Changed recommendations from original ASH guidelines to adapted LA ASH guidelines on VTE
| OG . | LAG . | PICO . | Original . | Adapted . | Direction . | Strength . | CoE . | Balance of benefits and harms . | Resources . | Other observations . |
|---|---|---|---|---|---|---|---|---|---|---|
| Guidelines for management of VTE in LA | ||||||||||
| Rec 2 | Rec 2 | For patients with PE and a low risk of complications, should we suggest home treatment or hospital treatment? | Suggests offering home treatment over hospital treatment | Suggests using either home treatment or hospital treatment | Changed | No change | Very low | May be favorable | Less costly for patients | Important barriers to providing appropriate home care for individuals with PE include an insufficient number of clinicians, inappropriate support from hospitals for patients being treated at home, and cost of drugs. |
| Rec 18 | Rec 10 | For patients with a provoked DVT or PE related to a chronic risk factor (eg, chronic immobility), should we use indefinite anticoagulation or discontinue anticoagulation after a period of 3 to 6 months? | Suggests indefinite antithrombotic therapy over stopping anticoagulation | Recommends indefinite anticoagulation | No change | Changed | Moderate | Will depend on the specific cause of chronic immobility | More costly for patients and providers | Clinicians should carefully examine the nature of the chronic risk factor. If the risk factor is not related with a high risk of VTE, or if it will disappear in time, clinicians and patients may consider using a definite period of anticoagulation. |
| Rec 22 | Rec 13 | For patients for whom an indefinite duration of DOAC treatment is preferred after completion of an initial defined duration course of therapy (3-6 months), should we use a standard dose or a lower dose of DOACs? | Suggests using either standard-dose DOAC or lower-dose DOAC | Suggests using standard-dose DOAC | Changed | No change | Low | Probably favorable | Cost might not be different between conventional and low-dose DOAC | This recommendation applies for patients on high risk of VTE recurrence (ie, unprovoked events related to a chronic risk factor or recurrent events). Therefore, they might benefit from standard doses of DOACs. However, lower doses may be appropriate if the risk of VTE is not considered high or if there are reasonable concerns regarding the risk of bleeding. |
| Rec 17 | Rec 17 | For patients with VKA-related life-threatening bleeding during treatment for VTE, should we use 4-factor PCCs or FFP? | Suggests using 4-factor PCCs rather than FFP as an addition to cessation of VKA and IV vitamin K | Suggests using either 4-factor PCCs or FFP | Changed | No change | Very low | Favorable | Less costly for providers | The identified evidence did not show substantial differences in outcomes important to patients with PCCs or FFP. Although PCCs are easier and faster to administer, their price is higher than that of FFP, and they are not typically available in many settings in the region. |
| Guidelines for prevention of VTE in surgical and medical patients and long-distance travelers in LA | ||||||||||
| Thromboprophylaxis in surgical procedures | ||||||||||
| Rec 27a and 27b | Rec 2 | For patients undergoing surgery following major trauma, should we use pharmacological thromboprophylaxis? | Suggests using prophylaxis in individuals who are at low to moderate risk for bleeding and against prophylaxis for patients at high risk of bleeding | Suggests using prophylaxis when the risk of bleeding is considered low or moderate and mechanical prophylaxis when this risk is high | Changed | No change | Very low | Probably favorable, safer | May be more costly for providers | Access to mechanical prophylaxis, especially compression devices, may be limited within the region. Therefore, barriers to the implementation of this recommendation may exist in some settings. |
| Rec 19 | Rec 6 | For patients undergoing major neurosurgical procedures, should we use pharmacological thromboprophylaxis? | Suggests against using pharmacological prophylaxis | Suggests thromboprophylaxisover no prophylaxis | Changed | No change | Very low | Probably favorable, safer | May be more costly for providers | These patients may also have a high risk of VTE. The LA panel considered that mechanical prophylaxis could be an appropriate alternative for patients at high risk of bleeding, especially early after surgery. Thus, the panel suggested using prophylaxis and deciding on the specific modality according to the risk of bleeding. |
| Rec 7 | Rec 9 | For patients undergoing major surgery in whom pharmacological thromboprophylaxis is preferred, should we use short or extended prophylaxis? | Suggests using extended antithrombotic prophylaxis over short-term antithrombotic prophylaxis, basing their judgment mainly on individuals athigh risk of VTE, such as patients undergoing cancer surgery ororthopedic surgery | Suggests short prophylaxis (7 to 10 days) over extended prophylaxis(30 days) | Changed | No change | Very low | Probably favorable, safer | Less costly for patients and providers | Original ASH guideline made a recommendation in favor of extended prophylaxis, basing their judgment mainly on individuals athigh risk of VTE, such as patients undergoing cancer surgery or orthopedic surgery. |
| Rec 8 | Rec 10 | For surgical patients in whom pharmacological thromboprophylaxis is preferred, should we use delayed or early prophylaxis? | Suggests using early or delayed antithrombotic prophylaxis | Suggests delayed prophylaxis (12 hours after surgery)over early administration (before surgery or within 12hours after surgery) | Changed | No change | Very low | Probably favorable, safer (less bleeding risk) | Less costly for patients and providers | The LA panel judged that, for most patients undergoingsurgery, the risk of VTE before the procedure was very small. In addition,the use of early prophylaxis might slightly increase the risk of bleeding during surgery. |
| Thromboprophylaxis in medical patients and long-distance travelers | ||||||||||
| Rec 1 | Rec 11 | For medically ill patients, should we use heparins asthromboprophylaxis? | Suggests using UFH, LMWH, or fondaparinux rather than no parenteral anticoagulant | Suggests against routinely use of heparins (UFH or LMWH) | Changed | No change | Low | Probably favorable, safer (less bleeding risk) | Less costly for patients and providers | For the majority of patients admitted to hospital for noncritical medical conditions, the risk of VTE is likely small, especially if they are able to walk or perform physical therapy. In those cases, the benefit of prophylaxis with heparins may be very small. This change of direction had to do with the baseline risk of VTE in average medical patients. The LA panel considered that most patients admitted to hospital for noncritical medical conditions have a low risk of VTE, especially if they retain their mobility. |
| Rec 4 | Rec 12 | For patients who are critically ill, should we use heparins as thromboprophylaxis? | Recommends using UFH or LMWH over no UFH or LMWH | Suggests the use of heparins (UFH orLMWH) over no use | No change | Changed | Moderate | Probably favorable, safer (less bleeding risk) | Less costly for patients and providers | The panel considered that for most patients who are critically ill, the benefits of thromboprophylaxis (moderate reduction of VTE risk) probably outweigh the potential harms (small increase of bleeding). However, a proportion of individuals, for example, neurosurgical patients or patients who have experienced trauma, may not obtain a net benefitfrom thromboprophylaxis, given their increased risk of bleeding. |
| Rec 2 and 5 | Rec 13 | For patients who are critically ill or have medical conditions and require pharmacologic prophylaxis, should we use LMWH or UFH? | Suggests using LMWH rather than UFH | Suggests either UFH or LMWH | Changed | No change | Low | Increase accessibility; maybe more bleeding risk and longer hospital stay | Probably less costly for providers; one has to consider that hospital stay length might increase | The absolute differences betweenthe effects of LMWH and UFH in patient important outcomes(thrombotic events and bleeding) are very small, that is, less than1%. In addition, LMWH is significantly more expensive in LA, and there are important access barriers within the region.Therefore, both options are reasonable management alternatives,and the final decision likely will depend on contextual factors suchas affordability and availability. |
| Rec 13 and 14 | Rec 16 | For patients who are critically ill or have medical conditions and require pharmacological thromboprophylaxis, should we use a short period of prophylaxis or an extended period? | Recommends short VTE prophylaxis (inpatients), rather than extended-duration VTE prophylaxis | Suggests using a short period of prophylaxis(inpatients) over an extended period (inpatients andextended-duration outpatients) | No change | Changed | Moderate | Probably favorable, if thrombotic risk is high and bleeding risk is low | Probably more costly for patients and providers | Although for most patient the baseline risk of VTE is small, and thus, an extended prophylaxis will not result in a significant benefit, there are some patients with a higher baseline risk of VTE who maintain this risk after discharge, especially if they need a long rehabilitation and are not able to ambulate. Those patients may benefit from a longer prophylaxis. |
| Rec 11 | Rec 18 | For patients who are acutely ill and hospitalized with medical conditions and require pharmacological thromboprophylaxis, should we use LMWH or DOACs? | Recommends using LMWH over DOACs for VTE prophylaxis | Suggests using LMWH over DOACs | No change | Changed | Moderate | Probable less safe (increased bleeding risk), but more convenient (oral administration) | Less costly | An increased risk of bleeding was observed with a short course and with an extended prophylaxis with DOAC. Therefore, the current evidence suggests that in medical patients, DOACs increase bleeding with no additional benefit on VTE prevention. However, the difference is of small absolute magnitude. In settings where DOACs are available, some patients may place more value on the convenience of an oral medication than the small increase of the risk of bleeding, especially if the baseline risk of bleeding is small. |
| Rec 12 | Rec 19 | Should inpatient VTE prophylaxis be instituted with LMWH only or inpatient and extended-duration outpatient VTE prophylaxis with DOACs? | Recommends inpatient VTE prophylaxis with LMWH only, rather than inpatient and extended-duration outpatient VTE prophylaxis with DOACs | Suggests using LMWH over DOACs | No change | Changed | Moderate | Probable less safe (increased bleeding risk), but more convenient (oral administration) | Less costly | An increased risk of bleeding was observed with a short course and with an extended prophylaxis with DOAC. Therefore, the current evidence suggests that in medical patients, DOACs increase bleeding with no additional benefit on VTE prevention. However, the difference is of small absolute magnitude. In settings in which DOACs are available, some patients may place more value on the convenience of an oral medication than the small increase of the risk of bleeding, especially if the baseline risk of bleeding is small. |
| Diagnosis of VTE and management in special populations | ||||||||||
| Diagnosis of VTE | ||||||||||
| Rec 1a | Rec 1 | For a patient with low pretest probability of a first episode of PE (≤5%), what is the optimal diagnostic strategy to evaluate a suspected PE? | Recommends using a strategy starting with D-dimer for excluding PE, followed by VQ scan or CTPA for patients requiring additional testing | Recommends using the D-dimer for excluding PE followed by CTPA in patients with a positive D-dimer | Changed the preferred diagnostic pathway | Strong (D-dimer to exclude); very low (VQ or CTPA if positive D-dimer) | Probably safe | Less costly to patients and providers | D-dimer is affordable and generally available in the region; therefore, it was considered a reasonable first step to rule-out PE. However, in LA there is a very limited availability of VQ scan, and thus the panel opted for suggesting CTPA over VQ scan as a follow-up test to a positive D-dimer. | |
| Rec 4 | Rec 2 | For a patient with low pretest probability of a recurrent PE (≤5%), what is the optimal diagnostic strategy to evaluate a suspected PE? | Suggests using a strategy starting with D-dimer for excluding recurrent PE followed by a VQ scan or CTPA | Recommends using the D-dimer for excluding PE followed by CTPA in patients with a positive D-dimer | Changed the preferred diagnostic pathway | Low (D-dimer to exclude); very low (CTPA if positive D-dimer) | Probably safe | Less costly to patients and providers | D-dimer is affordable and generally available in the region; therefore, it was considered a reasonable first step to rule-out PE. However, in LA there is a very limited availability of VQ scan, and thus the panel opted for suggesting CTPA over VQ scan as a follow-up test to a positive D-dimer. | |
| Rec 2a | Rec 3 | For a patient population with an intermediate clinical probability of a first episode of PE (∼20%), what is theoptimal diagnostic strategy to evaluate for suspected first episode PE? | Suggests using a strategy starting with D-dimer for excluding PE, followed by VQ scan or CTPA for patients requiring additional testing | Suggests using the D-dimer for excluding PE, followed byCTPA in patients with a positive D-dimer | Changed the preferred diagnostic pathway | Strong (D-dimer to exclude); very low (CTPA if positive D-dimer) | Probably safe | Less costly to patients and providers | At 20% probability, D-dimer still can safely rule out a first episode of PE. However, patients with an intermediate probability of recurrent PE (∼20%) may not be adequality categorized by D-dimer alone and hence, the panel suggests following recommendation 5 in this situation. As before, it should be noted that an abnormal D-dimer can be observed in many clinical conditions apart from VTE, and therefore, a positive D-dimer should not be the sole basis for VTE diagnosis. Given the limited availability of VQ scan on the region, the LA panel opted for suggesting CTPA over VQ scan as a follow-up test to a positive D-dimer. | |
| Prevention and management of VTE during pregnancy | ||||||||||
| Rec 8 | Rec 13 | For pregnant women with PE and hemodynamic failure, should we use thrombolytic therapy in addition to anticoagulation? | Suggests administering systemic thrombolytic therapy in addition to anticoagulant therapy | Recommends thrombolytic therapy in addition to anticoagulation | No change | Changed | Very low | May be favorable but higher bleeding risk | More costly for patients and providers | The evidence that informs this recommendation comes primarily from general adult population, and therefore, there is considerable uncertainty regarding the effect of thrombolytic therapy in pregnant women. The LA panel, however, considered that in a situation of high mortality, thrombolytictherapy may be a life-saving intervention, and placed a higher value in preserving maternal life. |
| Rec 11 | Rec 17 | For pregnant women receiving prophylactic dose LMWH, should we offer scheduled delivery with prior discontinuation of LMWH or cessation of LMWH with spontaneous onset of labor? | Suggests against scheduled delivery with discontinuation of prophylactic anticoagulation compared with allowing spontaneous labor | Suggests scheduled delivery with prior discontinuation of LMWH over cessation of LMWH with spontaneous onset of labor | Changed | No change | Very low | May be safer | More costly for patients and providers | Although most women receiving prophylactic dose LMWH may go through a spontaneous labor safely, many women in LA have a poor access to skilled birth attendance. In this scenario, a scheduled delivery conducted at hospitals may be safer for women receiving LMWH. |
| Rec 16 and 17 | Rec 19 | For women with previous VTE, should we use antepartum anticoagulant prophylaxis? | Recommends antepartum anticoagulant prophylaxis over no prophylaxis (if VTE is unprovoked or associated with a hormonal risk factor) | Suggests antepartum anticoagulant prophylaxis over no prophylaxis (if VTE is unprovoked or provoked) | No change | Changed | Low | Probably safer | Less costly | The original ASH guideline panel made a strong recommendation in favor of prophylaxis in women at high risk for VTE recurrence and a conditional recommendation against prophylaxis in women at low risk for recurrence. Therefore, to best implement this recommendation, clinicians may explore the baseline risk for VTE recurrence and, concomitantly, women preferences. |
| Rec 18 | Rec 20 | For women with previous VTE not already receiving long-term anticoagulant therapy, should we use postpartum anticoagulant prophylaxis? | Recommends postpartum anticoagulant prophylaxis | Suggests postpartum anticoagulant prophylaxis over no prophylaxis | No change | Changed | Low | Probably more risk of thrombosis and less risk of bleeding | Less costly | The ASH-GRADE rules specified in this article are intended to prevent a strong recommendation in such situations. The reason for the discrepancy is the uncertain benefit of the intervention (low certainty evidence). |
| Management of VTE in children | ||||||||||
| Rec 2 | Rec 23 | For children with asymptomatic VTE, should we use anticoagulation? | Suggests either using anticoagulation or no anticoagulation in pediatric patients with asymptomatic DVT or PE | Suggests against anticoagulation | Changed | No change | Very low | Less risk of bleeding | Less costly | Asymptomatic VTE in children are usually detected in the context of a central venous access device. Given the provoked nature of the event, the risk of recurrence is generally small, and the use of anticoagulants may result in a net harm. However, anticoagulation for a limited period may benefit children with other risk factors for VTE (ie, thrombophilia) or those who require multiple central venous access devices. |
| Rec 5 | Rec 24 | For children with PE and hemodynamic failure, should we use thrombolytic therapy? | Suggests using thrombolysis followed by anticoagulation, rather than anticoagulation alone | Recommends thrombolytic therapy in addition to anticoagulation | No change | Changed | Low | Probably favorable but more risk of bleeding | More costly for patients and providers | There is considerable uncertainty regarding the effect of thrombolytics in children given the lack of appropriately designed and powered studies. However, the available evidence suggests a significant effect of thrombolytics in preserving life in a condition of high mortality. This scenario justifies a strong recommendation in favor of the intervention following the ASH-GRADE rules. |
| OG . | LAG . | PICO . | Original . | Adapted . | Direction . | Strength . | CoE . | Balance of benefits and harms . | Resources . | Other observations . |
|---|---|---|---|---|---|---|---|---|---|---|
| Guidelines for management of VTE in LA | ||||||||||
| Rec 2 | Rec 2 | For patients with PE and a low risk of complications, should we suggest home treatment or hospital treatment? | Suggests offering home treatment over hospital treatment | Suggests using either home treatment or hospital treatment | Changed | No change | Very low | May be favorable | Less costly for patients | Important barriers to providing appropriate home care for individuals with PE include an insufficient number of clinicians, inappropriate support from hospitals for patients being treated at home, and cost of drugs. |
| Rec 18 | Rec 10 | For patients with a provoked DVT or PE related to a chronic risk factor (eg, chronic immobility), should we use indefinite anticoagulation or discontinue anticoagulation after a period of 3 to 6 months? | Suggests indefinite antithrombotic therapy over stopping anticoagulation | Recommends indefinite anticoagulation | No change | Changed | Moderate | Will depend on the specific cause of chronic immobility | More costly for patients and providers | Clinicians should carefully examine the nature of the chronic risk factor. If the risk factor is not related with a high risk of VTE, or if it will disappear in time, clinicians and patients may consider using a definite period of anticoagulation. |
| Rec 22 | Rec 13 | For patients for whom an indefinite duration of DOAC treatment is preferred after completion of an initial defined duration course of therapy (3-6 months), should we use a standard dose or a lower dose of DOACs? | Suggests using either standard-dose DOAC or lower-dose DOAC | Suggests using standard-dose DOAC | Changed | No change | Low | Probably favorable | Cost might not be different between conventional and low-dose DOAC | This recommendation applies for patients on high risk of VTE recurrence (ie, unprovoked events related to a chronic risk factor or recurrent events). Therefore, they might benefit from standard doses of DOACs. However, lower doses may be appropriate if the risk of VTE is not considered high or if there are reasonable concerns regarding the risk of bleeding. |
| Rec 17 | Rec 17 | For patients with VKA-related life-threatening bleeding during treatment for VTE, should we use 4-factor PCCs or FFP? | Suggests using 4-factor PCCs rather than FFP as an addition to cessation of VKA and IV vitamin K | Suggests using either 4-factor PCCs or FFP | Changed | No change | Very low | Favorable | Less costly for providers | The identified evidence did not show substantial differences in outcomes important to patients with PCCs or FFP. Although PCCs are easier and faster to administer, their price is higher than that of FFP, and they are not typically available in many settings in the region. |
| Guidelines for prevention of VTE in surgical and medical patients and long-distance travelers in LA | ||||||||||
| Thromboprophylaxis in surgical procedures | ||||||||||
| Rec 27a and 27b | Rec 2 | For patients undergoing surgery following major trauma, should we use pharmacological thromboprophylaxis? | Suggests using prophylaxis in individuals who are at low to moderate risk for bleeding and against prophylaxis for patients at high risk of bleeding | Suggests using prophylaxis when the risk of bleeding is considered low or moderate and mechanical prophylaxis when this risk is high | Changed | No change | Very low | Probably favorable, safer | May be more costly for providers | Access to mechanical prophylaxis, especially compression devices, may be limited within the region. Therefore, barriers to the implementation of this recommendation may exist in some settings. |
| Rec 19 | Rec 6 | For patients undergoing major neurosurgical procedures, should we use pharmacological thromboprophylaxis? | Suggests against using pharmacological prophylaxis | Suggests thromboprophylaxisover no prophylaxis | Changed | No change | Very low | Probably favorable, safer | May be more costly for providers | These patients may also have a high risk of VTE. The LA panel considered that mechanical prophylaxis could be an appropriate alternative for patients at high risk of bleeding, especially early after surgery. Thus, the panel suggested using prophylaxis and deciding on the specific modality according to the risk of bleeding. |
| Rec 7 | Rec 9 | For patients undergoing major surgery in whom pharmacological thromboprophylaxis is preferred, should we use short or extended prophylaxis? | Suggests using extended antithrombotic prophylaxis over short-term antithrombotic prophylaxis, basing their judgment mainly on individuals athigh risk of VTE, such as patients undergoing cancer surgery ororthopedic surgery | Suggests short prophylaxis (7 to 10 days) over extended prophylaxis(30 days) | Changed | No change | Very low | Probably favorable, safer | Less costly for patients and providers | Original ASH guideline made a recommendation in favor of extended prophylaxis, basing their judgment mainly on individuals athigh risk of VTE, such as patients undergoing cancer surgery or orthopedic surgery. |
| Rec 8 | Rec 10 | For surgical patients in whom pharmacological thromboprophylaxis is preferred, should we use delayed or early prophylaxis? | Suggests using early or delayed antithrombotic prophylaxis | Suggests delayed prophylaxis (12 hours after surgery)over early administration (before surgery or within 12hours after surgery) | Changed | No change | Very low | Probably favorable, safer (less bleeding risk) | Less costly for patients and providers | The LA panel judged that, for most patients undergoingsurgery, the risk of VTE before the procedure was very small. In addition,the use of early prophylaxis might slightly increase the risk of bleeding during surgery. |
| Thromboprophylaxis in medical patients and long-distance travelers | ||||||||||
| Rec 1 | Rec 11 | For medically ill patients, should we use heparins asthromboprophylaxis? | Suggests using UFH, LMWH, or fondaparinux rather than no parenteral anticoagulant | Suggests against routinely use of heparins (UFH or LMWH) | Changed | No change | Low | Probably favorable, safer (less bleeding risk) | Less costly for patients and providers | For the majority of patients admitted to hospital for noncritical medical conditions, the risk of VTE is likely small, especially if they are able to walk or perform physical therapy. In those cases, the benefit of prophylaxis with heparins may be very small. This change of direction had to do with the baseline risk of VTE in average medical patients. The LA panel considered that most patients admitted to hospital for noncritical medical conditions have a low risk of VTE, especially if they retain their mobility. |
| Rec 4 | Rec 12 | For patients who are critically ill, should we use heparins as thromboprophylaxis? | Recommends using UFH or LMWH over no UFH or LMWH | Suggests the use of heparins (UFH orLMWH) over no use | No change | Changed | Moderate | Probably favorable, safer (less bleeding risk) | Less costly for patients and providers | The panel considered that for most patients who are critically ill, the benefits of thromboprophylaxis (moderate reduction of VTE risk) probably outweigh the potential harms (small increase of bleeding). However, a proportion of individuals, for example, neurosurgical patients or patients who have experienced trauma, may not obtain a net benefitfrom thromboprophylaxis, given their increased risk of bleeding. |
| Rec 2 and 5 | Rec 13 | For patients who are critically ill or have medical conditions and require pharmacologic prophylaxis, should we use LMWH or UFH? | Suggests using LMWH rather than UFH | Suggests either UFH or LMWH | Changed | No change | Low | Increase accessibility; maybe more bleeding risk and longer hospital stay | Probably less costly for providers; one has to consider that hospital stay length might increase | The absolute differences betweenthe effects of LMWH and UFH in patient important outcomes(thrombotic events and bleeding) are very small, that is, less than1%. In addition, LMWH is significantly more expensive in LA, and there are important access barriers within the region.Therefore, both options are reasonable management alternatives,and the final decision likely will depend on contextual factors suchas affordability and availability. |
| Rec 13 and 14 | Rec 16 | For patients who are critically ill or have medical conditions and require pharmacological thromboprophylaxis, should we use a short period of prophylaxis or an extended period? | Recommends short VTE prophylaxis (inpatients), rather than extended-duration VTE prophylaxis | Suggests using a short period of prophylaxis(inpatients) over an extended period (inpatients andextended-duration outpatients) | No change | Changed | Moderate | Probably favorable, if thrombotic risk is high and bleeding risk is low | Probably more costly for patients and providers | Although for most patient the baseline risk of VTE is small, and thus, an extended prophylaxis will not result in a significant benefit, there are some patients with a higher baseline risk of VTE who maintain this risk after discharge, especially if they need a long rehabilitation and are not able to ambulate. Those patients may benefit from a longer prophylaxis. |
| Rec 11 | Rec 18 | For patients who are acutely ill and hospitalized with medical conditions and require pharmacological thromboprophylaxis, should we use LMWH or DOACs? | Recommends using LMWH over DOACs for VTE prophylaxis | Suggests using LMWH over DOACs | No change | Changed | Moderate | Probable less safe (increased bleeding risk), but more convenient (oral administration) | Less costly | An increased risk of bleeding was observed with a short course and with an extended prophylaxis with DOAC. Therefore, the current evidence suggests that in medical patients, DOACs increase bleeding with no additional benefit on VTE prevention. However, the difference is of small absolute magnitude. In settings where DOACs are available, some patients may place more value on the convenience of an oral medication than the small increase of the risk of bleeding, especially if the baseline risk of bleeding is small. |
| Rec 12 | Rec 19 | Should inpatient VTE prophylaxis be instituted with LMWH only or inpatient and extended-duration outpatient VTE prophylaxis with DOACs? | Recommends inpatient VTE prophylaxis with LMWH only, rather than inpatient and extended-duration outpatient VTE prophylaxis with DOACs | Suggests using LMWH over DOACs | No change | Changed | Moderate | Probable less safe (increased bleeding risk), but more convenient (oral administration) | Less costly | An increased risk of bleeding was observed with a short course and with an extended prophylaxis with DOAC. Therefore, the current evidence suggests that in medical patients, DOACs increase bleeding with no additional benefit on VTE prevention. However, the difference is of small absolute magnitude. In settings in which DOACs are available, some patients may place more value on the convenience of an oral medication than the small increase of the risk of bleeding, especially if the baseline risk of bleeding is small. |
| Diagnosis of VTE and management in special populations | ||||||||||
| Diagnosis of VTE | ||||||||||
| Rec 1a | Rec 1 | For a patient with low pretest probability of a first episode of PE (≤5%), what is the optimal diagnostic strategy to evaluate a suspected PE? | Recommends using a strategy starting with D-dimer for excluding PE, followed by VQ scan or CTPA for patients requiring additional testing | Recommends using the D-dimer for excluding PE followed by CTPA in patients with a positive D-dimer | Changed the preferred diagnostic pathway | Strong (D-dimer to exclude); very low (VQ or CTPA if positive D-dimer) | Probably safe | Less costly to patients and providers | D-dimer is affordable and generally available in the region; therefore, it was considered a reasonable first step to rule-out PE. However, in LA there is a very limited availability of VQ scan, and thus the panel opted for suggesting CTPA over VQ scan as a follow-up test to a positive D-dimer. | |
| Rec 4 | Rec 2 | For a patient with low pretest probability of a recurrent PE (≤5%), what is the optimal diagnostic strategy to evaluate a suspected PE? | Suggests using a strategy starting with D-dimer for excluding recurrent PE followed by a VQ scan or CTPA | Recommends using the D-dimer for excluding PE followed by CTPA in patients with a positive D-dimer | Changed the preferred diagnostic pathway | Low (D-dimer to exclude); very low (CTPA if positive D-dimer) | Probably safe | Less costly to patients and providers | D-dimer is affordable and generally available in the region; therefore, it was considered a reasonable first step to rule-out PE. However, in LA there is a very limited availability of VQ scan, and thus the panel opted for suggesting CTPA over VQ scan as a follow-up test to a positive D-dimer. | |
| Rec 2a | Rec 3 | For a patient population with an intermediate clinical probability of a first episode of PE (∼20%), what is theoptimal diagnostic strategy to evaluate for suspected first episode PE? | Suggests using a strategy starting with D-dimer for excluding PE, followed by VQ scan or CTPA for patients requiring additional testing | Suggests using the D-dimer for excluding PE, followed byCTPA in patients with a positive D-dimer | Changed the preferred diagnostic pathway | Strong (D-dimer to exclude); very low (CTPA if positive D-dimer) | Probably safe | Less costly to patients and providers | At 20% probability, D-dimer still can safely rule out a first episode of PE. However, patients with an intermediate probability of recurrent PE (∼20%) may not be adequality categorized by D-dimer alone and hence, the panel suggests following recommendation 5 in this situation. As before, it should be noted that an abnormal D-dimer can be observed in many clinical conditions apart from VTE, and therefore, a positive D-dimer should not be the sole basis for VTE diagnosis. Given the limited availability of VQ scan on the region, the LA panel opted for suggesting CTPA over VQ scan as a follow-up test to a positive D-dimer. | |
| Prevention and management of VTE during pregnancy | ||||||||||
| Rec 8 | Rec 13 | For pregnant women with PE and hemodynamic failure, should we use thrombolytic therapy in addition to anticoagulation? | Suggests administering systemic thrombolytic therapy in addition to anticoagulant therapy | Recommends thrombolytic therapy in addition to anticoagulation | No change | Changed | Very low | May be favorable but higher bleeding risk | More costly for patients and providers | The evidence that informs this recommendation comes primarily from general adult population, and therefore, there is considerable uncertainty regarding the effect of thrombolytic therapy in pregnant women. The LA panel, however, considered that in a situation of high mortality, thrombolytictherapy may be a life-saving intervention, and placed a higher value in preserving maternal life. |
| Rec 11 | Rec 17 | For pregnant women receiving prophylactic dose LMWH, should we offer scheduled delivery with prior discontinuation of LMWH or cessation of LMWH with spontaneous onset of labor? | Suggests against scheduled delivery with discontinuation of prophylactic anticoagulation compared with allowing spontaneous labor | Suggests scheduled delivery with prior discontinuation of LMWH over cessation of LMWH with spontaneous onset of labor | Changed | No change | Very low | May be safer | More costly for patients and providers | Although most women receiving prophylactic dose LMWH may go through a spontaneous labor safely, many women in LA have a poor access to skilled birth attendance. In this scenario, a scheduled delivery conducted at hospitals may be safer for women receiving LMWH. |
| Rec 16 and 17 | Rec 19 | For women with previous VTE, should we use antepartum anticoagulant prophylaxis? | Recommends antepartum anticoagulant prophylaxis over no prophylaxis (if VTE is unprovoked or associated with a hormonal risk factor) | Suggests antepartum anticoagulant prophylaxis over no prophylaxis (if VTE is unprovoked or provoked) | No change | Changed | Low | Probably safer | Less costly | The original ASH guideline panel made a strong recommendation in favor of prophylaxis in women at high risk for VTE recurrence and a conditional recommendation against prophylaxis in women at low risk for recurrence. Therefore, to best implement this recommendation, clinicians may explore the baseline risk for VTE recurrence and, concomitantly, women preferences. |
| Rec 18 | Rec 20 | For women with previous VTE not already receiving long-term anticoagulant therapy, should we use postpartum anticoagulant prophylaxis? | Recommends postpartum anticoagulant prophylaxis | Suggests postpartum anticoagulant prophylaxis over no prophylaxis | No change | Changed | Low | Probably more risk of thrombosis and less risk of bleeding | Less costly | The ASH-GRADE rules specified in this article are intended to prevent a strong recommendation in such situations. The reason for the discrepancy is the uncertain benefit of the intervention (low certainty evidence). |
| Management of VTE in children | ||||||||||
| Rec 2 | Rec 23 | For children with asymptomatic VTE, should we use anticoagulation? | Suggests either using anticoagulation or no anticoagulation in pediatric patients with asymptomatic DVT or PE | Suggests against anticoagulation | Changed | No change | Very low | Less risk of bleeding | Less costly | Asymptomatic VTE in children are usually detected in the context of a central venous access device. Given the provoked nature of the event, the risk of recurrence is generally small, and the use of anticoagulants may result in a net harm. However, anticoagulation for a limited period may benefit children with other risk factors for VTE (ie, thrombophilia) or those who require multiple central venous access devices. |
| Rec 5 | Rec 24 | For children with PE and hemodynamic failure, should we use thrombolytic therapy? | Suggests using thrombolysis followed by anticoagulation, rather than anticoagulation alone | Recommends thrombolytic therapy in addition to anticoagulation | No change | Changed | Low | Probably favorable but more risk of bleeding | More costly for patients and providers | There is considerable uncertainty regarding the effect of thrombolytics in children given the lack of appropriately designed and powered studies. However, the available evidence suggests a significant effect of thrombolytics in preserving life in a condition of high mortality. This scenario justifies a strong recommendation in favor of the intervention following the ASH-GRADE rules. |
CoE, certainty of evidence; CTPA, computed tomography pulmonary angiography; DOAC, direct oral anticoagulant; DVT, deep venous thrombosis; FFP, fresh-frozen plasma; LAG, Latin America guideline; LMWH, low molecular weight heparin; OG, original guideline; PCC, prothrombin complex concentrate; PE, pulmonary embolism; Rec, recommendation; UFH, unfractionated heparin; VKA, vitamin K-antagonist; VQ, ventilation perfusion.