Table 1.
Synopsis of the recommendations
| Recommendation (R) no. | Population | Recommendation | Strength, certainty in evidence∗ |
|---|---|---|---|
| Patients with symptomatic VTE | |||
| R1 | Unprovoked VTE | Do not test for thrombophilia | Conditional, ⊕○○○ |
| R2 | VTE provoked by surgery | Do not test for thrombophilia | Conditional, ⊕○○○ |
| R3 | VTE provoked by nonsurgical major transient risk factor | Test for thrombophilia, and indefinite anticoagulant treatment for patients with thrombophilia | Conditional, ⊕○○○ |
| R4 | VTE provoked by pregnancy or postpartum | Test for thrombophilia, and indefinite anticoagulant treatment for patients with thrombophilia | Conditional, ⊕○○○ |
| R5 | VTE associated with use of COC | Test for thrombophilia, and indefinite anticoagulant treatment for patients with thrombophilia | Conditional, ⊕○○○ |
| R6 | An unspecified type of VTE (ie, not specified as provoked or unprovoked VTE) | Do not test for thrombophilia | Conditional, ⊕○○○ |
| Patients with symptomatic VTE in unusual sites | |||
| There is no unanimous approach to the optimal duration of anticoagulation treatment of CVT and splanchnic venous thromboses, with some providers and settings adopting long- and other short-term anticoagulation, and others deciding based on the clinical presentation. The panel issued 2 recommendations for each clinical scenario, separately for (a) settings where the standard of care would be stopping treatment in most patients after primary treatment of 3-6 months and (b) for settings where the standard of care would be treating most patients with indefinite anticoagulation. | |||
| R7 | CVT | (a) In settings when anticoagulation would otherwise be discontinued after primary short-term treatment: test for thrombophilia, and indefinite anticoagulant treatment for patients with thrombophilia | Conditional, ⊕○○○ |
| R8 | (b) In settings when anticoagulation would otherwise be continued indefinitely: do not test for thrombophilia | Conditional, ⊕○○○ | |
| R9 | Splanchnic venous thrombosis | (a) In settings when anticoagulation would otherwise be discontinued after primary short-term treatment: test for thrombophilia, and indefinite anticoagulant treatment for patients with thrombophilia | Conditional, ⊕○○○ |
| R10 | (b) In settings when anticoagulation would otherwise be continued indefinitely: do not test for thrombophilia | Conditional, ⊕○○○ | |
| Asymptomatic individuals with a family history of VTE and/or thrombophilia | |||
| Individuals with a minor transient risk factor for VTE | |||
| The panel considered the scenario where an individual with a family history of VTE and/or thrombophilia was presenting with a minor transient risk factor for VTE. The clinical question was if testing and providing pharmacological prophylaxis to individuals with thrombophilia would be beneficial. Two testing strategies were separately considered: (a) doing a thrombophilia panel (ie, testing for all hereditary thrombophilias) and (b) selective testing for the thrombophilia known in the family. | |||
| R11 | Individuals with a family history of VTE and known thrombophilia | Strategy #1: selective testing for the thrombophilia known in the family | |
| Heterozygous FVL or heterozygous PGM | Do not test for thrombophilia | Conditional, ⊕○○○ | |
| Protein C, S, or antithrombin deficiency | Test for the thrombophilia known in the family and use thromboprophylaxis in individuals with thrombophilia | Conditional, ⊕○○○ | |
| R12 | Individuals with a family history of VTE and known thrombophilia | Strategy #2: doing a thrombophilia panel | |
| Heterozygous FVL or heterozygous PGM | Do not test for a panel of hereditary thrombophilias (panel) | Conditional, ⊕○○○ | |
| Protein C, S, or antithrombin deficiency | Test for all hereditary thrombophilia (panel) and use thromboprophylaxis in individuals with thrombophilia | Conditional, ⊕○○○ | |
| R13 | Individuals with a family history of VTE and unknown thrombophilia status | Do not test for thrombophilia | Conditional, ⊕○○○ |
| R14 | Individuals with a family history of thrombophilia but no VTE | ||
| Heterozygous FVL or heterozygous PGM | Do not test for thrombophilia | Conditional, ⊕○○○ | |
| Protein C, S, or antithrombin deficiency in first-degree relatives | Test for the thrombophilia known in the family and use thromboprophylaxis in individuals with thrombophilia | Conditional, ⊕○○○ | |
| Protein C, S, or antithrombin deficiency in second-degree relatives | Either test or do not test for the thrombophilia known in the family to guide thromboprophylaxis | Conditional, ⊕○○○ | |
| Women considering using COC or HRT | |||
| The panel considered the scenario where a woman, either from the general population or with a family history of VTE and/or thrombophilia, considers using hormones that increase VTE risk, that is, COCs or HRT. The clinical question was if it would be beneficial to test and avoid these hormones in women with thrombophilia. Two testing strategies were separately considered: (a) doing a thrombophilia panel (ie, testing for all hereditary thrombophilias) and (b) selective testing for the thrombophilia known in the family. | |||
| R15 | Women from the general population considering COCs | Do not test for thrombophilia | Strong, ⊕⊕○○ |
| R16 | Women from the general population considering HRT | Do not test for thrombophilia | Conditional, ⊕⊕○○ |
| R17 | Women with a family history of VTE and unknown thrombophilia in the family considering COCs | Do not test for thrombophilia | Conditional, ⊕○○○ |
| R18 | Women with a family history of VTE and unknown thrombophilia in the family considering HRT | Do not test for thrombophilia | Conditional, ⊕○○○ |
| R19 | Women with a family history of VTE and thrombophilia considering COCs | Strategy: selective testing for the thrombophilia known in the family | |
| FVL or PGM | Do not test for thrombophilia | Conditional, ⊕○○○ | |
| Protein C, S, or antithrombin deficiency | Test for thrombophilia and avoid COCs in women with thrombophilia | Conditional, ⊕○○○ | |
| R20 | Women with a family history of VTE and thrombophilia considering HRT | Strategy: selective testing for the thrombophilia known in the family | |
| FVL or PGM | Do not test for thrombophilia | Conditional, ⊕○○○ | |
| Protein C, S, or antithrombin deficiency | Test for thrombophilia and avoid HRT in women with thrombophilia | Conditional, ⊕○○○ | |
| Women who are planning pregnancy | |||
| The panel considered the scenario where a woman with a family history of VTE and thrombophilia is planning a pregnancy. The clinical question was if testing and using antepartum and/or postpartum thromboprophylaxis in women with thrombophilia would be beneficial. Only the strategy of selective testing for the thrombophilia known in the family was considered. Recommendations on antepartum and postpartum prophylaxis in women with thrombophilia are already given in the ASH guidelines on the management of VTE in the context of pregnancy.27 Hence, the panel did not review the evidence for women with heterozygous FVL or heterozygous PGM, as the ASH guidelines on the management of VTE in the context of pregnancy already suggest not to prescribe thromboprophylaxis in these women. | |||
| Antepartum prophylaxis | |||
| R21 | Women with a family history of VTE and thrombophilia | Strategy: selective testing for the thrombophilia known in the family | |
| Known homozygous FVL, combination of FVL and PGM, or antithrombin deficiency | Test for the thrombophilia known in the family and use antepartum thromboprophylaxis in women with thrombophilia | Conditional, ⊕○○○ | |
| Known protein C or protein S deficiency in the family | Either test or do not test for the thrombophilia known in the family to guide antepartum thromboprophylaxis | Conditional, ⊕○○○ | |
| Postpartum prophylaxis | |||
| R22 | Women with a family history of VTE and thrombophilia | Strategy: selective testing for the thrombophilia known in the family | |
| Known homozygous FVL, combination of FVL and PGM, or antithrombin, protein C, or protein S deficiency | Test for the thrombophilia known in the family and use postpartum thromboprophylaxis in women with thrombophilia | Conditional, ⊕○○○ | |
| Known combination of FVL and PGM, or antithrombin deficiency in second-degree relatives | Test for the thrombophilia known in the family and use postpartum thromboprophylaxis in women with thrombophilia | Conditional, ⊕○○○ | |
| Known protein C or protein S deficiency in the family | Either test or do not test for the thrombophilia known in the family to guide postpartum thromboprophylaxis | Conditional, ⊕○○○ | |
| Patients with cancer | |||
| The panel only addressed patients with cancer who are classified to be at low or moderate risk of VTE, as the ASH VTE guidelines on prevention and treatment for patients with cancer already suggest using DOAC prophylaxis in all ambulatory patients with cancer at high risk of VTE. | |||
| R23 | Ambulatory patients with cancer who are classified to be at low or intermediate risk for VTE, who have a family history of VTE in first-degree relatives | Strategy: doing a thrombophilia panel Test for all hereditary thrombophilia (panel) and use thromboprophylaxis in individuals with thrombophilia |
Conditional, ⊕○○○ |
∗
For an explanation of conditional and strong recommendations, see Table 2.