Presentazione sul tema: "IL RISCHIO TROMBOEMBOLICO IN"— Transcript della presentazione:
1 IL RISCHIO TROMBOEMBOLICO IN LAPAROSCOPIAProf.ssa L. AnninoU.O.D Ematologia
2 NUOVA TEORIA DELLA COAGULAZIONE VIAINTRINSECATISSUE FACTOR (Tromboplastina)VII/VIIaCaIXIXaVIIIaPLCAXXaVaPLCAprotrombinatrombina
3 ATTIVAZIONE DELLA TROMBINA TFTFX+VIX+VIIITF+VIIaTROMBINA
4 ATTIVAZIONE DELLA TROMBINA FIBRINOGENOFIBRINAVIXaVIIIXaPIASTRINAPARVVIIIIXIXaVIIaXaMONONUCLEATOPARTFIIaVIXIXaVIIaTMPCPCaTFPARCELL. ENDOTELIALE
5 ATTIVAZIONE DELLA TROMBINA PROTROMBINATROMBINAEMOSTASITFVIIaTFVIIaXaANGIOGENESIVEGFPROTEINASIPAR 1PAR 3PAR 4PAR 2VEGFPGFHIF-1AGGREGAZIONEPIASTRINICAEMOSTASI
6 Predictors of thromboembolic risk in medical and surgical patients Clinical settingPatient risk factorsClinicalMolecularInheritedAcquiredType/duration ofPrevious VTEFactor V LeidenLupussurgeryVaricose veinsProthrombinanticoagulantType ofMalignancy20210A mutationAnticardiolipinanaesthesiaAge > 70Deficiencies:antibodiesStrokeObesityAntithrombin IIIMyeloproliferativeMIProlonged bed restProtein CdiseaseSo far thromboembolic risk levels have only been discussed in terms of clinical background (i.e. type of surgery; medical condition).It is clear, however, that patient factors are also important.The factors listed on this slide have all been identified as contributors to thromboembolic risk.In order to devise a useful risk-assessment model, it is necessary to know to what extent each of these factors influences thromboembolic risk, both individually and in combination.Hyperhomocystei-naemiaCongestive heartLevel of hydrationProtein SfailureSevere medicalHyperhomocystei-naemiaChest infectionillnessIntensive careInfection/sepsisSpinal cord injuryPregnancy/Multiple traumapuerperiumCombined oralcontraceptive
7 Classification of level of VTE risk in surgical patients (6th ACCP Consensus Conference on Antithrombotic Therapy)Low risk Moderate risk High risk Highest riskMinor surgery Major surgery Major surgery Major surgery in patients in patients in patients in patients >40 years plus: <40 years, no risk <40 years, >40 years, Previous VTEfactors no other additional risk Malignancyrisk factors factors or MI Hip or knee surgery Stroke or spinal cordMinor surgery Non-major injuryand risk surgery in Hip fracturefactors patients Major trauma>60 years, Hypercoagulable stateNon-major or with surgery additionalin patients risk factorsaged yearsKnowledge of specific risk factors in patient groups, or in individual patients, forms the basis for appropriate use of prophylaxis.Clinical risk factors include the following: increased age; prolonged immobility; stroke; paralysis; major surgery (particularly operations involving the abdomen, pelvis, and lower extremities); trauma; obesity; varicose veins; cardiac failure; indwelling central venous catheters; inflammatory bowel disease; nephrotic syndrome; and pregnancy or oestrogen use.The hypercoagulable states (thrombophilia) include the following: activated protein C resistance (factor V Leiden); prothrombin variant 20210A; antiphospholipid antibodies (lupus and anticardiolipin antibody); deficiency of antithrombin III, proteins C and S, heparin cofactor II; dysfibrinogenaemia; deceased levels of plasminogen and plasminogen activators; heparin-induced thrombocytopenia; hyperhomocysteinaemia and myeloproliferative disorders.Geerts et al. Chest 2001
8 Markers for specific risk classifications High-risk markersthrombophilia; age >60 years; history of DVT/PE (certain patients)Moderate-risk markersage 40–60 years (certain patients)Low-risk markersage <40 years (in absence of other risk factors)The risk factor indices we saw a moment ago were rather complicated, which would tend to reduce their value in clinical practice.It would greatly simplify risk assessment if we could just identify markers for specific risk classifications.As shown on this slide, a few markers associated with specific levels of risk have emerged from the International Consensus Statement.According to the Consensus Statement, however, thrombophilia is the only marker for a specific risk level (i.e. high risk). In the case of other markers, additional factors, particularly the clinical background, have to be taken into account to assess overall clinical risk.Nicolaides et al. Int Angiol 1997
9 Definition of thromboembolic risk categories Frequency of VTE without prophylaxisCategory Calf-vein Proximal Fatal PE (%)thrombosis (%) vein thrombosis (%)High risk > 1Moderate riskLow risk < 10 < 1 < 0.1This slide defines the three risk categories according to the frequency of calf-vein thrombosis, proximal-vein thrombosis and fatal PE when prophylaxis is not implementedUsing this scheme, most people undergoing orthopaedic surgery or who had medical conditions such as stroke would be classified as high risk.General surgery, acute myocardial infarction, heart failure, chest infection and intensive care patients would all be classified as moderate risk.Modified from Salzman and Hirsh. In: Colman RW et al, eds. Hemostasis and thrombosis; basic principles and clinical practice. New York: Lippincott, 1982 Nicolaides AN et al. Int Angiol 1997PE, pulmonary emobolism
10 Surgical risk-assessment model from the Paris public assistance hospitals General/digestive surgeryStructure of risk-assessment modelRisk associated Risk Risk associatedwith surgery level with patientLess than 45 min, 1 No risk factors no dissectionModerate dissection, 2 Age >40 years less than 45 min confined to bed >4 daysComplicated appendectomy Varicose veins, obesity Inflammatory GI diseaseNeoplastic surgery 3 Actual/developing cancerPrevious thromboembolismThrombophiliaThis practical and easy-to-use model used existing consensus reports and other published reports to draw up risk-assessment tables in four surgical categories, listed on the slide.Risk associated with surgery was rated 1-3 according to type of surgery and other relevant factors (e.g. simple versus complicated procedure; means of surgical access, etc.).Risk of thromboembolism as a result of patient risk factors (e.g. age, use of combined oral contraception, actual/developing cancer) was rated separately using the same scale, 1-3.The risk ratings criteria are clearly summarized in accessible tables; additional notes indicate criteria for raising risk levels (e.g. surgical factors: large dissection; surgery lasting longer than 45 minutes; patient factors: presence of several risk factors).Separate tables have been devised for each type of surgery, with relevant surgical and patient risk factors.Chapuis et al. Sang Thromb Vaiss 1995
11 Paris public assistance hospitals’ recommendations for general surgery Surgical risk + Patient risk = Thromboembolic Recommended factors factors risk therapeutic regimen123LowNo treatment1LMWH, UFHor graduated compression stockings (GCS)Moderate1232This model used existing consensus reports and other published reports to draw up risk-assessment tables in four surgical categories, listed on the slide.Risk associated with surgery was rated 1-3 according to type of surgery and other relevant factors (e.g. simple versus complicated procedure; means of surgical access, etc.)Risk of thromboembolism due to patient factors (e.g. age; use of combined oral contraception; actual/developing cancer) was rated separately using the same scale, 1-3.The risk ratings criteria are clearly summarized in accessible tables; additional notes indicate criteria for raising risk levels (e.g. surgical factors: large dissection; surgery lasting longer than 45 minutes; patient factors: presence of several risk factors).Separate tables have been devised for each type of surgery, with relevant surgical and patient risk factors.It is interesting to note that this model recommends combined pharmacological and mechanical prophylaxis for high-risk patients.123LMWH + GCS orUFH + GCSHigh3Chapuis et al. Sang Thromb Vaiss 1995
12 Laparoscopic surgery and thrombosis Pneumoperitoneum haemodynamicchanges:Increase in the venous pressuredistal to the obstacleDecrease in the blood flowDecrease in the blood venousreturn in lower limbsTHROMBOSISDuration of surgeryReverse Trendelenburg position
13 Laparoscopic surgery and thrombosis Thromboembolism prophylaxis and incidence ofthromboembolic complications of laparoscopic surgeryCatheline JM, Int. Surg. Investig. 2000; 2(1):41-47Non-oncologic surgery: 2384 pts8 DVT (0.33%)0 PE
14 Laparoscopic surgery and thrombosis Thromboembolism prophylaxis and incidence ofthromboembolic complications of laparoscopic surgery6Trendelenburg > 1h8 DVT2Trendelenburg > 3hCatheline JM, Int. Surg. Investig. 2000; 2(1):41-47
15 Laparoscopic surgery and thrombosis Thromboembolism prophylaxis and incidence ofthromboembolic complications of laparoscopic surgeryIn 6/8 cases the DVT occurs:after cessation of LWMH deliveryafter discharge at homebefore post-operative day 10Catheline JM, Int. Surg. Investig. 2000; 2(1):41-47
17 IIa V IXa Xa TF VIIa IFN IL 1 IX VIIa TF IXa V Xa TM PC PCa TF PAR VIIIXaPIASTRINAFIBRINOGENOFIBRINATFPCVIIaIFNIL 1CELL. NEOPLASTICAPARIXVIIaTFIIaIXaVXaVIIIIXaIXTMPCPCaMONONUCLEATOVIIaVTFPARCELL. ENDOTELIALE
18 Complex Relation Between Cancer and VTE VTE occult cancerCancer increased risk of VTE - peri-operatively - in non-surgical patientsCancer resistance to prophylaxis and treatmentCancer central catheter thrombosis
20 Embolia Polmonare e Mortalità 2a causa di morte nel paziente oncologico20% delle TVPPaziente con TVP e tumore:Mortalità a 6 mesi elevata, 3 volte maggiore di quelli senza tumore e non sempre correlata alla gravità del cancroAbbiamo che il 20 % delle trpmbosi insorgono nel paziente neoplasticoIn modo,particolare, si conosce che l’EP rappresenta la II causa di morte nel paziente oncologico.Abbiamo infatti che nel pz. Neoplastico affetto da TVP, la mortalità a 6 mesi risulta molto elevata.La mortalità è 3 volte maggiore ma quello che va sottolineato che non sempre la mortalità è correlata alla gravità del cancro.Hillen HFP: Ann Oncol 2000Levitan et al, Medicine 1999Shen & Pollock South Med J 1980
21 Tasso di trombosi in pazienti neoplastici Correlazioni 9881766111011712020406080100140OvaioEncefaloPancreasLinfomaLeucemiaColonPolmoneTasso di tromboembolismo in base alla localizzazione del tumoreTasso/ pazientiLevitan et al 1999
22 Cancer and Post-operative VTE More extensive surgeryVenous traumaProthrombotic haemostasisChemotherapyRadiationIndwelling vascular linesProlonged immobilization
23 Independent Risk Factors for Major Post-operative Thromboembolism 2,070 patients undergoing elective abdominal surgeryRisk factor OR P Prevalence (%)Malignant disease 1.7 <Duration of surgery >150 min 1.4 <Pre-op hospital stay 6 days 1.6 <Previous major orthopaedic event 1.7 <Pre-op transfusion >1 unit 2.0 <Previous thromboembolism 1.7 <Leg ulcer <Flordal PA et al. Eur J Surg 1996;162:783–9.
24 ENOXACAN StudyEfficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessmentBr J Surg 1997;84:1099–103.
25 ENOXACAN Study Prophylaxis of VTE in Abdominal and Pelvic Cancer Surgery 631 evaluable patientsUFH Enoxaparin (n=319) (n=312)Overall 58 (18.2%) 46 (14.7%)DVT only 56 45PE + DVT 2 0Death 0 1In a randomized study of patients undergoing major elective surgery for abdominal or pelvic malignancy, there were no significant differences in VTE between the 2 groups: enoxaparin 40 mg once daily was as effective as UFH 5,000 units 3 times per day.Br J Surg 1997;84:1099–103.
26 ENOXACAN Study Blood Loss and Haemorrhagic Complications 1,115 patientsUFH Enoxaparin (n=560) (n=555)Intra-op bleeding (ml), median (range) 500 (11–9,670) 500 (22–7,000)Post-op bleeding (ml), median (range) 434 (2–11,250) 385 (2–6,520)Major bleeding, n (%) 16 (2.9) 23 (4.1)Discontinued prophylaxis, n (%) 12 (2.1) 18 (3.2)Injection-site haematoma, n (%) 11 (2.0) 6 (1.1)No difference was observed in bleedings in the same randomized study.Br J Surg 1997;84:1099–103.
27 Duration of Thromboprophylaxis 1 weekor1 month?
28 Risk of VTE over TimeRisk of VTE?TimeSurgeryDischarge
29 Reasons for Prolonged Prophylaxis Late DVTLate fatal PEImpaired haemodynamicsProximal-vein injuryPoor post-discharge mobilizationChange in clinical routinesCommercial interests
30 ENOXACAN IIDuration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancerBergqvist D et al. N Engl J Med 2002;346(13):975–80.
31 Inclusion Criteria Age 40 years Life expectancy 6 months Open, elective, curative surgeryAbdominal/pelvic cancerDuration of surgery 45 minGeneral anaesthesiaBergqvist D et al. N Engl J Med 2002;346(13):975–80.
32 Primary Endpoint Venographically confirmed DVT at Day 28±3 All objectively verified VTE before Day 28±3Bergqvist D et al. N Engl J Med 2002;346(13):975–80.
33 Risk Factors at Baseline Intent-to-treat for efficacy population, n (%)Placebo Enoxaparin (n=167) (n=165)History of VTE 4 (2.4) 5 (3.0)Varicose veins 24 (14.4) 17 (10.3)Obesity 23 (13.8) 22 (13.3)Chronic heart failure 6 (3.6) 7 (4.2)Chronic lung disease 4 (2.4) 10 (6.1)Hormone replacement 4 (2.4) 4 (2.4)Bergqvist D et al. N Engl J Med 2002;346(13):975–80.
34 Characteristics of Surgical Procedures Intent-to-treat for efficacy population, n (%)Placebo Enoxaparin(n=167) (n=165)Location of surgeryGastrointestinal 137 (82) 141 (86)Gynaecological 11 (7) 17 (10)Urological 17 (10) 11 (7)Others 3 (2) 2 (1)2 sites 11 (7) 9 (6)Palliative surgery (3.6) (9.7)*Bleeding complications 8 (5) 10 (6)Duration of surgery, h:min 3: :13median (range) (0:45–11:00) (0:23–9:35)*P=0.024Bergqvist D et al. N Engl J Med 2002;346(13):975–80.
35 Incidence of VTE Intent-to-treat for efficacy population, n (%) Placebo Enoxaparin RRR (%) P(n=167) (n=165) (95% CI)In double-blind periodAll DVT 20 (12.0) 8 (4.8) 60 (10–82) 0.02Proximal DVT 3 (1.8) 1 (0.6)Distal DVT 17 (10.2) 7 (4.2)PE 1 0At 3 monthsAll DVT 23 (13.8) 9 (5.5) 60 (17–81) 0.02Proximal DVT 4 (2.4) 2 (1.2)PE **One fatalThe results of this randomized study of patients undergoing surgery for abdominal or pelvic cancer show that prolonged thromboprophylaxis (lasting approximately 1 month) with enoxaparin is significantly better than conventional prophylaxis (lasting about 1 week). The effect of prolonged thromboprophylaxis is also seen after 3 months, thus there is no rebound phenomenon.
36 Incidence of Haemorrhage Placebo Enoxaparin (n=248) (n=253) n (%)In double-blind periodMinor 9 (3.6) 12 (4.7)Major 0 1 (0.4)Total 9 (3.6) 13 (5.1)At 3 monthsMajor 1 (0.4) 2 (0.8)Cumulative incidence at 3 monthsMajor 1 (0.4) 3 (1.2)Total 11 (4.4) 18 (7.1)**P=0.2No differences were observed in the incidence of haemorrhagic complications between conventional (lasting about 1 week) and prolonged (lasting about 1 month) prophylaxis in cancer surgery.Bergqvist D et al. N Engl J Med 2002;346(13):975–80.
37 Mortality Placebo Enoxaparin (n=167) (n=165) In double-blind period 0 0At follow-up 6 (3.6%) 3 (1.8%)The study was not powered to analyse mortality but it is important to note that the number of deaths is higher in the placebo group. This may be in agreement with other observations where the use of LMWH resulted in a reduction in mortality due to cancer.Bergqvist D et al. N Engl J Med 2002;346(13):975–80.
38 EPARINA NON FRAZIONATA PESO MOLECOLARE MEDIO: dSOLO UN TERZO SI LEGA ALL’AT IIIEFFETTO ANTICOAGULANTE NON PREVEDIBILETERAPIA CON DOSI PERSONALIZZATENECESSARI FREQUENTI ESAMI DI LABORATORIOAT IIIPROTEINE PLASMATICHEEPARINA
39 EPARINA A BASSO PESO MOLECOLARE PESO MOLECOLARE MEDIO: dALTA ATTIVITA’ ANTI Xa/BASSA ATTIVITA’ ANTI IIaMIGLIORE BIODISPONIBILITA’EMIVITA PIU LUNGAATTIVITA’ ANTICOAGULANTE PREVEDIBILEAT IIIPROTEINE PLASMATICHEEPARINA
40 PROFILASSI TVP E/O EP 5000 U/ s.c. X 2 o 3 volte/die EPARINA CALCICA EPARINE A BASSO PESO MOLECOLAREENOXAPARINA U s.c./dieDALTEPARINA U s.c./dieNADROPARINA U s.c./die
42 PROFILASSI PAZIENTI NON CHIRURGICI ICTUS +PARESIBPCO CON RESP. MECCANICAINFARTOSCOMPENSO CARDIACOSEPSIIMMOBILIZZAZIONECATETERE VENOSO (?)MALATTIA INFETTIVANO RISCHIONORISCHIOV.VARICOSETVPFAMILIAREOBESITA’PILLOLA>65 aaGRAVIDANZAS. NEFROSICATROMBOFILIATVP PRECED.CANCROPROFILASSI CON:EPARINA NON FRAZIONATAEPARINE A BASSO PESO MOLECOLARE
43 TERAPIA CON EPARINA SODICA e.v. TERAPIA TVPTERAPIA EPTERAPIA DELL’IMAVANTAGGI:PER e.v. EFFETTO ANTICOAGULANTE IMMEDIATOPOSSIBILITA’ DI MONITORARE L’EFFETTOANTICOAGULANTEBREVE EMIVITAESISTENZA DELL’ANTIDOTO
44 MONITORAGGIO DELL’EFFETTO TERAPIA CON EPARINANON FRAZIONATAMONITORAGGIO DELL’EFFETTOANTICOAGULANTEPTTRANGE TERAPEUTICO:PTT in secondi paziente=PTT in secondi pool normale
45 TERAPIA CON EPARINA NON FRAZIONATA NORMOGRAMMA DI RASCHKEBOLO DI 5000 U DI EPARINA SODICA EVIN PAZ A BASSORISCHIO EMORRAGICO:1680 U/h (40.000/24 ore)IN PAZ AD ALTORISCHIO EMORRAGICO:1240 U/h (30.000/24 ore)PRIMO PTT DOPO 6 ORE POI CONTROLLI OGNI 6 OREpaz. ad alto rischio emorragico:soggetti > 60 annipazienti con gravi patologie intercorrenti di altra naturapazienti reduci da interventi e/o traumialcoolistipazienti con storia di emorragia gastrica/ulcera pepticapazienti con predisposizione emorragicapazienti con piastrine < /mm3
46 CONTROLLO DEL PTT OGNI 6 ORE BOLOEPARINASOSPENSIONEVARIAZIONEDOSE EPARINA<1.280 U/Kg+ 4 U/kg/h40 U/Kg+ 2 U/kg/h- 2 U/kg/h>31 ora- 3 U/kg/h
47 EPARINA A BASSO PESO MOLECOLARE (LWMH)INDICAZIONI TERAPEUTICHEENOXAPARINADALTEPARINANADROPARINATRATTAMENTO DELLA TVP ACUTAPROFILASSI DELLA COAGULAZIONE IN EMODIALISITRATTAMENTO DELL’ANGINA INSTABILE E DELL’IMA NON QPROFILASSI DELLA TVP IN CHIRURGIA GENERALEE IN CHIRURGIA ORTOPEDICAPROFILASSI DELLA TVP IN PAZIENTINON CHIRURGICI
49 EPARINA A BASSO PESO MOLECOLARE (LWMH)Confronto LWMH /EPARINASTANDARD nella terapiadella TVP e/o EPRIDUZIONE RECIDIVE TROMBOEMBOLICHE: 2.7% vs 7%RIDUZIONE EVENTI EMORRAGICI MAGGIORI: 0.9% vs 3.2%RIDUZIONE MORTALITA’ A LUNGO TERMINE: 4.3% vs 8.1%
50 DELL’IPERDOSAGGIO DA EPARINA TRATTAMENTODELL’IPERDOSAGGIO DA EPARINASOLFATO DI PROTAMINAINATTIVA:100% EPARINA NON FRAZIONATA(1 mg per 100 U di Eparina)30% ENOXAPARINA40% DALTEPARINA60% TINZAPARINA
51 PROFILASSI TVP IN PAZIENTI CHIRURGICI ENOXAPARINA U s.c./dieDALTEPARINA U s.c./dieNADROPARINA U s.c./dieINTERVENTODIMISSIONEemocromoLWMH??emocromoLWMHSlide 20Therapy with Coumadin® can be initiated as early as day 1 of heparin therapy, thus minimizing the length of hospitalization. Because of its delayed effect, Coumadin® and heparin therapy should be overlapped for 4–5 days, and heparin therapy should be discontinued once the INR has been stabilized in the therapeutic range of 2.0 to 3.0.*Oral anticoagulant therapy is currently recommended for virtually all patients who have suffered an acute venous thromboembolic episode because the recurrence rate is significantly reduced if such therapy is continued for several months, especially in patients who have ongoing risk factors.*Anticoagulation therapy for pulmonary embolism is the same as that for DVT.1 mese ?giorni
52 TERAPIA ANTICOAGULANTE DELLA TVP Anticoagulante oraleINR > 2emocromoeparinaSlide 20Therapy with Coumadin® can be initiated as early as day 1 of heparin therapy, thus minimizing the length of hospitalization. Because of its delayed effect, Coumadin® and heparin therapy should be overlapped for 4–5 days, and heparin therapy should be discontinued once the INR has been stabilized in the therapeutic range of 2.0 to 3.0.*Oral anticoagulant therapy is currently recommended for virtually all patients who have suffered an acute venous thromboembolic episode because the recurrence rate is significantly reduced if such therapy is continued for several months, especially in patients who have ongoing risk factors.*Anticoagulation therapy for pulmonary embolism is the same as that for DVT.a 6mesiemocromogiorni
53 Terapia/profilassi con anticoagulanti orali nel paziente neoplastico Gravata da un maggior numero di fallimenti:maggior rischio di recidivemaggior rischio di emorragiemonitoraggio più frequente
54 AO nei pazienti oncologici DietaFarmaci (Interazione)Assorbimento intestinale (vomito)Funzionalità epaticaCausano imprevedibili cambiamenti della dose/rispostaCausano impreviste fluttuazioni dell’ INR con necessità di frequenti monitoraggi e frequenti sospensioni222
56 EBPM: alternativa agli AO Vantaggi:non necessita monitoraggioassenza d’ interazione con le piastrinerisposta anticoagulante costante (non interferenza con fattori dietetici o con farmaci concomitanti)rapidità del meccanismo d’azionepiù maneggevoli per le interruzioni/ripristino della terapia anticoagulante (piastrinopenia, manovre invasive)
57 Laparoscopic surgery and thrombosis … all patients will undergo laparoscopy surgerymust be prophylaxed with LWMH…….continued prophylaxis after discharge should beconsidered in individual patients….Catheline JM, Int. Surg. Investig. 2000; 2(1):41-47
58 Laparoscopic surgery and thrombosis RECOMMENDATIONSROUTINE ADMINISTRATION OF PHARMACOLOGICAL ANTI DVTPROPHILAXISHEPARIN IS CONTINUED AL LEAST UNTIL THE PATIENT IS FULLYAMBULANTAVOIDANCE OF PROLONGED REVERSE TRENDELENBURG POSITIONAVOIDANCE OF HIGH INSUFFLATION PRESSUREINTERMITTENT RELEASE OF PNEUMOPERITONEUM ESPECIALLYIN LENGTHY PROCEDUREEARLY POSTOPERATIVE MOBILIZATION OR DISCHARGEMeshinkhes 2003
59 ConclusionsCancer surgery is a high-risk situation for post-operative thromboembolismCancer surgery may be a situation where prolonged thromboprophylaxis is indicatedLWMH for 1 month is significantly better than for 1 week in reducing phlebographically confirmed thrombosisThe benefit is maintained at 3 monthsThe optimal duration is not knownThe optimal pharmacological substance is not known