium heparin, and were continued for 15 days or until discharge. Venography was performed in all patients. Two hundred thirty-seven patients were included in the study: 113 received unfractionated heparin and 124 received enoxaparin. The incidence of proximal deep vein thrombosis was reduced from 18.5% in the unfractionated heparin group to 7.5% in the enoxaparin group (p = 0.014), and the incidence of total deep vein thrombosis was similarly reduced from 25% to 12.5% (p = 0.03). There were two major bleeding episodes and one minor bleed in the enoxaparin group compared to two minor bleeds in the unfractionated heparin group. Patients who received enoxaparin required fewer red blood cell transfusions and had a significantly higher hemoglobin on postoperative days 3 and 4. Thus prophylaxis with enoxaparin, 40 mg once daily, is simple, safe and more effective than standard low dose unfractionated heparin in preventing deep vein thrombosis in patients undergoing elective hip replacement.

9 Blood rheology in general medicine and surgery

Traditionally, blood rheology tests have been used in diagnosis and monitoring of infection, rheumatic diseases and malignancy, and are still of clinical value in these conditions. In the last twenty years, clinical and epidemiological studies have shown that the haematological determinants of blood flow resistance (haematocrit, fibrinogen, white cell count and altered red and white cell rigidity) are also associated with nutritional, metabolic, endocrine and vascular disorders. Decreased red cell deformability may contribute to reduced red cell survival and anaemia in burns, malaria, liver disease and kidney failure. In trauma and inflammatory disease, overt hyperviscosity is usually prevented by vasodilatation and reduction in the haematocrit. However, low-flow states may arise systemically from haemoconcentration (contracted plasma volume, Chapter 3) in severe burns, inappropriate red cell transfusion, or dehydration due to illness; systemically in circulatory shock; and locally in venous thrombosis or arterial disease. In such circumstances, the intrinsic flow resistance of blood may perpetuate flow disturbance, ischaemia and thrombosis. Conversely, optimal levels of haematocrit, fibrinogen and white cell count may be lower than normal in low-flow states. Haemodilution by colloid infusion is beneficial in burns, shock, major surgery, prevention of postoperative venous thrombosis, chronic stable claudication and possibly in acute stroke and retinal vein thrombosis. Plasma exchange may be beneficial in severe Raynaud's phenomenon. Defibrination with ancrod is effective in prevention and treatment of venous thrombosis but its role in arterial disease is unproven. The benefits of streptokinase therapy in venous thrombo-embolism and acute myocardial infarction may be partly rheological, due to fibrinogen depletion. Drugs with rheological effects may be beneficial in intermittent claudication.

The Use of Prostacyclin Analogue-Containing Suture for the Prevention of Postoperative Venous Thrombosis in the Rat

The ability of prostacyclin analogue incorporated into a controlled-release suture to prevent postoperative venous thrombosis was investigated. Thirteen rats underwent bilateral transection and anastomosis of the common femoral vein. In each animal, polycaprolactone suture containing 0.25 micrograms/cm of the prostacyclin analogue Iloprost (Schering Ag, Berlin, West Germany) was used to perform the anastomosis on one vessel. Similar suture without prostacyclin analogue was used on the contralateral vessel, which served as a control. Functional patency and luminal surface morphology were assessed 24 hours postoperatively. All anastomoses performed using suture containing prostacyclin analogue were patent. Among controls, five anastomoses were patent and eight were occluded. This difference was highly significant (p less than 0.005). All anastomoses performed with prostacyclin analogue-containing suture exhibited a uniform absence of thrombosis. In contrast, eight control veins exhibited a dense, well-organized fibrinous clot that filled the entire lumen, effectively sealing off the vessel. These results suggest that the prostacyclin analogue released from the suture was highly effective in inhibiting thrombus formation without adversely affecting the vessel's ability to achieve hemostasis.

The Use of Prostacyclin Analogue-Containing Suture for the Prevention of Postoperative Venous Thrombosis in the Rat

The Use of Prostacyclin Analogue-Containing Suture for the Prevention of Postoperative Venous Thrombosis in the Rat