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378 The effect of intraoperative heparin on markers of thrombosis during hybrid total hip arthroplasty
POSTER PRESENTATIONS P-XV P a t h o p h y s i o l o g i c a l S t u d i e s
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379
THE EFFECT OF INTRAOPERATIVE HEPARIN ON MARKERS OF THROMBOSIS DURING HYBRID TOTAL HIP ARTHROPLASTY
INFLUENCE OF ORAL ANTICOAGULANT THERAPY ON FIBRINOLYSIS
NE Sharrock. G Go. PC Hamel. EA Salvati. TP Sculco, and GH Westrich Depts. of Anes~esia and Orthopaedic Surgery, The Hospital for Special Surgery and Division of Hematology, Mt. Sinai Hospital New York, NY USA
Stancheva A. and Danchev D.
Introduction: Thrombogenesis begins during total hip replacement (THR) during surgery on the femur. Intraoperative heparin has been shown to reduce thrombogenesis during THR. This study assesses the effect of two doses of unfractionated intravenous heparin, administered prior to surgery on the femur, on markers of thrombosis during THR. Methods: Following Institutional Review Board approval and patient consent, 60 patients were randomly assigned to receive blinded intravenous injection of either saline, 10 or 20 Units/kg of unfractionated heparin following insertion of the cup (prior to surgery on the lemur). Central venous samples were drawn at the following points: (1) prior to epidural anesthesia, (2) following insertion of the acetabular component, (3) following reaming of the femur, (4) following relocation of the hip after implantation of a cemented femoral component and (5) 30 minutes postoperatively. Enzyme-linked imraunosorbent assay (ELISA) for prothrombin Fl+2 (Fl+2), fibrinopeptide A (FPA), and D-Direct were performed. Results: No changes in the three markers were noted following insertion of the acetabular component. During surgery on the femur, significant increase in all markers were noted in the saline group. Both 10 and 20 Units/kg of hepurin significantly suppressed the increase in FPA (p<0.001) during and following surgery on the femur (ANOVA). Fl+2 was significantly lower in the 20 Units/kg than saline upon relocation of the hip (p=0.01) (ANOVA) There were no differences in D-Dimer between groups. Intraoperative heparin did not 'affect intra- or postoperative blood loss, postoperative hematocrit or platelet comlts, or surgeon's subjective assessments of bleeding. There was one proximal DVT in the saline group but none in either of the heparin groups. Conclusion: Intravenous unfl'actionated heparin (10-20 Units&g) administered inwaoperatively during THR suppressed formation of FPA by acting primarily as a thrombin inhibitor. This is a sale and effective form of thromboprophylaxis in conjunction with hypotensive epidural anesthesia.
Department of Haemostasis, Government Hospital "Lozenec",Sofia, BULGARIA and Central Clinical Laboratory, Military Medical Academy, Sofia, BULGARIA. Protein C activity is reduced in patients under stable anticoagulant therapy. This would lead to a reduced release of plasminogen activator/tPA/,to a relatively increased level of plasminogen activator inhibitor/PAI- 1/and presumably to a low fibrinolytic activity. Aims: To investigate fibrinolytic activity and residual coagulation activation in patients under stable O.A.T.We assessed PAl-1, Ddimer, TAT and F 1+2. Platelet aggregation to collagen and ADP was assessed. We examined two groups of patients under stable anticoagulant therapy against referent group. Results: The means and the standard deviation for TAT, F I+2, D-dimer and PAl- l were calculated for each of the groups. An evident increase of D-dimet and PAI-I values were registrated in both anticoagulated groups, compared to the reference one, while TAT and F 1+2 values were lowered. We proved no statisticallysignificant correlation between INR/D-dimer and INR/PAI-1 in both groups. Good correlation was observed between INR/TAT r=0.71 p< 0.05 and INR/ F 1+2 r-0.74 p<0.05. Platelet aggregation was decreased both to ADP and collagen. This effect could be explained partially by the disaggregating effect of fibrin fragments on platelets and partially by the slightly enhanced values o~ tPA. In this study we confirm ours and other authors prior oppinion, that there is an activation of fibrinolysis during anticoagulant treatment, and that there is no correlation between INR therapeutic values and increased concentration of D-dimer and PAL 1.
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381
CONCENTRATION OF INMIBITOR OF PLASMLNOGEH ACTIVATOR IN PREGNANT WITH LUPUS ANTICOAGULANT (LA) A.L,Mishenko,A,D.Makatsaria Moscow Medical Academy In the p9thogenesis of throldooohylia~circulation of antiphospholipidic antitels type LA plays an important role.During imcomplicated pregnancy, decreasment of fibrinolytic potential is due to increasment of inhibitor of plasminogen a c t i v a t o r , d u e to addittional production of in the placentae vessels. To it physiological function PAJ and PAJ2(placentae) are practically same. Functional impeirment of ~ndothelial cells by antigen-antibody complexes in pregnants with LA brings to decreasment of AT-lll,impeirment of protein C activation.Decreasment of PAJpsynthesis in placentae vessels,can be seen a~ defensive-adaption mechanisms,leading to reduction of fibrinolysis inhibitors function. From 80 observed pregnants c LA circulation, much differences of PAJ concentration was seen at the II and III trimester of pregnancy. Concentration of PAJ at the I trimester of pregnancy was not much different and was 3,8+0,2(in control group-a,2±0,8:/~l). In II ~IIT trimester 5,~iI,2V~ml and 6,I-I,SV/ml + accordingly(control group 8,6ZI,4 and I0,5 0,6°/ml aecordingly).It is considered that reduction of PAJ2synthesis in placentae,helps to treat thromoogenic tendency in preg~ants with LA and dont block the process of repairasive fibrino!ysis.
DIFFERENT INFLUENCE OF THROMBOLYT1C AND PHYSIOLOGICAL DOSES OF SINGLE-CHAIN UROKINASE-TYPE PLASMINOGEN ACTIVATOR ON WASHED PLATELETS AGGREGATION. IE.Romanova, 2J.Jitkova, 2 0 . N e v e d r o v a , IN.Gorbunova, 2V.Makarov 1Lab. o f P a t h o p h y s i o l o g y , 2Lab. o f P a t h o l o g y a n d P h a r macology of Hemostasis, National Haematological Scientific Center, Moscow, Russia In a recent study we have shown that single-chain urokinase-type plasminogen activator (scu-PA) in a wide concentration range inhibits platelet (PL) aggregation in PRP. To exclude the possible influence of scu-PA/plasma i n t e r f e r e Oll t h i s p r o c e s s t h e a g g r e g a t i o n o f w a s h e d PKs was m~der the investigation. PLs were washed according to modified Mustard's method, suspended in buffer and a d j u s t e d t o 2 5 0 * 109/I. T h e r e s u s p e n d e d P L s w e r e e x p o s e d t o 0 . 0 5 - 1 0 0 n M o f s c u - P A f o r 30 r a i n at 3 7 ° C . T h e a g g r e g a t i o n w i t h 0.6 l U / n d o f t h r o m b i n w a s s t u d i e d . I t w a s f o u n d t h a t t h e e x p o s u r e o f Pl_s t o s c u - P A ( 0 . 0 5 - 0 . 5 n M ) for 1 r a i n r e s u l t e d i n t h e i n h i b i t i o n o f t h e i r a g g r e g a t i o n (75-65% versus control), and inhibitory effect of 5-100 nM scu-PA was more pronounced (48-52% respectively). When PLs were incubated with 0.05-0.5 nM scu-PA for 30 r a i n t i m e - d e p e n d e n t inhibitory effect increase was observed (54-40%). Oil the contrary inhibitory effect of 5-100 nM scu-PA continuously decreased (84-75 %) and s o m e t i m e s a b s o l u t e l y e l i m i n a t e d i n 30 r a i n p e r i o d .
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378
379
THE EFFECT OF INTRAOPERATIVE HEPARIN ON MARKERS OF THROMBOSIS DURING HYBRID TOTAL HIP ARTHROPLASTY
INFLUENCE OF ORAL ANTICOAGULANT THERAPY ON FIBRINOLYSIS
NE Sharrock. G Go. PC Hamel. EA Salvati. TP Sculco, and GH Westrich Depts. of Anes~esia and Orthopaedic Surgery, The Hospital for Special Surgery and Division of Hematology, Mt. Sinai Hospital New York, NY USA
Stancheva A. and Danchev D.
Introduction: Thrombogenesis begins during total hip replacement (THR) during surgery on the femur. Intraoperative heparin has been shown to reduce thrombogenesis during THR. This study assesses the effect of two doses of unfractionated intravenous heparin, administered prior to surgery on the femur, on markers of thrombosis during THR. Methods: Following Institutional Review Board approval and patient consent, 60 patients were randomly assigned to receive blinded intravenous injection of either saline, 10 or 20 Units/kg of unfractionated heparin following insertion of the cup (prior to surgery on the lemur). Central venous samples were drawn at the following points: (1) prior to epidural anesthesia, (2) following insertion of the acetabular component, (3) following reaming of the femur, (4) following relocation of the hip after implantation of a cemented femoral component and (5) 30 minutes postoperatively. Enzyme-linked imraunosorbent assay (ELISA) for prothrombin Fl+2 (Fl+2), fibrinopeptide A (FPA), and D-Direct were performed. Results: No changes in the three markers were noted following insertion of the acetabular component. During surgery on the femur, significant increase in all markers were noted in the saline group. Both 10 and 20 Units/kg of hepurin significantly suppressed the increase in FPA (p<0.001) during and following surgery on the femur (ANOVA). Fl+2 was significantly lower in the 20 Units/kg than saline upon relocation of the hip (p=0.01) (ANOVA) There were no differences in D-Dimer between groups. Intraoperative heparin did not 'affect intra- or postoperative blood loss, postoperative hematocrit or platelet comlts, or surgeon's subjective assessments of bleeding. There was one proximal DVT in the saline group but none in either of the heparin groups. Conclusion: Intravenous unfl'actionated heparin (10-20 Units&g) administered inwaoperatively during THR suppressed formation of FPA by acting primarily as a thrombin inhibitor. This is a sale and effective form of thromboprophylaxis in conjunction with hypotensive epidural anesthesia.
Department of Haemostasis, Government Hospital "Lozenec",Sofia, BULGARIA and Central Clinical Laboratory, Military Medical Academy, Sofia, BULGARIA. Protein C activity is reduced in patients under stable anticoagulant therapy. This would lead to a reduced release of plasminogen activator/tPA/,to a relatively increased level of plasminogen activator inhibitor/PAI- 1/and presumably to a low fibrinolytic activity. Aims: To investigate fibrinolytic activity and residual coagulation activation in patients under stable O.A.T.We assessed PAl-1, Ddimer, TAT and F 1+2. Platelet aggregation to collagen and ADP was assessed. We examined two groups of patients under stable anticoagulant therapy against referent group. Results: The means and the standard deviation for TAT, F I+2, D-dimer and PAl- l were calculated for each of the groups. An evident increase of D-dimet and PAI-I values were registrated in both anticoagulated groups, compared to the reference one, while TAT and F 1+2 values were lowered. We proved no statisticallysignificant correlation between INR/D-dimer and INR/PAI-1 in both groups. Good correlation was observed between INR/TAT r=0.71 p< 0.05 and INR/ F 1+2 r-0.74 p<0.05. Platelet aggregation was decreased both to ADP and collagen. This effect could be explained partially by the disaggregating effect of fibrin fragments on platelets and partially by the slightly enhanced values o~ tPA. In this study we confirm ours and other authors prior oppinion, that there is an activation of fibrinolysis during anticoagulant treatment, and that there is no correlation between INR therapeutic values and increased concentration of D-dimer and PAL 1.
380
381
CONCENTRATION OF INMIBITOR OF PLASMLNOGEH ACTIVATOR IN PREGNANT WITH LUPUS ANTICOAGULANT (LA) A.L,Mishenko,A,D.Makatsaria Moscow Medical Academy In the p9thogenesis of throldooohylia~circulation of antiphospholipidic antitels type LA plays an important role.During imcomplicated pregnancy, decreasment of fibrinolytic potential is due to increasment of inhibitor of plasminogen a c t i v a t o r , d u e to addittional production of in the placentae vessels. To it physiological function PAJ and PAJ2(placentae) are practically same. Functional impeirment of ~ndothelial cells by antigen-antibody complexes in pregnants with LA brings to decreasment of AT-lll,impeirment of protein C activation.Decreasment of PAJpsynthesis in placentae vessels,can be seen a~ defensive-adaption mechanisms,leading to reduction of fibrinolysis inhibitors function. From 80 observed pregnants c LA circulation, much differences of PAJ concentration was seen at the II and III trimester of pregnancy. Concentration of PAJ at the I trimester of pregnancy was not much different and was 3,8+0,2(in control group-a,2±0,8:/~l). In II ~IIT trimester 5,~iI,2V~ml and 6,I-I,SV/ml + accordingly(control group 8,6ZI,4 and I0,5 0,6°/ml aecordingly).It is considered that reduction of PAJ2synthesis in placentae,helps to treat thromoogenic tendency in preg~ants with LA and dont block the process of repairasive fibrino!ysis.
DIFFERENT INFLUENCE OF THROMBOLYT1C AND PHYSIOLOGICAL DOSES OF SINGLE-CHAIN UROKINASE-TYPE PLASMINOGEN ACTIVATOR ON WASHED PLATELETS AGGREGATION. IE.Romanova, 2J.Jitkova, 2 0 . N e v e d r o v a , IN.Gorbunova, 2V.Makarov 1Lab. o f P a t h o p h y s i o l o g y , 2Lab. o f P a t h o l o g y a n d P h a r macology of Hemostasis, National Haematological Scientific Center, Moscow, Russia In a recent study we have shown that single-chain urokinase-type plasminogen activator (scu-PA) in a wide concentration range inhibits platelet (PL) aggregation in PRP. To exclude the possible influence of scu-PA/plasma i n t e r f e r e Oll t h i s p r o c e s s t h e a g g r e g a t i o n o f w a s h e d PKs was m~der the investigation. PLs were washed according to modified Mustard's method, suspended in buffer and a d j u s t e d t o 2 5 0 * 109/I. T h e r e s u s p e n d e d P L s w e r e e x p o s e d t o 0 . 0 5 - 1 0 0 n M o f s c u - P A f o r 30 r a i n at 3 7 ° C . T h e a g g r e g a t i o n w i t h 0.6 l U / n d o f t h r o m b i n w a s s t u d i e d . I t w a s f o u n d t h a t t h e e x p o s u r e o f Pl_s t o s c u - P A ( 0 . 0 5 - 0 . 5 n M ) for 1 r a i n r e s u l t e d i n t h e i n h i b i t i o n o f t h e i r a g g r e g a t i o n (75-65% versus control), and inhibitory effect of 5-100 nM scu-PA was more pronounced (48-52% respectively). When PLs were incubated with 0.05-0.5 nM scu-PA for 30 r a i n t i m e - d e p e n d e n t inhibitory effect increase was observed (54-40%). Oil the contrary inhibitory effect of 5-100 nM scu-PA continuously decreased (84-75 %) and s o m e t i m e s a b s o l u t e l y e l i m i n a t e d i n 30 r a i n p e r i o d .
111