IL RISCHIO TROMBOEMBOLICO IN LAPAROSCOPIA Prof.ssa L. Annino U.O.D Ematologia

NUOVA TEORIA DELLA COAGULAZIONE VIA INTRINSECA TISSUE FACTOR (Tromboplastina) VII/VIIa Ca IX IXa VIIIa PL CA X Xa Va PL CA protrombina trombina

ATTIVAZIONE DELLA TROMBINA TF TF X+V IX+VIII TF+VIIa TROMBINA

ATTIVAZIONE DELLA TROMBINA FIBRINOGENO FIBRINA V IXa VIII Xa PIASTRINA PAR V VIII IX IXa VIIa Xa MONONUCLEATO PAR TF IIa V IX IXa VIIa TM PC PCa TF PAR CELL. ENDOTELIALE

ATTIVAZIONE DELLA TROMBINA PROTROMBINA TROMBINA EMOSTASI TF VIIa TF VIIa Xa ANGIOGENESI VEGF PROTEINASI PAR 1 PAR 3 PAR 4 PAR 2 VEGF PGF HIF-1 AGGREGAZIONE PIASTRINICA EMOSTASI

Predictors of thromboembolic risk in medical and surgical patients Clinical setting Patient risk factors Clinical Molecular Inherited Acquired Type/duration of Previous VTE Factor V Leiden Lu pus surgery Varicose veins Prothrombin anticoagulant Type of Malignancy 20210A mutation Anticardiolipin anaesthesia Age > 70 Deficiencies: antibodies Stroke Obesity Antithrombin III Myeloproliferative MI Prolonged bed rest Protein C disease So 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- naemia Congestive heart Level of hydration Protein S failure Severe medical Hyperhomocystei- naemia Chest infection illness Intensive care Infection/sepsis Spinal cord injury Pregnancy/ Multiple trauma puerperium Combined oral contraceptive

Classification of level of VTE risk in surgical patients (6th ACCP Consensus Conference on Antithrombotic Therapy) Low risk Moderate risk High risk Highest risk Minor 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 VTE factors no other additional risk Malignancy risk factors factors or MI Hip or knee surgery Stroke or spinal cord Minor surgery Non-major injury and risk surgery in Hip fracture factors patients Major trauma >60 years, Hypercoagulable state Non-major or with surgery additional in patients risk factors aged 40-60 years Knowledge 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

Markers for specific risk classifications High-risk markers thrombophilia; age >60 years; history of DVT/PE (certain patients) Moderate-risk markers age 40–60 years (certain patients) Low-risk markers age <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

Definition of thromboembolic risk categories Frequency of VTE without prophylaxis Category Calf-vein Proximal Fatal PE (%) thrombosis (%) vein thrombosis (%) High risk 40-80 10-30 > 1 Moderate risk 10-40 1-10 0.1-1 Low risk < 10 < 1 < 0.1 This slide defines the three risk categories according to the frequency of calf-vein thrombosis, proximal-vein thrombosis and fatal PE when prophylaxis is not implemented Using 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 1997 PE, pulmonary emobolism

Surgical risk-assessment model from the Paris public assistance hospitals General/digestive surgery Structure of risk-assessment model Risk associated Risk Risk associated with surgery level with patient Less than 45 min, 1 No risk factors no dissection Moderate dissection, 2 Age >40 years less than 45 min confined to bed >4 days Complicated appendectomy Varicose veins, obesity Inflammatory GI disease Neoplastic surgery 3 Actual/developing cancer Previous thromboembolism Thrombophilia This 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

Paris public assistance hospitals’ recommendations for general surgery Surgical risk + Patient risk = Thromboembolic Recommended factors factors risk therapeutic regimen 1 2 3 Low No treatment 1 LMWH, UFH or graduated compression stockings (GCS) Moderate 1 2 3 2 This 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. 1 2 3 LMWH + GCS or UFH + GCS High 3 Chapuis et al. Sang Thromb Vaiss 1995

Laparoscopic surgery and thrombosis Pneumoperitoneum haemodynamic changes: Increase in the venous pressure distal to the obstacle Decrease in the blood flow Decrease in the blood venous return in lower limbs THROMBOSIS Duration of surgery Reverse Trendelenburg position

Laparoscopic surgery and thrombosis Thromboembolism prophylaxis and incidence of thromboembolic complications of laparoscopic surgery Catheline JM, Int. Surg. Investig. 2000; 2(1):41-47 Non-oncologic surgery: 2384 pts 8 DVT (0.33%) 0 PE

Laparoscopic surgery and thrombosis Thromboembolism prophylaxis and incidence of thromboembolic complications of laparoscopic surgery 6 Trendelenburg > 1h 8 DVT 2 Trendelenburg > 3h Catheline JM, Int. Surg. Investig. 2000; 2(1):41-47

Laparoscopic surgery and thrombosis Thromboembolism prophylaxis and incidence of thromboembolic complications of laparoscopic surgery In 6/8 cases the DVT occurs: after cessation of LWMH delivery after discharge at home before post-operative day 10 Catheline JM, Int. Surg. Investig. 2000; 2(1):41-47

Attività fibrinolitica Tissue Factor Procoagulant protein Attività fibrinolitica T-PA,u-PA,,u-Par Tf, PAI-1, PAI-2 Cellula tumorale Molecole di adesione IL 1, TNF, VEGF Effetto diretto Effetto indiretto

IIa V IXa Xa TF VIIa IFN IL 1 IX VIIa TF IXa V Xa TM PC PCa TF PAR VIII Xa PIASTRINA FIBRINOGENO FIBRINA TF PC VIIa IFN IL 1 CELL. NEOPLASTICA PAR IX VIIa TF IIa IXa V Xa VIII IXa IX TM PC PCa MONONUCLEATO VIIa V TF PAR CELL. ENDOTELIALE

Complex Relation Between Cancer and VTE VTE occult cancer Cancer increased risk of VTE - peri-operatively - in non-surgical patients Cancer resistance to prophylaxis and treatment Cancer central catheter thrombosis

Thrombopathogenetic Factors in Cancer Patients Hypercoagulability TF expression Endothelial damage tumour invasion, chemotherapy, radiation, catheters, host response Platelet dysfunction activation, thrombocytosis Venous stasis venous obstruction, immobility, increased blood viscosity TF, tissue factor

Embolia Polmonare e Mortalità 2a causa di morte nel paziente oncologico 20% delle TVP Paziente con TVP e tumore: Mortalità a 6 mesi elevata, 3 volte maggiore di quelli senza tumore e non sempre correlata alla gravità del cancro Abbiamo che il 20 % delle trpmbosi insorgono nel paziente neoplastico In 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 2000 Levitan et al, Medicine 1999 Shen & Pollock South Med J 1980

Tasso di trombosi in pazienti neoplastici Correlazioni 98 81 76 61 110 117 120 20 40 60 80 100 140 Ovaio Encefalo Pancreas Linfoma Leucemia Colon Polmone Tasso di tromboembolismo in base alla localizzazione del tumore Tasso/10.000 pazienti Levitan et al 1999

Cancer and Post-operative VTE More extensive surgery Venous trauma Prothrombotic haemostasis Chemotherapy Radiation Indwelling vascular lines Prolonged immobilization

Independent Risk Factors for Major Post-operative Thromboembolism 2,070 patients undergoing elective abdominal surgery Risk factor OR P Prevalence (%) Malignant disease 1.7 <0.05 66 Duration of surgery >150 min 1.4 <0.05 35 Pre-op hospital stay 6 days 1.6 <0.02 24 Previous major orthopaedic event 1.7 <0.02 12 Pre-op transfusion >1 unit 2.0 <0.01 7 Previous thromboembolism 1.7 <0.04 6 Leg ulcer 4.2 <0.001 0.5 Flordal PA et al. Eur J Surg 1996;162:783–9.

ENOXACAN Study Efficacy 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 assessment Br J Surg 1997;84:1099–103.

ENOXACAN Study Prophylaxis of VTE in Abdominal and Pelvic Cancer Surgery 631 evaluable patients UFH Enoxaparin (n=319) (n=312) Overall 58 (18.2%) 46 (14.7%) DVT only 56 45 PE + DVT 2 0 Death 0 1 In 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.

ENOXACAN Study Blood Loss and Haemorrhagic Complications 1,115 patients UFH 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.

Duration of Thromboprophylaxis 1 week or 1 month ?

Risk of VTE over Time Risk of VTE ? Time Surgery Discharge

Reasons for Prolonged Prophylaxis Late DVT Late fatal PE Impaired haemodynamics Proximal-vein injury Poor post-discharge mobilization Change in clinical routines Commercial interests

ENOXACAN II Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer Bergqvist D et al. N Engl J Med 2002;346(13):975–80.

Inclusion Criteria Age 40 years Life expectancy 6 months Open, elective, curative surgery Abdominal/pelvic cancer Duration of surgery 45 min General anaesthesia Bergqvist D et al. N Engl J Med 2002;346(13):975–80.

Primary Endpoint Venographically confirmed DVT at Day 28±3 All objectively verified VTE before Day 28±3 Bergqvist D et al. N Engl J Med 2002;346(13):975–80.

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.

Characteristics of Surgical Procedures Intent-to-treat for efficacy population, n (%) Placebo Enoxaparin (n=167) (n=165) Location of surgery Gastrointestinal 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 6 (3.6) 16 (9.7)* Bleeding complications 8 (5) 10 (6) Duration of surgery, h:min 3:05 3:13 median (range) (0:45–11:00) (0:23–9:35) *P=0.024 Bergqvist D et al. N Engl J Med 2002;346(13):975–80.

Incidence of VTE Intent-to-treat for efficacy population, n (%) Placebo Enoxaparin RRR (%) P (n=167) (n=165) (95% CI) In double-blind period All DVT 20 (12.0) 8 (4.8) 60 (10–82) 0.02 Proximal DVT 3 (1.8) 1 (0.6) Distal DVT 17 (10.2) 7 (4.2) PE 1 0 At 3 months All DVT 23 (13.8) 9 (5.5) 60 (17–81) 0.02 Proximal DVT 4 (2.4) 2 (1.2) PE 2* 0 *One fatal The 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.

Incidence of Haemorrhage Placebo Enoxaparin (n=248) (n=253) n (%) In double-blind period Minor 9 (3.6) 12 (4.7) Major 0 1 (0.4) Total 9 (3.6) 13 (5.1) At 3 months Major 1 (0.4) 2 (0.8) Cumulative incidence at 3 months Major 1 (0.4) 3 (1.2) Total 11 (4.4) 18 (7.1)* *P=0.2 No 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.

Mortality Placebo Enoxaparin (n=167) (n=165) In double-blind period 0 0 At 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.

EPARINA NON FRAZIONATA PESO MOLECOLARE MEDIO: 15.000 d SOLO UN TERZO SI LEGA ALL’AT III EFFETTO ANTICOAGULANTE NON PREVEDIBILE TERAPIA CON DOSI PERSONALIZZATE NECESSARI FREQUENTI ESAMI DI LABORATORIO AT III PROTEINE PLASMATICHE EPARINA

EPARINA A BASSO PESO MOLECOLARE PESO MOLECOLARE MEDIO: 4.000-5.000 d ALTA ATTIVITA’ ANTI Xa/BASSA ATTIVITA’ ANTI IIa MIGLIORE BIODISPONIBILITA’ EMIVITA PIU LUNGA ATTIVITA’ ANTICOAGULANTE PREVEDIBILE AT III PROTEINE PLASMATICHE EPARINA

PROFILASSI TVP E/O EP 5000 U/ s.c. X 2 o 3 volte/die EPARINA CALCICA EPARINE A BASSO PESO MOLECOLARE ENOXAPARINA 2000-4000 U s.c./die DALTEPARINA 2500 U s.c./die NADROPARINA 3000 U s.c./die

PROFILASSI PAZIENTI CHIRURGICI CHIR. NEOPLASTICA CHIR. ADDOMINALE CHIR. ORTOPEDICA SPLENECTOMIA APPENDIC. COMPLICATA CHIR. MALATTIE INFIAMM. COLON /TENUE APPENDICECTOMIA ERNIA INGUINALE COLECISTECTOMIA ETA’> 40aa ALLETTATO OBESITA’ POST – PARTUM CANCRO PRECEDENTE TVP TROMBOFILIA PROFILASSI CON: EPARINA NON FRAZIONATA EPARINE A BASSO PESO MOLECOLARE ETA’ < 40aa

PROFILASSI PAZIENTI NON CHIRURGICI ICTUS +PARESI BPCO CON RESP. MECCANICA INFARTO SCOMPENSO CARDIACO SEPSI IMMOBILIZZAZIONE CATETERE VENOSO (?) MALATTIA INFETTIVA NO RISCHIO NO RISCHIO V.VARICOSE TVP FAMILIARE OBESITA’ PILLOLA >65 aa GRAVIDANZA S. NEFROSICA TROMBOFILIA TVP PRECED. CANCRO PROFILASSI CON: EPARINA NON FRAZIONATA EPARINE A BASSO PESO MOLECOLARE

TERAPIA CON EPARINA SODICA e.v. TERAPIA TVP TERAPIA EP TERAPIA DELL’IMA VANTAGGI: PER e.v. EFFETTO ANTICOAGULANTE IMMEDIATO POSSIBILITA’ DI MONITORARE L’EFFETTO ANTICOAGULANTE BREVE EMIVITA ESISTENZA DELL’ANTIDOTO

MONITORAGGIO DELL’EFFETTO TERAPIA CON EPARINA NON FRAZIONATA MONITORAGGIO DELL’EFFETTO ANTICOAGULANTE PTT RANGE TERAPEUTICO: PTT in secondi paziente = 1.5- 2.5 PTT in secondi pool normale

TERAPIA CON EPARINA NON FRAZIONATA NORMOGRAMMA DI RASCHKE BOLO DI 5000 U DI EPARINA SODICA EV IN PAZ A BASSO RISCHIO EMORRAGICO: 1680 U/h (40.000/24 ore) IN PAZ AD ALTO RISCHIO EMORRAGICO: 1240 U/h (30.000/24 ore) PRIMO PTT DOPO 6 ORE POI CONTROLLI OGNI 6 ORE paz. ad alto rischio emorragico: soggetti > 60 anni pazienti con gravi patologie intercorrenti di altra natura pazienti reduci da interventi e/o traumi alcoolisti pazienti con storia di emorragia gastrica/ulcera peptica pazienti con predisposizione emorragica pazienti con piastrine <150.000/mm3

CONTROLLO DEL PTT OGNI 6 ORE BOLO EPARINA SOSPENSIONE VARIAZIONE DOSE EPARINA <1.2 80 U/Kg + 4 U/kg/h 1.2 - 1.5 40 U/Kg + 2 U/kg/h 1.5 - 2.3 2.3 - 3.0 - 2 U/kg/h >3 1 ora - 3 U/kg/h

EPARINA A BASSO PESO MOLECOLARE (LWMH) INDICAZIONI TERAPEUTICHE ENOXAPARINA DALTEPARINA NADROPARINA TRATTAMENTO DELLA TVP ACUTA PROFILASSI DELLA COAGULAZIONE IN EMODIALISI TRATTAMENTO DELL’ANGINA INSTABILE E DELL’IMA NON Q PROFILASSI DELLA TVP IN CHIRURGIA GENERALE E IN CHIRURGIA ORTOPEDICA PROFILASSI DELLA TVP IN PAZIENTI NON CHIRURGICI

EPARINA A BASSO PESO MOLECOLARE (LWMH) DOSI TERAPEUTICHE NELLA TVP/EP NADROPARINA ENOXAPARINA DALTEPARINA ARDEPARINA TINZAPARINA REVIPARINA 90U /Kg/ 12 ORE 180U /Kg/ 24 ORE 100U /Kg/ 12 ORE 200U /Kg/ 24 ORE 130U /Kg/ 12 ORE 175U /Kg/ 24 ORE 100U /Kg/ 12 ORE

EPARINA A BASSO PESO MOLECOLARE (LWMH) Confronto LWMH /EPARINA STANDARD nella terapia della TVP e/o EP RIDUZIONE 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%

DELL’IPERDOSAGGIO DA EPARINA TRATTAMENTO DELL’IPERDOSAGGIO DA EPARINA SOLFATO DI PROTAMINA INATTIVA: 100% EPARINA NON FRAZIONATA (1 mg per 100 U di Eparina) 30% ENOXAPARINA 40% DALTEPARINA 60% TINZAPARINA

PROFILASSI TVP IN PAZIENTI CHIRURGICI ENOXAPARINA 4000 U s.c./die DALTEPARINA 2500 U s.c./die NADROPARINA 3000 U s.c./die INTERVENTO DIMISSIONE emocromo LWMH ?? emocromo LWMH Slide 20 Therapy 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 1 2 3 4 5 6 1 mese ? giorni

TERAPIA ANTICOAGULANTE DELLA TVP Anticoagulante orale INR > 2 emocromo eparina Slide 20 Therapy 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 2 3 4 5 6 3 a 6 mesi emocromo giorni

Terapia/profilassi con anticoagulanti orali nel paziente neoplastico Gravata da un maggior numero di fallimenti: maggior rischio di recidive maggior rischio di emorragie monitoraggio più frequente

AO nei pazienti oncologici Dieta Farmaci (Interazione) Assorbimento intestinale (vomito) Funzionalità epatica Causano imprevedibili cambiamenti della dose/risposta Causano impreviste fluttuazioni dell’ INR con necessità di frequenti monitoraggi e frequenti sospensioni 2 2 2

Sanguinamento degli AO Gitter 1995 Neoplastici 10.6% Non neoplastici 5.3% Prandoni 1996 Neoplastici 8.6% (3.4% mag) Non neoplastici 5.3% (3.0% mag) Palareti 2000 Neoplastici 21.6% Non neoplastici 4.5%

EBPM: alternativa agli AO Vantaggi: non necessita monitoraggio assenza d’ interazione con le piastrine risposta anticoagulante costante (non interferenza con fattori dietetici o con farmaci concomitanti) rapidità del meccanismo d’azione più maneggevoli per le interruzioni/ripristino della terapia anticoagulante (piastrinopenia, manovre invasive)

Laparoscopic surgery and thrombosis … all patients will undergo laparoscopy surgery must be prophylaxed with LWMH… ….continued prophylaxis after discharge should be considered in individual patients…. Catheline JM, Int. Surg. Investig. 2000; 2(1):41-47

Laparoscopic surgery and thrombosis RECOMMENDATIONS ROUTINE ADMINISTRATION OF PHARMACOLOGICAL ANTI DVT PROPHILAXIS HEPARIN IS CONTINUED AL LEAST UNTIL THE PATIENT IS FULLY AMBULANT AVOIDANCE OF PROLONGED REVERSE TRENDELENBURG POSITION AVOIDANCE OF HIGH INSUFFLATION PRESSURE INTERMITTENT RELEASE OF PNEUMOPERITONEUM ESPECIALLY IN LENGTHY PROCEDURE EARLY POSTOPERATIVE MOBILIZATION OR DISCHARGE Meshinkhes 2003

Conclusions Cancer surgery is a high-risk situation for post-operative thromboembolism Cancer surgery may be a situation where prolonged thromboprophylaxis is indicated LWMH for 1 month is significantly better than for 1 week in reducing phlebographically confirmed thrombosis The benefit is maintained at 3 months The optimal duration is not known The optimal pharmacological substance is not known