د. حسين محمد جمعه
اختصاصي الامراض الباطنةالبورد العربي
كلية طب الموصل
2010
ANTITHROMBOTIC AND THROMBOLYTIC THERAPY GUIDELINES
Chest Jun 20088TH ED: ACCP
د. حسين محمد جمعة
اختصاصي الامراض الباطنة
البورد العربي
كلية طب الموصل
2009
• Class I Benefit >>> Risk
• Procedure/ Treatment SHOULD be performed/ administered• Class IIa Benefit >> RiskAdditional studies with focused objectives needed
• IT IS REASONABLE to perform procedure/administer treatment
• Class IIb Benefit ≥ RiskAdditional studies with broad objectives needed; Additional registry data would be helpful
• Procedure/Treatment
• MAY BE CONSIDERED
• Class III
• Risk ≥ BenefitNo additional studies needed
• Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL
• Level A: Data derived from multiple randomized clinical trials or meta-analyses
• Multiple populations evaluated
• Level B: Data derived from a single randomized trial or nonrandomized studies
• Limited populations evaluated
• Level C: Only consensus of experts opinion, case studies, or standard of care
• Very limited populations evaluated
Applying Classification of Recommendations and Level of Evidence
Level of Evidence:
The strength of any recommendation depends on two facors:
the trade-off between benefits, risks, burden, and cost.and the level of confidence in estimates of those benefits and risks.
Grade 1:
a strong recommendation,If benefits do or do not outweigh risks, burden, and costs,
Grade 2:
a weaker recommendation there is less certainty about the magnitude of the benefits and risks, burden, and costs.Support for these recommendations may come from high-quality,moderate-quality,orlow-qualityevidence, labeled, respectively, A, B, and C.
The phrase “we recommend” is used for strong recommendations
Grade 1A, 1B, 1C) and “we suggest” for weaker recommendations (2A, 2B, 2C).
grading system in the 8th edition of the ACCP
• In patients treated with low-molecular-weight heparin (LMWH), we recommend against routine coagulation monitoring (Grade1C)
• In pregnant women treated with therapeutic doses of LMWH, we recommend monitoring of anti-Xa levels (Grade 1C).
In obese patients receiving LMWH prophylaxis or treatment, we suggest weight-based dosing (Grade 2C).
In severe renal insufficiency (creatinine clearance [CrCl] < 30mL/min) who require therapeutic anticoagulation, we suggest the use of unfractionated heparin (UFH) instead of LMWH (Grade 2C).
If LMWH is used in patients with severe renal insufficiency (CrCl < 30 mL/min) who require therapeutic anticoagulation, we suggest using 50% of the recommended dose (Grade 2C).
In patients beginning VKA therapy, we recommend the initiation of oral anticoagulation with doses between
5 and 10 mg for the first 1 or 2 days for most individuals, with subsequent dosing based on the international normalized ratio (INR) response (Grade 1B).
In elderly patients or patients who are debilitated, are malnourished, have congestive heart failure, have liver disease, have had recent major surgery, or are taking medications known to increase the sensitivity to warfarin
(eg, amiodarone), we recommend the use of astarting dose of < 5mg (Grade 1C),
with subsequent dosing based on the INR response.
In patients beginning VKA therapy, we suggest that INR monitoring should be started after the initial two or three doses of oral anticoagulation therapy (Grade 2C).
For patients who are receiving a stable dose of oral anticoagulants, we suggest monitoring at an interval of no longer than every 4weeks (Grade 2C).
Management of Nontherapeutic INRs
For patients with INRs above the therapeutic range,but<5.0 and with no significant bleeding,we recommend lowering the dose or omitting a dose, monitoring more frequently, and resuming therapy at an appropriately adjusted dosewhen the INR is at a therapeutic level.
If only minimally above therapeutic range, or associated with a transient causative factor, no dose reduction may be required (all Grade 1C).
For patients with INRs > 5.0 but < 9.0 and
no significant bleeding, we recommendomitting the next one or two doses, monitoring more frequently, and resuming therapy at an appropriately adjusted dose when the INR is at a therapeutic level (Grade 1C). Alternatively, we suggest omitting a dose and administering vitamin K (1 to 2.5 mg) orally, particularly if the patient is at increased risk of bleeding (Grade2A).
For patients with INRs of >9.0 and no significant bleeding,we re commend holding warfarin therapy and administering a higher dose of vitamin K (2.5 to 5 mg) orally, with the expectation that the INR will be reduced substantially in24 to 48 h (Grade 1B). Clinicians should monitor the INR more frequently, administer additional vitamin K if necessary, and resume therapy at an appropriately adjusted dose when the INR reaches the therapeutic range.
In patients with serious bleeding and elevated INR, regardless of the magnitude of the elevation, we recommend holding warfarin therapy and giving vitamin K (10 mg) by slow IV infusion supplemented with fresh frozen plasma,prothrombin complex concentrate, or recombinant factor VIIa,depending on the urgency of the situation.
We recommend repeating vitamin K administration every 12 h for persistent INR elevation (all 1C).
In patients with life-threatening bleeding (eg, intracranial hemorrhage) and elevated INR, regardless of the magnitude of the elevation, we recommend holding warfarin therapy and administering fresh frozen plasma, prothrombin complex concentrate, or recombinant factor VIIa supplemented with vitamin K, 10 mg by slow IV infusion, repeated, if necessary,depending on the INR (Grade 1C).
Inpatients with mild-to-moderately elevated INRs without major bleeding, we recommend that when vitamin K is to be given, it be administered orally rather than subcutaneously (Grade 1A).
Inpatients who have alupus inhibitor,who have no additional risk factors, and no lack of response to therapy, we recommend a therapeutic target INR of 2.5 (INRrange,2.0 to 3.0) [Grade1A].
In patients who have recurrent thromboembolic events with a therapeutic INR or other additional risk factors for thromboembolic events, we suggest a target INR of 3.0 (INR range, 2.5 to 3.5) [Grade 2C].
Management of INRs in Antiphospholipid Syndrome
Perioperative Management ofAntithrombotic Therapy Perioperative Management of Patients Who AreReceiving VKAs
In patients who require temporary interruption of aVKA before surgery or aprocedure and require normalization of the INR for the surgery or procedure, we recommend stopping VKAs approximately 5 days before surgery over
stopping VKAs within a shorter time interval before surgery to allow adequate time for the INR to normalize (Grade 1B).
In patients who have had temporary interruption of a VKA before surgery or a procedure, we recommend resuming VKAs approximately 12 to 24 h (the evening of or the next morning) after surgery and when there is adequate hemostasis over resumption of VKAs closer to surgery (1C).
In patients who require temporary interruption of aVKA before surgery or aprocedure and whose INR is still elevated (ie, > 1.5) 1 to 2 days before surgery, we suggest administering low-dose (ie, 1 to 2 mg) oral vitamin K to normalize the INR instead of not administering vitamin K (Grade 2C).
In patients with a mechanical heart valve or atrial fibrillation (AF) or venous thromboemboism (VTE) at high risk for thromboembolism, we recommend bridging anticoagulation with therapeutic-dose subcutaneous (SC) LMWH or IVUFH over no bridging during temporary interruption of VKA therapy (Grade 1C);
we suggest therapeutic-dose SC LMWH over IV UFH (Grade2C).
In patients with amechanical heart valve or AF or VTE at moderate risk for thromboembolism,we suggest bridging anticoagulation with therapeutic dose SC LMWH, therapeutic-dose IV UFH, or low-dose SC LMWH over no bridging during temporary interruption of VKA therapy (Grade2C); we suggest therapeutic-dose SC LMWH over other management options (Grade 2C).
Inpatients with a mechanical heart valve or AF orVTE at low risk for thromboembolism, we suggest low-dose SC LMWH or no bridging over bridging with therapeutic-dose SC LMWH or IV UFH (Grade 2C).
Perioperative Management of Patients Who AreReceiving Bridging Anticoagulation
In patients who are receiving bridging anti-coagulation with therapeutic-dose SC LMWH,we recommend administering the last dose of LMWH24 h before surgery or a procedure over administering LMWH closer to surgery )Grade 1C); for the last preoperative dose of LMWH, we recommend administering approximately half the total daily dose instead of100% of the total daily dose (Grade 1C).
In patients who are receiving bridging anticoagulation with therapeutic-dose IV UFH, we recommend stopping UFH approximately 4 h before surgery overstopping UFH closer to surgery(Grade1C).
In patients undergoing a minor surgical or Other invasive procedure and who are receiving bridging anticoagulation with therapeutic-dose LMWH, we recommend resuming this regimen approximately 24 h after (eg, the day after) the procedure when there is adequate hemostasis over ashorter
(eg, < 12 h) time interval (Grade 1C).
In patients undergoing major surgery or ahigh bleeding risk surgery/procedure and for whom postoperative therapeutic-dose LMWH/UFH is planned, we recommend either delaying the initiation of therapeutic-dose LMWH/UFH for 48 to 72 h after surgery when hemostasis is secured, administering low-dose LMWH/UFH after surgery when hemostasis is secured, or completely avoiding LMWH or UFH after surgery over the administration of therapeutic- dose LMWH/UFH in close proximity to surgery (Grade 1C).
We recommend considering the anticipated bleeding risk and adequacy of post-operative hemostasis in individual patients to determine the timing of LMWH or UFH resumption after surgery instead of resuming LMWH or UFH at a fixed time after surgery in all patients (Grade 1C). In patients who are receiving bridging anticoagulation with LMWH, we suggest against the routine use of anti-factor Xa levels to monitor the anticoagulant effect of LMWHs (Grade 2C).
Perioperative Management of Patients Who AreReceiving Antiplatelet Therapy
In patients who require temporary interruption of aspirin- or clopidogrel-containing drugs before surgery or a procedure, we suggest stopping this treatment 7 to 10 days before the procedure over stopping this treatment closer to surgery (Grade 2C).In patients who have had temporary interruption of aspirin or clopidogrel therapy because of surgery or a procedure, we suggest resuming aspirin or clopidogrel approximately 24 h (or the next morning) after surgery when there is adequate hemostasis in-stead of resuming closer to surgery (Grade 2C).
For patients who are not at high risk for cardiac events, we recommend interruption of antiplatelet drugs (Grade 1C).
For patients at high risk of cardiac events (exclusive of coronary stents) scheduled for noncardiac surgery,we suggest continuing aspirin up to and beyond the time of surgery (Grade 2C);
if patients are receiving clopidogrel, we suggest interrupting clopidogrel at least 5 days and, preferably, within 10 days prior to surgery
(Grade 2C).
In patients scheduled for coronary artery bypass grafting (CABG), we recommend continuing aspirin up to and beyond the time of CABG (Grade1C)
In patients scheduled for CABG, we recommend interrupting clopidogrel at least 5 days and, preferably, 10 days prior to surgery (Grade 1C).
In patients scheduled for percutaneus coronary intervention (PCI), we suggest continuing aspirin up to and beyond the time of the procedure; if clopidogrel is interrupted prior to PCI, we suggest resuming clopidogrel after PCI with a loading dose of 300 to 600 mg (Grade 2C).
In patients with a drug-eluting coronary stent who require surgery within 12 months of stent placement, we recommend continuing aspirin and clopidogrel in the perioperative period (Grade 1C).
In patients who are receiving antiplatelet
drugs, we suggest against the routine use of platelet function assays to monitor the anti-thrombotic effect of aspirin or clopidogrel (Grade 2C).Perioperative Management of AntithromboticTherapy in Patients Who Require Dental,Dermatologic, or Ophthalmologic Procedures
In patients who are undergoing minor dental procedures minor dermatologic procedures and are receiving VKAs, we recommend continuing VKAs around the time of the procedure and coadministering an oral prohemostatic agent(Grade1B)for dental procedures
Inpatients who are undergoing minor dental procedures and are receiving aspirin, we recommend continuing aspirin around the time of the procedure (Grade 1C).
In patients who are undergoing minor dental procedures and are receiving clopidogrel, please refer to the previous recommendations
In patients who are undergoing cataract removal and are receiving VKAs, we recommend continuing VKAs around the time of the procedure (Grade 1C).
In patients who are undergoing cataract removal and are receiving aspirin, we recommend continuing aspirin around the time of the procedure (Grade 1C).
Perioperative Management of AntithromboticTherapy Patients Who Require Urgent Surgical orOther Invasive Procedures
In patients who are receiving VKAs and require reversal of the anticoagulant effect for an urgent surgical or other invasive procedure,we recommend treatment with low-dose (2.5 to 5.0 mg) IV or oral vitamin K (Grade 1C).
For more immediate reversal of the anticoagulant effect, we suggest treatment with fresh-frozen plasma or another prothrombin concentrate in addition to low-dose IV or oral vitamin K (Grade2C).
For patients receiving aspirin,clopidogrel,or both, are undergoing surgery and have excessive or life-threatening perioperative bleeding, we suggest transfusion of platelets or administration of other prohemostatic agents (Grade 2C).
Treatment and Prevention ofHeparin-Induced Thrombocytopenia
For patients receiving heparin in whom the clinician considers the risk of heparin-induced Thrombocytopenia (HIT)tobe>1.0%,we recommend platelet count monitoring over no platelet count monitoring (Grade 1C).For patients receiving heparin who have an estimated risk of HIT of 0.1to1.0%,we suggest platelet count monitoring over no platelet count monitoring (Grade 2C).
For patients who are starting UFH or LMWH treatment and who have received UFH within the past 100 days, or those patients in whom exposure history is uncertain, we recommend obtaining a baseline platelet count and then a repeat platelet count within 24 h of starting heparin over not obtaining a repeat platelet count (Grade 1C).
For patients who are receiving therapeutic-dose UFH, we suggest platelet count monitoring at least every 2 or 3 days from day 4 to day 14 or until heparin is stopped.
Platelet Count Monitoring in Postoperative Patients Receiving UFH AntithromboticProphylaxis (Highest Risk Group for HIT)
For patients who are receiving postoperative antithrombotic prophylaxis with UFH, ie,the patient population at highest risk for HIT (HIT risk > 1%), we suggest at least every other-day platelet count monitoring between postoperative days 4 to 14 (or until UFH is stopped, whichever occurs first) over less frequent platelet count monitoring (Grade 2C).
Platelet Count Monitoring in Patients inWhom HIT Is Infrequent (0.1 to 1%)
For medical/obstetrical patients who are receiving prophylactic-dose UFH, postoperative patients receiving prophylactic-dose LMWH,postoperative patients receiving intravascular catheter UFH “flushes,” or medical/obstetrical patients receiving LMWH after first receiving UFH (estimated HIT risk, 0.1 to 1%), we suggest platelet count monitoring at least every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first).Platelet Count Monitoring When HIT Is Rare0.1%): UFH and LMWH
For medical/obstetrical patients who are receiving only LMWH, or medical patients who are receiving only intravascular catheter UFH flushes (HIT risk < 0.1%),
we suggest clinicians do not use routine platelet count monitoring (Grade 2C).
Screening for Subclinical HIT AntibodySeroconversion
In patients who receive heparin, or in whom heparin treatment is planned (eg, for cardiac or vascular surgery), we recommend against routine HIT antibody testing in the absence of thrombocytopenia, thrombosis, heparin-induced skin lesions,or other signs pointing to apotential diagnosis of HIT (Grade 1C).When Should HIT Be Suspected?
For patients who are receiving heparin or have received heparin within the previous 2 weeks, we recommend investigating for a diagnosis of HIT if the platelet count falls by> 50%,and/ or athrombotic event occurs,between days 5 and 14 (inclusive) following initiation of heparin, even if the patient is no longer receiving heparin therapy when thrombosis or thrombocytopenia has occurred (Grade 1C).Treatment of HIT Nonheparin Anticoagulants for Treating HIT(With or Without Thrombosis)
For patients with strongly suspected (or confirmed) HIT,whether or not complicated by thrombosis,we recommend use of an alternative,nonheparin anticoagulant (danaparoid [Grade 1B], lepirudin [Grade 1C], argatroban [Grade 1C], fondaparinux [Grade 2C], bivalirudin [Grade 2C]) over the further use of UFH or LMWH therapyor initiation/ continuation of a VKA (1B).For patients with strongly suspected or confirmed HIT, we recommend against the use of VKA(coumarin)therapy until after the plateet count has substantially recovered (ie,usually to at least 150 ×109 /L) over starting VKA ther-apy at a lower platelet count (Grade 1B); that VKA therapy be started only with low, maintenance doses (maximum, 5 mg of warfarin or 6 mg of phenprocoumon) rather than with higher initial doses (Grade 1B);
and the nonheparin anticoagulant (eg, lepirudin, argatroban, dan-aparoid) be continued until the platelet count has reached a stable plateau, the INR has reached the intended target range, and after a minimum overlap of at least 5 days between nonheparin anticoagulation and VKA therapy rather than a shorter overlap (Grade 1B).
For patients receiving aVKA at the time of diagnosis of HIT,we recommend use of vitamin K 10 mg po or 5 to 10 mg IV) [Grade 1C].
For patients with strongly suspected HIT,whether or not complicated by thrombosis, we recommend against use of LMWH (Grade 1B).
For patients with strongly suspected or confirmed HIT who do not have active bleeding, we suggest that prophylactic platelet transfusions should not be given (Grade 2C).
For patients with ahistory of HIT who are HIT antibody negative and require cardiac surgery, we recommend the use of UFH over anonheparin anticoagulant (Grade 1B).
For patients with a history of HIT who are antibody positive by platelet factor 4-dependent enzyme immunosorbent assay but antibody Negative by washed platelet activation assay,we recommend the use of UFH over a nonheparin
anticoagulant (Grade 2C).
(Remark: Preoperative and postoperative anticoagulation, if indicated, should be given with a nonheparin anticoagulant).
We recommend that mechanical methods of thromboprophylaxis be used primarily in
patients at high risk of bleeding (Grade 1A),orpossibly as an adjunct to anticoagulant-based
thromboprophylaxis (Grade 2A).
We recommend against the use of aspirin alone as thromboprophylaxis against VTE for any patient group (Grade 1A).
We recommend that renal function be considered when making decisions about the use and/or the dose of LMWH, fondaparinux,And other antithrombotic drugs that are cleared by the kidneys, particularly in elderly patients,patients with diabetes mellitus, and those at High risk for bleeding (Grade1A).
Depending on the circumstances, we recommend one of the following options in this situation:
avoiding the use of an anticoagulant that bioaccumulates in the presence of renal impairment, using alower dose of the agent,
or monitoring the drug level or its anticoagulant effect (Grade 1B).
General Surgery
For low-risk general surgery patients who are undergoing minor procedures and have no additional thromboembolic risk factors, we recommend against the use of specific thromboprophylaxis other than early and frequent ambulation (Grade 1A).For moderate-risk general surgery patients who are undergoing a major procedure for benign disease, we recommend thromboprophylaxis with LMWH,low-doseUFH(LDUH),or fondaparinux (each Grade 1A).
For higher-risk general surgery patients who are undergoing a major procedure for cancer, we recommend thromboprophylaxis with LMWH, LDUH tid, or fondaparinux (each Grade1A).
For general surgery patients with multiple risk factors for VTE who are thought to be at particularly high risk, we recommend that:
apharmacologic method (ie, LMWH, LDUH tid,or fondaparinux) be combined with the optimal use of amechanical method (ie,graduated compression stockings [GCS] and/or intermittent pneumatic compression [IPC]) [Grade 1C].
For general surgery patients with a high risk of bleeding,we recommend the optimal use of mechanical thromboprophylaxis with properly fitted GCS or IPC (Grade 1A). When the high bleeding risk decreases, we recommend that pharmacologic thromboprophylaxis be
substituted for or added to the mechanical thromboprophylaxis (Grade 1C).
For all patients undergoing major gynecologic surgery, we recommend that thromboprophylaxis be used routinely (Grade 1A).
major gynecologic surgery
For patients undergoing CABG, we recommend the use of thromboprophylaxis with LMWH, LDUH, or optimally used bilateral GCS or IPC (Grade 1C).
For patients undergoing CABG, we suggest the use of LMWH over LDUH (Grade 2B).
For patients undergoing CABG with ahigh risk of bleeding, we recommend the optimal use of mechanical thromboprophylaxis with properly fitted bilateral GCS or IPC (Grade 1C).
For acutely ill medical patients admitted to hospital with congestive heart failure or severe respiratory disease, or who are confined to bed and have one or more additional risk factors, including active cancer, previous VTE,sepsis, acute neurologic disease, or inflammatory bowel disease, we recommend thromboprophylaxis with LMWH (Grade 1A), LDUH (Grade 1A), or fondaparinux (Grade 1A).
For medical patients with risk factors for VTE,and in whom there is acontraindication to anticoagulant thromboprophylaxis, we recommend the optimal use of mechanical thromboprophylaxis with GCS or IPC (Grade 1A).
Acutely ill medical patients
For cancer patients receiving chemotherapy or hormonal therapy,we recommend against the routine use of thromboprophylaxis for the primary prevention of VTE (Grade 1C).
For cancer patients,we recommend against the routine use of primary thromboprophylaxis to try to improve survival (Grade 1B).
For travelers who are taking flights>8h,we recommend the following general measures:
a voidance of constrictive clothing around the lower extremities or waist, maintenance of adequate hydration, and frequent calf muscle contraction (1C).For long-distance travelers with additional risk factors for VTE, we recommend the general measures listed above. If active thromboprophylaxis is considered because of a perceived high risk of VTE,we suggest the use of properly fitted,below-knee GCS, providing 15 to 30 mm Hg of pressure at the ankle (Grade 2C), or a single prophylactic dose of LMWH, injected prior to departure (Grade 2C).
For long-distance travelers, we recommend against the use of aspirin for VTE prevention (Grade 1B).
Antithrombotic Therapy for VenousThromboembolic DiseaseInitial Anticoagulation of Acute DVT of the Leg
For patients with objectively confirmed DVT, we recommend short-term treatment with SC LMWH (Grade 1A),IVUFH (Grade 1A),monitored SC UFH (Grade 1A), fixed-dose SC UFH (Grade 1A), or SC fondaparinux (Grade 1A) rather than no such acute treatment.
For patients with a high clinical suspicion of DVT, we recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C).
In patients with acute DVT, we recommend initial treatment with LMWH, UFH, or fondaparinux for at least 5 days and until the INR is > 2.0 for 24 h (Grade 1C).
In patients with acute DVT, we recommend initiation of VKA together with LMWH,UFH, or fondaparinux on the first treatment day rather than delayed initiation of VKA (Grade 1A).
In patients with acute DVT, if IV UFH is chosen, we recommend that, after an initial IV bolus (80U/kg or5,000U) it be administered by continuous infusion (initially at a dose of 18 U/kg/h or 1,300 U/h) with dose adjustment to achieve and maintain an APTT prolongation that corresponds to plasma heparin levels of 0.3 to 0.7 IU/mL anti-Xa activity by the amidolytic assay rather than administration as IV boluses throughout treatment, or administration with out coagulation monitoring (Grade 1C).
In patients with acute DVT, if monitored SC UFH is chosen, we recommend an initial dose of 17,500 U, or a weight-adjusted dose of about 250 U/kg, bid, with dose adjustment to achieve and maintain an APTT prolongation that corresponds to plasma heparin levels of 0.3 to 0.7 IU/mL anti-Xa activity when measured 6 h after injection rather than starting with a smaller initial dose (Grade 1C)
In patients with acute DVT, if fixed dose, unmonitored SC UFH is chosen, we recommend an initial dose of 333 U/kg followed by a twice-daily dose of 250 U/kg rather than non weight-based dosing (Grade 1C)
In patients with acute DVT, we recommend initial treatment with LMWH SC once or twice daily, as an out patient if possible (Grade 1C) or as an inpatient if necessary (Grade 1A),rather than treatment with IV UFH.
In patients with acute DVT treated with LMWH, we recommend against routine monitoring with anti-factor Xa level measurements (Grade 1A).
In patients with acute DVT and severe renal failure, we suggest UFH over LMWH (Grade 2C).
Catheter-Directed Thrombolysis for Acute DVT
In selected patients with extensive acute proximal DVT (eg, iliofemoral DVT, symptoms for < 14 days, good functional status, life expectancy of > 1 year) who have a low risk of bleeding, we suggest that catheter-directed thrombolysis may be used to reduce acute symptoms and postthrombotic morbidity if appropriate expertise and resources are available (Grade 2B).After successful catheter-directed thrombolysis in patients with acute DVT, we suggest correction of underlying venous lesions using balloon angioplasty and stents (Grade 2C).
• We suggest pharmacomechanical thrombolysis (eg, with inclusion of thrombus fragmentation and/or aspiration) in preference to catheter-directed thrombolysis alone to shorten treatment time if appropriate expertise and resources are available (Grade 2C).
• After successful catheter-directed thrombolysis in patients with acute DVT, we recommend the same intensity and duration of antico-agulant therapy as for comparable patients who do not undergo catheter-directed thrombolysis (Grade 1C).
Systemic Thrombolytic Therapy for Acute DVT
In selected patients with extensive proximal DVT (eg, symptoms for < 14 days, good functional status, life expectancy of > 1 year) Who have alow risk of bleeding,we suggest that systemic thrombolytic therapy may be used to reduce acute symptoms and postthrombotic morbidity if catheter-directed thrombolysis is not available (Grade 2C).
In selected patients with acute iliofemoral DVT (eg, symptoms for < 7 days, good functional status, and life expectancy of > 1 year), we suggest that operative venous thrombectomy may be used to reduce acute symptoms and postthrombotic morbidity if appropriate expertise and resources are available (Grade 2B).
If such patients do not have a high risk of bleeding, we suggest that catheter-directed thrombolysis is usually preferable to operative venous thrombectomy (Grade 2C).
In patients who undergo operative venous thrombectomy, we recommend the same intensity and duration of anticoagulant therapy afterwards as for comparable patients who do not undergo venous thrombectomy (Grade 1C).
• For patients with DVT, we recommend against the routine use of a vena cava filter in addition to anticoagulants (Grade 1A).For patients with acute proximal DVT,if anticoagulant therapy is not possible because of the risk of bleeding, we recommend placement of an inferior vena cava filter (Grade 1C).
• For patients with acute DVT who have an inferior vena cava filter inserted as an alternative to anticoagulation, we recommend that they should subsequently receive a conventional course of anticoagulant therapy if their risk of bleeding resolves (Grade 1C).
Immobilization for the Treatment of Acute DVT
In patients with acute DVT, we recommend early ambulation in preference to initial bed rest when this is feasible (Grade 1A).For patients with DVT secondary to atransient( reversible) risk factor, we recommend treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A).
we recommend the same initial and long-term anticoagulation as for comparable patients with symptomatic DVT
Treatment of Asymptomatic DVT of the Leg
For a patient who has had a symptomatic proximal DVT, we recommend the use of an elastic compression stocking with an ankle pressure gradient of 30-40mmHg if feasible(Grade 1A).
Compression therapy,which may include use of bandages acutely, should be started as soon as feasible after starting anticoagulant therapy and should be continued for a minimum of 2 years,and longer if patients have symptoms of the postthrombotic syndrome (PTS).
(Note: feasibility, both short and long term, refers to ability of patients and their caregivers to apply and remove stockings.)
For patients with severe edema of the leg due to PTS, we suggest a course of IPC (Grade 2B).
For patients with mild edema of the leg due to PTS, we suggest the use of elastic compression stockings (Grade 2C).
For patients with venous ulcers,we suggest that hyperbaric oxygen not be used (Grade 2B).
In patients with venous leg ulcers, we suggest pentoxifylline, 400 mg po tid, in addition to local care and compression and/or IPC (Grade 2B).
In patients with persistent venous ulcers,
we suggest that rutosides, in the form of micronized purified flavonoid fraction given orally, or sulodexide administered intramuscularly and then orally, be added to local care and compression (Grade 2B).For patients in whom there is a high clinical suspicion of PE, we recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C).
Inpatients with acute PE,we recommend initial treatment with LMWH, UFH, or fondaparinux for at least 5days and until the INR is >2.0 for at least 24 h (Grade 1C).
In patients with acute PE, we recommend initiation of VKA together with LMWH, UFH, or fondaparinux on the first treatment day rather than delayed initiation of VKA (Grade 1A).
In patients with acute nonmassive PE, we recommend initial treatment with LMWH over IVUFH (Grade1A).
Inpatients with massive PE,In other situations where there is concern about SC absorption, or in patients in whom thrombolytic therapy is being considered or planned,we suggest IV UFH over SC LMWH, SC fondaparinux, or SC UFH (Grade 2C).
All PE patients should undergo rapid risk stratification (Grade 1C). For patients with evidence of hemodynamic compromise, we recommend use of thrombolytic therapy unless there are major contraindications owing to bleeding risk (Grade 1B). Thrombolysis in these patients should not be delayed, because irreversible cardiogenic shock may ensue. In selected high risk patients without hypotension who are judged to have a low risk of bleeding, we suggest administration of thrombolytic therapy (Grade 2B).
The decision to use thrombolytic therapy depends on the clinician’s assessment of PE severity, prognosis, and risk of bleeding.
For the majority of patients with PE, we recommend against using thrombolytic therapy (Grade 1B).
In patients with acute PE, with administration of thrombolytic therapy,we recommend use of regimens with short infusion times (eg,a 2-h infusion) over those with prolonged infusion times (eg, a 24-h infusion) [Grade 1B].
In selected highly compromised patients who are unable to receive thrombolytic therapy because of bleeding risk, or whose critical status does not allow sufficient time for systemic thrombolytic therapy to be effective,we suggest that pulmonary embolectomy may be used if appropriate expertise is available (Grade 2C).
For patients with PE secondary to atransient (reversible) risk factor, we recommend treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A).
For patients with unprovoked PE, we recommend treatment with a VKA for at least 3 months (Grade 1A). We recommend that after 3 months of anticoagulant therapy, all patients with unprovoked PE should be evaluated for the risk-benefit ratio of long-term therapy (Grade 1C).
For patients with a first unprovoked episode of VTE that is a PE, and in whom risk factors for bleeding are absent and for whom good anticoagulant monitoring is achievable, We recommend long-term treatment (Grade1A).
In patients who are unexpectedly found to have asymptomatic PE, we recommend the same initial and long-term anticoagulation as for comparable patients with symptomatic PE (Grade 1C).
In selected patients with chronic thromboembolic pulmonary hypertension (CTPH),such as those with central disease under the care of an experienced surgical/medical team,we recommend pulmonary thromboendarterectomy (Grade 1C).
For all patients with CTPH, we recommend life-long treatment with a VKA targeted to an INR of 2.0 to 3.0 (Grade 1C).
For patients with CTPH undergoing pulmonary thrombo endarterectomy , we suggest the placement of apermanent vena caval filter before or at the time of the procedure (Grade 2C).
For patients with symptomatic infusion thrombophlebitis as a complication of IV infusion, we suggest oral diclofenac or another nonsteroidal antiinflammatory drug (Grade 2B), topical diclofenac gel (Grade 2B), or heparin gel
) Grade 2B) until resolution of symptoms or for up to 2 weeks. We recommend against the use of systemic anticoagulation (Grade 1C).
For patients with acute upper-extremity DVT, we recommend initial treatment with therapeutic doses of LMWH, UFH, or fondaparinux as described for leg DVT [Grade 1C]. In selected patients with acute upper-extremity DVT (eg, those with primary thrombolytic treatment who have severe persistent symptoms), we suggest that catheter extraction, surgical thrombectomy, transluminal angioplasty, or a staged approach of lysis followed by a
Vascular interventional or surgical procedure may
be used, if appropriate expertise and resources
are available (all Grade 2C).
In selected patients with acute upper extremity DVT (eg, those in whom anticoagulant treatment is contraindicated and there is clear evidence of DVT progression or clinically significant PE),we suggest placement of asuperior vena cava filter (Grade 2C).
Antithrombotic Therapy in AF
In patients with AF, including those with paroxysmal AF, who have had a prior ischemic stroke, transient ischemic attack, or systemic embolism, we recommend long-term anticoagulation with an oral VKA, such as warfarin,
targeted at an INR of 2.5 (range, 2.0 to 3.0) because of the high risk of future ischemic stroke faced by this set of patients (Grade 1A).
• In patients with AF, including those with paroxysmal AF, who have two or more of the following risk factors for future ischemic stroke,We recommend long-term anticoagulation with an oral VKA, such as warfarin,targeted at an INR of 2.5 (range, 2.0 to 3.0) because of the increased risk of future ischemic stroke faced by this set of patients (Grade 1A). Two or more of the following
• Risk factors apply:
• (1)age>75years,
• (2)historyof hypertension,
• (3) diabetes mellitus,
• (4) moderately or severely impaired left ventricular systolic function and/or heart failure.
long-term therapy, means
lifelong unless a contraindication emerges.
Remark:
In patients with AF, including those with paroxysmal AF aged <75 years and with none of
The other risk factors listed above, we recommend
long-term aspirin therapy at a dose of 75 to 325 mg/d (Grade 1B) because of their low risk of ischemic stroke.
Underlying values and preferences:
Anticoagulation with oral VKAs, such as warfarin, has far greater efficacy than aspirin in preventing stroke,and particularly in preventing severe ischemic stroke, in AF. We recommend the option of aspirin therapy for lower risk groups, estimating the absolute expected benefit of anticoagulant therapy may not be worth the increased hemorrhagic risk and burden of anticoagulation. Individual lower-risk patients may rationally choose anticoagulation over aspirin therapy to gain greater protection against ischemic stroke if they value protection against stroke much more highly than reducing risk of hemorrhage and the burden of managing anticoagulation. Our recommendations assume that the patient is not at high risk for bleeding and that good control of anticoagulation will occur.Remarks:
These recommendations apply to patients with persistent or paroxysmal AF and not to patients with a single brief episode of AF due to a reversible cause, such as an acute pulmonary infection. The optimal dose of aspirin for patients with AF is unclear. The largest effect of aspirin was seen in the first Stroke Prevention in AF (SPAF I) trial, which used aspirin at 325 mg/d.However, generalizing from trials of aspirin for all antithrombotic indications and from physiologic studies, we feel the best balance of efficacy and safety is achieved at low doses of aspirin, ie,75 to 100 mg/d
• For patients with atrial flutter, we recommend that antithrombotic therapy decisions follow the same risk-based recommendations as for AF (Grade 1C).
For patients with AF and mitral stenosis,we recommend long-term anticoagulation with an oral VKA, such as warfarin (target INR 2.5;range, 2.0 to 3.0) [Grade 1B].
For patients with AF and prosthetic heart valves, we recommend long-term anti-coagulation with an oral VKA, such as warfarin, at a dose intensity appropriate for the
specific type of prosthesis (Grade 1B). See the “Valvular and Structural Heart Disease”
For patients with AFoccurring shortly after open-heart surgery and lasting > 48 h, we suggest anticoagulation with an oral VKA, such as warfarin,if bleeding risks are acceptable (Grade 2C).The target INR is 2.5 (range,2.0to3.0).We suggest continuing anticoagulation for 4 weeks following reversion to and maintenance of normal sinus rhythm, particularly if patients have risk factors for thromboembolism (Grade 2C).
For patients with AF of > 48h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA, such as warfarin, at a target INR of 2.5 (range, 2.0 to 3.0) for 3 weeks before elective cardioversion
and for at least 4 weeks after sinus rhythm has
been maintained (Grade 1C).
Remark: This recommendation applies to all patients with AF, including those whose risk factor status would otherwise indicate a low risk for stroke.Patients with risk factors for thromboembolism should continue anticoagulation beyond 4 weeks Unless there is convincing evidence that sinus rhythm is maintained.
For patients with AF of known duration < 48 h, we suggest that cardioversion be performed without prolonged anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin (target PTT, 60 s; range, 50 to 70 s) or LMWH (at full DVT treatment doses) at presentation (Grade 2C).
For emergency cardioversion in the hemodynamically unstable patient, we suggest that IV UFH (targetPTT of 60s with atarget range of 50 to 70 s) or LMWH (at full DVT treatment doses) be started as soon as possible,followed by at least 4weeks of anticoagulation with an oral VKA, such as warfarin (target INR of 2.5;range,2.0 to3.0) if cardioversion is successful and sinus rhythm is maintained (Grade 2C).
For patients with rheumatic mitral valve disease with AF who suffer systemic embolism or have left atrial thrombus while receiving VKAs at a therapeutic INR, we suggest the addition of low-dose aspirin (50 to 100 mg/d) therapy after consideration of the additional hemorrhagic risks (Grade 2C). An alternative strategy might be the adjustment of VKA dosing to achieve a higher target INR (target INR, 3.0; range, 2.5 to 3.5) [Grade 2C].
In patients with rheumatic mitral valve disease and normal sinus rhythm with the left atrial diamter > 55 mm, we suggest VKA therapy (target INR, 2.5; range, 2.0 to 3.0) [Grade 2C].
Underlying values and preferences:
This recommendation places a relatively high value on preventing systemic embolism and its consequences, and arelatively low value on avoiding the bleeding risk and inconvenience associated with VKA therapy.In patients with rheumatic mitral valve disease and normal sinus rhythm with a left atrial diameter < 55 mm, we do not suggest antithrombotic therapy, unless a separate indication exists (Grade 2C).
In patients with mechanical heart valves who have additional risk factors for thromboembolism,such as AF,hypercoagulable state,or low ejection fraction, or who have a history of atherosclerotic vascular disease, we recommend the addition of low-dose aspirin (50 to 100mg/d)to long-term VKA therapy (Grade1B).
Antithrombotic Therapy and ThrombolyticTherapy for Ischemic StrokeTissue Plasminogen Activator for AcuteIschemic Stroke Within 3h of Symptom Onset
For eligible patients (see inclusion and exclusion criteria listed below) we recommend administration of IV tissue plasminogen activator (tPA) in a dose of 0.9 mg/kg (maximum of 90 mg), with 10% of the total dose given as an initial bolus and the remainder infused over 60 min, provided that treatment is initiated within 3h of clearly defined symptom onset (Grade 1A).
For patients with acute ischemic stroke, we recommend against streptokinase (Grade 1A).
Underlying values and preferences:
This recommendation places relatively more weight on overall prospects for long-term functional improvement despite the increased risk of symptomatic intracerebral hemorrhage in the immediate peristroke period.Remark: All unnecessary delays must be avoided as the benefits of tPA therapy diminish rapidly over time.
For patients with extensive (>1/3 of the middle cerebral artery territory)and clearly identifiable hypodensity on CT, we suggest not using of tPA (Grade 2B).
IV tPA for Acute Ischemic Stroke Between 3 h and 6h of Symptom Onset
For patients with acute ischemic stroke of > 3 h but < 4.5 h, we suggest clinicians do not use IV tPA (Grade 2A). For patients with acute stroke onset of > 4.5 h we recommend against the use of IV tPA (Grade 1A).Underlying values and preferences:
This recommendation assumes a relatively low value on small increases in long-term functional improvement, a relatively high value on avoiding acute intracranial hemorrhage and death, and a relatively high degree of risk aversion.
Intraarterial Thrombolysis for Acute Ischemic Stroke
For patients with angiographically demonstrated middle cerebral artery occlusion and without signs major early infarct signs on the baseline CT or MRI scan, who can be treated within 6h of symptom onset, we suggest intraarterial thrombolytic therapy with tPA for selected patients in centers with the appropriate neurologic and interventional expertise (Grade 2C).
For patients with acute basilar artery thrombosis and without major CT/MRI evidence of infarction, we suggest either intraarterial or IV thrombolysis with tPA depending on available resources and capabilities (Grade 2C).
Anticoagulants for Altering Outcomes AmongAcute Stroke in Patients Not Eligible forThrombolysis
For patients with acute ischemic stroke,we recommend against full-dose anticoagulation with IV, SC, or LMWHs or heparinoids (Grade 1B).
Antiplatelet Agents for Altering Outcomes in Acute Stroke Patients Not Eligible for Thrombolysis
For patients with acute ischemic stroke who are not receiving thrombolysis, we recommend early aspirin therapy (initial dose of to 325 mg) [Grade 1A].
For acute stroke patients with restricted mobility, we recommend prophylactic low-dose SC heparin or LMWHs (Grade 1A).
For patients who have contraindications to anticoagulants, we recommend IPC devices or elastic stockings (Grade 1B).
Antithrombotic Therapy for Prevention of DVT
and PE in Acute Ischemic Stroke
Heparin for DVT/PE Prophylaxis in PatientsWith Intracerebral Hematoma
In stable patients, we suggest low-dose SC heparin as soon as the second day after the onset of the hemorrhage (Grade 2C).Underlying values and preferences:
Given the uncertainty about the risk of heparin in this setting, this recommendation places a relatively high value on reducing the consequences of thromboembolism And arelatively lower value on minimizing the risk of cerebral rebleeding.
Prevention of Cerebral Ischemic Events inPatients With Noncardioembolic TransientIschemic Attack or Stroke: Antiplatelet Drugs vsPlacebo or vs an Alternative Antiplatelet Drug
In patients who have experienced a non-cardioembolic stroke or transient ischemic attack (ie, atherothrombotic, lacunar, or cryptogenic), we recommend treatment with an antiplatelet drug (Grade 1A). Aspirin, the combination of aspirin (25 mg) and extended-release dipyridamole (200 mg bid) and clopidogrel (75 qd) are all acceptable options for initial therapy.
We recommend an aspirin dose of 50–100 mg/d over higher aspirin doses (Grade 1B).
In most patients with a noncardioembolic stroke or transient ischemic attack, we recommend avoiding long-term use of the combination of aspirin and clopidogrel (Grade 1B).
In those with a recent acute myocardial infarction, other acute coronary syndrome, or a recently placed coronary stent, we recommend clopidogrel plus aspirin (75–100 mg) [Grade 1A].
The optimal duration of dual antiplatelet therapy depends on the specific cardiac indication For patients who are allergic to aspirin,we recommend clopidogrel (Grade 1A).
For patients with noncardioembolic stroke or transient ischemic attack, we recommend antiplatelet agents over oral anticoagulation (Grade 1A).
Antithrombotic Therapy forNon–ST-Segment Acute CoronarySyndromes
Antiplatelet TherapiesFor all patients presenting with NSTE ACS,without aclear allergy to aspirin,we recommend immediate aspirin (162 to 325mg po)and then daily oral aspirin(75 to 100 mg) [Grade 1A].
For all NSTE ACS patients with an aspirin allergy, we recommend immediate treatment with clopidogrel, 300 mg po bolus, followed by 75 mg/d indefinitely (1A).
For all patients presenting with NSTE ACS, we recommend anticoagulation with UFH or LMWH or bivalirudin or fondaparinux over no anticoagulation (Grade 1A).
For NSTE ACS patients who will undergo an early invasive strategy of management (ie, diagnostic catheterization followed by anatomy-driven revascularization),
a. We recommend UFH (with a GP IIb/IIIa inhibitor) over either LMWH or fondaparinux (Grade 1B)
b. We suggest bivalirudin over UFH in combination with a thienopyridine as an initial antithrombotic strategy in patients with moderate-to-high risk features presenting with a NSTE ACS and scheduled for very early coronary angiography (< 6h) [Grade 2B].
Acute St-Segment Elevation Myocardial Infarction
Reperfusion Therapy:For patients with ischemic symptoms characteristic of acute myocardial infarction of < 12 h duration and persistent ST-segment elevation, we recommend that all undergo rapid evaluation for reperfusion (primary PCI or fibrinolytic) therapy and have areperfusion strategy implemented promptly after contact with the health-care system (Grade 1A).
Inpatients with any history of intracranial hemorrhage, or with history of head trauma, or with ischemic stroke within the past 6 months,we recommend against administration of fibrinolytic therapy (Grade 1C).
For patients with acute ST-segment elevation myocardial infarction who have not received a coronary stent, we suggest that clopidogrel 75 mg/d could be continued beyond 28 days and up to 1 year (Grade 2B).
For patients with ST-segment elevation myocardial infarction undergoing primary PCI,we recommend administration of IV UFH over no UFH therapy (Grade 1C).
LMWH
For patients with acute ST-segment elevation myocardial infarction, regardless of whether or not they receive reperfusion therapy, we recommend the use of reviparin over no therapy (Grade 1B).For patients with acute ST-segment elevation myocardial infarction receiving fibrinoLytic therapy who have preserved renal function we recommend the use of enoxaparin over UFH, continued up to 8 days (Grade 2A).
For patients with acute ST-segment elevation myocardial infarction receiving fibrinolytic therapy and thought not to have an indication for anticoagulation, we recommend
fondaparinux over no therapy (2.5 mg IV for the.
For patients with acute ST-segment elevation myocardial infarction receiving fibrinolytic therapy and thought to have an indication for anticoagulation, we suggest fondaparinux could be used as an alternative to UFH (Grade 2B).
For patients with acute ST-segment elevation myocardial infarction and undergoing primary PCI, we recommend against using fondaparinux (Grade 1A).
GP IIb/IIIa Inhibitors
For patients with acute ST-segment elevation myocardial infarction undergoing primary PCI (with or without stenting), we recommend the use of abciximab (Grade 1B).Rescue PCI
For patients with ST-segment elevation myocardial infarction who have received fibrinolysis but who have persistent ST-segment elevation (< 50% resolution 90 min after treatment initiation compared with the pretreatment ECG), we recommend rescue PCI should be performed over repeat fibrinolysis or no additional reperfusion therapy (Grade 1B), and suggest as soon as possible and within 2h of identification of lack of ST-segment elevation resolution (Grade 2C).For patients with ACS with and without ST-segment elevation, we recommend aspirin given initially at a dose of 75–162 mg and then indefinitely at adose of 75–100mg/d (Grade1A).
For patients with ST-segment elevation ACS, with or without fibrinolytic therapy, we recommend clopidogrel, administered as a300-mg po loading dose for patients < 75 years of age and 75-mg starting dose for those > 75
years of age and continued at a daily dose of 75 mg for 2–4 weeks (Grade 1A).
We suggest continuing clopidogrel for up to 12 months following hospital discharge (Grade 2B).
For patients with NSTE ACS, we recommend combination therapy with aspirin(75–100mg/d) and clopidogrel (75 mg/d) for 12 months (Grade 1A).
For patients in whom aspirin is contraindicated or not tolerated, we recommend clopidogrel monotherapy (75 mg/d) [Grade 1A].
Underlying values and preferences:
This recommendation places a high value on the probable small reduction in arterial vascular risk consequent on adding clopidogrel to aspirin and a low value on avoiding the additional bleeding and high cost associated with clopidogrel.
For high-risk patients with myocardial infarction, including those with a large anterior myocardial infarction, those with significant heart failure, those with intracardiac thrombus visible on transthoracic echocardiography, those with AF, and those with ahistory of athromboembolic event,
we suggest the combined use of moderate-intensity (INR, 2.0 to 3.0) oral VKA plus low-dose aspirin ( 100 mg/d) for at least 3 months after the MI (Grade 2A).
For patients who have received clopidogrel for ACS and are scheduled for CABG,we suggest discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A).
For patients undergoing CABG who have no other indication for VKA, we recommend clinicians not administer VKAs (Grade 1C).
For patients undergoing CABG in whom oral anticoagulants are indicated ,such as those with heart valve replacement, we suggest clinicians administer VKA in addition to aspirin (Grade 2C).
Antithrombotic Therapy in PeripheralArtery Occlusive Disease
Chronic Limb Ischemia and Intermittent Claudication.In peripheral artery occlusive disease patients with clinically manifest coronary or cerebrovascular disease, we recommend life -long antiplatelet therapy in comparison to no antiplatelet therapy (Grade 1A).
In those without clinically manifest coronary or cerebrovascular disease, we suggest aspirin (75–100 mg/d) over clopidogrel (Grade 2B).In patients who are aspirin intolerant, we recommend clopidogrel over ticlopidine (Grade 1B).
In patients with peripheral artery occlusive disease and intermittent claudication, we recommend against the use of anticoagulants to prevent vascular mortality or cardiovascular events (Grade 1A).
For patients with moderate-to-severe disabling intermittent claudication who do not respond to exercise therapy, and who are not candidates for surgical or catheter-based intervention, we recommend cilostazol (Grade 1A).
We suggest that clinicians not use cilostazol in those with less disabling claudication (Grade 2A). We recommend against the use of pentoxifylline (Grade 2B).
In patients who suffer from acute arterial emboli or thrombosis, we recommend immediate systemic anticoagulation with UFH, over no anticoagulation (Grade 1C).
In patients undergoing embolectomy, we suggest following systemic anticoagulation with UFH with long-term anticoagulation with VKA (Grade 2C).
For patients under going lower-extremity balloon angioplasty (with or without stenting), we recommend long-term aspirin (75–100 mg/d) [Grade 1C].
For patients undergoing lower extremity balloon angioplasty (with or without stenting), we recommend against anticoagulation with heparin or VKA (Grade 1A).
VTE, Thrombophilia, AntithromboticTherapy, and Pregnancy
For women with “higher-risk” thrombophilias (eg, antithrombin deficiency, persistent positivity for the presence of antiphospholipid antibodies; compound heterozygosity for prothrombin G20210A variant and factor V Leiden or homozygosity for these conditions) who have had a single prior episode of VTE and are not receiving long-term anticoagulants, we suggest,in addition to postpartum prophylaxis, antepartum prophylactic or intermediate-dose LMWH or prophylactic or intermediate-dose UFH,rather than clinical surveillance (Grade 2C).For all pregnant women with previous DVT, we suggest the use of GCS both antepartum and postpartum (Grade 2C).
For pregnant patients with thrombophilia but no prior VTE, we recommend that physicians do not use routine pharmacologic antepartum prophylaxis but instead perform an individualized risk assessment (Grade 1C).
For pregnant women with no history of VTE but antithrombin deficiency, we suggest antepartum and postpartum prophylaxis (Grade 2C).
For all other pregnant women with thrombophilia and no prior VTE, we suggest antepartum clinical surveillance or prophylactic LMWH or UFH,plus postpartum anticoagulants (Grade2C).
Prevention of Recurrent Preeclampsia inWomen Without Thrombophilia
For women considered high risk for preeclampsia, we recommend low-dose aspirin therapy throughout pregnancy (Grade 1B).For women with a history of preeclampsia,we suggest that UFH and LMWH should not be used as prophylaxis in subsequent pregnancies (2C).
Abciximab is made from the Fab fragments of an immunoglobulin that targets the glycoprotein IIb/IIIa receptor on the platelet membrane.
is a platelet aggregation inhibitor mainly used during and after angioplasty to prevent platelets from sticking together and causing thrombus. Its mechanism of action is inhibition of glycoprotein IIb/IIIa.
In practice, platelet aggregation gradually returns to normal about 24 to 48 hours after discontinuation of the drug. While Abciximab has a short plasma half life, due to its strong affinity for its receptor on the platelets, it may occupy some receptors for weeks. Abciximab has a plasma half life of about ten minutes, with a second phase half life of about 30 minutes. However, its effects on platelet function can be seen for up to 48 hours after the infusion has been terminated, and low levels of glycoprotein IIb/IIIa receptor blockade are present for up to 15 days after the infusion is terminated.
Many of the side effects of abciximab are due to its anti-platelet effects. This includes an increased risk of bleeding. The most common type of bleeding due to abciximab is gastrointestinal hemorrhage.
Thrombocytopenia is a rare but known serious risk. Abciximab-induced thrombocytopenia can typically be treated with transfusion of platelets. Abciximab induced thrombocytopenia can last for five days after initial drug administration. Transfusing platelets is the only known treatment and may have limited effectiveness as the drug may also bind to the new platelets. Platelet counts which should average 250,000-400,000 can effectively drop to zero
ReoPro is a clear, colorless, sterile, non-pyrogenic solution for intravenous (IV) use.
Each single use vial contains 2 mg/mL of Abciximab in a buffered solution (pH 7.2) of 0.01 M sodium phosphate, 0.15 M sodium chloride and 0.001% polysorbate 80 in Water for Injection. No preservatives are added.Abciximab is indicated as an adjunct
to patients undergoing percutaneous coronary interventionin patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours
Safety and efficacy of Abciximab use in patients not undergoing percutaneous coronary intervention have not been established.
Abciximab is intended for use with aspirin and heparin and has been studied only in that setting, as described in CLINICAL STUDIES.
The safety and efficacy of Abciximab have only been investigated with concomitant administration of heparin and aspirin as described in Clinical Studies. In patients with failed PCIs, the continuous infusion of Abciximab should be stopped because there is no evidence for Abciximab efficacy in that setting.
In the event of serious bleeding that cannot be controlled by compression, Abciximab and heparin should be discontinued immediately.
The recommended dosage of Abciximab in adults is a 0.25 mg/kg intravenous bolus administered 10-60 minutes before the start of PCI, followed by a continuous intravenous infusion of 0.125 µg/kg/min (to a maximum of 10 µg/min) for 12 hours.
Patients with unstable angina not responding to conventional medical therapy and who are planned to undergo PCI within 24 hours may be treated with an Abciximab 0.25 mg/kg intravenous bolus followed by an 18- to 24-hour intravenous infusion of 10 µg/min, concluding one hour after the PCI.
Hypersensitivity reactions should be anticipated whenever protein solutions such as Abciximab are administered. Epinephrine, dopamine, theophylline, antihistamines and corticosteroids should be available for immediate use. If symptoms of an allergic reaction or anaphylaxis appear, the infusion should be stopped and appropriate treatment given .
